gebhart/patrepeval huggingface dataset:
Lung fibroblasts from patients with emphysema show markers of senescence in vitro (2006)

Abstract Background The loss of alveolar walls is a hallmark of emphysema. As fibroblasts play an important role in the maintenance of alveolar structure, a change in fibroblast phenotype could be involved in the pathogenesis of this disease. In a previous study we found a reduced in vitro proliferation rate and number of population doublings of parenchymal lung fibroblasts from patients with emphysema and we hypothesized that these findings could be related to a premature cellular aging of these cells. In this study, we therefore compared cellular senescence markers and expression of respective genes between lung fibroblasts from patients with emphysema and control patients without COPD. Methods Primary lung fibroblasts were obtained from 13 patients with moderate to severe lung emphysema (E) and 15 controls (C) undergoing surgery for lung tumor resection or volume reduction (n = 2). Fibroblasts (8E/9C) were stained for senescence-associated β-galactosidase (SA-β-Gal). In independent cultures, DNA from lung fibroblasts (7E/8C) was assessed for mean telomere length. Two exploratory 12 k cDNA microarrays were used to assess gene expression in pooled fibroblasts (3E/3C). Subsequently, expression of selected genes was evaluated by quantitative PCR (qPCR) in fibroblasts of individual patients (10E/9C) and protein concentration was analyzed in the cell culture supernatant. Results The median (quartiles) percentage of fibroblasts positive for SA-β-Gal was 4.4 (3.2;4.7) % in controls and 16.0 (10.0;24.8) % in emphysema (p = 0.001), while telomere length was not different. Among the candidates for differentially expressed genes in the array (factor ≥ 3), 15 were upregulated and 121 downregulated in emphysema. qPCR confirmed the upregulation of insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-rP1 (p = 0.029, p = 0.0002), while expression of IGFBP-5, -rP2 (CTGF), -rP4 (Cyr61), FOSL1, LOXL2, OAZ1 and CDK4 was not different between groups. In line with the gene expression we found increased cell culture supernatant concentrations of IGFBP-3 (p = 0.006) in emphysema. Conclusion These data support the hypothesis that premature aging of lung fibroblasts occurs in emphysema, via a telomere-independent mechanism. The upregulation of the senescence-associated IGFBP-3 and -rP1 in emphysema suggests that inhibition of the action of insulin and insulin-like growth factors could be involved in the reduced in vitro -proliferation rate.
Advanced sacrificial poly-Si technology for fluidic systems (2002)

Sacrificial poly-Si etching can be used to create thin cavities and channels. By combining it with anisotropic KOH etching of a mono-Si substrate, important components for fluidic systems, such as V-grooved channels, thin sandwiched channels, channel crossings and membrane filters and injectors, have been fabricated in a single etch step.
Administration of mAb against alpha E beta 7 prevents and ameliorates immunization-induced colitis in IL-2-/- mice. (1999)

We previously demonstrated that 2,4,6-trinitrophenol (TNP)-OVA immunization leads to a transmural colitis in the IL-2-/- mouse that is caused by IL-12-driven CD4+ Th1 T cells and resembles human Crohn's disease. The integrin alpha E beta 7 is highly expressed on colonic intraepithelial lymphocytes and has been suggested to function as a homing or retention molecule for intraepithelial lymphocytes. To evaluate the role of alpha E beta 7 in colitis, we administered a mAb against alpha E beta 7 to IL-2-/- mice that were immunized at the same time with TNP-OVA in CFA. To our surprise, this treatment resulted in a significantly reduced colitis severity score, 0-2 vs 3-4, that was associated with a significant reduction in CD4+ lamina propria lymphocyte subpopulation (p < 0.01). In contrast, the total number of splenic CD4+ T cells of treated animals was significantly elevated compared with that of untreated animals (3.2 +/- 0.6 x 107 vs 1.2 +/- 0.2 x 107; p < 0.05). Similarly, functional studies revealed that IFN-gamma production by lamina propria lymphocytes isolated from IL-2-/- TNP-OVA-immunized mice treated with anti-alpha E beta 7 was significantly lower than in untreated IL-2-/- TNP-OVA-immunized mice. In contrast, IFN-gamma production by splenic cells isolated from treated IL-2-/- TNP-OVA-immunized mice was significantly higher than in untreated mice. Finally, TNP-OVA-immunized IL-2-/- mice that were treated after the colitis had been established also showed a significant decrease in mucosal inflammation after alpha E beta 7 mAb administration. Thus, the above findings demonstrate that the onset and maintenance of inflammatory bowel disease depends on the colonic localization of lamina propria CD4+ lymphocytes expressing alpha E beta 7.
Post bone marrow transplant sera and persisting mast cell colonies. (1988)

