gebhart/patrepeval huggingface dataset:
Induction of Tumor-Reactive Cytotoxic T-Lymphocytes Using a Peptide from NY-ESO-1 Modified at the Carboxy-terminus to Enhance HLA-A2.1 Binding Affinity and Stability in Solution (2001)

NY-ESO-1 is an attractive candidate tumor antigen for the development of immunotherapy for a wide variety of cancers. It is expressed in multiple types of tumors, but its normal tissue distribution is predominantly limited to the testes and ovaries; furthermore, both humoral and cellular immune responses can be mounted against this protein. Three overlapping HLA-A2.1-restricted T-cell epitopes have been identified within NY-ESO-1. In this investigation, the authors evaluated the in vitro immunogenicity of these peptides. From 2 of 12 HLA-A2.1+ patients with metastatic melanoma, peptide-reactive cytotoxic T-lymphocytes were generated using either NY-ESO-1:157-167 or NY-ESO-1:157-165 but not NY-ESO-1:155-163. Because NY-ESO-1:157-165 is a 9 amino acid peptide completely contained within NY-ESO-1:157-167, it seemed likely that this peptide was the minimal determinant, and thus it was selected for continued study. An amino acid substitution of C to V was introduced into NY-ESO-1:157-165 at P9 to attempt to improve its immunogenicity by enhancing its binding affinity to HLA-A2.1 and increasing its stability in solution, because the C residue is readily oxidized, leading to dimerization of the peptide. From 5 of 20 HLA-A2.1+ patients with metastatic melanoma, NY-ESO-1:157-165(165V) stimulated cytotoxic T-lymphocytes in vitro, which recognized peptide-pulsed target cells and HLA-A2.1+ NY-ESO-1+ tumor cells, suggesting that this peptide may be clinically valuable for the treatment of patients with NY-ESO-1+ tumors.
Effects of oral Enterococcus faecium strain DSM 10663 NCIMB 10415 on diarrhoea patterns and performance of sucking piglets (2014)

Effects of probiotic Enterococcus faecium DMS 10663 NCIMB 10415 on diarrhoea and performance of sucking piglets were evaluated in a double-blind, placebo-controlled study. Piglets from treatment group (TG, n=56) and placebo group (PG, n=53) sows were included in the study. Immediately after birth and at day 2 and 3 post natum, each of the TG piglets received 2.8×10(9) colony forming units (cfu) per os. From day 4 until weaning (day 26), 1.26×10(9) cfu E. faecium/piglet were given twice a day via a liquid additive. Piglets already suffering from diarrhoea additionally got a glucose-electrolyte solution enriched with 2.9×10(8) (week 1) and 5.8×10(8) (week 2) cfu E. faecium/day. PG piglets received corresponding placebo preparations. A score was defined to characterise the severity of diarrhoea, including accompanying symptoms. The counts of viable born, stillborn and weaned piglets were similar in TG and PG litters (P>0.05). The probiotic treatment mitigated incidence and severity of diarrhoea (P<0.05) with no impact on diarrhoea length (P>0.05). Probiotic treatment improved daily weight gain (P<0.05) yet with no provable effect on body weight at weaning (P>0.05). The additional supply of E. faecium in piglets suffering from diarrhoea had no further beneficial effect.
Efficient Convolution Kernels for Computerized Tomography (1979)

Three concepts are presented: 1) Extended kernels: The Ramachandran-Lakshminarayanan convolution kernel has one zero between each non-zero value in the spatial domain. By extending the kernel in Fourier space, it is shown that each extension leads to two additional zeros in the spatial domain of the convolution kernel, thus decreasing the required number of multiplications necessary for convolution. Any known kernel can be extended and in the limit of extension a simple backprojection reconstruction is obtained. 2) Binary kernels: A technique for generating binary approximations to any convolution kernel is described. Excluding the central element, all other elements of the kernel are approximated by an even power of two thus, multiplications are replaced by shift operations in the convolution procedure. 3) Recursive convolution: It is shown how additions can be saved by using a recursive formulation which generates new elements in the convolution procedure utilizing only a few summation steps. Results from both extended kernels and their binary approximations are described for simulated phantoms and ultrasound data obtained from breast scans of patients.
Applications of time-frequency and time-scale representations to fault detection and classification (2003)

