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Outstanding Speaker Lineup for WeatherReady Fest in Huntsville Saturday: Including NWS SKYWARN Spotter Training
Bring your friends and join us on Saturday, September 7th, for this year's biggest weather festival: WeatherReady Fest in Huntsville! What makes this event so big? Once a year, hundreds of the nation's top operational meteorologists come together for the NWA annual meeting at a different city. Kicking off this event is a fun, community-outreach extravaganza: WeatherReady Fest!
With a variety of exciting activities for children and adults alike, you will get to rub shoulders with the nation's top meteorologists. A fascinating speaker lineup includes a SKYWARN spotter training by the National Weather Service and a question & answer session about climate change by Sean Sublette of Climate Central. Local speakers include the Alabama Emergency Manager, Brian Hastings; Madison County's Emergency Manager, Chris Reed; the Huntsville Chief of Police; and more!
Adults will enjoy the rare opportunity to tour the National Weather Service Office and get a first-hand look at forecasting technology at SWIRLL. Kids will jump at the chance to climb in Storm Chasing & Research Vehicles and will be thrilled to spot weather mascots, such as Owlie Skywarn. Fun opportunities for learning about all things weather will continue throughout the day with weather balloon launches, hands-on activities & demonstrations, stage shows, door prize drawings and more!
Come out to UAH's Charger Student Union and Shelby Center between 10 a.m. and 4 p.m. and boost your weather knowledge at this once-a-year festival! Details can be found at the festival website: www.weatherreadyfest.com. Admission to the WeatherReady Fest event is free. Guests are encouraged to get their free timed tickets at the website.
Category: Headlines, Uniquely Alabama


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Kaunas Castle (Lithuanian)
Kaunas Castle is a medieval castle situated in Kaunas, the second-largest city in Lithuania. Archeological evidence suggests that it was originally built during the mid-14th century, in the Gothic style. Its site is strategic – a rise on the banks of the Nemunas River near its confluence with the Neris River. At the beginning of the 21st century, about one-third of the castle was still standing.

