gebhart/patrepeval huggingface dataset:
BCR-ABLalternative splicing as a common mechanism for imatinib resistance: evidence from molecular dynamics simulations (2008)

Rare cases of chronic myelogenous leukemia (CML) express high levels of alternatively spliced BCR-ABL mRNA with a 35-bp insertion (35INS) between ABL kinase domain exons 8 and 9. This insertion results in a frameshift leading to the addition of 10 residues and truncation of 653 residues due to early termination. Sensitive PCR-based testing showed that 32 of 52 (62%) imatinib-resistant CML patients in chronic phase and 8 of 38 (21%) in accelerated or blast crisis expressed varying levels of the alternatively spliced BCR-ABL mRNA. A three-dimensional structural model of the 35INS ABL kinase domain complexed with imatinib was built using homology modeling, followed by molecular dynamics simulations. Simulation results showed that the new residues cause a significant global conformational change, altering imatinib binding in a way similar to that of the T315I mutation and, therefore, providing resistance to imatinib that depends on the level of expression.
Novel Functional Biodegradable Polymer:  Synthesis and Anticoagulant Activity of Poly(γ-Glutamic Acid)sulfonate (γ-PGA-sulfonate) (2001)

gamma-Poly(glutamic acid) (gamma-PGA), which is produced by Bacillus subtilis, was sulfonated using 2-aminoethane-1-sulfonic acid (taurine) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC) to give sulfonated gamma-PGA (gamma-PGA-sulfonate). From (1)H NMR spectroscopy and IR spectroscopy, it was confirmed that taurine was introduced to the side chain of gamma-PGA via an amide linkage. By altering the synthetic conditions, it was possible to control the content of sulfonate in gamma-PGA-sulfonate. Anticoagulant activity was investigated in order to evaluate the biological activity of gamma-PGA-sulfonate by the Lee-White test. The clotting time was prolonged when the concentration of gamma-PGA-sulfonate on the degree of sulfonation was increased. It becomes clear that gamma-PGA-sulfonate is potentially useful for various medical applications, such as drug delivery, tissue engineering, and medical materials.
Analysis of human tumor associated Thomsen-Friedenreich antigen. (1990)

The Thomsen-Friedenrich (TF) antigen is a precursor structure of MN blood group antigens and is also expressed by about 90% of human carcinomas. The immunodominant group of TF antigen [beta-galactosyl(1-3)-alpha-N-acetylglactosamine] is present in cryptic form in normal RBC and is revealed by neuraminidase treatment. A murine monoclonal antibody (Mab 49H.8) developed against neuraminidase treated human RBC was reactive against a variety of human tumors. We have characterized the human tumor associated TF antigen detected by this antibody from a human transitional bladder carcinoma cell line (647V), a human colon adenocarcinoma cell line (LS174T), and a pleural effusion fluid of a breast adenocarcinoma patient (PE 89). A heterologous sandwich radioimmunoassay for TF antigen was developed using Mab 49H.8 as the catcher and 125I-peanut agglutinin as the probe. Detergent extracts of 647V and LS174T cells, media conditioned by culturing these cells, and PE 89 were shown to contain the antigen by this assay. The specificity of the antigen capture by Mab 49H.8 in this assay was demonstrated by its selective inhibition by nitrophenyl-beta-D-galactoside, phenyl-beta-D-galactoside, and a TF hapten. Preliminary studies on TF antigen in serum samples using this assay showed that about 53.7% of the carcinoma samples contained an antigen concentration greater than 200 units/ml whereas for 90.9% of the normal samples the antigen concentration was below 200 units/ml. These studies demonstrated that the TF antigen is shed by the tumor cells both in vitro and in vivo. The TF antigen was sensitive to treatment with alkali (0.1 M NaOH for 5 h at 37 degrees C) and periodate (10 mM sodium periodate for 1 h at room temperature), was resistant to acidic pH (50 mM acetate buffer, pH 4.5, for 5 h at 37 degrees C), and could be extracted with perchloric acid (0.6 M for 1 h at 4 degrees C). The antigen was shown to be a high molecular weight glycoprotein (Mr greater than 1,000,000) by gel filtration chromatography. The density of the antigen was estimated to be about 1.35 g/ml by cesium chloride density gradient centrifugation. The antigen could be isolated from conditioned media by a combination of affinity chromatography and gel filtration with an overall purification of about 61,432-fold and a final recovery of 53.2%.(ABSTRACT TRUNCATED AT 400 WORDS)
HMAC-based Extract-and-Expand Key Derivation Function (HKDF) (2010)

