gebhart/patrepeval huggingface dataset:
Non-planar nanofluidic devices for single molecule analysis fabricated using nanoglassblowing (2008)

A method termed 'nanoglassblowing' is presented for fabricating integrated microfluidic and nanofluidic devices with gradual depth changes and wide, shallow nanochannels. This method was used to construct fused silica channels with out-of-plane curvature of channel covers from over ten micrometers to a few nanometers, nanochannel aspect ratios smaller than 2 × 10(-5):1 (depth:width), and nanochannel depths as shallow as 7 nm. These low aspect ratios and shallow channel depths would be difficult to form otherwise without collapse of the channel cover, and the gradual changes in channel depth eliminate abrupt free energy barriers at the transition from microfluidic to nanofluidic regions. Devices were characterized with atomic force microscopy (AFM), white light interferometry, scanned height measurements, fluorescence intensity traces, and single molecule analysis of double-stranded deoxyribonucleic acid (DNA) velocity and conformation. Nanochannel depths and aspect ratios formed by nanoglassblowing allowed measurements of the radius of gyration, R(g), of single λ DNA molecules confined to slit-like nanochannels with depths, d, ranging from 11 nm to 507 nm. Measurements of R(g) as a function of d agreed qualitatively with the scaling law R(g)∝d(-0.25) predicted by Brochard for nanochannel depths from 36 nm to 156 nm, while measurements of R(g) in 11 nm and 507 nm deep nanochannels deviated from this prediction.
Inflammatory Caspases: Targets for Novel Therapies (2007)

This review provides an overview of the biochemistry and activation of inflammatory caspases, and focuses on their therapeutic potential as disease targets in pathologies such as sepsis, Crohns disease, rheumatoid arthritis, traumatic brain injury and amyotrophic lateral sclerosis (ALS). We summarize the proof-of-principal evidence obtained by studies in several corresponding experimental disease models confirming the validity of strategies targeting inflammatory caspases. We discuss the use of inflammatory caspase inhibitors, such as VX-740 (Pralnacasan) and VX-765, in clinical studies for rheumatoid arthritis and osteoarthritis. Finally, we point out recent approaches identifying novel peptidomimetic or non-peptide caspase inhibitors with suitable clinical profiles. Keywords: Peptide inhibitor, caspases, apoptosis, neurodegeneration, inflammation, inflammasome, utoimmune disease, pralnacasan, animal model
Hypoxic human umbilical vein endothelial cells induce activation of adherent polymorphonuclear leukocytes (1994)

Several pieces of evidence are reported for the accumulation of activated neutrophils in ischemic and reperfused tissues leading to the transformation of the ischemic tissue into an inflammatory territory and to an enhancement of tissue damages during reoxygenation. However, the molecular mechanisms responsible for these observations and the precise role played by endothelial cells in this process are still poorly understood. In this study, an in vitro model that mimics this situation was used to investigate the effects of hypoxia-incubated human umbilical vein endothelial cells (HUVEC) on polymorphonuclear leukocyte (PMN) functions. A strong PMN activation characterized by an increase in intracellular calcium concentration as well as by superoxide anion release and leukotriene B4 production was observed when these cells were coincubated with hypoxic HUVEC. On the other hand, conditioned medium from hypoxia-incubated HUVEC failed to activate PMN, as determined by the lack of PMN calcium concentration increase, the failure of superoxide anion production enhancement, as well as the absence of effects on the integrin CD18, CD11a, and CD11b expression. These results indicate that the presence of hypoxia- incubated HUVEC is necessary to obtain an activation of the PMN, probably via the adherence process. Once activated by coincubation with hypoxic HUVEC, PMN became cytotoxic, as evidenced by 51Cr released from prelabeled HUVEC. This cytotoxic effect of activated PMN for hypoxic endothelial cells could be prevented by a combination of superoxide dismutase and catalase (94% inhibition), whereas superoxide dismutase alone was inefficient. Antiprotease (alpha 2-macroglobulin) and a specific elastase inhibitor (MAAPV-CMK) were also inefficient. These results correlate very well with the fact that no increase in elastase release could be observed in supernatants from PMN coincubated with hypoxic HUVEC. Furthermore, when adherence process was blocked by oleic acid or by anti-ICAM-1 monoclonal antibodies, protection was, respectively, 90% and 72%. We thus evidenced that free radicals but not elastase released from activated PMN coincubated with hypoxic HUVEC are involved in HUVEC injury. We conclude from these results that PMN activation is initiated by PMN adherence to hypoxic HUVEC. These observations indicate that hypoxic HUVEC may be partly responsible for neutrophil activation observed in ischemic tissues, which is part of the amplification process of tissue damage.
Localization of IQGAP1 is inversely correlated with intercellular adhesion mediated by e-cadherin in gastric cancers (2001)

