gebhart/patrepeval huggingface dataset:
Engineering type 1 copper sites in proteins (1993)

The use of site-directed mutagenesis methods has revolutionalized the study of the so-called type 1 and type 2 copper sites in proteins. In particular our understanding of the relation between the structure, and the mechanistic and spectroscopic features of these sites is benefitting from the application of these techniques. Recent progress in the field is reviewed with emphasis on the study of type 1 sites. Topics covered comprise the characteristics of the natural type 1 and type 2 sites, the genetics of blue copper proteins, the modification of Cu sites, the spectroscopy of natural and engineered type 1 and type 2 sites, the effect of mutations on midpoint potentials and the mechanism of electron transfer as carried out by the blue copper proteins.
Apoptosis in erythroid progenitors deprived of erythropoietin occurs during the G1 and S phases of the cell cycle without growth arrest or stabilization of wild-type p53. (1994)

Erythropoietin (Epo) inhibits apoptosis in murine proerythroblasts infected with the anemia-inducing strain of Friend virus (FVA cells). We have shown that the apoptotic process in FVA cell populations deprived of Epo is asynchronous as a result of a heterogeneity in Epo dependence among individual cells. Here we investigated whether apoptosis in FVA cells correlated with cell cycle phase or stabilization of p53 tumor suppressor protein. DNA analysis in nonapoptotic FVA cell subpopulations cultured without Epo demonstrated little change in the percentages of cells in G1,S, and G2/M phases over time. Analysis of the apoptotic subpopulation revealed high percentages of cells in G1 and S, with few cells in G2/M at any time. When cells were sorted from G1 and S phases prior to culture without Epo, apoptotic cells appeared at the same rate in both populations, indicating that no prior commitment step had occurred in either G1 or S phase. Steady-state wild-type p53 protein levels were very low in FVA cells compared with control cell lines and did not accumulate in Epo-deprived cultures; however, p53 protein did accumulate when FVA cells were treated with the DNA-damaging agent actinomycin D. These data indicate that erythroblast apoptosis caused by Epo deprivation (i) occurs throughout G1 and S phases and does not require cell cycle arrest, (ii) does not have a commitment event related to cell cycle phase, and (iii) is not associated with conformational changes or stabilization of wild-type p53 protein.
Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2k) mice (1997)

These results suggest the existence of at least 2 CTL populations in this mouse model: one recognizing peptide of bacteria-infected cells restricted by HLA-B*2705 and the other recognizing peptide of bacteria-infected cells restricted by the murine H-2Kk molecule. It does not appear that hsp57 is a major target for the CD8 T cell response directed against Chlamydia. This animal model opens the way for identifying bacterial epitopes presented by HLA-B27, and might thus help to clarify the pathogenesis of B27-associated diseases.
Efficient fair queuing using deficit round-robin (1996)

Fair queuing is a technique that allows each flow passing through a network device to have a fair share of network resources. Previous schemes for fair queuing that achieved nearly perfect fairness were expensive to implement; specifically, the work required to process a packet in these schemes was O(log(n)), where n is the number of active flows. This is expensive at high speeds. On the other hand, cheaper approximations of fair queuing reported in the literature exhibit unfair behavior. In this paper, we describe a new approximation of fair queuing, that we call deficit round-robin. Our scheme achieves nearly perfect fairness in terms of throughput, requires only O(1) work to process a packet, and is simple enough to implement in hardware. Deficit round-robin is also applicable to other scheduling problems where servicing cannot be broken up into smaller units (such as load balancing) and to distributed queues.
Synthesis and antifungal properties of certain 7-alkylaminopyrazolo[1,5-a]pyrimidines (1977)

A series of 7-alkylaminopyrazolo[1,5-alpha]pyrimidines (5-25) and one 7-alkylthiopyrazolo[1,5-alpha]pyrimidine (4) were synthesized from the corresponding 7-chloro precursors 3, which were prepared in turn from the 7-hydroxy analogues 2, obtained via condensation of 3-aminopyrazoles with acetoacetate esters, malonate esters, or acetylenedicarboxylate ester. Compounds 4-25 were found to inhibit Trichophyton mentagrophytes (in vitro). The degree of inhibition increased with increasing 7-alkylamino chain length up to C8 units and then began to decrease with longer chain lengths. Unsaturated chains were more fungitoxic than saturated chains, 5-methyl-7-oleylaminopyrazolo[1,5alpha]pyrimidine [22, R7=NH(CH2)8CH=CH(CH2)7CH3] being four times more inhibitory and 16 times more fungicidal (against T. mentagrophytes) than 5-methyl-7-n-octylaminopyrazolo[1,5-alpha] pyrimidine [11, R7=NH(CH2)7CH3]. Although 11 and 22 appeared to have some efficacy as topical antifungeal agents, when applied to T. mentagrophytes infections in vivo, both caused irritation (of abraded and unabraded guinea pig skin) as did compound 4 (R5=Me; R7=SC8H17).
Ankyrin binding activity shared by the neurofascin/L1/NrCAM family of nervous system cell adhesion molecules. (1994)

