gebhart/patrepeval huggingface dataset:
Physiological and glycomic characterization of N-acetylglucosaminyltransferase-IVa and -IVb double deficient mice (2009)

N-Acetylglucosaminyltransferase-IV (GnT-IV) has two isoenzymes, GnT-IVa and GnT-IVb, which initiate the GlcNAcbeta1-4 branch synthesis on the Manalpha1-3 arm of the N-glycan core thereby increasing N-glycan branch complexity and conferring endogenous lectin binding epitopes. To elucidate the physiological significance of GnT-IV, we engineered and characterized GnT-IVb-deficient mice and further generated GnT-IVa/-IVb double deficient mice. In wild-type mice, GnT-IVa expression is restricted to gastrointestinal tissues, whereas GnT-IVb is broadly expressed among organs. GnT-IVb deficiency induced aberrant GnT-IVa expression corresponding to the GnT-IVb distribution pattern that might be attributed to increased Ets-1, which conceivably activates the Mgat4a promoter, and thereafter preserved apparent GnT-IV activity. The compensative GnT-IVa expression might contribute to amelioration of the GnT-IVb-deficient phenotype. GnT-IVb deficiency showed mild phenotypic alterations in hematopoietic cell populations and hemostasis. GnT-IVa/-IVb double deficiency completely abolished GnT-IV activity that resulted in the disappearance of the GlcNAcbeta1-4 branch on the Manalpha1-3 arm that was confirmed by MALDI-TOF MS and GC-MS linkage analyses. Comprehensive glycomic analyses revealed that the abundance of terminal moieties was preserved in GnT-IVa/-IVb double deficiency that was due to the elevated expression of glycosyltransferases regarding synthesis of terminal moieties. Thereby, this may maintain the expression of glycan ligands for endogenous lectins and prevent cellular dysfunctions. The fact that the phenotype of GnT-IVa/-IVb double deficiency largely overlapped that of GnT-IVa single deficiency can be attributed to the induced glycomic compensation. This is the first report that mammalian organs have highly organized glycomic compensation systems to preserve N-glycan branch complexity.
Metal induced crystallization of amorphous silicon for photovoltaic solar cells (2011)

A silicon thin-film technology could lead to less expensive modules by the use of less silicon material and by the implementation of monolithic module processes. A technology based on polycrystalline-silicon thin-films with a grain size between 1 μm and 1 mm (pc-Si), seems particularly promising since it combines the low-cost potential of a thin-film technology with the high efficiency potential of crystalline silicon. One of the possible approaches to fabricate pc-Si absorber layers is metal induced crystallization (MIC). For solar cell applications mainly aluminium is investigated as metal because 1) it forms a eutectic system with silicon instead of a silicide-metal system like e.g. Ni 2) only shallow level defects are formed in the forbidden bandgap of silicon and 3) a layer exchange process can be obtained in combination with a-Si. Aluminum induced crystallization (AIC) of a-Si on non-silicon substrates can results in grains with a preferential (100) orientation and a maximum grain sizes above 50 micrometer. These layers can act as seed layers for further epitaxial growth. Based on this two-step approach (AIC + epitaxial growth) we made solar cells with an energy conversion efficiency of 8%. Based on TEM, EBIC, SEM, defect etch and EBSD measurements we showed that the efficiency is nowadays mainly limited by the presence of electrical intragrain defects.
Two issues in reservation establishment (1995)

This paper addresses two issues related to resource reservation establishment in packet switched networks offering real-time services. The first issue arises out of the natural tension between the local nature of reservations (i.e., they control the service provided on a particular link) and the end-to-end nature of application service requirements. How do reservation establishment protocols enable applications to receive their desired end-to-end service? We review the current one-pass and two-pass approaches, and then propose a new hybrid approach called one-pass-with-advertising. The second issue in reservation establishment we consider arises from the inevitable heterogeneity in network router capabilities. Some routers and subnets in the Internet will support real-time services and others, such as ethernets, will not. How can a reservation establishment mechanism enable applications to achieve the end-to-end service they desire in the face of this heterogeneity? We propose an approach involving replacement services and advertising to build end-to-end service out of heterogeneous per-link service offerings.
Evaluation of alternate routes for the synthesis of methyl methacrylate (1998)

