gebhart/patrepeval huggingface dataset:
4-(Tetralin-1-yl)- and 4-(Naphthalen-1-yl)alkyl Derivatives of 1-Cyclohexylpiperazine as σ Receptor Ligands with Agonist σ2 Activity (2004)

Several 1-cyclohexylpiperazine derivatives related to sigma(2) receptor ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (33, K(i) = 0.34 nM) were synthesized and tested in radioligand binding assays, to attempt a structure-affinity relationship study. Intermediate alkyl chain length and methoxyl group position on the tetralin nucleus were varied. A few naphthalene analogues were also prepared. High affinities were found in sigma(2) receptor binding for almost all compounds, some of which displayed K(i) values in subnanomolar range, but low sigma(2)/sigma(1) selectivities were found. The highest sigma(2) affinities were displayed by compounds with an intermediate alkyl chain of three (32 and 43) or five methylenes (39 and 46). Quite high sigma(1) receptor affinity was found for compounds with a four-methylene chain; 36 (K(i) = 0.036 nM) and 45 (K(i) = 0.22 nM) displaying good sigma(1)/sigma(2) selectivity (406- and 139-fold, respectively). Moreover, homologues of compound 33 displayed also satisfactory selectivities over dopamine D(2)-like, serotonin 5-HT(3), and adrenergic alpha(1) receptors. These compounds and a few others were tested in the inhibition of the electrically evoked contractions in guinea pig bladder and were demonstrated to be full sigma(2) agonists. The activity values correlated well to the affinity scale (EC(50) in microM range). 33 and related compounds are proposed as a class of potential antineoplastic and PET diagnosis agents.
A robust model-based approach to indoor positioning using signal strength (2008)

A simple technique to estimate the position of a mobile node inside a building is based on the Received Signal Strength (RSS). In previous publications, we investigated the effectiveness of using circular array antennas and beamforming in order to enable an access point to estimate the position of a mobile inside a building. We also discussed the feasibility of using model-based radio maps to reduce the need for extensive offline measurements. In this paper, a positioning algorithm based on the relative order of the received signal strengths is discussed. This algorithm in conjunction with the ray-tracing propagation model can have promising performance for indoor environments and essentially eliminates the needs for an extensive set of a priori measurement, training or intricate calibration.
Reduction of Yellow Fever Virus Mouse Neurovirulence by Immunization with a Bacterially Synthesized Non-structural Protein (NS1) Fragment (1988)

Part of a yellow fever virus-specified non-structural protein (NS1) was expressed in Escherichia coli as a fusion protein with beta-galactosidase. Immunization of mice with this partially purified NS1-beta-galactosidase fusion protein induced yellow fever virus-specific antibodies and provided some protection against intracerebral challenge with the virus.
Electrochemical and Structural Properties of xLi2M‘O3·(1−x)LiMn0.5Ni0.5O2 Electrodes for Lithium Batteries (M‘ = Ti, Mn, Zr; 0 ≤ x ⩽ 0.3) (2004)

Electrochemical and structural properties of xLi2M‘O3·(1−x)LiMn0.5Ni0.5O2 electrodes (M‘ = Ti, Mn, Zr; 0 ≤ x ≤ 0.3) for lithium batteries are reported. Powder X-ray diffraction, lattice imaging by transmission electron microscopy, and nuclear magnetic resonance spectroscopy provide evidence that, for M‘ = Ti and Mn, the Li2M‘O3 component is structurally integrated into the LiMn0.5Ni0.5O2 component to yield “composite” structures with domains having short-range order, rather than true solid solutions in which the cations are uniformly distributed within discrete layers. Li2TiO3 and Li2ZrO3 components are electrochemically inactive, whereas electrochemical activity can be induced into the Li2MnO3 component above 4.3 V vs Li0. When cycled in lithium cells, xLi2MnO3·(1−x)LiMn0.5Ni0.5O2 electrodes with x = 0.3 provide capacities in excess of 300 mA·h/g over the range 4.6−1.45 V.
Preclinical Characterization of GLPG0634, a Selective Inhibitor of JAK1, for the Treatment of Inflammatory Diseases (2013)

