gebhart/patrepeval huggingface dataset:
A comprehensive review of the preclinical efficacy profile of the ErbB family blocker afatinib in cancer (2014)

Afatinib (also known as BIBW 2992) has recently been approved in several countries for the treatment of a distinct type of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. This manuscript comprehensively reviews the preclinical data on afatinib, an irreversible inhibitor of the tyrosine kinase activity of members of the epidermal growth factor receptor family (ErbB) including EGFR, HER2 and ErbB4. Afatinib covalently binds to cysteine 797 of the EGFR and the corresponding cysteines 805 and 803 in HER2 and ErbB4, respectively. Such covalent binding irreversibly inhibits the tyrosine kinase activity of these receptors, resulting in reduced auto- and transphosphorylation within the ErbB dimers and inhibition of important steps in the signal transduction of all ErbB receptor family members. Afatinib inhibits cellular growth and induces apoptosis in a wide range of cells representative for non-small cell lung cancer, breast cancer, pancreatic cancer, colorectal cancer, head and neck squamous cell cancer and several other cancer types exhibiting abnormalities of the ErbB network. This translates into tumour shrinkage in a variety of in vivo rodent models of such cancers. Afatinib retains inhibitory effects on signal transduction and in vitro and in vivo cancer cell growth in tumours resistant to reversible EGFR inhibitors, such as those exhibiting the T790M mutations. Several combination treatments have been explored to prevent and/or overcome development of resistance to afatinib, the most promising being those with EGFR- or HER2-targeted antibodies, other tyrosine kinase inhibitors or inhibitors of downstream signalling molecules.
New Human Embryonic Stem-Cell Lines — More Is Better (2004)

It is rare that a field of scientific research can simultaneously represent a domain of fundamental discovery in human biology and potentially have major effects on human health and the quality of life. Human embryonic stem cells serve not only as a resource for basic research, but also as the starting material for the development of cell-based therapies. Formidable scientific challenges face those who aim to develop cell-based therapies. It will take the efforts of many scientists and clinicians in a variety of disciplines to bring this endeavor to fruition. Of immediate importance and concern is whether or not we . . .
Invasive and non-invasive feedback for ultrasound phased array thermometry (1994)

The use of high-intensity focused ultrasound for cancer therapy and tissue ablation has been receiving increased attention recently. Currently, fine-wire thermocouple sensors represent the only practical means of feedback for these treatments. Difficulties in placing thermocouples in many clinical situations represent a major limitation on the amount of feedback that can be obtained with these versatile sensors. For this purpose, invasive and non-invasive feedback methods for ultrasound thermotherapy have been developed. Invasive methods for acoustic feedback are based on implantable hydrophone arrays, and non-invasive methods for temperature feedback are based on signal processing of the backscattered diagnostic ultrasound pulse. Experimental results demonstrating quantitative, non-invasive, tissue temperature change measurements are shown. The methods for temperature change estimation presented are independent of the heating modality
Comparative immunopeptidomics of humans and their pathogens (2004)

Major histocompatibility complex class I molecules present peptides of 8-10 residues to CD8+ T cells. We used 19 predicted proteomes to determine the influence of CD8+ T cell immune surveillance on protein evolution in humans and microbial pathogens by predicting immunopeptidomes, i.e., sets of class I binding peptides present in proteomes. We find that class I peptide binding specificities (i) have had little, if any, influence on the evolution of immunopeptidomes and (ii) do not take advantage of biases in amino acid distribution in proteins other than the concentration of hydrophobic residues in NH(2)-terminal leader sequences.
Superconducting d-wave junctions: The disappearance of the odd ac components (1997)

We study voltage-biased superconducting planar d-wave junctions for arbitrary transmission and arbitrary orientation of the order parameters of the superconductors. For a certain orientation of the superconductors the odd ac components disappear, resulting in a doubling of the Josephson frequency. We study the sensitivity of this disappearance to orientation and compare with experiments on grain boundary junctions. We also discuss the possibility of a current flow parallel to the junction.
Measuring Fate and Rate of Single‐Molecule Competition of Amplification and Restriction Digestion, and Its Use for Rapid Genotyping Tested with Hepatitis C Viral RNA (2014)

