gebhart/patrepeval huggingface dataset:
A compartmentalized regulator of developmental gene expression in Bacillus subtilis (1996)

We have identified a new Bacillus subtilis gene, spoVT, whose gene product is homologous to the transcriptional regulator AbrB and serves as a regulator of E sigmaG-controlled gene expression. SpoVT acts both positively and negatively in controlling sigmaG-dependent gene expression, providing an additional level of refinement to forespore gene regulation and feedback control of spoIIIG expression.
Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis (2007)

This review presents recent data supporting the methotrexate (MTX) mechanisms of action, which are likely to account for its anti-proliferative and immunosuppressive effects in rheumatoid arthritis (RA). The effects of MTX in vivo may be mediated by reducing cell proliferation, increasing the rate of apoptosis of T cells, increasing endogenous adenosine release, altering the expression of cellular adhesion molecules, influencing production of cytokines, humoral responses and bone formation. Several reports indicate that the effects of MTX are influenced by genetic variants, specific dynamic processes and micro-environmental elements such as nucleotide deprivation or glutathione levels. The challenge for the future will be linking biological and genetic markers relevant to the response to MTX in RA.
Treatment of adult systemic mastocytosis with interferon‐α: results of a multicentre phase II trial on 20 patients (2002)

Systemic mastocytosis (SM) is characterized by proliferation of mast cells in various organs, which may release a wide variety of mediators, thereby explaining the broad clinical spectrum of disease manifestations. The potentially life-threatening systemic symptoms and tumoral proliferation are poorly controlled despite the use of several cytotoxic chemotherapies and/or symptomatic treatments. Twenty consecutive adult SM patients with histologically confirmed bone marrow (BM) involvement received interferon-alpha subcutaneously (1-5 million units/m2/d, with progressive dose intensification over the first month of treatment) and were evaluated after 6 months of therapy. Seven of them had previously received symptomatic treatments, including steroids, which were ineffective. Among the 13 patients treated for at least 6 months, seven partial and six minor responses, mainly concerning vascular congestion and skin lesions, were obtained, while BM infiltration remained unchanged in 12 patients. The significant reduction of mast-cell mediator levels after 6 months of treatment was not predictive of clinical remission. The rate of depression was unexpectedly high (seven patients; 35%). Two patients died soon after starting therapy (one myocardial infarction, one septic shock). Six months of interferon-alpha may relieve vascular congestion in adults with SM, probably by inhibiting mast-cell degranulation.
Orientational Order in Block Copolymer Films Zone Annealed below the Order−Disorder Transition Temperature (2007)

We report measurements of rapid ordering and preferential alignment in block copolymer films zone annealed below the order-disorder transition temperature. The orientational correlation lengths measured after approximately 5 h above the glass-transition temperature ( approximately 2 microm) were an order of magnitude greater than that obtained under equivalent static annealing. The ability to rapidly process polymers with inaccessible order-disorder transition temperatures suggests zone annealing as a route toward more robust nanomanufacturing methods based on block copolymer self-assembly.
ELL: Extendable Library Language (2002)

The authors summarize an approach that considers reuse as a higher-level specification method with its own environment. A prototype for semiautomatic software generation has been developed by combination of a reuse process with knowledge of an application domain in terms of objects, functions, templates, and rules. The prototyped reuse environment is described with emphasis on the Extendable Library Language (ELL). ELL allows users to input the specification of their systems in terms of different components of the library. In conjunction with the reuse environment, ELL provides for incremental decomposition of the missing library components into lower-level, and combination of the components of the library that generate the code for the missing module.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dravet syndrome: a genetic epileptic disorder. (2012)

