gebhart/patrepeval huggingface dataset:
Aromatische Phosphine mit Substituenten zweiter Ordnung, XIII. Triarylphosphine mit mehreren Carbonyl‐Funktionen durch Grignard‐Synthese (1973)

Abstract Die Triarylphosphine 1 – 6 mit einer oder mehreren Formyl‐ oder Acetyl‐Gruppen in p‐, m ‐ oder o ‐Stellung sind aus den Äthylenketalen isomerer Brombenzaldehyde und Bromacetophenone glatt zugänglich.
A simple direct assay of 3',5'-cyclic nucleotide phosphodiesterase activity based on the use of polyacrylamide-bononate affinity gel chromatography. (1979)

A rapid, simple, and direct assay for 3',5'-cyclic nucleotide phospho-diesterase activity is based on the effective separation of cyclic AMP, cyclic GMP or cyclic CMP from their corresponding 5'-nucleotides and nucleosides by chromatography on a polyacrylamide-boronate gel. The affinity of the boronate residue for cis-diols results in the retention of 5'nucleotides and nucleosides while 3',5'-cyclic nucleotides are not retained. The coelution of all 5'-nucleotides and nucleosides allows for the accurate assessment of phosphodiesterase activity in preparations contaminated by other purine metabolizing enzymes such as 5'-nucleotidases and nucleotide and nucleoside deaminases. Phosphodiesterase activity assayed by this means yields linear reaction kinetics with respect to time and amount of enzyme protein. Low blank values obtained allow for detection of as little as 2-3% conversion of substrate to product.
Isolation and Culture of Adult Mouse Hepatocytes (2010)

The liver performs a multitude of functions including the regulation of carbohydrate, fat, and protein metabolism, the detoxification of endo- and xenobiotics, and the synthesis and secretion of plasma proteins and bile. Isolated hepatocytes constitute a useful technique for studying liver function in an in vitro setting. Here we describe a method for the isolation of hepatocytes from adult mouse liver. The principle of the method is the two-step collagenase perfusion technique which involves sequential perfusion of the liver with ethylenediaminetetraacetic acid and collagenase. Following isolation, the cells can either be used for short-term studies or, alternatively, maintained in culture for prolonged periods to study long-term changes in gene expression. The protocol for mouse hepatocyte isolation may be applied to both normal and transgenic mice.
A new algorithm for transistor sizing in CMOS circuits (1990)

This paper describes a new algorithm for automatic transistor sizing in CMOS circuits. The algorithm consists of three phases: critical path analysis, transistor sizing and transistor desizing. This approach is different from conventional sizing methods that optimize a given design locally, using one or several paths at a time. The authors' algorithm reduces the delays of all paths in a given design simultaneously. Using their transistor desizing approach, the minimal transistor areas can be achieved to meet a set of timing requirements. Furthermore, by tuning NFET and PFET transistor sizes separately, this algorithm has control over rise and fall time delays of a gate depending on the input trigger signal. Experimental results show that this algorithm can improve the delay in approximately linear time. >
Proteins released by cultured Day 15–16 conceptuses prolong luteal maintenance when introduced into the uterine lumen of cyclic ewes (1984)

Experiments were performed to determine whether proteins, produced and released into the incubation medium by Day 15-16 sheep conceptuses cultured for 24-48 h, could prolong the functional lifespan of the corpus luteum (CL) when infused into the uterine lumen of cyclic ewes. Beginning on Day 12 (oestrus = Day 0) either a concentrated (2 ml) solution of total conceptus culture medium protein (2.2 mg) or diluted sheep serum (2.2 mg protein) was introduced daily via an indwelling catheter into the uterine lumen of 3 ewes for 7 days (Days 12-18). Peripheral blood samples were collected daily for 14 days (Days 12-25). On Day 25 all ewes were laparotomized and ovaries observed to determine whether CL previously marked with India ink were maintained. All controls had ovulated and formed new CL. By contrast none of the conceptus protein-treated ewes had ovulated, and their peripheral progesterone levels remained elevated. One ewe maintained a functional CL until Day 52 when she was hysterectomized. Light microscopy of histological sections prepared from the endometrium revealed glandular development comparable to that in the endometrium of cyclic animals during late dioestrus. The cells of the CL were similar to those from cyclic animals during mid- to late dioestrus. Ovine trophoblast protein ( oTP -1), a major protein secreted by the sheep conceptus between Days 13 and 21 of pregnancy, was purified from conceptus incubation medium and injected (0.2 mg protein/day) into the uterine lumen of 3 animals. Plasma progesterone concentrations indicated that oTP -1-treated animals maintained luteal function 4 days longer than did control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Penetration of Host Cell Membranes by Adenovirus 2 (1973)