The authors propose the use of generalized time-frequency and time-scale representations coupled with a hierarchy of neural nets to solve the problem of the automatic detection and classification of faults in mechanical systems such as the gearboxes and transmissions onboard helicopters. With this technique, no underlying model for the events of interest is assumed. Rather the system learns to detect and classify faults by examination and fusion of features from training data which have known fault conditions. Results of processing real helicopter gearbox vibration data with seeded faults are given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling (2005)

MicroRNAs (miRNAs) are genomically encoded small RNAs that hybridize with messenger RNAs, resulting in degradation or translational inhibition of targeted transcripts. The potential for miRNAs to regulate cell-lineage determination or differentiation from pluripotent progenitor or stem cells is unknown. Here, we show that microRNA1 (miR-1) is an ancient muscle-specific gene conserved in sequence and expression in Drosophila. Drosophila miR-1 (dmiR-1) is regulated through a serum response factor-like binding site in cardiac progenitor cells. Loss- and gain-of-function studies demonstrated a role for dmiR-1 in modulating cardiogenesis and in maintenance of muscle-gene expression. We provide in vivo evidence that dmiR-1 targets transcripts encoding the Notch ligand Delta, providing a potential mechanism for the expansion of cardiac and muscle progenitor cells and failure of progenitor cell differentiation in some dmiR-1 mutants. These findings demonstrate that dmiR-1 may "fine-tune" critical steps involved in differentiation of cardiac and somatic muscle progenitors and targets a pathway required for progenitor cell specification and asymmetric cell division.
Pharmacological approach towards the development of indolequinone bioreductive drugs based on the clinically inactive agent EO9 (2002)

The bioreductive drug EO9 (3-hydroxy-5-aziridinyl-1-methyl-2[indole-4,7-dione]-prop-beta-en-alpha-ol) has good pharmacodynamic properties in vitro, modest anti-tumour activity in experimental tumour models, but failed to show activity in clinical trials. Understanding the reasons for its poor efficacy in vivo is important in terms of progressing second generation analogues into the clinic. In two human tumour xenografts, direct intra-tumoural injection resulted in improved anti-tumour activity compared with intravenous administration suggesting that drug delivery to tumours is suboptimal. Compared with Mitomycin C (MMC) and the experimental agent MeDZQ, EO9 was rapidly cleared from the systemic circulation (t1/2=1.8 min) whereas MMC and MeDZQ had significantly increased plasma t1/2 values (14 and 22 min respectively). These three compounds demonstrated similar pharmacodynamic properties in terms of potency towards the NQO1 (NAD(P)H:Quinone oxidoreductase) rich H460 cell line in vitro but differed significantly in their in vivo activity with growth delays of 17.7, 4.5 and 1.0 days for MMC, MeDZQ and EO9 respectively. EO9 was rapidly metabolized by red blood cells in vitro (t1/2=14.5 min) which must contribute to its rapid pharmacokinetic elimination in vivo whereas MMC and MeDZQ were metabolized at comparatively slower rates (t1/2>120 min and 77.0 min respectively). In conclusion, the development of second generation EO9 analogues should address the issue of drug delivery and analysis of drug metabolism by murine whole blood in vitro could be utilized as a preliminary screen to identify lead compounds that are likely to have improved pharmacokinetic profiles in vivo.
Influence of Minor Ions on the Stability and Hydration Rates of β‐Dicalcium Silicate (2004)

The effects of Al 3+ , B 3+ , P 5+ , Fe 3+ , S 6+ , and K + ions on the stability of the β‐phase and its hydration rate were studied in reactive dicalcium silicate (C 2 S, Ca 2 SiO 4 ) synthesized using the Pechini process. In particular, the dependences of the phase stability and degree of hydration on the calcination temperature (i.e., particle size) and the concentration of the stabilizing ions were investigated. The phase evolution in doped C 2 S was determined using XRD, and the degree of hydration was estimated by the peak intensity ratio of the hydrates to the nonhydrates in 29 Si MAS NMR spectra. The stabilizing ability of the ions varied significantly, and the B 3+ ions were quite effective in stabilizing the β‐phase over a wide range of doping concentrations. The hydration results indicated that differently stabilized β‐C 2 S hydrated at different rates, and Al 3+ ‐ and B 3+ ‐doped C 2 S exhibited increased degree of hydration for all doping concentration ranges investigated. The effect of the doping concentration on degree of hydration was strongly dependent on the stabilizing ions.
Laser-nanostructured Ag films as substrates for surface-enhanced Raman spectroscopy (2006)

