gebhart/patrepeval huggingface dataset:
Crowdsourcing Science and Technology Expertise to Empower Legislative Branch Oversight and Policymaking (2022)

As the U.S. and the world struggle through the COVID-19 pandemic, the need for science and technology (S&T) expertise in governance has become even more stark. But in the U.S., the vast majority of legislators and their staffs is generalist, and they have limited resources for engaging with S&T. This can be a barrier to both legislative branch oversight of S&T-related issues and the development of evidence-based public policies, two functions that are especially critical in times of crisis. The obstacles to addressing these gaps have, however, created opportunities for innovations in how lawmakers connect with S&T resources, resulting in new models for scientist-policymaker engagement. Our program, the Congressional Science Policy Initiative , experiments with models for connecting crowdsourced S&T expertise with policymakers, namely, by enriching key congressional hearings with contributions gathered from the science community, organizing advisory councils of scientists and engineers that brief lawmakers, and crowdsourcing technical assistance from the S&T community for legislative initiatives. These activities, which rely on the collective intelligence of the S&T community and have been readily applied to supporting lawmakers’ decision-making processes during the pandemic, have bolstered legislative branch oversight of the executive branch, fact-finding into corporate practices, and evidence-based policymaking.
Hepatitis C Virus Nonstructural 5B Protein Regulates Tumor Necrosis Factor Alpha Signaling through Effects on Cellular IκB Kinase (2006)

Hepatitis C virus (HCV) NS5B protein is a membrane-associated phosphoprotein that possesses an RNA-dependent RNA polymerase activity. We recently reported that NS5A protein interacts with TRAF2 and modulates tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB and Jun N-terminal protein kinase (JNK). Since NS5A and NS5B are the essential components of the HCV replication complex, we examined whether NS5B could modulate TNF-alpha-induced NF-kappaB and JNK activation. In this study, we have demonstrated that TNF-alpha-induced NF-kappaB activation is inhibited by NS5B protein in HEK293 and hepatic cells. Furthermore, NS5B protein inhibited both TRAF2- and IKK-induced NF-kappaB activation. Using coimmunoprecipitation assays, we show that NS5B interacts with IKKalpha. Most importantly, NS5B protein in HCV subgenomic replicon cells interacted with endogenous IKKalpha, and then TNF-alpha-mediated IKKalpha kinase activation was significantly decreased by NS5B. Using in vitro kinase assay, we have further found that NS5B protein synergistically activated TNF-alpha-mediated JNK activity in HEK293 and hepatic cells. These data suggest that NS5B protein modulates TNF-alpha signaling pathways and may contribute to HCV pathogenesis.
The Integrated Role of Desferrioxamine and Phenserine Targeted to an Iron‐Responsive Element in the APP‐mRNA 5′‐Untranslated Region (2004)

The Alzheimer's amyloid precursor protein (APP) is the metalloprotein that is cleaved to generate the pathogenic Abeta peptide. We showed that iron closely regulated the expression of APP by 5'-untranslated region (5'-UTR) sequences in APP mRNA. Iron modulated APP holoprotein expression by a pathway similar to iron control of the translation of the ferritin-L and -H mRNAs by iron-responsive elements in their 5'-UTRs. APP gene transcription is also responsive to copper deficit where the Menkes protein depleted fibroblasts of copper to suppress transcription of APP through metal regulatory and copper regulatory sequences upstream of the APP 5' cap site. APP is a copper-zinc metalloprotein and chelation of Fe(3+) by desferrioxamine and Cu(2+) by clioquinol appeared to provide effective therapy for the treatment of AD in limited patient studies. We have introduced an RNA-based screen for small APP 5'-UTR binding molecules to identify leads that limit APP translation (but not APLP-1 and APLP-2) and amyloid Abeta peptide production. A library of 1200 drugs was screened to identify lead drugs that limited APP 5'-UTR-directed translation of a reporter gene. The efficacy of these leads was confirmed for specificity in a cell-based secondary assay to measure the steady-state levels of APP holoprotein relative to APLP-1/APLP-2 by Western blotting. Several chelators were identified among the APP 5'-UTR directed leads consistent with the presence of an IRE stem-loop in front of the start codon of the APP transcript. The APP 5'-UTR-directed drugs--desferrioxamine (Fe(3+) chelator), tetrathiomolybdate (Cu(2+) chelator), and dimercaptopropanol (Pb(2+) and Hg(2+) chelator)--each suppressed APP holoprotein expression (and lowered Abeta peptide secretion). The novel anticholinesterase phenserine also provided "proof of concept" for our strategy to target the APP 5'-UTR sequence to identify "anti-amyloid" drugs. We further defined the interaction between iron chelation and phenserine action to control APP 5'-UTR-directed translation in neuroblastoma (SY5Y) transfectants. Phenserine was most efficient to block translation under conditions of intracellular iron chelation with desferrioxamine suggesting that this anticholinesterase operated through an iron (metal)-dependent pathway at the APP 5'-UTR site.
A potential mediator of collagenous block copolymer gradients in mussel byssal threads (1998)

