gebhart/patrepeval huggingface dataset:
Characterization of a Neuregulin-Related Gene, Don-1, That Is Highly Expressed in Restricted Regions of the Cerebellum and Hippocampus (1997)

Members of the epidermal growth factor family of receptors have long been implicated in the pathogenesis of various tumors, and more recently, apparent roles in the developing heart and nervous system have been described. Numerous ligands that activate these receptors have been isolated. We report here on the cloning and initial characterization of a second ligand for the erbB family of receptors. This factor, which we have termed Don-1 (divergent of neuregulin 1), has structural similarity with the neuregulins. We have isolated four splice variants, two each from human and mouse, and have shown that they are capable of inducing tyrosine phosphorylation of erbB3, erbB4, and erbB2. In contrast to those of neuregulin, high levels of expression of Don-1 are restricted to the cerebellum and dentate gyrus in the adult brain and to fetal tissues.
Nonlinear analyses on CMOS integrated silicon pressure sensor (1985)

This paper reports theoretical and experimental results of analysis on nonlinear characteristics, for the newly designed CMOS integrated pressure sensor with square silicon diaphragm. It is shown that nonlinearity is caused by both the large diaphragm deflection effect and nonlinear piezoresistance effect of resistors. The optimum layout for piezoresistors to minimize their nonlinearity is also shown. The measured nonlinearity for the fabricated device quantitatively agrees well with the numerically analyzed nonlinearity.
Resource Competition Shapes the Response of Genetic Circuits (2017)

A common approach to design genetic circuits is to compose gene expression cassettes together. While appealing, this modular approach is challenged by the fact that expression of each gene depends on the availability of transcriptional/translational resources, which is in turn determined by the presence of other genes in the circuit. This raises the question of how competition for resources by different genes affects a circuit's behavior. Here, we create a library of genetic activation cascades in E. coli bacteria, where we explicitly tune the resource demand by each gene. We develop a general Hill-function-based model that incorporates resource competition effects through resource demand coefficients. These coefficients lead to nonregulatory interactions among genes that reshape the circuit's behavior. For the activation cascade, such interactions result in surprising biphasic or monotonically decreasing responses. Finally, we use resource demand coefficients to guide the choice of ribosome binding site and DNA copy number to restore the cascade's intended monotonically increasing response. Our results demonstrate how unintended circuit's behavior arises from resource competition and provide a model-guided methodology to minimize the resulting effects.
Human Serum Albumin and p53-Activating Peptide Fusion Protein Is Able to Promote Apoptosis and Deliver Fatty Acid-Modified Molecules (2013)

Therapeutic peptides offer a high degree of specificity, potency, and low toxicity; making them promising candidates for cancer therapy. Despite these advantages, a number of hurdles, such as poor serum stability and inefficient cellular penetration, must be overcome. Fusing a therapeutic peptide to human serum albumin (HSA) is a common approach to extend the serum stability of a peptide that binds to extracellular receptors. However, no study has shown that this approach can be applied to target intracellular proteins. Here we demonstrate the feasibility of using a recombinant human serum albumin (rHSA) fusion protein to simultaneously deliver two types of molecules: a peptide capable of binding an intracellular target, as well as fatty acid (FA)-modified FITC (FA-FITC). Two peptides reported to disrupt the intracellular p53 and MDM2/MDMX interaction were fused to the C-terminal of HSA. Cellular and biochemical studies indicate that rHSA fusion proteins were efficiently taken up by SJSA-1 cells and retained MDM2- and MDMX-binding activity. By inducing the accumulation of p53, both fusion proteins promoted efficient cytotoxicity in SJSA-1 cells via caspase activation. Long chain fatty acid (LCFA) transportation is an essential endogenous function of HSA. This study also demonstrates that rHSA fusion proteins formed highly stable complexes with FA-FITC via non-covalent interactions. FA-FITC complexed with HSA could be internalized efficiently and rHSA-P53i and rHSA-PMI retained apoptotic activity as complex components. It is expected that such an approach can ultimately be used to facilitate intracellular delivery of two anticancer therapeutics, each with distinct but complimentary mechanisms, to achieve synergistic efficacy.
Evaluation of an Isothermal Signal Amplification Method for Rapid Detection of Methicillin-Resistant Staphylococcus aureus from Patient-Screening Swabs (2003)