This document specifies a simple Hashed Message Authentication Code (HMAC)-based key derivation function (HKDF), which can be used as a building block in various protocols and applications. The key derivation function (KDF) is intended to support a wide range of applications and requirements, and is conservative in its use of cryptographic hash functions.
Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. (2006)

Addition of dexamethasone to bortezomib in patients with relapsed and/or refractory myeloma who had suboptimal responses to bortezomib alone was associated with improvement in responses without prohibitive toxicity.
Paranasal Sinus Mucormycosis: a Report of Two Cases (2001)

Mucormycosis of the nose and paranasal sinuses is a rare invasive fungal infection, which often has a very fulminant course and characteristic clinical findings. The patients are usually immunocompromised, with diabetic ketoacidosis being the commonest underlying disorder. In some immunocompetent patients, the disease is associated with local predisposing factors, such as chronic sinusitis. Although the prognosis has improved in recent decades, the disease can still be fatal. The underlying disease is an important determinant of prognosis and correction of the metabolic disorder, if present, is essential. Herein we report two cases: one of our patients was immunocompetent but had earlier suffered from polypous rhinosinusitis whereas the other had mild adult-type diabetes. Both patients were successfully treated with surgical debridement and amphotericin B.
Germanium photodetectors on amorphous substrates for electronic-photonic integration (2016)

A germanium photodetector is fabricated on silicon dioxide at low temperature in order to demonstrate monolithic compatibility with back-end-of-line CMOS manufacturing. Final MSM photodetectors demonstrate net gain with an internal quantum efficiency greater than 100%.
Mitochondrial proteome: Cancer‐altered metabolism associated with cytochrome c oxidase subunit level variation (2004)

Shifts in metabolism associated with tumorigenesis were first noted by Otto Warburg in the 1920s. In the ensuing decades many examples of the phenomenon have been elucidated while the underlying molecular mechanism has remained elusive. As the enzyme complex at the crux of oxidative phosphorylation, cytochrome c oxidase is uniquely positioned to have a very high impact on cellular metabolism. In this study, we test the hypothesis that there is a specific association between altered cytochrome c oxidase subunit levels and altered metabolism by combining the technique of reverse-phase protein microarray with radiolabeled glucose metabolic studies. Such a relationship is observed with five different cell lines, two of which (1542N and 1542T) are a matched set of normal and tumor-based lineages derived from the same prostate gland. By measuring the [(14)C]carbon dioxide production of a cell line metabolizing [1-(14)C]glucose and comparing those measurements to values obtained for the same cell line metabolizing [6-(14)C]glucose, we determined the relative utilization of the hexose monophosphate shunt and glycolysis progressing through the Krebs cycle metabolic pathway in each cell line. In all cases there is an increased utilization of hexose monophosphate shunt relative to glycolysis progressing through the Krebs cycle in tumor derived relative to normal derived cell lines. Additionally, there is an associated increase in the ratio of nuclear encoded cytochrome c oxidase subunits to mitochondrially encoded cytochrome c oxidase subunits in the tumor-derived cell lines. These results demonstrate an alteration in subunit levels of a single enzyme complex (cytochrome c oxidase) commensurate with tumor-altered metabolism.
La Désamidation Enzymatique De L'asparagine Chez Les Différentes Espéces Animales Et La Signification Physio Logique De Sa Presence Dans L'organisme (1922)

au mois d'avril 1 9 1 (4).
Chronic obstructive pulmonary disease * 12: New treatments for COPD (2003)

Drugs currently available or under development for the treatment of chronic obstructive pulmonary disease (COPD) are reviewed. More research on the basic cellular and molecular mechanisms of COPD and emphysema is urgently needed to aid the logical development of new treatments for this common and important disease for which no effective preventative treatments currently exist.

