gebhart/patrepeval huggingface dataset:
A microarray-based DNA methylation study of glioblastoma multiforme (2009)

Glioblastoma multiforme (GBM) is the most frequent and devastating primary brain tumor in adults. The presence of epigenetic lesions, like hypermethylation of known tumor suppressor genes such as MGMT, has been widely described in GBM, but to our knowledge, a genome-wide profile of DNA methylation changes in these lethal tumors is not yet available. In the present analysis, we have quantified the DNA methylation level of 1,505 CpG dinucleotides (807 genes) in 87 consecutive GBMs using universal BeadArrays. Supervised cluster analyses identified 25 and seven genes that were respectively hypermethylated and hypomethylated in more than 20% of the cases studied. The most frequently hypermethylated genes were HOXA11, CD81, PRKCDBP, TES, MEST, TNFRSF10A and FZD9, being involved in more than half of the cases. Studying the biological features of hypermethylated genes, we found that the group of genes hypermethylated in GBM was highly enriched (41%, p < 0.001) for targets of the PRC2 (Polycomb repressive complex 2) in embryonic stem cells. This suggests that GBM might be derived from precursor cells with stem cell-like features. DNA methylation profiles were associated with overall survival in GBM, and we confirmed the favorable prognostic impact of MGMT methylation in patients treated with alkylating agents. Furthermore, we identified that promoter hypermethylation of the transcription factor gene GATA6 (occurring in 30% of GBM) was significantly associated with unfavorable patient survival.
Immunotherapy with FBTA05 (Bi20), a trifunctional bispecific anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion (DLI) in relapsed or refractory B-cell lymphoma after allogeneic stem cell transplantation: study protocol of an investigator-driven, (2013)

Patients with B cell malignancies refractory to allogeneic stem cell transplantation (SCT) can be treated by subsequent immunotherapy with donor lymphocyte infusions (DLI). But unlike myeloid leukemia, B cell leukemia and lymphoma are less sensitive to allogeneic adoptive immunotherapy. Moreover, the beneficial graft-versus-lymphoma (GVL) effect may be associated with moderate to severe graft-versus-host disease (GVHD). Thus, novel therapeutic approaches augmenting the anti-tumor efficacy of DLI and dissociating the GVL effect from GVHD are needed. The anti-CD20 x anti-CD3 trifunctional bispecific antibody (trAb) FBTA05 may improve the targeting of tumor cells by redirecting immune allogeneic effector cells while reducing the risk of undesirable reactivity against normal host cells. Hence, FBTA05 may maximize GVL effects by simultaneously decreasing the incidence and severity of GVHD.Based on this underlying treatment concept and on promising data taken from preclinical results and a small pilot study, an open-label, non-randomized, uncontrolled, dose-escalating phase I/II-study is conducted to evaluate safety and preliminary efficacy of the investigational antibody FBTA05 in combination with DLI for patients suffering from rituximab- and/or alemtuzumab-refractory, CD20-positive low- or high-grade lymphoma after allogeneic SCT. During the first trial phase with emphasis on dose escalation a maximum of 24 patients distributed into 4 cohorts will be enrolled. For the evaluation of preliminary efficacy data a maximum of 12 patients (6 patients with low-grade lymphoma and/or Chronic Lymphocytic Leukemia (CLL) / 6 patients with high-grade or aggressive lymphoma) will attend the second phase of this clinical trial.Promising data (e.g. induction of cellular immunity; GVL predominance over GVHD; achievement of partial or complete responses; prolongation of time-to-progression) obtained from this phase I/II trial would represent the first milestone in the clinical evaluation of a novel immunotherapeutic concept for treatment-resistant low- and high-grade lymphoma and NHL patients in relapse.NCT01138579.
Intravitreal injections: a review of the evidence for best practice (2012)