Serum samples were collected from eight recipients of allogeneic bone marrow transplants (BMT) following the normalization of peripheral blood counts. Three patients (11 samples) were in the early engraftment period (less than 6 months post-BMT) and still receiving cyclosporin A or methotrexate and the remaining five patients (18 samples) were in stable engraftment (12-84 months post-BMT) and not on immunosuppressive therapy. All post-BMT serum samples supported the growth of increased numbers of mast cell colonies in long-term agar cultures when compared with normal controls (p less than 0.025-0.005), irrespective of the time from BMT or the presence of clinical graft-versus-host disease (GVHD). In contrast, the numbers of neutrophil, monocyte and eosinophil colonies were equivalent in test and control groups. It is proposed that post-BMT sera contain higher levels of a mast cell stimulating activity(s) than does normal sera. Such increased levels might be associated with clinical or subclinical GVHD.
Multi-Step Regression Learning for Compositional Distributional Semantics (2013)

We present a model for compositional distributional semantics related to the framework of Coecke et al. (2010), and emulating formal semantics by representing functions as tensors and arguments as vectors. We introduce a new learning method for tensors, generalising the approach of Baroni and Zamparelli (2010). We evaluate it on two benchmark data sets, and find it to outperform existing leading methods. We argue in our analysis that the nature of this learning method also renders it suitable for solving more subtle problems compositional distributional models might face.
Design for Testability (1985)

Today's computers must perform with increasing reliability, which in turn depends on the problem of determining whether a circuit has been manufactured properly or behaves correctly. However, the greater circuit density of VLSI circuits and systems has made testing more difficult and costly. This book notes that one solution is to develop faster and more efficient algorithms to generate test patterns or use techniques to enhance testability - that is, design for testability. Design for testability techniques offer one approach toward alleviating this situation by adding enough extra circuitry to a circuit or chip to reduce the complexity of testing. Because the cost of hardware is decreasing as the cost of testing rises, there is now a growing interest in these techniques for VLSI circuits.The first half of the book focuses on the problem of testing: test generation, fault simulation, and complexity of testing. The second half takes up the problem of for testability: techniques to minimize test application and/or test generation cost, scan for sequential logic circuits, compact testing, built-in testing, and various techniques for testable systems.Hideo Fujiwara is an associate professor in the Department of Electronics and Communication, Meiji University. Logic Testing and Design for Testability is included in the Computer Systems Series, edited by Herb Schwetman.
Identification of Optimized Target Sequences for the GLI3 Zinc Finger Protein (1995)

GLI3 represents an important control gene for development and differentiation of several body structures. Reduction in gene dosage already leads to severe perturbation, especially of limb morphogenesis. The gene encodes a zinc finger protein that likely functions as a transcriptional modulator. Because the five zinc fingers should be capable of recognizing an extended stretch of genomic DNA, we sought to identify sequences bound by GLI3 that may facilitate the search for target genes acting downstream of GLI3. Starting from the nonamer DNA binding sequence of the highly related GLI protein, we employed an oligonucleotide selection protocol to determine an optimized binding sequence for the GLI3 protein. The resulting sequence bound by the GLI3 zinc fingers consists of 16 nucleotides and shows a high degree of similarity to sequences bound by the GLI and tra-1 proteins. Comparison with protein-DNA interactions in the known crystal structure of the GLI-DNA complex suggests relevant interactions of additional amino acids of GLI3 with its target site. The newly identified GLI3 target sequence should prove very useful for both the structural analysis of the protein-DNA complex and the search for genes whose expression is subject to regulation by the GLI3 gene product.
Synthesis and Surface Investigations of N-Substituted 2,5-Dithio-7-azabicyclo[2.2.1]heptanes on Gold Surfaces (2012)

