gebhart/patrepeval huggingface dataset:
The development of hyaluronic acid as a targeted transport vehicle for chemotherapeutic drugs (2005)

Introduction: The non-selective nature of systemic chemotherapeutic drugs necessitates the administration of high doses to achieve and maintain therapeutic levels within the tumor, which often results in severe side-effects. The efficacy of the drug could be maintained and the toxicity alleviated by direct targeting of anticancer agents to the tumor. The observation that the naturally occurring polysaccharide, hyaluronic acid (HA) has high affinity for tumors and that numerous tumors over-express HA receptors has lead to the development of a series of proprietary HA/cytotoxic drug formulations. The purpose of this study was to evaluate if such formulations could target and expedite the delivery of anticancer agents to solid tumors and enhance their function. Methodology: The mode of interaction between HA and the cytotoxic drugs was investigated using CD and NMR spectroscopy. The ability of HA to target anticancer agents to the HA receptor, CD44, was demonstrated by IV injection of radioactive anticancer agents ᠱ2.5mg/kg of HA (Mr 750 kDa) into nude mice bearing human breast cancer xenografts. The effect of HA on the therapeutic index of chemotherapeutic drugs was established by treatment of nude mice carrying human breast xenografts with methotrexate, 5-fluorouracil (5FU) and doxorubicin (DOX) + HA for six cycles of one week. The safety of HyFIVETM (HA/5-FU) and HyDOXTM (HA/DOX) drug formulations was established in Phase l clinical trials where 30 patients with metastatic cancer were administered 500mg/m2 HA in combination with escalating doses of DOX (30-60mg/m2) or 5FU (cumulative dose of 1350-2250mg/m2 per cycle). Results: Chemical interaction studies demonstrated that no ionic, hydrophobic or covalent interaction existed between the HA and drugs but instead, the small anti-cancer agents were entrained within the HA matrix through a viscosity related effect. It was demonstrated that HA could target anticancer drugs to tumors where, within 10min, HA directed up to 400% more anticancer agent to the tumor and lymph nodes whilst reducing the gastrointestinal (GI) and cardiac drug content by up to 660%. Efficacy studies in breast cancer xenograft models demonstrated a greater tumor response, elimination of secondary cancer and a significant reduction in both Gl and cardiac toxicities. The Phase l studies showed that the HA formulations were well tolerated; tumour responses were observed and the co-administration of HA did not alter the pharmacokinetics of clinically relevant doses of 5FU or DOX. Conclusions: These studies demonstrate that HA can act as a targeted transport vehicle for chemotherapeutic drugs thereby potentially increasing treatment efficacy while reducing treatment toxicity.
Single-Channel Backward-Compatible EDTV Systems (1989)

This article describes some methods for adding supplementary information to a compatible NTSC broadcast signal so that an advanced receiver can decode that information to provide improved picture quality (Extended-Definition Television, or EDTV), while a standard NTSC receiver will display an image with minimally visible impairments. In particular, chrominance information is transmitted at one-half the frame rate and alternate frames are used to encode high-definition luminance information in the chrominance signal. This is useful for any EDTV system. A particular design is suggested where some active lines are usurped from the top and bottom of the picture and augmentation information is encoded into this region so that both the EDTV and the NTSC receiver receive similar-looking widescreen pictures, with the EDTV picture containing greater resolution.
GCN2-like eIF2α kinase manages the amino acid starvation response in Toxoplasma gondii (2014)

