gebhart/patrepeval huggingface dataset:
Androgen Replacement Therapy (1997)

Androgen therapy has been primarily used for replacement therapy in symptomatic hypogonadal men. Other indications under clinical investigation include androgen replacement therapy for older men with age-associated decline in serum testosterone levels, muscle-wasting disease, male contraception and as adjunctive therapy to oestrogen (and progesterone) hormone replacement for postmenopausal women. Recent scientific and pharmaceutical interests led to development of new long-acting injectables, transdermal delivery systems and sublingual preparations. The benefits of androgen replacement must be weighed against the potential risks when androgens are used in conditions other than male hypogonadism. In the future, designer androgens with specific beneficial effect on sexual function, mood, bone and muscle mass but with attenuated effects on serum lipid profiles and the prostate gland may be developed.
Design, synthesis and conformational analysis of hGM-CSF[13-31]-Gly-Pro-Gly-[103-116] (1997)

On the basis of the X-ray structure and results from structure-activity relationship studies, the following GM-CSF analogue was designed and synthesized by solid-phase methodology: hGM-CSF[13-31]-Gly-Pro-Gly-[103-116]-NH2. This analogue was constructed to comprise helices A and D of the native hGM-CSF, covalently linked in an antiparallel orientation by the tripeptide spacer Gly-Pro-Gly, which is known as a turn-inducing sequence. The conformational analysis of the analogue by CD spectroscopy revealed an essentially random structure in water, while alpha-helix formation was observed upon addition of TFE. In 40% TFE the helix content was approximately 45%. By two-dimensional NMR experiments in 1:1 water/trifluoroethanol mixture two helical sequences were identified comprising the segments corresponding to helix A and helix D. In addition to medium-range NOESY connectivities, a long-range cross-peak was found involving the leucine residues at positions 13 and 35. Based on the experimentally derived data (54 NOEs), the structure was refined by restrained molecular dynamics simulations over 120 ps at various temperatures. A representative conformation derived from the computer simulation is mainly characterized by two helical segments connected by a loop region. The overall three-dimensional structure of the analogue is comparable to the X-ray structure of hGM-CSF in that helices A and D are oriented in an antiparallel fashion, forming a two alpha-helix bundle. Nevertheless, there are small differences in the topology of the helices between the solution structure of the designed analogue and the X-ray structure of hGM-CSF. The possible implications of these conformational features at the effects of biological activity are discussed.
Melanoma Antigen-11 Inhibits the Hypoxia-Inducible Factor Prolyl Hydroxylase 2 and Activates Hypoxic Response (2009)

Activation of hypoxia-inducible factors (HIF), responsible for tumor angiogenesis and glycolytic switch, is regulated by reduced oxygen availability. Normally, HIF-alpha proteins are maintained at low levels, controlled by site-specific hydroxylation carried out by HIF prolyl hydroxylases (PHD) and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitin ligase. Using a yeast two-hybrid screen, we identified an interaction between melanoma antigen-11 (MAGE-11) cancer-testis antigen and the major HIF-alpha hydroxylating enzyme PHD2. The interaction was confirmed by a pull-down assay, coimmunoprecipitation, and colocalization in both normoxic and hypoxic conditions. Furthermore, MAGE-9, the closest homologue of MAGE-11, was also found to interact with PHD2. MAGE-11 inhibited PHD activity without affecting protein levels. This inhibition was accompanied by stabilization of ectopic or endogenous HIF-1alpha protein. Knockdown of MAGE-11 by small interfering RNA results in decreased hypoxic induction of HIF-1alpha and its target genes. Inhibition of PHD by MAGE-11, and following activation of HIFs, is a novel tumor-associated HIF regulatory mechanism. This finding provides new insights into the significance of MAGE expression in tumors and may provide valuable tools for therapeutic intervention because of the restricted expression of the MAGE gene family in cancers, but not in normal tissues.
Synthetic transcription elongation factors license transcription across repressive chromatin (2017)

