gebhart/patrepeval huggingface dataset:
Novel dominant KATP channel mutations in infants with congenital hyperinsulinism: Validation by in vitro expression studies and in vivo carrier phenotyping (2019)

Inactivating mutations in the genes encoding the two subunits of the pancreatic beta-cell K<sub>ATP</sub> channel, ABCC8 and KCNJ11, are the most common finding in children with congenital hyperinsulinism (HI). Interpreting novel missense variants in these genes is problematic, because they can be either dominant or recessive mutations, benign polymorphisms, or diabetes mutations. This report describes six novel missense variants in ABCC8 and KCNJ11 that were identified in 11 probands with congenital HI. One of the three ABCC8 mutations (p.Ala1458Thr) and all three KCNJ11 mutations were associated with responsiveness to diazoxide. Sixteen family members carried the ABCC8 or KCNJ11 mutations; only two had hypoglycemia detected at birth and four others reported symptoms of hypoglycemia. Phenotype testing of seven adult mutation carriers revealed abnormal protein-induced hypoglycemia in all; fasting hypoketotic hypoglycemia was demonstrated in four of the seven. All of six mutations were confirmed to cause dominant pathogenic defects based on in vitro expression studies in COSm6 cells demonstrating normal trafficking, but reduced responses to MgADP and diazoxide. These results indicate a combination of in vitro and in vivo phenotype tests can be used to differentiate dominant from recessive K<sub>ATP</sub> channel HI mutations and personalize management of children with congenital HI.
Complement-dependent Clearance of Apoptotic Cells by Human Macrophages (1998)

Apoptotic cells are rapidly engulfed by phagocytes, but the receptors and ligands responsible for this phenomenon are incompletely characterized. Previously described receptors on blood- derived macrophages have been characterized in the absence of serum and show a relatively low uptake of apoptotic cells. Addition of serum to the phagocytosis assays increased the uptake of apoptotic cells by more than threefold. The serum factors responsible for enhanced uptake were identified as complement components that required activation of both the classical pathway and alternative pathway amplification loop. Exposure of phosphatidylserine on the apoptotic cell surface was partially responsible for complement activation and resulted in coating the apoptotic cell surface with C3bi. In the presence of serum, the macrophage receptors for C3bi, CR3 (CD11b/CD18) and CR4 (CD11c/CD18), were significantly more efficient in the uptake of apoptotic cells compared with previously described receptors implicated in clearance. Complement activation is likely to be required for efficient uptake of apoptotic cells within the systemic circulation, and early component deficiencies could predispose to systemic autoimmunity by enhanced exposure to and/or aberrant deposition of apoptotic cells.
Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection (2017)

Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).
Innovative pain therapy with a fixed combination of prolonged-release oxycodone/naloxone: a large observational study under conditions of daily practice (2010)

PR oxycodone/PR naloxone achieved good pain control and significantly reduced constipation and associated opioid-induced gastrointestinal symptoms in this observational 4-weeks-trial.
An update on vaccines against Shigella (2013)

Despite intensive research efforts for more than 60 years, utilizing diverse vaccine strategies, a safe and efficacious vaccine against shigellosis is not available yet. We are currently witnessing innovative approaches based on elucidation of the virulence mechanisms of Shigella, understanding the immune response to the pathogen and progress in molecular technology for developing Shigella vaccines. It is hoped that these will lead to a licensed effective Shigella vaccine to protect humans against the significant worldwide morbidity and mortality caused by this microorganism.
Emerging Technologies for Pulmonary Vein Isolation (2020)