The apicomplexan protozoan Toxoplasma gondii is a significant human and veterinary pathogen. As an obligate intracellular parasite, Toxoplasma depends on nutrients provided by the host cell and needs to adapt to limitations in available resources. In mammalian cells, translational regulation via GCN2 phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) is a key mechanism for adapting to nutrient stress. Toxoplasma encodes two GCN2-like protein kinases, TgIF2K-C and TgIF2K-D. We previously showed that TgIF2K-D phosphorylates T. gondii eIF2α (TgIF2α) upon egress from the host cell, which enables the parasite to overcome exposure to the extracellular environment. However, the function of TgIF2K-C remained unresolved. To determine the functions of TgIF2K-C in the parasite, we cloned the cDNA encoding TgIF2K-C and generated knockout parasites of this TgIF2α kinase to study its function during the lytic cycle. The TgIF2K-C knockout did not exhibit a fitness defect compared with parental parasites. However, upon infection of human fibroblasts that were subsequently cultured in glutamine-free medium, the intracellular TgIF2K-C knockout parasites were impeded for induced phosphorylation of TgIF2α and showed a 50% reduction in the number of plaques formed compared with parental parasites. Furthermore, we found that this growth defect in glutamine-free media was phenocopied in parasites expressing only a non-phosphorylatable TgIF2α (TgIF2α-S71A), but not in a TgIF2K-D knockout. These studies suggest that Toxoplasma GCN2-like kinases TgIF2K-C and TgIF2K-D evolved to have distinct roles in adapting to changes in the parasite’s environment.
Lower-Temperature Epitaxial Growth of 4H-SiC Using CH<sub>3</sub>Cl Carbon Gas Precursor (2006)

The advantages of the CH3Cl carbon precursor were investigated in order to achieve good-quality homoepitaxial layers of the 4H-SiC polytype at temperatures lower than what was considered practical (or even possible) with C3H8-based growth. It was observed that the process window for good epilayer morphology becomes narrower when the growth temperature is decreased. Successful growth experiments have been conducted in this work down to a temperature of 1290-13000C, with the growth rate in excess of 2 +m/hr and a mirror-like defect-free epilayer surface morphology. Growth on a 2” substrate produced promising growth rate homogeneity. The dependence of the growth rate on SiH4 flow followed a clear exponential dependence. This trend is tentatively attributed to Si vapor condensation. Photoluminescence results suggest that the crystalline quality of the epilayers grown at 13000C is comparable to that of 17000C growth.
Human Aromatase: Gene Resequencing and Functional Genomics (2005)

Aromatase [cytochrome P450 19 (CYP19)] is a critical enzyme for estrogen biosynthesis, and aromatase inhibitors are of increasing importance in the treatment of breast cancer. We set out to identify and characterize genetic polymorphisms in the aromatase gene, CYP19, as a step toward pharmacogenomic studies of aromatase inhibitors. Specifically, we "resequenced" all coding exons, all upstream untranslated exons plus their presumed core promoter regions, all exon-intron splice junctions, and a portion of the 3'-untranslated region of CYP19 using 240 DNA samples from four ethnic groups. Eighty-eight polymorphisms were identified, resulting in 44 haplotypes. Functional genomic studies were done with the four nonsynonymous coding single nucleotide polymorphisms (cSNP) that we observed, two of which were novel. Those cSNPs altered the following amino acids: Trp39Arg, Thr201Met, Arg264Cys, and Met364Thr. The Cys264, Thr364, and double variant Arg39Cys264 allozymes showed significant decreases in levels of activity and immunoreactive protein when compared with the wild-type (WT) enzyme after transient expression in COS-1 cells. A slight decrease in protein level was also observed for the Arg39 allozyme, whereas Met201 displayed no significant changes in either activity or protein level when compared with the WT enzyme. There was also a 4-fold increase in apparent K(m) value for Thr364 with androstenedione as substrate. Of the recombinant allozymes, only the double mutant (Arg39Cys264) displayed a significant change from the WT enzyme in inhibitor constant for the aromatase inhibitors exemestane and letrozole. These observations indicate that genetic variation in CYP19 might contribute to variation in the pathophysiology of estrogen-dependent disease.
Supramolecular Perylene Bisimide-Polysulfide Gel Networks as Nanostructured Redox Mediators in Dissolved Polysulfide Lithium–Sulfur Batteries (2015)

