gebhart/patrepeval huggingface dataset:
Androgen Levels Increase by Intratumoral De novo Steroidogenesis during Progression of Castration-Resistant Prostate Cancer (2008)

Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of a castration-resistant prostate cancer (CRPC) as indicated by recurring PSA. This complex process of progression does not seem to be stochastic as the timing and phenotype are highly predictable, including the observation that most androgen-regulated genes are reactivated despite castrate levels of serum androgens. Recent evidence indicates that intraprostatic levels of androgens remain moderately high following systemic androgen deprivation therapy, whereas the androgen receptor (AR) remains functional, and silencing the AR expression following castration suppresses tumor growth and blocks the expression of genes known to be regulated by androgens. From these observations, we hypothesized that CRPC progression is not independent of androgen-driven activity and that androgens may be synthesized de novo in CRPC tumors leading to AR activation. Using the LNCaP xenograft model, we showed that tumor androgens increase during CRPC progression in correlation to PSA up-regulation. We show here that all enzymes necessary for androgen synthesis are expressed in prostate cancer tumors and some seem to be up-regulated during CRPC progression. Using an ex vivo radiotracing assays coupled to high-performance liquid chromatography-radiometric/mass spectrometry detection, we show that tumor explants isolated from CRPC progression are capable of de novo conversion of [(14)C]acetic acid to dihydrotestosterone and uptake of [(3)H]progesterone allows detection of the production of six other steroids upstream of dihydrotestosterone. This evidence suggests that de novo androgen synthesis may be a driving mechanism leading to CRPC progression following castration.
Isolation of the human insulin-like growth factor genes: insulin-like growth factor II and insulin genes are contiguous. (1985)

Overlapping recombinant clones that encompass the insulin-like growth factor (IGF) I and II genes have been isolated from a human genomic DNA library. Each gene is present once per haploid genome; the IGF-I gene spans greater than 35 kilobase pairs (kbp) and the IGF-II gene is at least 15 kbp. The exon-intron organization of these genes is similar, each having four exons, which is one more than the related insulin gene. Comparison of the restriction endonuclease cleavage maps of the IGF-II and insulin genes, including their flanking regions and hybridization with an IGF-II cDNA probe, revealed that they are adjacent to one another. The IGF-II and insulin genes have the same polarity and are separated by 12.6 kbp of intergenic DNA that includes a dispersed middle repetitive Alu sequence. The order of the genes is 5'-insulin-IGF-II-3'.
THERAPY—BOTULINUM TOXIN (2002)

Botulinum toxin is licensed for the symptomatic treatment of blepharospasm and hemifacial spasm. It is used without licence to relieve pains due to other types of muscle spasm.The pharmaceutical preparation contains botulinum toxin of the type A serotype, serum albumin and sodium chloride. The botulinum toxin was first isolated in 1895 from the food of victims of food poisoning. It was then first recognized as a neurotoxin.
Magnetoencephalography with a two-color pump-probe, fiber-coupled atomic magnetometer (2010)

The authors have detected magnetic fields from the human brain with a compact, fiber-coupled rubidium spin-exchange-relaxation-free magnetometer. Optical pumping is performed on the D1 transition and Faraday rotation is measured on the D2 transition. The beams share an optical axis, with dichroic optics preparing beam polarizations appropriately. A sensitivity of &amp;lt;5 fT/Hz is achieved. Evoked responses resulting from median nerve and auditory stimulation were recorded with the atomic magnetometer. Recordings were validated by comparison with those taken by a commercial magnetoencephalography system. The design is amenable to arraying sensors around the head, providing a framework for noncryogenic, whole-head magnetoencephalography.
In Vitro Testing of Antimicrobial Activity of Bone Cement (2004)