The use of coal-derived syngas to produce high value chemicals is an important means of upgrading this resource. One example of a chemical that can be produced from coal-derived syngas is methyl methacrylate (MMA). Poly-methyl methacrylate is widely used in coatings and in various industrial molded products. The most widely practiced commercial technology for the synthesis of MMA is the acetone cyanohydrin (ACH) process. This process requires handling of large quantities of toxic hydrogen cyanide and generates one mole of ammonium bisulfate waste per mole of MMA. This bisulfate must either be regenerated or discarded, either of which substantially increases the cost. The ACH technology is thus environmentally and economically untenable for any new MMA plant expansions that would be needed to meet increasing demand. The RTI-Eastman-Bechtel research team is developing an alternative, environmentally benign route to MMA consisting of three steps; (step 1) synthesis of a propionate from ethylene, carbon monoxide, and steam, (step 2) condensation of this propionate with formaldehyde, and (step 3) esterification of resulting methacrylic acid with methanol to form MMA. This paper describes the preliminary economics of the overall process compared to other emerging processes, and focuses on step 2, including long term testing ofmore » catalysts for the condensation of propionic acid with formaldehyde to form MAA.« less
An Experimental Study of Machine Recognition of Hand-Printed Numerals (1968)

The recognition of hand-printed numerals is studied on a broad experimental basis within the constraints imposed by a raster scanner generating binary video patterns, a mixed measurement set, and a statistical decision function. A computer-controlled scanner is used to acquire the characters, to adjust the raster resolution and registration, and to monitor the black-white threshold of the quantizer. The dimensionality of the decision problem is reduced by a hybrid system of measurements. In the measurement design, three types of measurements are generated: a set of "topological" measurements, a set of logical "n-tuples," both designed by hand, and a large set of n-tuples machine generated at random under special constraints. The final set of 100 measurements is selected automatically by a programmed algorithm that attempts to minimize the maximum expected error rate between every character pair. Computer simulation experiments show the effectiveness of the selection procedure, the contribution of the different types of measurements, the effect of the number of measurements selected on recognition, and the desirability of size and shear normalization. The final system is tested on four data sets printed under different degrees of control on the writers. Each data set consists of approximately 10 000 characters. For this comparison, a first-order maximum likelihood function with weights quantized to 100 levels is used. Error versus reject curves are given on several combinations of training and test sets.
Integration of transcription and flux data reveals molecular paths associated with differences in oxygen-dependent phenotypes of Saccharomyces cerevisiae (2014)

The molecular paths associated with the phenotype differences of S. cerevisiae under conditions of different oxygen provisions revealed paths of molecular interactions that could potentially mediate information transfer between processes that respond to the particular oxygen availabilities.
Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes (2020)

SUMMARY The COVID-19 pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options and an urgent need to understand the pathogenesis of multi-organ failure and lung damage. Cytokine storm is associated with severe inflammation and organ damage during COVID-19. However, a detailed molecular pathway defining this cytokine storm is lacking, and gaining mechanistic understanding of how SARS-CoV-2 elicits a hyperactive inflammatory response is critical to develop effective therapeutics. Of the multiple inflammatory cytokines produced by innate immune cells during SARS-CoV-2 infection, we found that the combined production of TNF-α and IFN-γ specifically induced inflammatory cell death, PANoptosis, characterized by gasdermin-mediated pyroptosis, caspase-8-mediated apoptosis, and MLKL-mediated necroptosis. Deletion of pyroptosis, apoptosis, or necroptosis mediators individually was not sufficient to protect against cell death. However, cells deficient in both RIPK3 and caspase-8 or RIPK3 and FADD were resistant to this cell death. Mechanistically, the JAK/STAT1/IRF1 axis activated by TNF-α and IFN-γ co-treatment induced iNOS for the production of nitric oxide. Pharmacological and genetic deletion of this pathway inhibited pyroptosis, apoptosis, and necroptosis in macrophages. Moreover, inhibition of PANoptosis protected mice from TNF-α and IFN-γ-induced lethal cytokine shock that mirrors the pathological symptoms of COVID-19. In vivo neutralization of both TNF-α and IFN-γ in multiple disease models associated with cytokine storm showed that this treatment provided substantial protection against not only SARS-CoV-2 infection, but also sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock models, demonstrating the broad physiological relevance of this mechanism. Collectively, our findings suggest that blocking the cytokine-mediated inflammatory cell death signaling pathway identified here may benefit patients with COVID-19 or other cytokine storm-driven syndromes by limiting inflammation and tissue damage. The findings also provide a molecular and mechanistic description for the term cytokine storm. Additionally, these results open new avenues for the treatment of other infectious and autoinflammatory diseases and cancers where TNF-α and IFN-γ synergism play key pathological roles.
Cooperation of the Ce(IV)/EDTA Complex and Oligoamine for Prompt Scission of DNA (2001)

Abstract DNA hydrolysis by the Ce(IV)/EDTA complex is enormously accelerated by the cooperation with selected oligoamines. The reaction in the presence of ethylenediamine (100 mmol dm−3) is 50 times as fast as that in its absence.
Computational discovery of pathway-level genetic vulnerabilities in non-small-cell lung cancer (2016)

