gebhart/patrepeval huggingface dataset:
Stereochemical course of polymerization catalyzed by avian myeloblastosis virus reverse transcriptase. (1982)

The Sp diastereomer of thymidine 5'-O-(1-thiotriphosphate) was polymerized by avian myeloblastosis virus reverse transcriptase using poly(A) . d(pT)10 as template-primer. Degradation of the template poly(A) by alkaline hydrolysis and isolation by gel chromatography gave a single-stranded poly(d(p(S)T)), a polymer of thymidine 5'-phosphorothioate. To determine the configuration of the phosphorothioate internucleotide linkage, this material was degraded by snake venom phosphodiesterase. Comparison of the rates of degradation by snake venom phosphodiesterase of poly(d(p(S)T)) prepared by reverse transcriptase and DNA polymerase I showed them to be very similar. Since it has been established earlier than the latter enzyme produces polymers with phosphorothioate linkages of the Rp configuration (Burgers, P. M. J., and Eckstein, F. (1979) J. Biol. Chem. 254, 6889-6893), it is concluded that the polymer produces by reverse transcriptase has the same stereochemistry. Further proof for this assignment comes from comparison by 31P nmr of this polymer with the diastereomers of synthetic 5'-O-thymidyl 3'-O-thymidyl phosphorothioate. The chemical shift observed for the polymer was identical with that of the Rp isomer of 5'-O-thymidyl 3'-O-thymidyl phosphorothioate. Avian myeloblastosis virus reverse transcriptase therefore polymerizes deoxynucleoside 5'-triphosphates with inversion of configuration at the alpha-phosphorus. This result indicates that direct nucleophilic attack by the 3-hydroxyl group of the growing polymer on the alpha-phosphoryl group occurs without formation of a covalent enzyme intermediate.
Principles of Motor Unit Physiology Evolve With Advances in Technology (2016)

Movements are generated by the coordinated activation of motor units. Recent technological advances have made it possible to identify the concurrent activity of several tens of motor units, in contrast with much smaller samples available in classic studies. We discuss how these advances in technology have enabled the development of a population perspective of how the central nervous system controls motor unit activity and thereby the forces exerted by muscles.
Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol (2008)

Using transcript profiling, we have identified the cellular pathways targeted by pterostilbene, an analog of resveratrol. The observed response in lipid metabolism genes is consistent with its known hypolipidemic properties, and the induction of mitochondrial genes is consistent with its demonstrated role in apoptosis in human cancer cell lines. Furthermore, our data show that pterostilbene has a significant effect on methionine metabolism, a previously unreported effect for this compound.
Compilation framework for code size reduction using reduced bit-width ISAs (rISAs) (2006)

For many embedded applications, program code size is a critical design factor. One promising approach for reducing code size is to employ a “dual instruction set”, where processor architectures support a normal (usually 32-bit) Instruction Set, and a narrow, space-efficient (usually 16-bit) Instruction Set with a limited set of opcodes and access to a limited set of registers. This feature however, requires compilers that can reduce code size by compiling for both Instruction Sets. Existing compiler techniques operate at the routine-level granularity and are unable to make the trade-off between increased register pressure (resulting in more spills) and decreased code size. We present a compilation framework for such dual instruction sets, which uses a profitability based compiler heuristic that operates at the instruction-level granularity and is able to effectively take advantage of both Instruction Sets. We demonstrate consistent and improved code size reduction (on average 22%), for the MIPS 32/16 bit ISA. We also show that the code compression obtained by this “dual instruction set” technique is heavily dependent on the application characteristics and the narrow Instruction Set itself.
Asymmetrical synthesis of L-homophenylalanine using engineered Escherichia coli aspartate aminotransferase (2005)

