gebhart/patrepeval huggingface dataset:
Anthracyclines as effective anticancer drugs (2006)

Anthracyclines have received significant attention due to their effectiveness and extensive use as anticancer agents. At present, the clinical use of these drugs is offset by drug resistance in tumours and cardiotoxicity. Therefore, a relentless search for the 'better anthracycline' has been ongoing since the inception of these drugs > 30 years ago. This review focuses on the most recent pharmacology and medicinal chemistry developments on the design and use of anthracyclines. Based on their crystal structures as well as molecular modelling, a more detailed mechanism of topoisomerase poisoning by these new anthracyclines has emerged. Chemical modifications of anthracyclines have been found to possibly change the target selectivity among various topoisomerases and, thus, vary their anticancer activity. Additionally, recent sugar modifications of anthracyclines have also been found to overcome P-glycoprotein-mediated drug resistance in cancer therapy. The continued improvement of anthracycline clinical applications so far and the clinical trials of the 'third generation' of anthracyclines (such as sabarubicin) are also discussed. To finally find the 'better' anthracycline, further areas of research still need to be explored such as: the elucidation of the topoisomerase and P-glycoprotein crystal structures, molecular modelling based on crystal structure in order to design the next generation of better anthracycline drugs, the continued modifications of the anthracycline sugar moieties, and the further improvement of anthracycline drug delivery methods.
Topotecan inhibits human immunodeficiency virus type 1 infection through a topoisomerase-independent mechanism in a cell line with altered topoisomerase I (1997)

Topotecan (TPT), a known inhibitor of topoisomerase I, has previously been shown to inhibit the replication of several viruses. The mechanism of inhibition was proposed to be the inhibition of topoisomerase I. We report that TPT decreased replication of human immunodeficiency virus type 1 (HIV-1) in CPT-K5, a cell line with a topoisomerase I mutation. TPT inhibited production of HIV-1 RNA and p24 in CPT-K5 and wild-type cells equally effectively. The antiviral effects of TPT were observed not only in the topoisomerase-mutated CPT-K5 line but also in peripheral blood mononuclear cells (PBMC) acutely infected with clinical isolates and in OM10.1 cells latently infected with HIV and activated by tumor necrosis factor alpha. Little toxicity from TPT was noted in HIV-1-infected PBMC and in CPT-K5 and OM10.1 cells as measured by cell growth and proliferation assays. These observations suggest that TPT targets factors in virus replication other than cellular topoisomerase I and inhibits cytokine-mediated activation in latently infected cells by means other than cytotoxicity. These results suggest a potential for TPT and for other camptothecins in anti-HIV therapy alone and in combination with other antiretroviral drugs.
Diagnosis of metastatic neoplasms: molecular approaches for identification of tissue of origin. (2010)

Molecular tests for tissue-of-origin determination in metastatic tumors are available and have the potential to significantly impact patient management. However, available validation data indicate that not all tests have shown adequate performance characteristics for clinical use. Pathologists and oncologists should carefully evaluate claims for accuracy and clinical utility for tissue-of-origin tests before using test results in patient management. The personalized medicine revolution includes the use of molecular tools for identification/confirmation of the site of origin for metastatic tumors, and in the future, this strategy might also be used to determine specific therapeutic approaches.
Higher Plasma S100B Concentrations in Schizophrenia Patients and Dependently Associated with Inflammatory Markers (2016)

