gebhart/patrepeval huggingface dataset:
Sequence-discriminative training of deep neural networks (2013)

Sequence-discriminative training of deep neural networks (DNNs) is investigated on a standard 300 hour American English conversational telephone speech task.Different sequencediscriminative criteria -maximum mutual information (MMI), minimum phone error (MPE), state-level minimum Bayes risk (sMBR), and boosted MMI -are compared.Two different heuristics are investigated to improve the performance of the DNNs trained using sequence-based criteria -lattices are regenerated after the first iteration of training; and, for MMI and BMMI, the frames where the numerator and denominator hypotheses are disjoint are removed from the gradient computation.Starting from a competitive DNN baseline trained using cross-entropy, different sequence-discriminative criteria are shown to lower word error rates by 7-9% relative, on average.Little difference is noticed between the different sequencebased criteria that are investigated.The experiments are done using the open-source Kaldi toolkit, which makes it possible for the wider community to reproduce these results.
Fibrinogen‐CD11b/CD18 interaction activates the NF‐κB pathway and delays apoptosis in human neutrophils (2003)

The regulation of neutrophil half-life by members of the coagulation cascade is critical for the resolution of the inflammatory response. We have demonstrated that soluble fibrinogen (sFbg) delays human neutrophil (PMN) apoptosis through a mechanism that involves CD11b interactions, and phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2). Since NF-kappa B is a key element in the regulation of apoptotic mechanisms in several immune cells, we investigated whether NF-kappa B is involved in the control of PMN survival by sFbg. We show that sFbg triggers inhibitor protein kappa B (I kappa B-alpha) degradation and NF-kappa B activation. Furthermore, pharmacological inhibition of NF-kappa B abrogates sFbg effects on apoptosis. In addition, specific inhibition of MAPK ERK1/2 significantly reduces NF-kappa B translocation by sFbg, suggesting a relationship between ERK1/2 and NF-kappa B activation. Similar results are obtained when granulocytic-differentiated HL-60 cells are treated with sFbg, making this model highly attractive for integrin-induced gene expression studies. It can be concluded that NF-kappa B participates in the prevention of apoptosis induced by sFbg with the participation of MAPK ERK1/2. These results shed light on the molecular mechanisms that control human granulocyte apoptosis, and suggest that NF-kappa B regulation may be of benefit for the resolution of the inflammatory response.
The dynamics of the CHO host cell protein profile during clarification and protein A capture in a platform antibody purification process (2012)

Recombinant protein products such as monoclonal antibodies (mAbs) for use in the clinic must be clear of host cell impurities such as host cell protein (HCP), DNA/RNA, and high molecular weight immunogenic aggregates. Despite the need to remove and monitor HCPs, the nature, and fate of these during downstream processing (DSP) remains poorly characterized. We have applied a proteomic approach to investigate the dynamics and fate of HCPs in the supernatant of a mAb producing cell line during early DSP including centrifugation, depth filtration, and protein A capture chromatography. The primary clarification technique selected was shown to influence the HCP profile that entered subsequent downstream steps. MabSelect protein A chromatography removed the majority of contaminating proteins, however using 2D-PAGE we could visualize not only the antibody species in the eluate (heavy and light chain) but also contaminant HCPs. These data showed that the choice of secondary clarification impacts upon the HCP profile post-protein A chromatography as differences arose in both the presence and abundance of specific HCPs when depth filters were compared. A number of intracellularly located HCPs were identified in protein A elution fractions from a Null cell line culture supernatant including the chaperone Bip/GRP78, heat shock proteins, and the enzyme enolase. We demonstrate that the selection of early DSP steps influences the resulting HCP profile and that 2D-PAGE can be used for monitoring and identification of HCPs post-protein A chromatography. This approach could be used to screen cell lines or hosts to select those with reduced HCP profiles, or to identify HCPs that are problematic and difficult to remove so that cell-engineering approaches can be applied to reduced, or eliminate, such HCPs.
A randomized controlled trial of telemedicine in an emergency department (1998)