The reaction of various primary amines and 2,5-dihydroxy-1,4-dithiane in the presence of a catalytic amount of Mg(II) in distilled water provided a series of N-substituted 2,5-dithia-7-azabicyclo[2.2.1]heptanes. The adsorption profiles of the sulfur-containing heterocycles on gold surfaces have been explored by time-of-flight secondary ion mass spectrometry (TOF-SIMS), X-ray photoelectron spectroscopy (XPS), and electrochemistry. SIMS data indicated that these novel bicyclic sulfides interact with gold surfaces favorably, independent of the N-substitution, with minimal fragmentation. An XPS study revealed the three component core levels of S 2p with binding energies at 161, 162, and 163 eV, indicating a combination of the bound and unbound sulfur species. Using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), we found the efficient adsorption of heterocycles onto gold and the formation of densely packed films for alkyl and phenyl analogues. However, the adsorption and film packing properties were greatly compromised by an N-pyridyl substitution. The findings indicate that the surface behavior of N-substituted 2,5-dithia-7-azabicyclo[2.2.1]heptanes varies with respect to the N-substitution and the nature of the substituent, suggesting that the adsorption profiles and the film packing of bicyclic sulfides on gold surfaces are highly dependent on the binding interface and the molecular orientation.
Sacral neuromodulation with implanted devices for urinary storage and voiding dysfunction in adults (2009)

In spite of methodological problems, it would appear that some people benefit from implants which provide continuous nerve stimulation. More research is needed on the best way to improve patient selection, carry out the implant, and to find why so many fail. The effectiveness of implants should be tested against other interventions, particularly in people with an overactive bladder.
The influence of membrane components on regulation of alternative pathway activation by decay-accelerating factor. (1990)

Decay-accelerating factor (DAF) is a C regulatory protein which functions in membranes to inhibit autologous C activation on cell surfaces. A liposome model was used to study the mechanism of DAF action and examine the effects of membrane-bound glycophorin and LPS on the regulatory activity of DAF. Liposomes were incubated in MgEGTA-treated human serum and activation of the alternative pathway measured by C3b binding. Liposomes composed of phosphatidylcholine, phosphatidylethanolamine, and cholesterol activated the alternative pathway in proportion to their content of PE. Incorporation of 10(-7) mol/mol phospholipid of either human E or HeLa cell-derived DAF inhibited C activation by liposomes containing 40% phosphatidylethanolamine by 50%, an efficiency comparable to that observed in intact E. HeLa DAF that had been treated with phosphatidylinositol-specific phospholipase C to remove its glycolipid anchor had no effect on C activation by liposomes at concentrations as high as 10(-5) mol/mol phospholipid. Incorporation of DAF into liposomes prepared with bound C3b inhibited the deposition of additional C3b by C3bBbP. However, the incorporated DAF increased the amount of Bb generated from B in the presence of D indicating that accelerated decay of the convertase was the primary effect of DAF. Similarly, treatment of intact human E with anti-DAF decreased the amount of Bb generated by the alternative pathway convertase. To study the effects of other membrane components on DAF activity, liposomes were prepared with purified human glycophorin A or LPS. In glycophorin liposomes the presence of PE was required to activate the alternative pathway and DAF inhibited this activation. In contrast, LPS liposomes bound C3b independently of PE and the incorporation of DAF had no effect. These results demonstrate that within a membrane, DAF's inhibitory activity on the alternative pathway C3 convertase is mediated independently of other membrane proteins, that in this model the major activity of DAF is to accelerate convertase decay, and that the presence of other membrane molecules that may serve as C3 acceptors can circumvent DAF function.
A cross-sample statistical model for SNP detection in short-read sequencing data (2011)

Highly multiplex DNA sequencers have greatly expanded our ability to survey human genomes for previously unknown single nucleotide polymorphisms (SNPs). However, sequencing and mapping errors, though rare, contribute substantially to the number of false discoveries in current SNP callers. We demonstrate that we can significantly reduce the number of false positive SNP calls by pooling information across samples. Although many studies prepare and sequence multiple samples with the same protocol, most existing SNP callers ignore cross-sample information. In contrast, we propose an empirical Bayes method that uses cross-sample information to learn the error properties of the data. This error information lets us call SNPs with a lower false discovery rate than existing methods.
Long-term seizure outcome after mesial temporal lobe epilepsy surgery: corticalamygdalohippocampectomy versus selective amygdalohippocampectomy (2008)