Atrial fibrillation is the most common sustained cardiac arrhythmia and is associated with considerable morbidity and mortality. Electrically isolating the pulmonary veins from the left atrium by catheter ablation is superior to antiarrhythmic drug therapy for maintaining sinus rhythm, but its success varies depending on multiple factors, including arrhythmic burden. Although procedural outcomes have improved over the years, further gains are limited by a seemingly zero-sum relationship between effectiveness and safety, which is largely a product of the available technologies. Current energies used to create contiguous, transmural, and durable atrial lesions can result in serious complications if they reach the esophagus or phrenic nerve, for instance-structures that can be adjacent to the atrial myocardium, often within millimeters of the energy source. Consequently, high rates of pulmonary vein-left atrium reconnections are consistently seen in clinical studies and in clinical practice as operators appropriately forgo ablation effectiveness to protect patients from harm. However, as ablative technologies evolve to circumvent this stalemate, safer, and more effective pulmonary vein isolation seems increasingly realistic. Furthermore, the innovative nature of these technologies raises the prospect of markedly improved procedural efficiency, which could increase patient comfort, reduce operator occupational injuries, and enhance the use of health resources-all of which are increasingly important considerations particularly as the demand for catheter ablation for atrial fibrillation continues to rise. We herein review 3 promising candidate ablation technologies with the potential to revolutionize the management of patients with atrial fibrillation: electroporation (pulsed-field ablation), expandable lattice-tip radiofrequency ablation/electroporation, and ultra-low temperature cryoablation.
Vortex Rings in Bio-Inspired and Biological Jet Propulsion (2008)

Pulsed-jets are commonly used for aquatic propulsion, such as squid and jellyfish locomotion. The sudden ejection of a jet with each pulse engenders the formation of a vortex ring through the roll-up of the jet shear layer. If the pulse is too long, the vortex ring will stop forming and the remainder of the pulse is ejected as a trailing jet. Recent results from mechanical pulsedjets have demonstrated that vortex rings lead to thrust augmentation through the acceleration of additional ambient fluid. This benefit is most pronounced for short pulses without trailing jets. Simulating vehicle motion by introducing background co-flow surrounding the jet has shown that vortex ring formation can be interrupted, but only if the co-flow is sufficiently fast. Recent in situ measurements on squid have captured vortical flows similar to those observed in the laboratory, suggesting thrust augmentation may play a role in their swimming performance. Likewise, recent measurements with a mechanical self-propelled pulsed-jet vehicle (“robosquid”) have shown a cruise-speed advantage obtained by pulsing.
A Critical Review of the Preetham Skylight Model (2007)

The Preetham skylight model is currently one of the most widely used analytic models of skylight luminance&#13;\nin computer graphics. Despite its widespread use, very little work has been carried out to verify&#13;\nthe results generated by the model, both in terms of the luminance patterns it generates, and in terms of&#13;\nnumerical reliability and stability.&#13;\nIn this paper, we show where the model exhibits problematic behaviour, and compare the computed luminance&#13;\nvalues with the CIE 2003 Standard General Sky, and our own measurements of real, cloudless skies.
Biosynthesis of N‐Acetylneuraminic Acid in Morris Hepatomas (1973)

The biosynthesis of N ‐acetylneuraminic acid was studied in liver, neonatal liver, regenerating liver and Morris hepatomas 7777, 5123 TC, 5123 C, 5123 D, 7800, 7795, 9121 and 9618 A. The following three parameters were investigated: the biosynthesis of N ‐acetylneuraminic acid from d ‐[1‐ 14 C]glucosamine and d ‐ N ‐acetyl‐[U‐ 14 C]mannosamine; the content of free and protein bound N ‐acetylneuraminic acid and of CMP‐ N ‐acetylneuraminic acid; the activity of the key enzyme (UDP‐ N ‐acetylglucosamine‐2′‐epimerase). The biosynthesis of N ‐acetylneuraminic acid was investigated in vivo by labelling experiments using [1‐ 14 C]glucosamine and N ‐acetyl‐[U‐ 14 C]mannosamine as precursors revealing the same metabolic route in liver and hepatoma. The biosynthesis of N ‐acetylneuraminic acid deriving from [1‐ 14 C]glucosamine in vivo is diminished to about 15% in hepatoma compared to liver, whereas the synthesis of UDP‐ N ‐acetylglucosamine is not altered. The uptake of N ‐acetyl‐[U‐ 14 C]mannosamine and its conversion to N ‐acetylneuraminic acid in liver and hepatoma is demonstrated. The synthesis of free N ‐acetylneuraminic acid deriving from N ‐acetyl‐[U‐ 14 C]‐mannosamine is not changed in hepatoma. The incorporation of this precursor into protein‐bound N ‐acetylneuraminic acid of hepatoma is four‐times higher. The content of free and protein bound N ‐acetylneuraminic acid and CMP‐ N ‐acetylneuraminic acid have been measured in livers and hepatomas by isotope dilution technique. About 90% of total N acid content in both livers and hepatomas is protein‐bound. In Morris hepatomas the content of protein‐bound N ‐acetylneuraminic acid is elevated (between 5.93 and 8.38 nmol/mg protein) compared to liver (4.50 ± 0.52 nmol/mg protein). However the content of free. N ‐acetylneuraminic acid including CMP‐ N ‐acetylneuraminic acid is diminished in Morris hepatomas (between 108 and 164 nmol/g hepatoma in comparison to 196 ± 28 nmol/g liver), whereas the content of CMP‐ N ‐acetylneuraminic acid alone is not greatly changed (31.4 ± 8.5 nmol/g Morris hepatoma 9121 in comparison to 40.8 ± 10.1 nmol/g liver). The activity of UDP‐ N ‐acetylglucosamine‐2′‐epimerase of all Morris hepatomas investigated was diminished to between 6% and 13% compared to that of host liver. In other fast growing liver tissue (neonatal and regenerating liver) this enzyme activity was not diminished but slightly increased showing that the decreased enzyme activity is a characteristic feature of Morris hepatomas.
Melting of DNA (1968)