Highly purified human adenovirus type 2 directly penetrated the plasma membranes of KB cells. The process of membrane penetration resulted in the appearance of large numbers of adenovirions free in the cytoplasm of the infected cells. The virions underwent a morphological change as they penetrated the cell surface. Penetration of the plasma membranes and the accompanying alteration in virion morphology was dependent on a function associated with the intact cells, because neither event occurred when purified virions were added to isolated cell membranes. Inactivation of the adenovirions with heat or antibodies before inoculation of the cells reduced the infectivity of the virus population and prevented the appearance of virions free in the cytoplasm. The inactivation of the virions did not significantly reduce the number of virus particles which were found in cell vacuoles and pinocytotic vesicles.
Pulmonary and Systemic Host Response toStreptococcus pneumoniaeandKlebsiella pneumoniaeBacteremia in Normal and Immunosuppressed Mice (2001)

Mortality related to bacteremic pneumonia remains high, and the role of sepsis in inflammation, pulmonary injury, and death remains unclear, mostly in leukopenic states. In the present study, the microbiology, histopathology, and host response to Streptococcus pneumoniae and Klebsiella pneumoniae infection were determined in an experimental model of bacteremia in immunocompetent and leukopenic mice. Leukocyte depletion by cyclophosphamide did not impair the early clearance of pneumococci from blood but facilitated growth in lungs. By contrast, klebsiellae rapidly grew in blood of leukopenic mice. These observations suggest that tissue-based phagocytes and circulating leukocytes, respectively, play prominent roles in S. pneumoniae and K. pneumoniae eradication. The kinetics of leukocyte recruitment in lungs during S. pneumoniae bacteremia suggested early strong inflammation in immunocompetent mice that is associated with tumor necrosis factor alpha release and histological disorders, including cell debris and surfactant in alveolar spaces. Leukocyte depletion further stimulated pulmonary capillary leakage both in S. pneumoniae and K. pneumoniae bacteremia, which seemed attributable to bacterial virulence factors. Nitric oxide production did not differ significantly among groups. Leukopenia and low platelet counts characterized the late stage of bacteremia for both strains, but only K. pneumoniae altered renal function. Understanding the pathogenesis of bacteremia will help establish beneficial therapies for both sepsis and pneumonia.
Differential expression of selected genes in human leukemia leukocytes. (1982)

cDNA clones complementary to mRNA of cells from patients having chronic lymphocytic leukemia (CLL) were used to examine quantitative changes in the mRNA levels of specific genes in human leukemia leukocytes. Fourteen (of 400) CLL-positive clones that did not hybridize with placental mRNA were studied. Three of the 14 clones were highly represented in mRNA from CEM, a T-cell line. One clone was highly represented in mRNA from CLL and two were highly represented in mRNA from patients with chronic myelocytic leukemia. Ten clones were not significantly represented in normal leukocytes and spleen mRNA. We have identified several genes that are differentially expressed in human leukemia leukocytes.
A single chip video signal processing architecture for image processing, coding, and computer vision (1995)

