gebhart/patrepeval huggingface dataset:
Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance. (2000)

OC144-093 is a novel substituted diarylimidazole (Mr 495) generated using the OntoBLOCK system, a solid-phase combinatorial chemistry technology, in combination with high-throughput cell-based screening. OC144-093 reversed multidrug resistance (MDR) to doxorubicin, paclitaxel, and vinblastine in human lymphoma, breast, ovarian, uterine, and colorectal carcinoma cell lines expressing P-glycoprotein (P-gp) with an average EC50 of 0.032 microM. Inhibition of MDR by OC144-093 was reversible, but the effect persisted for at least 12 h after removal of compound from the culture medium. OC144-093 had no effect on the response to cytotoxic agents by cells in vitro lacking P-gp expression or expressing a multidrug resistance-associated protein (MRP-1). OC144-093 was not cytotoxic by itself against 15 normal, nontransformed, or tumor cell lines, regardless of P-gp status, with an average cytostatic IC50 of >60 microM. OC144-093 blocked the binding of [3H]azidopine to P-gp and inhibited P-gp ATPase activity. The compound was >50% p.o. bioavailable in rodents and dogs and did not alter the plasma pharmacokinetics of i.v.-administered paclitaxel. OC144-093 increased the life span of doxorubicin-treated mice engrafted with MDR P388 leukemia cells by >100% and significantly enhanced the in vivo antitumor activity of paclitaxel in MDR human breast and colon carcinoma xenograft models, without a significant increase in doxorubicin or paclitaxel toxicity. The results demonstrate that OC144-093 is an orally active, potent, and nontoxic inhibitor of P-gp-mediated multidrug resistance that exhibits all of the desired properties for treatment of P-gp-mediated MDR, as well as for prevention of MDR prior to selection and/or induction of refractory disease.
Which are the antibodies to watch in 2012? (2012)

As we enter the new year of 2012, the realm of antibody therapeutics development seems full of possibilities for antibodies to watch. The commercial pipeline of antibody-based therapeutics continues to grow and now totals nearly 350 candidates. The molecular diversity of the candidates, especially those for cancer, is remarkable. Modified antibodies such as antibody-drug conjugates (ADCs), bispecific antibodies, Fc or glyco-engineered antibodies and antibody fragments/domains now comprise more than half of the anticancer antibodies at Phase 1, and ~40% of those at Phase 2 and Phase 3. These types of modified antibodies have not been developed as frequently for other disorders–by comparison, ~90% of antibodies developed for non-cancer indications are unmodified IgG–but development of the new formats for inflammatory and autoimmune disorders is expected to grow. In addition, antibody mixtures and antibodies with indirect mechanisms of action (e.g., agonism of immune activation receptors or antagonism of immune inhibitory receptors) are entering clinical study more frequently.
Airway Smooth Muscle and Asthma (2006)

The airway smooth muscle is the key determinant of airway narrowing in asthma but its function in the absence of disease is unknown. Evidence for an intrinsic abnormality in the muscle in asthma is only just emerging. The airway smooth muscle is not merely a contractile cell, but also one which determines the composition of, and interacts with the extracellular matrix, and which may participate in inflammatory and allergic reactions and viral infections. The reason for the differences which have been observed in the in vitro properties of airway smooth muscle derived from asthmatic individuals may result from an inherent "supercontractility", an increased tendency to proliferate due to the absence of an inhibitory transcription factor C/EBP-alpha, the influence of an altered extracellular matrix and/or a decrease in release of factors such as PGE(2) which would under normal circumstances inhibit both proliferation and contraction. Although long acting beta agonists and corticosteroids are successful treatments for inflammation and bronchoconstriction, the structural changes which constitute airway remodelling may require additional therapeutic intervention, the nature of which will be determined by thorough investigation of the mechanisms underlying the asthmatic phenotype.
ID-based signatures from pairingson elliptic curves (2002)

An efficient identity-based signature scheme is presented which makes use of bilinear pairings on elliptic curves. This scheme is similar to the generalised ElGamal signature scheme. The security of the scheme is considered.
Sex hormone binding globulin response to testosterone. An androgen sensitivity test (1985)

