gebhart/patrepeval huggingface dataset:
Recombinant vWF Type 2A Mutants R834Q and R834W Show a Defect in Mediating Platelet Adhesion to Collagen, Independent of Enhanced Sensitivity to a Plasma Protease (1999)

Type 2A von Willebrand Disease (vWD) is characterized by the absence of high molecular weight von Willebrand factor (VWF) multimers in plasma which is caused by enhanced extracellular proteolysis or defective intracellular transport. We identified in vWD type 2A patients two mutations in the A2 domain at position 834 in which arginine (R) was substituted for glutamine (R834Q) or tryptophan (R834W). We reproduced these mutations in vWF cDNA and expressed the recombinant proteins in furin cDNA containing baby hamster kidney (fur-BHK) cells. The subunit composition and the multimeric structure of both mutants was similar to wild-type (WT) vWF. Characterization of mutant R834Q by ristocetin or botrocetin induced platelet binding, and by binding to heparin showed no abnormality. R834W had normal botrocetin induced platelet binding, but ristocetin induced platelet binding and binding to heparin were decreased. Under static conditions R834Q and R834W, at 10 microg/ml, bound equally well to collagen type III as WT-vWF. At high shear rate conditions both mutants supported platelet adhesion normally when coated to a glass surface or preincubated on collagen. When R834Q or R834W was added to the perfusate, adhesion to collagen type III was 50% of the WT-vWF value, which was not due to a decreased collagen binding under flow. A divalent cation dependent protease, purified from plasma, degraded the 2A mutants rapidly while WT-vWF was not affected. In conclusion, the mutations present in the A2 domain of vWF result in an enhanced proteolytic sensitivity to a divalent ion-dependent protease. When present in the perfusate, R834Q and R834W show a decrease in platelet adhesion to collagen type III under flow conditions, which is not caused by decreased binding of the mutant vWF to collagen or enhanced proteolysis.
Nitrogen‐Use Efficiency among Flue‐Cured Tobacco Genotypes (1991)

Today's flue‐cured tobacco ( Nicotiana tabacum L.) cultivars differ significantly in yield and quality from cultivars grown early in the 20th century. One major change in crop management has been an increase in fertilizer use, especially N. In view of the changing fertilization practices and the current importance of N in crop production, this study was initiated to evaluate genetic variability in N‐use efficiency in flue‐cured tobacco. Twelve popular cultivars spanning a period of development from the 1920s through the 1980s were evaluated at fertilizer N rates of 47, 68, and 89 kg ha ‐1 in 1986, 1987, and 1988 at the Upper Piedmont Research Station, Reidsville, NC. Measures of cured‐leaf yield and total N concentration in leaves were used to determine N‐use efficiency and its component parts, N‐uptake efficiency and N‐utilization efficiency. Significant differences were found among cultivars and among N rates for all traits. Modern cultivars were higher yielding at all N fertility levels. Values for N‐use efficiency increased from the oldest to the newest cultivars. Variation in N‐use efficiency among the cultivars tested was due to increases in both N‐uptake efficiency and the efficiency of utilization of accumulated N in the production of dry matter. Nitrogen‐use efficiency of all cultivars examined decreased as the level of applied N increased. Nitrogen‐use efficiency was positively correlated with chemical quality of the cured leaf. Breeding for improved yield and quality of flue‐cured tobacco cultivars has indirectly led to improvements in N‐use efficiency.
Dynamics of Pressure-Induced Phase Separation in Polymer Solutions. The Dependence of the Demixing Pressures on the Rate of Pressure Quench in Solutions of Poly(dimethylsiloxane) in Supercritical Carbon Dioxide (1999)