The release of paused RNA polymerase II into productive elongation is highly regulated, especially at genes that affect human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators. Here we present Syn-TEF1, a molecule that actively enables transcription across repressive GAA repeats that silence frataxin expression in Friedreich's ataxia, a terminal neurodegenerative disease with no effective therapy. The modular design of Syn-TEF1 defines a general framework for developing a class of molecules that license transcription elongation at targeted genomic loci.
Synthesis of the next-generation therapeutic antibodies that combine cell targeting and antibody-catalyzed prodrug activation (2007)

An obstacle in the utilization of catalytic Abs for selective prodrug activation in cancer therapy has been systemic tumor targeting. Here we report the generation of catalytic Abs that effectively target tumor cells with undiminished prodrug activation capability. Ab conjugates were prepared by covalent conjugation of an integrin alpha(v)beta(3)-targeting antagonist to catalytic Ab 38C2 through either sulfide groups of cysteine residues generated by reduction of the disulfide bridges in the hinge region or surface lysine residues not involved in the catalytic activity. Using flow cytometry, the Ab conjugates were shown to bind efficiently to integrin alpha(v)beta(3)-expressing human breast cancer cells. The Ab conjugates also retained the retro-aldol activity of their parental catalytic Ab 38C2, as measured by methodol and doxorubicin (dox) prodrug activation. Complementing these Ab conjugates, an evolved set of dox prodrugs was designed and synthesized. Dox prodrugs that showed higher stability and lower toxicity were evaluated both in the presence and absence of the integrin alpha(v)beta(3)-targeting 38C2 conjugates for cell-killing efficacy by using human breast cancer cells. Our study reveals that cell targeting and prodrug activation capabilities can be efficiently combined for selective chemotherapy with novel dox prodrugs.
[Clinical evaluation of schizophyllan (SPG) in advanced gastric cancer (the second report)--a randomized controlled study]. (1985)

We reported previously that Schizophyllan (SPG) combined with MMC + 5-FU (MF regimen) or Tegafur (F regimen) had a significant life-prolonging effect over chemotherapeutic regimens in patients with inoperable and recurrent gastric cancer in a randomized controlled study. In the present paper, we have further investigated the effect of SPG on life-span followed-up for more than 2 years. A significant life-prolonging effect of SPG was reconfirmed in patients given either the MF regimen (154 patients) or the F regimen (213 patients). Thus, SPG combined with chemotherapeutics has proved to be useful for treating patients with inoperable and recurrent gastric cancer, resulting in a significant prolongation of life-span without serious side effects despite having no influence on tumor size.
Bottom-up approach for carbon nanotube interconnects (2003)

We report a bottom-up approach to integrate multiwalled carbon nanotubes (MWNTs) into multilevel interconnects in silicon integrated-circuit manufacturing. MWNTs are grown vertically from patterned catalyst spots using plasma-enhanced chemical vapor deposition. We demonstrate the capability to grow aligned structures ranging from a single tube to forest-like arrays at desired locations. SiO2 is deposited to encapsulate each nanotube and the substrate, followed by a mechanical polishing process for planarization. MWNTs retain their integrity and demonstrate electrical properties consistent with their original structure.
A direct role for C/EBP and the AP-I-binding site in gene expression linked to adipocyte differentiation. (1989)

Adipocyte differentiation is accompanied by the transcriptional activation of many new genes, including the gene encoding adipocyte P2 (aP2), an intracellular lipid-binding protein. Using specific deletions and point mutations, we have shown that at least two distinct sequence elements in the aP2 promoter contribute to the expression of the chloramphenicol acetyltransferase gene in chimeric constructions transfected into adipose cells. An AP-I site at -120, shown earlier to bind Jun- and Fos-like proteins, serves as a positive regulator of chloramphenicol acetyltransferase gene expression in adipocytes but is specifically silenced by adjacent upstream sequences in preadipocytes. Sequences upstream of the AP-I site at -140 (termed AE-1) can function as an enhancer in both cell types when linked to a viral promoter but can stimulate expression only in fat cells in the intact aP2 promoter. The AE-1 sequence binds an adipocyte protein identical or very closely related to an enhancer-binding protein (C/EBP) that has been previously implicated in the regulation of several liver-specific genes. A functional role for C/EBP in the regulation of the aP2 gene is indicated by the facts that C/EBP mRNA is induced during adipocyte differentiation and the aP2 promoter is transactivated by cotransfection of a C/EBP expression vector into preadipose cells. These results indicate that sequences that bind C/EBP and the Fos-Jun complex play major roles in the expression of the aP2 gene during adipocyte differentiation and demonstrate that C/EBP can directly regulate cellular gene expression.
Design and Implementation of a Self-Securing Storage Device (2000)