A prospective study of emergency department telemedicine was carried out at two hospitals in northern New Jersey. One hundred and twenty-two patients met the inclusion criteria. One hundred and four (85%) consented to participate, with 54 being randomized to the telemedicine group and 50 to the control group. Four patients did not complete the protocol. No significant differences were seen between the groups for: occurrence of 72 h emergency department return visits (0% vs 0%); need for additional care (2.3% vs 2.4%); positive patient-physician interaction (98% vs 100%); positive patient-nurse interaction (98% vs 98%); positive overall patient satisfaction (98% vs 95%). The average patient throughput time (time from admission to discharge) for the telemedicine group was 106 min; the average for the control group was 117 min. Telemedicine was found to be a satisfactory technique for pre-selected emergency department patients and was viewed by the physicians as an acceptable method of complementary care.
Atomistic Simulations of a Multicomponent Asymmetric Lipid Bilayer (2012)

The cell membrane is inherently asymmetric and heterogeneous in its composition, a feature that is crucial for its function. Using atomistic molecular dynamics simulations, the physical properties of a 3-component asymmetric mixed lipid bilayer system comprising an unsaturated POPC (palmitoyloleoylphosphatidylcholine), a saturated PSM (palmitoylsphingomyelin), and cholesterol are investigated. Our simulations explore both the dynamics of coarsening following a quench from the mixed phase and the final phase-segregated regime obtained by equilibrating a fully segregated configuration. Following a quench, the membrane quickly enters a coarsening regime, where the initial stages of liquid ordered, l(o), domain formation are observed. These growing domains are found to be highly enriched in cholesterol and PSM. Consistent with this, the final phase-segregated regime contains large l(o) domains at equilibrium, enriched in cholesterol and PSM. Our simulations suggest that the cholesterol molecules may partition into these PSM-dominated regions in the ratio of 3:1 when compared to POPC-dominated regions. PSM molecules exhibit a measurable tilt and long-range tilt correlations within the l(o) domain as a consequence of the asymmetry of the bilayer, with implications to local membrane deformation and budding. Tagged particle diffusion for PSM and cholesterol molecules, which reflects spatial variations in the physical environment encountered by the tagged particle, is computed and compared with recent experimental results obtained from high-resolution microscopy.
<i>Caenorhabditis elegans</i> MPP<sup>+</sup> Model of Parkinson’s Disease for High-Throughput Drug Screenings (2004)

The neurotoxin MPTP and its active metabolite MPP+ cause Parkinson's disease (PD)-like symptoms in vertebrates by selectively destroying dopaminergic neurons in the substantia nigra. MPTP/MPP+ models have been established in rodents to screen for pharmacologically active compounds. In addition to being costly and time consuming, these animal models are not suitable for large scale testings using compound libraries. We present a novel MPP+-based model for high-throughput screenings using the nematode Caenorhabditis elegans. Incubation of C. elegans with MPTP or its active metabolite MPP+ resulted in strong symptomatic defects including reduced mobility and increased lethality, and is correlated with a specific degeneration of the dopaminergic neurons. The phenotypic consequences of MPTP/MPP+ treatments were recorded using automated hardware and software for quantification. Incubation of C. elegans with a variety of pharmacologically active components used in PD treatment reduced the MPP+-induced defects. Our data suggest that the C. elegans MPTP/MPP+ model can be used for the quantitative evaluation of anti-PD drugs.
Dissociation of human follicle-stimulating hormone. Comparison with luteinizing hormone. (1975)