The JAKs receive continued interest as therapeutic targets for autoimmune, inflammatory, and oncological diseases. JAKs play critical roles in the development and biology of the hematopoietic system, as evidenced by mouse and human genetics. JAK1 is critical for the signal transduction of many type I and type II inflammatory cytokine receptors. In a search for JAK small molecule inhibitors, GLPG0634 was identified as a lead compound belonging to a novel class of JAK inhibitors. It displayed a JAK1/JAK2 inhibitor profile in biochemical assays, but subsequent studies in cellular and whole blood assays revealed a selectivity of ∼30-fold for JAK1- over JAK2-dependent signaling. GLPG0634 dose-dependently inhibited Th1 and Th2 differentiation and to a lesser extent the differentiation of Th17 cells in vitro. GLPG0634 was well exposed in rodents upon oral dosing, and exposure levels correlated with repression of Mx2 expression in leukocytes. Oral dosing of GLPG0634 in a therapeutic set-up in a collagen-induced arthritis model in rodents resulted in a significant dose-dependent reduction of the disease progression. Paw swelling, bone and cartilage degradation, and levels of inflammatory cytokines were reduced by GLPG0634 treatment. Efficacy of GLPG0634 in the collagen-induced arthritis models was comparable to the results obtained with etanercept. In conclusion, the JAK1 selective inhibitor GLPG0634 is a promising novel therapeutic with potential for oral treatment of rheumatoid arthritis and possibly other immune-inflammatory diseases.
Intel MPX Explained (2018)

Memory-safety violations are the primary cause of security and reliability issues in software systems written in unsafe languages. Given the limited adoption of decades-long research in software-based memory safety approaches, as an alternative, Intel released Memory Protection Extensions (MPX)---a hardware-assisted technique to achieve memory safety. In this work, we perform an exhaustive study of Intel MPX architecture along three dimensions: (a) performance overheads, (b) security guarantees, and (c) usability issues. We present the first detailed root cause analysis of problems in the Intel MPX architecture through a cross-layer dissection of the entire system stack, involving the hardware, operating system, compilers, and applications. To put our findings into perspective, we also present an in-depth comparison of Intel MPX with three prominent types of software-based memory safety approaches. Lastly, based on our investigation, we propose directions for potential changes to the Intel MPX architecture to aid the design space exploration of future hardware extensions for memory safety. A complete version of this work appears in the 2018 proceedings of the ACM on Measurement and Analysis of Computing Systems.
Direct PCR Sequencing with Boronated Nucleotides (1997)

A method is described to simultaneously amplify and sequence DNA using a new class of nucleotides containing boron. During the polymerase chain reaction, boron-modified nucleotides, i.e. 2'-deoxynucleoside 5'-alpha-[P-borano]-triphosphates, are incorporated into the product DNA. The boranophosphate linkages are resistant to nucleases and thus the positions of the boranophosphates can be revealed by exonuclease digestion, thereby generating a set of fragments that defines the DNA sequence. The boranophosphate method offers an alternative to current PCR sequencing methods. Single-sided primer extension with dideoxynucleotide chain terminators is avoided, with the consequence that the sequencing fragments are derived directly from the original PCR products. Boranophosphate sequencing is demonstrated with the Pharmacia and the Applied Biosystems 373A automatic sequencers, producing data that is comparable with cycle sequencing.
Mechanotransduction Across the Cell Surface and Through the Cytoskeleton (1993)

Mechanical stresses were applied directly to cell surface receptors with a magnetic twisting device. The extracellular matrix receptor, integrin beta 1, induced focal adhesion formation and supported a force-dependent stiffening response, whereas nonadhesion receptors did not. The cytoskeletal stiffness (ratio of stress to strain) increased in direct proportion to the applied stress and required intact microtubules and intermediate filaments as well as microfilaments. Tensegrity models that incorporate mechanically interdependent struts and strings that reorient globally in response to a localized stress mimicked this response. These results suggest that integrins act as mechanoreceptors and transmit mechanical signals to the cytoskeleton. Mechanotransduction, in turn, may be mediated simultaneously at multiple locations inside the cell through force-induced rearrangements within a tensionally integrated cytoskeleton.
Mechanism for the Action of Bone Morphogenetic Proteins and Regulation of Their Activity (2002)