A new molecular assay (CytAMP) utilizing isothermal signal-mediated amplification of RNA was evaluated for rapid detection of methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA). The assay targeted the coa (coagulase) and mecA genes, thereby simultaneously identifying S. aureus and methicillin (oxacillin) resistance. Results were obtained in approximately 3.5 h as a color signal in 96-well microtiter plates. The detection limit was between 2 x 10(5) and 10(6) CFU/assay, equivalent to 4 x 10(6) to 2 x 10(7) CFU/ml in an overnight broth. This level of growth was obtained with an initial inoculum of 10 to 50 CFU. The CytAMP assay and a mecA-femB PCR assay both detected 113 MRSA strains among 396 clinical isolates of bacteria (CytAMP sensitivity and specificity were both 100% relative to those of PCR). Conventional culture detected 109 MRSA strains, but with 19 false-positive and 23 false-negative results relative to both molecular methods. Discrepancies were also observed for 100 enrichment broths containing MRSA screening swabs, with 11 broths culture negative but PCR positive. CytAMP and PCR were more in agreement, but six broths were CytAMP negative and PCR positive. Five of these contained 10(2) to 10(5) CFU/assay (below the CytAMP detection limit of 2 x 10(5) CFU/assay), and the sixth contained 10(6) CFU/assay. Overall, culture and CytAMP had similar sensitivities and specificities relative to those of PCR, but the CytAMP assay enabled swabs to be analyzed as a batch following overnight incubation in enrichment broth, with results reported before 12 noon the next day.
Microeconomic algorithms for load balancing in distributed computer systems (2003)

A novel approach to allocating and sharing communication and computational resources in a distributed system is described. The approach, which is based on concepts drawn from microeconomics, uses algorithms that are competitive rather than cooperative. The effectiveness of these concepts is demonstrated by describing an economy that improves the performance of a distributed system by implementing load balancing. In this economy, competition sets prices for the resources in the system. Jobs complete for the resources by issuing bids, and the resource allocation decisions are made through auctions held by the processors. The benefits of the method include limited complexity and algorithms that are intrinsically decentralized and modular. Simulation studies show that these economies achieve substantial performance benefits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
<title>Delta-doped CCDs: high QE with long-term stability at UV and visible wavelengths</title> (1994)

Delta-doped CCDs, developed at JPL's Microdevices Laboratory, have achieved stable 100% internal quantum efficiency in the visible and near UV regions of the spectrum. In this approach, an epitaxial silicon layer is grown on a fully-processed commercial CCD using molecular beam epitaxy. During the silicon growth on the CCD, 30% of a monolayer of boron atoms are deposited on the surface, followed by a 15 $angstrom silicon layer for surface passivation. The boron is nominally incorporated within a single atomic layer at the back surface of the device, resulting in the effective elimination of the backside potential well. The measured quantum efficiency is in good agreement with the theoretical limit imposed by reflection from the Si surface. Enhancement of the total quantum efficiency in the blue visible and near UV has been demonstrated by depositing antireflection coatings on the delta-doped CCD. Recent results on antireflection coatings and quantum efficiency measurements are discussed.
Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help (2012)

We have developed an in vitro model that advances our understanding of the immunobiology of human CD4+ T cell help of CD8+ T cells. Our data suggests that human CD4+ T cell help can be leveraged to expand CD8+ T cells in vitro.
Genetic variation in MKL2 and decreased downstream PCTAIRE1 expression in extreme, fatal primary human microcephaly (2013)