Rat testis tissue receptor assays were utilized to study the kinetics of dissociation of human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) under varying conditions of urea concentration and pH. In these competitive protein binding assays, 125I-hFSH and 125I-hLH were the radioligands and hormone dissociation was followed by a decrease in the ability of the dissociating hormone to inhibit uptake of the radioligand by tissue receptors. Rate data for dissociation of the gonadotropins were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. Treatment of hFSH with 4 M urea at pH 8 and 25 degrees for 22 hours did not result in significant dissociation, whereas in 8 M urea, over 90% dissociation was observed. The rate of dissociation of hFSH in 8 M urea was increased approximately 4-fold by raising the temperature from 25 to 37 degrees. Similar results were obtained when dissociation of hFSH was followed through use of an accepted whole animal bioassay for FSH, thus confirming the reliability of the tissue receptor assay for such dissociation studies. Kinetic studies showed that hFSH was undissociated by incubation in 6 M urea of pH 8 after 4 hours at 25 degrees. In contrast, hLH was 90% dissociated under similar conditions. This differential rate of inactivation of hLH allowed preparation of hFSH having significant reduced levels of contaminating LH activity, as determined by tissue receptor assays and by whole animal bioassays. Marked differences were noted in the rate of dissociation of hFSH and hLH under acid conditions. hFSH completely dissociated after approximately 2 min of incubation of pH 2 (25 degrees), and over 90% dissociated after 15 min of incubation at pH 3. In contrast, hLH was dissociated 60% after 20 min of incubation at pH 2 (25 degrees) and 40% dissociated after 60 min at pH 3. Neither hormone was significantly dissociated at pH 4.4 after 60 min, but hFSH showed a slightly greater rate of dissociation than did LH in the period between 1 and 23 hours of incubation at that pH. hFSH and hLH were relatively resistant to dissociation after incubation at pH 12 for 1 hour, bu;t dissociated significantly after incubation for 22 hours at that pH. The time course for dissociation of hFSH or hLH under the various conditions described above did not conform clearly to either first or second order kinetics, indicating that the over-all dissociation process represents a mixed order reaction. It appears that urea or acid-induced denaturation of one or both subunits of hLH and hFSH may occur prior to their dissociation. The very rapid rate of dissociation at acid pH values, particularly of hFSH, indicate that ionic interactions contribute importantly to the subunit association phenomenon.
Nucleotide sequence of the gene for ribosomal protein S20 and its flanking regions. (1981)

The sequence of almost 700 nucleotides encompassing the gene for ribosomal protein S20 of Escherichia coli has been determined using the chemical technique of Maxam and Gilbert (Maxam, A. M., and Gilbert, W. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 560-564). Comparison of this sequence with that of known bacterial promoters reveals two promoter-like sequences whose putative initiation sites for transcription lie 132 ("site 1") and 42 ("site 2") base pairs to the 5' side of the coding sequence. Partial digestion experiments demonstrate that RNA polymerase is capable of binding to and protecting both of these sites from DNase 1 digestion, consistent with their functioning as promoters. Interestingly, site 1 is more compact that any previously described bacterial promoter. A second feature of the sequence is the presence of UUG as the translational initiation codon. Finally, the nucleotide sequence supports the hypothesis (Jue, R. A., Woodbury, N. W., and Doolittle, R. F. (1980) J. Mol. Evol. 15, 129-148) that S20 is composed of three tandemly repeated domains.
The effect of surface topography of retrieved femoral heads on the wear of UHMWPE sockets (1997)

The study was undertaken to investigate the association, if any, between the surface roughness of 35 explanted femoral heads and the clinical wear factors of the corresponding polyethylene sockets. The wear of the socket was measured using a shadowgraph technique. The surface topography was investigated using a Rodenstock RM 600 non-contacting profilometer, and six parameters were used to characterise the roughness. Further, qualitative inspections of the femoral surface were undertaken using both a Joel JSM-IC-848 scanning electron microscope and a Zeiss Axiotech microscope with a differential interference contrast facility. Two parameters were found to correlate with the clinical wear factor, namely the skewness of the amplitude distribution function, Sk, and the arithmetic mean roughness, Ra. Simple parameters describing the peak heights of the asperities were found not to have a significant association with the clinical wear factor. The exponent in the power relationship between the arithmetic mean roughness and kclinical was found to be equal to 0.5 (SE: 0.2). This value is significantly smaller than that found in laboratory experiments and may be due to the non-uniform nature of the roughening of the femoral head, three-body wear and the effect of other clinical factors on the wear process. Further, extremely strong correlations were detected between the differing roughness parameters, which would suggest that any attempt to deduce which one is the most important in affecting the wear of the polymeric counterface is fraught with difficulty. However, further investigation of those parameters, such as the reduced peak height or the material filled profile peak area, which may better describe the effect of the counterface on the wear of the UHMWPE surface would appear to be prudent.
Genotyping SNPs Using a UV-Photocleavable Oligonucleotide in MALDI-TOF MS (2004)

