gebhart/patrepeval huggingface dataset:
Preparation of a purified antigenic cholera toxoid (1976)

Purified cholera enterotoxin was prepared by methods described by Finkelstein and Lo Spalluto (1970). This toxin was detoxified by treatment with heat and formaldehyde. Heating cholera toxin at 60 C for 25 min resulted in the formation of a polymer named procholeragenoid by Finkelstein et al. (1971). The weak toxic activity of this product was removed by treatment with formalin. No residual toxicity could be demonstrated in formalinized procholeragenoid by the rabbit ileal loop assay and the highly sensitive rabbit skin tests. This toxoid was nevertheless at least as antigenic in the rabbit as was the toxin. No reversion to toxicity was observed in vivo and in vitro at 4 C. The toxicity of formalinized procholeragenoid never exceeded 1/5,000 to 1/10,000 that of the toxin.
Three Neocallimastix patriciarum esterases associated with the degradation of complex polysaccharides are members of a new family of hydrolases (1997)

Acetylesterase and cinnamoyl ester hydrolase activities were demonstrated in culture supernatant of the anaerobic ruminal fungus Neocallimastix patriciarum. A cDNA expression library from N. patriciarum was screened for esterases using beta-naphthyl acetate and a model cinnamoyl ester compound. cDNA clones representing four different esterase genes (bnaA-D) were isolated. None of the enzymes had cinnamoyl ester hydrolase activity, but two of the enzymes (BnaA and BnaC) had acetylxylan esterase activity, bnaA, bnaB and bnaC encode proteins with several distinct domains. Carboxy-terminal repeats in BnaA and BnaC are homologous to protein-docking domains in other enzymes from Neocallimastix species and another anaerobic fungus, a Piromyces sp. The catalytic domains of BnaB and BnaC are members of a recently described family of Ser/His active site hydrolases [Upton, C. & Buckley, J.T. (1995). Trends Biochem Sci 20, 178-179]. BnaB exhibits 40% amino acid identity to a domain of unknown function in the CelE cellulase from Clostridium thermocellum and BnaC exhibits 52% amino acid identity to a domain of unknown function in the XynB xylanase from Ruminococcus flavefaciens. BnaA, whilst exhibiting less than 10% overall amino acid identity to BnaB or BnaC, or to any other known protein, appears to be a member of the same family of hydrolases, having the three universally conserved amino acid sequence motifs. Several other previously described esterases are also shown to be members of this family, including a rhamnogalacturonan acetylesterase from Aspergillus aculeatus. However, none of the other previously described enzymes with acetylxylan esterase activity are members of this family of hydrolases.
Accelerometer based horizon and keystone perspective correction (2012)

Because of improper camera orientation, pictures are often affected by perspective distortions. In this paper, we show how to use the on-board camera accelerometer to correct the horizon and keystone distortions, without requiring any human intervention. The experimental results demonstrate the feasibility of the proposed approach; they also suggest that an accurate accelerometer calibration is necessary to get a satisfying distortion removal.
FOXM1 is a downstream target of Gli1 in basal cell carcinomas. (2002)

Forkhead box (FOX) proteins have been shown to play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, longevity, and transformation. The functional importance of this gene family in normal human skin physiology and disease processes is not well understood. Activation of Sonic Hedgehog (Shh) signaling plays a key role in the development of basal cell carcinomas (BCCs) of the skin in humans. Recent studies have established that some FOX genes are downstream targets of Shh signaling. We have investigated the role of FOX proteins in transducing Shh effects in human skin by using degenerate PCR to identify FOX genes differentially expressed in BCCs. All three known FOXM1 isoforms (a, b, and c) were detected in human skin and cultured keratinocytes, and the transcriptionally active FOXM1b isoform was found to be up-regulated in BCCs. Real-time quantitative RT-PCR showed that the increase in FOXM1 mRNA levels was specific for BCCs and not a reflection of increased cell proliferation in that no up-regulation was seen in squamous cell carcinomas or proliferating primary human keratinocyte cultures. Immunostaining studies showed intense nuclear and cytoplasmic staining throughout BCC tumor islands and not confined to the periphery regions of the tumor where proliferating Ki-67-immunopositive cells are predominantly localized. Expression of the Shh target glioma transcription factor-1 (Gli1) in primary keratinocytes and other cell lines caused a significant elevation of FOXM1 mRNA level and transcriptional activity, indicating that FOXM1 is a downstream target of Gli1. Our data provide the first evidence that activation of Shh signaling via Gli1 is an important determinant of FOXM1 expression in mammalian cells. Given the role of FOXM1 in cell proliferation, the up-regulation of FOXM1 in BCCs may be one of the mechanisms whereby Shh signaling exerts its mitogenic effect on basal keratinocytes, leading to the development of this common human cancer.
Total Synthesis of (±)-Marinopyrrole A and Its Library as Potential Antibiotic and Anticancer Agents (2010)

