Sub-threshold Operation of a Timing Error Detection Latch

Ajoitusvirheentunnistus (TED) mahdollistaa energian kulutuksen vähentämisen mikroprosessoreissa. Tässä diplomityössä on kaksi versiota ajoitusvirheentunnistavasta salvasta (esim. TDTBsubI ja TDTBsubII) ja systeemitason testipiiri (SystemTest), joka käyttää TDTBsub salpaa, mikä on suunniteltu toimimaan kynnysalueen alapuolella. Diplomityö esittelee ensin dynaamisen jännitteen skaalauksen (DVS), koska TED käytetään sellaisissa järjestelmissä. Seuraavaksi esitellään teoriaa kynnysalueen alapuolen suunnittelun haasteista. Sitten esitellään molempien TDTBsub salpojen ja SystemTest-lohkojen suunnittelu. Simulaatiotuloksia esitellään keskittyen operaatiotaajuuteen, energian kulutukseen ja toimintavarmuuteen variaatiot huomioon ottaen. Operoitaessa kynnysalueen alapuolella TDTB-piirillä keskityttiin koon mitoittamiseen ja suunnittelutyyliin. Ennen kaikkea kaikkien komponenttien mitoituksen piti olla suurempi kuin minimi CMOS-tekniikan leveydet. Vaikka mitoittamisella saavutettiin toimintavarmuutta kynnysalueen alapuolella toimittaessa myös energian kulutus kasvoi siellä toimittaessa. Perinteisiä vuotovirtojen vähentäviä mitoitustoimenpiteitä tehtiin suurimmalle osalle komponenteista. Logiikkatyyli on tärkeää kynnysalueen alapuolella operoitaessa. TDTBsubII salvassa uuden tekniikan näytetään antavan systeemitason suorituskykyä. Simulaatioilla näytettiin kuinka ajoitusvirheentunnistus kykeni toimimaan kynnystason alapuolella. TDTBsubI:n ja yhteenlaskun testipiirin piirinkuvio tehtiin 65nm CMOS-prosessilla. TDTBsubII salpaa ei tehty, koska se suunniteltiin piirin määräajan jälkeen. Piiriä tarkasteltaessa osoittautui, että piiri ei toiminut. Piirin toimimattomuus johtui tuotantovaiheessa tapahtuneesta virheestä eikä suunnittelusta.Timing error detection (TED) is used to enable the reduction the energy consumption of microprocessors. In this thesis work, two versions of TED latches (i.e. TDTBsubI and TDTBsubII) and a system-level test circuit (SystemTest) that utilizes the TDTBsubI latch have been designed to operate in sub-threshold. The thesis first introduces dynamic voltage scaling (DVS) since TED is utilized with such a system. Next, theory is given to highlight the challenges within sub-threshold. The design of the both TDTBsub latches and SystemTest are then given. Simulation results follow with a focus on operation frequency, energy consumption, and robustness in the presence of variations. To operate TDTBsub into sub-threshold, attention was given to sizing and logic style. In general, the sizing of all components was required to be larger than the minimum CMOS width. Although this provided robustness in sub-threshold, the energy consumption in above sub-threshold was much higher. General leakage reduction sizing techniques were also applied to the majority of components. The choice of logic style is important for sub-threshold operation. In the TDTBsubII latch, a new technique is shown to provide system-level capability. Simulations displayed the capability of TED in sub-threshold. The layout of TDTBsubI and an adder test circuit were constructed in 65 nm CMOS. The TDTBsubII latch was not built since it was designed after the chip deadline. Upon inspection of the chip, it was determined to be inoperative. This mistake was a result of the manufacturering process and not the design in this work

Validity of neonatal POC glucose testing

Background: Glucose monitoring a common invasive intervention in newborn period •most commonly obtained laboratory value Appropriate identification of hypoglycemia is critical: •Severe hypoglycemia can lead to neurologic insult •Cerebral palsy, developmental delay, seizures, deat

Fresh Fruits and Vegetables Really Do Keep the Doctor Away: Symptomatic Vitamin Deficiency in a Middle Aged Man

Introduction We present a clinical case of symptomatic vitamin deficiency typically seen only in resource limited environments or alcoholics, presenting in an adult male with frequent oral intake, but limited diet of prepared foods, as well as co-occurring pernicious anemia. Clinical Findings The patient presented with complaints of ascending paresthesia leading to near syncope, lower extremity edema and hyperpigmentation on his anterior legs bilaterally which had been present for years. Diagnosis and interventions He was found to have mixed B12, thiamine, and folate deficiency. These were attributed to a combination of nutritional deficiency due to a diet of exclusively cooked foods, and pernicious anemia. He was treated with parenteral and oral vitamin supplementation and noted to improve, but was lost to follow up. Conclusion This case highlights the importance of social and nutritional history in health maintenance, as well as the clinical significance of prolonged mixed vitamin deficiency

Swine influenza A virus: challenges and novel vaccine strategies

Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination strategies are often not updated frequently enough to address the continuously evolving nature of IAV-S, fail to induce broadly cross-reactive responses, are susceptible to interference, may enhance respiratory disease, and can be expensive to produce. Here, we review the challenges and current status of universal IAV-S vaccine research. We also detail the current standard of licensed vaccines and their limitations in the field. Finally, we review recently described novel vaccines and vaccine platforms that may improve upon current methods of IAV-S control

