gebhart/patrepeval huggingface dataset:
Caprine Mucopolysaccharidosis-IIID (1998)

Several animal models have been developed for the mucopolysaccharidoses (MPSs), a group of lysosomal storage disorders caused by lysosomal hydrolase deficiencies that disrupt the catabolism of glycosaminoglycans (GAG). Among the MPS, the MPS-III (Sanfilippo) syndromes lacked an animal counterpart until recently. In this investigation of caprine MPS-IIID, the clinical, biochemical, morphological, and immunohistochemical studies revealed severe and mild phenotypes like those observed in human MPS III syndromes. Both forms of caprine MPS IIID result from a nonsense mutation and consequent deficiency of lysosomal N-acetylglucosamine 6-sulfatase (G6S) activity and are associated with tissue storage and urinary excretion of heparan sulfate (HS). Using special stains, immunohistochemistry, and electron microscopy, secondary lysosomes filled with GAG were identified in most tissues from affected goats. Primary neuronal accumulation of HS and the secondary storage of gangliosides were observed in the central nervous system (CNS) of these animals. In addition, morphological changes in the CNS such as neuritic expansions and other neuronal alterations that may have functional significance were also seen. The spectrum of lesions was greater in the severe form of caprine MPS IIID and included mild cartilaginous, bony, and corneal lesions. The more pronounced neurological deficits in the severe form were partly related to a greater extent of CNS dysmyelination. These findings demonstrate that caprine MPS IIID is a suitable animal model for the investigation of therapeutic strategies for MPS III syndromes.
I n s i t u cleaning of silicon substrate surfaces by remote plasma-excited hydrogen (1989)

We have demonstrated a low-temperature cleaning technique for removing both carbon and oxygen from a Si surface. It uses a combination of ex situ wet chemical clean and an in situ remote rf plasma-excited hydrogen clean in an ultrahigh vacuum chamber. Since a remote rf plasma is used, there is insignificant plasma damage or other deleterious effects on surface morphology. A combination of in situ Auger and RHEED analysis has been used to confirm the removal of surface contaminants and the reconstruction of the Si surface. From mass spectroscopy studies, we believe that the hydrogen cleaning is due to a chemical etching of the Si by atomic hydrogen produced by the plasma. This clean is compatible with UHV processing and yields Si substrates that can be used for successful very low temperature (220–400 °C) Si homoepitaxy by remote plasma-enhanced chemical vapor deposition.
Evaluation of In Vitro Capacitation of Stallion Spermatozoa1 (2001)

The primary aim of this study was to establish a flow cytometric technique for determining the capacitation status of stallion spermatozoa. To this end, a flow cytometric technique that demonstrates changes in plasma membrane fluidity; namely, merocyanine 540 staining, was compared with the more conventional Ca(2+)-dependent fluorescence microscopic technique, chlortetracycline (CTC) staining, for assessing capacitation status. In addition, the effect of bicarbonate/CO(2) on the progress of capacitation and the acrosome reaction (AR) and on temporal changes in sperm motility, with particular regard to hyperactivation, was analyzed. For the study, fresh semen was washed and then incubated for 5 h in bicarbonate-containing or bicarbonate-free medium, with or without Ca(2+) ionophore to induce the AR, and at intervals during incubation aliquots were taken and analyzed for capacitation and acrosome status. The AR was assessed using both the CTC and fluorescein isothiocyanate-peanut agglutinin (FITC-PNA) staining techniques with similar results. In brief, it was found that merocyanine 540 detects capacitation-related changes much earlier than CTC does (0.5 h versus approximately 3 h), and that flow cytometry for evaluation of capacitation and AR was a quicker (10 sec per sample) and more accurate (10,000 cells counted) technique than fluorescence microscopy. Furthermore, it was observed that Ca(2+) ionophore could not induce the AR in the absence of bicarbonate, but that the ionophore synergized the bicarbonate-mediated induction of the AR as detected by CTC (although it was not significant when evaluated using FITC-PNA). The percentage of hyperactive sperm in each sample was not affected by time of incubation under the experimental conditions studied. In conclusion, merocyanine 540 staining is a better method than CTC staining for evaluating the early events of capacitation for stallion spermatozoa incubated in vitro. Furthermore, bicarbonate sperm activation clearly plays a vital role in the induction of the AR in stallion spermatozoa.
Bayesian probabilistic matrix factorization using Markov chain Monte Carlo (2008)