Here we report a new redox-active perylene bisimide (PBI)-polysulfide (PS) gel that overcomes electronic charge-transport bottlenecks common to lithium–sulfur (Li–S) hybrid redox flow batteries designed for long-duration grid-scale energy storage applications. PBI was identified as a supramolecular redox mediator for soluble lithium polysulfides from a library of 85 polycyclic aromatic hydrocarbons by using a high-throughput computational platform; furthermore, these theoretical predictions were validated electrochemically. Challenging conventional wisdom, we found that π-stacked PBI assemblies were stable even in their reduced state through secondary interactions between PBI nanofibers and Li2Sn, which resulted in a redox-active, flowable 3-D gel network. The influence of supramolecular charge-transporting PBI-PS gel networks on Li–S battery performance was investigated in depth and revealed enhanced sulfur utilization and rate performance (C/4 and C/8) at a sulfur loading of 4 mg cm–2 and energy density of 44 Wh L–1 in the absence of conductive carbon additives.
A Food-Grade Cloning System for Industrial Strains of <i>Lactococcus lactis</i> (2000)

We have previously reported the construction of a food-grade cloning vector for Lactococcus using the ochre suppressor, supB, as the selective marker. This vector, pFG1, causes only a slight growth inhibition in the laboratory strain MG1363 but is unstable in the industrial strains tested. As supB suppresses both amber and ochre stop codons, which are present in 82% of all known lactococcal genes, this undesirable finding may result from the accumulation of elongated mistranslated polypeptides. Here, we report the development of a new food-grade cloning vector, pFG200, which is suitable for overexpressing a variety of genes in industrial strains of Lactococcus lactis. The vector uses an amber suppressor, supD, as selectable marker and consists entirely of Lactococcus DNA, with the exception of a small polylinker region. Using suppressible pyrimidine auxotrophs, selection and maintenance are efficient in any pyrimidine-free medium including milk. Importantly, the presence of this vector in a variety of industrial strains has no significant effect on the growth rate or the rate of acidification in milk, making this an ideal system for food-grade modification of industrially relevant L. lactis strains. The usefulness of this system is demonstrated by overexpressing the pepN gene in a number of industrial backgrounds.
An LC-Compensated Electric Field Repeater for Long-Distance Capacitive Power Transfer (2017)

This paper proposes an LC-compensated electric field repeater to extend the transfer distance of a capacitive power transfer (CPT) system. The repeater contains two metal plates connected with an external capacitor and an external inductor. The plates are used to generate electric fields to transfer power. The external inductor and capacitor are used to resonate with the plates in order to increase the voltage levels. The repeater is placed between a transmitter and a receiver, which also contains metal plates compensated by an LC network. The repeater can increase the transfer distance of the CPT system without significantly influencing the system power and efficiency. In this paper, the capacitive coupler structure and dimensions are designed and simulated using Maxwell software. Considering all the capacitive coupling between plates, an equivalent circuit model is derived. The fundamental harmonics approximation method is used to analyze the working principle of the circuit. A 150 W input power CPT system is designed as an example to validate the proposed repeater structure and compensation circuit topology. The system can achieve an efficiency of 66.9% from dc source to dc load, when the transfer distance is 360 mm and the repeater is placed between the transmitter and the receiver.
Next-generation LTR-specific Tre-recombinase targets a majority of HIV-1 isolates (2014)

HIV-1 integrates into the host chromosome and persists as a provirus flanked by long terminal repeats (LTR). To date, treatment regimens primarily target the virus enzymes, virus attachment or virus-cell fusion, but not the integrated provirus. Thus, current antiretroviral therapies (i.e. cART) cannot eradicate HIV-1, a fact that highlights the urgency of pursuing new strategies to find a cure for HIV/AIDS.

Previously, we engineered an experimental LTR-specific recombinase (Tre-recombinase) that can effectively excise integrated HIV-1 proviral DNA from infected human cell cultures (Sarkar et al. 2007 Science 316:1912). Subsequently, we demonstrated highly significant antiviral activity of this HIV-1 subtype A-specific Tre in humanized mice (Hauber et al. 2013 PLOS pathogens 9:e1003587). Broad clinical application, however, requires availability of a tre-recombinase that recognizes a majority of clinical HIV-1 isolates.
‘Living’ Controlled <i>in Situ</i> Gelling Systems: Thiol−Disulfide Exchange Method toward Tailor-Made Biodegradable Hydrogels (2010)