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Christopher C Broder, Dawn L Weir, Peter A Reid. Vaccine Volume 34, Issue 30. June 2016.
Hendra virus (HeV) and Nipah virus (NiV) are enveloped, single-stranded negative sense RNA viruses and the prototype members of the genus Henipavirus in the family Paramyxoviridae. Recently, a third virus isolate Cedar virus (CedPV) has been added to the Henipavirus genus. Whereas HeV and NiV are bat-borne disease-causing zoonoses, CedPV is not known to be zoonotic nor has it been shown to be pathogenic in any animal, including those susceptible to HeV and NiV, although it does reside in nature in the same bat species as HeV. To date, bats appear to be predominant natural reservoir hosts for henipaviruses. Although nucleic acid based detection studies have identified related Henipavirus species, including complete genomic sequences, HeV, NiV, and CedPV are the only virus isolates that have been reported.
In several disease-susceptible animal species, and in people, the major pathological observation of HeV and NiV infection is a severe systemic and often fatal neurologic and/or respiratory disease. However, HeV and particularly NiV can also cause relapsed encephalitis which follows a recovery from an acute infection and appears to result from a recrudescence of virus replication in the central nervous system (CNS). Outbreaks or spillovers of NiV in Bangladesh and India, since its first emergence in peninsular Malaysia, have continued to occur, as has HeV in Australia, making these henipaviruses important transboundary biological threats. Both HeV and NiV are highly pathogenic in a number of mammalian species and possess several characteristics that distinguish them from all other known paramyxoviruses and are classified as Biosafety Level-4 (BSL-4) agents. Indeed, NiV is considered to have the potential to be a pandemic threat since it can infect humans directly from natural reservoirs (bats) or indirectly following amplification in a susceptible animal species (pig) and has a recognized capacity of, albeit limited, human-to-human transmission. Since their discovery and recognition, a variety of approaches have been taken by multiple research groups to devise countermeasures as a means of addressing the transboundary threat issues brought about by HeV and NiV. Several active and passive immunization approaches have been explored and some have led to successful deployment and human clinical trials. Concurrent with these developments, several animal challenge models of HeV and NiV infection and pathogenesis have been established which have provided insight into the nature of HeV and NiV disease and afforded the possibility of testing vaccine and therapeutic countermeasures.
Hendra Virus and Nipah Virus Emergence
In 1994 an outbreak of fatal cases of a severe respiratory disease in horses and humans occurred in the Brisbane suburb of Hendra, Australia. The infectious cause of this event was discovered to be a previously unknown paramyxovirus that was distantly related to certain morbilliviruses. In all, 13 horses and a trainer succumbed to infection together with the non-fatal infection of 7 additional horses and a stable hand. In a separate incident that was retrospectively recognized, this same virus caused a brief aseptic meningitic illness in one person after he had cared for and assisted in the necropsies of two horses near Mackay in central Queensland ~1000km north of Brisbane, and these animals were later shown to have died from this virus infection. Remarkably, 13 months following his recovery, this individual suffered an episode of relapsed fatal encephalitis characterized by uncontrolled focal and generalized epileptic-activity caused by this virus. Provisionally termed equine morbillivirus, this new paramyxovirus was later re-named Hendra virus (HeV), after the location of the first recognized outbreak. To date, HeV has appeared in Eastern Australia on 55 occasions, with the three most recent in 2015, causing the death or euthanasia of 97 horses, 2 HeV antibody positive and euthanized dogs, and 4 fatalities of 7 human cases. In all recognized HeV spillovers and those cases of confirmed human infections, the horse is the predominant target host acquiring infection from virus-shedding bats and is also the intermediate host from which humans have acquired infection. The epidemiological characteristics and the possible underlying mechanisms behind HeV spillovers have been examined and reviewed. In 2011, the first confirmed infection of HeV in a dog was reported. The dog was shown to be seropositive for HeV and was euthanized despite showing no clinical signs of disease. A postmortem was not performed and it was thought that transmission of infection had occurred by close contact with an infected horse. A second confirmed HeV infection in a dog was reported in 2013. The dog tested positive to HeV by quantitative reverse transcription PCR (q-RT-PCR) during the apparent early stages of an acute infection and had appeared to have become naturally infected with HeV following close exposure to blood from a euthanized HeV infected horse. This dog was euthanized and extensively analyzed via postmortem examination. Although the dog had appeared clinically healthy, histopathologic findings of widespread necrotizing vasculitis was noted, with the most severe lesions recorded in the kidney, brain and lymph nodes, with little involvement of the lungs. Additionally, HeV RNA was detected in multiple tissues. Presently, the extent of HeV transmission from bats to dogs in Australia is an unknown concern and should be the focus of future studies.
A few years following the appearance of HeV there was a large outbreak of encephalitis among pig farmers in Peninsular Malaysia which began in the fall of 1998 and continued into the spring of the next year. A virus was isolated from the cerebrospinal fluid (CSF) of two patients and shown to cross-react with antibodies against HeV. Subsequent molecular genetic studies revealed a new paramyxovirus that was most closely related to HeV. This Hendra-like virus was named Nipah virus (NiV) after the town of Nipah in the state of Perak, Malaysia where it was first isolated from a case of fatal encephalitis. In total there were 265 cases of human infection with 105 fatalities in Malaysia along with an additional 11 cases and one fatality among abattoir workers in Singapore. The epidemiological features of this outbreak, its likely causes, and the factors that exacerbated it have been reviewed elsewhere. Although NiV has not re-emerged in Malaysia, nearly annual outbreaks of human cases of NiV infection have been recorded since 2001 in Bangladesh and a few in India. The most recent cases of human infections occurred in early 2015 with 9 human fatalities. The outbreaks of NiV in Bangladesh and India have had lower total numbers of human cases but the fatality rates have been notably higher, ranging from 75 to 100%. In these instances, the direct transmission of NiV from bats to humans following the consumption of contaminated fruits or date palm sap has been noted along with several instances of significant human-to-human transmission of NiV infection being documented. The epidemiological details of the spillovers of both HeV and NiV into humans have been recently reviewed. In all, there have been ~620 cases of human NiV infection with 322 fatalities.
Pteropus bat species appear to be the major natural reservoir hosts for henipaviruses and all bat isolates of HeV, NiV as well as CedPV have been derived from Pteropus bats. As natural reservoir hosts, overt disease has not been reported in wild bats, nor are there signs of clinical illness in experimentally infected pteropid bats. Nevertheless, there continues to be ever expanding evidence of the presence of henipaviruses in a wide variety of other bat species in both Megachiroptera and Microchiroptera suborders, as well as the existence of other henipa-like viruses in rodents. Further, serological and/or nucleic acid evidence of henipaviruses in domestic livestock and in human populations have also been reported, providing evidence of sporadic henipavirus spillover events and also suggesting the existence of related henipaviruses.
The Viruses, Tropism, and Entry
HeV and NiV particles are enveloped and pleomorphic with spherical or filamentous forms observed by electron microscopy. The viral envelope carries surface projections composed of the viral transmembrane anchored fusion (F) and attachment (G) glycoproteins which have been the major target of antiviral strategies. HeV and NiV are classified into the Henipavirus genus, Paramyxoviridae family and their genomes are unsegmented, single-stranded, negative-sense RNA. Genomic sequence analysis of many HeV isolates obtained from horses, a human case, and pteropid bats, have shown them to be ~99% identical. In the initial Malaysian outbreak of NiV, both pig and human isolates were genetically highly similar to those obtained years later from bats. However, some diversity among NiV isolates can be noted when comparing Malaysian isolates to NiV isolates from other areas of Southeast Asia, with NiV-Bangladesh sharing ~92% identity with NiV-Malaysia, and a third lineage of NiV was isolated from Lyle's flying fox (Pteropus lylei) in Cambodia that is more closely related to NiV-Malaysia than to NiV-Bangladesh.
HeV and NiV are also distinguished by their exceptionally broad species tropism and in addition to pteropid bats, natural or experimental infection has been documented in pigs, horses, cats, dogs, guinea pigs, mice, hamsters, ferrets, squirrel monkeys and African green monkeys and humans. NiV can also productively infect chicken embryos spanning 7 orders (6 mammalian and one avian).
The major determinant of species and cellular tropism of HeV and NiV is derived from the functions of the viral envelope glycoproteins (G and F) which are the mediators of virus attachment and host cell infection. The HeV and NiV G glycoprotein bind to the host cell membrane proteins ephrin-B2 and ephrin-B3. The ephrin-B2 and -B3 molecules are members of a large family of cell surface expressed glycoprotein ligands that bind to Eph receptors and are highly sequence conserved across known susceptible hosts with amino acid identities ranging from 95 to 98%. Ephrin-B2 expression is prominent in arteries, arterioles and capillaries in multiple organs and tissues while ephrin-B3 is found predominantly in the nervous system and the vasculature). Their identification as major receptors for HeV and NiV has helped clarify their broad species and tissue tropisms and pathogenic features observed in both animals and humans.
The HeV and NiV G glycoprotein is a type II membrane glycoprotein consisting of a stalk and globular head domain which binds ephrin receptors. The native conformation of G is a tetramer comprised of a dimer of dimers. The crystal structures of both NiV and HeV G globular head domains have been determined both alone and in complex with the ephrin-B2 and -B3 receptors, revealing the exact G-receptor interactions and identical receptor binding sites with four binding pockets in G for the residues in the ephrin-B2 and -B3 G-H loop that are highly conserved. The second viral envelope glycoprotein is the fusion (F) glycoprotein that mediates the membrane fusion process between the virion and host cell. F is a type I membrane glycoprotein and is a class I viral fusion protein sharing several conserved features with other viral fusion glycoproteins. F is initially expressed as a precursor (F0) which forms an oligomeric homotrimer that is cleaved into two disulfide bond-linked subunits (F1 and F2) by the endosomal protease cathepsin L. Following virus attachment to a ephrin receptor-bearing host cell, the fusion-promoting activity of G is initiated through its binding to receptor and then in turn facilitates the triggering of conformational changes in F, transitioning the molecule from its pre-fusion to post-fusion form driving the membrane fusion process between the virion and host cell, resulting in delivery of the viral nucleocapsid into the cytoplasm.
Clinical and Pathological Features of Human HeV and NiV Infection
Human HeV and NiV infections have an incubation period ranging from a few days to about 3 weeks. All human cases of HeV infection have been the result of exposure and transmission of the virus from infected horses to humans. Following an influenza-like illness (fever, myalgia, headaches, lethargy, vertigo, cough, pharyngitis, and cervical lympadenopathy), the majority of human HeV cases developed severe disease and died; only 3 of 7 patients have survived (~60% mortality rate). The first human case presented as an acute severe respiratory disease but no clinical evidence of acute encephalitis. At autopsy, the lungs showed macroscopic evidence of congestion, hemorrhage and edema associated with focal necrotizing alveolitis and evidence of syncytia and multinucleated giant cell formation, and viral inclusions. Although clinical encephalitis was apparently absent, the brain pathology clearly showed acute encephalitis characterized by mild meningitis, parenchymal and perivascular inflammation. More importantly, there was evidence of neuronal viral inclusions, vasculitis and necrotic/vacuolar plaques. A second fatality occurred in an individual who first experienced an aseptic meningitic illness associated with drowsiness caused by HeV infection acquired after assisting at the necropsies of two horses that were only later shown to have died from HeV infection. Approximately 13 months later this individual suffered a recurrence of severe encephalitis characterized by uncontrolled focal and generalized epileptic-activity. Inflammatory lesions were only found in the CNS, not in other organs obtained at autopsy; this was the first case of relapsing henipavirus encephalitis. The other two fatal cases presented as an acute encephalitic syndrome characterized by drowsiness, confusion, ataxia, ptosis, dysarthria and seizures and the patients died soon after. Of the 3 human Hendra virus survivors, there is evidence in one patient who previously developed acute encephalitis in 2008 of the persistence of postencephalitic, high level cognitive deficits, but no evidence of relapse or of viral shedding in 2 of the survivors who were studied.
In contrast to human cases of HeV infection, there have been many more cases of human NiV infection. The main features of acute human NiV infection were fever, headache, dizziness and vomiting and a majority of patients had reduced consciousness levels and signs of brainstem dysfunction. A small number, probably <10%, of patients with acute NiV infection developed a late-onset encephalitis or a relapsing encephalitis a few weeks later with a mortality rate of ~18%, considerably lower than that for acute encephalitis which was ~40% in the initial NiV outbreak in Malaysia. The clinical features of late-onset encephalitis and relapsing encephalitis are similar to acute encephalitis. Although most NiV-infected human patients presented with acute encephalitis, ~25% of patients also presented with respiratory signs. In addition, NiV infection could also take a quiescent course with neurological disease occurring later (>10 weeks) following a non-encephalitic or asymptomatic infection. Here, there appears to be a recrudescence of virus replication in the CNS. Most reported cases of relapsed encephalitis occurred between a few months to 2 years following the initial acute infection, however 2 cases were observed in 2003, 4 years later, and one case of relapsed encephalitis 11 years later. Persistent neurological deficits have been observed in >15% of NiV infection survivors. In Bangladesh, the outcomes among 22 of 45 serologically confirmed cases of NiV infection revealed neurological sequelae in survivors, and patients who initially had encephalitis could continue to exhibit neurological dysfunction for several years. Viral persistence and/or recrudescence within the CNS are suspected to be at play in these individuals, however, attempts at virus isolation from relapsed HeV and NiV patients have been unsuccessful, and there is no evidence to date indicating that relapsed patients are potentially infectious because of shedding. The mechanisms that allow NiV and HeV to escape immunological clearance for such an extended period and later result in disease are unknown, and this feature has important implications for therapeutics development.
In the first NiV outbreak in Malaysia and Singapore, autopsies were conducted on >30 individuals and the most distinctive microscopic feature was disseminated vasculitis in most organs examined, particularly in the CNS and lungs. Extravascular necrotic lesions and inflammation in many organs were also reported. In the CNS parenchyma, distinct necrotic plaques as a result of vasculitis-induced vascular obstruction, ischemia and infarction and/or neuronal infection were commonly found. Viral inclusions in neurons in the CNS and other cells in non-CNS tissues were also observed. The pathological features in a few autopsy cases of NiV relapsing or late-onset encephalitis and the single case of HeV relapsing encephalitis were similar and confined mainly to the CNS.
Clinical and Pathological Features of HeV and NiV Infection in Animals
Naturally acquired HeV infections have almost exclusively been observed in horses, and only recently have two dogs been reported HeV antibody positive. Whereas in addition to pigs, naturally acquired NiV infection was noted in dogs, cats and horses in the initial Malaysian outbreak. Since their discovery, however, a large number of different species have been examined under experimental conditions for the purposes of developing infection models and characterizing the viral pathogenic processes. Detailed reviews of the disease manifestations observed in natural and experimental infections of animals, including bats, with HeV and NiV have recently been reported.
Animal models of HeV and NiV infection and pathogenesis have played a critical role in aiding our understanding of henipavirus pathogenesis and are also an absolute necessity for the testing and validation of potential vaccines and therapeutic countermeasures. There are now several well-established animal models of HeV and NiV infection and pathogenesis including the guinea pig, hamster, cat, pig, ferret, African green monkey (AGM), squirrel monkey and horse. Among these models, the hamster, ferret and AGM best represent HeV and NiV pathogenesis observed in humans, whereas the most appropriate models for livestock are the pig and horse. Here, for the purposes of highlighting the findings to date on animal HeV and NiV vaccines and potential therapeutic modalities for people, a focus on the pig, horse and non-human primate models of infection will be summarized.
The Pig
Experimental NiV infection of pigs has revealed an incubation period of ~5-7 days post-infection and the respiratory system serving as a major site of virus replication and pathology, with viral antigen and syncytia formation present in the respiratory epithelium (tracheal, bronchial, bronchiolar, and alveolar) and small blood and lymphatic vessels. Virus was also observed in the kidneys and in endothelial and smooth muscle cells of small blood vessels. CNS involvement is less common in the pig, with meningitis or meningoencephalitis observed as opposed to encephalitis. NiV infection of piglets generally resulted in a mild clinical illness with respiratory signs and fever, along with virus replication in the respiratory system, lymphoid tissues and CNS. Recoverable virus was seen in the respiratory, lymphatic and nervous systems, and there is virus shedding in nasal, pharyngeal and ocular fluids. HeV infection of pigs also presents primarily as a respiratory disease with possible CNS involvement observed in minipigs, along with similar patterns of virus shedding. Overall, HeV appears to cause a more severe respiratory illness in pigs when contrasted to NiV in these experiments. However, the disease in pigs in Peninsular Malaysia in 1998-1999 was characterized by a pronounced respiratory and neurological syndrome, sometimes accompanied by sudden death of sows and boars. It was referred to in Peninsular Malaysia as "barking pig syndrome" because of the characteristic cough. Although HeV and NiV disease in pigs can be less severe in comparison to other animal models, the virus does replicate and disseminate to a variety of organs along with significant levels of virus shedding.
The Horse
Naturally acquired HeV infection in horses often results in severe disease, with fever and increased heart rate common, and a rapid deterioration with respiratory and/or neurological clinical signs. The case fatality rate is ~75%. In some naturally occurring cases HeV infection has presented with more subtle clinical signs including absence of fever. An apparent incubation period in naturally infected horses appears to be 5-16 days based on the events of the two large outbreaks; the first in 1994, where the ill index equine case was brought to stable in Hendra and died two days later, with other horses becoming ill 8-11 days following the death of the first horse, and the second in 2008 at Redlands, Queensland.
Experimental infections have been essentially uniformly fatal. Experimentally infected horses become ill ~3-11 days post-infection and animals initially present as anorexic and depressed with general uneasiness and ataxia, with the development of fever with sweating. Respiration becomes rapid, shallow and labored with pulmonary edema and congestion, along with nasal discharge 1-3 days following the onset of clinical signs typically just before death. In severe cases the airways of horses are often filled with a blood-tinged frothy exudate. Hemorrhage, thrombosis of capillaries, necrosis, and syncytial cells in the endothelium of pulmonary vessels are observed, and viral antigen within endothelial cells is seen in a wide variety of organs. Recoverable virus is present in a number of internal organs and also from saliva and urine. Neurologic clinical signs can also present, but in experimentally infected horses, meningitis (with vasculitis) is typically noted with viral antigen in the meninges. In other experiments, HeV antigen was reported in blood vessels within the brain, but to date HeV antigen has not been reported in the neurons of infected horses, but this may be because of experimental limitations. However, the meningitis and inflammation of cerebral blood vessels in the experimentally infected horses may be sufficient explanation for the neurological clinical signs in naturally acquired cases of HeV infection (Deborah Middleton, personal communication). Experimental infection of horses with NiV has not been performed but the brain and spinal cord of one naturally infected horse was examined and immunohistochemical staining of viral antigen revealed non-suppurative meningitis.
Non-Human Primates
The only nonhuman primate model that has uniformly recapitulated human disease for both NiV and HeV infection was developed using the African green monkey (AGM). Both NiV and HeV produce a uniformly lethal illness following low dose virus challenge by intratracheal inoculation within 7-10 days post-infection. NiV and HeV spread rapidly to numerous organ systems within the first 3-4 days following challenge, followed by the development of a progressive and severe respiratory disease ~7 days post-infection. The lungs become enlarged and high levels of virus replication, congestion, hemorrhage and polymerized fibrin are present. Wide-spread vasculitis with endothelial and smooth muscle cell syncytia with viral antigen and viral genome is detected in most organs and tissues with associated pathology. AGMs infected with either NiV or HeV also exhibit neurological disease signs with the presence of meningeal hemorrhaging and edema, and vascular and parenchymal lesions in the brain including infection of neurons with the brainstem particularly involved.
The squirrel monkey was also found to be susceptible to experimental NiV infection via intravenous and intranasal routes demonstrating findings similar to AGM and human infection, but only some animals demonstrated NiV pathogenesis and not all challenged animals exhibited clinical signs of disease and remained well, even after high dose administration of NiV.
Therapeutics and Vaccines
There are no approved HeV or NiV antiviral therapeutics or vaccines for human use, however, several countermeasure approaches have been evaluated in animal challenge models and have been recently reviewed in detail elsewhere. Here, the focus will be an up to date summary of the HeV and NiV animal vaccine approaches that have been examined in vivo along with the one therapeutic approach for human use that has reached phase I clinical trial evaluation.
Active Immunization Strategies
There has been a variety of immunization strategies developed for HeV and NiV infection including live-recombinant virus platforms, protein subunit, virus-like particles and DNA vaccines; many of these approaches have only been examined for their ability to illicit HeV- or NiV-specific neutralizing antibody responses. Some approaches, however, have been examined for both immune response and efficacy using a variety of animal challenge models (Table 1 ). The first vaccine approach tested utilized the attenuated vaccinia virus strain NYVAC, whereby recombinant viruses encoding either the NiV F or G glycoproteins were examined both individually and in combination to immunize hamsters. This study revealed that complete protection from NiV-mediated disease was achievable following vaccination and that an immune response to the viral envelope glycoproteins could be an important mechanism of protection. A second poxvirus-based vaccine approach was examined as a potential livestock vaccine using recombinant canarypox virus in swine. Similar to the recombinant vaccinia virus approach, the NiV F and G glycoprotein genes were inserted into canarypox virus (ALVAC) vectors and then used to immunize piglets (Table 1). The ALVAC vectors expressing either NiV F or NiV G were tested individually and in combination and following vaccination, piglets were challenged intranasally with NiV. This study showed that protection from NiV-mediated illness was achievable in immunized piglets by either ALVAC vector alone or in combination, and also that vaccinated animals shed only low levels of nucleic acid detectable virus and no recoverable virus was evident.
More recently, several additional viral vector-based NiV vaccines have been examined in animal challenge studies (Table 1). An adeno-associated virus (AAV) platform using the NiV G glycoprotein was examined in mice and revealed a strong antibody response following immunization and was then tested in the hamster model using NiV challenge, showing complete protection against NiV, however, only low level cross-protection (3 of 6 animals) against a HeV challenge. Recombinant measles virus vectors encoding the NiV G glycoprotein have also been explored, using two different vectors based on the HL (rMV-HL-G) and Edmonston (rMV-Ed-G) measles virus strains. This study revealed that complete protection from NiV disease was achievable in the hamster challenge model using NiV after vaccination with either rMV-HL-G or rMV-Ed-G, and the rMV-Ed-G was also used in a small nonhuman primate study showing 2 of 2 AGMs protected against NiV challenge (Table 1).
Several groups have also used the vesicular stomatitis virus (VSV) based platform using the NiV F or G envelope glycoproteins (Table 1). This was explored first in the ferret model and showed that a single immunization with either recombinant virus (NiV F or NiV G) afforded complete protection from NiV challenge. Similarly, NiV G or F enveloped glycoproteins in recombinant VSV vectors were also successful in protection from NiV challenge in the hamster model. One study also tested a NiV nucleoprotein (N) encoding recombinant VSV vector and revealed, not surprisingly, only partial protection from challenge but that cell-mediated immunity to NiV infection can also be relevant. All these studies demonstrated that a single dose of vaccine (recombinant VSV-based) could induce strong neutralizing antibody responses and could afford protection from NiV challenge, highlighting their potential usefulness as either a livestock vaccine or one suitable in an emergency-use or outbreak scenario.
The most extensively examined vaccine approach against HeV or NiV has been a recombinant protein subunit strategy, primarily because of the inherent safety of such vaccine. Soluble, secreted, oligomeric forms of the G glycoprotein (sG) from both NiV and HeV were developed early on as a possible vaccine; HeV-sG was the most extensively studied because of its utility in eliciting the more potent cross-protective immune response. The HeV-sG glycoprotein is a secreted version of the molecule with a genetically deleted transmembrane and cytoplasmic tail that is produced in mammalian cell culture systems and is properly N-linked glycosylated. HeV-sG has been shown to retain many native characteristics including oligomerization and the ability to bind ephrin receptors, and is capable of eliciting potent cross-reactive (HeV and NiV) neutralizing antibody responses in a variety of animals including mice, rabbits, cats, ferrets, monkeys and horses. The first studies using the HeV-sG subunit immunogen in the cat model demonstrated that it could elicit a completely protective immune response against a lethal subcutaneous NiV challenge , showing that a single subunit vaccine (HeV-sG) could be effective against both HeV and NiV. Follow-up studies in the cat model demonstrated that pre-challenge virus neutralizing antibody titers as low as 1:32 were completely protective from a high dose oronasal challenge of NiV (50,000 TCID50). Additional studies with the HeV-sG vaccine in the ferret model using either 100μg, 20μg or 4μg doses of HeV-sG formulated in the vaccine adjuvants CpG and Allhydrogel(TM) could all afford complete protection from a 5000 TCID50 dose of HeV (100 times the minimal lethal dose) with no disease or evidence of virus or viral genome in any tissues or body fluids in the 100μg and 20μg vaccine groups; only a low level of HeV genome was detected in the nasal washes from 1 of 4 animals in the 4μg vaccine group, and no infectious HeV could be recovered from any immunized ferrets. In a similar immunization study carried out in ferrets but utilizing the NiV-Bangladesh strain, all animals challenged with NiV following vaccination remained disease free, and virus or viral genome was undetectable in all tissues and fluids examined, with no lesions and no viral antigen observed in all examined tissues. Further, there was no increase in antibody titer following challenge, consistent with failure of virus replication and lack of stimulation of a humoral memory response. The study also revealed good durable immunity with other ferrets challenged 434 days post-vaccination; 5 of 5 animals were disease free following challenge and viral genome was detected only from the nasal secretions of one ferret and the bronchial lymph nodes of another ferret that were given an intermediate vaccine dose.
The HeV-sG subunit vaccine has also been evaluated in nonhuman primates (AGMs). In the first study, a range of doses (10, 50, or 100μg of HeV-sG) were mixed with Allhydrogel(TM) and CpG and the vaccine was given to three animals in each dosing group twice, three weeks apart. These animals were challenged 21 days later by intratracheal administration with a 10-fold lethal dose of NiV (1×10 5 TCID50). Complete protection was observed in all vaccinated animals with some having pre-challenge NiV neutralizing titers as low as 1:28. No evidence of clinical disease, virus replication, or pathology was observed in any vaccinated animals. A second study also examined HeV-sG vaccination and protection from a HeV challenge in AGMs, but evaluated the HeV-sG subunit (100μg doses) in Allhydrogel(TM) and CpG or in Allhydrogel(TM) alone. Similarly, animals were vaccinated twice, 3 weeks apart, and challenged intratracheally with a 10-fold lethal dose of HeV (~5×105 plaque-forming units) 21 days after the booster immunization. All vaccinated animals remained disease-free and there was no evidence of virus replication or pathology observed. Importantly, this study also clearly demonstrated that HeV-sG-Allhydrogel(TM) alone is capable of providing complete protection from a HeV challenge in a nonhuman primate providing support for its preclinical development as a HeV and NiV vaccine for use in people.
The inherent safety and simplicity of the HeV-sG subunit vaccine approach along with the numerous successful vaccination and challenge studies that have been carried out in multiple animal models, provided the information that justified the evaluation of the HeV-sG subunit vaccine as a possible equine vaccine to prevent not only HeV infection of horses, but also as the means to reduce the risk of HeV transmission to people. HeV-sG was licensed by Zoetis(TM) (formerly Pfizer Animal Health) and developed as an equine vaccine for use in Australia. Horse HeV-sG vaccination and HeV challenge studies were conducted at the BSL-4 facilities of the Australian Animal Health Laboratory (AAHL) in Geelong. Here, the purified recombinant HeV-sG glycoprotein was formulated in an equine vaccine adjuvant (Zoetis, Inc.). In two initial efficacy studies in horses, either a 50μg or 100μg dose of the same sourced HeV-sG glycoprotein which was used in all the HeV-sG animal challenge studies described above was used to immunize horses. Two additional studies used 100μg of recombinant HeV-sG produced from clarified CHO cell culture supernatant (Zoetis, Inc.). Immunizations were two 1-mL doses administered intramuscularly 3 weeks apart. All horses in theses efficacy studies were exposed oronasally to 2×10 6 TCID50 of HeV. Seven horses were challenged 28 days, and three horses were challenged 194 days, after the second immunization. All vaccinated horses remained clinically healthy following challenge, showing protection with HeV neutralizing titers as low as 1:16 or 1:32 pre-challenge. There was no gross or histologic evidence of HeV infection in any of the vaccinated horses at study completion and all tissues examined were negative for HeV antigen by immunohistochemistry. Additionally, there was no detectable viral genome in any tissue. In 9 of 10 vaccinated horses, HeV nucleic acid was not detected in daily nasal, oral, or rectal swab specimens or from blood, urine, or feces samples collected before euthanasia, and no recoverable virus was present. Only in 1 of 3 horses challenged 6 months after vaccination was viral nucleic acid detected in nasal swab samples collected on post-challenge days 2, 4 and 7, a finding consistent with either self-limiting local replication or possibly remnant challenge virus nucleic acid, but again no recoverable virus was present. The equine vaccine against HeV (Equivac® HeV) was launched in November 2012 initially on a Minor Use Permit by the regulatory authority, the Australian Pesticides and Veterinary Medicines Authority (APVMA), and is the first commercially developed and deployed vaccine as a countermeasure for a BSL-4 agent, and is the only licensed antiviral approach for henipavirus infection. A database was established for all vaccinated horses by microchip use, and in August 2015 Equivac ® HeV received full registration by the APVMA. To date, ~430,000 doses of Equivac® HeV vaccine have been administered to approximately 120,000 horses, and since vaccine release, laboratory confirmed HeV infections in horses (n=15) have only occurred in unvaccinated horses. Injection site reaction calculated by the APVMA at 367,759 doses of vaccine administered from launch to 30 June 2015 was 0.18%, probable plus possible reaction incidence was <0.25%. In the vast majority of horses there is no observable adverse clinical reaction to vaccination reported by veterinarians in the field.
The Passive Immunization Approach
The first passive immunization studies were conducted in the hamster NiV-challenge model and demonstrated that antibody immunotherapy against NiV infection through the targeting of the viral envelope glycoproteins was possible. Protective passive immunotherapy using either NiV G and F-specific polyclonal antiserums, or mouse monoclonal antibodies (mAbs) specific for the NiV or HeV G or F glycoproteins has been demonstrated. These studies demonstrated the importance of viral glycoprotein specific antibody in protection from NiV- and HeV-mediated disease.
Previously, using recombinant antibody technology, HeV- and NiV-neutralizing human mAbs reactive to the G glycoproteins of both HeV and NiV were identified. One mAb, m102, possessed strong cross-reactive neutralizing activity against HeV and NiV and was affinity maturated and converted to an IgG1 format (m102.4) and produced in a CHO-K1 cell line. The m102.4 mAb epitope maps to the receptor binding site of G and engages G in a similar fashion as the ephrin receptors. The m102.4 mAb can neutralize all HeV and NiV isolates tested, including HeV-1994, HeV-Redlands, NiV-Malaysia and NiV-Bangladesh. In a post-exposure NiV challenge experiment in the ferret, a single dose of m102.4 mAb administered by intravenous infusion 10h following a lethal virus challenge could provide complete protection. The therapeutic efficacy of mAb m102.4 has also been examined in monkeys against both NiV and HeV challenge in a study design reflective of a potential real life virus exposure scenario that would call for a post-exposure therapeutic modality. In one study, animals were challenged intratracheally with HeV and following virus administration they were infused twice with m102.4 (~15mg/kg) beginning at 10h, 24h or 72h post-infection followed by a the second infusion ~48h after the first. In this study, all subjects became infected following challenge, and all animals that received m102.4 survived whereas all controls succumbed to severe systemic disease eight days following virus exposure. Animals in a 72h treatment group did exhibit neurological signs but all recovered by day 16. There was no evidence of HeV-specific pathology in any of the m102.4-treated animals, and no infectious HeV could be recovered from any tissues from any m102.4-treated subjects at the termination of the study. A later study evaluated the efficacy of m102.4 against NiV challenge in AGMs, also at several time points after virus exposure by intratracheal challenge including as late as the onset of clinical illness. In this study, animals were infused twice with m102.4 (15mg/kg) beginning at either 1, 3, or 5 days following NiV challenge and again 48h after the first dose. All animals became infected following virus exposure, and again all subjects that received m102.4 therapy survived the infection, whereas the untreated control subjects succumbed to disease between days 8 and 10 following virus exposure. Animals in the day 5 treatment group exhibited clinical signs of disease, but all recovered by day 16. Taken together, these studies have shown that m102.4 mAb therapy can prevent HeV or NiV disease in exposed subjects with a remarkably long window of therapeutic opportunity and the mAb is the only effective post-exposure therapeutic tested in vivo in nonhuman primates and one with clear potential for use in people.
Conclusions and Future Directions
Because of the potential environmental accessibility of HeV and NiV, their highly pathogenic characteristics and ability to infect a broad range of mammalian hosts including people, the development of effective countermeasures against these biothreats has been a major area of research focus. These efforts have led to the development and testing of potential vaccine candidates and antiviral therapeutics. In 2010, the m102.4 mAb producing cell line was provided to the Queensland Government, Queensland Health, Australia to produce the m102.4 mAb for compassionate emergency use basis in the event of future high-risk human HeV exposure. Queensland Health Authorities announced in 2013 plans for the first phase 1 clinical safety trial of m102.4 in human subjects, which is now underway in Australia. In addition, since 2010, there have been 11 individuals that have received high-dose m102.4 therapy on an emergency use basis because of high-risk exposure to HeV in Australia (10 people) or NiV in the United States (one person), and all have remained well with no associated adverse events. In addition, the horse vaccine against HeV (Equivac ® HeV) is expected to provide a substantial health benefit to humans and fits well within the concept of the 'One Health' approach for addressing infectious diseases of both human and animal populations.
|Table 1
Advanced active vaccination and passive immunization platforms tested in Hendra virus and/or Nipah virus animal challenge models.
|Viral antigen target or immunogen
|Animal challenge model
|Active vaccination
|Recombinant vaccinia virus
|Nipah F and/or G glycoprotein
|Hamstera (NiV)
|Recombinant canarypox virus
|Nipah F and/or G glycoprotein
|Pigb (NiV)
|Recombinant VSV
|Nipah F and/or G glycoprotein
|Ferretc (NiV), Hamsterd (NiV), nonhuman primatee (NiV)
|Recombinant AAV
|Nipah G glycoprotein
|Hamsterf (NiV, HeV)
|Recombinant measles virus
|Nipah G glycoprotein
|Hamster and nonhuman primateg (NiV)
|Recombinant subunit
|Hendra soluble G glycoprotein
|Cath (NiV), Ferreti (HeV, NiV), nonhuman primatej (HeV, NiV), horsek (HeV)
|Passive immunization
|Human monoclonal antibody m102.4
|Hendra/Nipah G glycoprotein
|Ferretl (NiV)Nonhuman primatem (HeV, NiV)


