gebhart/patrepeval huggingface dataset:
Enhanced translocation of single DNA molecules through α-hemolysin nanopores by manipulation of internal charge (2008)

Both protein and solid-state nanopores are under intense investigation for the analysis of nucleic acids. A crucial advantage of protein nanopores is that site-directed mutagenesis permits precise tuning of their properties. Here, by augmenting the internal positive charge within the alpha-hemolysin pore and varying its distribution, we increase the frequency of translocation of a 92-nt single-stranded DNA through the pore at +120 mV by approximately 10-fold over the wild-type protein and dramatically lower the voltage threshold at which translocation occurs, e.g., by 50 mV for 1 event.s(-1).muM(-1). Further, events in which DNA enters the pore, but is not immediately translocated, are almost eliminated. These experiments provide a basis for improved nucleic acid analysis with protein nanopores, which might be translated to solid-state nanopores by using chemical surface modification.
Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer. (2002)

The results of the Phase I clinical trial suggest that DENSPM can safely be administered to patients with minimal toxicity. Furthermore, the observed dose-limiting toxicity is unique to DENSPM, thus underscoring the potential for DENSPM to be a suitable agent for chemotherapy in combination with agents possessing different spectrums of toxicities.
Protection against Simian Immunodeficiency Virus Vaginal Challenge by Using Sabin Poliovirus Vectors (2001)

Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to <10(3) copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population.
Quantification of plasma lipoproteins by proton nuclear magnetic resonance spectroscopy (1991)

A new analytical procedure for quantifying plasma lipoproteins by proton nuclear magnetic resonance (NMR) spectroscopy has been developed that potentially offers significant advantages over existing clinical methods used for assessing risk of coronary heart disease. Analysis of a single spectrum of a nonfasting plasma sample, acquired simply and rapidly at moderate magnetic field strength (250 MHz), yields a complete profile of lipoprotein concentrations: chylomicrons and very-low-, low-, and high-density lipoproteins. The method is based on curve-fitting (spectral deconvolution) of the plasma methyl lipid resonance envelope, the amplitude and shape of which depend directly on the amplitudes of the superimposed methyl resonances of the lipoprotein components. A linear least-squares curve-fitting algorithm was developed to efficiently extract the signal amplitudes (concentrations) of the lipoproteins from the plasma spectrum. These signal amplitudes correlate well with lipoprotein concentrations determined by triglyceride and cholesterol measurements.
Secure physical system design leveraging PUF technology (2012)

Physical systems are becoming increasingly computationally powerful as faster microprocessors are installed. This allows many types of applications and functionality to be implemented. Much of the security risk has to do with confirming the device as an authentic device. This risk can be mitigated using a technology known as Physically Unclonable Functions (PUFs). PUFs use the intrinsic differences in hardware behavior to produce a random function that is unique to that hardware instance. When combined with existing cryptographic techniques, these PUFs enable many different types of applications, such as read once keys, secure communications, and secure smart grids.
Reading performance after implantation of a small-aperture corneal inlay for the surgical correction of presbyopia: Two-year follow-up (2011)

After implantation of the small-aperture intracorneal inlay, there was an improvement in all tested reading performance parameters in emmetropic presbyopic patients; the improvement was the result of an increased depth of field. These 2-year results indicate that the inlay is an effective treatment for presbyopia.
Cytosolic Phospholipase A2α–deficient Mice Are Resistant to Collagen-induced Arthritis (2003)

Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A2alpha (cPLA2alpha) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA2alpha plays a key role in the development of CIA, we backcrossed cPLA2alpha-deficient mice on the DBA/1LacJ background that is susceptible to CIA. The disease severity scores and the incidence of disease were markedly reduced in cPLA2alpha-deficient mice compared with wild-type littermates. At completion of the study, >90% of the wild-type mice had developed disease whereas none of the cPLA2alpha-deficient mice had more than one digit inflamed. Furthermore, visual disease scores correlated with severity of disease determined histologically. Pannus formation, articular fibrillation, and ankylosis were all dramatically reduced in the cPLA2alpha-deficient mice. Although the disease scores differed significantly between cPLA2alpha mutant and wild-type mice, anti-collagen antibody levels were similar in the wild-type mice and mutant littermates. These data demonstrate the critical role of cPLA2alpha in the pathogenesis of CIA.
On-Bead Screening of Combinatorial Libraries: Reduction of Nonspecific Binding by Decreasing Surface Ligand Density (2009)