Abstract: "Self-securing storage prevents intruders from undetectably tampering with or permanently deleting stored data. To accomplish this, self-securing storage devices internally audit all requests and keep all versions of all data for a window of time, regardless of the commands received from potentially compromised host operating systems. Within the window, system administrators are guaranteed to have this valuable information for intrusion diagnosis and recovery. The S4 implementation combines log-structuring with novel metadata journaling and data replication techniques to minimize the performance costs of comprehensive versioning. Experiments show that self-securing storage devices can deliver performance that is comparable with conventional storage. Further, analyses indicate that several weeks worth of all versions can reasonably be kept on state-of-the-art disks, especially when differencing and compression technologies are employed."
A model-based algorithm for blood glucose control in Type I diabetic patients (1999)

A model-based predictive control algorithm is developed to maintain normoglycemia in the Type I diabetic patient using a closed-loop insulin infusion pump. Utilizing compartmental modeling techniques, a fundamental model of the diabetic patient is constructed. The resulting nineteenth-order nonlinear pharmacokinetic-pharmacodynamic representation is used in controller synthesis. Linear identification of an input-output model from noisy patient data is performed by filtering the impulse-response coefficients via projection onto the Laguerre basis. A linear model predictive controller is developed using the identified step response model. Controller performance for unmeasured disturbance rejection (50 g oral glucose tolerance test) is examined. Glucose setpoint tracking performance is improved by designing a second controller which substitutes a more detailed internal model including state-estimation and a Kalman filter for the input-output representation. The state-estimating controller maintains glucose within 15 mg/dl of the setpoint in the presence of measurement noise. Under noise-free conditions, the model-based predictive controller using state estimation outperforms an internal model controller from literature (49.4% reduction in undershoot and 45.7% reduction in settling time). These results demonstrate the potential use of predictive algorithms for blood glucose control in an insulin infusion pump.
Growth of aligned SWNT arrays from water-soluble molecular clusters for nanotube device fabrication (2004)

A simple method to fabricate parallel and/or crossed networks of ultra-long single-walled carbon nanotube (SWNT) arrays based on carbon monoxide-chemical vapor deposition (CO-CVD) by a “fast-heating” growth process is reported. The catalysts which are water-soluble inorganic molecular clusters containing Fe and Mo atoms can be easily “drawn” on the substrate by an ink pen using the cluster solution as “ink” or transferred by micro-contact printing (μCP) using poly (dimethylsiloxane) (PDMS) elastomer stamp onto substrate. The as-grown SWNTs are millimetres in length with diameters ranging from 0.7 to 2.0 nm and with controllable location and direction. Multi-dimensional crossed-networks of SWNTs can be easily fabricated by multi-step growth processes. Patterning catalysts using water-soluble clusters can be compatible with ink-jet printing techniques for generating large-area well-oriented and precisely-located SWNTs. We have also demonstrated that the ease of patterning and growing aligned nanotube arrays provides a reliable way to fabricate nanotube electronic devices.
Silica Particles: A Novel Drug‐Delivery System (2004)