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Alma Extract – Uses
Using the organic Amla extract continuously will bring effectiveness in your body within a short span of time. Here are few:
- Male and female having High cholesterol in their body can use the juice to reduce the low-density lipoprotein cholesterol. The person who intakes this amla extract need to use it for a period of 4 – 12 weeks to see the drastic changes in their body.
- Protective cartilage gets wore done due to the age factor, and it will bring Osteoarthritis. Using the amla fruit extract for around 24 weeks (three times daily) will help the person to feel better with the knee osteoarthritis.
- Many types of research have also proved using the amla extract for hair helped the women to grow long hair without any side effects. Both Men and Women can directly apply the amla extract in their hair to stop the hair loss with immediate effect.
- The Indian gooseberry essence for skin can be used against the person who is suffering from the un-pigmented skin for years. Using the berry essence daily for three times for time duration of 6 months will increase the skin re-pigmentation in an effective way.
Amla Extract – Health benefits:
When it comes to mentioning the benefits, there are many to discuss in detail. Here are few for you:
Improves metabolic activity:
As the Indian Gooseberry fruit has high protein content, you will remain healthy for years. Also, juice will improve muscle development, cell growth, organ health, and much more.
Best for Eye Care:
Using the berry fruit juice which is rich in vitamin A is good for improving your eyesight. Indian gooseberry fruit reduces the intra-ocular tension in your eye and improves the nearsightedness in a short time. Also, Vitamin A and carotene will improve your vision, and lowers the risk of night blindness.
Treats Menstrual Cramps:
Are you women having the menstrual problem? Then Amla extract is the right choice to overcome the problem. The minerals and vitamins available remain very effective for the treatment of menstrual cramps.
Control the blood sugar level:
This fruit has proven results for diabetics as it used to stimulate the isolated cells which secrete insulin in the human body. As a result of this, the blood sugar level will get reduced effectively. Even kids with diabetics can intake the juice to control their sugar level in the body.
Prevents heart diseases:
Strengthening the heart muscles is one of the biggest amla extract benefits. Because of this process, the blood circulation will get more effective, and the excess cholesterol in the body will also get reduced. Plaque buildup in the arteries and blood vessels get reduced with the regular intake of amla extract.
Boosts your immunity:
Amla is a natural immune booster, so using the juice will help you to gain the antibacterial and anti-inflammatory properties. Also, the amla extract will also increase the white blood cells in the body which is the most essential one for the immune system.
Amla Extract – Side Effects
The amla fruit extract side effects will affect your normal health at the time of intake. Few of the important side effects are as follows:
- The acidic nature of the fruit increases the upset your stomach by triggering the Hyperacidity state of the body. The person having the sensitivity to Vitamin C will get affected with the stomach upset in large numbers.
- In general, amla fruit extract is known to be the best medicine for constipation. But when you intake less amount of water and juice in large quantity, and then it will bring a constipation problem.
- Indian gooseberry fruit act as a good antidote for the diabetics. If a person is under the medication for the diabetics, the essence will reduce the sugar level in the body, and will bring hypoglycemia problem.
- The person using the essence for months will experience the absence of moisture content in the body. This problem will occur due to the presence of antioxidants in the Indian gooseberry fruit.
- If you use the berry essence more than the recommended dose, you will experience the problems like dehydration and weight-loss in a quick time.
Using the berry fruit in the form of the extract is always a preferred option. Still, it is always to purchase the quality product from the producers like us for better results. Be cautious with yourself at the time of using it, and enjoy the numerous benefits of berry for the skin, health, and hair. Choose wisely and live happily!