The purpose of this study was to establish a reliable and cost-effective microplate proliferation assay for in vitro antimicrobial testing of bone cement samples. Cement samples devoid of antimicrobial agents, loaded with 2% gentamicin or with different concentrations of high-porosity silver, were incubated in a 96-well microplate with several staphylococcal, Pseudomonas aeruginosa, and Enterococcus faecium isolates exhibiting different susceptibilities to gentamicin. After being rinsed, the samples were brought into a soy medium in which adherent cells on the cement surface either were killed by the antimicrobial surface or started to release clonal counterparts. The medium was monitored in real time by recording a time proliferation curve for each well. Microplate testing revealed no antibacterial effect of plain bone cement. The antibacterial activity of gentamicin-loaded bone cement was shown by the microplate test to depend on the gentamicin susceptibilities of the strains. The effect of high-porosity silver was dose dependent. Bactericidal activity against all tested strains was found for bone cement loaded with 1% high-porosity silver. The accuracy of this new proliferation assay was shown by the high correlation between the types of proliferation curves and antibiotic susceptibility. In contrast to routine agar diffusion testing, it assesses the dynamic response of microorganisms to antimicrobial agents in biomaterials and allows high-throughput screening and detection of antimicrobial properties of poorly water-soluble compounds like silver.
Effect of Botulinum Toxin Type A on Nasal Symptoms in Patients with Allergic Rhinitis: A Double-blind, Placebo-controlled Clinical Trial (2003)

Objective—To investigate the possible beneficial effects of botulinum toxin type A (BTX-A) on nasal symptoms in patients with allergic rhinitis (AR).Material and Methods—Thirty-four patients (21 females, 13 males; mean age 28 years) were included in the study. AR was diagnosed by means of history, clinical examination and skin prick test. Patients were randomly divided into 3 subgroups a follows: in Group A, 20 units of BTX-A was injected into each nasal cavity (total 40 units); in Group B, 30 units of BTX-A was injected into each nasal cavity (total 60 units); and in Group C, 2 ml of isotonic saline was injected as placebo. The symptoms of AR (rhinorrhea, nasal obstruction, sneezing, itching) were scored by the patient on a six-point scale (from 0 to 5). All of the patients were followed up at Weeks 1, 2, 4, 6 and 8; at each visit an anterior rhinoscopic examination was done and symptom scores were recorded.Results—There was no statistically significant difference between Groups A and B in terms of average symptom scores. Rhinorrhea, nasal obstruction and sneezing scores in Groups A and B were significantly better than those in Group C at all time points. Although itching scores were significantly lower at Weeks 1 and 2, there was no difference in the Week 4,6 and 8 scores in Groups A and B. When total symptom scores were evaluated, the results for Groups A and B were similar but significantly better than those for Group C.Conclusion—In selected cases, injection of 40 units of BTX-A into the turbinates, as a single agent, may help the symptomatic control of AR for up to 8 weeks.
Multilevel millimeter wave beamforming for wireless backhaul (2011)

Due to the projected increased demand for high data rate mobile services, interest has grown in new cellular network architectures such as a tiered networks. This paper proposes a beam searching algorithm and a codebook design for multilevel beamforming in outdoor millimeter wave communication systems. In an outdoor millimeter wave scenario, the received signal suffers from severe path loss and various attenuation factors. Beamforming is an essential component to establish the wireless link in 60GHz up to 80GHz. A millimeter wave beamforming method based on joint transmitter-receiver searching of an adaptive codebook is described. To reduce search complexity, an adaptive beam width beamforming technique is developed based on a sub-array method using squinting angles. A multilevel codebook having a hierarchical tree-structure on different beam width is adaptively designed. The performance of the proposed codebook design is analyzed, and the joint search algorithm is compared with other search methods. The proposed search method and the codebook design show performance improvement with small complexity.
HER2-Mediated Internalization of a Targeted Prodrug Cytotoxic Conjugate Is Dependent on the Valency of the Targeting Ligand (2005)