The genetic mechanisms driving normal brain development remain largely unknown. We performed genomic and immunohistochemical characterization of a novel, fatal human phenotype including extreme microcephaly with cerebral growth arrest at 14-18 weeks gestation in three full sisters born to healthy, non-consanguineous parents. Analysis of index cases and parents included familial exome sequencing, karyotyping, and genome-wide single nucleotide polymorphism (SNP) array. From proband, control and unrelated microcephalic fetal cortical tissue, we compared gene expression of RNA and targeted immunohistochemistry. Each daughter was homozygous for a rare, non-synonymous, deleterious variant in the MKL2 gene and heterozygous for a private 185 kb deletion on the paternal allele, upstream and in cis with his MKL2 variant allele, eliminating 24 CArG transcription factor binding sites and MIR4718. MKL1 was underexpressed in probands. Dysfunction of MKL2 and its transcriptional coactivation partner, serum response factor (SRF), was supported by a decrease in gene and protein expression of PCTAIRE1, a downstream target of MKL2:SRF heterodimer transcriptional activation, previously shown to result in severe microcephaly in murine models. While disruption of the MKL2:SRF axis has been associated with severe microcephaly and disordered brain development in multiple model systems, the role of this transcription factor complex has not been previously demonstrated in human brain development.
Synthesis, Two-Dimensional Assembly, and Surface Pressure-Induced Coalescence of Ultranarrow PbS Nanowires (2007)

Ultranarrow (1.8 nm) PbS nanowires are synthesized in a single step, under benchtop conditions at relatively low temperature (90 °C). The nanowires exhibit a nearly perfect crystal lattice, high width uniformity, and tight side-by-side registry. Two-dimensional (2D) assembly over large areas (>15 μm2) is achieved using the Langmuir Blodgett method. The wire width can be readily controlled in the range 1.8−10 nm by a surface pressure-induced coalescence reaction, as monitored by transmission electron microscopy and Raman spectroscopy. The fluorescence of the 2D assembly shows strong polarization dependence along the long axis of the wires, making the system potentially suitable for orientation-sensitive devices.
Human neuronal cells in culture: from concepts to basic methodology. (1990)

The paper reviews some conceptual and methodological aspects of the tissue culture models which, during the past three decades, demonstrated a remarkable mimicry of many important structures and functions of the mammalian Central Nervous System (CNS) and related peripheral sensory and motor elements. Emphasis is placed on an original human neuronal tissue culture model obtained from selective CNS areas. The different cell types were identified and the neurotrophic interactions preliminary characterized. Neuropathological findings suggest hypothesis that can be fully tested using in vitro human models of affected cerebral specific areas.
A novel environment for situated vision and behavior (2002)

We present a new environment for the development of active vision algorithms that are situated in a behavioral context. Our environment allows an unencumbered person to interact with a simulated graphical world which contains autonomous agents. Active vision techniques are used to observe the person and provide perceptual stimuli to the agents. An image of the person is composited together with the graphical world and projected onto a large video screen which the person can observe. The agents inhabiting the world are modeled as autonomous entities which have their own simulated sensors and goals and which can interpret the actions of the participant and react to them in real-time. The goals of these agents provide behavioral context for the execution of the low-level vision routines which observe the person. Several prototypical worlds have been implemented in this environment and tested on hundreds of users at a large-scale public installation.
Cubic AgPb m SbTe 2+ m : Bulk Thermoelectric Materials with High Figure of Merit (2004)

The conversion of heat to electricity by thermoelectric devices may play a key role in the future for energy production and utilization. However, in order to meet that role, more efficient thermoelectric materials are needed that are suitable for high-temperature applications. We show that the material system AgPb(m)SbTe(2+m) may be suitable for this purpose. With m = 10 and 18 and doped appropriately, n-type semiconductors can be produced that exhibit a high thermoelectric figure of merit material ZTmax of approximately 2.2 at 800 kelvin. In the temperature range 600 to 900 kelvin, the AgPb(m)SbTe(2+m) material is expected to outperform all reported bulk thermoelectrics, thereby earmarking it as a material system for potential use in efficient thermoelectric power generation from heat sources.
Prediction of Local Recurrence, Distant Metastases, and Death After Breast-Conserving Therapy in Early-Stage Invasive Breast Cancer Using a Five-Biomarker Panel (2009)

The 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT.
The quality of life impact of acne and rosacea compared to other major medical conditions. (2014)