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. Rat neurofascin and NrCAM together comprise over 0.5% of the membrane protein in adult brain tissue. Linkage of these ankyrin-binding cell adhesion molecules to spectrin-based structures may provide a major class of membrane-cytoskeletal connections in adult brain as well as earlier stages of development.
Nonstandard for transmission of IP datagrams over serial lines: SLIP (1988)

The TCP/IP protocol family runs over a variety of network media: IEEE
802.3 (ethernet) and 802.5 (token ring) LAN's, X.25 lines,
satellite links, and serial lines. There are standard encapsulations
for IP packets defined for many of these networks, but there is no
standard for serial lines. SLIP, Serial Line IP, is a currently a de
facto standard, commonly used for point-to-point serial connections
running TCP/IP. It is not an Internet standard.
Duration of effect of oral long-acting stimulant medications for ADHD throughout the day (2010)

Most long-acting stimulants exerted beneficial effects on ADHD symptoms for up to 12 hours as measured by the PERMP; the longest duration of efficacy versus placebo was seen with lisdexamfetamine dimesylate (14 hours postdose).
LY2189265, a long‐acting glucagon‐like peptide‐1 analogue, showed a dose‐dependent effect on insulin secretion in healthy subjects (2011)

LY showed an acceptable safety profile and exhibited the expected glucagon-like peptide-1 pharmacological effects on glucose suppression and insulin secretion with a half-life that supports once-weekly dosing.
Role of interleukin 1 in promoting human monocyte-mediated tumor cytotoxicity. (1985)

Human peripheral blood monocytes from normal donors obtained by separation on a Percoll gradient showed considerable cytotoxicity against tumor cells when preincubated in vitro for 24 hr with human monocyte-derived interleukin 1 (IL 1). In contrast, monocytes after pretreatment in medium alone had low cytotoxic activity. All the IL 1 preparations, including IL 1 which was purified by high-performance liquid column chromatography (HPLC), as well as crude culture supernatant from human monocytes promoted monocyte-mediated cytotoxicity in the same dose-dependent manner as the thymocyte growth-promoting activity. There was no endotoxin or interferon (IFN) activity in the highly purified IL 1, suggesting that IL 1 itself was the active moiety. The effect of IL 1 on monocyte-mediated cytotoxicity was partially inhibited by indomethacin, whereas pretreatment of monocytes with prostaglandin (PG) E1 or E2 rather than IL 1 also resulted in substantial monocyte cytotoxicity. Thus, the effect of IL 1 on monocyte-mediated cytotoxicity is presumably mediated by PGE. Since fresh monocytes that were not preincubated exhibited levels of spontaneous cytotoxic activity similar to that of monocytes preincubated with IL 1, it seemed likely that the effect of IL 1 was to maintain the spontaneous level of activity rather than to induce cytotoxic activity. To elucidate this possibility, monocytes were first preincubated in medium alone for a longer period, and after losing their spontaneous activity they were further incubated with or without IL 1. Such "aged" monocytes did not develop cytotoxic activity in response to IL 1 but did in response to other agents known to induce macrophage cytotoxicity, such as endotoxin or lymphokine-containing supernatants. Therefore, the major effect of IL 1 actually seemed to prolong the cytotoxic state of monocytes. These results also suggest that IL 1 released by macrophages or monocytes may play a role in host defense against neoplastic cells by acting on monocytes as an autostimulating factor.
Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk (2014)

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.
Microvascular occlusions promote coronary collateral growth (1990)

The objective of this study was to examine whether myocardial ischemia without alterations in pressure gradients between large epicardial coronary arteries was a sufficient stimulus to produce coronary collateral growth and development. To accomplish this aim, we partially embolized the circumflex coronary perfusion territory with 25-microns diameter microspheres to produce multiple microvascular occlusions, sufficient to abolish or greatly attenuate coronary vasodilator reserve. The embolization procedure was performed in two groups of dogs during aseptic surgery. After the dogs recovered for 1-3 wk (short-term embolization) or 6-8 wk (long-term embolization), indexes of vascular growth were compared with a group of control animals in which all operative procedures were performed, except embolization. Retrograde blood flow, an index of collateral blood flow and coronary vascular resistance, was determined in an isolated beating empty heart preparation during coronary vasodilation with adenosine. Circumflex retrograde blood flow from the left anterior descending artery was increased from 0.09 ml.min-1.g-1 (sham) to 0.21 and 0.17 ml.min-1.g-1 in the short-term and long-term groups, respectively (P less than 0.05). Collateral blood flow from the septal artery was also increased from 0.03 ml.min-1.g-1 (sham) to 0.08 ml.min-1.g-1 (P less than 0.05) in the short-term group. Collateral contribution from the right coronary artery was not significantly altered in either group of embolization animals. The contributions of epicardial and intramyocardial collaterals to the total retrograde flow were also determined and were found to be different among the three experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Dietrichs Flucht. Textgeschichtliche Ausgabe, hg. v. Elisabeth Lienert u. Gertrud Beck, Rabenschlacht. Textgeschichtliche Ausgabe, hg. v. Elisabeth Lienert u. Dorit Wolter, Alpharts Tod. Dietrich und Wenezlan, hg. v. Elisabeth Lienert und Viola Meyer (2011)