Both CorAH and SelAH can lead to similar favorable seizure control in patients with MTLE/HS. However, the authors suggest that the transcortical selective approach has the great advantage of minimizing or completely abolishing the impact of dividing several venous and arterial adhesions which are tedious, time consuming, and, at times, associated with some degree of cerebral swelling.
Lack of expression from a retroviral vector after transduction of murine hematopoietic stem cells is associated with methylation in vivo. (1994)

We describe studies of gene transfer and expression of the human glucocerebrosidase cDNA by a Moloney murine leukemia virus (MoMuLV)-based retroviral vector in a murine gene transfer/bone marrow transplant (BMT) model. Pluripotent hematopoietic stem cells (HSCs) were assayed as the colony-forming units, spleen (CFU-S) generated after serial transplantation. Transcriptional expression from the MoMuLV long-terminal repeat (LTR) was detected at a high level in the primary (1 degree) CFU-S and tissues of reconstituted BMT recipients. However, we observed transcriptional inactivity of the proviral MoMuLV-LTR in > 90% of the secondary (2 degrees) CFU-S and in 100% of the tertiary (3 degrees) CFU-S examined. We have compared the methylation status of the provirus in the 1 degree CFU-S, which show strong vector expression, to that of the transcriptionally inactive provirus in the 2 degrees and 3 degrees CFU-S by Southern blot analysis using the methylation-sensitive restriction enzyme Sma I. The studies demonstrated a 3- to 4-fold increase in methylation of the Sma I site in the proviral LTR of 2 degrees and 3 degrees CFU-S compared to the transcriptionally active 1 degree CFU-S. These observations may have important implications for future clinical applications of retroviral-mediated gene transfer into HSCs, where persistent gene expression would be needed for an enduring therapeutic effect.
Mechanistic insights on the conversion of sugars into 5-hydroxymethylfurfural (2010)

A sustainable bio-economy requires the efficient utilization of all of the components of biomass. After glucose, mannose and galactose are the most abundant 6-carbon sugars in plant hemicellulose; lactose is a common dairy byproduct. Here, we demonstrate the conversion of these sugars into 5-hydroxymethylfurfural (HMF), a key intermediate for renewable fuels and chemicals. Chromium salts enable the efficient conversion of mannose into HMF but are less effective for galactose, lactose, and the related hexulose, tagatose. Isotopic labeling studies and the reactivity of psicose and sorbose indicate that the key aldose-to-ketose conversion occurs via a 1,2-hydride shift, which is followed by dehydration of the furanose tautomer. These data valorize mannose, galatactose, and lactose as sources of HMF, and inform the design of new catalysts for the conversion of aldoses to ketoses.
Dorsal Root Ganglionectomy for Intractable Monoradicular Sciatica (1995)

Dorsal root ganglionectomy was introduced in 1975 as a procedure with theoretical advantages over dorsal rhizotomy for the treatment of intractable radicular pain. Results of the few clinical reports have been generally favorable. The authors report the largest and most comprehensively studied series to date. 61 patients (33 men, 28 women) underwent dorsal root ganglionectomy for intractable sciatica, most often monoradicular. Patients were selected for surgery only if the clinical history, physical examination, radiologic studies, and diagnostic radicular block all predicted a favorable outcome. Sciatica was markedly reduced or eliminated in 36 patients (59%). Dysesthesia following ganglionectomy was observed frequently, but not invariably (approximately 60% of cases). Dysesthesia was generally of mild or moderate severity, self-limited, and responsive to treatment.
Distinct Motifs in the Intracellular Domain of Human CD30 Differentially Activate Canonical and Alternative Transcription Factor NF-κB Signaling (2012)

