gebhart/patrepeval huggingface dataset:
원저 : 전신성 홍반성 낭창환자에서 IMMUNOBLOT 법에 의한 항ENA 항체조사 -이중면역 확산법과 IMMUNOBLOT법의 비교- (1995)

목적: SLE의 다양한 자가항체중 ENA에 대한 항체는 류마티스 질환의 조기진단 및 질환의 분류에 도움이 되며, 특정, 임상양상과의 연관성에 대한 유용한 정보를 얻을 수 있다. 본 연구는 SLE 환자에서 immunoblot법을 이용한 자가항체 검사의 유용성을 알아보고자 하였다. 방법: 전신성 홍반성 낭창으로 진단된 127명 환자의 혈청을 이중면역 확산법 및 immunoblot법으로 항 ENA항체 검사를 동시에 시행하여 항 ENA 항체의 출현 빈도를 조사, 비교하였다. 결과: 이중 면역 확산법에 의한 항 ENA항체의 출현 빈도는 항Sm항체 15%, 항 RNP항체 24.5%, 항 Ro항체 54.3%, 항 La 항체 9.4%였으며 immunoblot법에 의한 항 ENA 항체의 출현빈도는 항 Sm항체 27%, 항 RNP항체 33.6%, 항 Ro항체 41.8%, 항 La항체 14%에서 양성반응을 보였고 이증면역 확산법으로 발견할수 없었던 ribosomal P 단백에 대한 항체 및 항 Ku항체가 각각 14%, 4%에서 양성 반응을 보였다. 결론: 이상의 결과로 이중면역 확산법과 비교해 볼 때 immunoblot법에서 항 ENA항체가 항 Ro항체를 제외하고는 검출율이 높다는 사실을 바탕으로, 많은 환자를 대상으로 계속적인 추적조사를 하여 항체의 immunoblot 양상을 조사하면 각각의 특정 peptide에 대한 항체와 임상 양상과의 관련성을 파악하는데 도움이 될 것으로 생각된다.
Construction of Genes or Gene Fragments by Use of Two Long Synthetic Oligonucleotides Representing the Coding and Noncoding Strands (1988)

Abstract The construction of genes as exemplified for a gene encoding salmon calcitonin-gly(33) from only two long synthetic oligonucleotides (coding/noncoding strand) is described. The type of solid support used in oligonucleotide preparation strongly influences synthesis yields and mutation rates in the cloning of the synthetic DNA.
Non–Small Cell Lung Cancer (2008)

Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.
Research on mRNA degradation and drug discovery (2010)

通常のmRNA分解は3’末端ポリ（A）鎖の短縮化が第1段階であり，翻訳終結と共役して開始される．一方，ナンセンス変異を有する異常mRNAは，NMDと呼ばれるmRNA分解機構により正常なmRNAとは別経路を介して即座に分解される．NMDはナンセンス変異に起因する異常な短鎖タンパク質の生成を防ぐ防御機構として重要であるが，mRNAの急速な分解に伴う機能性タンパク質の欠如により致死的な疾患の原因となることがある．そのような疾患の治療薬として，最近PTC Therapeutics社において開発されたAtalurenが注目されている．Atalurenはナンセンス変異の結果生じた異常な終止コドンの読み飛ばしを引き起こし，機能性タンパク質の産生を可能にする．現在，臨床試験の段階にあるAtalurenだが，有効性，安全性ともに優れておりナンセンス変異に起因する多くの疾患への適応の拡大が期待される．
Formulation and antitumor efficacy of liposomal-caprylated-TNF-SAM2. (1995)

The tumor necrosis factor (TNF) mutant TNF-SAM2 has previously been shown to have a therapeutic profile superior to parental TNF. To initially evaluate the characteristics of liposomal formulations of TNF-SAM2, it was modified with the N-hydroxysuccinimide ester of caprylic acid to increase its hydrophobic binding to multilamellar and small unilamellar vesicles (MLVs and SUVs). Native PAGE and fluorescamine analysis of acetylated parental TNF and TNF-SAM2 indicated that these proteins both displayed trimeric structures based on crosslinking/SDS-PAGE analysis and behaved similarly with respect to reactivity of their amino functions. Limited N-terminal sequencing analysis of partially acetylated (approx 3 acetyl groups per trimer) TNF-SAM2 indicated that the N-terminal Val was not modified; this was also concluded based on HPLC/mass spectrometric (LC-MS) analysis of Glu C digests. LC-MS analysis of tryptic digests of the acetylated TNF-SAM2 indicated that Lys-98 was unreactive. Molecular ions corresponding to acetylated Lys-containing peptides for all five other Lys residues could be detected; none appeared hyperreactive, but Lys-11 appeared hyporeactive. MLVs composed of DMPC/DMPG (7:3) and SUVs composed of DPPC/DSPC (1:1) displayed high capacity for binding to caprylated TNF-SAM2. These formulations of caprylated TNF-SAM2 displayed tumor necrotizing and growth-inhibitory activity in a syngeneic tumor model, and may be candidates for clinical development.
Channel engineering for the reduction of random-dopant-placement-induced threshold voltage fluctuation (2002)

A simple model is proposed, which is able to calculate V/sub TH/ standard deviation due to random dopant placement in the channel, for arbitrary vertical impurity distributions. Substantial decrease in V/sub TH/ fluctuation, while keeping V/sub TH/ the same, is confirmed for low surface impurity channel MOSFETs, in agreement with the model prediction.
Anti‐tumour activity of interferon‐alpha in multiple myeloma: role of interleukin 6 and tumor cell differentiation (2003)

Interferon-alpha (IFN-alpha) is a pleotropic cytokine that has clinical activity against a wide variety of malignancies, including multiple myeloma (MM). In vitro, IFN-alpha has diverse effects on both normal and malignant cells, however, the exact mechanisms responsible for its clinical anti-tumour activity remain unclear. We found that IFN-alpha inhibited MM cell proliferation in association with cell cycle arrest at G1 and limited the clonogenic growth of both MM cell lines and primary patient specimens. At the doses tested, IFN-alpha was not cytotoxic, but induced terminal plasma cell differentiation resulting in the loss of clonogenicity. These activities were markedly enhanced by the major MM growth factor interleukin 6 (IL-6). Moreover, IL-6 was required for this process, as neutralizing antibodies against IL-6 inhibited the effects of IFN-alpha. IL-6 also induced MM cell terminal differentiation when combined with a second, unrelated, antiproliferative agent bryostatin-1, suggesting that its differentiating activities are preferentially enhanced in the presence of agents that inhibit cell cycling. These results suggest that the differentiating activities of IFN-alpha may play a role in its clinical antimyeloma activity and provide the rationale for clinical differentiation therapy in MM.
Toward Living Radical Polymerization (2008)

Radical polymerization is one of the most widely used processes for the commercial production of high-molecular-weight polymers. The main factors responsible for the preeminent position of radical polymerization are the ability to polymerize a wide array of monomers, tolerance of unprotected functionality in monomer and solvent, and compatibility with a variety of reaction conditions. Radical polymerization is simple to implement and inexpensive in relation to competitive technologies. However, conventional radical polymerization severely limits the degree of control that researchers can assert over molecular-weight distribution, copolymer composition, and macromolecular architecture. This Account focuses on nitroxide-mediated polymerization (NMP) and polymerization with reversible addition-fragmentation chain transfer (RAFT), two of the more successful approaches for controlling radical polymerization. These processes illustrate two distinct mechanisms for conferring living characteristics on radical polymerization: reversible deactivation (in NMP) and reversible or degenerate chain transfer (in RAFT). We devised NMP in the early 1980s and have exploited this method extensively for the synthesis of styrenic and acrylic polymers. The technique has undergone significant evolution since that time. New nitroxides have led to faster polymerization rates at lower temperatures. However, NMP is only applicable to a restricted range of monomers. RAFT was also developed at CSIRO and has proven both more robust and more versatile. It is applicable to the majority of monomers subject to radical polymerization, but the success of the polymerization depends upon the selection of the RAFT agent for the monomers and reaction conditions. We and other groups have proposed guidelines for selection, and the polymerization of most monomers can be well-controlled to provide minimal retardation and a high fraction of living chains by using one of just two RAFT agents. For example, a tertiary cyanoalkyl trithiocarbonate is suited to (meth)acrylate, (meth)acrylamide, and styrenic monomers, while a cyanomethyl xanthate or dithiocarbamate works with vinyl monomers, such as vinyl acetate or N-vinylpyrrolidone. With the appropriate choice of reagents and polymerization conditions, these reactions possess most of the attributes of living polymerization. We have used these methods in the synthesis of well-defined homo-, gradient, diblock, triblock, and star polymers and more complex architectures, including microgels and polymer brushes. Applications of these polymers include novel surfactants, dispersants, coatings and adhesives, biomaterials, membranes, drug-delivery media, electroactive materials, and other nanomaterials.
Highly attenuated modified vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus propagation, but not in various human transformed and primary cells. (1998)

Although desirable for safety reasons, the host range restrictions of modified vaccinia virus Ankara (MVA) make it less applicable for general use. Propagation in primary chicken embryo fibroblasts (CEF) requires particular cell culture experience and has no pre-established record of tissue culture reproducibility. We investigated a variety of established cell lines for productive virus growth and recombinant gene expression. Baby hamster kidney cells (BHK), a well-characterized, easily maintained cell line, supported MVA growth and as proficient expression of the E. coli lacZ reporter gene as the highly efficient CEF, whereas other cell lines were non-permissive or allowed only very limited MVA replication. Importantly, no virus production occurred in patient-derived infected primary human cells. These results emphasize the safety and now improved accessibility of MVA for the development of expression vectors and live recombinant vaccines.
Multi-style language model for web scale information retrieval (2010)

Web documents are typically associated with many text streams, including the body, the title and the URL that are determined by the authors, and the anchor text or search queries used by others to refer to the documents. Through a systematic large scale analysis on their cross entropy, we show that these text streams appear to be composed in different language styles, and hence warrant respective language models to properly describe their properties. We propose a language modeling approach to Web document retrieval in which each document is characterized by a mixture model with components corresponding to the various text streams associated with the document. Immediate issues for such a mixture model arise as all the text streams are not always present for the documents, and they do not share the same lexicon, making it challenging to properly combine the statistics from the mixture components. To address these issues, we introduce an 'open-vocabulary' smoothing technique so that all the component language models have the same cardinality and their scores can simply be linearly combined. To ensure that the approach can cope with Web scale applications, the model training algorithm is designed to require no labeled data and can be fully automated with few heuristics and no empirical parameter tunings. The evaluation on Web document ranking tasks shows that the component language models indeed have varying degrees of capabilities as predicted by the cross-entropy analysis, and the combined mixture model outperforms the state-of-the-art BM25F based system.
Polymerase Chain Reaction: Basic Protocols (2003)

The melding of a technique for repeated rounds of DNA synthesis with the discovery of a thermostable DNA polymerase has given scientists the very powerful technique known as polymerase chain reaction (PCR). PCR is based on three simple steps required for any DNA synthesis reaction: (1) denaturation of the template into single strands; (2) annealing of primers to each original strand for new strand synthesis; and (3) extension of the new DNA strands from the primers. These reactions may be carried out with any DNA polymerase and result in the synthesis of defined portions of the original DNA sequence. However, in order to achieve more than one round of synthesis, the templates must again be denatured, which requires temperatures well above those that inactivate most enzymes. Therefore, initial attempts at cyclic DNA synthesis were carried out by adding fresh polymerase after each denaturation step (1,2). The cost of such a protocol becomes rapidly prohibitive.
Cyclic olefin homopolymer-based microfluidics for protein crystallization andin situX-ray diffraction (2009)

Microfluidics is a promising technology for the rapid identification of protein crystallization conditions. However, most of the existing systems utilize silicone elastomers as the chip material which, despite its many benefits, is highly permeable to water vapour. This limits the time available for protein crystallization to less than a week. Here, the use of a cyclic olefin homopolymer-based microfluidics system for protein crystallization and in situ X-ray diffraction is described. Liquid handling in this system is performed in 2 mm thin transparent cards which contain 500 chambers, each with a volume of 320 nl. Microbatch, vapour-diffusion and free-interface diffusion protocols for protein crystallization were implemented and crystals were obtained of a number of proteins, including chicken lysozyme, bovine trypsin, a human p53 protein containing both the DNA-binding and oligomerization domains bound to DNA and a functionally important domain of Arabidopsis Morpheus' molecule 1 (MOM1). The latter two polypeptides have not been crystallized previously. For X-ray diffraction analysis, either the cards were opened to allow mounting of the crystals on loops or the crystals were exposed to X-rays in situ. For lysozyme, an entire X-ray diffraction data set at 1.5 A resolution was collected without removing the crystal from the card. Thus, cyclic olefin homopolymer-based microfluidics systems have the potential to further automate protein crystallization and structural genomics efforts.
Atriopeptin Lowers Aqueous Humor Formation and Intraocular Pressure and Elevates Ciliary Cyclic GMP But Lacks Uveal Vascular Effects in the Bovine Perfused Eye (1997)

The effects of atriopeptin (AP) on intraocular pressure (IOP), aqueous humor formation (AHF) and ciliary cyclic GMP in bovine eyes perfused in vitro through a ciliary artery were investigated. AHF was monitored fluorophotometrically by perfusing the anterior chamber with Bárány's mock aqueous humor containing fluorescein. To study the effect of AP on cyclic GMP synthesis, eyes were injected with an intra-arterial bolus of AP prior to dissection of the ciliary processes. For comparison, individual ciliary processes, or isolated ciliary epithelial cells were incubated with AP. Cyclic GMP was extracted by homogenization, aqueous partition and column chromatography, and measured by radioimmunoassay (RIA). Decreases in IOP or AHF were seen approximately 15 min after the injection of AP and persisted throughout a 60-80 min perfusion. Arterial perfusion pressure was not significantly altered by AP, even when vascular tone was raised by adding noradrenaline to the perfusate. In whole eyes, ciliary cyclic GMP increased in response to AP. Cyclic GMP in isolated ciliary processes, or cultured ciliary epithelial cells incubated with AP also increased. We conclude that the decrease in IOP in the bovine eye by AP is due to a reduction in AHF, which is independent of any vascular effect. Ciliary cyclic GMP may be the intracellular mediator involved.
Reducible Dimeric Conjugates of Small Internally Segment Interfering RNA for Efficient Gene Silencing (2016)

The condensation of nucleic acids into compact nanoparticles with cationic carriers is a powerful tool for translocating exogenous nucleic acids into cells. To date, most efforts have been focused on the development of novel gene carriers for safe and efficient gene delivery. However, small interfering RNA (siRNA) is generally not strongly associated with cationic carriers due to its stiff structure and low spatial charge density. To overcome this limitation, this work introduces a well-defined dimeric conjugate of small internally segment interfering RNA (sisiRNA) linked via a disulfide bond for enhanced cellular uptake and gene silencing. Dimeric sisiRNA is synthesized through oxidizing two monomeric sisiRNA molecules, each of which consists of a sense strand carrying a nick and an antisense strand modified with a thiol group at the 3'-end. The nick in the sense strand enables the dimeric sisiRNA to be more effectively condensed into nanosized complexes due to the increased structural flexibility, which results in a higher gene silencing efficiency compared with the dimeric siRNA containing the intact sense strands. The results indicate that the discontinuity of the sense strands is a simple method of adding more flexibility to various siRNA-based nanostructures for enhanced gene silencing.
Monocytes and polymorphonuclear neutrophils of patients with streptococcal pharyngitis express increased numbers of type I IgG Fc receptors. (1990)

Studies using cultured cells have shown that gamma interferon (IFN-gamma) induces the expression of Fc gamma RI (the type I Fc receptor for IgG) on human polymorphonuclear neutrophils (PMN) and greatly increases the number of these receptors on human monocytes. Administration of rIFN-gamma in vivo also causes enhanced Fc gamma RI expression on these cell populations. Because streptococcal antigens are potent inducers of IFN-gamma in vitro, we postulated that IFN-gamma would be produced endogenously in vivo in patients with streptococcal infections. Such production of IFN-gamma in vivo, even at low levels, might be expected to induce the expression of Fc gamma RI on monocytes and neutrophils. To evaluate this possibility, we used monoclonal antibody 32 (mAb 32), which is specific for Fc gamma RI, to quantitate the expression of this receptor on human peripheral blood cells. We measured the binding of mAb 32 to monocytes and PMNs isolated from healthy donors and from patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis. PMNs from healthy donors (n = 12) had 700 +/- 600 (mean +/- SD) mAb 32 binding sites. Patients with pharyngitis and negative throat culture for GABHS (n = 11) had 2,100 +/- 1,600 sites on their PMNs. In contrast, the PMNs from patients with documented GABHS pharyngitis (n = 12) had 11,600 +/- 7,500 mAb 32 binding sites on their surface. There was a similar change in the expression of Fc gamma RI on monocytes, with control monocytes having a mean of 19,900 +/- 3,200 mAb 32 binding sites per cell and the GABHS-positive monocytes having 47,500 +/- 21,400 sites. The GABHS-negative throat culture group had a slightly elevated number of Fc gamma RI with a mean of 28,200 +/- 8,400 sites. 10 patients with documented urinary tract infections and three patients with uncomplicated pyelonephritis had no elevation in Fc gamma RI expression. These studies demonstrate that a localized group A streptococcal infection can cause systemic activation of the entire circulating pool of phagocytes, and suggest that a similar level of activation is uncommon in localized gram-negative infections of the urinary tract.
Calcium receptor is functionally expressed in rat neonatal ventricular cardiomyocytes (2005)

Both intra- and extracellular calcium play multiple roles in the physiology and pathophysiology of cardiomyocytes, especially in stimulus-contraction coupling. The intracellular calcium level is closely controlled through the concerted actions of calcium channels, exchangers, and pumps; however, the expression and function(s) of the so-called calcium-sensing receptor (CaR) in the heart remain less well characterized. The CaR is a seven-transmembrane receptor, which, in response to noncovalent binding of extracellular calcium, activates intracellular effectors, including G proteins and extracellular signal-regulated kinases (ERK1/2). We have shown that cultured neonatal cardiomyocytes express the CaR messenger RNA and the CaR protein. Furthermore, increasing concentrations of extracellular calcium and a type II CaR activator "calcimimetic" caused inositol phosphate (IP) accumulation, downregulated tritiated thymidine incorporation, and supported ERK1/2 phosphorylation, suggesting that the CaR protein is functionally active. Interestingly, the calcimimetic induced a more rapid ERK1/2 phosphorylation than calcium and left-shifted the IP concentration-response curve for extracellular calcium, supporting the hypothesis that CaR is functionally expressed in cardiac myocytes. This notion was underscored by studies using a virus containing a dominant-negative CaR construct, because this protein blunted the calcium-induced IP response. In conclusion, we have shown that the CaR is functionally expressed in neonatal ventricular cardiomyocytes and that the receptor activates second messenger pathways, including IP and ERK, and decreases DNA synthesis. A specific calcium-sensing receptor on cardiac myocytes could play a role in regulating cardiac development, function, and homeostasis.
Spinal-Fusion Surgery — The Case for Restraint (2004)

The use of spinal-fusion surgery is increasing rapidly in the United States. Most of these expensive, complex procedures are now being done for back pain and degenerative disease. Spinal fusions require long operations and are associated with an increase in the rate of complications, particularly in older patients. The benefits of surgery may be only modest, and pain relief is affected by many factors besides the anatomy. The authors of this article argue for restraint in the use of spinal-fusion surgery and for controlled trials to define more clearly the associated benefits and the indications.
Preparation and proton spectra of 1‐aryl‐1,2‐dihydro‐2‐quinolones (1988)

Abstract 1‐Phenyl‐, 1‐ m ‐tolyl‐ and 1‐ p ‐tolyl‐1,2‐dihydro‐2‐quinolone have been prepared by treating the potassium derivative of 1,2‐dihydro‐2‐quinolone with the corresponding aryl bromide in the presence of finely divided copper. The use of o ‐bromotoluene in this reaction gave trace amounts of a crystalline material which upon the basis of mass spectrum analysis was assigned 2‐ o ‐tolyloxyquinoline as a structure. The 1‐aryl groups caused an unusual chemical shift of the 8‐proton to the Δ 6.64–6.70 region. This behavior paralleled that observed for the 7‐proton of 6‐phenyl‐6 H ‐indeno[1,2‐ c ]isoquinoline‐5,11‐dione in earlier studies.
On the mechanism of the hydrogen-induced exfoliation of silicon (1997)

We have investigated the fundamental mechanism underlying the hydrogen-induced exfoliation of silicon, using a combination of spectroscopic and microscopic techniques. We have studied the evolution of the internal defect structure as a function of implanted hydrogen concentration and annealing temperature and found that the mechanism consists of a number of essential components in which hydrogen plays a key role. Specifically, we show that the chemical action of hydrogen leads to the formation of (100) and (111) internal surfaces above 400 °C via agglomeration of the initial defect structure. In addition, molecular hydrogen is evolved between 200 and 400 °C and subsequently traps in the microvoids bounded by the internal surfaces, resulting in the build-up of internal pressure. This, in turn, leads to the observed “blistering” of unconstrained silicon samples, or complete layer transfer for silicon wafers joined to a supporting (handle) wafer which acts as a mechanical “stiffener.”