We experimentally monitored, at the single-molecule level, the competition among reverse transcription, exponential amplification (RT-LAMP), and linear degradation (restriction enzymes) starting with hepatitis C viral RNA molecules. We found significant heterogeneity in the rate of single-molecule amplification; introduction of the restriction enzymes affected both the rate and the "fate" (the binary outcome) of single-molecule amplification. While end-point digital measurements were primarily sensitive to changes in fate, the bulk real-time kinetic measurements were dominated by the rate of amplification of the earliest molecules, and were not sensitive to fate of the rest of the molecules. We show how this competition of reactions can be used for rapid HCV genotyping with either digital or bulk readout. This work advances our understanding of single-molecule dynamics in reaction networks and may help bring genotyping capabilities out of clinical labs and into limited-resource settings.
Connective Tissue, Glycosaminoglycans, and Diseases the Thyroid* (1989)

CONNECTIVE tissue imparts cohesion, strength, and form to the organs that it invests. It is comprised of several discrete cellular and noncellular components. The fibroblast and its more specialized derivatives (such as chondrocytes and osteocytes) elaborate and release several important molecules such as fibrous proteins (collagen), attachment proteins (fibronectin), glycoproteins, and ground substance. In this article we review the now abundant evidence that fibroblasts and their products are important mediators of some peripheral expressions of thyroid disease, including myxedema, pretibial dermopathy, thyroid acropachy, and ophthalmopathy of Graves' disease. Our review concentrates predominantly on the glycosaminoglycans that comprise ground substance. The fibrous proteins are given less attention. The early prejudice that the ground substance and connective tissue in general were rather unimportant becomes apparent in a quote attributed to Von Haller (1), who in 1757 wrote that “it is evident that a considerable part of the human body consists of matter which for so many centuries has been regarded as rubbish.” Yet it is widely appreciated in contemporary biology that ground substance and the connective tissues play a crucial role in defining the microenvironment for specialized cells to function. They are important in cell attachment and cell-to-cell communication, and they influence the manner in which cells negotiate the extracellular milieu. A brief review of the physicochemical properties of the glycosaminoglycans that compose ground substance precedes the more detailed analysis of the impact that thyroid dysfunction can have on its synthesis and disposal.
A capacitorless DRAM cell on SOI substrate (2002)

We propose a capacitorless DRAM (CDRAM) cell on SOI substrate with large READ current (>100 /spl mu/Aspl mu/m), small cell size, and simple fabrication process. PISCES simulations are used to analyze the memory cell operations. The CDRAM cell size is that of a transistor, which makes it very attractive for high density memory applications. Since the fabrication process of CDRAM is compatible with that of the general purpose SOI CMOS and complementary BiCMOS process, CDRAM can also be used for integrated on-chip memory and is an interesting candidate as the technology driver of SOI VLSI.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Growth regulation of human prostate cancer cells by bone morphogenetic protein-2. (1997)

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGF-beta) family and have been identified as factors that stimulate bone formation in vivo. They turned out to be multifunctional molecules regulating the growth, differentiation, and apoptosis in various target cells. Some BMPs and their receptors (BMPRs) are expressed on prostate cancer cells. We have reported previously that BMPR-IB mRNA expression is highest in the prostate, a characteristic that is not shared by the other BMPRs, BMPR-IA and BMPR-II. However, the amounts of BMPR-IB mRNA were significantly low in prostate tissues after androgen withdrawal therapy. They were also low in prostate cancer cell lines. Semiquantitative RT-PCR showed that BMPR-IB mRNA was induced by androgen in the androgen-sensitive human prostatic cancer cell line LNCaP, whereas the expression of BMPR-IA and BMPR-II mRNAs was not affected by androgen. When the recombinant human BMP-2 was added to the LNCaP cells in the presence of androgen, cell growth was inhibited. In contrast, the growth rate was increased by the addition of the same ligand when the cells were cultured in the absence of androgen; under this condition, the amounts of BMPR-IB mRNA were decreased significantly. These observations showed that the amounts of BMPR-IB, but not those of BMPR-IA, were regulated by androgen and further suggest that BMPR-IA and BMPR-IB differentially modulate prostate cancer cell growth in response to BMP under different hormonal conditions; BMPR-IA elicits growth stimulation, and BMPR-IB conveys a negative regulatory signal in response to BMP-2.
Routes for salmonella contamination of poultry meat: epidemiological study from hatchery to slaughterhouse (2002)