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Table Dressing
April 1, 2010
It's important. (Especially if one lacks decent cooking skills.)
Let it be known, that if Nick had his way…(which he will not)…there would be a stash of paper napkins smack dab in the center of our table. Aren't these faux artichokes delightful? I've eyed them for many years in my mommy-in-law's condo. Thanks to her redecorating, I not only acquired them, but also a perfectly matching bowl for them to rest in. They have, however, been temporarily relieved of their central duties, and replaced by these…
Thank you Easter Bunny (aka Mama-Bear) for the lovely tulips! Fresh trumps faux any day.
feeling loved
March 30, 2009
It always makes me happy to see that my babies have found good homes. These three made it all the way to Chicago. Thanks Val!
I still have an Artichoke Blossom and a Fresh Herb or two…but Sweet Potato Blossom has sold out!
These two prints, went to Anna in Athens. A happy home indeed!
Ah…Monday morning, and I'm content. Life is good!
I've been a cookin'
September 17, 2008
(well, not really…we all know that's dangerous)…but I have whipped up some seriously delicious new prints for your modern gal's kitchen. "Green Things" can be mixed and matched to your heart's content! These charming 6×6 canvas prints can go it alone, or in a group of 3, or 9, or all 19! Whatever suits your fancy or your wall space. Each one is hand-signed with love by yours truly, and is named on the back. The perfect gift for your foodie friends! For the full line up, skip on over to The Produce Stand.
and remember…Mama always said to "Eat Your Greens"
another green thing…
July 7, 2008
a sneak peek…
February 22, 2008
at my new line of prints!!! They have been sent to press, and hopefully, by the end of next week I will have my hands on them! They are to be printed on canvas, 8×10, ready to hang…of course each one will be hand-signed and have some hand-painted elements…oh I can't wait for them to get here!…it will be like Christmas…(aunt jess save room in that new kitchen of yours…lol! )
All work seen above is copyright 2008 Heather L. Young, FLYoung Studio
P.S. all you foodie's out there, be sure to check out Savannah Dining Tidbits for all you need to know about the Savannah Dining scene…(and then some…)