The dynamics of pressure-induced phase separation (PIPS) is important to processes that use near-critical or supercritical fluids. In this study, controlled pressure quench experiments were conducted in a 5 wt % solution of poly(dimethylsiloxane) (Mw = 93 700; Mw/Mn = 2.99) in supercritical carbon dioxide to determine the demixing pressures and its dependence on the rate of pressure change. Pressure quench rates were changed from extremely slow (ca. 0.008 MPa/s) to extremely rapid (ca. 500 MPa/s), and the system behavior was documented by real time recording of the changes in the transmitted light intensity, temperature, and pressure during the quench using a specially designed experimental system. The experiments were conducted on both the lower and the upper critical solution temperature (LCST and UCST) branches of the liquid−liquid-phase separation boundary. Apparent demixing pressures strongly depend on the rate and the depth of the pressure quench imposed and shift to significantly higher pressures with an increase in the rate of quench if the initial temperature of the homogeneous solution is in the range where the system behavior is of the UCST type. The opposite is observed if the initial temperature is in the range where the system behavior is of the LCST type, and the demixing pressures shift to lower values. These are explained in terms of the actual pressure−temperature path the system follows because of significant cooling effects that accompany deep quenches.
Cell Surface Display of Cycloinulooligosaccharide Fructanotransferase Gene in Saccharomyces cerevisiae (2007)

Paenibacillus macerans 유래의 cycloinulooligosaccharide fructanotransferase (CFTase) 유전자(cft, 2832 bp, 103.8 kDa)를 효모 표층발현 vector인 pCTcon (GAL1 promoter)에 subcloning 하였다. 구축된 pCTECFTN (9.0 kb)를 숙주세포인 s. cerevisiae EBY100에 형질전환한 후, uracil이 결핍된 배지와 inulin 함유배지에서 선별하였다. cft 유전자는 GAL1 promoter에 의해 효모 형질전환체에서 성공적으로 발현되었다. inulin으로부터 cyclofructans (CFs)로 생산하는 효소적 능력으로부터 표층발현 유무를 확인하였다. YPDG배지에서 48시간 배양 후 분획한 균체는 5.52 unit/ l 의 활성을 보였다. CF 생산을 위한 효소의 최적 반응 조건으로 pH 8.0, 반응온도 <TEX>$50^{\circ}C$</TEX>, 기질농도 5%, 기질은 Jerusalem artichoke 등의 inulin과 표층 발현 CFTase 효소반응 결과, cycloinulohexaose (CF6), cycloinuloheptaose (CF7), 그리고 cycloinulooctaose (CF8)이 생성되었고, 이 중에서 CF6가 주 생성물이었다. The cycloinulooligosaccharide fructanotransferase (CFTase) gene (cft) from Paenibacillus macerans was subcloned into the surface display vector, pCTcon (GAL1 promoter). The constructed plasmid, pCTECFTN (9.0 kb) was introduced to S. cerevisiae EBY100 cell and then east transformants were selected on the synthetic defined medium lacking uracil and on the inulin containing medium. The surface display of CFTase was confirmed by immunofluorescence microscopy and its enzymatic ability to form cycloinulooligosaccharides(cyclofructans, CFs) from inulin. The total activity of the CFTase was reached about 5.52 unit/1 by cultivation of yeast transformant on YPDG medium. The optimized conditions determined were as follows; pH, 8.0; temperature, <TEX>$50^{\circ}C$</TEX> ; substrate concentration, 5%; inulin source, Jerusalem artichoke. By the reaction with inulin, CFs consisting of cycloinulohexaose (CF6), cycloinuloheptaose (CF7), and cycloinulooctaose (CF8) were produced and CF6 was the major product.
Blind adaptive equalizer for IIR channels with common zeros (2006)

This paper considers the problem of blind adaptive equalization of single-input multiple-output IIR channels without requiring the channel diversity condition. That is, the parallel sub-channels in the fractionally sampled model can have common factors. We develop an equalizer based on IIR prediction of the received signal. The predictor parameters are estimated by using the recursive extended least squares (RELS) algorithm. It is proved that the adaptive equalizer is globally stable and the prediction error converges in a Cesaro sense almost sure (a.s.) (with probability one) towards a scalar multiple of the input symbol sequence
Modulation of Protein–Protein Interactions with Small Organic Molecules (2003)