There is a major need to develop new treatments for chronic obstructive pulmonary disease (COPD), as no currently available drug therapy reduces the relentless progression of the disease. In particular, there is a need to develop drugs that control the underlying inflammatory and destructive processes. There have been few therapeutic advances in the drug treatment of COPD, in contrast to the enormous advances made in asthma management which reflect a much better understanding of the underlying disease.1–3 Although COPD is commonly treated with drugs developed for asthma, this is often inappropriate as the inflammatory processes in the two conditions differ markedly.4,5 Recognition of the global importance and rising prevalence of COPD and the absence of effective treatments has now led to a concerted effort to develop new drugs for this disease.6,7

Rational treatment depends on understanding the underlying disease process and there have been recent advances in understanding the cellular and molecular mechanisms that may be involved. COPD involves a chronic inflammation in the small airways and lung parenchyma with the involvement of neutrophils, macrophages, and cytotoxic (CD8+) T lymphocytes. This inflammation results in fibrosis with narrowing of the small airways (chronic obstructive bronchitis) and lung parenchymal destruction due to the action of various proteases such as neutrophil elastase and matrix metalloproteinases (emphysema). This inflammation is quite different from that seen in asthma, indicating that different treatments are likely to be needed.4

There are several reasons why drug …
A double-blind, vehicle-controlled study of the safety and efficacy of Fungoid Tincture in patients with distal subungual onychomycosis of the toes. (1994)

Onychomycosis is one of the most common causes of nail disease and one of the hardest to treat among fungal infections. A double-blind, vehicle-controlled study has been conducted to evaluate the safety and efficacy of Fungoid Tincture (Pedinol Pharmacal, Inc), for the treatment of fungal infection of the toenails. Ten patients with distal subungual onychomycosis were treated for twelve months with topical Fungoid Tincture. Another ten patients with the same ailment were treated with the vehicle alone. Once a month, clinical and global evaluation of the target nail was done, in addition to trimming and debridement of the nails. After twelve months of treatment, 90 percent of patients applying Fungoid Tincture showed negative results on culture. There were minimal adverse effects.
Application of monoclonal antibody 44‐3A6 in the cytodiagnosis and classification of pulmonary carcinomas (1985)

Thirty-five pulmonary carcinomas were studied retrospectively with monoclonal antibody (MCA) 44-3A6 raised against a human adenocarcinoma cell line. The antibody was applied to cytologic smears of bronchial brushings originally stained with the Papanicolau method, and to conventional tissue sections. Ten of 12 adenocarcinomas (ADC) immunostained strongly in sections and smears, as did five of seven large-cell "undifferentiated" carcinomas (LCUC). Eight neuroendocrine carcinomas (NEC) and eight squamous-cell carcinomas (SCC) were negative, except for rare weakly positive foci. We conclude that MCA 44-3A6 can be effectively applied on cytologic smears, and that it could be valuable in the precise classification of pulmonary carcinomas. The immunoreactivity of the ADC and SCC was predictable. Positive immunostaining in some LCUC confirms that these constitute a heterogeneus tumor class that includes cases that are phenotypically ADC despite the absence of obvious glands. Occasional immunostaining in NEC suggests focal exocrine differentiation as previously noted by electron microscopy.
Photosensitive Self-Assembled Monolayers on Gold: Photochemistry of Surface-Confined Aryl Azide and Cyclopentadienylmanganese Tricarbonyl (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotosensitive Self-Assembled Monolayers on Gold: Photochemistry of Surface-Confined Aryl Azide and Cyclopentadienylmanganese TricarbonylEric W. Wollman, Doris Kang, C. Daniel Frisbie, Ivan M. Lorkovic, and Mark S. WrightonCite this: J. Am. Chem. Soc. 1994, 116, 10, 4395–4404Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/ja00089a030https://doi.org/10.1021/ja00089a030research-articleACS PublicationsRequest reuse permissionsArticle Views1036Altmetric-Citations139LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Elevated HDL Cholesterol Is a Risk Factor for Ischemic Heart Disease in White Women When Caused by a Common Mutation in the Cholesteryl Ester Transfer Protein Gene (2000)