Adequate distinction between an abnormality in androgen secretion or in target cell response is important in the diagnosis and management of male pseudohermaphroditism. Hormone serum levels give reasonable information on steroid secretion, but there are no simple methods, in clinical practice, to evaluate target cell response to androgens. In this work, we have evaluated the validity of the acute decrease in serum (SHBG) after administration of hCG or exogenous testosterone, as an indicator of androgen sensitivity in prepubertal subjects. The results were expressed as percentage of basal values. In control subjects, after hCG, SHBG dropped below 85% of basal, mean 55 +/- 17, and, after exogenous testosterone, below 80%, mean 62.18 +/- 8.85. In 23 patients studied with the hCG test, 10 positive and 13 negative results were found, but most of the negative responses became positive after exogenous testosterone. Of 25 patients studied with the exogenous testosterone test, 19 positive and 6 negative results were found. Clinical analysis of these 6 patients with negative responses showed that 4 subjects had a confirmed androgen insensitivity syndrome, while clinical information was compatible with this diagnosis in the other 2 patients. Furthermore, in 4 additional patients with the androgen insensitivity syndrome, but with high basal serum testosterone, this test was also negative. It is concluded that determination of serum SHBG after hCG is not reliable as an androgen sensitivity test, but the detection of the decrease in serum SHBG after exogenous testosterone is a useful and simple test of androgen sensitivity.
Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein (2016)

The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.
Specific Adsorption of Copper on an Hydroxy‐Aluminum‐Montmorillonite Complex (1984)

Abstract The adsorption of Na on a prepared hydroxy‐aluminum‐montmorillonite complex (OH‐Al‐SWy‐l) was investigated as a function of pH, time, and Cu concentration ([Cu]). It was found that Na adsorption from 0.01 M NaClO 4 increased with pH from 0.015 mol kg −1 at pH 4.5 to 0.33 mol (Na + ) kg −1 clay at pH 6.6 Adsorption of 0.16 mol (1/2 Cu 2+ ) kg −1 clay did not affect the amount of Na adsorption, showing that specific sites existed for Cu. Adsorption of Cu was found to increase with pH and both adsorption and resistance to extraction with 0.25 M Ba(NO 3 ) 2 increased with time. At pH 4.6, Cu adsorption approached a maximum near 0.3 mol (1/2 Cu 2+ ) kg −1 clay of which 0.13 mol (1/2 Cu 2+ ) were extracted with Ba(NO 3 ) 2 . Electron spin resonance (ESR) of the Cu on OH‐Al‐SWy‐l showed that both physi‐ and chemisorbed Cu were present and that solubilization as Cu(NH 3 ) 2+ 4 through exposure to NH 3 vapor overnight was possible only if the sample had been previously treated with BaCl 2 . It was concluded that the OH‐Al‐SWy‐l system provided a much more reactive surface toward Cu adsorption than either montmorillonite or hydrous aluminum oxides. In comparison to smectites Cu was less labile to Ba extraction due, in part, to chemisorption by Al‐OH groups. Relative to values reported for Al(OH) 3 polymorphs, Al x (OH) y 3 x‐y precipitated in the presence of montmorillonite adsorbed more Cu on a mass basis presumably due to a higher surface to mass ratio.
Tolonium (toluidine blue) rinse--a screening method for recognition of squamous carcinoma. Continuing study of oral cancer IV. (1981)