Many proteins exert their biological roles as components of complexes, and the functions of proteins are often determined by their specific interactions with other proteins. Because of the central importance of protein-protein interactions for cellular processes, the ability to interfere with specific protein-protein interactions provides a powerful means of influencing the function of selected proteins within the cell. Cell-permeable small organic modulators of protein-protein interactions are thus highly desirable tools both for the study of physiological cellular processes and for the treatment of numerous diseased states. Herein a number of protein-protein interactions that are considered to be pharmaceutical targets are presented, which will familiarize the reader with the strategies that have been employed for the successful identification of small molecule modulators of these protein-protein interactions. These encouraging examples suggest that combined research efforts in the areas of functional proteomics, assay development, and organic synthesis will open up novel possibilities for the treatment of human diseases in the future.
Production and purification of recombinants of mouse MASP-2 and sMAP (2005)

Small mannose-binding lectin (MBL)-associated protein (sMAP) is a component of the complex consisting of MBL and MBL-associated serine proteases (MASPs) in the lectin complement pathway. sMAP is a truncated form of MASP-2, which is generated by an alternative splicing from a single structural MASP-2 gene. Upon activation of the MBL—MASPs complex, MASP-2 cleaves the complement C4, but the role of sMAP which lacks the serine protease domain is not clear. To clarify the role of sMAP in activation of the lectin pathway, we have generated sMAP-gene deficient mice which are also deficient for MASP-2. In this study, we generated and purified mouse recombinant sMAP (rsMAP) and rMASP-2 using the Drosophila expression system for the reconstitution assay of the deficient mice. In preliminary experiments, these purified recombinants were able to reconstitute the MBL—MASPs—sMAP complexes and the addition of rMASP-2 to deficient serum restored the C4 cleavage activity of the MBL—MASPs complex. From these data, rsMAP and rMASP-2 generated in this study seem to be useful in analysis of the deficient mice.
Self-coded 3′-Extension of Run-off Transcripts Produces Aberrant Products during in Vitro Transcription with T7 RNA Polymerase (1995)

More than 70% of the RNA synthesized by T7 RNA polymerase during run-off transcription in vitro can be incorrect products, up to twice as long as the expected transcripts. Transcriptions with model templates indicate that false transcription is mainly observed when the correct product cannot form stable secondary structures at the 3'-end. Therefore, the following hypothesis is tested: after leaving the DNA template, the polymerase can bind a transcript to the template site and the 3'-end of the transcript to the product site and extend it, if the 3'-end is not part of a stable secondary structure. Indeed, incubation of purified transcripts with the polymerase in transcription conditions triggers a 3'-end prolongation of the RNA. When two RNAs of different lengths are added to the transcription mix, both generate distinct and specific patterns of prolonged RNA products without any interference, demonstrating the self-coding nature of the prolongation process. Furthermore, sequencing of the high molecular weight transcripts demonstrates that their 5'-ends are precisely defined in sequence, whereas the 3'-ends contain size-variable extensions which show complementarity to the correct transcript. Surprisingly, a reduction of the UTP concentration to 0.2-1.0 mM in the presence of 3.5-4.0 mM of the other NTPs leads to faithful transcription and good yields, irrespective of the nucleotide composition of the template.
Intensive care of patients with acute liver failure: Recommendations of the U.S. Acute Liver Failure Study Group (2007)

The present consensus details the intensive care management of patients with acute liver failure. Such guidelines may be useful not only for the management of individual patients with acute liver failure, but also to improve the uniformity of practices across academic centers for the purpose of collaborative studies.
Novel approaches in the treatment of ankylosing spondylitis and other spondyloarthritides (2003)