An exact statistical-mechanical treatment is given for the nearest-neighbor coupled model of DNA, allowing for the difference in bonding stability of the two base pairs, adenine–thymine and gaunine–cytosine. Treatments are given for random as well as pair-correlated sequences, both for finite and infinite degrees of polymerization. In addition, sequence-ensemble average thermal properties are compared with the corresponding properties of single molecules. The breadth in temperature of the helix–coil transition is shown to be a marked function of base composition. It is also shown that nonrandomness in nearest-neighbor base sequence of the magnitude observed in typical bacterial and viral DNA's has little effect on the thermodynamic properties.
The Prehistory of the Hammett Equation (2000)

The evolution of linear free energy relationships is traced from the Bronsted equation for general acid-base catalysis (1924) to the Hammett rho-sigma equation for the effects of meta or para substituents on the rate or equilibrium constants of side-chain reactions of benzene derivatives (1937). In addition to a natural emphasis on Louis P. Hammett´s own contributions, those of G.N. Burkhardt and his colleagues are also described, along with the extent to which these two authors interacted.
A prospective randomized trial of alpha 2B-interferon/gamma-interferon or the combination in advanced metastatic renal cell carcinoma. (1988)

Eighty-nine patients with advanced measurable metastatic renal cell carcinoma were entered into a prospective randomized trial comparing alpha-interferon to gamma-interferon and to the combination. The trial was performed in order to confirm the activity of gamma-interferon and assess the potential clinical synergism. Response rates were 5, 10, and 5%, respectively. The low response rate may have been due to the inability to raise the doses of the interferons to higher levels. Clinical synergy at this dose, route, and schedule of administration in renal cell carcinoma does not exist.
Freshman Design Course: Device Design for Low-Resource Settings (2018)

She has graduate training in both the natural and social sciences, with a PhD in biochemistry and an MSc in science & technology studies. Emma is
Proteomic differential display analysis shows up-regulation of 14-3-3 sigma protein in human scirrhous-type gastric carcinoma cells. (2010)

This study performed proteomic differential display analysis of human scirrhous-type gastric carcinoma (SGC) cell lines and normal gastric mucosa (NGM) tissues by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The human SGC cell lines were OCUM-1, OCUM-2M, OCUM-2MLN, OCUM-2D, OCUM-D3, OCUM-9 and OCUM-12. Among the SGC cell lines and the NGM tissues, 28 protein spots were found whose expression levels were different from the results of 2-DE: 19 protein spots appeared higher, and 9 other protein spots appeared lower in SGCs than in NGM tissues. These spots were analysed by LC-MS/MS analysis and identified by a peptide sequence tag. Identified increased spots included elongation factor 1-beta, 14-3-3 sigma, tropomyosin alpha-4 chain, protein DJ-1, nucleoside diphosphate kinase A, elongation factor Tu and peroxiredoxin-1. Western blot analysis showed increased protein level of 14-3-3 sigma in SGCs. Although OCUM-1 and AGS (gastric cancer) showed up-regulation of 14-3-3 sigma, MiaPaca-2 (pancreatic cancer), Huh-7 (HCC) and NCI-H2052 (malignant pleural mesothelioma) showed very weak expression of 14-3-3 sigma. The up-regulation of 14-3-3 sigma may play an important role in SGC carcinogenesis and progression and may be used as a diagnostic biomarker of SGC.
Fluorescence polarization studies of the interaction of Escherichia coli protein synthesis initiation factor 3 with 30S ribosomal subunits (1981)