Tolonium chloride (toluidine blue) application is useful for identifying malignant changes in squamous mucosa. However, early asymptomatic mucosal changes may remain undetected by tolonium application. A study was carried out to determine the feasibility of using a tolonium mouth rinse as a routine procedure after thorough clinical examination, to discover undetected cancers. A proved, effective tolonium application method was compared with a rinse sequence. One hundred five asymptomatic oral lesions (51 carcinomas and 54 nonmalignant lesions) that persisted for ten to 14 days were evaluated with application and rinse modalities and biopsies. There were 2% false-negatives (1/51) with the application as opposed to 5.9% (3/51) with the rinse and 9.3% false-positives (5/54) with the application as compared to 7.4% (4/54) with the rinse. Four inapparent, second primary cancers, unobserved for application, were delineated by the rinse (three oral, one pharyngeal). Tolonium blue rinse may be used to detect unobserved, asymptomatic oral mucosal cancers after clinical examination. After a positive rinse stain, a subsequent positive application stain ten to 14 days later mandates a biopsy of the lesion.
Epigenetic quantification of tumor-infiltrating T-lymphocytes (2011)

The immune system plays a pivotal role in tumor establishment. However, the role of T-lymphocytes within the tumor microenvironment as major cellular component of the adaptive effector immune response and their counterpart, regulatory T-cells (Treg), responsible for suppressive immune modulation, is not completely understood. This is partly due to the lack of reliable technical solutions for specific cell quantification in solid tissues. Previous reports indicated that epigenetic marks of immune cells, such as the Treg specifically demethylated region (TSDR) within the FOXP3 gene, may be exploited as robust analytical tool for Treg-quantification. Here, we expand the concept of epigenetic immunophenotyping to overall T-lymphocytes (oTL). This tool allows cell quantification with at least equivalent precision to FACS and is adoptable for analysis of blood and solid tissues. Based on this method, we analyse the frequency of Treg, oTL and their ratio in independent cohorts of healthy and tumorous ovarian, colorectal and bronchial tissues with 616 partly donor-matched samples. We find a shift of the median ratio of Treg-to-oTL from 3-8% in healthy tissue to 18-25% in all tumor entities. Epigenetically determined oTL frequencies correlate with the outcome of colorectal and ovarian cancers. Together, our data show that the composition of immune cells in tumor microenvironments can be quantitatively assessed by epigenetic measurements. This composition is disturbed in solid tumors, indicating a fundamental mechanism of tumor immune evasion. Epigenetic quantification of T-lymphocytes serves as independent clinical parameter for outcome prognosis.
Synthesis and Characterization of Novel Surfactants: Combination Products of Fatty Acids, Hydroxycarboxylic Acids and Alcohols (2010)

Abstract The reaction of hydroxycarboxylic acids, such as citric, malic and tartaric species with an excess of fatty acid chlorides produces the corresponding O ‐acylated hydroxycarboxylic anhydrides in one step and in a near quantitative yield. These molecules are excellent electrophiles which react readily with a variety of nucleophiles including alcohols, diols and polyols. Their reaction with triethylene glycol and triethylene glycol monomethyl ether leads to two series of novel anionic surfactants, which are unsymmetrical gemini surfactants. The determination of their properties (CMC, foaming, HLB) revealed that these molecules are—depending on the chain length of the fatty acid—excellent emulsifiers, and that they also display interesting antimicrobial activity. These novel functional surfactants are of interest for applications in food and personal care products and for the formulation of pharmaceuticals.
27.1: A Novel Structure of AMLCD Panel Using Poly‐Si CMOS TFT (2005)

Abstract In the fabrication of CMOS AMLCD panel, there has been much effort to reduce the number of mask steps in order to achieve the simpler process as well as the low‐cost production. In this paper, two methods for mask reduction; storage mask and LDD mask as well as self‐aligned sub micron LDD n‐channel TFT are introduced with good uniformity concept.
A review and selection of simple laboratory methods used for the study of glycosaminoglycan excretion and the diagnosis of the mucopolysaccharidoses. (1976)

The current state of knowledge on the biochemical abnormalities in the mucopolysaccharidoses is reviewed. Methods for the estimation and identification of glycoasminoglycans excreted in the mucopolysaccharidoses are discussed and a selection of simple and reliable methods of value in a small hospital laboratory have been given in detail in an appendix.
Regulatory Considerations for Physiological Closed-Loop Controlled Medical Devices Used for Automated Critical Care: Food and Drug Administration Workshop Discussion Topics (2017)