Site-directed mutagenesis was performed to change the substrate specificity of Escherichia coli aspartate aminotransferase (AAT). A double mutant, R292E/L18H, with a 12.9-fold increase in the specific activity toward L-lysine and 2-oxo-4-phenylbutanoic acid (OPBA) was identified. E. coli cells expressing this mutant enzyme could convert OPBA to L-homophenylalanine (L-HPA) with 97% yield and more than 99.9% ee using L-lysine as amino donor. The transamination product of L-lysine, 2-keto-6-aminocaproate, was cyclized nonenzymatically to form Delta(1)-piperideine 2-carboxylic acid in the reaction mixture. The low solubility of L-HPA and spontaneous cyclization of 2-keto-6-aminocaproate drove the reaction completely toward L-HPA production. This is the first aminotransferase process using L-lysine as inexpensive amino donor for the L-HPA production to be reported.?
The effect of conduction band non-parabolicity on inter-sub-band absorption in doped quantum wells (1988)

The authors have theoretically treated the effect of conduction band non-parabolicity on inter-sub-band absorption in doped semiconductor quantum wells. The authors have derived an analytical expression for the absorption at zero temperature. The absorption peak is shifted to lower energies and the peak height is reduced by non-parabolicity. These effects are small for GaAs-based quantum wells, but may be detrimental to InGaAs quantum wells.
Progression-Specific Genes Identified by Expression Profiling of Matched Ductal Carcinomas In situ and Invasive Breast Tumors, Combining Laser Capture Microdissection and Oligonucleotide Microarray Analysis (2006)

Abstract Becoming invasive is a crucial step in breast cancer oncogenesis. At this point, a lesion carries the potential for spreading and metastasis—a process, whose molecular characteristics still remain poorly understood. In this article, we describe a matched-pair analysis of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of nine breast ductal carcinomas to identify novel molecular markers characterizing the transition from DCIS to IDC. The purpose of this study was to better understand the molecular biology of this transition and to identify candidate genes whose products might serve as prognostic markers and/or as molecular targets for treatment. To obtain cellular-based gene expression profiles from epithelial tumor cells, we combined laser capture microdissection with a T7-based two-round RNA amplification and Affymetrix oligonucleotide microarray analysis. Altogether, a set of 24 tumor samples was analyzed, comprised of nine matched DCIS/IDC and replicate DCIS/IDC preparations from three of the nine tumors. Cluster analysis on expression data shows the robustness and reproducibility of the techniques we established. Using multiple statistical methods, 546 significantly differentially expressed probe sets were identified. Eighteen candidate genes were evaluated by RT-PCR. Examples of genes already known to be associated with breast cancer invasion are BPAG1, LRRC15, MMP11, and PLAU. The expression of BPAG1, DACT1, GREM1, MEF2C, SART2, and TNFAIP6 was localized to epithelial tumor cells by in situ hybridization and/or immunohistochemistry, confirming the accuracy of laser capture microdissection sampling and microarray analysis. (Cancer Res 2006; 66(10): 5278-86)
Demonstration of the neurotransmitter role of calcitonin gene‐related peptides (CGRP) by immunoblockade with anti‐CGRP monoclonal antibodies (1994)

1. Monoclonal antibodies (MAbs) against rat alpha-calcitonin gene-related peptide (alpha CGRP) were produced. Those which bound CGRP in a radioimmunoassay and inhibited the binding of 2-[125I]-iodohistidyl10-CGRP in a receptor binding assay were selected for immunoblockade experiments. 2. The effect of MAbs on CGRP inhibition of electrically stimulated contractions of the rat isolated vas deferens was characterized. Four out of 11 MAbs tested shifted the concentration-response curve of CGRP to the right compared with vehicle or irrelevant MAb control. MAb C4.19 produced equipotent blockade of rat alpha CGRP and rat beta CGRP and was chosen for further studies. MAb C4.19 had no pharmacologically significant effect on the concentration-response relationship of isoprenaline, rat beta-endorphin or somatostatin. 3. We demonstrated that the pharmacological response to CGRP in the presence of MAb C4.19 could be predicted when the dissociation constant and concentration of binding sites of the antibody were known. Comparison of experimental and computer simulated data showed good agreement for EC50 and maximum effect of CGRP in the presence of MAb C4.19. 4. Capsaicin at 1 microM inhibited the electrically stimulated contractions by 60.8% (95% confidence interval 51.8% to 69.9%). This effect was significantly attenuated by MAb C4.19 to 26.0% (95% confidence interval 15.2% to 36.8%; P < 0.003). 5. The immunoblockade of exogenous and endogenous CGRP described here, together with complementary evidence from other studies, strongly suggest that CGRP has a major neurotransmitter role at the neuroeffector junction of the rat vas deferens.
De novo peptide sequencing by deep learning (2017)