Although the bone morphogenetic proteins (BMPs) are multifunctional proteins, implantation of osteogenic BMPs such as BMP-2 and BMP-7 at an osseous or extraosseous site results in bone and cartilage formation. These molecules are soluble, local-acting signaling proteins, which bind to specific receptors on the surface of the cell. The receptors then transduce the signal via a group of proteins called Smads, which in turn activate particular genes. In vivo, these BMPs act primarily as differentiation factors, turning responsive mesenchymal cells into cartilage- and bone-forming cells. A summary of the in vitro and in vivo studies suggests that implantation of these BMPs stimulates cells from the soft and hard tissues (e.g., muscle, bone marrow, periosteum) to become bone, and in some cases, cartilage forming cells. The activity of BMPs is tightly controlled at many levels. The tissue-specific transcription factor (basic helix-loop-helix factor) and its binding sequence (E-box) together play a critical role in deciding the expression of BMPs. Outside the cell, soluble inhibitory proteins such as noggin, chordin, and follistatin can bind certain of the BMPs and inhibit their binding to cell surface receptors. Inside the cell, the activity of BMPs is controlled through the combination of signal-transducing and inhibitory Smad proteins. Bone morphogenetic proteins can upregulate expression of the inhibitory Smad proteins. These Smads are phosphorylated and translocate into the nucleus, where they regulate the transcription of target genes together with other transcription factors including PEBP2alphaA/Cbfa1. Cooperation between PEBP2alphaA/Cbfa1 and BMP-activated Smad (Smad1/5) in the nucleus induces the expression of the genes related to the osteoblast phenotype. In addition, a number of negative regulators of BMP action exist within the nucleus. All of these regulatory mechanisms together cause the bone-induction process to be controlled tightly and self-limiting. Thus, bone induction is observed only locally at the site of BMP and matrix implantation, as defined by the volume of matrix, and it is limited temporally only to the time when the BMP is present.
Selective non-adsorption preparative chromatography of proteins (1989)

A novel approach to protein purification is developed and evaluated where the protein of interest is allowed to pass through a series of chromatographic columns while contaminating proteins are retained. This approach has the combined advantages of speed, economy, scalability and gentleness to the purified proteins. Use of combined anion and cation exchange sorbents at a protein's isoelectric point and low salt concentrations results in a situation where the protein is not retained while many others are. This combination was used in the purification of IgGl from bovine serum to 95% purity in a single step. The preparative aspects of this purification were investigated, including frontal loading, scalability, continuous processing and effect of increasing mobile phase flow. The potential of this ion exchange combination for other proteins was evaluated and the technique for selecting proper mobile phase conditions for any protein was developed. Additional separation modes developed for this non-adsorption approach were size exclusion and affinity chromatography. A series of varying high ligand density sorbents was synthesized. These sorbents allow the frontal purification of proteins via their hydrophobic interaction at moderate ionic strength. A series of these columns was used to fractionate bovine serum. Large pore polystyrene sorbents were evaluated for the rapid separation of proteins. It was demonstrated that these sorbents allow the mobile phase to flow through them at high flow rate. This allows the sorbents to bind more protein at higher flow rates rather than less. The preparative application of this phenomenom was investigated.
Cystatin E1 and E2, New Members of Male Reproductive Tract Subgroup Within Cystatin Type 2 Family1 (2003)

The family of type 2 cystatin proteins is a class of cysteine proteinase inhibitors that function as potent inhibitors of papain-like cysteine proteinases. Recent studies have suggested that cystatins in the male reproductive tract subgroup may perform functions distinct from those of typical cystatins. The objective of the present study was to identify and characterize the expression of new gene members of the cystatin family 2 in mouse male reproductive tissues. Two new members of cystatin family 2, named mouse Cystatin E1 and mouse Cystatin E2 (mCST E1 and mCST E2, respectively), were identified in mice by searching the National Center for Biotechnology Information database for proteins containing homology to known type 2 cystatins. Human CST E1 has recently been reported independently under the name CST 11. The deduced amino acid sequences of these genes have significant homology with the family 2 cystatins, including four conserved cysteine residues at the C-terminus. Similar to other male reproductive subgroup cystatins, the inhibitory motifs are not well conserved in these genes. Northern blot analyses showed that both genes were highly expressed only in the epididymis. In situ hybridization demonstrated that both genes were restricted in their expression to the epithelial cells of the caput and that the highest expression was localized to the initial segment of caput epididymis. Northern blot analyses and in situ hybridization showed that both mCST E1 and E2 mRNA decreased after castration, and treatment with testosterone propionate (T) did not maintain expression of these genes. In fact, T treatment further repressed the expression of these genes in the epididymis following castration. Efferent ductule ligation resulted in a dramatic decrease of epididymal expression of mCST E1 and E2. The expression of mCST E1 mRNA was up-regulated by 17 beta-estradiol (E) administration for 7 days postcastration, whereas no recovery of mCST E1 mRNA level was detected after 14 days of E treatment. Combined E and T (E+T) treatment for 1 and 2 wk reduced the mCST E1 transcripts. The expression of mCST E2 mRNA was maintained by E administration for both 7 and 14 days after castration, whereas treatment of both T and E repressed the expression of mCST E2. Although both mCST E1 and E2 share significant homology with family 2 cystatins, including similar distribution in tissues and localization in epididymis, these genes may have different functions, because their regulation involves different hormones and, probably, other testicular factors.
Reduction of carbon dioxide in 1-butyl-3-methylimidazolium acetate (2009)