Part of the mission of the Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration is to facilitate medical device innovation. Therefore, CDRH plays an important role in helping its stakeholders such as manufacturers, health care professionals, patients, patient advocates, academia, and other government agencies navigate the regulatory landscape for medical devices. This is particularly important for innovative physiological closed-loop controlled (PCLC) devices used in critical care environments, such as intensive care units, emergency settings, and battlefield environments. CDRH's current working definition of a PCLC medical device is a medical device that incorporates physiological sensor(s) for automatic manipulation of a physiological variable through actuation of therapy that is conventionally made by a clinician. These emerging devices enable automatic therapy delivery and may have the potential to revolutionize the standard of care by ensuring adequate and timely therapy delivery with improved performance in high workload and high-stress environments. For emergency response and military applications, automatic PCLC devices may play an important role in reducing cognitive overload, minimizing human error, and enhancing medical care during surge scenarios (ie, events that exceed the capability of the normal medical infrastructure). CDRH held an open public workshop on October 13 and 14, 2015 with the aim of fostering an open discussion on design, implementation, and evaluation considerations associated with PCLC devices used in critical care environments. CDRH is currently developing regulatory recommendations and guidelines that will facilitate innovation for PCLC devices. This article highlights the contents of the white paper that was central to the workshop and focuses on the ensuing discussions regarding the engineering, clinical, and human factors considerations.
c-Myc Functionally Cooperates with Bax To Induce Apoptosis (2002)

c-Myc promotes apoptosis by destabilizing mitochondrial integrity, leading to the release of proapoptotic effectors including holocytochrome c. Candidate mediators of c-Myc in this process are the proapoptotic members of the Bcl-2 family. We show here that fibroblasts lacking Bak remain susceptible to c-Myc-induced apoptosis whereas bax-deficient fibroblasts are resistant. However, despite this requirement for Bax, c-Myc activation exerts no detectable effects on Bax expression, localization, or conformation. Moreover, susceptibility to c-Myc-induced apoptosis can be restored in bax-deficient cells by ectopic expression of Bax or by microinjection of a peptide comprising a minimal BH3 domain. Microinjection of BH3 peptide also restores sensitivity to c-Myc-induced apoptosis in p53-deficient primary fibroblasts that are otherwise resistant. By contrast, there is no synergy between BH3 peptide and c-Myc in fibroblasts deficient in both Bax and Bak. We conclude that c-Myc triggers a proapoptotic mitochondrial destabilizing activity that cooperates with proapoptotic members of the Bcl-2 family.
Visualizing high-dimensional predictive model quality (2000)

Using inductive learning techniques to construct classification models from large, high-dimensional data sets is a useful way to make predictions in complex domains. However, these models can be difficult for users to understand. We have developed a set of visualization methods that help users to understand and analyze the behavior of learned models, including techniques for high-dimensional data space projection, display of probabilistic predictions, variable/class correlation, and instance mapping. We show the results of applying these techniques to models constructed from a benchmark data set of census data, and draw conclusions about the utility of these methods for model understanding.
Synthesis of some 5-halogenovinyl derivatives of uracil and their conversion into 2′-deoxyribonucleosides (1981)

