gebhart/patrepeval huggingface dataset:
High Resolution Genetic and Physical Mapping of Molecular Markers Linked to the Phytophthora Resistance Gene Rps1-k in Soybean (1997)

The resistance of soybean to Phytophthora root and stem rot caused by Phytophthora sojae is conferred by a series of single-dominant Rps genes. We have applied random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) analyses to isolate molecular markers linked to Rps1-k. Five RAPD markers were identified and mapped closely to one side of Rps1-k. AFLP analysis was carried out with near isogenic lines and bulks obtained from F 3 families. Twenty-seven markers were identified. Nineteen of these were specific to the resistant parent. Five AFLP markers were amplified from the susceptible parent. One of these markers, TC1, mapped at 0.07 centimorgans (cM) from the Rps1 locus. Three AFLP markers were co-dominant, and one of these, CG1, mapped at a distance of 0.06 cM from the Rps1 locus on the opposite side of the rest of the markers. Two RAPD, 17 AFLP, and 14 restriction fragment length polymorphism (RFLP) markers originating from duplicated sequences were mapped within a 3-cM map interval. These results suggest that Rps1-k is located at the end of an introgressed region. Physical mapping data indicate that the Rps1-k-flanking markers CG1 and TC1 may be located within a 125-kb chromosomal fragment.
Angiogenesis Inhibitors and Hypertension (2007)

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Use of Artificial Intelligence in the Design of Small Peptide Antibiotics Effective against a Broad Spectrum of Highly Antibiotic-Resistant Superbugs (2008)

Increased multiple antibiotic resistance in the face of declining antibiotic discovery is one of society's most pressing health issues. Antimicrobial peptides represent a promising new class of antibiotics. Here we ask whether it is possible to make small broad spectrum peptides employing minimal assumptions, by capitalizing on accumulating chemical biology information. Using peptide array technology, two large random 9-amino-acid peptide libraries were iteratively created using the amino acid composition of the most active peptides. The resultant data was used together with Artificial Neural Networks, a powerful machine learning technique, to create quantitative in silico models of antibiotic activity. On the basis of random testing, these models proved remarkably effective in predicting the activity of 100,000 virtual peptides. The best peptides, representing the top quartile of predicted activities, were effective against a broad array of multidrug-resistant "Superbugs" with activities that were equal to or better than four highly used conventional antibiotics, more effective than the most advanced clinical candidate antimicrobial peptide, and protective against Staphylococcus aureus infections in animal models.
A Comparative Analysis of Low-Dose Metronomic Cyclophosphamide Reveals Absent or Low-Grade Toxicity on Tissues Highly Sensitive to the Toxic Effects of Maximum Tolerated Dose Regimens (2004)

The survival benefits of traditional maximum tolerated dose (MTD) cytotoxic therapy have been modest for the treatment of most types of metastatic malignancy and, moreover, often come with increased acute and chronic toxicity. Recent studies have demonstrated that the frequent administration of comparatively low doses of cytotoxic agents, with no extended breaks [low-dose metronomic (LDM) chemotherapy], may not only be at least as efficient as MTD therapy but also less toxic. This coincides with an apparent selectivity for "activated" endothelial cells of the tumor vasculature. However, the impact of LDM chemotherapy on the most sensitive target cell populations normally affected by MTD therapy (i.e., bone marrow progenitors, gut mucosa, and hair follicle cells) has not been analyzed in experimental detail. Therefore, we compared effects of LDM and MTD cyclophosphamide (CTX) on bone marrow and gut mucosa. Furthermore, we studied the potential impact of LDM CTX on angiogenesis in the context of wound healing and evidence of organ toxicity. We show absent or moderate hematologic and intestinal toxicity of LDM as opposed to MTD CTX. Of note was the finding of sustained lymphopenia, which is not unexpected given the use of CTX as immunosuppressive drug. There was no negative impact on wound healing or evidence of organ toxicity. LDM offers clear safety advantages over conventional MTD chemotherapy and therefore would appear to be ideal for long-term combination therapy with targeted antiangiogenic drugs.
Long non-coding RNA HULC promotes tumor angiogenesis in liver cancer by up-regulating sphingosine kinase 1 (SPHK1) (2015)