Acne and rosacea impact HRQL to a similar degree as other major medical conditions by indirect comparison to psoriasis, a skin condition causing significant disability, and by direct comparison for acne. In the setting of limited health care resources, allocation should be grounded in the evidence that acne and rosacea are not trivial in their effects.
Thrombolysis-Related Hemorrhagic Infarction (2002)

Thrombolysis-related HI (HI1-HI2) represents a marker of early successful recanalization, which leads to a reduced infarct size and improved clinical outcome.
Identification and characterization of the high affinity [3H]ryanodine receptor of the junctional sarcoplasmic reticulum Ca2+ release channel. (1987)

The high affinity ryanodine receptor of the Ca2+ release channel from junctional sarcoplasmic reticulum of rabbit skeletal muscle has been identified and characterized using monoclonal antibodies. Anti-ryanodine receptor monoclonal antibody XA7 specifically immunoprecipitated [3H]ryanodine-labeled receptor from digitonin-solubilized triads in a dose-dependent manner. [3H]Ryanodine binding to the immunoprecipitated receptor from unlabeled digitonin-solubilized triads was specific, Ca2+-dependent, stimulated by millimolar ATP, and inhibited by micromolar ruthenium red. Indirect immunoperoxidase staining of nitrocellulose blots of various skeletal muscle membrane fractions has demonstrated that anti-ryanodine receptor monoclonal antibody XA7 recognizes a high molecular weight protein (approximately 350,000 Da) which is enriched in isolated triads but absent from light sarcoplasmic reticulum vesicles and transverse tubular membrane vesicles. Thus, our results demonstrate that monoclonal antibodies to the approximately 350,000-Da junctional sarcoplasmic reticulum protein immunoprecipitated the ryanodine receptor with properties identical to those expected for the ryanodine receptor of the Ca2+ release channel.
Generating Barcoded Libraries for Multiplex High-Throughput Sequencing (2011)

Molecular barcoding is an essential tool to use the high throughput of next generation sequencing platforms optimally in studies involving more than one sample. Various barcoding strategies allow for the incorporation of short recognition sequences (barcodes) into sequencing libraries, either by ligation or polymerase chain reaction (PCR). Here, we present two approaches optimized for generating barcoded sequencing libraries from low copy number extracts and amplification products typical of ancient DNA studies.
Low-loss fiber-matched low-temperature PECVD waveguides with small-core dimensions for optical communication systems (1997)

Plasma-enhanced chemical vapor deposition (PECVD) offers a simple way of fabricating (doped) silica layers on silicon. A new design of the waveguide core allows low-loss fiber matched waveguides with low birefringence without high-temperature annealing. The increased loss of doped plasma deposited silica due to hydrogen incorporation is overcome by reducing the core dimensions and increasing the refractive index contrast. The waveguides can easily be fabricated using standard PECVD technologies and resist masked reactive ion etching (RIE) etching. Integrated optical devices such as 1/spl times/8 power splitters, 1300/1550-nm wavelength multiplexers and thermooptical switches were successfully fabricated and tested.
Membrane Fusion (1992)

Common themes are emerging from the study of viral, cell-cell, intracellular, and liposome fusion. Viral and cellular membrane fusion events are mediated by fusion proteins or fusion machines. Viral fusion proteins share important characteristics, notably a fusion peptide within a transmembrane-anchored polypeptide chain. At least one protein involved in a cell-cell fusion reaction resembles viral fusion proteins. Components of intracellular fusion machines are utilized in multiple membrane trafficking events and are conserved through evolution. Fusion pores develop during and intracellular fusion events suggesting similar mechanisms for many, if not all, fusion events.
Phototherapy for psoriasis (2001)

This review covers the current practice of phototherapy with ultraviolet (UV) radiation without sensitizers and of psoralen photochemotherapy (PUVA) in the treatment of psoriasis. Both treatment modalities are well established in today's therapeutic armamentarium. Phototherapeutic regimens use repeated controlled UV exposures to alter cutaneous biology, aiming to induce remission of skin disease. Although UVB has been used for a longer time than PUVA, the latter has been evaluated and validated in a more detailed and coordinated fashion.
Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor (2012)