Dravet syndrome (DS), or severe myoclonic epilepsy in infancy, is one of the most severe types of genetic epilepsy. It is characterized by the initial occurrence of febrile or afebrile seizures that often evolve into status epilepticus in infants with normal development, and by the subsequent appearance of myoclonic and/or atypical absence seizures as well as complex partial seizures. The key feature that characterizes DS is fever sensitivity, although photosensitivity and pattern-sensitivity are also often seen. The prognosis is unfavorable in most cases. Seizures become drug-resistant and persist, with many patients suffering from motor and cognitive impairment. Mutations of SCN1A, which encodes the voltage-gated sodium channel NaV1.1, are the most frequent genetic cause of this syndrome. SCN1A mutations and/or microchromosomal rearrangements involving SCN1A are detected in about 85ｵ of patients. Mutations of PCDH19 have also been reported in female patients with clinical findings compatible with DS. PCDH19 mutations might account for 5ｵ of overall DS cases. Thirty years after its first description, DS is considered as a model of channelopathy. This survey reviews recent developments in the research literature on DS, focusing on the clinical course, as well as its genetic causes.
Performance of non-uniform 16QAM modulation over linear and nonlinear channels (2006)

A technique of using a non-uniform 16QAM modulation combined with bit interleaved coded modulation and a new iterative decoding (BICM-ID) scheme is investigated. Simulation results of a parallel concatenated convolutional code shows a gain of 0.95 dB at a BER of 10−5 compared to conventional uniform 16QAM modulation in a linear channel. For a nonlinear satellite channel, this scheme offers a gain of 1.2 dB at the same BER compared to a uniform constellation.
Construction, Expression, and Characterization of BD1-G28-5 sFv, a Single-chain Anti-CD40 Immunotoxin Containing the Ribosome-inactivating Protein Bryodin 1 (1997)

The major limitation to the use of immunotoxins in the clinic is the toxicity associated with the toxin moiety. BD1-G28-5 single-chain Fv (sFv) is a single-chain immunotoxin targeted to human CD40 and consists of bryodin 1 (BD1), a plant ribosome-inactivating protein that is 20-30-fold less toxic in animals than commonly used toxins, fused to the sFv region of the anti-CD40 monoclonal antibody G28-5. This immunotoxin was expressed in Escherichia coli and purified from refolded inclusion bodies. BD1-G28-5 sFv retained the full protein synthesis inhibition activity of recombinant BD1 and specifically bound to CD40 with a binding affinity, kd, of 1.5 nM, within 10-fold of the bivalent parental monoclonal antibody. BD1-G28-5 sFv was potently cytotoxic against CD40-expressing B lineage non-Hodgkin's lymphoma and multiple myeloma cell lines, with EC50 values in the ng/ml range, but not against a CD40-negative T cell line. Interestingly, BD1-G28-5 sFv was not cytotoxic against CD40-expressing carcinoma cell lines that were sensitive to a BD1-based immunotoxin conjugate targeted to the Ley carbohydrate antigen. These data represent the first report indicating that BD1 can be used in the construction of potent single-chain immunotoxins. Additionally, although BD1-G28-5 sFv effectively killed CD40-expressing hematologic malignancies, its lack of activity against CD40-expressing carcinomas suggests that CD40-mediated trafficking of BD1 differs in the two cancer types.
The Relationship Between Ect Nonresponsiveness and Calcification of the Pineal Gland in Bipolar Patients (1990)

It has been suggested recently that the therapeutic effects of electroconvulsive therapy (ECT) may be mediated in part through stimulation of pineal melatonin secretion. If melatonin does mediate the antidepressant effects of ECT and depression itself is associated in some patients with reduced melatonin secretion, patients with reduced melatonin secretion could respond less readily to ECT. There is evidence to suggest an inverse relationship between melatonin secretion and the degree of pineal calcification. Specifically, heavy pineal calcifications in animals have been reported to be associated with reduced plasma melatonin levels. In this study, an investigation was conducted to establish more precisely the relationship between the clinical response to ECT in 17 bipolar patients and the degrees of pineal calcification present on CT scan. There was a significant association between ECT nonresponsiveness and the presence of pathologically enlarged pineal calcification (i.e., greater than 1 cm in diameter) (p.01). In addition, there was a significant difference in ECT responsiveness in patients without pineal calcification compared to those with pathologically enlarged pineal calcification (F = 6.10; p = .01, one-way ANOVA). These findings indicate an association between enlarged pineal calcification and ECT nonresponsiveness and suggest that reduced melatonin secretion may be associated with ECT nonresponsiveness. An enlarged pineal calcification could be a useful radiological marker of ECT nonresponsiveness and administration of melatonin precursors (i.e., L-tryptophan; 5-HTP) and its cofactors (i.e., pyridoxine, folate) as well as melatonin-release enhancing agents (i.e., 5-methoxypsoralen) prior to ECT might augment its antidepressant effects in bipolar patients.
The effect of celecoxib on tissue factor expression in pancreatic cancer cells (2007)