Abstract In recent decades, significant advances in drug‐delivery systems have enabled more effective drug administration. To deliver drugs to specific organs, a range of organic systems (e.g., micelles, liposomes, and polymeric nanoparticles) have been designed. They suffer from limitations, including poor thermal and chemical stability, and rapid elimination by the immune system. In contrast, silica particles offer a biocompatible, stable, and “stealthy” alternative. Bioactive molecules can be easily encapsulated within silica particles by combining sol–gel polymerization with either spray‐drying or emulsion chemistry. Spray‐drying faces challenges, including low yield, surface segregation, and size limitations. In contrast, sol–gel emulsions enable the production of nanoparticles with homogeneous drug distribution, and permit ambient temperature processing, necessary for handling biologicals. Independent control of the size and release rate can be readily achieved. Preliminary in‐vivo experiments reveal enhanced blood stability of the nanoparticles, which, coupled with sustained release of anti‐tumor agents, show good potential for cancer treatment.
Some Cyclic Oligopeptide with S2n Symmetry (1987)

Some cyclic oligopeptides formed by an equal number of alternating D‐ and L‐amino‐acid residues have been synthesized by using the hydrochloride of the open‐chain peptide acid as precursor and the mixed‐anhydride condensation method. The cyclic oligopeptides (tetra‐, hexa‐, and octavaline, hexaleucine, and hexaphenylalanine) form very stable H‐bonded structures (IR‐amide band at 3270–3290 cm −1 ) which are insoluble in common organic solvents. In CF 3 COOH/CDCI 3 (25°), they yield 1 H‐NMR spectra snowing the expected equivalency of the various amino‐acid residues.
Crystal Structure of α 1 : Implications for Protein Design (1990)

X-ray diffraction shows the structure of a synthetic protein model, formed from noncovalent self-association of a 12-residue peptide and of sulfate ions at low pH. This peptide is a fragment of a 16-residue polypeptide that was designed to form an amphiphilic alpha helix with a ridge of Leu residues along one helical face. By interdigitation of the leucines of four such helices, the design called for self-association into a four-alpha-helical bundle. The crystal structure (2.7 angstrom resolution; R factor = 0.215) reveals a structure more complex than the design, with both a tetramer and a hexamer. The alpha-helical tetramer with leucine interior has more oblique crossing angles than most four-alpha-helical bundles; the hexamer has a globular hydrophobic core of 12 leucine residues and three associated sulfate ions. Computational analysis suggests that the hexameric association is tighter than the tetrameric one. The consistency of the structure with the design is discussed, as well as the divergence.
Aspects of the Structure, Function, and Applications of Superoxide Dismutas (1987)

The current status of superoxide dismutase (SOD) is that it is an enzyme with diverse ramifications. This review attempts an understanding of SOD as a structural, functional, and biological entity. Accordingly, the review is in three parts. The first part discusses SOD in terms of protein structure, proceeding from primary to secondary and three-dimensional structure for the three forms of SOD: copper/zinc SOD, manganese SOD, and iron SOD. This is the order of structural knowledge of the enzyme. Iron SOD is an enzyme of prokaryotes and some higher plants. Manganese SOD is an enzyme of prokaryotes and eukaryotes. Copper/zinc SOD is an enzyme of eukaryotes and certain prokaryotes. The evolutionary relationships of the three forms of SOD, the status of the copper/zinc SOD gene in prokaryotes, and the cloning and sequencing of SOD genes are discussed. The second part of the review deals with the catalytic mechanism of SOD in the three forms of the enzyme. Structural and mechanistic conclusions from various spectroscopic studies are critically considered. A detailed picture is given of the active site of copper/zinc SOD. The third part is a review of SOD in the general context of oxygen toxicity. After consideration of the question of superoxide toxicity and superoxide pathology, several areas in which SOD has been investigated or used as a tool in a biochemical, pharmacological, or clinical context are discussed, including population genetics; trisomy 21; development and senescence; the nutritional copper, zinc, and manganese status; hemolysis and anemia; oxygen toxicity in the lung and nervous system; inflammation, autoimmune disease and chromosome breakage, ischemia and degenerative changes; radiation damage; and malignancy. A comprehensive picture is given of measurements of SOD activity in disease states, and the question of superoxide-related disease is considered at several points.
Model Selection in an Ensemble Framework (2006)

We like to present a method to build ensemble models based on an extended cross-validation approach. The cross-validation puts several model classes in a tournament and selects the best performing model with respect to the validation set. This leads to a model selection strategy and an estimation of the expected modelling error.
An Interface Comprising Molecular Wires and Poly(ethylene glycol) Spacer Units Self-Assembled on Carbon Electrodes for Studies of Protein Electrochemistry (2006)

