gebhart/patrepeval huggingface dataset:
Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization‐defined chromosome 13 deletion in multiple myeloma: early results of total therapy II (2002)

Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.
Role of Cell Cycle Regulatory Proteins in Cerebellar Granule Neuron Apoptosis (1999)

Cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing concentrations of KCl, but the underlying molecular mechanisms are not yet clear. Although caspases have been postulated to be involved in CGN cell death, inhibitors of caspases failed to prevent apoptosis under our culture conditions, suggesting an involvement of other molecules and pathways. We find that inhibitors of cyclin-dependent kinases--flavopiridol, olomoucine, and roscovitine--protect CGNs from KCl withdrawal-induced apoptosis, suggesting that cell cycle components play a significant role in the death of these neurons. Analysis of the different cell cycle regulatory elements in this model revealed that apoptosis is preceded by an increase in the level of cyclin E protein, with elevated nuclear levels of cyclin D1 and with enhanced activity of the cyclin D1- and E- associated kinases. In addition, there was a significant decrease in the level of the cyclin-dependent kinase (cdk) inhibitor p27. In agreement with these changes, analysis of a major substrate of cyclin-activated cdks, retinoblastoma protein (Rb), showed an increase in the level of phosphorylated forms within 1 hr of KCl withdrawal. Moreover, the overall levels of Rb protein were significantly reduced within 6-12 hr of KCl withdrawal and did so by a caspase-independent mechanism. All of these responses were blocked by cdk inhibitors. These findings indicate that cdks act at an early step in the pathway by which KCl withdrawal induces apoptotic death of cerebellar granule cells and suggest that additional elements of the cell cycle machinery participate in this mechanism.
True Immunogenicity of Oncofetal Antigen/Immature Laminin Receptor Protein (2004)

Su et al . [(1)][1] described the detection of RNA present in renal cell carcinoma (RCC) that achieved expression of oncofetal antigen (OFA) in RCC patient’s monocytes and gave rise to OFA-expressing dendritic cells ex vivo . When these OFA-expressing dendritic cells were infused back into
Efficient Batch Top-k Search for Dictionary-based Entity Recognition (2006)

We consider the problem of speeding up Entity Recognition systems that exploit existing large databases of structured entities to improve extraction accuracy. These systems require the computation of the maximum similarity scores of several overlapping segments of the input text with the entity database. We formulate a Batch-Top-K problem with the goal of sharing computations across overlapping segments. Our proposed algorithm performs a factor of three faster than independent Top-K queries and only a factor of two slower than an unachievable lower bound on total cost. We then propose a novel modification of the popular Viterbi algorithm for recognizing entities so as to work with easily computable bounds on match scores, thereby reducing the total inference time by a factor of eight compared to stateof- the-art methods.
Resuscitation potentials after prolonged global cerebral ischemia in cats (1988)

Predictors of postischemic recovery were determined in adult cats subjected to one hour of global brain ischemia followed by blood recirculation for 3 h or longer. The incidence of postischemic recovery of evoked potentials and of spontaneous EEG activity was determined and related to the following variables: anesthesia (barbiturate or halothane/nitrous oxide), completeness of ischemia, body temperature, plasma glucose, arterial pH, blood gases, blood osmolality, postischemic BP, and cerebral blood flow (CBF). The closest correlation was obtained with the rate of initial postischemic recirculation; CBF above 40 ml/100 g.min resulted almost consistently in EEG recovery. Temperature, arterial pH, plasma glucose, and osmolality also influenced recovery. There was no correlation of EEG recovery with blood gases nor improvement of recovery after incomplete ischemia or barbiturate anesthesia. The results are interpreted in respect to common concepts of ischemic injury and the treatment of postischemic resuscitation disease.
Velocity Effect on Aptamer-Based Circulating Tumor Cell Isolation in Microfluidic Devices (2011)

The isolation and detection of rare circulating tumor cells (CTCs) has been one of the focuses of intense research recently. In a microfluidic device, a number of factors can influence the enrichment capability of surface-bound probe molecules. This article analyzes the important factor of flow velocity in a microfluidic channel. The competition of surface-grafted anti-EGFR aptamers to bind the overexpressed EGFR on cell membranes against the drag force from the fluid flow is an important efficiency determining factor. The flow rate variations are applied both in experiments and in simulation models to study their effects on CTC capture efficiency. A mixture of mononuclear cells and human Glioblastoma cells is used to isolate cancer cells from the cellular flow. The results show interdependence between the adhesion probability, isolation efficiency, and flow rate. This work can help in designing flow-through lab-on-chip devices that use surface-bound probe affinities against overexpressed biomarkers for cell isolation. This work demonstrates that microfluidic based approaches have strong potential applications in CTC detection and isolation.
ECG signal compression using Compressive Sensing and wavelet transform (2012)