A 'living' controlled hydrogel formation method was first reported to create loose and compact in situ biodegradable hydrogels. The method executed under mild reaction conditions can conveniently tailor the hydrogel properties, and it has the potential to develop into a powerful tool for the design, synthesis, and self-assembly of novel tailor-made biomaterials and drug delivery systems.
A very high sensitivity and very high speed light triggered and light quenched static induction thyristor (LTQSIThy) (1984)

The purpose of this paper is to describe a new operational mode of the Static Induction Thyristor (SIThy), namely the Light Triggered and Light Quenched Static Induction Thyristor (LTQSIThy) characterized by the very high triggering and quenching optical sensitivity and very high speed performance. The LTQSIThy is the totally light controlled self-turn-off type power switching device which is constructed by the optically triggerable Static Induction Photo-Thyristor (SIPThy) and the light sensitive element which is connected or integrated to the gate terminal of the SIPThy.
A Simplified Reconstitution of mRNA-Directed Peptide Synthesis: Activity of the Epsilon Enhancer and (2001)

The study of the early events in translation would be greatly facilitated by reconstitution with easily purified components. Here, Escherichia coli oligopeptide synthesis has been reconstituted using five purified recombinant His-tagged E. coli initiation and elongation factors. Highly purified ribosomes are required to yield products with strong dependencies on the translation factors. Based on HPLC separation of radiolabeled translation products from an mRNA encoding a tetrapeptide, approximately 80% of peptide products are full length, and the remaining 20% are the dipeptide and tripeptide products resulting from pausing or premature termination. Oligopeptide synthesis is enhanced when a commonly used epsilon (enhancer of protein synthesis initiation) sequence is included in the mRNA. The system incorporates a selectable, large, unnatural amino acid and may ultimately form the basis of a pure translation display technology for the directed evolution of peptidomimetic ligands and drug candidates. The recombinant clones can be exploited to prepare initiation factors and initiation complexes for structural studies, to study initiation and elongation in ribosomal peptide synthesis, and to screen for eubacterial-specific drugs. © 2001 Academic
Functional Summarization of Non-Text Data (2015)

Summarization techniques can be applied to non-text data in order to perform classification and clustering of important imaging, video and other document-associated but non-text content. The advantage to this approach is that there is a multiplicity of inexpensive (even free) summarization engines, and so a robust solution can be crafted with relatively modest effort. In this paper, we present the applicability of this approach to video and imaging data, in addition to broader binary and genetic data.
Verification of Object Relational Maps (2007)

Enterprise software systems need to deal with two dominant data models. While object oriented languages (such as Java, C#, C++) are the dominant ways to write business logic, relational databases are the dominant ways to store data. Object-relational (OR) maps are widely used to mediate between these two data models. We present a system to verify correctness of OR maps. We formulate simple correctness conditions for OR maps, and convert these conditions to validity of formulas in first order logic. We have built a verification tool called ROUND TRIP that is able to both validate and find errors in OR maps defined in the ESQL language of the Microsoft EDM data model.
<title>Method for color correction with noise consideration</title> (1999)

As the spectral sensitivities of most color devices are typically different from that of human vision or corresponding output devices, signals from different channels (such as Red, Green and Blue) of a color recording device need to be properly mixed to generate color information suitable for viewing. The mixing (or transformation) which minimizes some error measure between the target and the transformed colors of a large set of color patches is normally used for this purpose. As the color error is the only criterion in determining such transformation, the measurement noises of the color device may often be amplified in the target color space without much control. We present in this paper a new color correction method that takes account of both the color error and the noise variance in reproduced images. This method is useful in applications where the measurement noises of recording devices are not necessarily low. The proposed method is then extended to include other color reproduction constraints. Analytical solutions and experimental results of the proposed method are both reported in the paper.
Industrial Production of L-Tryptophan from Indole and DL-Serine with Two PLP-Dependent Enzymes (1987)

