gebhart/patrepeval huggingface dataset:
A novel CGRP‐neutralizing Spiegelmer attenuates neurogenic plasma protein extravasation (2015)

This is the first description of the CGRP-neutralizing Spiegelmer NOX-L41. Preclinical studies confirmed a role for CGRP in neurogenic PPE and provided proof-of-concept for the potential use of this new drug candidate for the treatment or prevention of migraine.
The Robustness and Design of Constrained Cross-Directional Control Via Integral Quadratic Constraints (2011)

A robust stability test for a class of constrained cross-directional controllers is found. Under special circumstances, the stability test is executed on a mode-by-mode basis and greatly simplified to a frequency-domain criterion. The test is also exploited to develop tuning algorithms. The control system involves a quadratic program embedded within an internal model control antiwindup structure and achieves optimal steady-state performance when the plant is known. Both the nonlinearity in the controller and the plant uncertainty satisfy certain integral quadratic inequalities. This allows us to obtain conditions for robust stability that can be expressed as linear matrix inequalities via the Kalman-Yakubovich-Popov lemma.
The vertebrate limb: A model system to study the Hox/hom gene network during development and evolution (1992)

The potential of the vertebrate limb as a model system to study developmental mechanisms is particularly well illustrated by the analysis of the Hox gene network. These genes are probably involved in the establishment of patterns encoding positional information. Their functional organisation during both limb and trunk development are very similar and seem to involve the progressive activation in time, along the chromosome, of a battery of genes whose products could differentially instruct those cells where they are expressed. This process may be common to all organisms that develop according to an anterior-posterior morphogenetic progression. The possible linkage of this system to a particular mechanism of segmentation as well as its phylogenetic implications are discussed.
Intelligent cruise control field operational test. Final report. Volume I: Technical report (1998)

The effect of weather on COVID-19 spread is poorly understood. Recently, few studies have claimed that warm weather can possibly slowdown the global pandemic, which has already affected over 1.6 million people worldwide. Clarification of such relationships in the worst affected country, the US, can be immensely beneficial to understand the role of weather in transmission of the disease in the highly populated countries, such as India. We collected the daily data of new cases in 50 US states between Jan 1-Apr 9, 2020 and also the corresponding weather information (i.e., temperature (T) and absolute humidity (AH)). Distribution modeling of new cases across AH and T, helped identify the narrow and vulnerable AH range. We validated the results for 10-day intervals against monthly observations, and also worldwide trends. The results were used to predict Indian regions which would be vulnerable to weather based spread in upcoming months of 2020. COVID-19 spread in the US is significant for states with 4 < AH < 6 g/m<sup>3</sup> and number of new cases > 10,000, irrespective of the chosen time intervals for study parameters. These trends are consistent with worldwide observations, but do not correlate well with India so far possibly due the total cases reported per interval < 10,000. The results clarify the relationship between weather parameters and COVID-19 spread. The vulnerable weather parameters will help classify the risky geographic areas in different countries. Specifically, with further reporting of new cases in India, prediction of states with high risk of weather based spread will be apparent.
Structure of the Mycobacterium tuberculosis proteasome and mechanism of inhibition by a peptidyl boronate (2006)

Mycobacterium tuberculosis (Mtb) has the remarkable ability to resist killing by human macrophages. The 750 kDa proteasome, not available in most eubacteria except Actinomycetes, appears to contribute to Mtb's resistance. The crystal structure of the Mtb proteasome at 3.0 A resolution reveals a substrate-binding pocket with composite features of the distinct beta1, beta2 and beta5 substrate binding sites of eukaryotic proteasomes, accounting for the broad specificity of the Mtb proteasome towards oligopeptides described in the companion article [Lin et al. (2006), Mol Microbiol doi:10.1111/j.1365-2958.2005.05035.x]. The substrate entrance at the end of the cylindrical proteasome appears open in the crystal structure due to partial disorder of the alpha-subunit N-terminal residues. However, cryo-electron microscopy of the core particle reveals a closed end, compatible with the density observed in negative-staining electron microscopy that depended on the presence of the N-terminal octapetides of the alpha-subunits in the companion article, suggesting that the Mtb proteasome has a gated structure. We determine for the first time the proteasomal inhibition mechanism of the dipeptidyl boronate N-(4-morpholine)carbonyl-beta-(1-naphthyl)-L-alanine-L-leucine boronic acid (MLN-273), an analogue of the antimyeloma drug bortezomib. The structure improves prospects for designing Mtb-specific proteasomal inhibitors as a novel approach to chemotherapy of tuberculosis.
Dexterity Measures for the Design and Control of Kinematically Redundant Manipulators (1987)

