gebhart/patrepeval huggingface dataset:
Arrays for protein expression profiling: Towards a viable alternative to two-dimensional gel electrophoresis? (2001)

Two-dimensional gel electrophoresis (2-DE) is used as a platform method for the measurement of protein expression patterns within cells, tissues or organisms. This approach can support expression profiling of several thousand proteins in multiple samples and as such it is currently unrivalled as a tool for the analysis of protein expression, which is a key component of the rapidly expanding field of proteomics. However, 2-DE has a number of significant limitations and as a consequence, alternative approaches for the measurement of expression of proteins within complex samples are actively being explored. Here we review some existing and emerging methods for protein expression analysis. In particular, we review a range of technologies that might be integrated to support the development of ‘arrays’ or ‘chips’ for rapid, high-throughput analysis of protein expression in a manner analogous to the current use of DNA arrays for mRNA expression analysis. We conclude that such separation-independent platforms may ultimately supersede two-dimensional (2-D) gel-based analyses for global protein expression analysis but that before this the technologies might provide important new platforms for diagnostic and prognostic monitoring of diseases.
Apocrustacyanin A1 from the lobster carotenoprotein α-crustacyanin: crystallization and initial X-ray analysis involving softer X-rays (2000)

The A1 subunit of the carotenoprotein alpha-crustacyanin, isolated from lobster carapace, has been crystallized using the vapour-diffusion method. The crystals, grown in solutions of ammonium sulfate containing methylpentanediol (MPD), diffracted to 2. 0 A. The crystals are stable to radiation. The space group of the crystals is P2(1)2(1)2(1). The unit-cell parameters are a = 41.9, b = 80.7, c = 110.8 A. 'Standard structure determination' has been unsuccessful within this crustacyanin family. Instead, an approach based on the S atoms is being undertaken involving softer X-rays at the SRS, Daresbury.
Binary translation (1993)

hen Digital started to design the Alpha AXP architecture in the fall of 1988, the Alpha AXP team was concerned with running existing VAX TM code and MIPS TM code on the new Alpha AXP computers To get full performance on a new computer architecture, an application must be ported by rebuilding, using native compilers. For a single program written in a standard programming language, this is a matter of recompile and run. A complex software application can be built, however, from hundreds of source pieces using dozens of tools. A native port of such an application is only possible when all parts of the build path are running on the new architecture.
Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine (1999)

Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing "multiple layers" of immunity. We have constructed a synthetic gene that encodes for 12 B cell, 6 T cell proliferative, and 3 cytotoxic T lymphocyte epitopes derived from 9 stage-specific P. falciparum antigens corresponding to the sporozoite, liver, erythrocytic asexual, and sexual stages. The gene was expressed in the baculovirus system, and a 41-kDa antigen, termed CDC/NIIMALVAC-1, was purified. Immunization in rabbits with the purified protein in the presence of different adjuvants generated antibody responses that recognized vaccine antigen, linear peptides contained in the vaccine, and all stages of P. falciparum. In vitro assays of protection revealed that the vaccine-elicited antibodies strongly inhibited sporozoite invasion of hepatoma cells and growth of blood-stage parasites in the presence of monocytes. These observations demonstrate that a multicomponent, multistage malaria vaccine can induce immune responses that inhibit parasite development at multiple stages. The rationale and approach used in the development of a multicomponent P. falciparum vaccine will be useful in the development of a multispecies human malaria vaccine and vaccines against other infectious diseases.
Analysis of body composition changes of swine during growth and development. (1999)

This study was conducted to model the growth of carcass, viscera, and empty body components and component composition of pigs. Quantitative tissue and chemical composition of 319 swine, representative of barrows and gilts from five commercial genetic populations, was determined at eight stages of growth between 25 and 152 kg. After whole body grinding and carcass dissection, proximate analyses were performed to calculate concentrations of protein, lipid, moisture, and ash of carcass, viscera, empty body, carcass lean, and carcass fat. Linear and nonlinear equations were developed to investigate the growth patterns of each component. Nonlinear growth functions accounted for the greatest amount of variation in empty body protein, lipid, moisture, and ash mass. Differences (P < .05) existed between barrows and gilts for nearly all components investigated. Carcass lean and fat tissues significantly increased in lipid percentage and decreased in moisture percentage as live weight increased. There were significant changes in the ratio and composition of the tissues of barrows and gilts during growth. Nonlinear models fitted the data better than allometric equations for nearly all of the components investigated.
Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness (2018)