Down-regulation of E-cadherin function is characteristic of cancer cells and might involve the small G-protein Rho family, including Rac1 and Cdc42. IQGAP1 has been reported to be one of the target proteins of Rac1 and Cdc42. To elucidate the role of IQGAP1 in cancer-cell adhesion, its expression was investigated in 47 cases of human gastric cancer by immunohistochemistry and Western blot upon protein fractionation, especially in comparison with E-cadherin and catenin expression. In the non-cancerous columnar epithelium of the stomach, IQGAP1, as well as E-cadherin/catenin, was expressed at the cell-cell boundary. IQGAP1 was frequently observed diffusely in the cytoplasm in intestinal-type tumors (20/22 cases) but was expressed at the cell membrane in diffuse-type tumors (19/25 cases), thus showing significant association with tumor differentiation (p < 0.01). Interestingly, membranous expression of IQGAP1 was inversely correlated with that of E-cadherin (p < 0.05) or alpha-catenin (p < 0.001). These observations were consistent with the Western blot results following protein fractionation. IQGAP1 was dominantly expressed in the soluble fraction in differentiated tumors; however, in undifferentiated tumors, it was mostly in the insoluble fraction. In contrast, both E-cadherin and alpha-catenin were detected only in the insoluble fraction. Thus, subcellular localization of IQGAP1 from the cytoplasm to the cell membrane was correlated with E-cadherin dysfunction and tumor dedifferentiation in gastric carcinogenesis.
Electrospinning: A study in the formation of nanofibers (2007)

Electrospinning is a technique to produce nanofibers more efficiently. In electrospinning, electricity spins fibers by extracting the polymer from the solvent and stretching it, all in one continuous electric field. Basics of electrospinning are discussed in sequence from simple homogenous fibers through a single nozzle to heterogeneous core-shell fibers from double, concentric nozzles. Experimental set-up is described and the effect of different variables in the process of electrospinning on nanofiber quality is illustrated. Formation of carbon nanotube fibers with porous walls from polyethylene oxide/polyacrylnitrile (PEO/PAN) core-shell fibers is the definitive objective.Zipped LaTex file
Conceptus Interferons and Maternal Recognition of Pregnancy1 (1989)

Ovine trophoblast protein-1 (oTP-1) and bovine trophoblast protein-1 (bTP-1) are secreted by ovine and bovine conceptuses for a restricted period when the conceptus acts to block regression of the corpus luteum. Both are considered to be antiluteolytic, acting locally on the endometrium to prevent the production of the uterine luteolysin prostaglandin F2 alpha. Molecular cloning of cDNAs for oTP-1 and bTP-1 has shown that both are structurally related to alpha interferons (IFN-alpha s). In particular, they resemble members of the 172-residue long IFN-alpha II (or IFN-omega) subfamily. Both proteins possess the antiviral and antiproliferative properties of IFN-alpha s and appear to bind IFN-alpha receptors. A novel and previously unsuspected role for IFNs in early pregnancy is apparent.
High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach (1990)

A new method is described for determining molecular structures from NMR data. The approach utilizes 2D NOESY back-calculations to generate simulated spectra for structures obtained from distance geometry (DG) computations. Comparison of experimental and back-calculated spectra, including analysis of cross-peak buildup and auto-peak decay with increasing mixing time, provides a quantitative measure of the consistence between the experimental data and generated structures and allows for use of tighter interproton distance constraints. For the first time, the "goodness" of the generated structures is evaluated on the basis of their consistence with the actual experimental data rather than on the basis of consistence with other generated structures. This method is applied to the structure determination of an 18-residue peptide with an amino acid sequence comprising the first zinc fingerlike domain from the gag protein p55 of HIV. This is the first structure determination to atomic resolution for a retroviral zinc fingerlike complex. The peptide [Zn(p55F1)] exhibits a novel folding pattern that includes type I and type II NH-S tight turns and is stabilized both by coordination of the three Cys and one His residues to zinc and by extensive internal hydrogen bonding. The backbone folding is significantly different from that of a "classical" DNA-binding zinc finger. Residues C(1)-F(2)-N(3)-C(4)-G(5)-K(6) fold in a manner virtually identical with the folding observed by X-ray crystallography for related residues in the iron domain of rubredoxin; superposition of all main-chain and Cys side-chain atoms of residues C(1)-K(6) of Zn(p55F1) onto residues C(6)-Y(11) and C(39)-V(44) of rubredoxin gives RMSDs of 0.46 and 0.35 A, respectively. The side chains of conservatively substituted Phe and Ile residues implicated in genomic RNA recognition form a hydrophobic patch on the peptide surface.
Housekeeping Genes in Cancer: Normalization of Array Data (2005)