HER2 is a validated therapeutic target for cancer. There are no natural ligands, but monoclonal antibodies and peptides that bind HER2 act as artificial ligands, selectively affecting HER2-overexpressing tumors. One reported mechanism for this effect is receptor downregulation, but the expected correlation of ligand-dependent HER2 internalization and tumor inhibition remain poorly characterized. Moreover, HER2 ligands have limited therapeutic efficacy and often they require adjuvant treatment with the chemotherapeutic Taxol. Here, we generated a series of HER2 ligands (Anti-HER2/neu peptide ligands, AHNPmonovalent and AHNPbivalent) with different valency and correlated their internalization-promoting ability to biological potency. Since AHNPbivalent (but not AHNPmonovalent) induces rapid receptor internalization, we exploited this feature to deliver cytotoxic conjugates coupling AHNPbivalent and Taxol (Taxol . AHNPbivalent). The prodrug conjugate releases Taxol after receptor-mediated internalization, and cytotoxicity can be used as a marker of internalization. Taxol . AHNPbivalent is significantly more cytotoxic than free Taxol + free AHNPbivalent. Hence, the Taxol x AHNP(bivalent) prodrug binds to HER2, induces receptor internalization and downregulation, and the subsequent release of free Taxol inside the targeted cell results in synergistic toxicity, The effect is selective towards HER2- expressing cells. This work links HER2 receptor internalization and growth arrest, and the chemical conjugation strategy may yield improved and HER2 selective therapeutics.
Thousand-Fold Volumetric Concentration of Live Cells with a Recirculating Acoustofluidic Device (2015)

The ability to concentrate cells from dilute samples into smaller volumes is an essential process step for most biological assays. Volumetric concentration is typically achieved via centrifugation, but this technique is not well suited for handling small number of cells, especially outside of the laboratory setting. In this work, we describe a novel device that combines acoustofluidics with a recirculating architecture to achieve >1000-fold enrichment of cells in a label-free manner, at high volumetric throughput (>500 μL min(-1)) and with high recovery (>98.7%). We demonstrate that our device can be used with a wide variety of different cell types and show that this concentration strategy does not affect cell viability. Importantly, our device could be readily adopted to serve as a "sample preparation" module that can be integrated with other microfluidic devices to allow analysis of dilute cellular samples in large volumes.
The molecular biology of taste transduction (1993)

Taste cells respond to a wide variety of chemical stimuli: certain ions are perceived as salty (Na+) or sour (H+); other small molecules are perceived as sweet (sugars) and bitter (alkaloids). Taste has evolutionary value allowing animals to respond positively (to sweet carbohydrates and salty NaCl) or aversively (to bitter poisons and corrosive acids). Recently, some of the proteins involved in taste transduction have been cloned. Several different G proteins have been identified and cloned from taste tissue: gustducin is a taste cell specific G protein closely related to the transducins. Work is under way to clone additional components of the taste transduction pathways. The combination of electrophysiology, biochemistry and molecular biology is being used to characterize taste receptor cells and their sensory transduction mechanisms.
Two Phases of V1 Activity for Visual Recognition of Natural Images (2009)

Present theories of visual recognition emphasize the role of interactive processing across populations of neurons within a given network, but the nature of these interactions remains unresolved. In particular, data describing the sufficiency of feedforward algorithms for conscious vision and studies revealing the functional relevance of feedback connections to the striate cortex seem to offer contradictory accounts of visual information processing. TMS is a good method to experimentally address this issue, given its excellent temporal resolution and its capacity to establish causal relations between brain function and behavior. We studied 20 healthy volunteers in a visual recognition task. Subjects were briefly presented with images of animals (birds or mammals) in natural scenes and were asked to indicate the animal category. MRI-guided stereotaxic single TMS pulses were used to transiently disrupt striate cortex function at different times after image onset (SOA). Visual recognition was significantly impaired when TMS was applied over the occipital pole at SOAs of 100 and 220 msec. The first interval has consistently been described in previous TMS studies and is explained as the interruption of the feedforward volley of activity. Given the late latency and discrete nature of the second peak, we hypothesize that it represents the disruption of a feedback projection to V1, probably from other areas in the visual network. These results provide causal evidence for the necessity of recurrent interactive processing, through feedforward and feedback connections, in visual recognition of natural complex images.
Intraprostatic Antibody Deposition in Chronic Abacterial Prostatitis (1990)