Steady-state fluorescence polarization techniques were used to study the binding of initiation factor 3 (IF3) to 30S ribosomal subunits. Covalent fluorescent derivatives of IF3 were prepared by treating the pure protein with fluorescein isothiocyanate. The fluorescein-labeled IF3 (F-IF3) contained 0.8--1.7 dye molecules per protein. Polyacrylamide gel electrophoretic analysis of the derivatized forms is consistent with the view that the probe is randomly attached, presumably to lysine epsilon-amino groups. The activity of F-IF3 is not impaired in assays for binding to 30S ribosomal subunits or in promoting formylmethionyl-tRNA binding to 70S ribosomes. Fluorescence polarization values were measured at different F-IF3 and 30S ribosomal subunit concentrations, and the association constant and number of binding sites were calculated. In buffer containing 10 mM magnesium acetate and 100 mM ammonium chloride, the association constant is (3.1 +/- 1.4) x 10(7) M-1, and the number of ribosomal binding sites is 1.2 +/- 0.2. The value for the association constant varies inversely with the ammonium chloride and magnesium acetate concentrations by a small amount. Competition studies show that nonderivatized IF3 binds to 30S ribosomal subunits with the same affinity as F-IF3. Therefore, the association constants measured for F-IF3 are valid for IF3 as well.
Glycosaminoglycan-protein interactions: definition of consensus sites in glycosaminoglycan binding proteins (1998)

Although interactions of proteins with glycosaminoglycans (GAGs), such as heparin and heparan sulphate, are of great biological importance, structural requirements for protein-GAG binding have not been well-characterised. Ionic interactions are important in promoting protein-GAG binding. Polyelectrolyte theory suggests that much of the free energy of binding comes from entropically favourable release of cations from GAG chains. Despite their identical charges, arginine residues bind more tightly to GAGs than lysine residues. The spacing of these residues may determine protein-GAG affinity and specificity. Consensus sequences such as XBBBXXBX, XBBXBX and a critical 20 A spacing of basic residues are found in some protein sites that bind GAG. A new consensus sequence TXXBXXTBXXXTBB is described, where turns bring basic interacting amino acid residues into proximity. Clearly, protein-GAG interactions play a prominent role in cell-cell interaction and cell growth. Pathogens including virus particles might target GAG-binding sites in envelope proteins leading to infection.
Application of the method of thermal denaturation for investigation of alpha-chymotrypsin adducts with poly. (1998)

The thermostability of conjugates, non-covalent complexes and mixtures of alpha-chymotrypsin (alpha-ChT) with poly(alkylene oxides)--poly(ethylene glycol) (PEG) with molecular mass of 1.9 kD and diblock copolymers of ethylene and propylene oxides (proxanols)--has been investigated. It was shown that the addition of PEG in concentration up to 2 wt. % to the solution of alpha-ChT did not affect the rate of the enzyme thermoinactivation. Meanwhile the addition of proxanol in the same concentration resulted in twofold decrease in the rate constant for the slow inactivation step, k2. Even more pronounced decrease in the thermoinactivation rate was observed for alpha-ChT--proxanol complexes obtained by heating or under the action of high pressure. The general tendency in the behavior of complexes of both types was the decrease in the k2 constant as the temperature or pressure used for complex preparation increased. The highest stabilizing effect was observed for complex obtained by heating up to 52 degreesC and containing maximal number of polymer chains (molar ratio proxanol/alpha-ChT was 10). For this complex fourfold decrease in the k2 value was observed. Covalent attachment of PEG or proxanol to enzyme gives maximal stabilizing effect with up to tenfold decrease in the k2 value. The investigation of the thermal denaturation kinetics of alpha-ChT and its adducts with poly(alkylene oxides) by means of fluorescence spectroscopy has shown that the presence of polymer chains practically does not affect the rate of protein denaturation registered by the decrease in the intensity of protein fluorescence. The polymer chains, probably, diminish the rate of melting of the active site-containing region of the protein molecule. At the same time, the overall denaturation rate is independent of the presence of polymer chains in the vicinity of the protein globule.
Towards Smart Farming and Sustainable Agriculture with Drones (2015)