In this paper, we have proposed a number of measures for the quantification of dexterity of manipulators. The use of such measures is especially important for kinematically redundant manipulators since they can satisfy secondary cri teria in addition to satisfying a specification of end-effector motion. We will compare several measures for the problems offinding an optimal configuration for a given end-effector position, finding an optimal workpoint, and designing the op timal link lengths of an arm.
Rosaramicin: in-vitro activity against common bacterial isolates (1981)

Journal Article Rosaramicin: in-vitro activity against common bacterial isolates Get access John A. Smith, John A. Smith *Divisions of Medical Microbiology Departments of Pathology and Medicine, The University of British Columbia, and Vancouver General HospitalVancouver, B.C., Canada V5Z 1M9 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ann G. Skidmore, Ann G. Skidmore *Divisions of Medical Microbiology Departments of Pathology and Medicine, The University of British Columbia, and Vancouver General HospitalVancouver, B.C., Canada V5Z 1M9 Search for other works by this author on: Oxford Academic PubMed Google Scholar Irving E. Salitff Irving E. Salitff †Infectious Diseases Departments of Pathology and Medicine, The University of British Columbia, and Vancouver General HospitalVancouver, B.C., Canada V5Z 1M9 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 7, Issue 5, May 1981, Pages 505–513, https://doi.org/10.1093/jac/7.5.505 Published: 01 May 1981 Article history Accepted: 20 August 1980 Published: 01 May 1981
Progress with covalent small-molecule kinase inhibitors (2018)

With reduced risk of toxicity and high selectivity, covalent small-molecule kinase inhibitors (CSKIs) have emerged rapidly. Through the lens of structural system pharmacology, here we review this rapid progress by considering design strategies and the challenges and opportunities offered by current CSKIs.
Underwater environment reconstruction using stereo and inertial data (2007)

The underwater environment presents many challenges for robotic sensing including highly variable lighting, the presence of dynamic objects, and the six degree of freedom (6DOF) 3D environment. Yet in spite of these challenges the aquatic environment presents many real and practical applications for robotic sensors. A common requirement of many of these tasks is the need to construct accurate 3D representations of structures in the environment. In order to address this requirement we have developed a stereo vision-inertial sensing device that we have successfully deployed to reconstruct complex 3D structures in both the aquatic and terrestrial domains. The sensor temporally combines 3D information, obtained using stereo vision algorithms with a 3DOF inertial sensor. The resulting point cloud model is then converted to a volumetric representation and a textured polygonal mesh is extracted for later processing. Recently obtained underwater reconstructions of wrecks and coral obtained with the sensor are presented.
Trib3 Is Elevated in Parkinson's Disease and Mediates Death in Parkinson's Disease Models (2015)

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Current treatments ameliorate symptoms, but not the underlying neuronal death. Understanding the core neurodegenerative processes in PD is a prerequisite for identifying new therapeutic targets and, ultimately, curing this disease. Here, we describe a novel pathway involving the proapoptotic protein Trib3 in neuronal death associated with PD. These findings are supported by data from multiple cellular models of PD and by immunostaining of postmortem PD brains. Upstream, Trib3 is induced by the transcription factors ATF4 and CHOP; and downstream, Trib3 interferes with the PD-associated prosurvival protein Parkin to mediate death. These findings establish this new pathway as a potential and promising therapeutic target for treatment of PD.
NMR Characterization of Hydrate and Aldehyde Forms of Imidazole-2-carboxaldehyde and Derivatives (2010)

The existence and stability of the aldehyde-hydrate form of imidazole-2-carboxaldehyde (4) were studied using FTIR together with solution- and solid-state NMR experiments. The results allowed us to conclude that the hydrate form was stable and precipitated at pH = 8.0 and that the aldehyde form was isolated at pH = 6.5 and 9.5. Moreover, the presence of the aldehyde-hydrate form was studied through NMR experiments in D(2)O at both alkaline and acidic pH. In addition, the tautomeric forms of the 2-substituted imidazole compounds were also analyzed to investigate the influence of the hybridization on the carbon adjacent to the imidazole ring, by (13)C NMR in DMSO-d(6), acetone-d(6), and CDCl(3). The presence of the syn- and anti-isomers of oxime 8 obtained from 4 were characterized by solid-state NMR and variable-temperature NMR experiments in acetone-d(6).
Hierarchical and Contractual Approaches to Budgetary Reform (1992)