Low-rank matrix approximation methods provide one of the simplest and most effective approaches to collaborative filtering. Such models are usually fitted to data by finding a MAP estimate of the model parameters, a procedure that can be performed efficiently even on very large datasets. However, unless the regularization parameters are tuned carefully, this approach is prone to overfitting because it finds a single point estimate of the parameters. In this paper we present a fully Bayesian treatment of the Probabilistic Matrix Factorization (PMF) model in which model capacity is controlled automatically by integrating over all model parameters and hyperparameters. We show that Bayesian PMF models can be efficiently trained using Markov chain Monte Carlo methods by applying them to the Netflix dataset, which consists of over 100 million movie ratings. The resulting models achieve significantly higher prediction accuracy than PMF models trained using MAP estimation.
GPU Computing (2008)

The graphics processing unit (GPU) has become an integral part of today's mainstream computing systems. Over the past six years, there has been a marked increase in the performance and capabilities of GPUs. The modern GPU is not only a powerful graphics engine but also a highly parallel programmable processor featuring peak arithmetic and memory bandwidth that substantially outpaces its CPU counterpart. The GPU's rapid increase in both programmability and capability has spawned a research community that has successfully mapped a broad range of computationally demanding, complex problems to the GPU. This effort in general-purpose computing on the GPU, also known as GPU computing, has positioned the GPU as a compelling alternative to traditional microprocessors in high-performance computer systems of the future. We describe the background, hardware, and programming model for GPU computing, summarize the state of the art in tools and techniques, and present four GPU computing successes in game physics and computational biophysics that deliver order-of-magnitude performance gains over optimized CPU applications.
Heat inactivation of Mycobacterium paratuberculosis in raw milk: are current pasteurization conditions effective? (1997)

Currently, it is not known whether commercial pasteurization effectively kills Mycobacterium paratuberculosis in contaminated raw milk. Results from holder test tube experiments indicated that a residual population of viable bacteria remained after treatment at 65, 72, 74, or 76 degrees C for 0 to 30 min. Use of a laboratory-scale pasteurizer unit demonstrated that treatment of raw milk at 72 degrees C for 15 s effectively killed all M. paratuberculosis.
Thermodynamic basis of selectivity in guide‐target‐mismatched rna interference (2012)

Silencing in RNAi is strongly affected by guide-strand/target-mRNA mismatches. Target nucleation is thought to occur at positions 2-8 of the guide ("seed region"); successful hybridization in this region is the primary determinant of target-binding affinity and hence target cleavage. To define a molecular basis for the target sequence selectivity in RNAi, we studied all possible distinct single mismatches in seven positions of the seed region-a total of 21 substitutions. We report results from soft-core thermodynamic integration simulations to determine changes in targeting binding-free energies to Argonaute due to single mismatches in the guide strand, which arise during binding of an imperfectly matched target mRNA. In agreement with experiment, most mismatches impair target binding, consistent with a prominent role for binding affinity changes in RNAi sequence selectivity. Individual Argonaute residues located near the mismatched base pair are found to contribute significantly to binding affinity changes. We also use this methodology to analyze the mismatch-dependent free energy changes for dissociation of a DNA•RNA hybrid from Argonaute, as a model for the escape of miRNAs from the silencing pathway. Several mismatched sequences of the miRNA have increased affinity to Argonaute, implying that some mismatches may reduce the probability for escape. Furthermore, calculations of base-substitution-dependent free energy changes for binding ssDNA reveal mild sequence sensitivity as expected for guide strand binding to Argonaute. Our findings give a thermodynamic basis for RNAi target sequence selectivity and suggest that miRNA mismatches may increase silencing effectiveness and thus could be evolutionarily advantageous.
Standardized assessment of cognitive functioning during development and aging using an automated touchscreen battery (2006)