Compressed Sensing (CS) is a novel approach of reconstructing a sparse signal much below the significant Nyquist rate of sampling. Due to the fact that ECG signals can be well approximated by the few linear combinations of wavelet basis, this work introduces a comparison of the reconstructed 10 ECG signals based on different wavelet families, by evaluating the performance measures as MSE (Mean Square Error), PSNR (Peak Signal To Noise Ratio), PRD (Percentage Root Mean Square Difference) and CoC (Correlation Coefficient). Reconstruction of the ECG signal is a linear optimization process which considers the sparsity in the wavelet domain. L1 minimization is used as the recovery algorithm. The reconstruction results are comprehensively analyzed for three compression ratios, i.e. 2&#x2236;1, 4&#x2236;1, and 6&#x2236;1. The results indicate that reverse biorthogonal wavelet family can give better results for all CRs compared to other families.
An assessment of the genetic toxicology of novel boron‐containing therapeutic agents (2013)

Boron-containing compounds are being studied as potential therapeutic agents. As part of the safety assessment of these therapeutic agents, a battery of genetic toxicology studies was conducted. The battery included a bacterial reverse mutation (Ames) assay, an in vitro chromosome aberration assay in peripheral human lymphocytes, and an in vivo rat micronucleus study. The following compounds represent some of the boron-containing compounds that have been advanced to human clinical trials in various therapeutic areas. The borinic picolinate, AN0128, is an antibacterial compound with anti-inflammatory activity that has been studied in clinical trials for acne and the treatment of mild to moderate atopic dermatitis. AN2690 (tavaborole) is a benzoxaborole in Phase 3 clinical trials for the topical treatment of onychomycosis, a fungal infection of the toenails and fingernails. Another benzoxaborole derivative, AN2728, a phosphodiesterase-4 (PDE4) inhibitor, is in Phase 2 clinical trials for the treatment of atopic dermatitis. AN2898, also a PDE4 inhibitor, has been studied in clinical trials for atopic dermatitis and psoriasis. AN3365 is a leucyl-tRNA synthetase inhibitor that has been in clinical development for the treatment of various Gram-negative bacterial infections. These five representative compounds were negative in the three genotoxicity assays. Furthermore, AN2690 has been studied in mouse and rat 2-year bioassays and was not found to have any carcinogenic potential. These results demonstrate that it is possible to design boron-based therapeutic agents with no genetic toxicology liabilities.
Signal transduction in inflammatory cells (1992)

The kinetics of ligand-receptor interactions modulation of receptor activity structure and function of nucleotide-binding proteins in signal transduction structure and functions of the phospholipase C enzymes phosphatidylcholine metabolism in signal transduction calcium translocations in signal tranduction inositol phosphate metabolism.
Escherichia coli 0157:H7 Visual Immunoprecipitate Assay: A Comparative Validation Study (1997)

A wide variety of food products, with emphasis on raw meat products, were analyzed simultaneously by 3 methods: the Escherichia coli O157:H7 (EHEC) visual immunoprecipitate assay (VIP), the Assurance EHEC enzyme immunoassay, and a modified Bacteriological Analytical Manual (BAM) culture method. This paper reports results of a comparative study of the VIP and modified BAM methods. In this comparative study, 1050 samples and controls gave false-negative rates of 1.0 and 0%, respectively, for the VIP and the modified BAM culture methods. The overall agreement between the 2 methods was 99.4%. Cultural confirmation of presumptive positive samples was problematic because competitive flora were present in higher levels than EHEC in the enrichment broth after incubation and the target organism had nondescript characteristics on the primary selective agar, hemorrhagic coli agar, which necessitated picking of additional colonies in many instances.
Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160. (1988)

The synthesis and processing of the human immunodeficiency virus 1 (HIV-1) envelope precursor glycoprotein gp 160 was studied in an infected CD4+ lymphocytic cell line. Surprisingly, only a small percentage (5-15%) of gp160 is cleaved to produce the mature gp120 component. Intracellular sorting results in the transfer of most uncleaved gp160 to lysosomes, where it is degraded, while gp120 is transported to the cell surface and subsequently secreted. Cleavage of gp160 to generate gp120 occurs intracellularly and can be inhibited by NH4Cl. Taken together, these results indicate that intracellular cleavage of gp160 determines the intracellular transport and survival of the envelope glycoproteins necessary to produce infectious virus.
Calorimetric calibration of head coil SAR estimates displayed on a clinical MR scanner (2008)