Mussel byssal threads contain unusual block copolymer-like proteins that combine collagen with flanking domains that resemble silk-fibroin (preCol-D) or elastin (preCol-P). These are distributed in complementary gradients along the length of the threads and as precursors in the mussel foot. We discuss a 76-kDa precursor, preCol-NG, from a cDNA library of the foot where it has no gradient but rather is distributed evenly along the distal to proximal axis. A pepsin-resistant fragment of preCol-NG has been confirmed in byssal threads. Like preCol-D and -P, this protein has a central collagenous domain, flanking domains, an acidic patch, and histidine-rich termini. The flanking domains of preCol-NG resemble the glycine-rich proteins of plant cell walls with tandem XGlyn repeats where X denotes alanine, leucine, or asparagine but not proline. Similarity with the (glycine-alanine) repeats and poly(alanine) runs of arthropod silks also exists. Based on available evidence, a model of preCol axial assembly is proposed in which preCol-NG functions as a mediator between preCol-D/-P molecules. This is consistent with the observed progression of mechanical properties in byssal threads.
Detection of Imported Malaria with the Cell-Dyn 4000 Hematology Analyzer (2002)

The sensitivity and specificity of the Cell-Dyn 4000 hematology analyzer in the diagnosis of imported malaria were studied with samples from patients in an academic hospital setting. The performance of the Cell-Dyn 4000 hematology analyzer was compared with that of conventional diagnostic methods for malaria. The Cell-Dyn 4000 hematology analyzer detected hemozoin-containing depolarizing monocytes in 29 of 58 patients with malaria and 2 of 55 patients without malaria. The presence or absence of depolarizing monocytes in patients with malaria was related to duration of symptoms before presentation for malaria analysis. A second parameter, pseudoreticulocytosis due to nuclear material of intraerythrocytic malaria parasites, was detected by the Cell-Dyn 4000 hematology analyzer almost exclusively in Plasmodium falciparum malaria patients with parasitemia levels of >/=0.5%. Attention to these abnormalities in medical centers without tropical disease expertise may decrease a delay in the diagnosis of malaria.
Complete Genome Sequence of Kluyveromyces lactis Strain GG799, a Common Yeast Host for Heterologous Protein Expression (2017)

We report the genome sequence of the dairy yeast <i>Kluyveromyces lactis</i> strain GG799 obtained using the Pacific Biosciences RS II platform. <i>K. lactis</i> strain GG799 is a common host for the expression of proteins at both laboratory and industrial scales.
Thermo‐hygro‐mechanical behavior of spider dragline silk: Glassy and rubbery states (2006)

Abstract Spider silk is considered as the basis of a new family of high performance fibers that would reproduce the excellent mechanical properties of the silk, in particular its extreme toughness. However, it has been observed that the mechanical properties of spider silk are severely influenced by humid environments that give rise to significant decreases in its length and elastic modulus. The change from stiff to compliant tensile properties is associated with the glass transition from a glassy to a rubbery state; here, we have found that it depends on both temperature and relative humidity. The glass transition was identified at different temperatures and relative humidities by monitoring the variation of the elastic modulus and observing the emergence of supercontraction. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 994–999, 2006
FReach Teach: A Computer-Based System for Teaching Advertising Media Planning (1998)

This paper describes a computer-based learning system, designed to teach media planning. The system consists of a case study, combined with a decision-support system through which students can practice applying the advanced analytical tools that might be discussed in the course. In addition to describing the system, the paper will discuss the systemâ€™s performance in a beta test at a major mid-western university.
Characterization of Intermediate Steps in Amyloid Beta (Aβ) Production under Near-native Conditions (2013)