Glial damage and immune dysfunction are involved in pathogenesis of schizophrenia. However, interaction between glial damage and immune dysfunction in schizophrenia is undefined. This study aims to compare plasma S100 calcium binding protein (S100B) levels between schizophrenia patients and healthy participants, and to determine if immune markers are independently related with concentration of S100B in schizophrenia patients. Forty-one schizophrenia patients and thirty-three healthy volunteers were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of plasma S100B and inflammatory markers. We found that concentrations of S100B were elevated in schizophrenia patients than healthy participants (p < 0.05), and were negatively related with the severity of symptoms (p = 0.046). Receiver operating characteristic (ROC) curve analysis showed that different S100B levels between schizophrenia and healthy participants can be used as a clinical diagnostic factor (predictive value: 0.666, p = 0.015). Multiple linear regression analysis found that length of illness (Beta = -0.161), plasma levels of inflammatory regulation factors (including TGF-β1, logIL-23 and logIL-10) (Beta = 0.119, 0.475, 0.514) were independently associated with concentrations of S100B (Adjusted R(2) = 0.897, p < 0.001). Therefore, our results suggest the possible function of S100B in pathogenesis of schizophrenia, and implicate the important role of autoimmune response and balance to glial dysfunction in patients with schizophrenia.
Antibodies in Human Sera Recognizing a Recombinant Outer Membrane Protein Encoded by the Envelope Gene of the Human Endogenous Retrovirus K (1993)

Human endogenous retrovirus (HERV) K is present in about 50 copies in the human genome and transcription of HERV-K has previously been detected in several tumor cell lines as well as in peripheral blood lymphocytes from healthy donors. By means of immunoblotting we investigated the presence of antibodies recognizing recombinant HERV-K-envelope outer membrane constructs in different serum collectives. A total of 12.6% of sera obtained from normal blood donors was found positive. In serum collectives from breast carcinoma patients, HIV-1-positive individuals, and persons with cytomegalovirus infections no significant difference from the normal blood donor serum collective could be observed. Only a group of persons with a repeatedly raised serum neopterin concentration (> 10 nmol/liter) of unknown cause (HIV and hepatitis B and C virus infections were excluded) showed a significant higher percentage of HERV-K-outer membrane envelope-positive sera (21%). Furthermore we could observe a parallel HIV-1/HERV-K seroconversion, which probably is not due to an HIV-1/HERV-K-outer membrane envelope cross-reactivity. Possible implications of these findings are discussed.
Inhibition of Notch signaling induces myotube hypertrophy by recruiting a subpopulation of reserve cells (2006)

During muscle differentiation, a population of quiescent undifferentiated myoblasts (reserve cells) emerges among mature muscle cells. However, the molecular mechanisms underlying such cell segregation and the characterization of this subpopulation of myoblasts remain to be determined. Notch is known to control the behavior and fate of murine muscle stem cells. In this study, we examined the role of Notch in myoblast segregation. We showed that inhibition of Notch activity by either overexpressing Numb or by using a pharmacological gamma-secretase inhibitor (DAPT) enhanced differentiation of murine and human myoblasts. This effect was not restricted to in vitro culture systems since DAPT-treated zebrafish embryos also showed increased differentiation. Using C2.7 myoblasts as a model, we showed that inhibition of Notch induced myotube hypertrophy by recruiting reserve cells that do not normally fuse. We further showed that endogenous Notch-signaling components were differentially expressed and activated in reserve cells with respect to Notch 1 and CD34 expression. We identified CD34 negative reserve cells as the subpopulation of myoblasts recruited to fuse into myotubes during differentiation in response to Notch inhibition. Therefore, we showed here that the activation of Notch 1 is important to maintain a subpopulation of CD34 negative reserve cells in an undifferentiated state.
Logic testing of bridging faults in CMOS integrated circuits (1998)

We describe a system for simulating and generating accurate tests for bridging faults in CMOS ICs. After introducing the Primitive Bridge Function, a characteristic function describing the behavior of a bridging fault, we present the Test Guarantee Theorem, which allows for accurate test generation for feedback bridging faults via topological analysis of the feedback-influenced region of the faulty circuit. We present a bridging fault simulation strategy superior to previously published strategies, describe the new test pattern generation system in detail, and report on the system's performance, which is comparable to that of a single stuck-at ATPG system. The paper reports fault coverage as well as defect coverage for the MCNC layouts of the ISCBS-85 benchmark circuits.
CLINICAL SIGNIFICANCE OF THE DIFFERENT FORMS OF THE KLEBS-LOEFFLER BACILLUS. (1898)