Based on a review of recent reforms of the budgetary systems used in the Danish public sector, the article argues that such reforms have not been effective instruments for public sector resource management. The reason for this lack of effectivity is found in the principles of hierarchical governance on which these reforms are based. The systems provide only weak incentives for respecting spending targets decided at superior levels, while, simultaneously, budget-holders are tempted to exceed these targets. Alternatively, the article argues for a contractual approach to budgetary reform where micro-level incentives are brought into operation.
Mitochondrial permeability transition is a central coordinating event in N-(4-hydroxyphenyl)retinamide-induced apoptosis. (2000)

The inhibitory effects of N-(4-hydroxyphenyl)retinamide (4HPR) on the process of carcinogenesis are not fully understood and may result from its ability to induce apoptosis in transformed cells. This study investigated the apoptotic properties of 4HPR in four human cutaneous squamous cell carcinoma cell lines. Apoptosis induction, detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling method, occurred in a dose- and time-dependent fashion after treatment with 4HPR. 4HPR promoted reactive oxygen species (ROS) determined by oxidation of 2',7'-dichlorofluorescin. 4HPR-induced ROS, and apoptosis could be inhibited by L-ascorbic acid. Rhodamine 123 retention revealed that 4HPR treatment promoted a gradual dissipation of mitochondrial inner transmembrane potential, and this could be inhibited by L-ascorbic acid, implying that mitochondrial permeability transition was involved in apoptosis induction. Cyclosporin A and bongkrekic acid inhibited dissipation of mitochondrial inner transmembrane potential, ROS production, and DNA fragmentation after exposure to 4HPR, demonstrating that mitochondrial permeability transition was a central coordinating feature of 4HPR-induced apoptosis.
Development of a humanized disulfide-stabilized anti-p185HER2 Fv-beta-lactamase fusion protein for activation of a cephalosporin doxorubicin prodrug. (1995)

The humanized anti-p185HER2 antibody, humAb4D5-8, has completed Phase II clinical trials for p185HER2-overexpressing breast cancer. Here, this antibody is used as a building block to engineer a disulfide-linked Fv (dsFv) beta-lactamase fusion protein for use in antibody-dependent enzyme-mediated prodrug therapy using cephalosporin-based prodrugs. Three Fv variants were designed with an interchain disulfide bond buried at the VL/VH interface and secreted from Escherichia coli. One variant, dsFv3 (VL L46C VH D101C0, has similar affinity for antigen (Kd = 0.7 nM) as the wild-type Fv and was used to construct a fusion protein in which beta-lactamase, RTEM-1, is joined to the carboxy terminus of VH. The dsFv3-beta-lactamase fusion protein secreted from E. coli efficiently activates a cephalothin doxorubicin prodrug (PRODOX, kcat/km = 1.5 x 10(5) s-1 M-1). PRODOX is approximately 20-fold less toxic than free doxorubicin against breast tumor cell lines SK-BR-3 and MCF7, which express p185HER2 at elevated and normal levels, respectively. Prebinding the dsFv3-beta-lactamase fusion protein specifically enhances the toxicity level of PRODOX to that of doxorubicin against SK-BR-3 but not MCF7 cells. The fusion protein retains both antigen-binding plus kinetic activity in murine serum and is cleared rapidly as judged by pharmacokinetic analysis in nude mice (initial and terminal half-lives of 0.23 and 1.27 h, respectively). Development and characterization of the dsFv3-beta-lactamase fusion protein is an important step toward targeted prodrug therapy of p185HER2-overexpressing tumors.
Clinical methods in psychiatric genetics: I. Robustness of genetic marker investigative strategies (1986)