Supplementary data are available at Bioinformatics online.
Polymerized liposomes as stable oxygen‐carriers (1985)

We have produced a surrogate erythrocyte ('hemosomes') by encapsulating human hemoglobin in polymerized vesicles composed of diacetylenic phospholipids plus or minus cholesterol. Hemoglobin (in the presence or absence of allosteric effectors) was encapsulated by a freeze-thaw method in large, unilamellar vesicles composed of monomeric lipids. Entrapment was demonstrated by molecular-sieve chromatography. Brief irradiation with ultraviolet light produced polymeric hemosomes with polymerization kinetics and conversions similar to liposomes in the absence of protein. Photo-induced oxidation of the heme was eliminated or severely limited by a combination of prior ligation with CO and the maintenance of high intravesicular hemoglobin concentrations (5-10 mM internal hemoglobin). The inclusion of allosteric effectors within polymerized hemosomes facilitated near-quantitative conversion to the oxy-HbA form. Gas permeability of monomeric and polymeric hemosomes was demonstrated by spectroscopic methods. Reversible spectral shifts, corresponding to oxygenation-deoxygenation, were obtained after brief evacuation and exposure to oxygen or nitrogen. The gas permeability of polymerized hemosomes appears sufficient for the vesicles to act as oxygen carriers in vivo, a notion that is strengthened by their apparent hemocompatibility.
Efficient data center design using novel modular DC UPS, server power supply with DC voltage and modular CDU cooling (2012)

An efficient cost effective novel modular scalable Data Center topology using Direct Current Uninterruptible Power Supply (DC UPS), server power supply with DC input and Cooling Distribution Unit (CDU) for IT load incorporating hybrid (both AC and DC voltage) distribution has been proposed in this paper. There is mismatch of infrastructure (both mechanical and electrical) capability and IT load in the existing Data Center. It takes years to reach equilibrium when IT load is balanced with infrastructure load capabilities. Major energy efficiency improvements and technological innovation of the Data Center industry had not been achieved for both electrical and mechanical infrastructure in the past, even as computing hardware and software follow Moore's law and has become efficient. A detailed analysis of the topology is presented to validate effectiveness of the proposed topology. Efficiency improvement and cost reduction of the proposed Data Center topology is found to be quite significant.
Mapping the landscape of genetic dependencies in chordoma (2023)

Identifying the spectrum of genes required for cancer cell survival can reveal essential cancer circuitry and therapeutic targets, but such a map remains incomplete for many cancer types. We apply genome-scale CRISPR-Cas9 loss-of-function screens to map the landscape of selectively essential genes in chordoma, a bone cancer with few validated targets. This approach confirms a known chordoma dependency, TBXT (T; brachyury), and identifies a range of additional dependencies, including PTPN11, ADAR, PRKRA, LUC7L2, SRRM2, SLC2A1, SLC7A5, FANCM, and THAP1. CDK6, SOX9, and EGFR, genes previously implicated in chordoma biology, are also recovered. We find genomic and transcriptomic features that predict specific dependencies, including interferon-stimulated gene expression, which correlates with ADAR dependence and is elevated in chordoma. Validating the therapeutic relevance of dependencies, small-molecule inhibitors of SHP2, encoded by PTPN11, have potent preclinical efficacy against chordoma. Our results generate an emerging map of chordoma dependencies to enable biological and therapeutic hypotheses.
Gigabit Logic Prospects of GaAs E-JFET Integrated Circuits (2005)

Computer simulation and experimental results will be presented for a 1 mu m GaAs enhancement mode JFET. Logic performance of 250 ps propagation delay time with a power dissipation of 200 mu W/gate at a fan-out of 3 offers gigabit logic for LSI, i.e. delay-power product of 50 fJ. A planar integration will be described which utilizes selective ion implantation of n- and p- impurities for the channel and pn-junction gate formation in semi-insulating GaAs substrate material.
Single-layer chemically amplified photoresists for 193-nm lithography (1993)

Recent advances in ArF excimer laser exposure tools have led to a search for new resist materials for use at 193 nm. To date much of this effort has been directed toward surface imaged or bilayer resist schemes and only recently have there been reports of single layer systems with sufficient transparency for use at this short wavelength. We will describe our approach to a 193 nm single layer resist system based on methacrylate terpolymers. A terpolymer system based on tert-butylmethacrylate, methyl methacrylate and methacrylic acid developed for laser direct imaging applications has been adapted for high resolution imaging by modifying the terpolymer composition and by optimizing the photoacid generator loading. This resist is useful for the characterization of new exposure systems and we will describe imaging results on a prototype 0.50-NA step and scan system. We will also describe the effect photoacid structure has on the imaging properties of the resist and compare the efficiency of deprotection chemistry at 193 and 248 nm. In addition, we will discuss modifications of the aliphatic polymer described above by replacement of the ‘‘inert’’ methyl methacrylate monomer by monomers containing alicyclic substituents to improve the resistance to reactive ion etching.
Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4+ and CD8+ T-cell responses in the elderly positively correlates with response size (2016)