Intravitreal injection is a common procedure performed by ophthalmologists. It is a quick and targeted treatment for a number of ophthalmic conditions. Despite this, the potential to cause serious complications and patient discomfort cannot be ignored. This article presents the level of evidence in the scientific literature supporting common practices such as location of the procedure, anaesthetic choice, sterile procedure techniques, comparison of some common pharmaceutical agents and the use of antibiotics.
Complete RF System Model for Analysis of Compact MIMO Arrays (2004)

A framework to analyze compact arrays for multiple-input-multiple-output (MIMO) is presented. Many handheld devices require very compact arrays. Small spacings between the antennas lead to mutual coupling, which decreases the efficiency of the antennas and therefor the signal-to-noise ratio and leads to correlated signals at the antennas. Both effects are completely taken into account in this framework; thus, it allows for a fair comparison of different antenna arrays for MIMO. It is distinguished between MIMO systems for multiplex transmission or pure beamforming, which have different requirements for the antennas. Different compact array configurations, which exploit spatial, polarization, and pattern diversity, are discussed and compared. For practical purposes, it is also shown how to connect this framework to standard path-based channel models.
Sequential circuit test generation in a genetic algorithm framework (1994)

Abstract|T est generation using deterministic faultoriented algorithms is highly complex and time-consuming. New approaches are needed to augment the existing techniques, both to reduce execution time and to improve fault coverage. In this work, we describe a genetic algorithm (GA) framew ork for sequential circuit test generation. The GA evolves candidate test vectors and sequences, using a fault simulator to compute the tness of each candidate test. Various GA parameters are studied, including alphabet size, tness function, generation gap, population size, and mutation rate, as well as selection and crossover schemes. High fault coverages were obtained for most of the IS-CAS89 sequential benchmark circuits, and execution times were signicantly lower than in a deterministic test generator in most cases.
Miniature spectrometers for biochemical analysis (1997)

Miniature spectrometers have been demonstrated by mounting micromachined diffraction gratings onto CCD imaging devices. Two implementations are tested: one for high-dispersion and -sensitivity applications, and the other for low-cost consumer applications. The first system shows a dispersion of 1.7 nm/pixel and a resolution of 74.4 for the bandwidth of interest. The free spectral range of the device is designed to be in the visible range for this particular application. The diffraction efficiency of the system is 63%. The second, low-cost system demonstrates a dispersion and resolution of 2.55 nm/pixel and 69.8, respectively. These specifications are comparable to that of a conventional, low-end commercial spectrometer. Results are shown for their applications in biochemical analysis. Further optimization is sought by adding micromachined lenses and creating specialized, computer-generated gratings to compress and shape the spectral signal.
Truncated Streptococcus pneumoniae PspA Molecules Elicit Cross-Protective Immunity against Pneumococcal Challenge in Mice (1996)

Immunization with pneumococcal surface protein A (PspA) from Streptococcus pneumoniae strain Rx1 cross-protects mice against challenge with diverse pneumococci. Truncated Rx1 PspA, consisting of amino acids 192-588, elicits protection against the mouse-virulent strain WU2. The possibility that homologous regions of other PspAs could also elicit cross-protection was investigated. Oligonucleotide primers designed according to the Rx1 pspA gene sequence were used to amplify chromosomal DNA from 15 diverse pneumococci. Three recombinant PspAs were evaluated for their ability to elicit protection in mice against challenge with 7 strains representing capsular types 3, 4, 5, 6A, and 6B. Two of the three truncated PspAs each elicited cross-protection against 71%-100% of the S. pneumoniae challenge strains examined. These data suggest that this technique may be useful for the generation of diverse PspAs for inclusion in a broadly protective pneumococcal vaccine.
A Dominant-Negative Cyclin D1 Mutant Prevents Nuclear Import of Cyclin-Dependent Kinase 4 (CDK4) and Its Phosphorylation by CDK-Activating Kinase (1997)