It is not necessary for me to enter into a detailed description of the bacillus of diphtheria, history of its discovery, growth in different culture media etc.; a few remarks however especially in regard to its morphology will be required in order to present this paper properly. Fraenkel in his work on bacteriology describes the Klebs-Loeffler bacillus as a bacterium, resembling in many respects Fraenkel's diplococcus of pneumonia. According to him, their habitat is in the oldest part of the pseudo-membrane. They are little rods of moderate size, usually slightly bent, about as long as the tubercle bacillus but twice as broad, hence of a rather coarse appearance and usually with rounded ends. But the form of this micro-organism is exceedingly variable, and the differences are striking in appearance. The bacteria are sometimes seen enveloped in a more or less capacious glassy membrane; sometimes the contents separate into several pieces
<title>Windowing effects on light scattering by sinusoidal surfaces</title> (1993)

A window function is used to represent the variation in the intensity of the radiation in a light beam. Windowing effects are factored into computations of the angular distribution of light scattered by a sinusoidal surface. These effects, as well as those of harmonics and noise, are shown for the angular distributions computed from simulated profiles. The integrated power in each diffraction peak computed for perfect sinusoids, measured profiles, and simulated profiles with different window functions is compared to that of a measured angular distribution.
Characterisation of polyphenols by HPLC‐PAD‐ESI/MS and antioxidant activity in <i>Equisetum telmateia</i> (2005)

The antioxidant activity of an aqueous extract (infusion) and respective ethyl acetate fraction of Equisetum telmateia Ehrh. (Equisetaceae), a plant used in traditional medicine for its anti-inflammatory and diuretic properties, has been evaluated by DPPH, TEAC and TBARS assays. A high and significant antioxidant activity was detected in the ethyl acetate fraction. Analysis of the aqueous extract and the ethyl acetate fraction by HPLC-PAD-ESI/MS allowed the identification of the major phenolic compounds as flavan-3-ol, kaempferol and phenolic acid derivatives. Among the flavan-3-ols, A-type proanthocyanidins and afzelechin derivatives were detected as well as the more common B-type procyanidins, B2 and C1, whose identification was further confirmed by HPLC using detection involving chemical reaction with p-dimethylamino-cinnamaldehyde. The results suggest that the anti-inflammatory activity of E. telmateia could be due, at least in part, to the presence of compounds with antioxidant activity.
A primary field compensation scheme for planar array magnetic induction tomography (2004)

In biomedical magnetic induction tomography (MIT), measurement precision may be improved by incorporating some form of primary field compensation/cancellation scheme. Schemes which have been described previously include gradiometric approaches and the use of 'back-off' coils. In each of these methods, however, the primary field cancellation was achieved only for a single transmitter/receiver combination. For the purpose of imaging, it would be desirable for a fully electronically scanned MIT system to provide a complete set of measurements, all with the primary field cancelled. A single channel suitable for incorporation into an MIT system with planar-array geometry is described. The transmitter is a 6-turn coil of wire 5 cm in diameter. The receiver is a surface mount inductor, of inductance 10 microH, mounted such that, in principle, no net primary field flux threads it. The results of measurements carried out with the single channel system suggest that the signal due to the primary excitation field can be reduced on average by a factor of 298 by the sensor geometry over the operating frequency range 1-10 MHz. The standard deviation and drift of the signal with the system adjusted for maximum primary field cancellation, expressed as a percentage of the signal when the receiver coil was rotated until its axis of sensitivity lay along the primary field, were 0.0009% and 0.009%, respectively. The filter time constant used was 30 ms.
The Authenticity of Business Simulations in ESP: Implications for Materials Design (2007)

In this article we set out how authentic materials for a performance appraisal simulation help MBA students—both full-time and professionals—to acquire the linguistic and management skills that they will need to carry out a practical business task. The simulation was designed for a course in Management Communication that has been taught as part of the MBA course at the University of Antwerp Management School (UAMS) and the Executive MBA courses at the University of Warsaw and the Institute of Business Studies in Moscow. The design of these materials will be explained with reference to the notion of authenticity.
Heart-type Fatty Acid-binding Protein Is Essential for Efficient Brown Adipose Tissue Fatty Acid Oxidation and Cold Tolerance (2010)

Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3(-/-) mice exhibit extreme cold sensitivity despite induction of uncoupling and oxidative genes and hydrolysis of brown adipose tissue lipid stores. However, using FABP3 gain- and loss-of-function approaches in brown adipocytes, we detected a correlation between FABP3 levels and the utilization of exogenous fatty acids. Thus, Fabp3(-/-) brown adipocytes fail to oxidize exogenously supplied fatty acids, whereas enhanced Fabp3 expression promotes more efficient oxidation. These results suggest that FABP3 levels are a determinant of fatty acid oxidation efficiency by brown adipose tissue and that FABP3 represents a potential target for modulation of energy dissipation.
Enseñemos a cooperar (2006)

Nuestros estudiantes de ELE aprenden en verdaderas comunidades de aprendizaje, pero sin ser del todo conscientes de lo que estan viviendo. Deben, la mayor parte del tiempo que pasan en clase, hacer cosas juntos: hablar con los companeros, repartirse el trabajo, comparar respuestas, hacer hipotesis de lectura, inferir, mejorar su escritura, tomar decisiones, etc? Nosotros, profesores y expertos comunicadores, damos por sentado que poseen habilidades sociales tales como ponerse en lugar de otro, emitir mensajes claros y convincentes, escuchar, no interrumpir, experimentar la empatia, dar y pedir ayuda, alentar, infundir energia, dar respuestas creativas ante los contratiempos y un sinfin de cosas mas esenciales para que el trabajo en equipo sea realmente esa sinergia que nos hace avanzar infinitamente mas ligeros que si aprendieramos solos. Ensenar de manera consciente las habilidades sociales en el aula permite dotar a los estudiantes de herramientas poderosas que les elevaran a la categoria de ?aprendices estrella?, no solo en el aprendizaje del espanol sino en todos los vastos dominios de la vida.
N-Terminal Isotope Tagging Strategy for Quantitative Proteomics:  Results-Driven Analysis of Protein Abundance Changes (2004)

Comparing the relative abundance of each protein present in two or more complex samples can be accomplished using isotope-coded tags incorporated at the peptide level. Here we describe a chemical labeling strategy for the incorporation of a single isotope label per peptide, which is completely sequence-independent so that it potentially labels every peptide from a protein including those containing posttranslational modifications. It is based on a gentle chemical labeling strategy that specifically labels the N-terminus of all peptides in a digested sample with either a d5- or d0-propionyl group. Lysine side chains are blocked by guanidination prior to N-terminal labeling to prevent the incorporation of multiple labels. In this paper, we describe the optimization of this N-terminal isotopic tagging strategy and validate its use for peptide-based protein abundance measurements with a 10-protein standard mixture. Using a results-driven strategy, which targets proteins for identification based on MALDI TOF-MS analysis of isotopically labeled peptide pairs, we also show that this labeling strategy can detect a small number of differentially expressed proteins in a mixture as complex as a yeast cell lysate. Only peptides that show a difference in relative abundance are targeted for identification by tandem MS. Despite the fact that many peptides are quantitated, only those few showing a difference in abundance are targeted for protein identification. Proteins are identified by either targeted LC-ES MS/MS or MALDI TOF/TOF. Identifications can be accomplished equally well by either technique on the basis of multiple peptides. This increases the confidence level for both identification and quantitation. The merits of ES MS/MS or MALDI MS/MS for protein identification in a results-driven strategy are discussed.
The provision of psychiatric treatment for mental health colleagues in the new market economy (1994)

This article outlines a problem in the referral pattern for mental health workers on the Isle of Wight, when they require psychiatric or psychological help. The authors are concerned that treatments are offered by colleagues. A survey undertaken of 12 community mental health units in Wessex seems to indicate that there are no dear policies or financial arrangements for referrals to other units. The authors agree that the treatment of mental health workers everywhere may be compromised in the market economy, if trusts start to function, because of economic pressures, as islands.
[Monocrotaline-induced pulmonary hypertension in animals]. (2001)