Pulsed-laser (248nm) irradiation of Ag thin films was employed to produce nanostructured Ag∕SiO2 substrates. By tailoring the laser fluence, it was possible to controllably adjust the mean diameter of the resultant near-spherical Ag droplets. Thin films of tetrahedral amorphous carbon (ta-C) were subsequently deposited onto the nanostructured substrates. Visible Raman measurements were performed on the ta-C films, where it was observed that the intensity of the Raman signal was increased by nearly two orders of magnitude, when compared with ta-C films grown on nonstructured substrates. The use of laser annealing as a method of preparing substrates, at low macroscopic temperatures, for surface-enhanced Raman spectroscopy on subnanometer-thick films is discussed.
Structural analysis of recombinant von Willebrand factor produced at industrial scale fermentation of transformed CHO cells co‐expressing recombinant furin (1995)

Thorough analysis of multimer composition and molecular structure of recombinant von Willebrand factor (r-vWF) produced by recombinant CHO cells demonstrated r-vWF to be more intact and less proteolytically degraded than plasma-derived vWF (pd-vWF) [B. Fischer et al. (1994) FEBS Lett. 351, 345-348]. In contrast to pd-vWF, r-vWF preparations consisted of pro-vWF (vWF containing covalently attached propeptide) as well as mature vWF subunits forming homo- and hetero-multimers. In order to ensure complete propeptide processing, a r-vWF-producing CHO cell clone was transfected with the cDNA of the human propeptide processing enzyme Furin. A r-vWF/r-Furin co-expressing cell clone was cultivated at industrial scale in high cell density perfusion fermenters. r-vWF obtained from these cells was fully processed. Analysis of r-vWF by multimer analysis revealed a multimer pattern equal in number of high molecular weight multimer to pd-vWF, but absence of satellite bands. Two-dimensional electrophoretic analysis of both the primary dimer and the complete multimer pattern of r-vWF showed that the recombinant coagulation factor was composed exclusively of intact and mature subunits. Since the triplet structure typical to pd-vWF is known to reflect proteolytic degradation, r-vWF thus exhibits an integrity far superior compared to pd-vWF.
INSECT DAMAGE, CONE DIMENSIONS, AND SEED PRODUCTION IN CROWN LEVELS OF PONDEROSA PINE (1984)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
TERMINATION OF EARLY PREGNANCY IN RATS AFTER OVARIECTOMY IS DUE TO IMMEDIATE COLLAPSE OF THE PROGESTERONEDEPENDENT DECIDUA (1973)

In guinea-pigs ovariectomized before implantation, where conceptuses continue to develop for some days, partial and finally complete haemorrhagic degeneration of the decidua takes place, usually terminating pregnancy by Day 16 or earlier. This can be prevented by exogenous progesterone (Deanesly, 1972). In pregnant rats, termination of pregnancy following ovariectomy is well known, but its immediate effect on the conceptuses does not appear to have been described. To compare their reactions with those in the guinea-pig, 6- to 9-day pregnant rats (vaginal plug, Day 0) were ovariectomized under ether anaesthesia and killed up to 2 days later, or after a longer interval if given progesterone. The 6- to 12-day conceptuses, fixed in Bouin's fluid and weighed from 70% alcohol, were compared with those from normal animals at corresponding ages. All were sectioned serially in the sagittal plane at 7 μm,
Decoupled deferred shading for hardware rasterization (2012)