Highly up-regulated in liver cancer (HULC) is a long non-coding RNA (lncRNA). We found that HULC up-regulated sphingosine kinase 1 (SPHK1), which is involved in tumor angiogenesis. Levels of HULC were positively correlated with levels of SPHK1 and its product, sphingosine-1-phosphate (S1P), in patients HCC samples. HULC increased SPHK1 in hepatoma cells. Chicken chorioallantoic membrane (CAM) assays revealed that si-SPHK1 remarkably blocked the HULC-enhanced angiogenesis. Mechanistically, HULC activated the promoter of SPHK1 in hepatoma cells through the transcription factor E2F1. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) further showed that E2F1 was capable of binding to the E2F1 element in the SPHK1 promoter. HULC increased the expression of E2F1 in hepatoma cells and levels of HULC were positively correlated with those of E2F1 in HCC tissues. Intriguingly, HULC sequestered miR-107, which targeted E2F1 mRNA 3'UTR, by complementary base pairing. Functionally, si-SPHK1 remarkably abolished the HULC-enhanced tumor angiogenesis in vitro and in vivo. Taken together, we conclude that HULC promotes tumor angiogenesis in liver cancer through miR-107/E2F1/SPHK1 signaling. Our finding provides new insights into the mechanism of tumor angiogenesis.
Oral Efficacy of a Respiratory Syncytial Virus Inhibitor in Rodent Models of Infection (2004)

BMS-433771 is a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. Mechanism of action studies have demonstrated that BMS-433771 halts virus entry through inhibition of F protein-mediated membrane fusion. BMS-433771 also exhibited in vivo efficacy following oral administration in a mouse model of RSV infection (C. Cianci, K. Y. Yu, K. Combrink, N. Sin, B. Pearce, A. Wang, R. Civiello, S. Voss, G. Luo, K. Kadow, E. Genovesi, B. Venables, H. Gulgeze, A. Trehan, J. James, L. Lamb, I. Medina, J. Roach, Z. Yang, L. Zadjura, R. Colonno, J. Clark, N. Meanwell, and M. Krystal, Antimicrob. Agents Chemother. 48:413-422, 2004). In this report, the in vivo efficacy of BMS-433771 against RSV was further examined in the BALB/c mouse and cotton rat host models of infection. By using the Long strain of RSV, prophylactic efficacy via oral dosing was observed in both animal models. A single oral dose, administered 1 h prior to intranasal RSV inoculation, was as effective against infection as a 4-day b.i.d. dosing regimen in which the first oral dose was given 1 h prior to virus inoculation. Results of dose titration experiments suggested that RSV infection was more sensitive to inhibition by BMS-433771 treatment in the BALB/c mouse host than in the cotton rat. This was reflected by the pharmacokinetic and pharmacodynamic analysis of the efficacy data, where the area under the concentration-time curve required to achieve 50% of the maximum response was approximately 7.5-fold less for mice than for cotton rats. Inhibition of RSV by BMS-433771 in the mouse is the result of F1-mediated inhibition, as shown by the fact that a virus selected for resistance to BMS-433771 in vitro and containing a single amino acid change in the F1 region was also refractory to treatment in the mouse host. BMS-433771 efficacy against RSV infection was also demonstrated for mice that were chemically immunosuppressed by cyclophosphamide treatment, indicating that compound inhibition of the virus did not require an active host immune response.
The "Annai" environment for portable distributed parallel programming (2002)