De novo peptide sequencing from tandem MS data is the key technology in proteomics for the characterization of proteins, especially for new sequences, such as mAbs. In this study, we propose a deep neural network model, DeepNovo, for de novo peptide sequencing. DeepNovo architecture combines recent advances in convolutional neural networks and recurrent neural networks to learn features of tandem mass spectra, fragment ions, and sequence patterns of peptides. The networks are further integrated with local dynamic programming to solve the complex optimization task of de novo sequencing. We evaluated the method on a wide variety of species and found that DeepNovo considerably outperformed state of the art methods, achieving 7.7-22.9% higher accuracy at the amino acid level and 38.1-64.0% higher accuracy at the peptide level. We further used DeepNovo to automatically reconstruct the complete sequences of antibody light and heavy chains of mouse, achieving 97.5-100% coverage and 97.2-99.5% accuracy, without assisting databases. Moreover, DeepNovo is retrainable to adapt to any sources of data and provides a complete end-to-end training and prediction solution to the de novo sequencing problem. Not only does our study extend the deep learning revolution to a new field, but it also shows an innovative approach in solving optimization problems by using deep learning and dynamic programming.
Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. (1999)

The findings indicate that accumulation of A2-E in RPE cells interferes with lysosomal functions as exemplified by its inhibitory effect on protein and glycosaminoglycan catabolic pathways. The quaternary amine character of the A2-E apparently causes a perturbation of the acidic intralysosomal milieu, resulting in diminished hydrolase action and consequent accumulation of undegraded material. Such mechanism could be operative in retinal diseases associated with excessive lipofuscin accumulation including age-related macular degeneration.
Separation and isolation of human apolipoproteins C-II, C-III0, C-III1, and C-III2 by chromatofocusing on the Fast Protein Liquid Chromatography system (1987)

Chromatofocusing, which separates proteins based on differences in isoelectric point, has been used on the Fast Protein Liquid Chromatography (FPLC) system (Pharmacia) to separate the C apolipoproteins from human very low density lipoproteins (VLDL). Using a Mono P column (Pharmacia), a pH gradient between pH 6.2 and pH 4.0 was generated using buffers containing 6 M urea, at a flow rate of 0.5 ml/min. Typically, runs took approximately 45 min. Chromatofocusing of delipidated whole VLDL produced sharp, well-resolved peaks for the C apolipoproteins. However, as determined by analytical isoelectric focusing (IEF), the apolipoprotein E isoforms were not separated from apoC-II, and they contaminated the other apoC species to a variable extent. In addition, apoC-II was not resolved from apoC-III0. Preliminary precipitation of VLDL with acetone prior to delipidation removed both apolipoproteins E and B. Using a start buffer of 25 mM histidine, pH 6.2, and a 1:30 dilution of the polybuffer exchanger (eluting buffer), apoC-II, C-III0, C-III1, and C-III2 were well resolved in run-times of approximately 60 min. The C apoproteins proved to be pure by analytical IEF and immunoassay with monospecific antisera against apoC-II and C-III. Recovery was over 90% of the protein chromatographed. In addition, a variant of apoC-II present in VLDL of a hypertriglyceridemic subject was clearly resolved from the other C apolipoproteins. This technique is superior to conventional methodology in terms of its time saving and high resolution. The application of this technique to the study of C apolipoprotein variants and C apolipoprotein specific radioactivity determinations is possible.
Major regulators of microRNAs biogenesis Dicer and Drosha are down-regulated in endometrial cancer (2011)