These annual efforts have strengthened public health communications products and supported timely assessment of the impact of vaccination through estimates of illness and hospitalizations averted. Additionally, annual estimates of influenza burden have highlighted areas where disease surveillance needs improvement to better support public health decision making for seasonal influenza epidemics as well as future pandemics.
Molecular Biomarkers for Quantitative and Discrete COPD Phenotypes (2008)

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disorder with complex pathological features and largely unknown etiology. The identification of biomarkers for this disease could aid the development of methods to facilitate earlier diagnosis, the classification of disease subtypes, and provide a means to define therapeutic response. To identify gene expression biomarkers, we completed expression profiling of RNA derived from the lung tissue of 56 subjects with varying degrees of airflow obstruction using the Affymetrix U133 Plus 2.0 array. We applied multiple, independent analytical methods to define biomarkers for either discrete or quantitative disease phenotypes. Analysis of differential expression between cases (n = 15) and controls (n = 18) identified a set of 65 discrete biomarkers. Correlation of gene expression with quantitative measures of airflow obstruction (FEV(1)%predicted or FEV(1)/FVC) identified a set of 220 biomarkers. Biomarker genes were enriched in functions related to DNA binding and regulation of transcription. We used this group of biomarkers to predict disease in an unrelated data set, generated from patients with severe emphysema, with 97% accuracy. Our data contribute to the understanding of gene expression changes occurring in the lung tissue of patients with obstructive lung disease and provide additional insight into potential mechanisms involved in the disease process. Furthermore, we present the first gene expression biomarker for COPD validated in an independent data set.
Integrated Microfluidic Electrochemical DNA Sensor (2009)

Effective systems for rapid, sequence-specific nucleic acid detection at the point of care would be valuable for a wide variety of applications, including clinical diagnostics, food safety, forensics, and environmental monitoring. Electrochemical detection offers many advantages as a basis for such platforms, including portability and ready integration with electronics. Toward this end, we report the Integrated Microfluidic Electrochemical DNA (IMED) sensor, which combines three key biochemical functionalities--symmetric PCR, enzymatic single-stranded DNA generation, and sequence-specific electrochemical detection--in a disposable, monolithic chip. Using this platform, we demonstrate detection of genomic DNA from Salmonella enterica serovar Typhimurium LT2 with a limit of detection of <10 aM, which is approximately 2 orders of magnitude lower than that from previously reported electrochemical chip-based methods.
Cytotoxic Chromosomal Targeting by CRISPR/Cas Systems Can Reshape Bacterial Genomes and Expel or Remodel Pathogenicity Islands (2013)

In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.
Diagnosis of interstitial fibrosis and tubular atrophy in kidney allograft: implementation of microRNAs. (2014)

Chronic allograft nephropathy is the major cause of kidney allograft loss, and recent advances in immunosuppression therapy do not alter the picture. Interstitial fibrosis and tubular atrophy is an early event that starts early after engraftment and even could be found in recipients with good allograft function. Serum creatinine and estimated glomerular filtration rate have limited clinical roles in estimating the histopathological changes and graft fibrosis. Recent progress in microRNA research has created a great promise to identify new diagnostic biomarkers and therapeutic targets in renal fibrosis.
The structure of an entire noncovalent immunoglobulin kappa light‐chain dimer (Bence‐Jones protein) reveals a weak and unusual constant domains association (1999)