Gaseous CO(2) is almost irreversibly absorbed by the room temperature ionic liquid 1-butyl-3-methylimidazolium acetate ([C(4)mim][Ac]) in which it undergoes a chemically irreversible, one electron electrochemical reduction, suggesting a means for the sequestration of the greenhouse gas.
Pilot Study of Stimulation of the Cholinergic Anti-Inflammatory Pathway with an Implantable Vagus Nerve Stimulation Device in Patients with Rheumatoid Arthritis. (2012)

Background/Purpose: The inflammatory reflex regulates innate and adaptive immunity (Andersson O, Tracey K, Annu. Rev. Immunol. 2012 ; 30:313). Activation of its efferent arm (the Cholinergic Antiinflammatory Pathway (CAP)), by electrical vagus nerve stimulation (VNS) reduces systemic inflammation and ameliorates disease in many acute and chronic animal models. We determined whether VNS could similarly improve clinical manifestations of rheumatoid arthritis (RA). Methods: This is an open label study of patients with active RA (_/_ 4 tender and 4 swollen joints (28 joint scoring), and CRP of at least 7 mg/L) despite stable methotrexate dose for 3 months. Patients failing TNF antagonists (only for safety or tolerability reasons) could also be enrolled after washout. After a pre-implantation baseline visit, patients were surgically implanted with a Cyberonics VNS system. The device delivered the first VNS during its standard intraoperative diagnostic check sequence. Two weeks following implantation patients returned for initial in-clinic VNS. One week after the first clinic visit (day 7), patients began self-delivery of 60 second, once daily home stimulations, escalated in output current intensity as tolerated, through day 28. At day 28 patients without a EULAR good or moderate response were increased to four times daily VNS. Primary endpoint results at day 42 are reported. Results: 8 patients (4 female, 7/8 RF_, 6/8 ACPA_, mean age 56 [range 39–70], mean disease duration 8 yrs [range 0.5–13]) were enrolled and implanted. Implantation and stimulation were generally well tolerated. Moderate postoperative hoarseness occurred in one patient. Pre implantation baseline values (mean, SD) were: DAS28-CRP: 6.06 (0.87), CRP: 17.5 mg/L (9.9), HAQ-DI: 1.63 (0.90). Changes at day 42 visit from pre-implantation values were: DAS28- CRP: _2.28 (1.65), CRP: _3.46 (17.95) mg/L, HAQ-DI: _0.44 (0.48). Similar levels of improvement were seen across all ACR core set assessments. ACR 20/50/70 response rates from pre-implantation baseline to day 42 were 75% (6/8), 50% (4/8), and 25% (2/8), respectively. Conclusion: In this pilot study VNS was generally well tolerated and improved signs and symptoms of RA. This is the first demonstration in humans that stimulation of the CAP can favorably impact clinical manifestations of systemic inflammation. If efficacy and safety are confirmed in larger controlled studies, implantable medical devices may offer a feasible alternative approach to the treatment of RA and other chronic inflammatory diseases.
In Vivo Evidence for the Contribution of Human Histocompatibility Leukocyte Antigen (Hla)-Dq Molecules to the Development of Diabetes (2000)