Increased HDL cholesterol levels caused by mutations in CETP are associated with an increased risk of ischemic heart disease in white women.
Studies of selective TNF inhibitors in the treatment of brain injury from stroke and trauma: a review of the evidence to date (2014)

The brain is very actively involved in immune-inflammatory processes, and the response to several trigger factors such as trauma, hemorrhage, or ischemia causes the release of active inflammatory substances such as cytokines, which are the basis of second-level damage. During brain ischemia and after brain trauma, the intrinsic inflammatory mechanisms of the brain, as well as those of the blood, are mediated by leukocytes that communicate with each other through cytokines. A neuroinflammatory cascade has been reported to be activated after a traumatic brain injury (TBI) and this cascade is due to the release of pro- and anti-inflammatory cytokines and chemokines. Microglia are the first sources of this inflammatory cascade in the brain setting. Also in an ischemic stroke setting, an important mediator of this inflammatory reaction is tumor necrosis factor (TNF)-α, which seems to be involved in every phase of stroke-related neuronal damage such as inflammatory and prothrombotic events. TNF-α has been shown to have an important role within the central nervous system; its properties include activation of microglia and astrocytes, influence on blood-brain barrier permeability, and influences on glutamatergic transmission and synaptic plasticity. TNF-α increases the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor density on the cell surface and simultaneously decreases expression of γ-aminobutyric acid receptor cells, and these effects are related to a direct neurotoxic effect. Several endogenous mechanisms regulate TNF-α activity during inflammatory responses. Endogenous inhibitors of TNF include prostaglandins, cyclic adenosine monophosphate, and glucocorticoids. Etanercept, a biologic TNF antagonist, has a reported effect of decreasing microglia activation in experimental models, and it has been used therapeutically in animal models of ischemic and traumatic neuronal damage. In some studies using animal models, researchers have reported a limitation of TBI-induced cerebral ischemia due to etanercept action, amelioration of brain contusion signs, as well as motor and cognitive dysfunction. On this basis, it appears that etanercept may improve outcomes of TBI by penetrating into the cerebrospinal fluid in rats, although further studies in humans are needed to confirm these interesting and suggestive experimental findings.
Scheduling Analysis of the Micro Channel Architecture for Multimedia Applications (1994)

In recent years, faed priorily real-time scheduling hus inude significant advances. These udvances ha vc becrr upplied primarily to CPU scheduling. While CPlJ scheduling is an important aspect of red-time designs. other shured system resources require the sume cllienlion in order ,for U system to transfer red-time trufic. This puper tiddresses one such resource, lhe system bus, und pre.scwt.r U methodology for analyzing bus structure.s, spccificully hi.i.rc.s currying continuous media (CM), using fised priorit! scheduling. A scheduling bus mode1,for the Micro Chutiticl Archilecture which incorporales the non-ideul, reul-world bus,fealures is presented. A continuous mediu (CM) tusk set is used to explore design issues. 7’hese issues includc thc ,following: priority level assignment on the his, the cffit:t of tusk period transformation, ihc use of multi-lcvcl scheduling, and the effect of limited priority levels on thc Dus. In addition formulations will be mude for sctting IMS parameters such as tenure time and DRAM refresh period. to optimize continuous media scheduling.
Transduction of primitive human hematopoietic cells with recombinant adenovirus vectors (1996)