We are developing a portable integrated tool environment, called "Annai", for distributed memory parallel processors (DMPPs), as part of the joint CSCS-ETH/NEC collaboration in parallel processing. As we design and implement a sequence of tool prototypes, these are used and evaluated by a team of application developers. This close interaction allows rapid feedback, as requests from the application developers for functionality enhancements can be promptly considered for inclusion in future tool designs and prototypes. Our tool environment consists of an extended High Performance Fortran (HPF) compiler, a performance monitor and analyzer and a source-level debugger for distributed programs, all sharing a common user interface. The recently-defined Message Passing Interface (MPI) serves as our low-level machine interface and allows portability independent of the target hardware architecture. The key features of the tool environment comprise HPF language extensions to allow dynamic data distributions, and support for both high-level data-parallel and low-level message-passing programming paradigms by the interactive debugger and the interactive performance monitor and analyzer. The language extensions are particularly useful for the efficient parallelization of unstructured problems, and they are fully supported by both the debugger and the performance analyzer. We outline the structure of the tool environment, and summarize the functionality of its components. We also demonstrate an example user session and present performance results on two DMPPs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Lactotetraose series ganglioside 3',6'-isoLD1 in tumors of central nervous and other systems in vitro and in vivo. (1993)

Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuAc or NeuGc)alpha 2-6GlcNAc. The distribution of 3',6'-isoLD1 in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Only 4 of 26 cell lines, 3 teratomas and 1 pancreatic adenocarcinoma, expressed detectable 3',6'-isoLD1 when cultured in vitro; none of 14 tested glioma lines, including 2 that expressed the monosialo-precursor IV3NeuAcLcOse4Cer in vitro, expressed detectable levels. Expression of 3',6'-isoLD1 was more frequent when neoplastic cells were grown in xenograft form in athymic mice; 4 of 10 glioma and 2 of 2 teratoma xenograft ganglioside extracts were positive for 3',6'-isoLD1. The absence of 3',6'-isoLD1 in cultured tumor cells of the central nervous system and its proportional increased presence in tumor cells of the same origin grown in vivo further supports previous studies suggesting that ganglioside expression may be modified by environmental forces. The expression of lacto series gangliosides both in vitro and in vivo by teratoma and pancreatic adenocarcinoma cells, as opposed to only in vivo expression by glioma cells, suggests that tissue-specific forces may also exist. Immunohistochemical localization of 3',6'-isoLD1 in frozen sections of primary central nervous system neoplasms including those of glial and nonglial origin was performed; 20 of 30 (67%) of glial tumors were positive. Among nonglial tumors, 21 of 34 (62%) of epithelial cancers were reactive with anti-3',6'-isoLD1 monoclonal antibodies; notably negative were carcinomas of the ovary and lung carcinomas of all subtypes. Lymphomas and infiltrative lymphocytes were uniformly negative. The restriction of 3',6'-isoLD1 expression within the human central nervous system to periods of fetal-neonatal astroglial proliferation, to intense reactive astrocytosis, and to primary neoplasms, and the production of specific monoclonal antibodies to this epitope provide a specific complex for immunolocalization and, eventually, immunotherapy.
Plasma microRNA biomarkers for detection of mild cognitive impairment: Biomarker Validation Study (2013)

A minimally invasive test for early detection and monitoring of Alzheimer's and other neurodegenerative diseases is a highly unmet need for drug development and planning of patient care. Mild Cognitive Impairment (MCI) is a syndrome characteristic of early stages of many neurodegenerative diseases. Recently, we have identified two sets of circulating brain-enriched miRNAs, the miR-132 family (miR-128, miR-132, miR-874) normalized per miR-491-5p and the miR-134 family (miR-134, miR-323-3p, miR-382) normalized per miR-370, capable of differentiating MCI from age-matched control (AMC) with high accuracy. Here we report a biomarker validation study of the identified miRNA pairs using larger independent sets of age- and gender- matched plasma samples. The biomarker pairs detected MCI with sensitivity, specificity and overall accuracy similar to those obtained in the first study. The miR-132 family biomarkers differentiated MCI from AMC with 84%-94% sensitivity and 96%-98% specificity, and the miR-134 family biomarkers demonstrated 74%-88% sensitivity and 80-92% specificity. When miRNAs of the same family were combined, miR-132 and miR-134 family biomarkers demonstrated 96% and 87% overall accuracy, respectively. No statistically significant differences in the biomarker concentrations in samples obtained from male and female subjects were observed for either MCI or AMC. The present study also demonstrated that the highest sensitivity and specificity are achieved with pairs of miRNAs whose concentrations in plasma are highly correlated.
Visual acuity degradation resulting from dispersion in polycarbonate. (1991)