Alterations in microRNAs expression have been proposed to play role in endometrial cancer pathogenesis. Dicer and Drosha are main regulators of microRNA biogenesis and deregulation of their expression has been indicated as a possible cause of microRNAs alterations observed in various cancers. The objective of this study was to investigate Dicer and Drosha genes expression in endometrial cancer and to analyze the impact of clinicopathological characteristics on their expression. Fresh tissue samples were collected from 44 patients (26 endometroid endometrial carcinoma and 18 controls). Clinical and pathological data were acquired from medical documentation. Dicer and Drosha genes expressions were assessed by qRT-PCR using validated reference genes. Dicer and Drosha expression levels were significantly lower in endometrial cancer samples comparing to controls. Dicer was down-regulated by the factor of 1.54 (p=0.009) and Drosha gene mean expression value was 1.4 times lower in endometrial cancer group versus control group (p=0.008). Down-regulation of Dicer significantly correlated with decreased expression of Drosha (coefficient value 0.75). Decreased expression of Drosha correlated with higher histological grade and was influenced by BMI. Lower Dicer expression was found in nulli- and uniparous females comparing to multiparous individuals (p=0.002). Neither the FIGO stage nor the menstrual status had significant influence on the expression of studied genes. This study revealed for the first time that expression alterations of main regulators of microRNAs biogenesis are present in endometrial cancer tissue and could be potentially responsible for altered microRNAs profiles observed in this malignancy.
Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor‐β1 in monolayer and insulin‐like growth factor‐I in a three‐dimensional matrix (2001)

This study evaluated chondrogenesis of mesenchymal progenitor stem cells (MSCs) cultured initially under pre-confluent monolayer conditions exposed to transforming growth factor-beta1 (TGF-beta1), and subsequently in three-dimensional cultures containing insulin-like growth factor I (IGF-I). Bone marrow aspirates and chondrocytes were obtained from horses and cultured in monolayer with 0 or 5 ng of TGF-beta 1 per ml of medium for 6 days. TGF-beta 1 treated and untreated cultures were distributed to three-dimensional fibrin disks containing 0 or 100 ng of IGF-I per ml of medium to establish four treatment groups. After 13 days, cultures were assessed by toluidine blue staining, collagen types I and II in situ hybridization and immunohistochemistry, proteoglycan production by [35S]-sulfate incorporation, and disk DNA content by fluorometry. Mesenchymal cells in monolayer cultures treated with TGF-beta1 actively proliferated for the first 4 days, developed cellular rounding, and formed cell clusters. Treated MSC cultures had a two-fold increase in medium proteoglycan content. Pretreatment of MSCs with TGF-beta1 followed by exposure of cells to IGF-I in three-dimensional culture significantly increased the formation of markers of chondrocytic function including disk proteoglycan content and procollagen type II mRNA production. However, proteoglycan and procollagen type II production by MSC's remained lower than parallel chondrocyte cultures. MSC pretreatment with TGF-beta1 without sequential IGF-I was less effective in initiating expression of markers of chondrogenesis. This study indicates that although MSC differentiation was less than complete when compared to mature chondrocytes, chondrogenesis was observed in IGF-I supplemented cultures, particularly when used in concert with TGF-beta1 pretreatment.
Online aggregation for large MapReduce jobs (2011)

In online aggregation, a database system processes a user's aggregation query in an online fashion. At all times during processing, the system gives the user an estimate of the final query result, with the confidence bounds that become tighter over time. In this paper, we consider how online aggregation can be built into a MapReduce system for large-scale data processing. Given the MapReduce paradigm's close relationship with cloud computing (in that one might expect a large fraction of MapReduce jobs to be run in the cloud), online aggregation is a very attractive technology. Since large-scale cloud computations are typically pay-as-you-go, a user can monitor the accuracy obtained in an online fashion, and then save money by killing the computation early once sufficient accuracy has been obtained.
Extracting depth and matte using a color-filtered aperture (2008)