Although DQA1*0301/DQB1*0302 is the human histocompatibility leukocyte antigen (HLA) class II gene most commonly associated with human type 1 diabetes, direct in vivo experimental evidence for its diabetogenic role is lacking. Therefore, we generated C57BL/6 transgenic mice that bear this molecule and do not express mouse major histocompatibility complex (MHC) class II molecules (DQ8(+)/mII(-)). They did not develop insulitis or spontaneous diabetes. However, when DQ8(+)/mII(-) mice were bred with C57BL/6 mice expressing costimulatory molecule B7-1 on beta cells (which normally do not develop diabetes), 81% of the DQ8(+)/mII(-)/B7-1(+) mice developed spontaneous diabetes. The diabetes was accompanied by severe insulitis composed of both T cells (CD4(+) and CD8(+)) and B cells. T cells from the diabetic mice secreted large amounts of interferon gamma, but not interleukin 4, in response to DQ8(+) islets and the putative islet autoantigens, insulin and glutamic acid decarboxylase (GAD). Diabetes could also be adoptively transferred to irradiated nondiabetic DQ8(+)/mII(-)/B7-1(+) mice. In striking contrast, none of the transgenic mice in which the diabetes protective allele (DQA1*0103/DQB1*0601, DQ6 for short) was substituted for mouse MHC class II molecules but remained for the expression of B7-1 on pancreatic beta cells (DQ6(+)/mII(-)/B7-1(+)) developed diabetes. Only 7% of DQ(-)/mII(-)/B7-1(+) mice developed diabetes at an older age, and none of the DQ(-)/mII(+)/B7-1(+) mice or DQ8(+)/mII(+)/B7-1(+) mice developed diabetes. In conclusion, substitution of HLA-DQA1*0301/DQB1*0302, but not HLA-DQA1*0103/DQB1*0601, for murine MHC class II provokes autoimmune diabetes in non-diabetes-prone rat insulin promoter (RIP).B7-1 C57BL/6 mice. Our data provide direct in vivo evidence for the diabetogenic effect of this human MHC class II molecule and a unique "humanized" animal model of spontaneous diabetes.
Incremental Analysis of Cyclo-Static Synchronous Dataflow Graphs (2015)

In this article, we present a mathematical characterisation of admissible schedules of cyclo-static dataflow ( csdf ) graphs. We demonstrate how algebra ic manipulation of this characterization is related to unfolding csdf actors and how this manipulation allows csdf graphs to be transformed into mrsdf graphs that are equivalent , in the sense that they admit the same set of schedules. The presented transformation allows the rich set of existing analysis techniques for mrsdf graphs to be applied to csdf graphs and generalizes the well-known transformations from csdf and mrsdf into hsdf . Moreover, it gives rise to an incremental approach to the analysis of csdf graphs, where approximate analyses are combined with exact transformations. We show the applicability of this incremental approach by demonstrating its effectiveness on the problem of optimizing buffer sizes under a throughput constraint.
Silage yield with different sowing dates and chemical control of rice black-streaked dwarf virus in maize. (1989)

Results indicate that RP is associated with variation in gene NOS1. This finding may be related to the observation that the significant SNP in NOS1 is known to exhibit functional influence on the gene expression.
KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells (2000)

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 3 genes that are homologous to cellular chemokines. vMIP-III, the product of open reading frame K4.1, is the most distantly related to human chemokines and has yet to be characterized. We have examined the interaction of vMIP-III with chemokine receptors, its expression in KS lesions, and its in ovo angiogenic properties. We show expression of vMIP-III in KS lesions and demonstrate the stimulation of angiogenesis by this chemokine, like vMIP-I and vMIP-II, in the chick chorioallantoic membrane assay. vMIP-III does not block human immunodeficiency virus entry through the coreceptors CCR3, CCR5, or CXCR4. However, vMIP-III is an agonist for the cellular chemokine receptor CCR4. CCR4 is expressed by TH2-type T cells. Consistent with this, vMIP-III preferentially chemoattracts this cell type. Because of these biologic properties and because it is expressed in KS lesions, vMIP-III may play an important role in the pathobiology of KS. (Blood. 2000;95:1151-1157)
Treatment of Heart Failure by Calcium Cycling Gene Therapy (2007)

Heart failure is a major cause of morbidity and mortality in Western countries. While progress in conventional treatment modalities is making steady and incremental gains to reduce this disease burden, there remains a need to explore new and potentially therapeutic approaches. Gene therapy, for example, was initially envisioned as a treatment strategy for inherited monogenic disorders. It is now apparent that gene therapy has broader potential, which also includes acquired polygenic diseases such as heart failure. Advances in the understanding of the molecular basis of conditions such as these, together with the evolution of increasingly efficient gene transfer technology, has placed congestive heart failure within the reach of gene-based therapy.