Visual acuities (VA) were measured through a series of prisms in order to quantify the blur that results from dispersion in polycarbonate. The mean VA of 40 eyes was reduced from a starting level of 20/13 unaided to 20/31 through 16 prism diopters of polycarbonate. The decline was a linear function of prismatic power. The blurring effect of polycarbonate was significantly greater than that of CR39. The blur from polycarbonate was found to be great enough that it should be taken into account whenever polycarbonate is considered for spectacle lenses. A graphical display is provided which can be used by the clinician to predict the degree of blur from a known polycarbonate lens.
Activated human B lymphocytes express three CTLA-4 counterreceptors that costimulate T-cell activation. (1993)

Signaling via the T-cell receptor complex is necessary but not sufficient to induce antigen-specific T lymphocytes to expand clonally. To proliferate, T cells must receive one or more costimulatory signals provided by antigen presenting cells (APCs). One such critical costimulatory signal is delivered by the CD28/CTLA-4 counterreceptor, B7, expressed on APCs. B7 costimulation induces CD28 signaling, resulting in interleukin 2 (IL-2) secretion, and T-cell proliferation. Conversely, T-cell receptor signaling in the absence of B7 costimulation results in induction of antigen-specific tolerance. Here, we show that activated human B lymphocytes express two additional CTLA-4 counterreceptors also capable of providing T-cell costimulation. At 24 hr postactivation, B cells express a CTLA-4 counterreceptor not recognized by anti-B7 or -BB-1 monoclonal antibodies (mAbs), which induces detectable IL-2 secretion and T-cell proliferation. At 48 and 72 hr postactivation, B cells express both B7 and a third CTLA-4 counterreceptor identified by the anti-BB-1 mAb. BB-1 appears to be a molecule distinct from B7 by its expression on B7- cells and its capacity to induce T cells to proliferate without significant accumulation of IL-2. As observed for B7, costimulatory signals mediated by these alternative CTLA-4/CD28 counterreceptors are likely to be essential for generation of an immune response and their absence may result in antigen-specific tolerance. We propose the following terminology for these CTLA-4 counterreceptors: (i) B7, B7-1; (ii) early CTLA-4 binding counterreceptor, B7-2; and (iii) BB-1, B7-3.
HERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine (1996)

Terfenadine carboxylate, the major metabolite of terfenadine, does not block either HERG or Kv1.5, which agrees with the hypothesis that the buildup of parent terfenadine is the likely explanation for its cardiotoxicity. We propose that the blocking of HERG by terfenadine explains the acquired long QT syndrome. HERG is likely to be the primary target for the known cardiotoxic effects of other, related antihistamines.
Increased sensitivity for Coomassie staining of sodium dodecyl sulfate‐polyacrylamide gels using PhastSystem Development Unit (1988)

Staining of proteins in PhastGel gradient media with Coomassie Blue R 350 was considerably improved using a lower concentration of methanol (10% v/v) and 2% ammonium sulfate in the staining solution and 10% acetic acid for destaining. The detection limit in sodium dodecyl sulfate-polyacrylamide gels was lowered by a factor of 10 to about 2 ng per protein band. The Coomassie staining method was adapted to the newly developed silver staining procedure so that both can be used in parallel in PhastSystem.
Efficient nonlinear optical conversion in porous GaP: the effect of light localization (2004)

We experimentally demonstrate very efficient non-phase-matched second- and third-harmonic generation from a macroporous GaP. The generated second-harmonic signal is independent of crystallographic orientation, and its enhancement is believed to be due to the light localization for which conditions exist in the studied samples of porous GaP. The nonlinear optical results are correlated with linear optical scattering studies and atomic-force microscopic images of the studied surfaces.
Learning cell geometry models for cell image simulation: An unbiased approach (2010)