The first total synthesis of marine natural product, (+/-)-marinopyrrole A, has been accomplished via a nine-step synthesis in an overall yield of 30%. A small focused library based on marinopyrrole has been designed and synthesized. The scope of chemistry was investigated, and a robust chemistry suitable for library synthesis has been developed in the current study. The method that we have developed has made it possible to generate diverse analogues based on structurally novel marinopyrroles for study of potential antibiotic and anticancer activities.
Linking 600-Hz “Spikelike” EEG/MEG Wavelets (“ς-Bursts”) to Cellular Substrates (2000)

Somatosensory evoked human EEG and magnetoencephalographic (MEG) responses comprise a brief burst of low-amplitude, high-frequency (approximately 600 Hz) spikelike wavelets ("sigma-bursts") superimposed on the primary cortical response (e.g., the N20 to electrical median nerve stimulation). The recent surge of interest in these macroscopic sigma-burst responses is energized by the prospect of monitoring noninvasively, highly synchronized and rapidly repeating population spikes generated in the human thalamic and cortical somatosensory system. Thus, analyses of spike-related sigma-bursts could uniquely complement conventional low-frequency EEG/MEG, reflecting mass excitatory and inhibitory postsynaptic potentials that potentially also incorporate subthreshold activities of undetermined functional relevance. Recent studies using spatiotemporal source analysis of multichannel recordings identified regional burst sources subcortically (near-thalamic) as well as cortically. At the primary somatosensory cortex, sigma-burst generators showed the well-established homuncular somatotopic ordering. Functionally, the 600-Hz burst appears to comprise multiple subcomponents with differential sensitivity to stimulus rate, intensity, sleep-wake cycle, tactile interference, subject age, and certain movement disorders. A plenitude of cellular candidates contributing to burst generation at different levels can already now be envisaged, including cuneothalamic and thalamocortical relay cells, as well as cortical bursting pyramidal cells and fast-spiking inhibitory interneurons. Although cellular burst coding might serve to relay information with high efficiency, concepts to link macroscopic sigma-bursts and cellular substrates call for additional study.
Tactile sensing and control of robotic manipulation (1993)

Abstract —This paper reviews the current state of the art and predicts the outlook in robotic tactile sensing for real-time control of dextrous manipulation. We begin with an overview of human touch sensing capabilities and draw lessons for robotic manipulation. Next, tactile sensor devices are described, including tactile array sensors, force-torque sensors, and dynamic tactile sensors. The information provided by these devices can be used in manipulation in many ways, such as finding contact locations and object shape, measuring contact forces, and determining contact conditions. Finally, recent progress in experimental use of tactile sensing in manipulation is discussed, and future directions for research in sensing and control are considered.
Cilengitide: An RGD Pentapeptide ανβ3 and ανβ5 Integrin Inhibitor in Development for Glioblastoma and Other Malignancies (2011)