We have examined the ability of recombinant adenoviral vectors to transduce human hematopoietic cells. Our findings indicate that adenovirus readily infects a large proportion of CD34+ cells. Using adenovirus vectors that transduce either a lacZ or an alkaline phosphatase reporter gene, we observed up to 45% of total CD34+ cells infected. Upon more detailed analysis, we observed comparable levels of transduction for CD34+/CD38- cells and for CD34+ cells in G(zero) phase of the cell cycle. Importantly, exposure to adenovirus resulted in negligible levels of toxicity as assayed by propidium iodide staining and colony-forming ability. Using adenovirus vectors, we also describe a model system for regulated gene expression in early hematopoietic tissues. CD34+ cells were simultaneously infected with two viruses, one carrying a TetR/VP16 transactivator (tTA) and the second carrying a tTA-dependent lacZ reporter gene. Using this approach, beta-gal expression was only observed upon coinfection with the transactivator vector. In addition, as shown previously (Gossen and Bujard, Proc Natl Acad Sci USA 89:5547, 1992), tetracycline was able to inhibit tTA mediated induction, thereby providing an effective means to regulate expression of the reporter gene. We conclude that recombinant adenovirus is an effective vehicle for transiently expressing genes in primitive human hematopoietic cells.
[Irritable bowel syndrome: pathophysiology and (future) treatment options]. (2002)

Abnormalities of intestinal motility, altered visceral perception and psychological influences are the most important factors in the pathogenesis of irritable bowel syndrome. Current pharmacological treatment options are limited and lack specificity. In the future, it is likely that a number of therapeutic agents with stronger spasmolytic effects (selective muscarinic receptor antagonists), more specific colokinetic properties (5-hydroxytryptamine (5HT)4 agonists) and a positive influence on visceral perception (serotonin (5HT3) receptor antagonists, kappa-agonists) will become available.
Biomarker discovery by proteomics‐based approaches for early detection and personalized medicine in colorectal cancer (2016)

About one million people per year develop colorectal cancer (CRC) and approximately half of them die. The extent of the disease (i.e. local invasion at the time of diagnosis) is a key prognostic factor. The 5-year survival rate is almost 90% in the case of delimited CRC and 10% in the case of metastasized CRC. Hence, one of the great challenges in the battle against CRC is to improve early diagnosis strategies. Large-scale proteomic approaches are widely used in cancer research to search for novel biomarkers. Such biomarkers can help in improving the accuracy of the diagnosis and in the optimization of personalized therapy. Herein, we provide an overview of studies published in the last 5 years on CRC that led to the identification of protein biomarkers suitable for clinical application by using proteomic approaches. We discussed these findings according to biomarker application, including also the role of protein phosphorylation and cancer stem cells in biomarker discovery. Our review provides a cross section of scientific approaches and can furnish suggestions for future experimental strategies to be used as reference by scientists, clinicians and researchers interested in proteomics for biomarker discovery.
An association between schistosomes and contrapsin, a mouse serine protease inhibitor (serpin) (1988)

An antigen in homogenates of adult Schistosoma mansoni worms grown in mice, and immunoprecipitated by polyspecific rabbit antiserum, has been identified as contrapsin, a mouse serine protease inhibitor (serpin). In the serum of some mice infected with S. mansoni contrapsin was found with altered immunoelectrophoretic characteristics when compared with contrapsin from uninfected mice.
Intersubband absorption of silicon-based quantum wells for infrared imaging (1988)

We have calculated the 10-μm intersubband absorptoin in quantum wells made of the silicon-based system, Si/Si1−xGex. The necessary details of the effective-mass anisotropy are included in our analysis. We find that it is readily possible to achieve an absorption constant of order of 104 cm−1 in Si quantum wells with current doping technology. For [110] and [111] growth directions, a further advantage of Si quantum wells is pointed out, namely, an allowed absorption at normal incidence due to the anisotropic effective mass in Si.