Processing of the amyloid precursor protein (APP) by γ-secretase results in generation of Aβ peptides of different lengths ranging from 51 to 30 residues. Accumulation of Aβ and in particular Aβ42 is enhanced by familial Alzheimer disease (FAD) causing mutations in APP and is believed to play a pivotal role. The molecular mechanism underlying normal Aβ production, the impact of FAD mutations on this process and how anti-amyloidogenic γ-secretase modulators (GSMs) cause a selective decrease in Aβ40 and Aβ42 and an increase in shorter Aβ peptides, however, is poorly understood. By using a combined immuno- and LC-MS-based assay we identify several major intermediates, i.e. 3- and 4-peptides that line up head to head across the entire APP transmembrane sequence from Aβ51 to Aβ31/Aβ30 and from Aβ49 to Aβ30/31. FAD APP mutations displayed a relative increase in 3- and 4-peptides from Aβ48 to Aβ38 compared with Aβ49 to Aβ37. These findings correlate with an increase in the Aβ42/40 ratio. GSMs caused a decrease in Aβ40 and Aβ42 and an increase in Aβ37 and Aβ38 paralleled by an increase of the intermediates Aβ40-38 and Aβ42-39. Collectively, these data provide a thorough characterization of all intermediate steps in Aβ production in native cell membranes and provide key mechanistic insights to genetic and pharmacological modulation of Aβ generation.
Embedded Systems and Computer Architecture (2003)

Part One: The Building Blocks - Binary numbers Logic expressions Electronic logic circuits Computer arithmetic Part Two: Computing Machines - Computer design Instruction set and code assembly Program structures Simple computer circuits Input and output ports Input and output methods More devices Assembler and linker tools The control unit Part Three: Larger Computers - Larger computers Cache memory Memory management Appendix A G80 instruction set Appendix B ASCII character codes Appendix C Specifications of the input and output devices Appendix D The GDS assembler and linker Index
Immune cell and tumor cell-derived CXCL10 is indicative of immunotherapy response in metastatic melanoma (2021)

A T cell-inflamed tumor microenvironment is characterized by the accumulation and local activation of CD8<sup>+</sup> T cells and Bat3-lineage dendritic cells, which together are associated with clinical response to anti-programmed cell death protein 1 (anti-PD-1)-based immunotherapy. Preclinical models have demonstrated a crucial role for the chemokine CXCL10 in the recruitment of effector CD8<sup>+</sup> T cells into the tumor site, and a chemokine gene signature is also seen in T cell-inflamed tumors from patients. However, the cellular source of CXCL10 in human solid tumors is not known. To identify the cellular source of CXCL10 we analyzed 22 pretreatment biopsy samples of melanoma metastases from patients who subsequently underwent checkpoint blockade immunotherapy. We stained for CD45<sup>+</sup> and Sox10<sup>+</sup> cells with multiparameter immunofluorescence staining, and RNA in situ hybridization technology was used in concert to identify CXCL10 transcripts. The results were correlated with the expression levels of CXCL10 transcripts from bulk RNA sequencing and the best overall response to immune checkpoint inhibition (anti-PD-1 alone or with anti-CTLA-4) in the same patients. We identified CD45<sup>+</sup> cells as the major cellular source for CXCL10 in human melanoma metastases, with additional CXCL10 production seen by Sox10<sup>+</sup> cells. Up to 90% of CD45<sup>+</sup> cells and up to 69% of Sox10<sup>+</sup> cells produced CXCL10 transcripts. The CXCL10 staining result was consistent with the level of CXCL10 expression determined by bulk RNA sequencing. The percentages of CD45<sup>+</sup> CXCL10<sup>+</sup> cells and Sox10<sup>+</sup> CXCL10<sup>+</sup> cells independently predicted response (p<0.001). The average number of transcripts per cell correlated with the CD45<sup>+</sup> cell infiltrate (R=0.37). Immune cells and melanoma cells produce CXCL10 in human melanoma metastases. Intratumoral CXCL10 is a positive prognostic factor for response to immunotherapy, and the RNAscope technique is achievable using paraffin tissue. Strategies that support effector T cell recruitment via induction of CXCL10 should be considered as a mechanism-based intervention to expand immunotherapy efficacy.
New laterally selective growth technique by metalorganic chemical vapor deposition (1986)