Population stratification, secondary effects of illness or treatment, biological heterogeneity of a clinical syndrome, or complex biology underlying a syndrome (where only one component is measured) are conditions which may obscure the association of a genetic risk factor with a clinical syndrome. We consider several investigative strategies under each of these conditions. Only segregation-based paradigms are robust to genetic heterogeneity and population stratification. But secondary effects on the risk factor produced by illness or treatment require other strategies for their detection.
TGD1, -2, and -3 Proteins Involved in Lipid Trafficking Form ATP-binding Cassette (ABC) Transporter with Multiple Substrate-binding Proteins (2012)

Members of the ATP-binding cassette (ABC) transporter family are essential proteins in species as diverse as archaea and humans. Their domain architecture has remained relatively fixed across these species, with rare exceptions. Here, we show one exception to be the trigalactosyldiacylglycerol 1, 2, and 3 (TGD1, -2, and -3) putative lipid transporter located at the chloroplast inner envelope membrane. TGD2 was previously shown to be in a complex of >500 kDa. We demonstrate that this complex also contains TGD1 and -3 and is very stable because it cannot be broken down by gentle denaturants to form a "core" complex similar in size to standard ABC transporters. The complex was purified from Pisum sativum (pea) chloroplast envelopes by native gel electrophoresis and examined by mass spectrometry. Identified proteins besides TGD1, -2, or -3 included a potassium efflux antiporter and a TIM17/22/23 family protein, but these were shown to be in separate high molecular mass complexes. Quantification of the complex components explained the size of the complex because 8-12 copies of the substrate-binding protein (TGD2) were found per functional transporter.
Purification and properties of 4-aminobenzoate hydroxylase, a new monooxygenase from Agaricus bisporus. (1986)

A new FAD-dependent monooxygenase, 4-aminobenzoate hydroxylase that catalyzes the decarboxylative hydroxylation of 4-aminobenzoate and forms 4-hydroxyaniline in the presence of NAD(P)H and O2 has been purified to homogeneity by ammonium sulfate fractionation, affinity chromatography, chromatofocusing, and Sephadex G-100 chromatography from Agaricus bisporus, a common edible mushroom. The molecular weight of the enzyme, which consists of a single polypeptide, is 49,000. The enzyme contains 0.91 mol of FAD/mol of enzyme. Stoichiometric studies show that 1 mol of 4-aminobenzoate is converted to an equimolecular amount of 4-hydroxyaniline and CO2 with the consumption of 1 mol each of NADH and molecular oxygen. Results obtained isotopically with 18O2 show that one atom of molecular oxygen is incorporated into 4-hydroxyaniline formed from 4-aminobenzoate. The enzyme is most active between pH 6.5 and 8.0 in the oxidation of NADH and between pH 6.0 and 7.5 in the case of NADPH. The Km values for 4-aminobenzoate, NADH, and O2 are 20.4, 13.6, and 200 microM, respectively, and that for NADPH is 133 microM. Other substituted benzoates with free amino and carboxyl groups in the ortho or para position (e.g. 4-aminosalicylate and anthranilate) serve as substrates for hydroxylation, but, in these cases, H2O2 is formed simultaneously with the hydroxylation. The enzyme is insensitive to the chelators of iron and copper, sodium arsenite, and KCN. Heavy metal ions and p-chloromercuribenzoate severely inhibit the enzyme enzyme
Tumor induction by direct injection of cloned v-src DNA into chickens. (1983)

The in vitro transforming potential of Rous sarcoma viruses has been shown to reside in a gene segment, v-src. To provide direct proof that the isolated v-src sequence contains all the information necessary for sarcoma induction in vivo, we have injected subgenomic and genomic cloned DNA carrying v-src directly into chickens. We report that v-src, without the complements of other viral genes, can effectively induce sarcomas in the host within weeks after injection. The sarcoma tumors generated by subgenomic v-src DNA are of mono- or oligoclonal origin. They have acquired v-src sequences in the genome and expressed high levels of src messages. Intact long terminal repeats do not seem to be essential in the tumorigenic process.
Genome Analysis of Treponema pallidum subsp. pallidum and subsp. pertenue Strains: Most of the Genetic Differences Are Localized in Six Regions (2010)