The therapeutic options for patients suffering from severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-TNF therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on what is now several hundred AS and PsA patients, this treatment seems to be even more effective than the same therapy in rheumatoid arthritis (RA). The anti-TNF-alpha agents currently available, infliximab (Remicade); Centocor), etanercept (Enbrel); Amgen) and adalimumab (Humira; Abbott), are approved for the treatment of RA in the US; infliximab and etanercept are approved in Europe. The situation in SpA is different to RA because there is an unmet medical need, especially in AS, since no therapies with disease-controlling antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, TNF blockers might even be considered as first-line immunosuppressive agents in patients with active AS and PsA who are not sufficiently treated by non-steroidal anti-inflammatory drugs and sulfasalazine, if peripheral arthritis is present. For infliximab, a dosage of 5 mg/kg at intervals between 6 and 12 weeks was necessary to constantly suppress disease activity; this is also a major aim of long-term treatment. No dose-finding studies have yet been performed. The standard dose of etanercept is 25 mg s.c. twice-weekly. No studies on adalimumab (standard RA dose 20 - 40 mg s.c. every 2 weeks) have yet been conducted in SpA. The efficacy of etanercept was first demonstrated in PsA and etanercept is now approved for this indication. A double-blind study has also been performed in AS, with similarly clearcut efficacy. There is preliminary evidence that both agents do also work in other SpA such as undifferentiated SpA. Infliximab has recently been approved for short-term treatment of severe uncontrolled AS; the approval for etanercept is pending. Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis might be preventable but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. Tuberculosis can be mostly prevented if patients are checked for previous contact with tuberculosis. Currently, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.
Mechanisms Underlying Expression of Tn10-Encoded Tetracycline Resistance (1994)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
The HIV Nef Protein Associates with Protein Kinase C Theta (1996)

Expression of the human immunodeficiency virus (HIV) Nef protein has been linked to both decreased cell surface expression of CD4 and an impairment of signal transduction. The recently reported association of Nef with an unidentified serine kinase provides a clue as to how Nef might exert its effects. Considering the key role of protein kinase C (PKC) in T cell activation, we investigated the possibility that Nef interacts with PKC. Our results, using two approaches for detecting interactions between Nef and PKC isozymes in Jurkat cells, show that Nef interacts preferentially with thetaPKC. The interaction of Nef and thetaPKC is independent of calcium, enhanced by phospholipid activators of PKC and not affected by a PKC pseudosubstrate peptide. Phorbol 12-myristate 13-acetate and phytohemagglutinin stimulation of Jurkat cells expressing Nef fails to produce the usual translocation of thetaPKC from the cytosol to the particulate fraction; translocation of betaPKC and epsilonPKC was unaffected. Indeed, there appears to be a net loss of thetaPKC in Nef-expressing cells following stimulation. The loss of thetaPKC, which may be a result of inhibition of its binding to RACKs due to Nef binding, could contribute to the various impairments of T cell function associated with HIV infection and Nef expression.
C REACTIVE PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASES (2001)

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53+/-5.8 years with a mean creatinine clearance (C(Cr)) of 52+/-37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0+/-4.6 mg/L and 5.8+/-5.6 pg/mL, respectively and were not significantly correlated (r=0.11, p=n.s.). CRP and IL-6 were however related with renal function (CRP versus C(Cr) r=-0.40 p <0.001; IL- 6 versus C(Cr) r=-0.45; p <0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4+/-6.3 mg/L in the group of patients with a C(Cr) lower than 20 mL/min (n=32) and 2.76+/-4.35 in the group of patients with a C(Cr) higher than 20 mL/min (n = 70) (p <0.0001). CRP and IL-6 were positively related with ESR (r=0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2+/-0.4 versus 3.0+/-0.5 g/dL). CRP and serum albumin were not significantly related (r=0.17). CRP and IL-6 correlated positively with ESR (r=0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation - even in the predialysis phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.
Examination of the role of the amphipathic .alpha.-helix in the interaction of neuropeptide Y and active cyclic analogs with cell membrane receptors and dimyristoylphosphatidylcholine (1990)