A new VLSI (CMOS) architecture for an internally multiprocessing, single chip, SIMD-based video signal processor (VSP) is presented. The limitations of extended DSP architectures and conventional array processors are discussed in the context of image processing, coding and computer vision. How this gives rise to the architecture is described. Architectural flexibility is provided by the integration of a novel array-based processing core, together with a RISC processor, intelligent memory interface processor, and internal cache RAM. The array core architecture is a second generation, enhanced array whose key features are: 2 b datapath, dual processor mesh-connected array planes and combined SIMD/systolic functionality. The core is optimized for 2-D windowed operations, particularly 2-D multiply-accumulation and transforms. The device is expected to operate at 80 MHz on low voltage silicon and deliver real-time performance across a range of target applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In Vitro Antifungal Activity Screening of Some New Glutamoyl derivatives (2014)

This research was focused at synthesizing new antifungal N-tosyl-L-glutamoyl derivatives with the aim of relating the structure with the expected biological activities. Synthesis N-tosyl-L-glutamic acid was prepared by reacting p-tosyl chloride with L-glutamic acid in sodium hydroxide-ether mixture. The anhydride was prepared by refluxing N-tosyl-L-glutamic acid with acetic anhydride. N-tosyl-L-glutamoy lamino acids were obtained using 1:1 mole of the tosyl derivatives with amino acids: glycine, L- alanine, L-Leucine , L-valine and L-tyrosine.N-tosyl-L-glutamoylamino acid methyl esters were prepared by the action of thionyl chloride in methanol on N-tosyl-L-glutamoylamino acid derivatives. N-tosyl-L-glutamoylaniline derivatives and N-tosyl-L-glutamoyl-p-amino benzoic acid were achieved by refluxing the amines and p-aminobenzoic acid in glacial acetic acid with the anhydride. The acid chloride was synthesized by refluxing N-tosyl-L-glutamoyl-p-amino benzoic acid in thionyl chloride. Stirring the acid chloride with appropriate amino acid in triethylamine-benzene mixture yielded the N-tosyl-L-glutamoyl-p-aminobenzoylamino acids. Esterifying these derivatives with Methanol in thionylchloride afforded the methyl esters. The acid azide was prepared by stirring sodium azide in dry benzene with N-tosyl-L-glutamoyl-paminobenzoyl chloride. N-tosyl-L-glutamoylamino phenyl ureaswere obtained by Curtius rearrangement by coupling of acid azides with appropriate amino acids in dry benzene. The structures of synthesized derivatives were confirmed by IR spectroscopy, 1 H NMR spectroscopy at 90 MHz with TMS as internal standard and elemental analysis. The synthesized derivativeswere tested for their antifungal properties against five fungal isolates, Yeast, Fusariumsolani, Fusarium moniliforme, Penicillium expansum and cladosporiumcladosporioides. Twenty out of the 33 compounds of the NTosylglutamoyl derivatives had no activity on the tested micro-organisms, while 13 compounds were found to affect the growth of Yeast, Fusariumsolani, Fusarium moniliforme, Penicillium expansum and cladosporiumcladosporioides with varying degrees. The study showed that changing the structures of the synthesized compounds resulted in increased, decreased or a complete loss in biological activity, which proves that they could be of practical pharmaceutical application.
<title>Electrokinetic microfluidic systems</title> (1999)

There has been much attention devoted to microfluidic systems in recent years, and it has become clear that electrokinetics is one of the favored methods to drive systems with flow channel dimensions in the tens of microns and flow rates in the nanoliter per second range. At these small dimensions, sample and reagent consumption is very small, and analysis speeds are greatly improved. At Caliper, we have demonstrated applications including DNA separations, enzyme assays, and cell biology. Others in this field have shown other examples of applications, such as immunoassays on a chip. The trend in electrokinetically driven microfluidic circuits is toward more complexity and functionality, which has mostly been achieved through the use of parallelism. It is tempting to regard this as an extension of Moore's law, which predicts a constant rate of increase of the functionality of an electronic integrated circuit. This raises the issue of the scaling laws governing microfluidic circuits, and what the limits are the scaling will run into. This presentation will discuss the scaling laws for simple circuits such as a four-port device for injection and separation, followed by an analysis of the design issues involved in parallel devices.
Hydrolysis and mineralization of chitin in the Delaware Estuary (1999)