Cilengitide, a cyclicized arginine-glycine-aspartic acid-containing pentapeptide, potently blocks ανβ3 and ανβ5 integrin activation. Integrins are upregulated in many malignancies and mediate a wide variety of tumor-stroma interactions. Cilengitide and other integrin-targeting therapeutics have preclinical activity against many cancer subtypes including glioblastoma (GBM), the most common and deadliest CNS tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In Phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide and radiation demonstrate consistent antitumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized Phase III study (Cilengitide in Combination With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma Phase III Randomized Clinical Trial [CENTRIC]) for newly diagnosed GBM. In addition, randomized controlled Phase II studies with cilengitide are ongoing for non-small-cell lung cancer and squamous cell carcinoma of the head and neck. Cilengitide is the first integrin inhibitor in clinical Phase III development for oncology.
Psychostimulant augmentation of second generation antidepressants: A case series (1998)

Psychostimulant augmentation of the newer generation antidepressants is a promising new strategy. Further controlled investigation is warranted to explore various aspect of this method.
Flow conveying and diagnosis with carbon nanotube arrays (2006)

Dense arrays of aligned carbon nanotubes are designed into strips, nanowicks, as a miniature wicking element for liquid delivery and potential microfluidic chemical analysis devices. Liquid wicks away along the nanowicks spontaneously. This delivery function of nanowicks enables novel fluid transport devices to run without any power input, moving parts or external pump. Flow around the opaque nanotubes can be detected either directly or indirectly. Direct signals of the flow come out of dyed liquid or from the liquid-air interface; indirect signals are detected through observing surfacetension-induced deformation and dislocation of the nanotubes. Here we show that flow progression around and inside nanowicks is sensitive to liquid properties. Different flow progression leaves different traces of liquid. These traces not only allow liquid diagnosis any time after sampling, but also enable analysis of flow at a nanoscale resolution with scanning electron microscopy.
In vitro determination of uptake, retention, distribution, biological efficacy, and toxicity of boronated compounds for neutron capture therapy: a comparison of porphyrins with sulfhydryl boron hydrides. (1990)

A major problem remaining in the evaluation of boronated compounds for neutron capture therapy (NCT) is the need to know the intra- or extracellular microdistribution of boron. This is a consequence of the short range of the 10B(n,alpha)7Li reaction products (approximately 10 microns), such that biological efficacy is dependent upon intracellular distribution. In particular, if boron location is predominantly extracellular, a significant reduction in efficacy would be expected. The in vitro procedure described here was developed mainly to provide information regarding the intra- and extracellular location and concentration of boron. However, use of the technique also allows the measurement of compound uptake and retention (binding) and the determination of biological efficacy by the evaluation of survival curves obtained following irradiation with thermal neutrons. Comparison is made to results obtained with boric acid (H3(10)BO3) and to results calculated for various boron distributions. Concomitantly, an indication of compound toxicity can be obtained from the plating efficiency of unirradiated control cells. Currently, most investigators utilize in vivo systems for testing and evaluating boron uptake from various carrier molecules. Given the large number of boron compounds being synthesized and needing evaluation as to their usefulness for NCT, the in vitro technique described here is simple and advantageous for initial compound screening. In addition to sparing animal lives, it is both time and cost effective and utilizes much smaller quantities of test compound than are required for an in vivo assay. A boronated porphyrin (BOPP) evaluated by the above procedure shows an uptake and retention approximately 20 times that of sulfhydryl boron hydride monomer (BSH); the latter compound is currently being used clinically for NCT in Japan and is anticipated for use in clinical trials in the United States. If the advantages demonstrated by BOPP in these in vitro studies are validated in animal experiments, BOPP should be considered for clinical application.
Design and Characterization of a Micromachined Piezoelectric Microphone (2005)

*† ‡ ‡ This paper presents the development of a micromachined piezoelectric microphone for aeroacoustic measurement applications. The microphone consists of a circular diaphragm of silicon possessing a thin annular ring of piezoelectric material deposited at the edge of the diaphragm. The microphone was designed by combining a linear piezoelectric composite plate model with a lumped-element, electroacoustic model. Experimental characterization indicates a
Intravascular Drug Delivery With a Pulsed Liquid Microjet (2002)