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Casey Key / Osprey / Nokomis Events
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Netflix Could Actually Benefit From Increased Competition. Here's Why.
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New streaming video services should be good for the consumer—without representing too much of a threat to Netflix, according to new research.
Netflix stock (NFLX) was recently up 1.4% to $366.46. The company is scheduled to report first-quarter financial results in a week, a report to investors that will follow both Apple's (AAPL) announcement of its own streaming service and Thursday's expected update on Walt Disney's (DIS) at that company's investor day.
Stifel analyst Scott Devitt on Monday reiterated his Buy rating on Netflix stock, as well as a $400 price target that is right around FactSet's $399 average.
In his note, Devitt figured that the new Apple and Disney services, both due later this year, "could be good for consumers and not bad for Netflix." (That's not a unanimous opinion, as Connor Smith noted for Barron's late last month.)
"The Disney+ service will be targeted to the family-friendly programming tier, whereas many of Netflix's biggest original hits and original content spending have concentrated on the adult audience," Devitt wrote. "And the availability of even more subscription video on demand options, including sports content with ESPN+ and others, could actually accelerate cord- cutting/trimming, supporting Netflix's place in consumers' budgets."
Devitt's forecast for first-quarter domestic paid net new subscribers is 1.61 million, just ahead of the 1.6 million consensus (which tracks the company's guidance). Internationally, he's looking for 7.35 million new paid subscribers, also a bit ahead of guidance and the consensus.
At Imperial Capital, analyst David Miller has an Outperform rating and a $463 price target on the company's stock. He expects first-quarter net subscriber additions of 8.81 million, with 1.63 million of those domestic.
"Original series The Protector, Baby and Bodyguard [are] serving as core catalysts," Miller wrote Tuesday. "All [are] examples of overseas-produced series originally intended for specific territorial audiences, but that also have found an outside of those territories, including the U.S."
Email David Marino-Nachison at firstname.lastname@example.com. Follow him at @marinonachison and follow Barron's Next at @barronsnext.


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The navigation service from Avis Malta provides you with the best portable in-car navigation. Just choose your destination address, and let the Avis Malta GPS do the rest, directing you with clear turn-by-turn instructions.We have all experienced getting lost in a foreign country. Make this a thing of the past with our GPS to help guide you through your holiday destination without the trouble!
We've even pre-programmed the Avis Malta GPS with all the local places of interest in order to allow you the best possible use of your time and to discover the beautiful Islands of Malta and Gozo at your leisure.
How to book your Avis Malta GPS
The Avis Malta GPS can be reserved during your booking process by ticking the GPS request box which is located on the right hand side of the booking engine under Optional Accessories.
Alternatviely you may reserve a GPS via our call centre or add to an existing reservation by calling +356 25677 114 or by sending us an email on email@example.com.
Avis Malta's GPS price is €11.00 (incl VAT) per day and only charged for the first 10 days of the rental.
Terms of GPS rentals
Avis GPS is available at all Avis locations within Malta and Gozo.