Matrix-assisted laser desorption time-of-flight mass spectrometry coupled with allele-specific primer extension is a proven method for typing single nucleotide polymorphisms (SNPs). A novel modification upon this methodology is the incorporation of a photocleavable linker within the extension primer. After completion of the primer extension reaction, photocleavage of the extension products results in two deoxyribonucleic acid (DNA) fragments of lower mass. Typically, the smaller cleavage product, which contains the genotyping information, is in the range of 1000-3000 Daltons. The decrease in primer mass allows for higher sensitivity in mass spectrometric measurement and increases the potential for higher levels of multiplexing. The disturbing mass spectrometric analysis peaks caused by salt adducts and doubly charged ions are diminished when analyzing lower-mass DNA fragments. Here, we illustrate the methodology for using photocleavable modified extension primers for detection of SNPs located on the Y chromosome. Genomic templates were prepared from anonymous male donors. Five regions of the Y chromosome containing the SNP markers M9, M42, M45, M89, and M96 were amplified by polymerase chain reaction, treated with shrimp alkaline phosphatase, and subjected to primer extension reactions using primers containing a photocleavable building block at specific sites. After elongation, the extension primers were desalted and subjected to ultraviolet irradiation to cleave the products at the photocleavable site. Subsequently, the small fragments derived from the 3' ends of the molecules containing the genotype information were analyzed by matrix-assisted laser desorption ionization time-of-flight using a 3-hydroxypicolinic acid matrix.
Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67. (1986)

The growth fractions of 160 mammary carcinomas and 30 benign mammary lesions were determined in situ by immunostaining with the monoclonal antibody Ki-67. Benign lesions had a mean value of 3% Ki-67 positive cells, whereas the mean value of mammary carcinomas was 16.6%. A comparison of the mean values of Ki-67 positive cells with the histological grade of the tumours showed a correlation between these two variables--that is, histological grade 1 showed 9%, grade 2 16%, and grade 3 26% proliferating cells. Considering the individual Ki-67 values in the different histological grades, it was evident that there was considerable scatter in the number of proliferating cells, so that the proliferation rates of grades 1, 2, and 3 overlapped each other. This indicates a dissociation between histological grade of malignancy and size of the growth fraction in most breast cancers. Follow up studies are needed to establish which of the two variables--that is, morphological degree of malignancy, or the proportion of Ki-67 positive cells--correlates better with response to treatment and survival in individual cases.
Ledistor—a three-terminal double heterostructure optoelectronic switch (1987)

A three-terminal double heterostructure optoelectronic switching (DOES) device is demonstrated. By making ohmic contact to the active region of the DOES device the switching characteristic may be controlled up to the punchthrough limit. The device emits light in the on state only and various combinations of voltage and optical input power can be used to switch the device.
Design of a Bacterial Host for Site-Specific Incorporation of p-Bromophenylalanine into Recombinant Proteins (2006)

Introduction of a yeast suppressor tRNA (ytRNA(Phe)(CUA)) and a mutant yeast phenylalanyl-tRNA synthetase (yPheRS (T415G)) into an Escherichia coli expression host allows in vivo incorporation of phenylalanine analogues into recombinant proteins in response to amber stop codons. However, high-fidelity incorporation of non-natural amino acids is precluded in this system by mischarging of ytRNA(Phe)(CUA) with tryptophan (Trp) and lysine (Lys). Here we show that ytRNA(Phe)(CUA) and yPheRS can be redesigned to achieve high-fidelity amber codon suppression through delivery of p-bromophenylalanine (pBrF). Two strategies were used to reduce misincorporation of Trp and Lys. First, Lys misincorporation was eliminated by disruption of a Watson-Crick base pair between nucleotides 30 and 40 in ytRNA(Phe)(CUA). Loss of this base pair reduces mischarging by the E. coli lysyl-tRNA synthetase. Second, the binding site of yPheRS was redesigned to enhance specificity for pBrF. Specifically, we used the T415A variant, which exhibits 5-fold higher activity toward pBrF as compared to Trp in ATP-PP(i) exchange assays. Combining mutant ytRNA(Phe)(CUA) and yPheRS (T415A) allowed incorporation of pBrF into murine dihydrofolate reductase in response to an amber codon with at least 98% fidelity.
Constructing Gene Regulatory Networks using Knock-out Data (2007)