Monoclonal free light chains secreted in immunoproliferative disorders are frequently involved in renal complications, including a specific proximal tubule impairment, Fanconi's syndrome. The latter is characterized in most cases by intracellular crystallization including a light-chain variable-domain fragment which resists lysosomal proteases. Bence-Jones protein (BJP) DEL was isolated from a patient with myeloma-associated Fanconi's syndrome. The crystal structure of this human kappa immunoglobulin light-chain noncovalent dimer was determined using molecular replacement with the structure of molecule REI, as the variable domain, and that of BJP LOC as the constant domain. To our knowledge, DEL is the first complete kappa BJP structure described to date. The R-factor is 20.7% at 2.8 A resolution. The BJP DEL dimer was compared with other light-chain dimers and with Fab fragments with a kappa light chain. Although the domain-folding pattern was similar, the relative positions of the constant domains differed. BJP DEL showed a noncanonical quaternary structural arrangement which may be attributable to the poor CL-CL affinity and lack of an interchain disulfide bridge, combined with the conformational editing effect of the crystal-packing forces. Our results suggest that, in the absence of a disulfide bridge, most BJP CLs are probably mobile in solution. This may explain their high susceptibility to proteases and the absence of naturally occurring crystals for these dimers. Furthermore, these findings of an unusual quaternary structure of an immunoglobulin light-chain association extend our knowledge about the large and highly diverse structures of the immunoglobulin superfamily.
A frame-synchronous network search algorithm for connected word recognition (1989)

A description is given of an implementation of a novel frame-synchronous network search algorithm for recognizing continuous speech as a connected sequence of words according to a specified grammar. The algorithm, which has all the features of earlier methods, is inherently based on hidden Markov model (HMM) representations and is described in an easily understood, easily programmable manner. The new features of the algorithm include the capability of recording and determining (unique) word sequences corresponding to the several best paths to each grammar node, and the capability of efficiently incorporating a range of word and state duration scoring techniques directly into the forward search of the algorithm, thereby eliminating the need for a postprocessor as in previous implementations. It is also simple and straightforward to incorporate deterministic word transition rules and statistical constraints (probabilities) from a language model into the forward search of the algorithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enhanced Inhibition of Transcription Start by Targeting with 2′‐OMe Pentaribonucleotides Comprising Locked Nucleic Acids and Intercalating Nucleic Acids (2005)

Inhibition assay. Pentaribonucleotides can bind to a DNA template strand near the transcription start site of an open complex (−4 to +1). 2′-OMe-Pentamers encompassing locked nucleic acids (TL, GL and AL) and intercalating nucleic acids (INA monomer P) exhibited enhanced inhibition compared to the unmodified pentamer. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2005/z400457_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy (2000)

Adeno-associated viral (AAV) vectors have demonstrated considerable promise for gene therapy of inherited diseases. However, with a packaging size of <5 kb, applications have been limited to relatively small disease genes. Based on the finding that AAV genomes undergo intermolecular circular concatamerization after transduction in muscle, we have developed a paradigm to increase the size of delivered transgenes with this vector through trans-splicing between two independent vectors coadministered to the same tissue. When two vectors encoding either the 5' or 3' portions of the erythropoietin genomic locus were used, functional erythropoietin protein was expressed in muscle subsequent to the formation of intermolecular circular concatamers in a head-to-tail orientation through trans-splicing between these two independent vector genomes. These findings will allow for the application of AAV technologies to a wider variety of diseases for which therapeutic transgenes exceed the packaging limitation of present AAV vectors.
Maturational changes in the rhythms, patterning, and coordination of respiration and swallow during feeding in preterm and term infants (2006)

To study the coordination of respiration and swallow rhythms we assessed feeding episodes in 20 preterm infants (gestational age range at birth 26-33wks; postmenstrual age [PMA] range when studied 32-40wks) and 16 term infants studied on days 1 to 4 (PMA range 37-41wks) and at 1 month (PMA range 41-45wks). A pharyngeal pressure transducer documented swallows and a thoracoabdominal strain gauge recorded respiratory efforts. Coefficients of variation (COVs) of breath-breath (BR-BR) and swallow-breath (SW-BR) intervals during swallow runs, percentage of apneic swallows (at least three swallows without interposed breaths), and phase of respiration relative to swallowing efforts were analyzed. Percentage of apneic swallows decreased with increasing PMA (16.6% [SE 4.7] in preterm infants <or=35wks' PMA; 6.6% [SE 1.6] in preterms >35wks; 1.5% [SE 0.4] in term infants; p<0.001). Term infants had significantly lower BR-BR COV (0.405 [SE 0.016]) than preterm infants (0.641 [SE 0.052] at >35wks' PMA; 0.693 [SE 0.059] at <or=35wks' PMA). Phase relation between swallowing and respiration stabilized with increasing PMA, with decreased apnea, and a significant increase in percentage of swallows occurring at end-inspiration. These data indicate that unlike the stabilization of suck and suck-swallow rhythms, which occur before about 36 weeks' PMA, improvement in coordination of respiration and swallow begins later. Coordination of swallow-respiration and suck-swallow rhythms may be predictive of feeding, respiratory, and neurodevelopmental abnormalities.
Automatic Relocalization and Loop Closing for Real-Time Monocular SLAM (2011)