The use of drones in agriculture is becoming more and more popular. The paper presents a novel approach to distinguish between different field's plowing techniques by means of an RGB-D sensor. The presented system can be easily integrated in commercially available Unmanned Aerial Vehicles (UAVs). In order to successfully classify the plowing techniques, two different measurement algorithms have been developed. Experimental tests show that the proposed methodology is able to provide a good classification of the field's plowing depths.
Persistent and transient antibody responses to hepatitis E virus detected by western immunoblot using open reading frame 2 and 3 and glutathione S-transferase fusion proteins (1994)

Recombinant proteins containing amino acid sequences from open reading frame (ORF) 2 and ORF3 of a Chinese strain of hepatitis E virus (HEV) were constructed as fusions with glutathione S-transferase (GST). Stable fusion proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the proteins were transferred to nitrocellulose membranes, and the immobilized proteins were probed with sera from hepatitis E patients from various regions or from rhesus monkeys (Macaca mulatta) experimentally infected with the Chinese strain of HEV. Immunoglobulin G-class antibodies were detected with chemiluminescence and anti-human immunoglobulin G conjugated to horseradish peroxidase. Anti-ORF3 antibodies were detected in most patients and monkeys within 17 days of exposure, but this humoral response declined with time and was usually undetectable by approximately 100 days. Anti-ORF2.1 antibody was usually detected as early as anti-ORF3 but persisted in all animals and many patients, whereas reactivity to the larger GST-ORF2.2 fusion protein was more transient, even though all sequences present in GST-ORF2.1 are present in GST-ORF2.2. Rechallenge of these monkeys with HEV suggested that immunity to reinfection was incomplete, as levels of anti-ORF2.1 (but not anti-ORF2.2) were boosted after each rechallenge. The results demonstrate that the carboxy-terminal region of HEV ORF2 contains epitopes which are recognized by convalescent-phase antibody and are likely to be associated with limited immunity to infection, but these epitopes may be masked when larger portions of ORF2 are expressed as recombinant proteins.
Scalable high performance main memory system using phase-change memory technology (2009)

The memory subsystem accounts for a significant cost and power budget of a computer system. Current DRAM-based main memory systems are starting to hit the power and cost limit. An alternative memory technology that uses resistance contrast in phase-change materials is being actively investigated in the circuits community. Phase Change Memory (PCM) devices offer more density relative to DRAM, and can help increase main memory capacity of future systems while remaining within the cost and power constraints. In this paper, we analyze a PCM-based hybrid main memory system using an architecture level model of PCM.We explore the trade-offs for a main memory system consisting of PCMstorage coupled with a small DRAM buffer. Such an architecture has the latency benefits of DRAM and the capacity benefits of PCM. Our evaluations for a baseline system of 16-cores with 8GB DRAM show that, on average, PCM can reduce page faults by 5X and provide a speedup of 3X. As PCM is projected to have limited write endurance, we also propose simple organizational and management solutions of the hybrid memory that reduces the write traffic to PCM, boosting its lifetime from 3 years to 9.7 years.
Nonintrusive appliance load monitoring (1992)

A nonintrusive appliance load monitor that determines the energy consumption of individual appliances turning on and off in an electric load, based on detailed analysis of the current and voltage of the total load, as measured at the interface to the power source is described. The theory and current practice of nonintrusive appliance load monitoring are discussed, including goals, applications, load models, appliance signatures, algorithms, prototypes field-test results, current research directions, and the advantages and disadvantages of this approach relative to intrusive monitoring.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>