This study examined the effects of age, gender and education on subjects spanning nine decades on a new cognitive battery of 12 tests. One thousand and seven participants between 6 and 82 completed the battery under standardized conditions using an automated, computerized touchscreen. Sensitive indicators of change were obtained on measures of attention and working memory, learning and memory retrieval, and language, visuospatial function, sensori-motor and executive function. Improvement tended to occur through to the third and fourth decade of life, followed by gradual decrement and/or stabilized performance thereafter. Gender differences were obtained on measures of sustained attention, verbal learning and memory, visuospatial processing and dexterity. Years of education in adults was reflected in performance on measures of verbal function. Overall, the test battery provided sensitive indicators on a range of cognitive functions suitable for the assessment of abnormal cognition, the evaluation of treatment effects and for longitudinal case management.
Isolation and characterization of the human tissue-type plasminogen activator structural gene including its 5' flanking region. (1985)

mRNA specific for tissue type plasminogen activator (t-PA) is induced in HeLa cells by the tumor promoter phorbol myristate acetate (Waller, E.K., and Schleuning, W.D. (1985) J. Biol. Chem. 260, 6354-6360). To study the underlying mechanism, a cDNA library was constructed from phorbol myristate acetate stimulated HeLa cell mRNA and screened with two t-PA mRNA specific oligonucleotides (Edlund, T., Ny, T., Rånby, M., Heden, L.-O., Palm, G., Holmgren, E., and Josephson, S. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 349-352). Two nearly full length double-stranded cDNA clones were obtained. Suitable restriction fragments from the cDNA were employed as probes for the isolation of three recombinant bacteriophages, containing overlapping fragments of the t-PA gene. By restriction analysis, heteroduplex mapping, and DNA sequencing it was determined that the three overlapping fragments contain the complete t-PA structural gene and that the 2658 bases long t-PA mRNA is encoded by a gene of approximately 29 kilobases overall length, which is interrupted by 13 introns. To characterize the presumptive control region, a subcloned gene fragment, containing the 5' sequence of the cDNA, was sequenced, and the transcription initiation site was identified by nuclease S1 protection experiments. The putative transcription start site is located 24 base pairs (bp) downstream of a typical TATA consensus sequence. Two additional TATA motifs with hitherto unknown functions are found 93 and 226 bp upstream of the putative cap site. A recombinant plasmid was constructed, which accommodates the cap site including 475 bp of upstream sequences, fused to a double-stranded cDNA of t-PA mRNA which contains the complete translated and parts of the 5' and 3' untranslated regions. This plasmid directs t-PA biosynthesis in Xenopus laevis oocytes after microinjection into the germinal vesicle.
“Nonclassical” Secretion of Annexin A2 to the Lumenal Side of the Enterocyte Brush Border Membrane (2003)

Annexin A2 is a member of the annexin family of Ca(2+)-dependent lipid binding proteins and believed to be engaged in membrane transport processes in a number of cell types. In small intestinal enterocytes, we localized annexin A2 to the brush border region, where it was found mainly on the lumenal side of the microvilli, showing an apical secretion by a "nonclassical" mechanism. In addition, annexin A2 was associated with surface-connected, deep apical tubules in the apical terminal web region and with an underlying pleiomorphic, tubulo-vesicular compartment (subapical compartment/multivesicular bodies). By subcellular fractionation, the 36 kDa full-length form of annexin A2 was approximately equally distributed between the Mg(2+)-precipitated fraction (containing intracellular and basolateral membranes) and the microvillar membrane fraction. In addition, a 33 kDa molecular form of annexin A2 was seen in the latter fraction that could be generated from the full-length annexin A2 by digestion with trypsin. Taken together, the results suggest that annexin A2 acts in exocytic apical membrane trafficking and is proteolytically cleaved in situ by pancreatic proteinases once it has become externalized to the lumenal side of the brush border membrane. On the basis of its well-known membrane fusogenic properties, we propose a model for the nonclassical membrane translocation of annexin A2.
A high yielding mutant of mycobacteriophage L1 and its application as a diagnostic tool (2000)