On-bead screening of one-bead-one-compound (OBOC) libraries provides a powerful method for the rapid identification of active compounds against molecular or cellular targets. However, on-bead screening is susceptible to interference from nonspecific binding, which results in biased screening data and false positives. In this work, we have found that a major source of nonspecific binding is derived from the high ligand loading on the library beads, which permits a macromolecular target (e.g., a protein) to simultaneously interact with multiple ligands on the bead surface. To circumvent this problem, we have synthesized a phosphotyrosyl (pY)-containing peptide library on spatially segregated TentaGel microbeads, which feature a 10-fold reduced peptide loading on the bead surface but a normal peptide loading in the bead interior. The library was screened against a panel of 10 Src homology 2 (SH2) domains including those of Csk and Fyn kinases and adaptor protein SLAP, and the specific recognition motif(s) was successfully identified for each of the domains. In contrast, when the SH2 domains were screened against a control library that contained unaltered (high) ligand loading at the bead surface, six of them exhibited varying degrees of sequence biases, ranging from minor perturbation in the relative abundance of different sequences to the exclusive selection of false positive sequences that have no measurable affinity to the target protein. These results indicate that reduction of the ligand loading on the bead surface represents a simple, effective strategy to largely eliminate the interference from nonspecific binding, while preserving sufficient amounts of materials in the bead interior for compound identification. This finding should further expand the utility of OBOC libraries in biomedical research.
An Interpretation for the ROC Curve and Inference Using GLM Procedures (2000)

The accuracy of a medical diagnostic test is often summarized in a receiver operating characteristic (ROC) curve. This paper puts forth an interpretation for each point on the ROC curve as being a conditional probability of a test result from a random diseased subject exceeding that from a random nondiseased subject. This interpretation gives rise to new methods for making inference about ROC curves. It is shown that inference can be achieved with binary regression techniques applied to indicator variables constructed from pairs of test results, one component of the pair being from a diseased subject and the other from a nondiseased subject. Within the generalized linear model (GLM) binary regression framework, ROC curves can be estimated, and we highlight a new semiparametric estimator. Covariate effects can also be evaluated with the GLM models. The methodology is applied to a pancreatic cancer dataset where we use the regression framework to compare two different serum biomarkers. Asymptotic distribution theory is developed to facilitate inference and to provide insight into factors influencing variability of estimated model parameters.
Development of Churg Strauss Syndrome in an Asthma Patient Taking Montelukast (2012)

A very limited number of reports have documented the association between leukotriene receptor antagonist (LTRA) and Churg-Strauss syndrome (CSS), but to date, a clear relationship has not been established because of its rarity.We report a 69-year-old asthma patient who suffered from progressive bilateral lower legs numbness and weakness about 2 weeks after taking montelukast. Nerve conduction velocity (NCV) showed axonal degenerative polyneuropathy. Because of shortness of breath, she was admitted soon after these symptoms were noted. The initial laboratory analyses showed eosinophilia (74% of white cell count) with a high total IgE level (2,768 IU/mL). Chest radiograph revealed non-fixed bilateral pneumonia. Dramatic resolution of the pneumonia with steroid treatment was achieved and montelukast treatment was stopped. In addition, Waters' view showed bilateral maxillary sinusitis. With the above findings, including asthma, marked eosinophilia, polyneuropathy, sinusitis, and non-fixed radiographic pulmonary infiltrates, CSS was diagnosed. We believe that montelukast is a useful and relatively safe drug for treating asthma, but care should be taken regarding its linkage with CSS.
Metabolic Engineering to Produce Sesquiterpenes in Yeast (2003)

[reaction: see text] Presented here is a metabolically engineered yeast strain that produces sesquiterpenes. Epi-cedrol synthase expressed in a native yeast strain converted endogenous farnesyl pyrophosphate to 90 microg/L epi-cedrol. This system was genetically modified to increase foreign terpene yields to 370 microg/L. The best yields were obtained by overexpressing a truncated 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in a upc2-1 mating type a background. This system allows sufficient production to characterize novel sesquiterpene synthase genes.
The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas (2001)

Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in B cells of the pancreas has been intensively investigated and now is quite well understood. The cytotoxic action of both these diabetogenic agents is mediated by reactive oxygen species, however, the source of their generation is different in the case of alloxan and streptozotocin. Alloxan and the product of its reduction, dialuric acid, establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl radicals are formed by the Fenton reaction. The action of reactive oxygen species with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of B cells. Streptozotocin enters the B cell via a glucose transporter (GLUT2) and causes alkylation of DNA. DNA damage induces activation of poly ADP-ribosylation, a process that is more important for the diabetogenicity of streptozotocin than DNA damage itself. Poly ADP-ribosylation leads to depletion of cellular NAD+ and ATP. Enhanced ATP dephosphorylation after streptozotocin treatment supplies a substrate for xanthine oxidase resulting in the formation of superoxide radicals. Consequently, hydrogen peroxide and hydroxyl radicals are also generated. Furthermore, streptozotocin liberates toxic amounts of nitric oxide that inhibits aconitase activity and participates in DNA damage. As a result of the streptozotocin action, B cells undergo the destruction by necrosis.
Structure of lobster apocrustacyanin A1using softer X-rays (2001)

The molecular basis of the camouflage colouration of marine crustacea is often provided by carotenoproteins. The blue colour of the lobster carapace, for example, is intricately associated with a multimacromolecular 16-mer complex of protein subunits each with a bound astaxanthin molecule. The protein subunits of crustacyanin fall into two distinct subfamilies, CRTC and CRTA. Here, the crystal structure solution of the A(1) protein of the CRTC subfamily is reported. The problematic nature of the structure solution of the CRTC proteins (both C(1) and A(1)) warranted consideration and the development of new approaches. Three putative disulfides per protein subunit were likely to exist based on molecular-homology modelling against known lipocalin protein structures. With two such subunits per crystallographic asymmetric unit, this direct approach was still difficult as it involved detecting a weak signal from these sulfurs and suggested the use of softer X-rays, combined with high data multiplicity, as reported previously [Chayen et al. (2000), Acta Cryst. D56, 1064-1066]. This paper now describes the structure solution of CRTC in the form of the A(1) dimer based on use of softer X-rays (2 A wavelength). The structure solution involved a xenon derivative with an optimized xenon L(I) edge f" signal and a native data set. The hand of the xenon SIROAS phases was determined by using the sulfur anomalous signal from a high-multiplicity native data set also recorded at 2 A wavelength. For refinement, a high-resolution data set was measured at short wavelength. All four data sets were collected at 100 K. The refined structure to 1.4 A resolution based on 60 276 reflections has an R factor of 17.7% and an R(free) of 22.9% (3137 reflections). The structure is that of a typical lipocalin, being closely related to insecticyanin, to bilin-binding protein and to retinol-binding protein. This A(1) monomer or dimer can now be used as a search motif in the structural studies of the oligomeric forms alpha- and beta-crustacyanins, which contain bound astaxanthin molecules.
Towards fully autonomous driving: Systems and algorithms (2011)

In order to achieve autonomous operation of a vehicle in urban situations with unpredictable traffic, several realtime systems must interoperate, including environment perception, localization, planning, and control. In addition, a robust vehicle platform with appropriate sensors, computational hardware, networking, and software infrastructure is essential. We previously published an overview of Junior, Stanford's entry in the 2007 DARPA Urban Challenge. This race was a closed-course competition which, while historic and inciting much progress in the field, was not fully representative of the situations that exist in the real world. In this paper, we present a summary of our recent research towards the goal of enabling safe and robust autonomous operation in more realistic situations. First, a trio of unsupervised algorithms automatically calibrates our 64-beam rotating LIDAR with accuracy superior to tedious hand measurements. We then generate high-resolution maps of the environment which are subsequently used for online localization with centimeter accuracy. Improved perception and recognition algorithms now enable Junior to track and classify obstacles as cyclists, pedestrians, and vehicles; traffic lights are detected as well. A new planning system uses this incoming data to generate thousands of candidate trajectories per second, choosing the optimal path dynamically. The improved controller continuously selects throttle, brake, and steering actuations that maximize comfort and minimize trajectory error. All of these algorithms work in sun or rain and during the day or night. With these systems operating together, Junior has successfully logged hundreds of miles of autonomous operation in a variety of real-life conditions.
Hormonal control of interacting promoters introduced into cells by retroviruses (1991)