Monocular SLAM has the potential to turn inexpensive cameras into powerful pose sensors for applications such as robotics and augmented reality. We present a relocalization module for such systems which solves some of the problems encountered by previous monocular SLAM systems--tracking failure, map merging, and loop closure detection. This module extends recent advances in keypoint recognition to determine the camera pose relative to the landmarks within a single frame time of 33 ms. We first show how this module can be used to improve the robustness of these systems. Blur, sudden motion, and occlusion can all cause tracking to fail, leading to a corrupted map. Using the relocalization module, the system can automatically detect and recover from tracking failure while preserving map integrity. Extensive tests show that the system can then reliably generate maps for long sequences even in the presence of frequent tracking failure. We then show that the relocalization module can be used to recognize overlap in maps, i.e., when the camera has returned to a previously mapped area. Having established an overlap, we determine the relative pose of the maps using trajectory alignment so that independent maps can be merged and loop closure events can be recognized. The system combining all of these abilities is able to map larger environments and for significantly longer periods than previous systems.
Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011 (2004)

Fludarabine and rituximab combination therapies in chronic lymphocytic leukemia (CLL) have yielded promising early results, but no comparative efficacy data relative to standard fludarabine treatment regimens have been reported. To assess the effect of the addition of rituximab to fludarabine therapy, we retrospectively compared the treatment outcome of patients with similar clinical characteristics enrolled on 2 multicenter clinical trials performed by the Cancer and Leukemia Group B and the US Intergroup that used fludarabine and rituximab (CALGB 9712, n = 104) or fludarabine (CALGB 9011, n = 178). In multivariate analyses controlling for pretreatment characteristics, the patients receiving fludarabine and rituximab had a significantly better progression-free survival (PFS; P < .0001) and overall survival (OS; P = .0006) than patients receiving fludarabine therapy. Two-year PFS probabilities were 0.67 versus 0.45, and 2-year OS probabilities were 0.93 versus 0.81. Infectious toxicity was similar between the 2 treatment approaches. These comparative data are retrospective and could be confounded by differences in supportive care or dissimilar enrollment of genetic subsets on each trial. Confirmation of these findings will require a prospective randomized trial comparing fludarabine and rituximab to fludarabine.
Quantitative specificity‐based display library screening identifies determinants of antibody‐epitope binding specificity (2009)

Despite the critical importance of molecular specificity in bimolecular systems, in vitro display technologies have been applied extensively for affinity maturation of peptides and antibodies without explicitly measuring the specificity of the desired interaction. We devised a general strategy to measure, screen, and evolve specificity of protein ligand interactions analogous to widely used affinity maturation strategies. The specificity of binding to target and nontarget antibodies labeled with spectrally distinct fluorophores was measured simultaneously in protein mixtures via multiparameter flow cytometry, thereby enabling screening for high target antibody specificity. Isolated antibody specific ligands exhibited varying specificity, revealing critical amino acid determinants for target recognition and nontarget avoidance in complex mixtures. Molecular specificity in the mixture was further enhanced by quantitative directed evolution, yielding a family of epitopes exhibiting improved specificities equivalent, or superior to, the native peptide antigen to which the antibody was raised. Specificity screening simultaneously favored affinity, yielding ligands with three-fold improved affinity relative to the parent epitope. Quantitative specificity screening will be useful to screen, evolve, and characterize the specificity of protein and peptide interactions for molecular recognition applications.