L1 is a lysogenic phage of mycobacteria, which along with L5 and D29 constitute a closely linked family of homoimmune mycobacteriophages. These phages can be potentially used for genetic engineering of mycobacteria and diagnosis of mycobacterial infection. The effectiveness of such phage based systems depends on the efficiency with which they infect and grow within target cells. While working with phage L1c1ts which is a temperature sensitive mutant of phage L1, we observed that high yielding phage stocks were generated by repeated passage through the host, Mycobacterium smegmatis. A plaque purified mutant L1-P2, obtained from one such high yielding stock, when analyzed further was found to infect host cells with increased efficiency. The DNA obtained from L1-P2 was examined by restriction digestion, and it was observed that spontaneous loss of DNA fragment from the right arm, which encodes early regulatory factors, had occurred. It has been further demonstrated that the high yielding property of the mutant phage could be utilized to increase the sensitivity of mycobacteriophage-based detection systems.
Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96. (1995)

Vaccination of mice with heat shock proteins isolated from tumor cells induces immunity to subsequent challenge with those tumor cells the heat shock protein was isolated from but not with other tumor cells (Udono, H., and P.K. Srivastava. 1994. J. Immunol. 152:5398-5403). The specificity of this immune response is caused by tumor-derived peptides bound to the heat shock proteins (Udono., H., and P.K. Srivastava. 1993. J. Exp. Med. 178:1391-1396). Our experiments show that a single immunization with the heat shock protein gp96 isolated from beta-galactosidase (beta-gal) expressing P815 cells (of DBA/2 origin) induces cytotoxic T lymphocytes (CTLs) specific for beta-gal, in addition to minor H antigens expressed by these cells. CTLs can be induced in mice that are major histocompatibility complex (MHC) identical to the gp96 donor cells (H-2d) as well as in mice with a different MHC (H-2b). Thus gp96 is able to induce "cross priming" (Matzinger, P., and M.J. Bevan. 1977. Cell. Immunol. 33:92-100), indicating that gp96-associated peptides are not limited to the MHC class I ligands of the gp96 donor cell. Our data confirm the notion that samples of all cellular antigens presentable by MHC class I molecules are represented by peptides associated with gp96 molecules of that cell, even if the fitting MHC molecule is not expressed. In addition, we extend previous reports on the in vivo immunogenicity of peptides associated gp96 molecules to two new groups of antigens, minor H antigens, and proteins expressed in the cytosol.
THE ??-1,3-GALACTOSYLTRANSFERASE KNOCKOUT MOUSE (1996)

Organ xenografts in discordant combinations such as pig-to-man undergo hyperacute rejection due to the presence of naturally occurring human anti-pig xenoantibodies. The galactose alpha(1,3)-galactose epitope on glycolipids and glycoproteins is the major porcine xenoantigen recognized by these xenoantibodies. This epitope is formed by alpha(1,3)-galactosyltransferase, which is present in all mammals except man, apes, and Old World monkeys. We have generated mice lacking this major xenoantigen by inactivating the alpha(1,3)-galactosyltransferase gene. These mice are viable and have normal organs but develop cataracts. Substantially less xenoantibody from human serum binds to cells and tissues of these mice compared with normal mice. Similarly, there is less activation of human complement on cells from mice lacking the galactose alpha(1,3)-galactose epitope. These mice confirm the importance of the galactose alpha(1,3)-galactose epitope in human xenoreactivity and the logic of continuing efforts to generate pigs that lack this epitope as a source of donor organs.
Improved glycaemic control by switching from insulin NPH to insulin glargine: a retrospective observational study (2009)

In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.
Simultaneous Two‐Photon Activation of Type‐I Photodynamic Therapy Agents (1997)