The TNF-receptor superfamily member CD30 is expressed on normal and malignant lymphocytes, including anaplastic large cell lymphoma (ALCL) cells. CD30 transmits multiple effects, including activation of NF-κB signaling, cell proliferation, growth arrest and apoptosis. How CD30 generates these pleiotropic effects is currently unknown. Herein we describe ALCL cells expressing truncated forms of the CD30 intracellular domain that allowed us to identify the key regions responsible for transmitting its biological effects in lymphocytes. The first region (CD30(519-537)) activated both the alternative and canonical NF-κB pathways as detected by p100 and IκBα degradation, IKKβ-dependent transcription of both IκBα and the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and induction of cell cycle arrest. In contrast, the second region of CD30 (CD30(538-595)) induced some aspects of canonical NF-κB activation, including transcription of IκBα, but failed to activate the alternative NF-κB pathway or drive p21(WAF1/CIP1)-mediated cell-cycle arrest. Direct comparison of canonical NF-κB activation by the two motifs revealed 4-fold greater p65 nuclear translocation following CD30(519-537) engagement. These data reveal that independent regions of the CD30 cytoplasmic tail regulate the magnitude and type of NF-κB activation and additionally identify a short motif necessary for CD30-driven growth arrest signals in ALCL cells.
Synthesis of Novel Test Compounds for Antiviral Chemotherapy of Severe Acute Respiratory Syndrome (SARS) (2005)

This contribution reviews the synthesis of a range of experimental drugs designed for and aiming at antiviral chemotherapy of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)-induced human disease conditions. The selection of 25 test materials includes eleven trioxa-adamantane-triols (TATs) [BN, IBNCA, ABNCA, VANBA, ethylVANBA, euBN, euVANBA, ansaBN, Ehrlich BN, [6]prismaneBN, nitrodiBN], trivially termed bananins, one trioxa-adamantan-ol (TAO) THYMOBA, one bis-bananin pi-bananin (piBN), one triazaadamantane delta-bananin (deltaBN), seven potential nucleic acid-binding drugs (XBQC, INDO, PivINDO, AZTRION, AZADO, AZOCYS, AZOGALL), one potential antiviral interferon-inducer and distant nucleoside analog diazon, one potential HIV protein Vif antagonist AZODIAZON, one folic acid-diazon condensate DIAZONOFOL, and one special nucleoside analog (fructoinosine/fructovir). Four of the eleven bananins (BN, IBNCA, VANBA, euBN) were already demonstrated to constitute effective inhibitors of SARS-CoV NSP10/nsp13 RNA/DNA helicase/NTPase protein ATPase enzymatic function. Bananin (BN) was an effective inhibitor of both SARS-CoV RNA/DNA helicase nucleic acid unwinding function and SARS-CoV (Coronaviridae, Coronavirus) RNA-viral replication in cell culture. In summary, at least one selected compound of the synthesized test materials represents an interesting drug candidate for treatment of SARS-CoV-induced human disease (SARS). Viewed in aspects of organic chemistry [6]prismaneBN and nitrodiBN are the first true hexaprismane derivatives synthesized, and all reported compounds are entirely new.
Combinatorial Solid-Phase Synthesis of Multivalent Cyclic Neoglycopeptides (2000)

Conformationally restricted, multivalent cyclic neoglycopeptides, such as 1, are accessible by a convergent solid-phase synthesis in which an active carbonate is treated with immobilized cyclopeptides bearing free amino side chains. The libraries of glycoclusters obtainable by this procedure are suited for screening for lectin-binding properties.
Yearbook of Psychiatry and Applied Mental Health 1989. Edited by J. A. Talbot, A. Frances, D. X. Freedman, H. Y. Meltzer, J. E. Schowalter and Herbert Weiner. London: Wolff Medical Publications. 1989. 479 pp. £40.00. (1991)

Yearbook of Psychiatry and Applied Mental Health 1989. Edited by J. A. Talbot, A. Frances, D. X. Freedman, H. Y. Meltzer, J. E. Schowalter and Herbert Weiner. London: Wolff Medical Publications. 1989. 479 pp. £40.00. - Volume 158 Issue 1
Geometric diffusions as a tool for harmonic analysis and structure definition of data: Diffusion maps (2005)

We provide a framework for structural multiscale geometric organization of graphs and subsets of R(n). We use diffusion semigroups to generate multiscale geometries in order to organize and represent complex structures. We show that appropriately selected eigenfunctions or scaling functions of Markov matrices, which describe local transitions, lead to macroscopic descriptions at different scales. The process of iterating or diffusing the Markov matrix is seen as a generalization of some aspects of the Newtonian paradigm, in which local infinitesimal transitions of a system lead to global macroscopic descriptions by integration. We provide a unified view of ideas from data analysis, machine learning, and numerical analysis.