To test the potential importance of the putative C-terminal amphipathic alpha-helical region of neuropeptide Y (NPY) in receptor binding, the interactions of porcine NPY and several peptide analogues with lipid and cell membrane receptors were compared. Cyclic analogues were designed to constrain the N- and C-terminal regions of the peptide and to retain the folded conformation of NPY predicted from its sequence analogy with pancreatic polypeptide and its similar spectral behavior. The three cyclic peptides were [Cys2, 8-aminooctanoic acid5-24, D-Cys27]-NPY (C2-NPY), [Cys5, 8-aminooctanoic acid7-20, D-Cys24]-NPY (C5-NPY), and [D-Cys7, 8-aminooctanoic acid8-17, Cys20]-NPY (C7-NPY). All of the peptides bind with high affinity to pig spleen membranes, but only NPY and [Glu16, Ser18, Ala22, Leu28,31]-NPY (ESALL-NPY) bind quantitatively to dimyristoylphosphatidylcholine (DMPC) liposomes. C7-NPY and NPY20-36 bind with moderate affinity to liposomes, but only NPY and C7-NPY bind with high affinity to mouse brain receptors. Thus, lipid binding and receptor binding are not correlated in this series of peptides, and binding to the pig spleen receptor appears to require only the C-terminal region of the peptide. Simple lipid binding, as in NPY20-36, is insufficient for binding to the mouse brain receptor, suggesting that the N-terminal region of the peptide is required for high-affinity binding to this receptor. Data from fluorescence, differential scanning calorimetry, and liposome clearing experiments suggest that, although the interaction of NPY with lipid is consistent with formation of an amphipathic alpha-helix, a simple amphipathic alpha-helical model for the interaction with the high-affinity NPY receptor is insufficient to explain the data.(ABSTRACT TRUNCATED AT 250 WORDS)
Glucocorticoids and insulin resistance: old hormones, new targets (1999)

Insulin resistance has been proposed as a mediator of the association between risk factors for cardiovascular disease in the population. The clinical syndrome of glucocorticoid excess (Cushing's syndrome) is associated with glucose intolerance, obesity and hypertension. By opposing the actions of insulin, glucocorticoids could contribute to insulin resistance and its association with other cardiovascular risk factors. In this review, we describe briefly the known mechanisms of insulin resistance and highlight the potential mechanisms for the effect of glucocorticoids. We then discuss factors which modulate the influence of glucocorticoids on insulin sensitivity; this highlights a novel therapeutic strategy to manipulate glucocorticoid action which may prove to be a useful tool in treating subjects with insulin resistance. Finally, we describe evidence from human studies that glucocorticoids make an important contribution to the pathophysiology of insulin resistance in the population.
Selected mapping technique with novel phase sequences for PAPR reduction of an OFDM signal (2005)

High peak-to-average power ratio (PAPR) of the transmitted signal is a major drawback of orthogonal frequency division multiplexing (OFDM). The selected mapping (SLM) technique is one of the promising PAPR reduction techniques for OFDM. In the SLM technique, some statistically independent data blocks are generated from an OFDM data block using a set of phase sequences and the one with the lowest PAPR is chosen and transmitted. In this paper, we propose an SLM technique with novel phase sequences. In the proposed SLM technique, it is not required to exchange side information between transmitter and receiver, which is usually required in the ordinary SLM technique. It is shown that we can achieve comparable PAPR reduction performance to the ordinary SLM technique with no data rate loss and a small increase in transmitted signal power.
Estrogen-Induced c-fos Protooncogene Expression in MCF-7 Human Breast Cancer Cells: Role of Estrogen Receptor Sp1 Complex Formation (1998)

17-Estradiol (E 2 ) induces c-fos protooncogene expression in MCF-7 human breast cancer cells, and previous studies in HeLa cells identified an imperfect palindromic estrogen-responsive element (1212 to 1200) that was required for trans-activation.In contrast, the estrogen-responsive element was not required for E 2 responsiveness in MCF-7 cells, and using a series of constructs containing wildtype (pF1) and mutant 5-flanking sequences (1220 to 1155) from the c-fos protooncogene promoter in transient transfection assays, it was shown that a GC-rich motif (5-GGGGCGTGG) containing an imperfect Sp1-binding site was required for hormone-induced activity.This sequence also bound Sp1 protein in gel mobility shift assays, and coincubation with the estrogen receptor (ER) enhanced Sp1-DNA