In this paper we present decoupled deferred shading: a rendering technique based on a new data structure called compact geometry buffer, which stores shading samples independently from the visibility. This enables caching and efficient reuse of shading computation, e.g. for stochastic rasterization techniques. In contrast to previous methods, our decoupled shading can be efficiently implemented on current graphics hardware. We describe two variants which differ in the way the shading samples are cached: the first maintains a single cache for the entire image in global memory, while the second pursues a tile-based approach leveraging local memory of the GPU's multiprocessors. We demonstrate the application of decoupled deferred shading to speed up the rendering in applications with stochastic supersampling, depth of field, and motion blur.
Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC (2002)

The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the kappaB motif. Disruption of KRC expression in cell lines resulted in increased cell proliferation, anchorage independence of growth, and uncoupling of nuclear division and cell division. In this report, the function of KRC was studied in a RAG2-deficient blastocyst complementation animal model. KRC-deficient embryonic stem cells were generated by homologous recombination and were introduced into RAG2(-/-) blastocysts to generate KRC(-/-);RAG2(-/-) chimeric mice. The lymphoid compartments of chimeras examined at 5 weeks of age were developed, suggesting that KRC is not essential for V(D)J recombination development. However, by 6 months of age, there was a marked deficit in CD4(+)CD8(+) thymocytes in the chimeras, suggesting that KRC may be involved in T-lymphocyte survival. Additionally, one chimera developed anomalies, including postaxial polydactyly, hydronephrosis, and an extragonadal malignant teratoma. DNA analysis showed that the teratoma was derived from KRC(-/-) embryonic stem cells. The teratoma had compound tissue organization and was infiltrated with B lymphocytes. Subsequently, several immortalized KRC-deficient cell lines were established from the teratoma. In this study, growth anomalies and neoplasia were observed in animals and cells deficient in KRC, and other studies have shown allelic loss occurring at the chromosomal region of the human KRC counterpart in various tumors. We propose that KRC may be a previously unidentified tumor-suppresser gene.
Acromegaly (1990)

ACROMEGALY, well described in antiquity, was recognized as a distinct clinical syndrome by Marie in 1886.1 The pituitary source of the disorder was confirmed in 1909 by Cushing, who postulated the excessive secretion of growth-promoting hormone by a hyperfunctioning pituitary gland.2 Recent progress in the diagnosis and treatment of this fascinating clinical syndrome has been reviewed.3 4 5 6 7 Advances in neuroendocrinology have resulted in the development of novel neuropeptide medications that herald a new era of pharmacologic management of hormone-secreting tumors. This review focuses on advances in our understanding of the pathophysiology of acromegaly, diagnosis of the various forms of the disorder, . . .
The potential of compression to improve memory system performance, power consumption, and cost (2003)

The continuing exponential growth in processor performance, combined with technology, architecture, and application trends, places enormous demands on the memory system to allow information storage and exchange at a high-enough performance (i.e., to provide low latency and high bandwidth access to large amounts of information), at low power, and cost-effectively. The paper comprehensively analyzes the redundancy in the information (addresses, instructions, and data) stored and exchanged between the processor and the memory system and evaluates the potential of compression in improving performance, power consumption, and cost of the memory system. Traces obtained with Sun Microsystems' simulator simulating SPARC executables of nine integer and six floating-point programs in the SPEC CPU2000 benchmark suite and analyzed using Markov entropy models, existing compression schemes, and CACTI 3.0 and SimplePower timing, power, and area models yield impressive results.
Comparative analysis of PD-SOI active body-biasing circuits (2002)

The body of SOI partially depleted MOSFETs can be biased to control the threshold dynamically. In the dynamic threshold MOSFET (DTMOS) (Assaderaghi et al, 1997), the operation is limited to about V/sub dd/=0.7 V because of the forward bias of the B-D and B-S junctions. Active body-biasing circuits (ABC-SOI) use auxiliary transistors to implement the bias circuitry and to increase the V/sub dd/ limit (Chuang et al., 1998; Chung et al., 1997; Gil et al., 1998; Lee et al., 1998). In this paper, previously reported and new ABCs are analyzed. The speed-power trade-off and the delay stability, one of the most peculiar PD problems, are examined in several operating conditions.
Chemokines Are the Main Proinflammatory Mediators in Human Monocytes Activated by Staphylococcus aureus, Peptidoglycan, and Endotoxin (2000)