Article Dietrichs Flucht. Textgeschichtliche Ausgabe, hg. v. Elisabeth Lienert u. Gertrud Beck, Rabenschlacht. Textgeschichtliche Ausgabe, hg. v. Elisabeth Lienert u. Dorit Wolter, Alpharts Tod. Dietrich und Wenezlan, hg. v. Elisabeth Lienert und Viola Meyer was published on September 1, 2011 in the journal Beiträge zur Geschichte der deutschen Sprache und Literatur (volume 133, issue 2).
Dissection of the ion-induced folding of the hammerhead ribozyme using 19 F NMR (2001)

We have used (19)F NMR to analyze the metal ion-induced folding of the hammerhead ribozyme by selective incorporation of 5fluorouridine. We have studied the chemical shift and linewidths of (19)F resonances of 5-fluorouridine at the 4 and 7 positions in the ribozyme core as a function of added Mg(2+). The data fit well to a simple two-state model whereby the formation of domain 1 is induced by the noncooperative binding of Mg(2+) with an association constant in the range of 100 to 500 M(-1), depending on the concentration of monovalent ions present. The results are in excellent agreement with data reporting on changes in the global shape of the ribozyme. However, the NMR experiments exploit reporters located in the center of the RNA sections undergoing the folding transitions, thereby allowing the assignment of specific nucleotides to the separate stages. The results define the folding pathway at high resolution and provide a time scale for the first transition in the millisecond range.
Expression of cannabinoid receptors type 1 and type 2 in non‐Hodgkin lymphoma: Growth inhibition by receptor activation (2008)

Endogenous and synthetic cannabinoids exert antiproliferative and proapoptotic effects in various types of cancer and in mantle cell lymphoma (MCL). In this study, we evaluated the expression of cannabinoid receptors type 1 and type 2 (CB1 and CB2) in non-Hodgkin lymphomas of B cell type (n = 62). A majority of the lymphomas expressed higher mRNA levels of CB1 and/or CB2 as compared to reactive lymphoid tissue. With the exception of MCL, which uniformly overexpresses both CB1 and CB2, the levels of cannabinoid receptors within other lymphoma entities were highly variable, ranging from 0.1 to 224 times the expression in reactive lymph nodes. Low levels of the splice variant CB1a, previously shown to have a different affinity for cannabinoids than CB1, were detected in 44% of the lymphomas, while CB1b expression was not detected. In functional studies using MCL, Burkitt lymphoma (BL), chronic lymphatic leukemia (CLL) and plasma cell leukemia cell lines, the stable anandamide analog R(+)-methanandamide (R(+)-MA) induced cell death only in MCL and CLL cells, which overexpressed both cannabinoid receptors, but not in BL. In vivo treatment with R(+)-MA caused a significant reduction of tumor size and mitotic index in mice xenografted with human MCL. Together, our results suggest that therapies using cannabinoid receptor ligands will have efficiency in reducing tumor burden in malignant lymphoma overexpressing CB1 and CB2.
Reprogramming resistant genes: in-depth comparison of gene expressions among iPS, ES, and somatic cells (2013)

Transcription factor-based reprogramming reverts adult cells to an embryonic state, yielding potential for generating different tissue types. However, recent reports indicated the substantial differences in pattern of gene expression between induced pluripotent stem (iPS) cells and embryonic stem cells (ESC). In this study, we compare gene expression signatures of different iPS and ES cell lines and relate expression profiles of differently expressed genes to their expression status in somatic cells. As a result, we discovered that genes resistant to reprogramming comprise two major clusters, which are reprogramming dependent "Induced Genes" and somatic origin "Inherited Genes," both exhibiting preferences in methylation marks. Closer look into the Induced Genes by means of the transcription regulation analysis predicted several groups of genes with various roles in reprogramming and transcription factor DNA binding model. We believe that our results are a helpful source for biologists for further improvement of iPS cell technology.
Serum antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease are mainly associated with ulcerative colitis. A correlation study between perinuclear antineutrophil cytoplasmic autoantibodies and clinical parameters, medical, and surgical treatment. (1993)