Treatment of 5-formyluracil with malonic acid in the presence of piperidine gave (E)-5-(2-carboxyvinyl)uracil which, upon reaction with the appropriate N-halogenosuccinimide, gave (E)-5-(2-bromovinyl)uracil, (E)-5-(2-chlorovinyl)uracil, and (E)-5-(2-iodovinyl)uracil. The last mentioned compound was also obtained by the action of iodine chloride on 5-vinyluracil. 5-(1-Chlorovinyl)uracil upon treatment with bromine gave 5(2-bromo-1-chlorovinyl)uracil which reacted with sodium methoxide to give 5-bromoethynyluracil. (E)-5-(2-Bromovinyl)-uracil was converted into into its trimethylsilyl derivative which was condensed with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride to give the α- and β-anomers of the blocked deoxyribonucleoside. Removal of the p-toluoyl blocking groups with sodium methoxide afforded (E)-5-(2-bromovinyl)-1-(2-deoxy-α-D-erythro-pentofuranosyl)uracil and (E)-5-(2-bromovinyl)-2′-deoxyuridine. A similar series of reactions gave (E)-5-(2-iodovinyl)-2′-deoxyuridine and 5-(2-bromo-1-chlorovinyl)-2′-deoxyuridine. 5-(1-Chlorovinyl)uracil could be condensed similarly with the blocked sugar derivative to give the α- and β-anomers of the blocked deoxyribonucleoside. Attempted removal of the groups with sodium methoxide gave 2′-deoxy-5-ethynyluridine and mild treatment with methanolic ammonia gave the same product and some 2′-deoxy-5-ethynyl-5′-O-(p-toluoyl)-uridine. 5-(1-Chlorovinyl)-2′-deoxyuridine was obtained by the addition of HCl to 2′-deoxy-5-ethynyluridine. Aspects of the elimination reactions of 5-(halogenovinyl)uracil derivatives are discussed.
Disruption of the glucosylceramide biosynthetic pathway in <i>Aspergillus nidulans</i> and <i>Aspergillus fumigatus</i> by inhibitors of UDP‐Glc:ceramide glucosyltransferase strongly affects spore germination, cell cycle, and hyphal growth (2002)

The opportunistic mycopathogen Aspergillus fumigatus expresses both glucosylceramide and galactosylceramide (GlcCer and GalCer), but their functional significance in Aspergillus species is unknown. We here identified and characterized a GlcCer from Aspergillus nidulans, a non-pathogenic model fungus. Involvement of GlcCer in fungal development was tested on both species using a family of compounds known to inhibit GlcCer synthase in mammals. Two analogs, D-threo-1-phenyl-2-palmitoyl-3-pyrrolidinopropanol (P4) and D-threo-3',4'-ethylenedioxy-P4, strongly inhibited germination and hyphal growth. Neutral lipids from A. fumigatus cultured in the presence of these inhibitors displayed a significantly reduced GlcCer/GalCer ratio. These results suggest that synthesis of GlcCer is essential for normal development of A. fumigatus and A. nidulans.
Multispectral cytometry of single bio-particles using a 32-channel detector (2005)

Detecting biological particles and subsequently identifying them in a very short period of time is highly desirable, but a very difficult task. There are several pathways for developing rapid detection systems. For example, one can reduce sample size to a very small volume, and amplify cellular components by PCR technology with a view to identifying antigen-specific molecules. Alternatively, antibody-based assays allow for detection and identification of a variety of well-characterized pathogens. The system we propose utilizes flow cytometry technology to rapidly detect spectral fingerprints or organisms. However, the current limit for simultaneously detectable fluorescence signals in flow cytometry is around 12-15. Making these measurements is very complex and the necessity for advanced spectral overlap calculations creates a number of difficult problems to solve in a short period of time. Next-generation instruments can either increase the number of detectors or modify the principles of collection. If the detector system were simplified, the overall cost and complexity of single-cell analytical systems might be reduced. This requires changes in both hardware and software that allow for the analysis of 30 or more spectral signals. Further, analysis of complex data sets requires some completely new approaches, particularly in the area of multispectral analysis. This presentation describes the key components and principles involved in building a next-generation instrument which can collect simultaneously 32 bands of fluorescence from a particle in less than 5 microseconds. This would allow the analysis of several thousand bioparticles per second. The flow cytometry system based on our new detector would be designed to be portable and low cost.
A precise inter-procedural data flow algorithm (1981)

Data flow analysis is well understood at the intra-procedural level and efficient algorithms are available. When inter-procedural mechanisms such as recursion, procedure nesting, and pass-by-reference aliasing are introduced, the data flow problems become much more difficult. The avail, live, and must-summary data flow problems are shown to be NP-complete in the presence of aliasing. However, an algorithm is presented with O(SET*EDGE) time performance where EDGE is the size of the program's flow graph and SET is a possible exponential number which reflects the number of aliasing patterns of the program. It is argued that in practice SET is small and on the order of the number of variables of the program.