The genomes of eight treponemes including T. p. pallidum strains (Nichols, SS14, DAL-1 and Mexico A), T. p. pertenue strains (Samoa D, CDC-2 and Gauthier), and the Fribourg-Blanc isolate, were amplified in 133 overlapping amplicons, and the restriction patterns of these fragments were compared. The approximate sizes of the genomes investigated based on this whole genome fingerprinting (WGF) analysis ranged from 1139.3-1140.4 kb, with the estimated genome sequence identity of 99.57-99.98% in the homologous genome regions. Restriction target site analysis, detecting the presence of 1773 individual restriction sites found in the reference Nichols genome, revealed a high genome structure similarity of all strains. The unclassified simian Fribourg-Blanc isolate was more closely related to T. p. pertenue than to T. p. pallidum strains. Most of the genetic differences between T. p. pallidum and T. p. pertenue strains were accumulated in six genomic regions. These genome differences likely contribute to the observed differences in pathogenicity between T. p. pallidum and T. p. pertenue strains. These regions of sequence divergence could be used for the molecular detection and discrimination of syphilis and yaws strains.
Radical Ion Saturation in Some Sulfur Compounds X-Irradiated at 4.2°K (1972)

Single crystals of dimethylthiourea and dibenzoyldisulfide were exposed to ionizing radiation at 4.2°K. At this temperature positive and negative free radical ions are stable and can be identified from their electron spin resonance (esr) absorption spectra. The concentration of radical ions was measured as a function of dose and it was found that the concentrations approach limiting values of the order of 1018 radicals per gram. This saturation effect is attributed to nongeminate recombination of electrons with cations.
Enhanced Oligonucleotide Binding to Self-Assembled Nanofibers (2005)

A peptide nucleic acid/peptide amphiphile conjugate (PNA-PA) that self-assembles into fiber-shaped nanostructures was designed to bind oligonucleotides with high affinity and specificity. Oligonucleotide binding to PNA-PA nanofibers was studied using fluorescence polarization, and thermal stability was examined by UV-vis measurement of duplex melting temperatures. The self-assembled PNA-PA DNA system was observed to bind more strongly than the corresponding DNA-DNA duplex. We also observed single base specificity with a 16 degrees C in thermal stability. As expected from the previous PNA studies, PNA-PA RNA binding is also stronger than the corresponding RNA-RNA duplex.
Role of the renin-angiotensin system in the control of vasopressin and ACTH secretion during the development of renal hypertension in dogs. (1984)

Experiments were performed to determine if the activation of the renin-angiotensin system that occurs during the development of two-kidney, one clip Goldblatt hypertension in dogs is accompanied by increases in vasopressin and adrenocorticotrophic hormone (ACTH) secretion. Following renal artery constriction, there were marked increases in arterial blood pressure, plasma renin activity (PRA), and plasma angiotensin II (AII) concentration. These changes were accompanied by an increase in plasma vasopressin concentration during the second week following constriction, and there were significant correlations between plasma vasopressin concentration and PRA (r = 0.57, p less than 0.001), and between plasma vasopressin concentration and plasma AII concentration (r = 0.59, p less than 0.001). In contrast, plasma corticosteroid concentration, used as an index of changes in ACTH secretion, did not change significantly. Acute blockade of the renin-angiotensin system with captopril or saralasin produced the expected changes in blood pressure, PRA, and plasma AII concentration but did not decrease plasma vasopressin or corticosteroid concentrations. These results indicate that during the development of renal hypertension in dogs, there may be an interaction between the renin-angiotensin system and vasopressin, but not between the renin-angiotensin system and the pituitary-adrenal axis. They also show that the antihypertensive action of captopril in this experimental model is not mediated via suppression of vasopressin, ACTH, or corticosteroid secretion.
Electromagnetic Energy Harvesting Circuit With Feedforward and Feedback DC–DC PWM Boost Converter for Vibration Power Generator System (2007)

This paper presents an integrated vibration power generator system. The system consists of a mini electromagnetic vibration power generator and a highly efficient energy harvesting circuit implemented on a minute printed circuit board and a 0.35-mum CMOS integrated chip. By introducing a feedback control into the dc-dc pulsewidth modulation (PWM) boost converter with feedforward control, the energy harvesting circuit can adjust the duty ratio of the converter following the variation of the input voltage and the voltage of energy storage element to get high energy conversion efficiency. The energy harvesting circuit rectifies the input ac voltage, steps up the dc output of the rectifier by the dc-dc PWM boost converter with feedforward and feedback control and stores the electric energy into a super capacitor, which can be used as a small electrical power supply for an intelligent micro sensor network