The excitation and emission properties of several psoralen derivatives are compared using conventional single-photon excitation and simultaneous two-photon excitation (TPE). Two-photon excitation is effected using the output of a mode-locked titanium: sapphire laser, the near infrared output of which is used to promote nonresonant TPE directly. Specifically, the excitation spectra and excited-state properties of 8-methoxypsoralen and 4'-aminomethyl-4,5,8-trimethylpsoralen are shown to be equivalent using both modes of excitation. Further, in vitro feasibility of two-photon photodynamic therapy (PDT) is demonstrated using Salmonella typhimurium. Two-photon excitation may be beneficial in the practice of PDT because it would allow replacement of visible or UV excitation light with highly penetrating, nondamaging near infrared light and could provide a means for improving localization of therapy. Comparison of possible laser excitation sources for PDT reveals the titanium: sapphire laser to be exceptionally well suited for nonlinear excitation of PDT agents in biological systems due to its extremely short pulse width and high repetition rate that together provide efficient PDT activation and greatly reduced potential for biological damage.
Up-Regulation of Acid-Sensing Ion Channel 3 in Dorsal Root Ganglion Neurons Following Application of Nucleus Pulposus on Nerve Root in Rats (2006)

Our results suggest that ASIC3 in DRG neurons may play an important role in nerve root pain caused by lumbar disc herniation. Lidocaine decreased ASIC3 expression in DRG neurons and pain associated with the disc herniation model.
A 14-bit current-mode /spl Sigma//spl Delta/ DAC based upon rotated data weighted averaging (2000)

A new dynamic element matching (DEM) algorithm, referred to as rotated data weighted averaging (RDWA), is implemented in a third-order /spl Sigma//spl Delta/ digital-to-analog converter (DAC) with 64/spl times/ oversampling and a conversion bandwidth of 25 kHz. The systematic and random errors are considered in the design of the 14-bit converter. The /spl Sigma//spl Delta/ DAC is fabricated in a 2-/spl mu/m CMOS process and includes the on-chip reconstruction filter. The prototype was designed to test the performance of the DAC without DEM, with data weighted averaging (DWA), and with RDWA. The results show that the new RDWA algorithm is capable of achieving first-order noise shaping while eliminating the signal-dependent harmonic distortion present in DWA.
A mimotope from a solid-phase peptide library induces a measles virus-neutralizing and protective antibody response (1995)

A solid-phase 8-mer random combinatorial peptide library was used to generate a panel of mimotopes of an epitope recognized by a monoclonal antibody to the F protein of measles virus (MV). An inhibition immunoassay was used to show that these peptides were bound by the monoclonal antibody with different affinities. BALB/c mice were coimmunized with the individual mimotopes and a T-helper epitope peptide (from MV fusion protein), and the reactivity of the induced anti-mimotope antibodies with the corresponding peptides and with MV was determined. The affinities of the antibodies with the homologous peptides ranged from 8.9 x 10(5) to 4.4 x 10(7) liters/mol. However, only one of the anti-mimotope antibodies cross-reacted with MV in an enzyme-linked immunosorbent assay and inhibited MV plaque formation. Coimmunization of mice with this mimotope and the T-helper epitope peptide induced an antibody response which conferred protection against fatal encephalitis induced following challenge with MV and with the structurally related canine distemper virus. These results indicate that peptide libraries can be used to identify mimotopes of conformational epitopes and that appropriate immunization with these mimotopes can induce protective antibody responses.
Patient Compliance in Medical Practice and Clinical Trials (1991)

Patient noncompliance with medical regimens is a major factor in therapeutic failure and is particularly detrimental to clinical trials. This text aims to address the entire scope of compliance issues, and describes electronic monitoring devices that record actual dose times. Traditional methods of assessing compliance, such as patient history, drug levels, and counting pills or prescription refills, are also discussed. The review of everyday clinical problems facing practitioners everywhere is complemented by discussions on the impact of noncompliance in research and the drug regulatory process. Health care providers in all fields as well as clinical trial researchers should find useful ideas throughout the book.