背景组织因素(TF ) 是在许多恶性肿瘤的 overexpressed 并且被连接到如此的恶意的致病和预后。在 vitro，研究证明了 TF 的那减少的表情在 angiogenesis 和恶性肿瘤的房间增长上有禁止的效果。因此， TF 抑制为恶性肿瘤作为可能的治疗被提起了。这里，我们在瘤坏死因素(TNF ) 在 PANC-1 房间和位于 celecoxib effect.Methods 下面的可能的分子的机制导致的 TF 表示上调查了 celecoxib 的效果 celecoxib 答案的各种各样的剂量被加到与 TNF 的相等的剂量混合 6 个小时的 PANC-1 房间的标准房间数字。织物因素的表示是由西方的污点的检测份量上，虽然当 celecoxib 的剂量增加了，原子因素 B 的激活被 electromobility 移动 assay.Results 测试，织物因素表示在 PANC-1 房间被减少那么是织物因素的表示在 PANC-1 房间由 TNF 导致了的原子因素 B.Conclusions Celecoxib 罐头 downregulate 的激活。celecoxib 的这 antitumour 效果能在原子因素 KB 的激活经由它的镇压角色间接地被解释。
Up-regulation of Brain-Derived Neurotrophic Factor Expression by Brimonidine in Rat Retinal Ganglion Cells (2002)

<h3>Objectives</h3> Brimonidine tartrate ophth, an α<sub>2</sub>-adrenergic agonist, is widely used as an antiglaucoma agent for lowering intraocular pressure. Recent studies suggest that brimonidine may be neuroprotective for retinal ganglion cells (RGCs) following optic nerve crush injury. Brain-derived neurotrophic factor (BDNF), a potent neuroprotective factor present in the RGCs, promotes RGC survival in culture and following optic nerve injury. We tested the hypothesis that a possible mechanism of brimonidine neuroprotection is through up-regulation of endogenous BDNF expression in the RGCs. <h3>Methods</h3> A single dosage of brimonidine tartrate ophth solution (0.85-34µM) was injected intravitreally into Sprague-Dawley rat eyes. The fellow eyes of each animal were injected with balanced salt solution (BSS) and used as control eyes. To determine BDNF messenger RNA expression, animal eyes were enucleated and processed for in situ hybridization, or retinas were isolated and processed for Northern blot analysis using rat BDNF radiolabeled riboprobes. <h3>Results</h3> In the control eyes injected with saline, BDNF was present in a minority of the RGCs. Two days after brimonidine injection, the number of BDNF-positive RGCs was increased from 55% to 166%, depending on brimonidine concentrations, when compared with those in the controls. In addition, the BDNF signal intensities in individual RGCs were elevated 50% in brimonidine-injected eyes compared with control eyes. Northern blot revealed a 28% increase of BDNF expression in the brimonidine group compared with the controls (<i>P</i>&lt;.003). No significant difference was observed in BDNF receptor,<i>trk</i>B, expression between brimonidine, or BSS control groups. <h3>Conclusions</h3> A single dose of a low concentration of intravitreal brimonidine is sufficient to significantly increase endogenous BDNF expression in RGCs. These results suggest that brimonidine neuroprotection may be mediated through up-regulation of BDNF in the RGCs. The BDNF should be further investigated regarding its role in the neuroprotective effects reported with brimonidine. <h3>Clinical Relevance</h3> Brimonidine may be (potentially) used clinically as a neuroprotective agent in optic neuropathy, including glaucoma, and ischemic and traumatic optic neuropathy.
Intravesical Ad-IFNα Causes Marked Regression of Human Bladder Cancer Growing Orthotopically in Nude Mice and Overcomes Resistance to IFN-α Protein (2004)