Replacement of the central, para-substituted fluorophenyl ring in the γ-secretase inhibitor 1 (BMS-708,163) with the bicyclo[1.1.1]pentane motif led to the discovery of compound 3, an equipotent enzyme inhibitor with significant improvements in passive permeability and aqueous solubility. The modified biopharmaceutical properties of 3 translated into excellent oral absorption characteristics (~4-fold ↑ C(max) and AUC values relative to 1) in a mouse model of γ-secretase inhibition. In addition, SAR studies into other fluorophenyl replacements indicate the intrinsic advantages of the bicyclo[1.1.1]pentane moiety over conventional phenyl ring replacements with respect to achieving an optimal balance of properties (e.g., γ-secretase inhibition, aqueous solubility/permeability, in vitro metabolic stability). Overall, this work enhances the scope of the [1.1.1]-bicycle beyond that of a mere "spacer" unit and presents a compelling case for its broader application as a phenyl group replacement in scenarios where the aromatic ring count impacts physicochemical parameters and overall drug-likeness.
Prediction of proteasome cleavage motifs by neural networks (2002)

We present a predictive method that can simulate an essential step in the antigen presentation in higher vertebrates, namely the step involving the proteasomal degradation of polypeptides into fragments which have the potential to bind to MHC Class I molecules. Proteasomal cleavage prediction algorithms published so far were trained on data from in vitro digestion experiments with constitutive proteasomes. As a result, they did not take into account the characteristics of the structurally modified proteasomes--often called immunoproteasomes--found in cells stimulated by gamma-interferon under physiological conditions. Our algorithm has been trained not only on in vitro data, but also on MHC Class I ligand data, which reflect a combination of immunoproteasome and constitutive proteasome specificity. This feature, together with the use of neural networks, a non-linear classification technique, make the prediction of MHC Class I ligand boundaries more accurate: 65% of the cleavage sites and 85% of the non-cleavage sites are correctly determined. Moreover, we show that the neural networks trained on the constitutive proteasome data learns a specificity that differs from that of the networks trained on MHC Class I ligands, i.e. the specificity of the immunoproteasome is different than the constitutive proteasome. The tools developed in this study in combination with a predictor of MHC and TAP binding capacity should give a more complete prediction of the generation and presentation of peptides on MHC Class I molecules. Here we demonstrate that such an approach produces an accurate prediction of the CTL the epitopes in HIV Nef. The method is available at www.cbs.dtu.dk/services/NetChop/.
GPL, a Novel Cytokine Receptor Related to GP130 and Leukemia Inhibitory Factor Receptor (2003)

We describe a novel cytokine receptor named GP130 Like receptor, or GPL, that displays similarities with the interleukin-6 and interleukin-12 family of signaling receptors. Four different isoforms diverging in their carboxyl terminus were isolated, corresponding to proteins encompassing 560, 610, 626, and 745 amino acids. Sequences included a signal peptide of 32 amino acids, followed by a cytokine binding domain containing four conserved cysteines, a WSDWS motif, and a region consisting of three fibronectin type III domain repeats. No immunoglobulin-like module was identified in the GPL sequences. The intracellular part of longer isoforms contained a proline-rich region defining a box1 motif for interaction with the Janus kinases. The Gpl gene is organized in 15 exons and is located on 5q11.2 in tandem with the gp130 gene. Both genes were only separated by 24 kilobases, with opposite transcriptional orientations. The GPL receptor displayed a 28% identity with gp130. Specific GPL transcripts were observed in tissues involved in reproduction. Transcripts were also found in blood cells and in bone marrow, revealing expression of GPL in all of the myelomonocytic lineage, from hematopoietic stem cells to activated dendritic cells. In monocytes and dendritic cells, expression of GPL was strongly up-regulated by interferon-gamma, indicating a possible involvement of GPL in Th1-type immune responses. The molecular basis of cell signaling mediated by GPL was studied using chimeric receptors where external portions of alpha or beta interleukin-5 receptor subunits were fused to the internal portion of GPL or of related receptors. Results indicated that association of GPL to the intracellular portions of gp130, or LIF receptor, allowed the signaling cascade.