Data were collected on the prevalence of salmonella at different stages during the life cycle of 18 broiler flocks on different farms as well as during slaughter in different poultry slaughterhouses. For the isolation of salmonella, the highest sensitivity (93.9%) was obtained by enrichment in the semi-solid agar Diasalm. The 'overshoe method' utilizing several pairs of overshoes provided the highest sensitivity for determining the salmonella status of the broilers during rearing. A clear decrease of the relative importance of the first production stages was demonstrated for the salmonella contamination of the end product, whereas horizontal transmission of salmonella to broilers during rearing and to broiler carcasses in the slaughterhouse was shown to be the main determinative factor. Ten of the 18 flocks received a salmonella positive status with the highest shedding occurring during the first 2 weeks of rearing. The shedding of the animals was significantly negatively influenced by the use of subtherapeutic or therapeutic doses of antibiotics. The intake of portable material in the broiler house was identified as the most important risk factor for horizontal transmission. Significant associations were found between the contamination level of a flock and hygiene of the broiler house, feed and water in the broiler house and both animal and non-animal material sampled in the environment. No correlation was found between contamination during the rearing period and contamination found after slaughtering. The presence of faecal material in the transport crates and predominantly the identity of the slaughterhouse seemed to be the determining factors for carcass quality. Improved hygiene management during transport of broilers and in some slaughterhouses could significantly reduce the risk of salmonella contamination of poultry meat.
Outside Looking In: Nanotube Transistor Intracellular Sensors (2012)

Nanowire-based field-effect transistors, including devices with planar and three-dimensional configurations, are being actively explored as detectors for extra- and intracellular recording due to their small size and high sensitivities. Here we report the synthesis, fabrication, and characterization of a new needle-shaped nanoprobe based on an active silicon nanotube transistor, ANTT, that enables high-resolution intracellular recording. In the ANTT probe, the source/drain contacts to the silicon nanotube are fabricated on one end, passivated from external solution, and then time-dependent changes in potential can be recorded from the opposite nanotube end via the solution filling the tube. Measurements of conductance versus water-gate potential in aqueous solution show that the ANTT probe is selectively gated by potential changes within the nanotube, thus demonstrating the basic operating principle of the ANTT device. Studies interfacing the ANTT probe with spontaneously beating cardiomyocytes yielded stable intracellular action potentials similar to those reported by other electrophysiological techniques. In addition, the straightforward fabrication of ANTT devices was exploited to prepare multiple ANTT structures at the end of single probes, which enabled multiplexed recording of intracellular action potentials from single cells and multiplexed arrays of single ANTT device probes. These studies open up unique opportunities for multisite recordings from individual cells through cellular networks.
Sequence of the phosphoprotein gene of pneumonia virus of mice: expression of multiple proteins from two overlapping reading frames (1994)

The gene encoding the phosphoprotein of the pneumovirus pneumonia virus of mice (PVM) has been cloned and sequenced. The gene is 903 nucleotides in length and contains a long open reading frame (ORF) capable of encoding a polypeptide of 295 amino acid residues. A smaller, second, overlapping ORF encoding a polypeptide 137 amino acids in length was also present. The large ORF directed the synthesis of a 39-kDa polypeptide and four additional polypeptides with masses of 37 kDa, 26 kDa, 23 kDa, and 16 kDa in vitro. The smaller polypeptides were generated by internal initiation on in-frame AUG initiation codons to generate carboxy co-terminal products. Western immunoblot analysis indicated that at least two of these proteins and several other related polypeptides are present in infected cells, and the possible origins of these are discussed. Western blot analysis using antiserum raised against a synthetic peptide and specific for the predicted second ORF product identified a polypeptide of 23 kDa in PVM-infected cells. The pattern of PVM P gene expression is unlike that of the closely related respiratory syncytial virus and is reminiscent of that of paramyxoviruses such as Sendai virus. This is the first example of a pneumovirus encoding multiple polypeptide products from a single mRNA in vivo.
Real-time Skin Analysis Filters (2014)

This thesis presents a framework for real-time skin analysis. Our system consists of two filters for skin redness analysis and pigmented skin lesions analysis. In skin redness analysis, we search for skin regions in video frames and assess size and degree of redness in skin regions. In order to analyze pigmented skin lesions, we localize potential moles of different sizes utilizing multiple difference of Gaussian filters and apply trained Support Vector Machine and K-Nearest Neighbours to eliminate non-mole candidates from the previous stage. After finding mole candidates, we present information about the symmetry, border irregularity and color variegation of detected moles. To test the real-time performance of our system, a prototype application on the iPhone 4S and iPhone 5S was implemented.
Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine (2000)