The interaction of promoters contained in a Moloney murine leukemia virus (MoMLV)-based retroviral vector was studied after infection of FTO-2B rat hepatoma and NIH 3T3 mouse fibroblast cells. Segments of the phosphoenolpyruvate carboxykinase (PEPCK) promoter-regulatory region, which are known from previous studies to confer responsiveness to hormones, were linked to the structural genes for bovine growth hormone, amino-3'-glycosyl phosphotransferase (neo), and herpes-virus thymidine kinase and inserted into a MoMLV-based retroviral vector. In vectors in which PEPCK was the only internal promoter, it was the major site of gene transcription. This dominant effect was independent of the orientation of the PEPCK promoter relative to the 5' long terminal repeat of the provirus and was noted with as little as -174 base pairs of the 5'-flanking sequence. NIH 3T3 cells, which do not express the endogenous PEPCK gene, transcribed the transduced PEPCK-chimeric genes at the same high levels as was observed in hepatoma cells. When two promoters were present in the provirus, the expression of chimeric structural genes depended on the relative position and orientation of these genes as well as the type of cell infected by the retrovirus. Differential responses of proviral promoters in infected cells were also observed in the presence of hormones. Dibutyryl cyclic AMP increased the expression of genes linked to the PEPCK promoter in FTO-2B and NIH 3T3 cells, whereas glucocorticoids stimulated transcription from both the PEPCK promoter and the long terminal repeat in FTO-2B cells. The effect of these hormones on transcription of proviral promoters depended on their position relative to the 5' long terminal repeat. In contrast, insulin uniformly inhibited transcription from the PEPCK promoter in a position-independent manner but only in hepatoma cells and not in fibroblasts. In clonally isolated FTO-2B cells infected with a retrovirus, the site of proviral integration was also a major factor determining the expression and hormonal regulation from the internal promoters. The data suggest that the hormonal regulation of the expression of genes contained in retroviral vectors depends on the type and position of the regulatory elements present in the provirus and the lineage of the infected cell.
Web*-a technology to make information available on the Web (2002)

The goal of the Information Sharing System (ISS) Project at the Concurrent Engineering Research Center (CERC) is to provide the means for an organization to effectively disseminate information. Thus enabling effective work in collaborative endeavors. Because corporate information exists in a variety of computer information repositories, such as databases, documents, drawings, and datafiles, it is imperative that these sources be integrated with an information sharing system to enable wider use. CERC's Web* (pronounced "WebStar") software, currently released into the public domain, can be used to integrate multiple information sources. Web* allows the exploitation of the World-Wide Web and the CORBA environment.
Enlarged representative set of protein structures (1994)

To reduce redundancy in the Protein Data Bank of 3D protein structures, which is caused by many homologous proteins in the data bank, we have selected a representative set of structures. The selection algorithm was designed to (1) select as many nonhomologous structures as possible, and (2) to select structures of good quality. The representative set may reduce time and effort in statistical analyses.
Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. (1994)

Protein-tyrosine kinases (PTKs) are critical enzymes for receptor-mediated signaling in lymphocytes. Because natural killer (NK) cells are large granular lymphocytes with specialized effector function, we set out to identify PTKs preferentially expressed in these cells. One such PTK was identified and molecularly cloned. The predicted amino acid sequence shows that this kinase lacks SH2 or SH3 domains typical of src family kinases but has tandem nonidentical catalytic domains, indicating that it is a member of the Janus family of PTKs. Immunoprecipitation using antiserum generated against a peptide corresponding to the deduced amino acid sequence of this gene revealed a kinase with a molecular weight of approximately 125,000. The pattern of expression of this kinase contrasted sharply with that of other Janus kinases, which are ubiquitously expressed. The kinase described in the present study was found to be more limited in its expression; expression was found in NK cells and an NK-like cell line but not in resting T cells or in other tissues. In contrast, stimulated and transformed T cells expressed the gene, suggesting a role in lymphoid activation. Because of its homology and tissue expression, we have tentatively termed this PTK gene L-JAK for leukocyte Janus kinase.
Methylation and colorectal cancer (2001)

Statistics rate colorectal adenocarcinoma as the most common cause of cancer death on exclusion of smoking-related neoplasia. However, the reported accumulation of genetic lesions over the adenoma to adenocarcinoma sequence cannot wholly account for the neoplastic phenotype. Recently, heritable, epigenetic changes in DNA methylation, in association with a repressive chromatin structure, have been identified as critical determinants of tumour progression. Indeed, the transcriptional silencing of both established and novel tumour suppressor genes has been attributed to the aberrant cytosine methylation of promoter-region CpG islands. This review aims to set these epigenetic changes within the context of the colorectal adenoma to adenocarcinoma sequence. The role of cytosine methylation in physiological and pathological gene silencing is discussed and the events behind aberrant cytosine methylation in ageing and cancer are appraised. Emphasis is placed on the interrelationships between epigenetic and genetic lesions and the manner in which they cooperate to define a CpG island methylator phenotype at an early stage in tumourigenesis. Finally, the applications of epigenetics to molecular pathology and patient diagnosis and treatment are reviewed.