Occlusions of the retinal veins and arteries, associated with diseases such as hypertension and arteriosclerosis, are a major cause of severe and irreversible loss of vision. Treatments for retinal vascular diseases have been unsatisfactory owing in part to the difficulty of delivering drugs to the site of disease within the eye. In this article, we demonstrate that a new device, the vapor bubble-driven pulsed liquid microjet, can deliver drugs into the lumen of small vessels such as those found in the retina. A 15- micro m-diameter liquid jet traveling at more than 60 m/s was shown to penetrate and deliver fluid through the wall of a blood vessel that was 60 micro m in diameter. Perforation of the wall of the blood vessel did not extend beyond the jet diameter.
Short-Chain HDAC Inhibitors Differentially Affect Vertebrate Development and Neuronal Chromatin (2010)

Carboxylic acids with known central nervous system and histone deacetylase (HDAC) inhibitory activities were converted to hydroxamic acids and tested using a suite of in vitro biochemical assays with recombinant HDAC isoforms, cell based assays in human cervical carcinoma Hela cells and primary cultures from mouse forebrain, and a whole animal (Xenopus laevis) developmental assay. Relative to the parent carboxylic acids, two of these analogs exhibited enhanced potency, and one analog showed altered HDAC isoform selectivity and in vivo activity in the Xenopus assay. We discuss potential uses of these novel hydroxamic acids in studies aimed at determining the utility of HDAC inhibitors as memory enhancers and mood stabilizers.
Cyanuric Chloride as a Mild and Active Beckmann Rearrangement Catalyst (2005)

The first general organocatalytic Beckmann rearrangement of ketoximes into amides has been realized by the catalytic use of cyanuric chloride. Furthermore, acids such as HCl and ZnCl2 are effective as cocatalysts with cyanuric chloride. For example, azacyclotridecan-2-one, which is synthetically useful as a starting material for nylon-12, was prepared in quantitative yield by the Beckmann rearrangement of cyclododecanone oxime (100 mmol scale) catalyzed by cyanuric chloride (0.5 mol %) and ZnCl2 (1 mol %).
What predicts high risk acute graft‐versus‐host disease (GVHD) at onset?: identification of those at highest risk by a novel acuteGVHDrisk score (2012)

To define high-risk acute graft-versus-host disease (GVHD) at onset, we examined the initial GVHD stage and grade of 864 patients at the University of Minnesota who received uniform therapy with prednisone 60 mg/m(2) per d. We compared the prognostic utility of the Minnesota (MN; modified from Consensus) versus Center for International Blood and Marrow Transplant Research (CIBMTR) GVHD organ stage-derived grading systems. As neither GVHD grading system optimally predicted outcomes, a novel acute GVHD risk score was devised by combining the MN and CIBMTR systems. Using multiple regression analysis, we could dichotomize patients into high risk (HR, n = 86) acute GVHD with initial grade IIIC, IIID or IVD who were less likely to respond to steroid therapy by day 28 [relative risk (RR), 0·3, P < 0·001] and had a higher risk for transplant-related mortality (RR, 2·0, P < 0·001) than patients with standard risk (SR, initial grade IA-IIIB, n = 778) GVHD. Using this novel acute GVHD Risk Score, HR GVHD is either skin stage 4, lower gastrointestinal (GI) stage 3+, liver stage 3+, or skin stage 3 and lower GI or liver stage 2+ GVHD. Patients with HR acute GVHD have a poor prognosis, require alternative initial therapy and should be the focus of novel therapeutic trials.
Single-polarization operation of fiber distributed feedback (DFB) lasers by injection locking (1999)

This paper investigated injection locking characteristics of a fiber distributed feedback (DFB) laser operating in dual polarizations, and found that it could operate in a single polarization by injection locking. The locking bandwidth was less than 10 MHz, much narrower than DFB laser diodes as a consequence of longer cavity length and resulting longer photon lifetime. As a more practical method to realize single-polarization operation of the fiber DFB laser, we proposed self-injection locking with a polarization-selective optical feedback composed of a mirror and a polarizer, and demonstrated a stable single-polarization operation.
Lung fibroblast alpha-smooth muscle actin expression and contractile phenotype in bleomycin-induced pulmonary fibrosis. (1996)