Perinuclear antineutrophil cytoplasmic antibodies have recently been demonstrated in the sera of patients with inflammatory bowel disease. Three hundred and sixty six sera obtained from 120 patients with ulcerative colitis, 105 patients suffering from Crohn's disease and 49 non-inflammatory bowel disease controls were tested in two laboratories, using an indirect immunofluorescence assay. In addition, a fixed-neutrophil enzyme linked immunoadsorbent assay (ELISA) was evaluated in one of the two laboratories. The results in the immunofluorescence test showed a high degree of correlation between the two laboratories (Kappa coefficient = 0.8). Ninety five of the 120 (79%) ulcerative colitis patients had a positive test whereas only 14 of the 105 (13%) patients with Crohn's disease were positive. Sera from four patients suffering from primary sclerosing cholangitis were positive as well as four of the 45 control sera (9%). The sensitivity of the perinuclear antineutrophil cytoplasmic antibody immunofluorescence test for the diagnosis of ulcerative colitis was 0.75 with a specificity of 0.88 and a positive predictive value of 0.88 (all sera). In the ELISA technique 37 of 94 ulcerative colitis sera and one of the 68 Crohn's disease sera were positive. In the control group only one of the patients suffering from primary sclerosing cholangitis reacted positively (32 non-inflammatory bowel disease sera tested). The ELISA technique had a high specificity (0.97), but a low sensitivity (0.39). There was no relation of perinuclear antineutrophil cytoplasmic antibodies in ulcerative colitis patients or in Crohn's disease patients with disease activity, duration of illness, localisation, extent of disease, previous bowel operations or medical treatment. The clinical significance of perinuclear antineutrophil cytoplasmic antibody positive and negative subsets in both groups of patients thus remains unexplained. Our study confirms that determination of serum antineutrophil cytoplasmatic antibodies in patients with inflammatory bowel disease may differentiate ulcerative colitis from Crohn's disease. Further immunological studies are needed to explain the absence of these antibodies in a subset of ulcerative colitis patients and their role in the pathogenesis of the disease.
Growth of Engineered Human Myocardium With Mechanical Loading and Vascular Coculture (2011)

Our results indicate that both mechanical load and vascular cell coculture control cardiomyocyte proliferation, and that mechanical load further controls the hypertrophy and architecture of engineered human myocardium. Such constructs may be useful for studying human cardiac development as well as for regenerative therapy.
Microarrays Assembled in Microfluidic Chips Fabricated from Poly(methyl methacrylate) for the Detection of Low-Abundant DNA Mutations (2003)

Low-density arrays were assembled into microfluidic channels hot-embossed in poly(methyl methacrylate) (PMMA) to allow the detection of low-abundant mutations in gene fragments (K-ras) that carry point mutations with high diagnostic value for colorectal cancers. Following spotting, the chip was assembled with a cover plate and the array accessed using microfluidics in order to enhance the kinetics associated with hybridization. The array was configured with zip code sequences (24-mers) that were complementary to sequences present on the target. The hybridization targets were generated using an allele-specific ligase detection reaction (LDR), in which two primers (discriminating primer that carriers the complement base to the mutation being interrogated and a common primer) that flank the point mutation and were ligated joined together) only when the particular mutation was present in the genomic DNA. The discriminating primer contained on its 5'-end the zip code complement (directs the LDR product to the appropriate site of the array), and the common primer carried on its 3' end a fluorescent dye (near-IR dye IRD-800). The coupling chemistry (5'-amine-containing oligonucleotide tethered to PMMA surface) was optimized to maximize the loading level of the zip code oligonucleotide, improve hybridization sensitivity (detection of low-abundant mutant DNAs in high copy numbers of normal sequences), and increase the stability of the linkage chemistry to permit re-interrogation of the array. It was found that microfluidic addressing of the array reduced the hybridization time from 3 h for a conventional array to less than 1 min. In addition, the coupling chemistry allowed reuse of the array > 12 times before noticing significant loss of hybridization signal. The array was used to detect a point mutation in a K-ras oncogene at a level of 1 mutant DNA in 10,000 wild-type sequences.
Spline-based spectrum cartography for cognitive radios (2009)

A cooperative approach to the sensing task of wireless cognitive radio (CR) networks is introduced based on a spatial model of the power spectrum density (PSD). The model entails a basis expansion of the PSD in frequency, weighted by unknown spatial functions that are estimated from CR measurements. A novel model estimator is developed using a least-squares (LS) criterion regularized with a smoothing penalty. The estimator yields a finitely-parameterized two-dimensional surface spanned by thin-plate splines, which approximates the distribution of power in space. An online PSD tracker is also developed for slowly time-varying power spectra. Different from existing approaches to interference spectrum cartography, the novel sensing scheme neither requires knowledge of second-order spatial statistics, nor it relies on stationarity assumptions.