We have produced prolonged, high local concentrations of interferon in vivo by intravesical instillation of adenoviruses encoding interferon-alpha (Ad-IFNalpha) together with the gene transfer-enhancing agent Syn3. We found sustained interferon protein levels for days, both in normal mouse urothelium and in human bladder cancer cells growing as superficial bladder tumors in nude mice using an orthotopic bladder model developed by us. Tumor burden in the bladder was determined utilizing cancer cells containing the green fluorescent protein. Marked tumor regression was observed following two 1-h exposures of Ad-IFNalpha/Syn3 and little or no cytotoxicity was detected in normal cells. Similar intravesical instillation of clinically relevant concentrations of IFN protein alone or Ad-IFNalpha without Syn3 was ineffective. Surprisingly, in vitro, Ad-IFNalpha also caused caspase-dependent death of bladder cancer cell lines that were resistant to high concentrations of IFN-alpha protein, including the cell line used in vivo. These findings demonstrate that Ad-IFNalpha can overcome resistance to IFN-alpha protein both in vitro and in vivo and support evaluation of intravesical Ad-IFNalpha/Syn3 for the treatment of superficial bladder cancer.
The Use of Mesoporous Silica in Liquid Chromatography (1999)

Preparative chromatography is a potential application for mesoporous silica due to its high surface area. Mesoporous spheres (MSs) have been prepared quickly from acid solution (see Figure), and their properties with regard to liquid chromatography and high-performance liquid chromatography (HPLC) explored. A new chromatographic technique, reverse-phase flash HPLC, is presented that relies on the use of these acid-prepared MSs.
Effect of 6% hydroxyethyl starch-450 and low molecular weight dextran on blood sugar levels during surgery under subarachnoid block: A prospective randomised study (2010)

Dextrans and hydroxyethyl starches produce significant levels of free glucose residues following metabolism. The following study was designed to compare 6% hydroxyethyl starch-450 with Dextran 40, both used as preloading fluids, for their potential to raise peri-operative blood glucose levels. After taking an informed consent, 180 non-diabetic adult patients, posted for elective surgery under spinal anaesthesia, were randomly divided into three groups, to receive Ringer's Lactate 20 ml/kg (group 1), Dextran 40,10 ml/kg (group 2) and Hestar 6%-450, 10 ml/kg (group 3), over half an hour, prior to the subarachnoid block, as preloading fluid, and serial capillary blood glucose measurements were taken thereafter at regular intervals up to 240 minutes from the baseline reading. All the three preloading fluids, including Ringer's Lactate used as control, were seen to significantly increase the capillary blood glucose levels intra-operatively (P < 0.05), but the rise with Dextran-40 was seen to be sustained and highly significant (P < 0.001). We thus conclude that, Dextran40 causes a sustained and significant rise in peri-operative blood glucose levels.
Characterization of TectoRNA Assembly with Cationic Conjugated Polymers (2004)

Association between RNAs with preprogrammed molecular recognition units can be quantified by using cationic, water-soluble conjugated polymers. The method uses a fluorophore-labeled probe RNA (RNA-F*), which is treated with a target structure (RNA-T). Heterodimer formation, (RNA-T/RNA-F*), increases the total negative charge on the F*-bearing macromolecule and reduces the number of negatively charged molecules (relative to unbound RNA-T+ RNA-F*). On the basis of electrostatic interactions, we anticipated more effective binding between CCP and (RNAT/RNA-F*), a reduction of the average CCP- - -F* distance, and more effective FRET upon excitation of the conjugated polymer. The resulting signals benefit from the optical amplification characteristic of emissive conjugated polymers. Solution dissociation constants can be determined by monitoring F* intensity changes as a function of [RNA-F*] and the ratio: [I(T) - I(NB)]/I(NB), where I(T) and I(NB) are the F* intensities in the presence of the target RNA (RNA-T) and a nonbinding RNA (RNA-NB), respectively, while keeping the concentration of the conjugated polymer constant. By focusing on [I(T) - I(NB)]/I(NB) as a function of RNA concentration, one can detect the concentration range wherein increased fluorescence is the result of dimerization.
Isonicotinyloxycarbonyl a novel amino protecting group for peptide synthesis (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsonicotinyloxycarbonyl a novel amino protecting group for peptide synthesisDaniel F. Veber, William J. Paleveda Jr., Yung C. Lee, and Ralph HirschmannCite this: J. Org. Chem. 1977, 42, 20, 3286–3288Publication Date (Print):September 1, 1977Publication History Published online1 May 2002Published inissue 1 September 1977https://pubs.acs.org/doi/10.1021/jo00440a018https://doi.org/10.1021/jo00440a018research-articleACS PublicationsRequest reuse permissionsArticle Views518Altmetric-Citations52LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Conjugation of human Fc gamma in closed-hinge or open-hinge configuration to Fab'gamma and analogous ligands (1997)