Calorimetric measurements were performed to determine the average specific absorption rates (SAR) resulting from MRI head examinations. The data were compared with average head coil SAR estimates displayed by the MR scanner in order to refine the imaging protocols used in imaging patients with implanted deep brain stimulators (DBS). The experiments were performed using transmit-receive (TR) head coil on clinical 1.5 T General Electric MR scanners running 11.0 M4 revision software. The average applied SAR was derived from temperature increases measured inside a head phantom, due to deposition of RF energy during MRI scanning with a spin echo imaging sequence. The measurements were repeated for varied levels of RF transmit gain (TG) and analyzed with a range of entered patient weights. The measurements demonstrate that the ratio of the actual average head SAR to the scanner-displayed value (coil correction factor) decreases for decreasing TG or for increasing patient weight and may vary between 0.3 and 2.1. An additional retrospective patient study, however, shows that not all combinations of TG and patient weight are encountered clinically and, instead, TG generally increases with the patient weight. As a result, a much narrower range of coil correction factors (e.g., typically 0.5-1.0) will be encountered in practice. The calorimetric method described in this work could aid the physicians and technologists in refinement of the model-dependent SAR estimates displayed by the MR scanner, and in selection of imaging parameters for MR head examinations within allowable SAR safety levels.
An androgen receptor N-terminal domain antagonist for treating prostate cancer (2013)

Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). The mechanisms that drive CRPC are incompletely understood, but may involve constitutively active AR splice variants that lack the LBD. The AR N-terminal domain (NTD) is essential for AR activity, but targeting this domain with small-molecule inhibitors is complicated by its intrinsic disorder. Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. We found that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of CRPC xenografts. These findings suggest that the development of small-molecule inhibitors that bind covalently to intrinsically disordered proteins is a promising strategy for development of specific and effective anticancer agents.
Minimal homology requirements for PCR primers (1989)

Homologous genes from different species may be succesfully cloned by utilizing the PCR process (1-3). Since this becomes an increasingly attractive alternative to conventional low stringency screens, it is interesting to know which minimal homolgy a prime needs in order to be effective for the PCR process. We h a v e addressed this question by testing a preexisting set of primers on defined DNA templates. The latter were obtained from subcloned pieces of the hunchback genes of Drosophila melanogaster and Drosophila virilis (4) In the tests we used always one primer with a perfect homology and one primer with a partial homology in order to amplify pieces with a length of 200-lOOOnt. The amplification products were resolved on agarose gels. Table Primers with a lenigth between 17-20nt need at least three homologous nucleotides at their ' '-end for successful priming. Weak priming was however also obtained with a long primer having only 2 nucleotides homology (Table Surprisingly, the remainder of the primer needs only very little homology with the target sequence. This is particularly clear from the cases c,d and k (Table From these results we suggest the following criteria for primers to be employed in cloning homologous genes: the length should be preferably between 20-24nt and the three 3' nucleotides should match completely. This may be ensured by letting them end at a Met or Trp residue or by synthesizing appropriate redundant oligos for these positions. For the rest of the primer it appears to be sufficient to conform largely with the prefered codon usage of the organism. This allows to reduce the redundancy of the employed primers which should in turn reduce the amount of artefacts. Using primers based on these criteria we have successfully cloned the Ihunchback gene from Musca domestica (unpublished).
Modifications of a macrolide antibiotic midecamycin (SF-837). I. Synthesis and structure of 9,3"-diacetylmidecamycin. (1976)

9,3''-Diacetylmidecamycin (12) was synthesized from 4''-depropionyl-9,2',4''-triacetylmidecamycin (8) by heating the latter with propionic anhydride in pyridine followed by removal of 2'-acetyl group, with or without 18-enolpropionyl group. Direct acetylation of midecamycin (1) led to the formation of the 3'',4''-positional isomer (6). The structure of 12 was determined by mass, NMR and chemical degradation. The location of 3''-acetyl group was shown by the stereospecific 3 leads to 1 acetyl migration catalyzed by a base of 3-O-acetyl-4-O-propionyl-L-mycarose (13), and comparison of NMR and mass fragmentation with the 3,4-positional isomer (15). The latter's structure was independently supported by the nuclear Overhauser effect between methyl and propionyl group at C-3. The intramolecular 4 leads to 3 acyl shift that was taken place in the forced acylation of the mycarose moiety was found to be affected by the anomeric configuration, nature of aglycones and reaction temperature. Reverse 3 leads to 4 acyl migration occurred in acidic hydrolysis.
Is the Irritable Gut an Inflamed Gut? (1992)