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Playstation Network Scheduled Maintenance Occuring Today
If you can't connect to the Playstation Network today, don't worry. There's nothing wrong with your PS3 or internet. Sony informed us today via their Playstation Blog that there will be network maintenance happening today from about 8am to 11pm.
PlayStation Network is scheduled to undergo routine maintenance tomorrow, August 11th, from about 8am until approximately 7pm Pacific Time. During this time, registration and Account Management will be inaccessible, including the password reset process. While some users may experience difficulty signing into PSN and the PlayStation Store, the majority of users will be able to play online as well as sign in to external sites that require PSN authentication.
If you want any updates on the maintenance follow the Playstation Twitter Feed and stay informed. Like stated above, most of you will not experience many issues at all so you probably won't even notice that the maintenance is going on.


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thank you a great scan! for my pc
Studio Pierrot Studio Naruto Series Obito Uchiha Character Stick Poster Source
From Naruto Chara Pos 2.
While it's very easy to print these off, please buy your own set! I can refer you to very good retailers if interested. =)
More Naruto Scans
Browse Naruto Gallery: Recent | Popular.
Evita Feb 05, 2014
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President Donald Trump tweeted Sunday morning that "Bernie Sanders was cut off" of CNN "for using the term fake news to describe the network" — but CNN quickly responded that Sanders had used the term jokingly, and that he had not been cut off.
"They said technical difficulties!" Trump tweeted.
In the interview, Sanders had been responding to a video clip of Trump saying that he had not heard reports that national security adviser Michael Flynn had spoken with Russia about sanctions before the inauguration.
Anchor Erin Burnett asked Sanders if he thought it was a "problem" that Trump was not familiar with the reports.
Sanders responded: "Well, I don't know. Maybe he was watching CNN fake news. What do you think?"
Before the feed cut out and the network broke for commercials, Sanders said, "That was a joke." In response, Burnett said, "I know it was a joke."
CNN responded to Trump's tweet with a transcript of the interview.
@realDonaldTrump False. Transcript from @ErinBurnett intvu w @SenSanders. He was not cut off. Those are the facts. https://t.co/NzJNgdYSIX pic.twitter.com/AOFKLHUlGk
— CNN Communications (@CNNPR) February 12, 2017
From Michael Briggs, Senator Sanders' Communications Director: "The Senator was clearly joking" https://t.co/OzMj8pkTlv
— Jake Tapper (@jaketapper) February 12, 2017
Untrue. Sanders was *criticising Trump* for calling CNN "fake news." You can see for yourself, all 11 minutes, here: https://t.co/qhtlb5Wo6Q https://t.co/AcwOiNHi0j
— Brian Stelter (@brianstelter) February 12, 2017
NOW WATCH: Merriam-Webster can't stop trolling the Trump administration on Twitter
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If you are ordering a sign that requires graphic design work, please remember to send us your digital artwork.
What to Expect
Fast ServiceNeed a last minute sign change? Have an urgent printing project? No problem! We are here to help!
Easy OrderingOrder online, over the phone, via email, fax or in person. How could we forget about Facebook @AccelerateSigns!
Customer ServiceGreat customer service is our #1 priority!
Need a temporary sign? Accelerate Signs got me one within 1/2 hour!
Devon Wigglesworth Patch Java Coffee House
Thanks so much for doing our sign so quickly! We love it!
Waneta Henderson Peace Country DeLite


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It's a Play Date!
With the obvious signs that Nintendo is finally laying the 3DS line to rest, a hero emerges! Panic, a company known for highly regarded iOS games and Mac applications is […]
With the obvious signs that Nintendo is finally laying the 3DS line to rest, a hero emerges! Panic, a company known for highly regarded iOS games and Mac applications is […]
With the obvious signs that Nintendo is finally laying the 3DS line to rest, a hero emerges! Panic, a company known for highly regarded iOS games and Mac applications is making a handheld system. The Play Date is monochromatic, features a d pad, two buttons and a manual hand crank. It cetainly is very reminiscent of the original Gameboy and I for one am very excited.
Not much is known about the system, but we at Nerd Jock Blog will certainly keep you up to date. In the meantime, check out the official press release here:
Portland, OR — May 22, 2019 — After more than 20 years of making quality apps for Mac and iOS, Panic was, frankly, ready to try something new. Our first attempt: jumping into videogame publishing with Firewatch in 2016 and Untitled Goose Game later this year. That's felt great. But we wondered: what if Panic tried something really different?
Today, after more than four years of work by a small and talented team, Panic is extremely excited to introduce Playdate, a brand new handheld gaming system.
Playdate is both very familiar, and totally new. It's yellow, and fits perfectly in a pocket. It has a black-and-white screen with high reflectivity, a crystal-clear image, and no backlight. And of course, it has Wi-Fi, Bluetooth, USB-C, and a headphone jack. But it also has a crank. Yes, a crank: a cute, rotating analog controller that flips out from the side. It's literally revolutionary.
There's more: Playdate includes games — a full season of them. The games will be delivered over-the-air, once a week for 12 weeks, and they'll be a surprise: when the new game light flashes, you'll never know what you're about to play. Panic recruited some of the world's best game designers — some well known; others under the radar — to make games exclusively for our system. Playdate isn't just hardware: it's a complete experience.
Today, Panic is revealing one of these original Playdate games: Crankin's Time Travel Adventure, from Keita Takahashi, the creator of Namco's Katamari Damacy. This game uses the crank exclusively to control the flow of time, backwards and forwards. Your goal? Get Crankin' to his date with Crankette while avoiding an ever-increasing series of ridiculous obstacles — obstacles that aren't affected by the time control. Will Crankin' make it to his rendezvous on-time? (Spoiler alert: no)
Panic built every part of Playdate from scratch, starting with early board designs (using the hotplate in our kitchen to flow solder), our own Playdate OS, a full-featured SDK supporting C and Lua development, a Mac-based simulator and debugger, and more.
We then brought Playdate to one of our favorite companies on the planet — Teenage Engineering, the Stockholm-based creator of synthesizers and so much more — to begin a cross-company collaboration, designing and engineering Playdate's look. They came up with the crank!
Playdate will be revealed to the public on the cover of Edgemagazine issue #333, hitting the newsstands in the UK and available for online purchase on May 23rd. Covering "The Future of Interactive Entertainment", Edge has a rich history of celebrating the best of the gaming medium, and will offer an in-depth look at the creation of Playdate, including interviews with some of the developers.
Playdate will ship in early 2020, with pre-orders anticipated in late 2019 for US $149.
More information can be found on the official site at https://play.date, where users wanting to be first in line for a Playdate can sign up for our mailing list.
(We'll have limited stock and will e-mail people in the order they sign up, so we recommend people sign up early, of course.)
Twitter users can follow the device's progress @playdate.
Thank you for reading about Playdate. We can't believe this is happening either. But we couldn't be more excited.
Support Nerd Jock Blog and visit our store.
Like what you've read? Want more? Check out our Youtube channel here: Nerd Jock Blog Youtube
Follow us on Twitter: @NerdJockBlog33


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Maintaining a commercial building comes with many challenges, and energy usually is one of the top issues. Commercial buildings with multiple tenants may have particular issues with supplying energy and saving money at the same time. Here are several useful tips that will help commercial building owners better manage energy costs:
Upgrade the Lighting
One of the common reasons why commercial buildings have to spend a lot on energy is because of out-dated lighting systems. Buildings that continue to use old incandescent bulbs instead of switching to more modern LED bulbs will naturally have to spend more money on energy. Therefore, building owners should start by improving and replacing old lights to save up on energy costs.
Commercial buildings can certainly benefit from the latest business-specific lights. For example, ceramic metal halide lamps are perfect for illuminating displays, retail shops, and office lounges without overspending on energy. Fluorescent lights without the ballasts are highly recommended for lighting offices. Not only do fluorescent lights cast a bright light, these bulbs are also long lasting.
Choose the best type of light fixture and bulb depending on the area inside the commercial building. Use the latest technology to limit energy waste and save up on energy costs.
Switch to Solar Energy
Using solar energy to power up a commercial building can seem like a complicated, expensive, and daunting task. While installation can be complicated, solar energy offers many cost-saving benefits for commercial buildings. For starters, buildings with multiple tenants can benefit from embedded networks and solar, where separate meters can be installed to monitor energy consumption by different tenants.
Buildings that are self-sufficient in solar pay for itself. Surplus power directed to the grid can become eligible for government-provided feed-in tariffs. Businesses can additionally benefit from the financial incentives Australian states offer for using renewable energy in commercial settings. All in all, commercial building owners can save money in more ways than one by switching to solar energy.
Implement Thermal Energy Load Shifting to Reduce HVAC Costs
The air conditioning costs for commercial buildings are typically hefty. Owners or landlords can certainly reduce these costs by using what's called thermal energy load shifting. It's a system where the equipment makes ice or cold water when electricity demand periods are low. The system stores this chilled water, which reduces operating costs when cooling a building using an HVAC system. In the U.S., where the system is recommended to be implemented, studies have shown thermal energy storage to save HVAC operating costs up to 60 percent.
Run a Power Factor Correction
The power factor refers to the RPM of a motor with relation to voltage used. Most commercial entities have motors running during all hours, which leave the door open for energy waste. With power factor correction, commercial buildings run an engineering studies to evaluate whether motors inside the building, such as in HVAC systems, are over-consuming power. If so, a course correction is performed to save excess energy costs.
Use the above suggestions to control energy expenditure at your commercial building. Don't let any equipment inside to overuse energy. It's highly recommended to run a consultant evaluation to determine which areas demand the most attention when it comes to energy consumption inside the building.