We examined various aspects of chitin degradation in order to estimate degradation rates and the contribution of chltin to supporting bacterial growth in the Delaware estuary. Hydrolysis of the chtin analog, methylumbelliferyl-N,Nf-diacetyl-chitobioside (MUF-&NAG), and mineralization of 14Cchitin varied in a conlplex pattern in the estuary and correlated only weakly at best with various indices of chitin production. Rates of MUF-diNAG hydrolysis and '"-chitin degradation were within an order of magnitude of each other, with hydrolysis rates usually exceeding chtin mineralization. Consistent with hydrolysis being greater than mineralization, we found substantial release of I4C-labeled dissolved organic matter (DOM) during degradation of the '"-chitin; DOM release was roughly equal to respiration of 14C-chitin. This DOM release could support growth of bactena not attached or otherwise associated with the chitin, but rates of DOM release and direct chitin degradation seem low relative to bacterial production During 2 cruises in July and October, chitin appeared to support 5 % or less of bacterial production, whereas during one cruise in September the percentage was about 30%. Estimates of chitin inputs into marine systems indicate that on the order of 10% of bacterial production could be supported by chitin. Although it appears low, few individual biochemicals are likely to support much more bacterial growth than chitin, with the possible exception of protein and amino acids.
Reengineering dendritic cell‐based anti‐cancer vaccines (2008)

Despite initial enthusiasm, dendritic cell (DC)-based anti-cancer vaccines have yet to live up to their promise as one of the best hopes for generating effective anti-tumor immunity. One of the principal reasons for the generally disappointing results achieved thus far could be that the full potential of DCs has not been effectively exploited. Here, we argue that dramatic improvements in vaccine efficacy will probably require a careful re-evaluation of current vaccine design. The formulation of new strategies must take into account the natural history of DCs, particularly their role in helping the immune system deal with infection. Equally critical is the emerging importance of soluble factors, notably interleukin-12, in modulating the quality of immune responses. Vaccines should also be designed to recruit helper T cells and antibody-producing B cells rather than simply cytotoxic T lymphocytes. Finally, the judicious selection of tumor, target antigen, and disease stage best suited for treatment should serve as the foundation of trial designs. Our discussion addresses a recent clinical vaccine trial to treat early breast cancer, where many elements of this new strategy were put into practice.
Pressure promotes DNA synthesis in rat cultured vascular smooth muscle cells. (1994)

High blood pressure is one of the major risk factors for atherosclerosis. In this study, we examined the effects of pressure on cell proliferation and DNA synthesis in cultured rat vascular smooth muscle cells. Pressure without shear stress and stretch promotes cell proliferation and DNA synthesis in a pressure-dependent manner. Pressure-induced DNA synthesis was inhibited significantly by the phospholipase C (PLC) inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, the protein kinase C inhibitor H-7, 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine, staurosporine, and the tyrosine kinase inhibitor ([3,4,5-trihydroxyphenyl]methylene)propanedinitrile. To clarify whether activation of PLC and calcium mobilization are involved in pressure-induced DNA synthesis, production of 1,4,5-inositol trisphosphate (IP3) and intracellular Ca2+ was measured. Pure pressure increased IP3 and intracellular Ca2+ in a pressure-dependent manner. The increases in both IP3 and intracellular Ca2+ were inhibited significantly by 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate. This study demonstrates a novel cellular mechanism whereby pressure regulates DNA synthesis in vascular smooth muscle cells, possibly via activation of PLC and protein kinase C.
A double-blind, randomised, placebo-controlled trial of oral midazolam plus oral ketamine for sedation of children during laceration repair (2013)

The trial was registered in www.clinicaltrials.gov as NCT01470157.
Cloning and characterization of a fourth human somatostatin receptor. (1993)