The emergence of the myofibroblast phenotype (characterized by alpha-smooth muscle actin expression) in wound healing and in tissues undergoing fibrosis is thought to be responsible for the increased contractility of the affected tissues. In bleomycin-induced pulmonary fibrosis, the myofibroblast is also responsible for the observed increase in collagen gene expression. To evaluate further these phenotypic changes in lung fibroblasts, contractile and other phenotypic properties of fibroblasts isolated from lungs of rats with bleomycin-induced fibrosis were compared with those of normal rats using in vitro models. Pulmonary fibrosis was induced in rats by endotracheal injection on day 0, and 7 and 14 days later the animals were sacrificed and lung fibroblasts isolated. Using immunofluorescence, < 10% of fibroblasts from control animals express alpha-smooth muscle actin when cultured as a monolayer. In contrast, 19% and 21% of cells from day 7 and day 14 bleomycin-treated animals, respectively, expressed this actin and with greater intensity than in control lung cells. This increase in actin expression was associated with enhanced contractility when evaluated using a three-dimensional cell culture model consisting of fibroblast-populated collagen gels. This enhanced contractility was abolished by treatment with antibody to transforming growth factor-beta (TGF-beta), whereas exogenous TGF-beta 1 and serum-stimulated contraction of control lung fibroblasts. TGF-beta 1 gene expression was greater in cells from bleomycin-treated animals than those from control lungs. These results show that cells with the myofibroblast phenotype are more abundant in fibrotic lung, and that these cells possess greater contractile capacity in vitro at least partly by virtue of their enhanced endogenous TGF-beta 1 gene expression.
Human immunodeficiency virus type 1 protease inhibitors irreversibly block infectivity of purified virions from chronically infected cells (1992)

Synthetic peptide analog inhibitors of human immunodeficiency virus type 1 (HIV-1) protease were used to study the effects of inhibition of polyprotein processing on the assembly, structure, and infectivity of virions released from a T-cell line chronically infected with HIV-1. Inhibition of proteolytic processing of both Pr55gag and Pr160gag-pol was observed in purified virions from infected T cells after treatment. Protease inhibition was evident by the accumulation of precursors and processing intermediates of Pr55gag and by corresponding decreases in mature protein products. Electron microscopy revealed that the majority of the virion particles released from inhibitor-treated cells after a 24-h treatment had an immature or aberrant capsid morphology. This morphological change correlated with the inhibition of polyprotein processing and a loss of infectivity. The infectivity of virion particles purified from these chronically infected cell cultures was assessed following treatment with the inhibitor for 1 to 3 days. Virions purified from cultures treated with inhibitor for 1 or 2 days demonstrated a 95- to 100-fold reduction in virus titers, and treatment for 3 days resulted in complete loss of detectable infectivity. The fact that virions from treated cultures were unable to establish infection over the 7- to 10-day incubation period in the titration experiments strongly suggests that particles produced by inhibitor-treated cells were unable to reactivate to an infectious form when they were purified away from exogenous protease inhibitor. Thus, a block of HIV-1 protease processing of viral polyproteins by specific inhibitors results in a potent antiviral effect characterized by the production of noninfectious virions with altered protein structures and immature morphologies.
Verification data for electron beam dose algorithms (1992)

The Collaborative Working Group (CWG) of the National Cancer Institute (NCI) electron beam treatment planning contract has performed a set of 14 experiments that measured dose distributions for 28 unique beam-phantom configurations that simulated various patient anatomic structures and beam geometries. Multiple dose distributions were measured with film or diode detectors for each configuration, resulting in 78, 2-D planar dose distributions and one, 1-D depth-dose distribution. Measurements were made for 9- and 20-MeV electron beams, using primarily 6 x 6- and 15 x 15-cm applicators at several SSDs. Dose distributions were measured for shaped fields, irregular surfaces, and inhomogeneities (1-D, 2-D, and 3-D), which were designed to simulate many clinical electron treatments. The data were corrected for asymmetries, and normalized in an absolute manner. This set of measured data can be used for verification of electron beam dose algorithms and is available to others for that purpose.