Cyclins contain two characteristic cyclin folds, each consisting of five alpha-helical bundles, which are connected to one another by a short linker peptide. The first repeat makes direct contact with cyclin-dependent kinase (CDK) subunits in assembled holoenzyme complexes, whereas the second does not contribute directly to the CDK interface. Although threonine 156 in mouse cyclin D1 is predicted to lie at the carboxyl terminus of the linker peptide that separates the two cyclin folds and is buried within the cyclin subunit, mutation of this residue to alanine has profound effects on the behavior of the derived cyclin D1-CDK4 complexes. CDK4 in complexes with mutant cyclin D1 (T156A or T156E but not T156S) is not phosphorylated by recombinant CDK-activating kinase (CAK) in vitro, fails to undergo activating T-loop phosphorylation in vivo, and remains catalytically inactive and unable to phosphorylate the retinoblastoma protein. Moreover, when it is ectopically overexpressed in mammalian cells, cyclin D1 (T156A) assembles with CDK4 in the cytoplasm but is not imported into the cell nucleus. CAK phosphorylation is not required for nuclear transport of cyclin D1-CDK4 complexes, because complexes containing wild-type cyclin D1 and a CDK4 (T172A) mutant lacking the CAK phosphorylation site are efficiently imported. In contrast, enforced overexpression of the CDK inhibitor p21Cip1 together with mutant cyclin D1 (T156A)-CDK4 complexes enhanced their nuclear localization. These results suggest that cyclin D1 (T156A or T156E) forms abortive complexes with CDK4 that prevent recognition by CAK and by other cellular factors that are required for their nuclear localization. These properties enable ectopically overexpressed cyclin D1 (T156A), or a more stable T156A/T286A double mutant that is resistant to ubiquitination, to compete with endogenous cyclin D1 in mammalian cells, thereby mobilizing CDK4 into cytoplasmic, catalytically inactive complexes and dominantly inhibiting the ability of transfected NIH 3T3 fibroblasts to enter S phase.
The velocity measurement of cooling gas in SF6 gas transformer by reflective ultrasonic wave method (1998)

The improvement of the cooling-gas velocity distribution over the coil windings in SF6 gas transformer is very important to achieve high quality for designing. In this paper, the application results of the reflective-type ultrasonic wave method to measure the cooling gas distribution in the SP6 gas transformer are reported. This measurement can be performed without disturbance of the gas flow by the presence of the sensors, and this method is demonstrated to be more effective than the conventional fluid velocity measuring method. In this measurement, the velocity of gas flow at some locations in the transformer was not proportional to the volume of the input gas flow. It can be divided into three patterns corresponding to the location as follows. (a) Gas velocity increases with the increase of the input gas flow amount. (b) Gas velocity is constant regardless of the increase of the input gas flow amount. (c) Gas velocity decreases with the increase of the input flow in the first, and changes to increase with the further increase of the input flow. These characteristics are compared with the computational results of gas flow analysis. © 1998 Scripta Technica. Electr Eng Jpn, 122(3): 1–9, 1998
Novel Small-Molecule Inhibitors of Anthrax Lethal Factor Identified by High-Throughput Screening (2006)

Anthrax lethal factor (LF) is a key virulence factor of anthrax lethal toxin. We screened a chemolibrary of 10,000 drug-like molecules for their ability to inhibit LF and identified 18 novel small molecules with potent LF inhibitory activity. Three additional LF inhibitors were identified through further structure-activity relationship (SAR) analysis. All 21 compounds inhibited LF with an IC50 range of 0.8 to 11 muM, utilizing mixed-mode competitive inhibition. An evaluation of inhibitory activity against a range of unrelated proteases showed relatively high specificity for LF. Furthermore, pharmacophore modeling of these compounds showed a high degree of similarity to the model published by Panchal et al. (Nat. Struct. Mol. Biol. 2004, 11, 67-72), indicating that the conformational features of these inhibitors are structurally compatible with the steric constraints of the substrate-binding pocket. These novel LF inhibitors and the structural scaffolds identified as important for inhibitory activity represent promising leads to pursue for further LF inhibitor development.
Simple, Rapid, Sensitive, and Versatile SWNT−Paper Sensor for Environmental Toxin Detection Competitive with ELISA (2009)