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection against H2 Influenza a Virus

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the utility of serotype-switching to enhance the protective immune responses seen with homologous prime-boosting strategies. Immunization with an H2 centralized consensus showed a wide breadth of antibody responses after vaccination, protection against challenge with a divergent human H2 strain, and significantly reduced viral load in the lungs after challenge. Further, serotype switching between two species C adenoviruses enhanced protective antibody titers after heterologous boosting. These data support the notion that an adenoviral-vectored H2 centralized consensus vaccine has the ability to provide broadly cross-reactive immune responses to protect against divergent strains of H2 influenza and prepare for a possible pandemic

A fully integrated 2:1 self-oscillating switched-capacitor DC-DC converter in 28 nm UTBB FD-SOI

The importance of energy-constrained processors continues to grow especially for ultra-portable sensor-based platforms for the Internet-of-Things (IoT). Processors for these IoT applications primarily operate at near-threshold (NT) voltages and have multiple power modes. Achieving high conversion efficiency within the DC–DC converter that supplies these processors is critical since energy consumption of the DC–DC/processor system is proportional to the DC–DC converter efficiency. The DC–DC converter must maintain high efficiency over a large load range generated from the multiple power modes of the processor. This paper presents a fully integrated step-down self-oscillating switched-capacitor DC–DC converter that is capable of meeting these challenges. The area of the converter is 0.0104 mm2 and is designed in 28 nm ultra-thin body and buried oxide fully-depleted SOI (UTBB FD-SOI). Back-gate biasing within FD-SOI is utilized to increase the load power range of the converter. With an input of 1 V and output of 460 mV, measurements of the converter show a minimum efficiency of 75% for 79 nW to 200 µW loads. Measurements with an off-chip NT processor load show efficiency up to 86%. The converter’s large load power range and high efficiency make it an excellent fit for energy-constrained processors.</p

Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research

Multivalent Epigraph Hemagglutinin Vaccine Protects against Influenza B Virus in Mice

Influenza B virus is a respiratory pathogen that contributes to seasonal epidemics, accounts for approximately 25% of global influenza infections, and can induce severe disease in young children. While vaccination is the most commonly used method of preventing influenza infections, current vaccines only induce strain-specific responses and have suboptimal efficacy when mismatched from circulating strains. Further, two influenza B virus lineages have been described, B/Yamagatalike and B/Victoria-like, and the limited cross-reactivity between the two lineages provides an additional barrier in developing a universal influenza B virus vaccine. Here, we report a novel multivalent vaccine using computationally designed Epigraph hemagglutinin proteins targeting both the B/Yamagata-like and B/Victoria-like lineages. When compared to the quadrivalent commercial vaccine, the Epigraph vaccine demonstrated increased breadth of neutralizing antibody and T cell responses. After lethal heterologous influenza B virus challenge, mice immunized with the Epigraph vaccine were completely protected against both weight loss and mortality. The superior cross-reactive immunity conferred by the Epigraph vaccine immunogens supports their continued investigation as a universal influenza B virus vaccine

Adenoviral-vectored epigraph vaccine elicits robust, durable, and protective immunity against H3 influenza A virus in swine

Current methods of vaccination against swine Influenza A Virus (IAV-S) in pigs are infrequently updated, induce strain-specific responses, and have a limited duration of protection. Here, we characterize the onset and duration of adaptive immune responses after vaccination with an adenoviral-vectored Epigraph vaccine. In this longitudinal study we observed robust and durable antibody responses that remained above protective titers six months after vaccination. We further identified stable levels of antigen-specific T cell responses that remained detectable in the absence of antigen stimulation. Antibody isotyping revealed robust class switching from IgM to IgG induced by Epigraph vaccination, while the commercial comparator vaccine failed to induce strong antibody class switching. Swine were challenged six months after initial vaccination, and Epigraph-vaccinated animals demonstrated significant protection from microscopic lesion development in the trachea and lungs, reduced duration of viral shedding, lower presence of infectious virus and viral antigens in the lungs, and significant recall of antigen-specific T cell responses following challenge. The results obtained from this study are useful in determining the kinetics of adaptive immune responses after vaccination with adjuvanted whole inactivated virus vaccines compared to adenoviral vectored vaccines and contribute to the continued efforts of creating a universal IAVS vaccine

A robust ultra-low voltage CPU utilizing timing-error prevention

To minimize energy consumption of a digital circuit, logic can be operated at sub- or near-threshold voltage. Operation at this region is challenging due to device and environment variations, and resulting performance may not be adequate to all applications. This article presents two variants of a 32-bit RISC CPU targeted for near-threshold voltage. Both CPUs are placed on the same die and manufactured in 28 nm CMOS process. They employ timing-error prevention with clock stretching to enable operation with minimal safety margins while maximizing performance and energy efficiency at a given operating point. Measurements show minimum energy of 3.15 pJ/cyc at 400 mV, which corresponds to 39% energy saving compared to operation based on static signoff timing.</p