Computer generation of cell images can provide annotated data to simulate various imaging conditions with controllable parameters. Synthesized images based on simple models cannot reflect the complicated parameter constraints in simulating real objects in terms of their deformation with appropriate probabilities. Learning-based techniques can provide insight to these properties and impose constraints on deformation selections. In this work, we discuss the simulation of gray level images of healthy red blood cell populations. Different from existing techniques, we learn the unbiased average shape and deformation models of the cells. Both models are used to guide the selection of possible deformations. We also learn cell color models to govern the texture generation of simulated cells. We apply this technique to simulate cell populations and validate the results using cell segmentation and counting algorithms. The proposed learning and simulation technique is generic and can be applied to other types of cells as well.
Integrated Task Planning and Control for Mobile Manipulators (2003)

In this paper we present an approach to decoupled force/position control of the end-effector along the same direction for redundant robots, and an approach to nonholonomic cart pushing with mobile manipulators. The mobile manipulator is considered as a redundant robot, and a unified dynamic model for an integrated mobile platform and on-board manipulator is developed. The dynamic model is decoupled and linearized using the nonlinear feedback technique in a unified frame. Combining the event-based planning and control method with singularity analysis of the robot arm, a task level action controller is designed and an online kinematic redundancy resolution scheme is developed. The system is stable during normal operation as well as at the occurrence of unexpected obstacles. In addition, explicit force/position control along the same task direction for redundant robots is proposed. The kinematic redundancy of mobile manipulators enables independent control of force and position along the same task directions. To verify the decoupled force/postion scheme, an integrated task planning and control approach is further proposed for the mobile manipulator to complete complicated tasks by regulating its output force. A cart pushing task, which requires both force and position control along the same task direction, is discussed. The cart manipulation task fully integrates trajectory and force planning of the cart, and planning and control of the mobile manipulators. The approaches have been tested on a mobile manipulator consisting of a Nomadic XR4000 and a Puma 560 robot arm. The experimental results demonstrate the efficacy of the approach for the mobile manipulation of a nonholonomic cart.
Economics of Schizophrenia (1995)

Community-based care can be less costly than conventional hospital-based programs and can improve patient quality of life. Inhospital programs that reduce length of stay with the use of medication clinics or day hospital care may achieve significant cost savings. A special challenge is the subgroup of patients suffering from schizophrenia that is neuroleptic-resistant. New drugs, such as the atypical neuroleptics, clozapine and risperidone, may prove to be highly cost-effective in treating schizophrenia by preventing relapse and reducing hospital lengths of stay.
Envelope Glycoprotein Mutations Mediate Equine Amplification and Virulence of Epizootic Venezuelan Equine Encephalitis Virus (2005)

Epidemics of Venezuelan equine encephalitis (VEE) result from high-titer equine viremia of IAB and IC subtype viruses that mediate increased mosquito transmission and spillover to humans. Previous genetic studies suggest that mutations in the E2 envelope glycoprotein allow relatively viremia-incompetent, enzootic subtype ID strains to adapt for equine replication, leading to VEE emergence. To test this hypothesis directly, chimeric VEEV strains containing the genetic backbone of enzootic subtype ID strains and the partial envelope glycoprotein genes of epizootic subtype IC and IAB strains, as well as reciprocal chimeras, were used for experimental infections of horses. Insertion of envelope genes from two different, closely related enzootic subtype ID strains into the epizootic backbones resulted in attenuation, demonstrating that the epizootic envelope genes are necessary for the equine-virulent and viremia-competent phenotypes. The partial epizootic envelope genes introduced into an enzootic ID backbone were sufficient to generate the virulent, viremia-competent equine phenotype. These results indicate that a small number of envelope gene mutations can generate an equine amplification-competent, epizootic VEEV from an enzootic progenitor and underscore the limitations of small animal models for evaluating and predicting the epizootic phenotype.