Safety of water was for a long time and still is one of the most pressing needs for many countries and different communities. Despite the fact that there are potentially many methods to evaluate water safety, finding a simple, rapid, versatile, and inexpensive method for detection of toxins in everyday items is still a great challenge. In this study, we extend the concept of composites, impregnated porous fibrous materials, such as fabrics and papers, by single-walled carbon nanotubes (SWNTs), toward very simple but high-performance biosensors. They utilize the strong dependence of electrical conductivity through nanotubes percolation network on the width of nanotube-nanotube tunneling gap and can potentially satisfy all the requirements outlined above for the routine toxin monitoring. An antibody to the microcystin-LR (MC-LR), one of the common culprits in mass poisonings, was dispersed together with SWNTs. This dispersion was used to dip-coat the paper rendering it conductive. The change in conductivity of the paper was used to sense the MC-LR in the water rapidly and accurately. The method has the linear detection range up to 10 nmol/L and nonlinear detection up to 40 nmol/L. The limit of detection was found to be 0.6 nmol/L (0.6 ng/mL), which satisfies the strictest World Health Organization standard for MC-LR content in drinking water (1 ng/mL) and is comparable to the detection limit of the traditional ELISA method of MC-LR detection, while drastically reducing the time of analysis by more than an order of magnitude, which is one of the major hurdles in practical applications. Similar technology of sensor preparation can also be used for a variety of other rapid environmental sensors.
Effect of quiescence on integrin alpha5beta1 expression in human retinal pigment epithelium. (2003)

We demonstrated that cell confluence affected protein and gene expression of the integrin alpha5 subunit. Proliferating RPE cells expressed high levels of both the alpha5 protein and mRNA transcripts and showed a high promoter activity. However, when cells reached quiescence, alpha5 gene expression was substantially reduced and RPE cells expressed little alpha5 protein at their cell surface.
Predictors of deterioration of lung function in cystic fibrosis* (2002)

The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.The severity of pulmonary disease was to some extent predicted by CFTR genotype. Furthermore, the present investigation is the first long-term study showing a significantly more rapid deterioration of lung function in patients with concomitant diabetes mellitus. Besides diabetes mellitus, pancreatic insufficiency and chronic Pseudomonas colonization were found to be negative predictors of pulmonary function. In contrast to several other reports, we found no significant differences in lung function between genders. Patients with pancreatic sufficiency have no or only a slight decline of lung function with age once treatment is started, but an early diagnosis in this group is desirable.
Rescue of synthetic genomic RNA analogs of rabies virus by plasmid-encoded proteins (1994)

Proteins entirely expressed from cDNA were used to rescue synthetic RNA genome analogs into infectious defective particles of rabies virus (RV). Synthetic negative-stranded RNAs containing 3'- and 5'-terminal RV sequences and transcriptional signal sequences were transcribed from plasmids transfected into cells expressing T7 RNA polymerase from recombinant vaccinia virus. After simultaneous expression of RV N, P, and L proteins from plasmids containing a T7 RNA polymerase promoter, the synthetic genomes were encapsidated, replicated, and transcribed by the RV polymerase proteins. Insertion of the bacterial chloramphenicol acetyltransferase gene or beta-galactosidase (lacZ) gene between the 3' and 5' termini containing transcriptional signal sequences resulted in transcription of mRNAs and expression of chloramphenicol acetyltransferase and beta-galactosidase, respectively. Upon simultaneous expression of N, P, M, G, and L proteins, virions carrying the foreign genes were assembled and released into the supernatant. The possibility of rescuing cDNA into rabies virions by proteins also expressed entirely from cDNA opens the possibility of studying the functions of each RV protein and analyzing cis-acting signals of the RV genome.
Alkali Metal-Hydroxide-Catalyzed C(sp)–H Bond silylation (2016)