It is widely believed that the cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 are the main proinflammatory mediators induced in the host by bacteria and their cell wall components. To test this hypothesis, we compared the level of expression of 600 genes activated in human monocytes by Staphylococcus aureus, peptidoglycan, endotoxin, and interferon-gamma. These stimulants induced expression of over 120 genes, as identified by cDNA arrays. The highest activated genes for proinflammatory mediators induced by all three bacterial stimulants were chemokine genes (IL-8 and macrophage inflammatory protein (MIP)-1alpha), whereas cytokine genes (TNF-alpha, IL-1, and IL-6) were induced to a lower extent. Genes for other chemokines (MIP-2alpha, MIP-1beta, and monocyte chemoattractant protein-1) were also induced higher than the cytokine genes by peptidoglycan, and as high or higher than the cytokine genes by S. aureus and endotoxin. This high induction of chemokine genes was confirmed by quantitative RNase protection assay, and high secretion of chemokines was confirmed by enzyme-linked immunosorbent assays. Although genes for chemokines were the highest and genes for cytokines were the second highest induced genes by all three bacterial stimulants, each stimulus induced a unique pattern of gene expression. By contrast, expression of a completely different gene pattern was induced by a nonbacterial stimulus, interferon-gamma. These results establish chemokines as the main mediators induced by both Gram-positive and Gram-negative bacteria and are consistent with the highly inflammatory nature of bacterial infections.
Generation of dense range maps by data fusion from active and passive colour stereo vision (2002)

The problem of correspondence search in a stereo system may be alleviated if an active light source projects colour codes onto the scene. To reduce the amount of ambiguous or false matches, additional information drawn from feature-based passive stereo techniques can be used In this paper we discuss the application of fuzzy data fusion techniques to a dual-mode stereo system. Information from passive stereo is used whenever the active procedure cannot find an unambiguous match. The algorithm presented in the paper uses a fuzzy rule-based approach to integrate crisp as well as fuzzy input data. It is shown that the combination of data obtained in both modes of operation may lead to a significant increase in the number of matches meeting a certain credibility criterion. We present some of our experimental results based on real stereo image data and conclude the paper with a discussion of perspectives for possible future research.
Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin (2016)

By use of a structure-based computational method for identification of structurally novel Janus kinase (JAK) inhibitors predicted to bind beyond the ATP binding site, a potent series of indazoles was identified as selective pan-JAK inhibitors with a type 1.5 binding mode. Optimization of the series for potency and increased duration of action commensurate with inhaled or topical delivery resulted in potent pan-JAK inhibitor 2 (PF-06263276), which was advanced into clinical studies.
Peptides inhibit selectin-mediated cell adhesion in vitro, and neutrophil influx into inflammatory sites in vivo (1995)

The selectins are cell adhesion molecules whose carbohydrate-binding domain (C-type lectin) is thought to be involved in leukocyte adhesion to activated vascular endothelium in the inflammatory process. A series of peptides, based on a conserved region (48YYWIGIRK55-NH2) of the lectin domain of E-, L- and P-selectins, were analysed for their ability to block selectin-mediated cell adhesion in vitro, and neutrophil infiltration into sites of inflammation in vivo. The peptides inhibited the adhesion of myeloid cells to recombinant forms of E- and P-selectin. The adhesion of myeloid cells to human endothelial cells, stimulated to express E-selectin, was also inhibited by the peptides. Finally, the peptides blocked the adhesion of lymphocytes, expressing L-selectin, to high endothelial venules in lymph nodes which contain the ligand for L-selectin. A clear structure-activity relationship was established when peptides of different amino acid chain lengths were tested in these assays. Peptides lacking tyrosine residues (e.g. WIGIR-NH2) at their amino terminus were poor inhibitors of selectin-mediated cell adhesion in vitro. The peptides that were found to be inhibitors of cell adhesion in vitro were also found to inhibit (up to 70%) neutrophil infiltration into sites of inflammation in a thioglycollate-induced peritonitis mouse model system. They also significantly reduced (> 50%) the migration of neutrophils into cytokine-treated skin. These results strongly suggest that compounds based on these tyrosine-containing, selectin-derived peptides could be used as anti-inflammatory therapeutic agents.