Recent advances in the field of neuroimmunology have provided clear demonstrations of i) the neuromodulation of immune function, and ii) the involvement of the immune system in responses induced by psychologic stress in animals and in man. This has led to speculation about the role of the immune system in psychosocial disease. The irritable bowel syndrome (IBS) is characterized by chronic gastrointestinal dysfunction, which may reflect in altered motility, epithelial function, or sensory perception in the gut. IBS is heterogeneous not only in terms of its clinical presentation but also in terms of its pathogenesis, and factors ranging from psychoneurotic behavior and emotional stress, to dietary fiber deficiency, food intolerance, and enteric infection have been implicated. There is evidence of an increase in the inflammatory cells present in the gut of some IBS patients and in an emerging literature that demonstrates the immunomodulation of the motor system of the gut. These findings invite speculation that the immune system may play a role in the pathogenesis and pathophysiology of at least a subpopulation of IBS patients.
High-speed 3-D shape measurement based on digital fringe projection (2003)

A high-speed 3-D shape measurement technique based on digital fringe projection has been developed and experimented. This technique uses a computer-generated color fringe pattern whose red, green, and blue channels are sinusoidal fringe patterns with a 120-deg phase shift between neighboring channels. When this color fringe pat- tern is sent to a digital-micromirror-device (DMD) based video projector with no color filter, three gray-scale fringe patterns are repeatedly pro- jected to an object surface in sequence with a cycle time of approxi- mately 10 ms. The three phase-shifted fringe patterns deformed by the object surface are captured by a CCD camera with proper synchroniza- tion between the camera and the projector. The 3-D shape of the object surface is reconstructed by using a phase wrapping and unwrapping algorithm and a phase-coordinate conversion algorithm. Experimental results demonstrated the feasibility of this technique for high-speed 3-D shape measurement with a potential measurement speed up to 100 Hz. © 2003 Society of Photo-Optical Instrumentation Engineers. (DOI: 10.1117/1.1525272) Subject terms: fringe projection; phase shifting; digital micromirror device; 3-D shape measurement.
Resistance to ROS1 Inhibition Mediated by EGFR Pathway Activation in Non-Small Cell Lung Cancer (2013)

The targeting of oncogenic 'driver' kinases with small molecule inhibitors has proven to be a highly effective therapeutic strategy in selected non-small cell lung cancer (NSCLC) patients. However, acquired resistance to targeted therapies invariably arises and is a major limitation to patient care. ROS1 fusion proteins are a recently described class of oncogenic driver, and NSCLC patients that express these fusions generally respond well to ROS1-targeted therapy. In this study, we sought to determine mechanisms of acquired resistance to ROS1 inhibition. To accomplish this, we analyzed tumor samples from a patient who initially responded to the ROS1 inhibitor crizotinib but eventually developed acquired resistance. In addition, we generated a ROS1 inhibition-resistant derivative of the initially sensitive NSCLC cell line HCC78. Previously described mechanisms of acquired resistance to tyrosine kinase inhibitors including target kinase-domain mutation, target copy number gain, epithelial-mesenchymal transition, and conversion to small cell lung cancer histology were found to not underlie resistance in the patient sample or resistant cell line. However, we did observe a switch in the control of growth and survival signaling pathways from ROS1 to EGFR in the resistant cell line. As a result of this switch, ROS1 inhibition-resistant HCC78 cells became sensitive to EGFR inhibition, an effect that was enhanced by co-treatment with a ROS1 inhibitor. Our results suggest that co-inhibition of ROS1 and EGFR may be an effective strategy to combat resistance to targeted therapy in some ROS1 fusion-positive NSCLC patients.
Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. (2002)

The angiogenic factor vascular endothelial growth factor-D (VEGF-D) isa ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and receptor-2 (VEGFR-2/KDR)and is implicated in the development of lymphatic vessels and promotion of lymphatic metastases. We assessed the expression of VEGF-D and VEGFR-3 in relation to microvessel density (MVD) in colorectal carcinomas (CRC), adenomas, and adjacent normal tissue by immunohistochemistry on consecutive archival sections. VEGF-D was detected in malignant and benign epithelium and in some smooth muscle of the colorectum. High-grade VEGF-D expression was observed frequently (74%) in CRC compared with adenomas (0%) and adjacent normal mucosa (22%). High-grade VEGF-D expression was not correlated with MVD, Dukes' stage (A to C), or tumor differentiation, but was associated with lymphatic involvement and patient survival. By multivariate analysis, VEGF-D expression was found to be an independent prognostic factor for both disease-free and overall survival. VEGFR-3 expression was detected in a subset of vessels, typically thin-walled and devoid of RBCs, in 89% of CRC cases examined. VEGFR-3-positive vessel densities increased progressively from normal mucosa to adenomas and carcinomas and were correlated with MVD, but not with Dukes' stage (A to C), tumor differentiation, or VEGF-D expression. VEGFR-3 expression was spatially associated with macrophage-rich inflammatory infiltrates, which were significantly more frequent among VEGFR-3-positive cases. We conclude that VEGF-D expression, but not that of its receptor VEGFR-3, is an independent prognostic indicator in CRC. VEGF-D expression may be associated with disease outcome through the promotion of lymphatic involvement/metastases.