The characterization and application of a modified electrode interface for protein electrochemistry is reported. This generic interface is composed of a mixed monolayer of oligo(phenylethynylene) molecular wires (MWs) and poly(ethylene glycol) (PEG) deposited on glassy carbon electrodes by reductive adsorption of the respective aryl diazonium salts. Electrochemistry and scanning electron microscopy demonstrate that the PEG component exhibits a distinct decrease in nonspecific adsorption of blood serum and the proteins bovine serum albumin (BSA) and horseradish peroxidase (HRP) relative to a bare glassy carbon electrode. The ability of the MWs to facilitate efficient electron transfer through the PEG layer to the underlying electrode was demonstrated by covalently attaching ferrocenemethylamine to the end of the MWs. The calculated rate constant for this system was 229 +/- 30 s(-1). Covalent attachment of HRP to the MWs allowed direct electron transfer to the redox protein with almost ideal electrochemistry, indicating a specific interaction between the MW and HRP, with a rate constant of 13.4 +/- 2.3 s(-1). This rate constant is more rapid than previously reported for HRP shown to still be catalytically active. Retained catalytic activity of HRP was demonstrated by the enzyme responding to the addition of hydrogen peroxide. Similarly, by attaching myoglobin to the end of the MWs, a rate constant for this protein of 2 s(-1) was measured. The rigidity of the MWs, as well as it being longer than the PEG diluent, means this generic interface can be employed to investigate the electrochemistry of a wide range of redox proteins.
The Molecular Industrial Revolution: Automated Synthesis of Small Molecules (2018)

Today we are poised for a transition from the highly customized crafting of specific molecular targets by hand to the increasingly general and automated assembly of different types of molecules with the push of a button. Creating machines that are capable of making many different types of small molecules on demand, akin to that which has been achieved on the macroscale with 3D printers, is challenging. Yet important progress is being made toward this objective with two complementary approaches: 1) Automation of customized synthesis routes to different targets by machines that enable the use of many reactions and starting materials, and 2) automation of generalized platforms that make many different targets using common coupling chemistry and building blocks. Continued progress in these directions has the potential to shift the bottleneck in molecular innovation from synthesis to imagination, and thereby help drive a new industrial revolution on the molecular scale.
Vibrio harveyi RNA polymerase: purification and resolution from gyrase A (1992)

RNA polymerase was purified from Vibrio harveyi and found to contain polypeptides (beta, beta', alpha and sigma) closely corresponding to those of the Escherichia coli enzyme. In vitro transcription studies using V. harveyi and E. coli RNA polymerase demonstrated that the purified V. harveyi RNA polymerase is functional and that the two enzymes have the same promoter specificity. Chromatography through a monoQ column was required to remove a 100-kilodalton protein that was present in large amounts and copurified with the RNA polymerase. N-terminal amino acid sequencing showed that the first 18 amino acids of the 100-kilodalton protein shares 78% sequence identity with the A subunit of gyrase or topoisomerase II. The abundance of the gyrase A protein is unprecedented and may be linked to bioluminescence.
A Scale for the Assessment of Hedonic Tone the Snaith–Hamilton Pleasure Scale (1995)

The new scale, the Snaith-Hamilton Pleasure Scale (SHAPS), is an instrument which may be recommended for psychopathological research.
An Effective Architecture for Automated Appliance Management System Applying Ontology-Based Cloud Discovery (2010)

Cloud computing is a computing paradigm which allows access of computing elements and storages on-demand over the Internet. Virtual Appliances, pre-configured, ready-to-run applications are emerging as a breakthrough technology to solve the complexities of service deployment on Cloud infrastructure. However, an automated approach to deploy required appliances on the most suitable Cloud infrastructure is neglected by previous works which is the focus of this work. In this paper, we propose an effective architecture using ontology-based discovery to provide QoS aware deployment of appliances on Cloud service providers. In addition, we test our approach on a case study and the result shows the efficiency and effectiveness of the proposed work.