Somatic mutation accumulation has been implicated as a major cause of cancer and aging. By using a transgenic mouse model with a chromosomally integrated lacZ reporter gene, mutational spectra were characterized at young and old age in two organs greatly differing in proliferative activity, i.e., the heart and small intestine. At young age the spectra were nearly identical, mainly consisting of G. C to A.T transitions and 1-bp deletions. At old age, however, distinct patterns of mutations had developed. In small intestine, only point mutations were found to accumulate, including G.C to T.A, G.C to C.G, and A.T to C.G transversions and G.C to A.T transitions. In contrast, in heart about half of the accumulated mutations appeared to be large genome rearrangements, involving up to 34 centimorgans of chromosomal DNA. Virtually all other mutations accumulating in the heart appeared to be G.C to A.T transitions at CpG sites. These results suggest that distinct mechanisms lead to organ-specific genome deterioration and dysfunction at old age.
Statistical phrase-based translation (2003)

We propose a new phrase-based translation model and decoding algorithm that enables us to evaluate and compare several, previously proposed phrase-based translation models. Within our framework, we carry out a large number of experiments to understand better and explain why phrase-based models out-perform word-based models. Our empirical results, which hold for all examined language pairs, suggest that the highest levels of performance can be obtained through relatively simple means: heuristic learning of phrase translations from word-based alignments and lexical weighting of phrase translations. Surprisingly, learning phrases longer than three words and learning phrases from high-accuracy word-level alignment models does not have a strong impact on performance. Learning only syntactically motivated phrases degrades the performance of our systems.
All-digital PPM impulse radio for multiple-access through frequency-selective multipath (2002)

Impulse radio (IR) is an ultra-wideband system with attractive features for baseband asynchronous multiple access (MA), multimedia services, and tactical wireless communications. Implemented with analog components, the continuous-time IRMA model utilizes pulse-position modulation (PPM) and random time-hopping codes to alleviate multipath effects and suppress multiuser interference (MUI). We introduce a novel continuous-time PPM-IRMA model, deduce a low-complexity approximate one, and derive its discrete-time equivalent model. Relying on a time-division-duplex access protocol and orthogonal user codes, we design composite linear/non-linear receivers for the downlink. The linear step eliminates MUI deterministically and accounts for frequency-selective multipath while a maximum likelihood (ML) receiver achieves symbol detection.
Identification of an AUUUA-Specific Messenger RNA Binding Protein (1989)

An important control point in gene expression is at the level of messenger RNA (mRNA) stability. The mRNAs of certain regulatory cellular proteins such as oncogenes, cytokines, lymphokines, and transcriptional activators are extremely labile. These messages share a common AUUUA pentamer in their 3' untranslated region, which confers cytoplasmic instability. A cytosolic protein was identified that binds specifically to RNA molecules containing four reiterations of the AUUUA structural element. This protein consists of three subunits and binds rapidly to AUUUA-containing RNA. Such protein-RNA complexes are resistant to the actions of denaturing and reducing agents, demonstrating very stable binding. The time course, stability, and specificity of the protein-AUUUA interaction suggests the possibility that the formation of this complex may target susceptible mRNA for rapid cytoplasmic degradation.
Resting B Lymphocytes as APC for Naive T Lymphocytes: Dependence on CD40 Ligand/CD40 (2000)

Although resting B cells as APC are tolerogenic for naive T cells in vivo, we show here that they can provide all the costimulatory signals necessary for naive T cell proliferation in vivo and in vitro. In the absence of an activating signal through the B cell Ag receptor, T cell proliferation after Ag recognition on resting B cells depends on CD40 expression on the B cells, implying that naive T cells use the membrane-bound cytokine, CD40 ligand (CD154), to induce the costimulatory signals that they need. Induction of B7-1 (CD80) and increased or sustained expression of CD44H, ICAM-1 (CD54), and B7-2 (CD86) are dependent on the interaction of CD40 ligand with CD40. Transient expression (12 h) of B7-2 is T cell- and peptide Ag-dependent, but CD40-independent. Only sustained (>/=24 h) expression of B7-2 and perhaps increased expression of ICAM-1 could be shown to be functionally important in this system. T cells cultured with CD40-deficient B cells and peptide remain about as responsive as fresh naive cells upon secondary culture with whole splenic APC. Therefore, B cells, and perhaps other APC, may be tolerogenic not because they fail to provide sufficient costimulation for T cell proliferation, but because they are deficient in some later functions necessary for a productive T cell response.
Phosphodiesterase Isoenzymes in Human Ureteral Smooth Muscle: Identification, Characterization, and Functional Effects of Various Phosphodiesterase Inhibitors in vitro (1995)

Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The existence of three different PDE isoenzymes was shown in this study. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low effect on the systemic circulatory parameters, may open a possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or ureteral stones.