Laterally selective growth of III-V compounds has been successfully demonstrated by metalorganic chemical vapor deposition. This was achieved by using a specially designed growth chamber and susceptor that allows the substrate to move with respect to a stationary GaAs or Si mask. We have used this technique to selectively deposit GaAs1−xPx with different values of x and a GaAs-GaAsP superlattice on a single GaAs substrate. We have also selectively grown multiple color light-emitting diodes on a GaAs substrate.
Determining Information Signatures in Smart Spaces (2009)

A Smart spaces infrastructure is becoming popular due to high abstraction level of information that can be stored and retrieved from such environments. Since the amount of information is growing rapidly in modern world and one of the targets of the Smart spaces is to leverage the level of information between many information sources and consumers, it is crucial to provide efficient and reliable mechanism for information dispersing, processing and assembling around the number of physical or logical entities. Approach presented is targeted for the determining information signatures in Smart spaces which are the entities that are generated by means of isomorphic transformation thus represent information domain independent fragments and could be interpreted in some cases as a least meaningful information sets.
Chimeric Antigen Receptor T-Cells (CAR T-Cells) for Cancer Immunotherapy – Moving Target for Industry? (2018)

The first CD19 CAR T-cell products, Kymriah and Yescarta, are entering the US market and also being evaluated for marketing authorization in the EU. This breakthrough has expanded the interest and also investments towards novel chimeric antigen receptor (CAR) designs, both for hematological malignancies and solid tumors. At the same time, there is active development in moving from autologous products to allogeneic, off-the-shelf -products. New manufacturing technologies are also emerging for production of these complex genetically-modified cells and even decentralized manufacturing in hospitals is under consideration. However, the high potency of CAR T-cells is associated with toxicity and not all patients respond to the treatment. In addition, the number of patient and product variables impacting the clinical outcome is high. The race towards novel CAR T treatment options for cancer patients has begun, but without careful design of the constructs and overall understanding of the factors that impact the ultimate outcome in each case, the road towards commercial success may be long and winding. This review discusses the product- and patient-related variables that may pose challenges for the industry and developers both from the scientific and regulatory perspective.
Classic animal models of Parkinson’s disease: a historical perspective (2018)

The quest to better understand the pathophysiology of Parkinson's disease (PD) and to find new therapies to provide greater relief to affected patients continues. The use of animal models of PD has been invaluable in the process. Here, we review, through a historical lens, some of the contribution of the 6-hydroxydopamine-lesioned rat and of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned nonhuman primate, in refining our understanding of PD and its treatment-related complications. We examine the mechanisms underlying the toxicity of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and then explore some of the advances at the molecular, pharmacological, electrophysiological and surgical levels made while experimenting on these animal models. We also discuss behavioural testing that can be performed with these animal models and highlight some of their limitations.
Stimulation of Collagen Formation by Insulin and Insulin-Like Growth Factor I in Cultures of Human Lung Fibroblasts* (1989)

We examined the effects of insulin and insulin-like growth factor I (IGF-I) on the production of collagen by cultures of human embryonic lung fibroblasts. Insulin at 20 ng/ml increased collagen accumulation by 58% and total protein formation by 18%. At 2 micrograms/ml, insulin increased collagen production by 2- to 3-fold and total protein production by 2-fold. The mRNA levels for alpha 1(I) and alpha 1(III) collagen chains were elevated by insulin compared with untreated control values. IGF-I at 10 ng/ml increased collagen production 2-fold. IGF-I at 100 ng/ml maximally increased collagen production 3-fold. A specific antibody to the IGF-I receptor (alpha IR-3) caused a concentration-related decline in insulin-induced collagen formation. The addition of antibody at 1 micrograms/ml, resulted in 80% inhibition of insulin-induced collagen accumulation. Higher levels of antibody were required to inhibit IGF-I mediated collagen formation. The presence of antibody (alpha IR-3) also blocked fibroblast proliferation stimulated by epidermal growth factor plus insulin. These data show that insulin-induced collagen formation is mediated primarily through an interaction with the IGF-I receptor. The modulation of extracellular matrix production by insulin may influence the repair of tissue injury and the development of the accelerated atherosclerosis that accompanies the diabetic state in humans.
Androgen Receptor Promotes Abdominal Aortic Aneurysm Development via Modulating Inflammatory Interleukin-1α and Transforming Growth Factor-β1 Expression (2015)