Monocrotaline (MCT) is a pyrrolizidine alkaloid extracted from seeds of Crotalaria spectabilis that has been used to induce structural changes in the pulmonary arteries associated with progressive pulmonary hypertension in rodents. Recent studies have demonstrated that several mediators such as elastase, vasoconstrictors (Endotheline-1), vasodilators (Nitric oxide, PGI2) and cytokines (IL-1, MCP-1) play important roles in MCT-induced pulmonary hypertension, and that the changes in pulmonary hemodynamics are required for neointimal formation in pulmonary arteries. We have recently provided the evidence that macrophage migration inhibitory factor (MIF) is also involved in this model. The MCT-induced pulmonary hypertension in animals is useful as an experimental model for understanding the pathophysiology of primary pulmonary hypertension.
Assuring the Quality of Vaccines: Regulatory Requirements for Licensing and Batch Release (2003)

Ensuring the consistent safety and efficacy of a vaccine has long been recognized as an essential element in a successful disease-control program. Indeed, the development of appropriate laboratory methods to characterize a vaccine with respect to its component antigens, safety, and potency must be a prerequisite to the routine clinical use of any new bacterial, viral, or antiparasite vaccines, Adequate control measures serve to safeguard vaccinees both against unacceptable adverse effects and inadequate protection.
Influence of information technology on military radar systems (2005)

The paper discusses influence of information technology (IT) on military radar systems and how this impacts upon conducting military operations. Applications of new technologies in three basic areas of military radar systems are considered: surveillance and automatic target recognition systems; tracking systems and data and signal processing. Some possible uses of radar data are shown along with how this will improve the efficacy of planning, coordinating, directing and controlling of military actions.
Glucose-related protein (GRP78) and its relationship to the drug-resistance proteins P170, GST-pi, LRP56 and angiogenesis in non-small cell lung carcinomas. (2000)

Several studies have documented that induction of the glucose-related protein (GRP78) is associated with the development of drug-resistance to antitumor drugs. However, nothing has been reported concerning GRP78 in human lung tumors and its relationship to several resistance proteins and angiogenesis. Therefore, this study analyzed the expression of GRP78 in a series of 62 consecutive lung cancer patients and examined whether or not a relationship exists between GRP78, several resistance proteins and microvessel density (MVD). Secondary, it evaluated the relationship of GRP78, LRP56 and GST-pi in cancer cell lines under hypoxic conditions and in sensitive and resistant cell lines. We determined that a relationship exists between GRP78 and the resistance proteins P170, LRP56 and GST-pi in human lung cancer. Furthermore, we observed an up-regulation of GRP78 in the resistant cell lines LUTC-ML54, OAW-Dox and OAW-Tax, but not in sensitive cell lines. Abnormal vascularization of malignant tumors is associated with the development of hypoxic regions. In hypoxic regions, several proteins, including drug resistance proteins, are expressed in greater quantities. Our study detected an inverse correlation between GRP78 and MVD. Carcinomas with low MVD exhibited a higher expression of GRP78. Furthermore, protein expression of GRP78, GST-pi and LRP56 increased in the cell lines A-549, RPMI-2650 and SC-MES-1 under hypoxic conditions. These observations suggest that hypoxia, tumor vascularization and the simultaneous expression of many resistance-related proteins, including GRP78, may play an important role in drug response and therapeutic effectiveness.
RETRACTED: Metallic Conductivity in a Two-Dimensional Cobalt Dithiolene Metal–Organic Framework (2017)

Two-dimensional (2D) metal-organic frameworks (MOFs) have received a great deal of attention due to their relatively high charge carrier mobility and low resistivity. Here we report on the temperature-dependent charge transport properties of a 2D cobalt 2,3,6,7,10,11-triphenylenehexathiolate framework. Variable temperature resistivity studies reveal a transition from a semiconducting to a metallic phase with decreasing temperature, which is unprecedented in MOFs. We find this transition to be highly dependent on the film thickness and the amount of solvent trapped in the pores, with density functional theory calculations of the electronic-structure supporting the complex metallic conductivity of the material. These results identify the first experimentally observed MOF that exhibits band-like metallic conductivity.