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Minister of Interior, Abdulrahman Dambazau will on Monday officially launch the new Immigration Regulations.
Sunday James, the spokesperson for the Nigeria Immigration Service (NIS) disclosed this in an interview with the News Agency of Nigeria on Saturday in Abuja.
"The honourable Minister of Interior, Lt.-Gen. Abdulrahman Dambazau, (retired) will officially present the Immigration Regulations 2017 to the public on Monday, March, 20, 2017.
"The Immigration Regulations 2017 is a vital document that operationalises the Immigration Act 2015 and provides the legal framework for the effective implementation of the Act," he said.
He said the new immigration regulation was a result of deliberations with legal and migratory experts.
James expressed optimism that the document, if properly implemented, would go a long way in transforming the operations of NIS in line with international best practices.


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Boys Varsity Wrestling · Wrestling Parent Meeting
There will be a wrestling parent meeting the night of Open House which is Aug. 22. The meeting will start at 7:00pm and be located in the high school library. This meeting is for parents of 8th-12th grade students who are wrestling for Eagleville School. If you have any questions please contact Coach Wilson at


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Let's get to bottom of Gavin Watson crash
The appointment of accident reconstruction expert Konrad Lotter to investigate the crash that took the life of Gavin Watson, controversial CEO of the equally controversial company African Global Operations, would hopefully, in the long run, result in certainty over what caused the accident.
There is too much speculation, some of it really dangerous, going on about what may have killed the boss of a company that was previously known as Bosasa.
His death came at a time when he was at the centre of allegations that, for years, his company bought favours with ANC and government leaders which resulted in Bosasa benefitting handsomely from state contracts and in industries that are regulated by the state.
There were claims, made by his one-time close associate and former Bosasa chief operations officer Angelo Agrizzi, that former president Jacob Zuma's associates and ministers benefitted directly from this alleged corruption.
Furthermore, Watson's donation of R500,000 into CR17 - the campaign that propelled Cyril Ramaphosa into the presidency - caused public protector Busi Mkhwebane to start a probe into the president and what he knew about the sources of the funding.
It is therefore not surprising that, in the absence of answers to how the crash happened, people would speculate.
But we must caution against people spreading baseless rumours about who may have "killed" him or the "motives" for the crash.
Lest we forget, South Africa was in a similar space in 2005 when ANC benefactor and troubled businessman Brett Kebble was killed in a shooting.
Back then the immediate suspicion fell on political players, with factions within the ruling party pointing fingers at each other. As it later transpired, none of them were involved and the reasons for Kebble's "assisted suicide" hardly had anything to do with them.
We do not know the full facts of the Watson incident. But what we know is that tensions are high in the country currently and that, under such an environment, making wild claims about who may have "killed" him and why they may have done so, is tantamount to shouting "fire!" in a crowded theatre.
It can only have disastrous results.


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Inexpensive Car Insurance
We'll pay the worth that we agreed when you took out or last renewed your insurance policy, rather than the marketplace worth. Suppose the expense of the auto you are planning to buy is Rs. 5,00,000(5L) and you are availing a loan of Rs. 1, 00,000(1L). You could either approach your insurer's office for the very same or, if you have procured the car insurance on the internet, print-out the soft-copy of the policy that was forwarded to you. Presently, the excise duty that a tiny vehicle (much less than 4 metres long) attracts is 12.5%. The subsequent segment of vehicles (length of 4 metres) is charged 24% excise tax. If it is a minor harm that does not demand police intervention, move the car to a secure place & inform the insurer. Take a look at our price index calculator to get an estimated cost on your car insurance.
Some insurance companies offer you the cashless facility if the car is repaired at their authorized garages. This scope pays for genuine or lasting damage or demise to other individuals when you trigger an accident with your automobile. Practically all car insurance firms in India give their buyers the option to renew their policies on the internet, through straightforward net banking transactions, or the secure usage of credit/debit cards. In such cases, the impacted celebration is most likely to push you for damages/compensation and the identical will be serviced by the applicable third party liability insurance. Renew On the web- If acquiring car insurance on the internet was effortless, periodically renewing the identical is simpler.
The group are usually attempting to make it even less complicated to compare your very best prices and decrease the price tag of your insurance. This is an annual increase of a staggering £109 on drivers' premiums, generating it more important than ever to shop around and compare prices. Moreover, if we have in thoughts what we are shopping for we would not waste our time checking out anything else, so with your car insurance, it should be the identical way concentrate only on the type of insurance coverage plan you have in mind.
If you produced the selection to search for new vehicle insurance coverage rates every few years you'd finish track of a considerably greater deal in your insurance than you'd have skilled below other circumstances. The Golden State is property to more than 23.6 million licensed drivers who are all required to acquire a minimum quantity of automobile insurance coverage to legally drive. And given that these businesses are actually out on the web rather than holed in their higher towers it is basic to gather massive amounts of quotes.
To get the low-cost car insurance California automobile owners usually search for, drivers will have to sample a number of policy costs. When you know all you require to know, you can put in your info above and we'll get you began filing a quote. Examine- Diverse organizations, diverse car insurance merchandise, and hidden somewhere in this pile is your perfect motor insurance policy. The car insurance package from Reliance, 1 of India's iconic conglomerates, is tuned to be highly consumer oriented, hassle cost-free and reputable. In today's quickly paced planet, receiving things completed on-line is practically nothing brief of a divine boon. No wonder, when it comes to Bharti AXA car insurance review, there are cheers everywhere!


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Hello Again
Home › Forums › The Lounge › Hello Again
- This topic has 0 replies, 1 voice, and was last updated 9 years, 4 months ago by dunc.
June 22, 2011 at 7:35 pm #301519
Hello all! Hope your all doing well! /sad.gif" style="vertical-align:middle" emoid=":(" border="0″ alt="sad.gif" /> All within a very short time) Strangely, Non of the Acanthocobitis Zoonalternans caught this disease.
Then last December, my heater malfunctioned and took the tank to 40*C killing my Acanthocobitis, this included the ones that i bred, absolutely gutted, these loaches had developed into one of my favourites. /smile.gif" style="vertical-align:middle" emoid=":)" border="0″ alt="smile.gif" />
Plus, in the larger tub, i put some plants in there from the pond, and the two goldfish that are left, male and female, i now have a few goldfish fry growing in the tub. /smile.gif" style="vertical-align:middle" emoid=":)" border="0″ alt="smile.gif" />
RIPJune 22, 2011 at 10:24 pm #344260
Thanks muchly for the nice words and good to know you're back into it David – wondered where you'd gone!
You still have the A. vladykovi then?June 23, 2011 at 12:23 pm #344272
Nice to see you back mateJune 23, 2011 at 3:32 pm #344280
Welcome back David!June 23, 2011 at 5:09 pm #344282
Welcome back!June 25, 2011 at 8:59 pm #344338
Brilliant news, welcome back SirAuthorPostsViewing 6 posts - 1 through 6 (of 6 total)
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This machine is suitable for slitting various roll materials of Fabric PET, BOPP, CPP, PE, PVC, aluminum foil and paper. It is the ideal equipment for paper making, plastic, printing and packaging industry.
Main Features:
1. Main motor with VFD
2. Automatic tension controlling system.
3. EPC with servo motor
4. The slitting adopts flat and circular blade.
5. Waste edge automatic blowing device and automatic meter counter.


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If you want to see everything Sedona has to offer, there is no better way to do so from behind the wheel of a rental car from Hertz. Stop spending your vacation waiting on the bus, or being nickel and dimed with ride-shares or taxis. Having your own car enables you to go to the places you want to see the most, whenever you want. Make your next getaway to Arizona even more enjoyable with a Hertz car rental.
Sedona is a perfect spot when you want some respite from busyness of a big city. Travelers come to check out Sedona's rich past that is a beacon for history buffs and Pleasant winters. Whatever you decide on first, you'll want to take in as much of Sedona as possible while on your vacation. If you need to mix it up from Sedona's easy-going vibes, then jump behind the wheel of your Hertz car rental and see what else is out there.
CarRentals.com works with some of the finest rental car dealers in the business. Hertz has over one hundred years of experience and a fleet including many of the most respected in the business, like Hyundai and Kia. With Hertz history and thousands of franchises globally, you know you'll be in great hands.
CarRentals.com strives to get you the lowest price, no matter when you book. However, reserving your car ahead of time can help you save even more. Be sure to check the mileage policy and keeping it to one driver will reduce your expense.
Make sure to bring credit card, as well as your driver's license.
Hertz's minimum age to rent a car in Sedona is 21. Some rentals, especially higher category vehicles (luxury, SUVs, etc.), may have an added fee if you are under 25. Make sure to review Hertz's policies to determine what the total cost is for you.
That all depends on your needs and what you'll be doing when you visit Sedona. Compact or economy cars are easier to park and ideal for short drives. If you are traveling with coworkers, then a SUV or a sedan is going to have enough room for all of you and be a more comfortable ride on longer trips. Those looking for a little extravagance on their Sedona vacation can choose the premium category to get a car like a Cadillac or Audi or similar.
You are required to have insurance before you rent from Hertz in the United States. Although many of the major card issuers, like MasterCard or Visa, offer some coverage, there are usually restrictions. For instance, they may not cover your rental car if you book a larger or luxury vehicle. Make sure to check credit card company's policy before you decide. Otherwise, as a United States citizen, you can also book Collision Damage Coverage through CarRentals.com at checkout.
Hertz does require a deposit when you reserve your rental car. Hertz will block the deposit on your credit once you book your vehicle for your trip. Please be aware that the deposit will vary greatly based on the model and make of the vehicle.
We encourage a full to full policy. You receive the vehicle with a full tank, and you will want to refuel up to the amount you picked the car up with. If you want to save some money, it is best to fill up your tank before you return the car to Hertz.
Sedona's small-town atmosphere definitely is charming, however you may want to take to the road again after you've checked off all the activities in Sedona.
Hertz typically offers one-way rentals. You may find it more convenient to drop off your rental car at a different Hertz. Be aware there may be an additional fee when you pick one-way.
Once you've explored the must-see sights in Sedona, having access to an automobile will allow you to see what else Arizona offers. When you are ready to explore more of Arizona, you can drive when you want to, without trying to signal for a taxi or sign up for a ride-share.
Before your next family vacation, book your Hertz Sedona rental car and zip off to take in all the items on your itinerary at your leisure. Reserve with CarRentals.com and speed along the open road in Sedona, Arizona.