Disclosed is a mild, scalable, and chemoselective catalytic cross-dehydrogenative C-H bond functionalization protocol for the construction of C(sp)-Si bonds in a single step. The scope of the alkyne and hydrosilane partners is substantial, providing an entry point into various organosilane building blocks and additionally enabling the discovery of a number of novel synthetic strategies. Remarkably, the optimal catalysts are NaOH and KOH.
BALLAST: a methodology for partial scan design (1989)

In the proposed partial scan methodology, the scan path is constructed so that the rest of the circuit belongs to a class of circuits called balanced sequential structures. Test patterns for this structure are generated by treating it as being combinational. Each test pattern is applied to the circuit by shifting it into the scan path. holding it constant for a fixed number of clock cycles, loading the test result into the scan path, and then shifting it out. This technique achieves full coverage of all detectable faults with a minimal number of scannable storage elements and using only combinational test pattern generation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Biochemical and Genetic Definition of the Cellular Protease Required for HIV-1 gp160 Processing (1995)

The surface glycoproteins of enveloped viruses bind to target cell receptors and trigger membrane fusion for infection. The human immunodeficiency virus 1 (HIV-1) envelope glycoprotein gp120 (CD4 binding protein) and gp41 (transmembrane fusion protein) are initially synthesized as a gp160 precursor. The intracellular cleavage of gp160 by a host cell protease during transit through the secretory pathway is essential for viral activities such as infectivity, membrane fusion, and T-cell syncytium formation. We report that gp160 biogenesis, protein processing, and cell-surface expression have been successfully reproduced in the yeast Saccharomyces cerevisiae. Genetic and biochemical approaches are used for defining that the unique cellular protease, Kex2p, is directly responsible for HIV-gp160 processing in yeast, in vivo and in vitro. The yeast system described in this report represents a powerful strategy for identifying, characterizing and inhibiting the host T-cell protease essential for HIV infectivity and AIDS.
Regulation of Adipocyte Development (1994)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
MILD AND CONVENIENT ONE POT SYNTHESIS OFN-HYDROXYIMIDES FROMN-UNSUBSTITUTED IMIDES (2001)

A new, one pot synthesis of various N-hydroxyimides from N-unsubstituted imides is described. Imides are first transformed into their N-Boc derivatives, which are next reacted with aqueous hydroxylamine, providing crystalline hydroxylammonium salts of the corresponding N-hydroxyimides. Filtration and acidic workup affords pure N-hydroxyimides.
Cooperative, Nanoparticle‐Enabled Thermal Therapy of Breast Cancer (2011)

Hollow gold nanoshells are more efficient in heat generation triggered by near infrared laser when they are loaded into porous silicon particles, which results in effective cancer-cell killing in vitro and in vivo. Collective electromagnetic coupling of nanoconfined hollow gold nanoshells leads to dramatic enhancement of thermal ablation.
Clinical status and optimal use of rituximab for B-cell lymphomas. (1998)

Rituximab (IDEC-C2B8 [Rituxan]) is a chimeric anti-CD20 monoclonal antibody (MoAb) that was recently approved by the FDA for the treatment of patients with low-grade or follicular B-cell non-Hodgkin's lymphoma. Its potential efficacy in other B-cell malignancies is currently being explored. This article reviews the mechanisms of action of rituximab, as well as preclinical data and results of the clinical trials that led to its approval. Also discussed are the mechanics of administering rituximab on the recommended weekly x 4 outpatient schedule. Finally, the article describes ongoing and planned trials of rituximab in other dosage schedules, in other B-cell neoplasms, and in conjunction with chemotherapy. As the first MoAb to gain FDA approval for the treatment of a malignancy, rituximab signals the beginning of a promising new era in cancer therapy.