A gene regulatory network is a network of genes representing how genes influence the activities of other genes. Nowadays from microarray experiments, a large number of measurements on the expression levels of genes are available. One of typical data is the so-called steady-state data measuring the expression levels of other genes after knocking out a particular gene. This paper shows how to reverse engineer a parsimonious gene regulatory network, using these measurement data. Our model considers auto-regulation, which forms a cycle in a genetic network. We also model repressor and enhancer roles of genes. which are not considered in previous known methods.
A 22.4 dBm Two-Way Wilkinson Power-Combined Q-Band SiGe Class-E Power Amplifier with 23% Peak PAE (2012)

A Q-band two-stage Class-E power amplifier is designed and fabricated in a 0.13 μm SiGe HBT BiCMOS process. A low-loss wide-band two-way Wilkinson power combiner is used for on-chip power dividing and combining at the input and output of the design. A mm-wave layout-aware class-E design procedure has been followed to enable efficient switching mode operation of the power amplifier in the Q-band. Stabilization networks and subharmonic terminations have been included to prevent the occurrence of unwanted impact ionization-induced negative base current and even/odd mode oscillation in the power-combined design. The fabricated chip shows a measured performance of 22.4 dBm output power at 23% peak power added efficiency (PAE), and 9 dB power gain across 4 GHz centered around 45 GHz for a supply voltage of 2.5 V. The total chip area including the pads is 1.1 mm × 2.2 mm.
Air trenches for dense silica integrated optics (2002)

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2002.
A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding (1991)

The low-affinity human Fc gamma RIIa is encoded by a single gene with allelic variation, defined by low-responder and high-responder alleles (LR and HR). The HR Fc gamma RIIa transcript interacts strongly with murine (m) IgG1 complexes, in contrast to the LR Fc gamma RIIa. Furthermore, the transcripts can be discriminated by mAb 41H16, which recognizes an epitope expressed on the HR Fc gamma RIIa molecule. We report that this receptor is also polymorphic in its reactivity with human (h) IgG2. Binding studies using well-defined hIgG dimers revealed that LR Fc gamma RIIa molecules can efficiently bind hIgG2, in contrast to HR Fc gamma RIIa. Previous work of others showed one amino acid difference between the allelic forms of Fc gamma RII. We, however, found a second amino acid difference between both allelic forms. In this study, hybrid Fc gamma RIIa molecules were constructed to determine the epitope for mAb 41H16 and the binding domain for mIgG1 and hIgG2 complexes. Our data point to the importance of the amino acid at position 131, located in the second Ig-like domain of Fc gamma RIIa. When an arginine residue is present at amino acid position 131, the receptor is recognized by mAb 41H16. Furthermore, the receptor can bind mIgG1-sensitized indicator E, but binds hIgG2 dimers only weakly. When a histidine residue is present at this amino acid position, hIgG2 dimers do bind efficiently to Fc gamma RII, whereas mIgG1-sensitized E and mAb 41H16 exhibit a strongly diminished binding.
Molecular cloning and characterization of human SOX17 (2002)

SOX proteins are a family of transcription factors with high-mobility-group DNA-binding domain (HMG box) homologous to SRY, which are implicated in embryogenesis. Xenopus Sox17 alpha, Sox17 beta, and Sox3 are reported to negatively modulate the WNT - beta-catenin - TCF signaling pathway. Here, human SOX17 gene fragments were identified in human genome draft sequences by using bioinformatics, and SOX17 cDNAs were isolated by using cDNA-PCR. Human SOX17 was found to encode a 414-amino-acid protein with a HMG box, which was homologous to SOX18 and SOX7. SOX17 gene, consisting of 2 exons, was located in human chromosome 8q12-q13 region. SOX17 mRNAs of 2.5- and 2.2-kb in size were detected in adult heart, lung, spleen, testis, ovary, placenta, fetal lung, and kidney. In normal gastrointestinal tract, SOX17 mRNA was preferentially expressed in esophagus, stomach and small intestine than in colon and rectum. SOX17 mRNA was almost undetectable in human cancer cell lines HL-60, HeLa S3, K-562, MOLT-4, Raji, SW480, A549, G-361, and also in 66 cases of human primary tumors derived from various tissues, except one case of primary cervical cancer. This is the first report on molecular cloning and characterization of human SOX17.