Sex difference is a risk factor for abdominal aortic aneurysm (AAA) formation yet the reason for male predominance remains unclear. Androgen and the androgen receptor (AR) influence the male sex difference, indicating that AR signaling may affect AAA development. Using angiotensin II–induced AAA in apolipoprotein E null mouse models (82.4% AAA incidence), we found that mice lacking AR failed to develop AAA and aorta had dramatically reduced macrophages infiltration and intact elastic fibers. These findings suggested that AR expression in endothelial cells, macrophages, or smooth muscle cells might play a role in AAA development. Selective knockout of AR in each of these cell types further demonstrated that mice lacking AR in macrophages (20% AAA incidence) or smooth muscle cells (12.5% AAA incidence) but not in endothelial cells (71.4% AAA incidence) had suppressed AAA development. Mechanism dissection showed that AR functioned through modulation of interleukin-1α (IL-1α) and transforming growth factor-β1 signals and by targeting AR with the AR degradation enhancer ASC-J9 led to significant suppression of AAA development. These results demonstrate the underlying mechanism by which AR influences AAA development is through IL-1α and transforming growth factor-β1, and provides a potential new therapy to suppress/prevent AAA by targeting AR with ASC-J9.
Iron Chelation Decreases NF- <i>k</i> B and HIV Type 1 Activation due to Oxidative Stress (1995)

An important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) through redox-controlled signal transduction pathways. In this study, we demonstrate that iron chelation by deferoxamine (DFO) protects against the cytotoxic and reactivating effects of hydrogen peroxide (H2O2). These protective effects were observed both in lymphocytic (ACH-2) and promonocytic (U1) cells latently infected by HIV-1. Concomitantly, NF-kappa B activation by H2O2, when followed by gel retardation assay, was decreased in the DFO-treated U1 and ACH-2 cells. This latter DFO-mediated effect was specific, as DFO did not clearly affect AP-1 DNA-binding activity when studied after H2O2-induced stress. More importantly, DFO protected against the H2O2-induced activation of HIV-1 as evidenced by reverse transcriptase activity in the supernatant. DFO also protected against PMA-induced NF-kappa B activation as well as TNF-alpha-induced HIV-1 activation. Furthermore, DFO attenuated the p24 response in PBMC infected with HIV-1 and stimulated with IL-2. These different effects of DFO were obtained at DFO concentrations lower than 5 microM. Other chemically unrelated iron chelators also provided protection against cytotoxicity, NF-kappa B activation, and HIV-1 activation in U1 cells challenged with H2O2.
Eukaryotic control on bacterial cell cycle and differentiation in the <i>Rhizobium</i> –legume symbiosis (2006)

Symbiosis between legumes and Rhizobium bacteria leads to the formation of root nodules where bacteria in the infected plant cells are converted into nitrogen-fixing bacteroids. Nodules with a persistent meristem are indeterminate, whereas nodules without meristem are determinate. The symbiotic plant cells in both nodule types are polyploid because of several cycles of endoreduplication (genome replication without mitosis and cytokinesis) and grow consequently to extreme sizes. Here we demonstrate that differentiation of bacteroids in indeterminate nodules of Medicago and related legumes from the galegoid clade shows remarkable similarity to host cell differentiation. During bacteroid maturation, repeated DNA replication without cytokinesis results in extensive amplification of the entire bacterial genome and elongation of bacteria. This finding reveals a positive correlation in prokaryotes between DNA content and cell size, similar to that in eukaryotes. These polyploid bacteroids are metabolically functional but display increased membrane permeability and are nonviable, because they lose their ability to resume growth. In contrast, bacteroids in determinate nodules of the nongalegoid legumes lotus and bean are comparable to free-living bacteria in their genomic DNA content, cell size, and viability. Using recombinant Rhizobium strains nodulating both legume types, we show that bacteroid differentiation is controlled by the host plant. Plant factors present in nodules of galegoid legumes but absent from nodules of nongalegoid legumes block bacterial cell division and trigger endoreduplication cycles, thereby forcing the endosymbionts toward a terminally differentiated state. Hence, Medicago and related legumes have evolved a mechanism to dominate the symbiosis.