This paper presents a method for automatically extracting a scene depth map and the alpha matte of a foreground object by capturing a scene through RGB color filters placed in the camera lens aperture. By dividing the aperture into three regions through which only light in one of the RGB color bands can pass, we can acquir three shifted views of a scene in the RGB planes of an image in a single exposure. In other words, a captured image has depth-dependent color misalignment. We develop a color alignment measure to estimate disparities between the RGB planes for depth reconstruction. We also exploit color misalignment cues in our matting algorithm in order to disambiguate between the foreground and background regions even where their colors are similar. Based on the extracted depth and matte, the color misalignment in the captured image can be canceled, and various image editing operations can be applied to the reconstructed image, including novel view synthesis, postexposure refocusing, and composition over different backgrounds.
Formulation of the purified fusion protein of respiratory syncytial virus with the saponin QS-21 induces protective immune responses in mice that are similar to those generated by experimental infection (1995)

The feasibility of employing a vaccine composed of the purified fraction 21 of Quillaja saponaria (QS-21) and the fusion (F) protein of respiratory syncytial virus (RSV) to induce protective immune responses in the lower respiratory tract of Balb/c mice was examined. Our goal was to compare local and systemic immune responses with those induced following immunization with the protein adsorbed to aluminium hydroxide (F/ALOH) adjuvant or by experimental infection. Sera from mice vaccinated with the QS-21 formulation (F/QS-21) contained elevated anti-F protein IgG antibody titres that were dependent on the dose of QS-21 employed. Similar to the immune responses generated by experimental infection, the sera from mice vaccinated with F/QS-21 possessed greater capacity to neutralize virus infectivity that was associated with the generation of heightened complement-fixing IgG2a antibody titres. In contrast, vaccination with F/ALOH elicited systemic immune responses that were characterized by a predominance of protein-specific antibodies of the IgG1 subclass and lower neutralizing antibody titres. The capacity of F/QS-21 to facilitate local pulmonary immune responses was also examined and found to be similar to those induced by experimental infection. After virus challenge, a 90-fold increase in the number of F protein-specific antibody-secreting cells was observed and associated with the clearance of virus from the infected lungs. Moreover, elevated levels of antigen-dependent killer cell activity were detected and appeared to be mediated by class I major histocompatibility complex restricted CD8+ T cells. Additional characterization of the pulmonary immune response was performed on the cellular infiltrates obtained after bronchoalveolar lavage and on formalin-fixed lung tissue. The local protective immune responses induced after challenge of the groups immunized with F/QS-21 or infectious virus were significantly different from those elicited in naive control mice injected with adjuvant alone, or in mice immunized with F/ALOH. The cellularity of the lavage fluids from the former groups was characterized by a significantly greater percentage of lymphocytes and less neutrophils. In similar fashion histological evaluation of the lungs from mice immunized with F/QS-21 or infectious virus revealed significantly elevated local immune responses after challenge. In conclusion, the results suggest that formulation with F/QS-21 alters the qualitative and quantitative nature of the immune response to the F glycoprotein when compared with the traditional aluminium-based adjuvants.
Rooster comb hyaluronate—protein, a non-covalently linked complex (1986)

Hyaluronate from rooster comb was isolated by ion-exchange chromatography on DEAE-cellulose from tissue extracts and papain digests. The preparations were labelled with [14C]acetic anhydride and subjected to CsCl-density-gradient centrifugation in 4 M-guanidinium chloride in the presence and absence of 4% ZwittergentTM 3-12. A radioactive protein fraction was separated from the hyaluronate when the zwitterionic detergent was also present. The protein could also be separated from the glycosaminoglycan by chromatography on Sepharose CL-6B eluted with the same solvent mixture. The protein fraction contained three protein bands of Mr 15,000-17,000 as assessed by polyacrylamide-gel electrophoresis in 0.1% SDS, and seemed to lack lysozyme activity. No evidence of other protein or amino acid(s) covalently linked with the hyaluronate was obtained. The hyaluronate-protein complex may be re-formed upon mixing the components, the extent of its formation depending on the conditions used. The results show that, as in chondrosarcoma [Mason, d'Arville, Kimura & Hascall (1982) Biochem. J. 207, 445-457] and teratocarcinoma cells [Prehm (1983) Biochem. J. 211, 191-198] the rooster comb hyaluronate also is not linked covalently to a core protein.