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This nutrient packed thick & creamy Rejuvenating Green Detox Smoothie will help get your body get back on track and feeling it's best.
Check out the video to see how easy it comes together!
A new year usually means new goals and resolutions, with most of them being health or fitness related. It is great to see how everyone is so dedicated to eating healthy and being active. While I don't think we need the new year to make healthy changes, it is good to start somewhere. I think being active and healthy is a lifestyle and something that is worked on continuously throughout the year. The new year is a great place to start though!
While I like to keep it healthy all year, the holidays are definitely a time of indulging. I find myself eating things I normally wouldn't and drinking alcohol a lot more frequently. After a week of my family being here, I am so ready to get back to my daily routines and eating habits.
That is where this smoothie comes in. There is something about green smoothies that makes me feel refreshed and rejuvenated. They are a great way to get in some greens early in the morning and get your body/digestion going. Sometimes smoothies are loaded with fruit though, which essentially translates to sugar. This spikes your blood sugar, causing it to fall fast, and making you feel tired and sluggish. I tried to pack this one with not a lot of fruit, healthy fats, and lots of nutrients.
Ginger helps stimulates digestion and boosts circulation. By boosting circulation, ginger helps a systemic cleansing through the skin, bowels, and kidneys. Lemon also aids digestion by stimulating the flow of saliva, thus easing the work of the liver. It also works as a diuretic and laxative. Both of these ingredients are great in the morning to get your digestion system revving for the day. It has avocado in it, which helps give a creamy texture and adds healthy fats that keep you full for longer. Chia seeds are packed with omega 3s, antioxidants, and fiber. The apple also adds fiber, which helps keep you full.
Post Workout Chocolate Protein Smoothie
Overall, this smoothie packs a nutritional punch in the morning or any time of day you need a pick me up. Give it a try to get back on track to your healthy lifestyle!
By the way, check out my first video!! I told you guys you would be getting more videos and here is the first one! Let me know what you think! The sound is on Instagram, but I am working out the kinks to get it on here!
Make sure to check out the video at the top of the page to see how easy this recipe comes together!
Rejuvenating Green Detox Smoothie
- 1 cup unsweetened almond milk
- juice from 1/2-1 lemon or lime, depending on taste
- 3 cups packed kale or spinach or 1 1/2 cups frozen spinach
- 1/3 of a large cucumber (100 grams)
- 1/2 large green apple (100 grams)
- 1/4 of a large avocado (50 grams, frozen*)
- 1 tablespoon chia seeds
- 1-2 inches fresh ginger, depending on taste
- Add all ingredients in the order listed to a Vitamix or high powered blender and blend until smooth.
- Enjoy as a smoothie or as a smoothie bowl with desired toppings!
This post was posted last year and updated this year with a video and photography!
This post may contain affiliate links and I may make little bit of money if you click on and purchase the products that are linked. It doesn't cost you any extra money. The compensation helps with expenses to keep ETG up and running. I truly appreciate your support!


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How To Sell A House Fast for Cash
Do you plan of selling your house? When you are selling your house, it can be time consuming as compared to what you see around you. Within your neighborhood, you may have noticed that some of the houses that have been sold for a short period of time but in reality, the buyer did not simply went to the property and then agreed to the price that the seller gave them and then bought the house. If you must know, sellers are actually undergo a lot of difficult situations for them to attract good buyers and then close the deal.
Finding a good buyer for your house is a very hard task. It is important that you advertise your property in a newspaper, independent local broker or the internet for you to get a good buyer. One of the important thing that you have to know is that when you sell your house with the help of a broker, it can be very costly due to the fact that you have to pay for the broker. The broker will help you find a buyer for your property but the problem is that since the broker wants to earn a quick money, both you and the buyer is not sure whether you will get a good price. Now that you have a potential buyer, the next difficult step is the negotiations. When you are able to have a successful negotiations, it would also mean that you will get a good deal when it comes to the price. When you employ the help of a broker, legal formalities and negotiations will be handled by you.
Worry no more, there are a lot of ways for you to sell your house that is quick and hassle free. What every sellers dream is to sell their house quickly. If you are able to sell your house easily, it would also mean that you can end your mortgage and you also have enough cash to start a clean slate. You have to first know how much is your property worth. Free estimateare available for your home. Getting a free valuation for your home will also save you a lot of money. You have to understand that any real estate agent can charge you a lot of money by simply valuing your home. Any cash property buyers, you can get free quotes and all you have to do is to fill out the detailed form on the website. With the help of these quotes, this will give you a better idea on how much is the price of your property.Sales – Getting Started & Next Steps


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Permanent makeup is essentially a tattoo that makes you appear as if you're always wearing makeup. In fact, the procedure is much like that of getting a tattoo – the technician applies the pigment with a needle, and eventually you may have to return for touch-up visits. During the consultation, you can select the shades of your permanent makeup, and the technician will sketch the areas on your skin to be pigmented.
Permanent Makeup Technicians
Permanent makeup technicians use a hollow needle that releases color into a hole in your skin. Although pigment is applied to the top layer of skin only, the procedure may still sting – just like it does when you get a tattoo. It takes about three weeks for the pigment to fade to the color you selected. Our artist
Permanent Makeup Services
Permanent makeup is also called micropigmentation or permanent cosmetics. The art of permanent makeup has become a specialized service within both the tattoo community and the cosmetic industry, and the field is growing as more technicians become available to treat a growing number of clients. Our Services
Permanent Makeup Online Consultation
To help you get the best out of your upcoming permanent makeup procedure(s), fill out our free online consultation form.


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Among the terrific, and maybe the greatest, advantage of our online reputation management services services is that of the material created in the job of restoring control of your online credibility will end up being useful properties to your public relations project, or might assist you to develop one if you have not currently begun.
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text: David1967 0 Posted August 14, 2019 Share Posted August 14, 2019 Hi, All, I'm using CCleaner to locate duplicate files on Windows 10. Great tool. However, I've got thousands of duplicates! I've manually selected and deleted around a hundred and it took forever. Is there a way--either through CCleaner or another way--to select the files for me? Otherwise this will take weeks! Thanks in advance! Link to post Share on other sites


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The Nature and Scope of Spinoza's "One and the Same" Relation
I argue that we should rethink the nature and scope of Spinoza's "one and the same" relation (E2p7s). Contrary to the standard reading, the nature of this relation is not identity but a union, and its scope includes all idea-object pairs, even God and the idea of God. A crucial reason we should adopt this dual picture is that the idea of God must be one and the same as something found when Nature is conceived under each of the other attributes. If "one and the same" is interpreted as a relation of identity, this requirement cannot be met. However, maintaining that God and the idea of God are one and the same not only fulfills this requirement, but also is independently motivated. I also briefly consider how the thesis that God and the idea of God are one and the same affords us with positive insights concerning the nature of this relation.


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Continuously deploying my PowerShell Modules
Continuously building and deploying new versions of my modules to internal repositories (or PowerShell Gallery) is something I really like. That way I can just push my code and let the automation handle the rest. Here are some learnings I've made. Deploy on tag Firstly, I usually only trigger a deploy-workflow on tags, this way I can manually decide when to do a release and what version it will have without relying on any complex methods.


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Price: $5.00
Quantity: 1 available
Book Condition: Good
Softcover, First Edition, 225gms, 112 pages. Bush Basics, Preparing to go Bush, in the Bush, Surviving in the Bush, Cooking in the Bush, Bush Gear, Bush Walking and Bush Tips, this provides all the information you need to stay safe and survive in the bush. Book is in good condition with minor general wear and tear and mild page discolouration throughout, otherwise no other pre-loved markings.
Title: Going Bush
Categories: Travel/Exploration,
Edition: First Edition
Publisher: Kensington, Australia, Bay Books Pty Ltd:
ISBN Number: 1862564159
ISBN Number 13: 9781862564152
Binding: Soft Cover
Book Condition: Good
Jacket Condition: Not Applicable
Size: 4to - over 9¾" - 12" tall
Item: 1.00 Item
Seller ID: TRAAUS10
Keywords: BUSH BASICS; PREPARING TO GO BUSH; IN THE SURVIVING COOKING GEAR; WALKING; TIPS,