Biological maintenance of cells under variable conditions should affect gene expression of only certain genes while leaving the rest unchanged. The latter, termed "housekeeping genes," by definition must reflect no change in their expression levels during cell development, treatment, or disease state anomalies. However, deviations from this rule have been observed. Using DNA microarray technology, we report here variations in expression levels of certain housekeeping genes in prostate cancer and a colorectal cancer gene therapy model system. To highlight, differential expression was observed for ribosomal protein genes in the prostate cancer cells and beta-actin in treated colorectal cells. High-throughput differential gene expression analysis via microarray technology and quantitative PCR has become a common platform for classifying variations in similar types of cancers, response to chemotherapy, identifying disease markers, etc. Therefore, normalization of the system based on housekeeping genes, such as those reported here in cancer, must be approached with caution.
Two classes of cis sequences contribute to tissue‐specific expression of a PAL2 promoter in transgenic tobacco (1995)

Genes encoding phenylalanine ammonia-lyase (PAL) are expressed in a complex pattern during plant development and in response to light, pathogen ingress, mechanical damage and other stresses. Analysis of the promoter of the bean PAL2 gene in transgenic tobacco has shown that some regions responsible for developmental expression are functionally compensatory. The minimum sequence containing all cis sequences necessary for developmental patterns of expression is within -254 bp of the transcription start site. Footprinting and electrophoretic mobility shift assay studies of this region revealed potential cis sequences which coincided with the functional domains defined by small deletions and promoter fusions. Mutations in these potential cis sequences in the context of the minimal -254 bp promoter altered tissue-specific expression patterns, confirming the importance of these sequences for expression in vivo. A functional model for the promoter is presented which predicts that three AC-elements, which are possible Myb protein binding sites, together with a G-box, interact to direct the complex patterns of tissue-specific expression observed.
Specific Binding, Internalization, and Degradation of Human Neutrophil Activating Factor by Human Polymorphonuclear Leukocytes (1989)

The interaction of 125I-labeled recombinant human neutrophil activating factor (NAF) with polymorphonuclear leukocytes (PMN) was studied by means of a radioreceptor assay. The binding was characterized by a rapid transition (t1/2 less than or equal to 1 min) from a pH 3-sensitive state at 4 degrees C to pH 3 resistance at 37 degrees C. This was not caused by internalization of NAF since pH 3-resistant bound iodinated NAF could still be exchanged by an excess of nonlabeled NAF, i.e. was dissociable. Internalized iodinated NAF was processed into trichloroacetic acid-soluble forms. Scatchard transformation of binding isotherms at 4 and 37 degrees C led to nonlinear curves, a finding which is consistent with the expression of two receptor populations, one with high (KD = 11-35 pM) and the other with lower affinity (KD = 640-830 pM) at 4 degrees C. Numbers of the low affinity binding sites were approximately 34,000, and those with high affinity were 5,200/PMN when estimated at 4 degrees C. Binding of iodinated NAF to PMN was specific since it could be competed by an excess of nonlabeled NAF but not by two other activators of PMN function, formylmethionyl-leucyl-phenylalanine or human recombinant granulocyte-macrophage colony-stimulating factor. In addition to human PMN, NAF also bound specifically to two human monocytic cell lines; however, only the low affinity binding site could be detected on these cells.
Synthesis of functionalized bisphosphonates via click chemistry (2007)

An efficient general synthetic approach giving the possibility for facile, rapid and cheap access to a wide range of novel nitrogen-bisphosphonates (N-BPs) as potent drug candidates, based on the reaction of mono- and bis-propargyl-substituted bisphosphonates with a variety of azides under Cu(i) catalysis ("click" methodology), has been developed. The method allows the incorporation of two functionalities into the N-BP molecule simultaneously, as well as to ligate in situ two N-BPs to one another via the one-pot reaction of organic dibromides with propargyl-substituted bisphosphonates, generating both the diazide and Cu(I) moieties.
Template-Directed Oligonucleotide Strand Ligation, Covalent Intramolecular DNA Circularization and Catenation Using Click Chemistry (2007)

The copper-catalyzed azide-alkyne cycloaddition reaction has been used for the template-mediated chemical ligation of two oligonucleotide strands, one with a 5'-alkyne and the other with a 3'-azide, to produce a DNA strand with an unnatural backbone at the ligation point. A template-free click-ligation reaction has been used for the intramolecular circularization of a single stranded oligonucleotide which was used as a template for the synthesis of a covalently closed DNA catenane.
Expression of VEGF and VEGF mRNA after focal cerebral ischemia reperfusion in rats (2005)