SummaryA new enzymatic process of L-tryptophan production has been developed using indole and DL-serine. Two PLP-dependent enzymes simultaneously participate in this process. Tryptophan synthase of Escherichia coli catalyzes ß-substitution reaction of L-serine into L-tryptophan, while serine racemase of Pseudomonas putida converts unreacted D-serine into L-serine. Whole cells of each microorganism were used as the enzyme source. A large scale production was successfully carried out in a 200 liter reactor. After 24hr incubation, 110g/l of L-tryptophan was produced and conversion rates of indole and DL-serine were 100% and 91%, respectively.
Timing local streams (2010)

Data prefetching technique is widely used to bridge the growing performance gap between processor and memory. Numerous prefetching techniques have been proposed to exploit data patterns and correlations in the miss address stream. In general, the miss addresses are grouped by some common characteristics, such as program counter or memory region they belong to, into localized streams to improve prefetch accuracy and coverage. However, the existing stream localization technique lacks the timing information of misses. This drawback can lead to a large fraction of untimely prefetches, which in turn limits the effectiveness of prefetching, wastes precious bandwidth and leads to high cache pollution potentially. This paper proposes a novel mechanism named stream timing technique that can largely reduce untimely prefetches and in turn increase the overall performance. Based on the proposed stream timing technique, we extend the conventional stride prefetcher and propose a new stride prefetcher called Time-Aware Stride (TAS) prefetcher. We have carried out extensive simulation experiments to verify the design of the stream timing technique and the TAS prefetcher. The simulation results show that the proposed stream timing technique is promising in reducing untimely prefetches and the IPC improvement of TAS prefetcher outperforms the existing stride prefetcher by 11%.
Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy (2015)

Allergen immunotherapy (AIT) has been practised since 1911 and remains the only therapy proven to modify the natural history of allergic diseases. Although efficacious in carefully selected individuals, the currently licensed whole allergen extracts retain the risk of IgE-mediated adverse events, including anaphylaxis and occasionally death. This together with the need for prolonged treatment regimens results in poor patient adherence. The central role of the T cell in orchestrating the immune response to allergen informs the choice of T cell targeted therapies for down-regulation of aberrant allergic responses. Carefully mapped short synthetic peptides that contain the dominant T cell epitopes of major allergens and bind to a diverse array of HLA class II alleles, can be delivered intradermally into non-inflamed skin to induce sustained clinical and immunological tolerance. The short peptides from allergenic proteins are unable to cross-link IgE and possess minimal inflammatory potential. Systematic progress has been made from in vitro human models of allergen T cell epitope-based peptide anergy in the early 1990s, through proof-of-concept murine allergy models and early human trials with longer peptides, to the current randomized, double-blind, placebo-controlled clinical trials with the potential new class of synthetic short immune-regulatory T cell epitope peptide therapies. Sustained efficacy with few adverse events is being reported for cat, house dust mite and grass pollen allergy after only a short course of treatment. Underlying immunological mechanisms remain to be fully delineated but anergy, deletion, immune deviation and Treg induction all seem contributory to successful outcomes, with changes in IgG4 apparently less important compared to conventional AIT. T cell epitope peptide therapy is promising a safe and effective new class of specific treatment for allergy, enabling wider application even for more severe allergic diseases.
Depolymerization of lignin for biological conversion through sulfonation and a chelator-mediated Fenton reaction (2022)

A chelator-mediated Fenton reaction efficiently cleaves C–C bonds in sulfonated lignin at or near room temperature and the depolymerized streams are compatible with microbial conversion.
ESD robust bipolar transistors with variable trigger and sustaining voltages (2004)

A new pseudo-vertical integrated npn bipolar transistor with variable sustaining and trigger voltages is presented in this paper. It is shown that the sustaining voltage can be tuned to obtain the required high value. These devices are realized in a junction isolated (JI) mixed-signal power BiCMOS technology with maximum breakdown voltage requirements in excess of 60V. The ESD robustness of these bipolar transistors is verified using transmission line pulse (TLP) and HBM (human body model) measurements. It is now possible to use a single bipolar transistor as an ESD protection device for a high voltage pin application instead of using stacked bipolar devices. The net result is a better control and possible reduction in overall die area.