We describe a method for linking human normal Fc gamma1, via stable thioether bonds emerging from its hinge, to any molecule expressing a free sulfhydryl (SH) group. The Fc hinge may be closed by a disulfide (SS) bond or left open. Preparation begins with reduction of the Fc hinge to release four SH groups from its two parallel inter-gamma SS bonds. When the Fc is required in normal closed-hinge configuration, one SH group is alkylated with N-ethylmaleimide under limiting conditions, and one of the inter-gamma SS bonds is reconstituted by SS interchange. The residual SH group, to be used for linking, is left as a 4-dithiopyridyl group suitable for storage. When the Fc is required for conjugation the 4-dithiopyridyl is replaced by a metastable maleimidyl group, which reacts rapidly with SH on the partner molecule to form a tandem thioether link. If the partner is Ab Fab'gamma, linking to cysteines in the Fab'gamma hinge yields derivatives such as FabFc and FabFc2. Chimeric FabFc Abs (mouse Fab'gamma/human Fc gamma1) invoked cellular cytotoxicity in vitro, using human cell lines as targets and human lymphocytes as effectors, whether the Fc hinge was open or closed. The same Abs could kill the same targets by activating human complement, but only when the Fc hinge was closed. Both effector functions were enhanced by the presence of a second Fc in FabFc2. This method of Fc addition can be used to predict the performance of recombinant chimeric Abs and to provide novel molecular geometries.
microDuMIP: target-enrichment technique for microarray-based duplex molecular inversion probes (2015)

Molecular inversion probe (MIP)-based capture is a scalable and effective target-enrichment technol-ogy that can use synthetic single-stranded oligonu-cleotides as probes. Unlike the straightforward use of synthetic oligonucleotides for low-throughput target capture, high-throughput MIP capture has required laborious protocols to generate thousands of single-stranded probes from DNA microarray because of multiple enzymatic steps, gel purifications and ex-tensive PCR amplifications. Here, we developed a simple and efficient microarray-based MIP prepara-tion protocol using only one enzyme with double-stranded probes and improved target capture yields by designing probes with overlapping targets and unique barcodes. To test our strategy, we produced 11 510 microarray-based duplex MIPs (microDuMIPs) and captured 3554 exons of 228 genes in a HapMap genomic DNA sample (NA12878). Under our protocol, capture performance and precision of calling were compatible to conventional MIP capture methods, yet overlapping targets and unique barcodes allowed us to precisely genotype with as little as 50 ng of input genomic DNA without library preparation. microDu-MIP method is simpler and cheaper, allowing broader applications and accurate target sequencing with a scalable number of targets.
Routing indices for peer-to-peer systems (2003)

Finding information in a peer-to-peer system currently requires either a costly and vulnerable central index, or flooding the network with queries. We introduce the concept of routing indices (RIs), which allow nodes to forward queries to neighbors that are more likely to have answers. If a node cannot answer a query, it forwards the query to a subset of its neighbors, based on its local RI, rather than by selecting neighbors at random or by flooding the network by forwarding the query to all neighbors. We present three RI schemes: the compound, the hop-count, and the exponential routing indices. We evaluate their performance via simulations, and find that RIs can improve performance by one or two orders of magnitude vs. a flooding-based system, and by up to 100% vs. a random forwarding system. We also discuss the tradeoffs between the different RI schemes and highlight the effects of key design variables on system performance.