Objective:To study the expression of vascular endothelial growth factor (VEGF) and VEGF mRNA after focal cerebral ischemia reperfusion in rats.Methods:MCAO (Middle Cerebral Artery Occlusion) models were set up in rats,and the rats were divided into six groups:control group,5 groups of ischemia for 2h then respective reperfusion for 6h,12h,24h,48h and 72h.The samples were analyzed with immunohistochemical methods.The expression of VEGF mRNA was detected by RT-PCR analysis.Results:VEGF protein expression started at 6h.It increased remarkably at 24h,and it was strongest at 48h.VEGF mRNA increased at 6h,while reached peak value at 12h and reduced at 24h,finally returned to normal level at 48-72h.VEGF expression was mainly detected in the periphery of infarcts at every timepoint.Conclusion:These findings demonstrate that the VEGF strong expression can be induced in focal cerebral ischemia reperfusion in vivo.The changes of VEGF levels suggest that VEGF has neuroprotective effect against cerebral ischemic injury.
5′,6′‐Nucleoside Phosphonate Analogues Architecture: Synthesis and Comparative Evaluation towards Metabolic Enzymes (2011)

Nucleoside phosphonates have been designed as stable 5'-mononucleotide mimics and are nowadays considered a potent class of antiviral agents. Within cells, they must be metabolised to the corresponding diphosphate to exert their biological activity. In this process, the first phosphorylation step, catalysed by nucleoside monophosphate kinases (NMP kinases), has been proposed as a bottleneck. Herein, we report the synthesis of a series of ribonucleoside phosphonate derivatives isosteric to 5'-mononucleotides, with different degrees of flexibility within the 5',6'-C-C bond, as well as different polarities, through the introduction of hydroxy groups. The influence of these modifications on the capacity of the compounds to act as substrates for appropriate human NMP kinases, involved in nucleic acids metabolism, has been investigated. Low flexibility, as well as an absence of hydroxy groups within the ribose-phosphorus architecture, is critical for efficient phosphotransfer. Among the series of pyrimidine analogues, one derivative was shown to be phosphorylated by human UMP-CMP kinase, with rates similar to those of dUMP and even better than dCMP.
Primitive adult hematopoietic stem cells can function as osteoblast precursors (2003)

Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hematopoietic and mesenchymal cells. We show here that the "side population" (SP) of marrow stem cells, defined by their ability to rapidly expel a DNA-binding dye and to regenerate the hematopoietic compartment, can differentiate to osteoblasts through a mesenchymal intermediate. When transplanted into lethally irradiated mice, single gene-marked murine SP cells reconstituted depleted osteoprogenitor pools, such that a large proportion of the osteogenic cells in the epiphysis of long bone carried the donor SP cell marker. These findings suggest that the developmental capacity of SP cells is not restricted to the hematopoietic lineages but extends to osteogenic differentiation. This property not only elucidates a previously unrecognized step in osteoblast development, but also has intriguing implications for the use of SP cells in clinical orthopedics and stem cell-based disorders of bone.
Postoperative pain assessment tools in day surgery: literature review (2004)

Common guidelines on the definition and measurement of pain are needed. In day surgery, the availability of a unified and reliable measure of pain that can address its sensory component, such as the VAS, will provide more reliable information about the pain experience and, hence, improve its overall management.
Income Elasticity of Time Deposit in the Context of Bangladesh (2009)

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Transformation of toluene and benzene by mixed methanogenic cultures (1987)

The aromatic hydrocarbons toluene and benzene were anaerobically transformed by mixed methanogenic cultures derived from ferulic acid-degrading sewage sludge enrichments. In most experiments, toluene or benzene was the only semicontinuously supplied carbon and energy source in the defined mineral medium. No exogenous electron acceptors other than CO2 were present. The cultures were fed 1.5 to 30 mM unlabeled or 14C-labeled aromatic substrates (ring-labeled toluene and benzene or methyl-labeled toluene). Gas production from unlabeled substrates and 14C activity distribution in products from the labeled substrates were monitored over a period of 60 days. At least 50% of the substrates were converted to CO2 and methane (greater than 60%). A high percentage of 14CO2 was recovered from the methyl group-labeled toluene, suggesting nearly complete conversion of the methyl group to CO2 and not to methane. However, a low percentage of 14CO2 was produced from ring-labeled toluene or from benzene, indicating incomplete conversion of the ring carbon to CO2. Anaerobic transformation pathways for unlabeled toluene and benzene were studied with the help of gas chromatography-mass spectrometry. The intermediates detected are consistent with both toluene and benzene degradation via initial oxidation by ring hydroxylation or methyl oxidation (toluene), which would result in the production of phenol, cresols, or aromatic alcohol. Additional reactions, such as demethylation and ring reduction, are also possible. Tentative transformation sequences based upon the intermediates detected are discussed.