We have isolated a gene coding for a fourth human somatostatin (somatotropin release-inhibiting factor) receptor. This additional somatostatin receptor (hSSTR4) is specifically expressed in human fetal and adult brain and lung tissue. The deduced amino acid sequence of the receptor displays both sequence and structural homology to three cloned somatostatin receptors as well as to other members of the family of GTP-binding-protein-coupled seven-helix transmembrane-spanning receptors. Pharmacological characterization of the expressed receptor reveals specific, high-affinity binding of somatostatin 14 and somatostatin 28. Surprisingly, several well-characterized synthetic somatostatin analogs fail to exhibit high-affinity binding to hSSTR4, indicating the existence of pharmacologically different receptor subtypes. Our data suggest that the diverse biological effects exerted by somatostatin are mediated by a family of receptors with discrete patterns of expression and different pharmacological properties.
Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies (2013)

Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL-based methodologies can be utilized to infer the presence of specific latent epitopes, they do not allow a direct visualization or quantitation of these epitopes. Here, we describe the characterization of three TCR-like monoclonal antibodies (mAbs) targeting the latent epitopes LMP1(125-133), LMP2A(426-434) or EBNA1(562-570) in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1(562-570) in association with HLA-A0201 was consistently observed in cell lines and EBV-associated tumor biopsies. These data highlight the discordance between MHC-epitope density and frequencies of associated CTL with implications for cell-based immunotherapies and/or vaccines for EBV-associated disease.
Antibiotic treatment of biofilm infections (2017)

Bacterial biofilms are associated with a wide range of infections, from those related to exogenous devices, such as catheters or prosthetic joints, to chronic tissue infections such as those occurring in the lungs of cystic fibrosis patients. Biofilms are recalcitrant to antibiotic treatment due to multiple tolerance mechanisms (phenotypic resistance). This causes persistence of biofilm infections in spite of antibiotic exposure which predisposes to antibiotic resistance development (genetic resistance). Understanding the interplay between phenotypic and genetic resistance mechanisms acting on biofilms, as well as appreciating the diversity of environmental conditions of biofilm infections which influence the effect of antibiotics are required in order to optimize the antibiotic treatment of biofilm infections. Here, we review the current knowledge on phenotypic and genetic resistance in biofilms and describe the potential strategies for the antibiotic treatment of biofilm infections. Of note is the optimization of PK/PD parameters in biofilms, high-dose topical treatments, combined and sequential/alternate therapies or the use antibiotic adjuvants.
Topoisomerase Poisons: Harnessing the Dark Side of Enzyme Mechanism (1995)

Although the one-dimensional sequence of DNA determines the genetic constitution of an organism, topological relationships within the double helix modulate virtually every physiological function of the genome(1, 2). In the cell, the topology of DNA is orchestrated by enzymes known as topoisomerases(1, 2, 3, 4, 5, 6, 7). These ubiquitous enzymes are required for replication, transcription, and recombination and play critical roles in chromosome structure, condensation/decondensation, and segregation(1, 2, 3, 4, 5, 6, 7, 8, 9).
Autocrine Production of Interleukin-4 and Interleukin-10 Is Required for Survival and Growth of Thyroid Cancer Cells (2006)

Although CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIP(L) (cFLIP(L)) and PED/PEA-15, two antiapoptotic proteins whose exogenous expression in normal thyrocytes inhibited the death-inducing signaling complex of CD95. Additionally, small interfering RNA FLIP and PED antisense sensitized thyroid cancer cells to CD95-mediated apoptosis. Exposure of normal thyrocytes to IL-4 and IL-10 potently up-regulated cFLIP and PED/PEA-15, suggesting that these cytokines are responsible for thyroid cancer cell resistance to CD95 stimulation. Moreover, treatment with neutralizing antibodies against IL-4 and IL-10 or exogenous expression of suppressor of cytokine signaling-1 of thyroid cancer cells resulted in cFLIP and PED/PEA-15 down-regulation and CD95 sensitization. More importantly, prolonged IL-4 and IL-10 neutralization induced cancer cell growth inhibition and apoptosis, which were prevented by blocking antibodies against CD95 ligand. Altogether, autocrine production of IL-4 and IL-10 neutralizes CD95-generated signals and allows survival and growth of thyroid cancer cells. Thus, IL-4 and IL-10 may represent key targets for the treatment of thyroid cancer.