Abstract Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8+ and CD4+ T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8+ and CD4+ cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4+ and CD8+ T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging.
Noninvasive gene transfer to the lung for systemic delivery of therapeutic proteins (2002)

This study evaluates the use of vectors based on adeno-associated viruses (AAVs) to noninvasively deliver genes to airway epithelial cells as a means for achieving systemic administration of therapeutic proteins.We intranasally delivered AAV vectors to mice in which the same AAV2 genome encoding a cellular marker was packaged in capsids from AAV1, 2, or 5 (AAV2/1, AAV2/2, or AAV2/5, respectively).Gene expression levels achieved in both airways and alveoli were higher with AAV2/5 than with AAV2/1 and were undetectable with AAV2/2.The same set of vectors encoding a secreted therapeutic protein, erythropoietin (Epo), under the control of a lung-specific promoter (CC10) was intranasally delivered to mice, resulting in polycythemia with the highest levels of serum Epo obtained with AAV2/5 vectors.After a single intranasal administration of this vector, secretion of Epo was documented for 150 days.Similarly, intranasal administration of an AAV2/5-CC10-factor IX vector resulted in secretion of functional recombinant protein in the bloodstream of hemophiliac, factor IX-deficient mice.In addition, we demonstrate successful readministration of AAV2/5 to the lung 5 months after the first delivery of the same vector.In conclusion, we show that intranasal administration of AAV vectors results in efficient gene transfer to the lung only when the vector contains the AAV5 capsid and that this noninvasive route of administration results in sustained secretion of therapeutic proteins in the bloodstream.
KUB3 amplification and overexpression in human gliomas (2001)

Gene amplification is known to occur frequently in human glioma. Recently we reported cloning of a novel gene termed glioma-amplified sequence 16 (GAS16) by microdissection-mediated cDNA capture. In this article, we demonstrate that GAS16 results from an alternative splicing process of the Ku70 binding protein 3 (KUB3) that is essential for DNA double-strand break repair. The alternative splice product was found in glioblastoma and in normal fetal brain. We determined the amplification frequency of KUB3 in glioma with different grading. We analyzed a total of 102 glioma primary tumors and found KUB3 to be amplified in 12/82 (14%) glioblastomas, 4/13 anaplastic astrocytomas (30%), and 2/4 astrocytomas, but in none of three pilocytic astrocytomas. Northern blot analysis of glioblastoma shows a strong correlation between KUB3 amplification and overexpression. Amplification of KUB3 appears to be independent of other genetic changes frequently associated with the development of gliomas, including EGFR amplification, LOH of TP53, and LOH of chromosome 10. The KUB3 amplification and overexpression may interfere with the function of KUB3 in the DNA-PK complex involved in the maintenance of genome stability and reduction of mutation frequency.
CFD Investigation on the Influence of In-Cylinder Mixture Distribution from Multiple Pilot Injections on Cold Idle Behaviour of a Light Duty Diesel Engine (2014)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Cold idle operation of a modern design light duty diesel engine and the effect of multiple pilot injections on stability were investigated. The investigation was initially carried out experimentally at 1000rpm and at −20°C. Benefits of mixture preparation were initially explored by a heat release analysis. Kiva 3v was then used to model the effect of multiple pilots on in-cylinder mixture distribution. A 60° sector of mesh was used taking advantage of rotational symmetry. The combustion system and injector arrangements mimic the HPCR diesel engine used in the experimental investigation. The CFD analysis covers evolutions from intake valve closing to start of combustion. The number of injections was varied from 1 to 4, but the total fuel injected was kept constant at 17mm&lt;sup&gt;3&lt;/sup&gt;/stroke. Start of main injection timing was fixed at 7.5°BTDC. The experimental study shows that increasing the number of pilots improves stability and leads to fuel preparation resulting in higher initial peak rate of heat release. CFD results show that multiple pilot injections are capable of better fuel distribution; noticeable by injecting just one pilot compared to no pilot. A further pilot increases the surface area of the vapour cloud to a greater extent. Three pilots allow for fuel to be well distributed in the full bowl with no lean regions; a greater proportion of the fuel is exposed to the glow plug temperature. The glow plug is enclosed by a fuel cloud over a longer period of time as the number of pilot injections is increased.&lt;/div&gt;&lt;/div&gt;
Figure A3 from Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial (2023)

Figure A3 from Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial