gebhart/patrepeval huggingface dataset:
Quantitative aspects of the matrix‐assisted laser desorption mass spectrometry of complex oligosaccharides (1993)

Comparative studies of the matrix-assisted laser desorption ionization of complex oligosaccharides were made using a range of mono, di- and tri-substituted benzoic acids, substituted coumarins and cinnamic acids. The best results were obtained with 2,5-dihydroxybenzoic acid (2,5-DHB). Detection limits using this matrix were in the range of 100 fmol for complex and high mannose sugars, some 2-fold better than those obtained with alpha-cyano-4-hydroxycinnamic acid and 10-fold better than with an earlier oligosaccharide matrix, 3-amino-4-hydroxybenzoic acid. The strongest signals were achieved with a matrix-to-sample ratio of about 5000:1. Little correlation was found between the measured peak height and sample loading when 3-amino-4-hydroxybenzoic acid was used as the matrix and the signal appeared to saturate at a sample level of around 30 pmol. However, good correlation was found between the amount of sample loaded onto the target and the response when an analogous compound was used as an internal standard and peak ratios were measured. In contrast to this, the use of 2,5-dihydroxybenzoic acid as the matrix enabled the oligosaccharide to be measured over the range 100 fmol to at least 100 pmol with an excellent linear correlation between sample quantity and response and without the need of a standard. No evidence of saturation was found with this matrix. With 2,5-DHB (other matrices were not tested), the oligosaccharide signal strength was found to fall with increasing molecular weight in a linear manner and similar to that found previously with proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of MAP Kinase Kinase Blocks the Differentiation of PC-12 Cells Induced by Nerve Growth Factor (1995)

The mitogen-activated protein kinase (MAP kinase) pathway is thought to play an important role in the actions of neurotrophins. A small molecule inhibitor of the upstream kinase activator of MAP kinase, MAP kinase kinase (MEK) was examined for its effect on the cellular action of nerve growth factor (NGF) in PC-12 pheochromocytoma cells. PD98059 selectively blocks the activity of MEK, inhibiting both the phosphorylation and activation of MAP kinases in vitro. Pretreatment of PC-12 cells with the compound completely blocked the 4-fold increase in MAP kinase activity produced by NGF. Half-maximal inhibition was observed at 2 microM PD98059, with maximal effects at 10-100 microM. The tyrosine phosphorylation of immunoprecipitated MAP kinase was also completely blocked by the compound. In contrast, the compound was without effect on NGF-dependent tyrosine phosphorylation of the pp140trk receptor or its substrate Shc and did not block NGF-dependent activation of phosphatidylinositol 3'-kinase. However, PD98059 completely blocked NGF-induced neurite formation in these cells without altering cell viability. These data indicate that the MAP kinase pathway is absolutely required for NGF-induced neuronal differentiation in PC-12 cells.
Types and programming languages: the next generation (2003)

Summary form only given. This tutorial surveys the state of the art in type systems for programming languages, focusing on the achievements and changes in emphasis during the past decade. The first part of the talk considers the trajectory of work on object types, one of the major hot topics of the early and mid-'90s. Following some fundamental conceptual breakthroughs, the focus of attention in this area has shifted from foundational research to applications to the development and analysis of real-world language designs. The next part outlines recent progress on a number of "bread and butter" type systems topics and their applications in new programming languages: subtyping, polymorphism, type inference, effect systems, dependent types, and type systems for modular programming. The final section introduces some newer topics that have emerged (or gained unexpected prominence) in the past few years, including type systems for concurrent and distributed languages, high-level type systems for low-level languages such as assembly and C, substructural type systems based on linear logic and its relatives, modal type systems, the burgeoning area of language-based security, and native language support for statistically typed XML processing.
Mutational analysis of the autoinhibitory domain of calmodulin kinase II. (1994)

Calmodulin (CaM)-kinase II is inactive in the absence of Ca2+/CaM due to interaction of its autoinhibitory domain with its catalytic domain. Previous studies using synthetic autoinhibitory domain peptides (residues 281-302) identified several residues as important for inhibitory potency and suggested that His282 may interact with the ATP-binding motif of the catalytic domain. To further examine the autoinhibitory domain, site-specific mutants were expressed using the baculovirus/Sf9 cell system. The purified mutants had many biochemical properties identical to wild-type kinase, but mutants H282Q, H282R, R283E, and T286D had 10-20% constitutive Ca(2+)-independent activities, indicating that these residues are involved in the autoinhibitory interaction. The Ca(2+)-independent activities of the H282Q, H282R, and R283E mutants exhibited 10-fold lower Km values for ATP than the wild-type kinase. Wild-type and mutant kinases, except T286A and T286D, generated Ca2+ independence upon autophosphorylation in the presence of Ca2+/CaM, and those mutants having constitutive Ca2+ independence also exhibited enhanced Ca2+/CaM-independent autophosphorylation. This Ca(2+)-independent autophosphorylation resulted in a decrease in total kinase activity, but there was little increase in Ca(2+)-independent activity, consistent with autophosphorylation of predominantly Thr306 rather than Thr286. These results are consistent with an inhibitory interaction of His282 and possibly Arg283 with the ATP-binding motif of the catalytic domain, and they indicate that constitutively active CaM-kinase II cannot autophosphorylate on Thr286 in the absence of bound Ca2+/CaM. Based on these and other biochemical characterizations, we propose a molecular model for the interaction of a bisubstrate autoinhibitory domain with the catalytic domain of CaM-kinase II.
Second and third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer (2015)

Second-generation EGFR-TKI, afatinib, is available as first-line treatment of advanced NSCLC harboring activating EGFR mutations. Third-generation EGFR-TKIs are under development for tumors harboring acquired EGFR T790 M.
Cytokines and neuronal differentiation. (1995)

A diverse spectrum of complementary experimental investigations has demonstrated that two major cytokine superfamilies, the transforming growth factor-beta (TGF beta) and the hemopoietins, mediate an extensive range of developmental events in the nervous system that often rivals and frequently exceeds that of the classic neurotrophins. The exponential growth in the identification and physiological analysis of TGF beta subclasses of cytokines that transduce intracellular signals through intrinsic membrane serine/threonine kinase-associated receptor subunits has led to an increased understanding of their complex cellular actions in programming the temporospatial expression and maturation of anatomically distinct neuronal subpopulations. An analysis of the developmental parallels that exist between neural development and hematolymphopoiesis has fostered an expansion in the identification and classification of cellular actions of hematolymphopoietic cytokines that are also active during neural development. During the process of neural maturation, it has also become apparent that an extensive range of cell surface-associated and intracellular signalling molecules that are essential for hematopoietic and immunological development may also represent an important set of effector molecules that are active during neuronal differentiation. These recent advances in cell and molecular biology have allowed us to begin to construct an integrated model of the developmental signalling pathways and diverse cellular processes that are necessary for graded stages of neuronal maturation. These cumulative observations suggest that a dynamic hierarchy of epigenetic and genetic signals is essential for the growth, survival, and maturation of regional neuronal subpopulations that are derived from multipotent progenitor species within the central and peripheral nervous systems.
자궁경부암에서 HPV-16 단백질을 이용한 혈청내 진단물질의 임상적 효용성 (1997)

과거 자궁경부암의 종양 표지물질로 사용되어 왔던 carcinoembryonic antigen(CEA)나 squamous cell carcinoma(SCCA)은 자궁경부암의 진단과 임상기의 진행과의 연관에 대한 다양한 논란이 있으며 그들의 입상적 유용성과 그 한계에 대해서는 이미 알려진 바이며, 실질적인 유용성을 지닌 종양 표지물질의 개발이 절실하게 요구되고 있다. 이에 본 연구진은 자궁경부암 환자에서 SCCA,CEA에 대한 혈청내 항체반응과 분자생물학적 방법으로 baculovirus를 이용한 재조합된 HPV-16 L1/L2 VLPs와 in vitro translated HPV-16 E6, E7 단백질에 대한 혈청내 향체반응을 관찰하고 비교함으로써 자궁경부암에서 HPV-16 L1/L2 VLPs와 HPV-16 E6,E7 단백질의 진단물질과 종양 표지물질로서 임상적 가치를 검토하였다. 자궁경부암 전구병변 환자 28명과 자궁경부암 환자 124명을 대상으로 시행한 실험연구에서 HPV-16 L1/L2 VLPs, HPV-16 E6,E7 단백질과 SCCA,CEA에 대한 항체양성율은 자궁경부암 전구병변과 자궁경부암 환자들에서 각각 39%/56%, 7%/51%, 11%/33%와 0%/34%, 0%/18%로 나타나서 HPV-16 E6 항원은 자궁경부암 환자에서 50%이상의 높은 양성율을 나타냈으며, HPV-16 E7 항원과 SCCA에 대한 양성율은 CEA의 값에 비해 유의하여 높게 나타났다. 자궁경부암 환자에서 HPV DNA 아형에 따른 상기 항원들에 대한 항체양성 값은 PCR로 HPV-16 DNA에 양성인 경우에 HPV-16 L1/L2 VLPs와 HPV-16 E6에 대한 항체 값은 각각 55%(55/100)에서,HPV-16 E7에 대해서는 32%(32/100)에서 양성으로 나타났다. 또한, 다른 HPV 아형에만 양성인 경우와 HPV가 발견되지 않은 환자에서는 HPV-16 L1/L2 VLPs, HPV-16 E6,E7 단백질에 대해 각각 63%(15/24),37%(9/24),37%(9/24)에서 양성으로 나타나서 HPV 아형에 따른 항체의 특이성은 관찰할 수 없었다. 자궁경부암의 임상기 변화에 따른 항체 값의 변화를 치료 후 추적관찰에 따라 나타난 임상경과에 따른 종양 표지물질로서의 가치를 평가할 때 CEA의 항체값은 의미있는 변화가 없었으나, SCCA는 임상기가 증가할 수록 양성율이 높아짐을 알 수 있었다. HPV-16 L1/L2 VLPs,HPV-16 E6,E7 단백질에 대한 항체의 혈중 값은 자궁경부암 환자들에서 진단 물질로서의 임상적 가치를 지닌 항원단백질로 밝혀졌으며, 이들에 대한 항체값은 임상기가 진행됨에 따라 유의하게 높게 관찰되었다. 자궁경부암 환자들에서 21명은 치료 전후의 임상상태를 추적 평가할 수 있었고, 그들 중 14명은 병소의 완전소실을 가져왔으며, 7명은 잔류병변이 진형되거나 재발되었다. 또한, 이들에서 혈청을 채취하여 상기의 항원들에 대한 연속적인 항체 값을 측정함으로써 종양의 치료반응 결과와 비교할 수 있었다. 병소의 완전소실이 있었던 14명 중 8명에서 HPV-16 L1/L2 VLPs, HPV-16 E6,E7 단백질에 대한 항체의 혈중 값은 감소하였으나, SCCA와 CEA가 감소된 경우는 없었다. 병변이 진행되거나 재발된 7명에서는 HPV-16 E7 단백질에 대해 6명에서 항체값이 증가한 반면, 나머지 상기 항원들에 대한 항체값의 증가는 유의하게 관찰되지 않았다. 이상의 결과로 자궁경부암 환자에서 사용되었던 기종의 종양 표지물질인 SCCA,CEA의 임상적 효용성과 비교하여 볼 때 자궁경부암 환자에서 HPV-16 L1/L2 VLPs, HPv-16 E6,E7 항원에 대한 항체측정이 질환의 진단을 예측할 수 있는 보조적인 인자로서 도움을 줄 것이며, 특히 HPV-16 E7 단백항원은 재발의 예측 및 치료평가에 효과적인 종양표지물질로 이용될 수 있으리라 생각된다. 이와같이 직접적으로 임상적인 상태를 반영할 수 있는 자궁경부암을 유발시키는 HPV 단백질의 개발연구와 그들의 임상적인 도입은 자궁경부암의 조기진단과 추적관리에 큰 기여를 할 수 있을 것으로 보이며, 향후 자궁경부암과 연관된 연구에 기본적인 자료로서 가치가 있을 것으로 사료된다.
The value of provoked expectoration in obtaining sputum samples for cytologic investigation. A prospective, consecutive and controlled investigation of 134 patients. (1985)

A prospective controlled investigation in 134 consecutive outpatients compared the cytologic adequacy of sputum samples obtained by spontaneous and provoked expectoration. Inhalation of nebulized 10% sodium chloride was used for provoked expectoration. A significantly higher number of adequate samples was produced after provocation, as judged by the presence of alveolar macrophages (X2 = 5.63; p less than 0.02). The improvement in sample adequacy was limited to the nonsmokers and ex-smokers in the study. This result, together with the relatively high cost of cytologic sputum examinations, indicates that provoked expectoration should at least be applied to the collection of sputum samples from nonsmokers and ex-smokers.
Detection and identification of bacteria intimately associated with fungi of the orderSebacinales (2008)

Because of their beneficial impact on plants, the highly diverse mycorrhizal fungi grouped in the order Sebacinales lay claim to high ecological and agricultural significance. Here, we describe for the first time associations of Sebacinoid members with bacteria. Using quantitative PCR, denaturating gradient gel electrophoresis and fluorescence in situ hybridization, we detected an intimate association between Piriformospora indica and Rhizobium radiobacter, an alpha-Proteobacterium. The stability of the association, vertical transmission of the bacteria during asexual fungal reproduction and fungal plant colonization was monitored using R. radiobacter-specific primers. Treatment of mycelium or fungal protoplasts with antibiotics highly efficient against the free bacteria failed to cure the fungus. Barley seedlings dip-inoculated with R. radiobacter showed growth promotion and systemic resistance to the powdery mildew fungus Blumeria graminis comparable to P. indica inoculation. By screening additional isolates of the Sebacina vermifera complex, three species-specific associations with bacteria from the genera Paenibacillus, Acinetobacter and Rhodococcus were found. These findings suggest that Sebacinales species regularly undergo complex interactions involving host plants and bacteria reminiscent of other ectomycorrhizal and endomycorrhizal associations.
A Cerulenin Insensitive Short Chain 3-Ketoacyl-Acyl Carrier Protein Synthase in Spinacia oleracea Leaves (1989)

A cerulenin insensitive 3-ketoacyl-acyl carrier protein synthase has been assayed in extracts of spinach (Spinacia oleracea) leaf. The enzyme was active in the 40 to 80% ammonium sulfate precipitate of whole leaf homogenates and catalyzed the synthesis of acetoacetyl-acyl carrier protein. This condensation reaction was five-fold faster than acetyl-CoA:acyl carrier protein transacylase, and the initial rates of acyl-acyl carrier protein synthesis were independent of the presence of cerulenin. In the presence of fatty acid synthase cofactors and 100 micromolar cerulenin, the principal fatty acid product of de novo synthesis was butyric and hexanoic acids. Using conformationally sensitive native polyacrylamide gel electrophoresis for separation, malonyl-, acetyl-, butyryl-, hexanoyl, and long chain acyl-acyl carrier proteins could be detected by immunoblotting and autoradiography. In the presence of 100 micromolar cerulenin, the accumulation of butyryl- and hexanoyl-acyl carrier protein was observed, with no detectable long chain acyl-acyl carrier proteins or fatty acids being produced. In the absence of cerulenin, the long chain acyl-acyl carrier proteins also accumulated.
Hyaluronic Acid Gel (Restylane) Filler for Facial Rhytids: Lessons Learned From American Society of Ophthalmic Plastic and Reconstructive Surgery Member Treatment of 286 Patients (2006)

Injection techniques, volume, end points, and anesthesia vary for different facial areas and between practices. Patients experience mild to moderate injection discomfort that is lessened with injectable lidocaine. Self-limited problems occur in about 5% of patients. Physician-determined patient satisfaction is perceived to be higher than that of collagen injection but slightly lower than that of botulinum toxin injection. The major source of Restylane patients was from existing practice patients, especially botulinum toxin patients.
RPS2 of Arabidopsis thaliana : a Leucine-Rich Repeat Class of Plant Disease Resistance Genes (1994)

Plant disease resistance genes function is highly specific pathogen recognition pathways. PRS2 is a resistance gene of Arabidopsis thaliana that confers resistance against Pseudomonas syringae bacteria that express avirulence gene avrRpt2. RPS2 was isolated by the use of a positional cloning strategy. The derived amino acid sequence of RPS2 contains leucine-rich repeat, membrane-spanning, leucine zipper, and P loop domains. The function of the RPS2 gene product in defense signal transduction is postulated to involve nucleotide triphosphate binding and protein-protein interactions and may also involve the reception of an elicitor produced by the avirulent pathogen.
Diphtheria toxin-murine granulocyte-macrophage colony-stimulating factor–induced hepatotoxicity is mediated by Kupffer cells (2004)

DT388GMCSF, a fusion toxin composed of the NH2-terminal region of diphtheria toxin (DT) fused to human granulocyte-macrophage colony-stimulating factor (GMCSF) has shown efficacy in the treatment of acute myeloid leukemia. However, the primary dose-limiting side effect is liver toxicity. We have reproduced liver toxicity in rats using the rodent cell-tropic DT-murine GMCSF (DT390mGMCSF). Serum aspartate aminotransferase and alanine aminotransferase were elevated 15- and 4-fold, respectively, in DT390mGMCSF-treated rats relative to controls. Histologic analysis revealed hepatocyte swelling; however, this did not lead to hepatic necrosis or overt histopathologic changes in the liver. Immunohistochemical staining showed apoptotic cells in the sinusoids, and depletion of cells expressing the monocyte/macrophage markers, ED1 and ED2, indicating that Kupffer cells (KC) are targets of DT390mGMCSF. In contrast, sinusoidal endothelial cells seemed intact. In vitro, DT390mGMCSF was directly cytotoxic to primary KC but not hepatocytes. Two related fusion toxins, DT388GMCSF, which targets the human GMCSF receptor, and DT390mIL-3, which targets the rodent IL-3 receptor, induced a less than 2-fold elevation in serum transaminases and did not deplete KC in vivo. In addition, DTU2mGMCSF, a modified form of DT390mGMCSF with enhanced tumor cell specificity, was not hepatotoxic and was significantly less toxic to KC in vivo and in vitro. These results show that DT390mGMCSF causes liver toxicity by targeting KC, and establish a model for studying how this leads to hepatocyte injury. Furthermore, alternative fusion toxins with potentially reduced hepatotoxicity are presented.
Interactions between cancer cells and the endothelium in metastasis (2000)

The haematogenous phase of cancer metastasis facilitates the transport of metastatic cells within the blood and incorporates a sequence of interactions between circulating intravascular cancer cells and the endothelium of blood vessels at the sites of tumour cell arrest. Initial interactions involve mechanical contact and transient adhesion, mediated by endothelial selectins and their ligands on the neoplastic cells. This contact initiates a sequence of activation pathways that involves cytokines, growth factors, bioactive lipids, and reactive oxygen species produced by either the cancer cell or the endothelium. These molecules elicit expression of integrin adhesion molecules in cancer cells and the endothelium, matrix metalloproteinases, and chemotactic factors that promote the attachment of tumour cells to the vessel wall and/or transvascular penetration. Induction of endothelial free radicals can be cytotoxic to cancer cells. Collectively, the sum of these interactions constitutes an interdependent relationship, the outcome of which determines the fate of the metastatic process.
A log-linear discriminative modeling framework for speech recognition. (2010)

Conventional speech recognition systems are based on Gaussian hidden Markov models (HMMs).Discriminative techniques such as log-linear modeling have been investigated in speech recognition only recently. This thesis establishes a log-linear modeling framework in the context of discriminative training criteria, with examples from continuous speech recognition, part-of-speech tagging, and handwriting recognition. The focus will be on the theoretical and experimental comparison of different training algorithms. Equivalence relations for Gaussian and log-linear models in speech recognition are derived. It is shown how to incorporate a margin term into conventional discriminative training criteria like for example minimum phone error (MPE). This permits to evaluate directly the utility of the margin concept for string recognition. The equivalence relations and the margin-based training criteria lead to a unified view of three major training paradigms, namely Gaussian HMMs, log-linear models, and support vector machines (SVMs). Generalized iterative scaling (GIS) is traditionally used for the optimization of log-linear models with the maximum mutual information (MMI) criterion. This thesis suggests an extension of GIS to log-linear models including hidden variables, and to other training criteria (e.g. MPE). Finally, investigations on convex optimization in speech recognition are presented. Experimental results are provided for a variety of tasks, including the European Parliament plenary sessions task and Mandarin broadcasts.
Sleep Quality in Chronic Pain Patients (2002)

Chronic pain patients suffer from poor sleep quality--a function of depressed mood rather than pain intensity, duration, or anxiety. However, it is difficult to draw a causal relation in this relatively small sample size. Besides, our study sample comprised a mostly psychiatric population and may not represent the general group of patients with chronic pain.
Human plasma platelet-activating factor acetylhydrolase. Purification and properties. (1987)

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a biologically active phospholipid synthesized by a variety of cell types upon appropriate stimulation. PAF is a potent hypotensive factor and it activates platelets and inflammatory cells at concentrations as low as 10(-10) M. Removal of the acetyl moiety at the sn-2 position abolishes the biological activity and this reaction is catalyzed by a specific acetylhydrolase present in plasma and animal tissues. Ultracentrifugation in density gradients showed that 30% of the activity is associated with high density lipoproteins and 70% with low density lipoproteins. We have purified the plasma low density lipoprotein-associated activity to near homogeneity using a rapid assay based on the separation of [3H]acetate from 1-O-alkyl-2-[3H]acetyl-sn-glycerol-3-phosphocholine on disposable reversed-phase columns. The enzyme was purified by 25,000-fold and approximately 10% of the starting activity was recovered. Plasma PAF-acetylhydrolase has an apparent molecular weight of 43,000, does not require calcium, has preference for micellar versus monomeric substrate, and exhibits surface dilution kinetics. The purified protein has an apparent Km of 13.7 microM and a Vmax of 568 mumol/h/mg with micellar PAF. It can act both on 1-O-alkyl and 1-acyl substrates and on ethanolamine analogs of PAF. However, the enzyme has a marked preference for the sn-2 acetyl residue and therefore can be considered as a specific PAF-acetylhydrolase.
Statistical color models with application to skin detection (2003)

The existence of large image datasets such as photos on the World Wide Web make it possible to build powerful generic models for low-level image attributes like color using simple histogram learning techniques. We describe the construction of color models for skin and non-skin classes from a dataset of nearly 1 billion labeled pixels. These classes exhibit a surprising degree of separability which we exploit by building a skin pixel detector that achieves an equal error rate of 88%. We compare the performance of histogram and mixture models in skin detection and find histogram models to be superior in accuracy and computational cost. Using aggregate features computed from the skin detector we build a remarkably effective detector for naked people. We believe this work is the most comprehensive and detailed exploration of skin color models to date.