Sixty patients with chronic abacterial prostatitis and 21 men without prostatitis were studied. Transperineal prostatic biopsies taken under transrectal ultrasound control were examined for antibody, complement (C3) and fibrinogen deposition using a direct immunofluorescence (IF) technique; 34 patients (57%) had prostatic tissue that displayed IF staining compared with only 1 (5%) in the non-prostatitis group. IF staining for IgM was found in 85%, for C3 in 44%, for IgA in 35% and for fibrinogen in 24%, but the IgG subclass was not detected. Antibody deposition was mainly periglandular and glandular and in the wall of vessels. Five symptoms, particularly poor urinary flow, irritative voiding and urgency, were significantly correlated with IgM and C3 deposition and, to a lesser extent, fibrinogen deposition. The aetiology of chronic abacterial prostatitis remains obscure but several possible mechanisms are discussed. The link between symptomatology and immunology could rest with functional outflow obstruction causing intraprostatic reflux of urine, this in turn inciting an immunological response, the inducing antigens being organism remnants or products, urinary constituents or autoantibodies.
MTC Flow (2013)

This paper presents a tool called MTC Flow, which allows model-driven developers to design, develop, test and deploy Model Transformation Chains (MTCs). The tool offers a graphical DSL for defining MTC workflow models independently of the technologies that support the transformations. Using basic concepts such as metamodels, models and transformations (M2M, M2T and T2M) the user defines, executes and tests his MTC easily in the same development environment. MTC Flow has an abstraction layer to implement technology support. It facilitates the interoperability of model transformation and validation using the existing technologies without changes. Additionally, once the MTC is finished, MTC Flow offers an option to deploy it in any environment that support JAVA technology. The tool supports modularity and alternative execution paths of the MTCs. It was built on top of the Eclipse Modeling Framework (EMF) and the Graphical Modeling Framework (GMF). The tool offers a development environment using the extending capabilities of the Eclipse platform. We illustrate how MTC Flow supports MTCs development process using an example.
Gas chromatographic quality control for oil of Melaleuca terpinen-4-ol type (Australian tea tree) (1989)

Detailed GC and GC-MS analyses of oil of &lt;i&gt;Melaleuca&lt;/i&gt; have identified several constituents not previouslyreported from &lt;i&gt;Melaleuca alternifolia&lt;/i&gt; and clarified some earlier assignments. The range, mean, andcoefficient of variation for the principle constituents in 800 typical samples are presented along withthe compositions of several substandard oils. Isolation and storage procedures affecting the chemicalcomposition of the oil are reported. Ethanolic extraction of mature leaves gave solutions suitable fordirect injection into a gas chromatograph for the qualitative determination of tea tree oil. Comparisonwith conventional steam distillation showed that this technique was suitable for preliminary analysisof tea tree oil yield and quality.
Vacuum-Assisted Closure in the Treatment of Degloving Injuries (1999)

Degloving injuries range from the occult, easily missed injury to obvious massive tissue damage. The serious nature of these wounds is exacerbated by mismanagement. It is generally accepted that the degloved tissue should be excised, defatted, fenestrated, and reapplied as a full-thickness skin graft. Dressings are required that provide gentle, evenly distributed pressure and avoid shear stress to the newly grafted skin. Numerous types of dressings have been devised but all are cumbersome and time-consuming. We have found the Vacuum-Assisted Closure device to be a rapid, effective, and easy-to-use alternative to traditional methods. The authors examine their experience using a vacuum-assisted closure device to treat nine degloving injuries in 5 patients and discuss the important aspects in using this technique.
NetBill: an Internet commerce system optimized for network-delivered services (1995)

NetBill is a business model set of protocols, and software implementation for commerce in information goods and other network-delivered services. It has very low transaction costs for micropayments (around 1 cent for a 10 cent item), protects the privacy of the transaction, and is highly scalable. Of special interest is the authors new certified delivery mechanism which delivers information goods if and only if the consumer has paid for them. The article discusses the design of the NetBill protocol and the authors' World Wide Web (WWW) prototype implementation. As the explosive growth of the Internet continues, more people rely on networks for timely information. However, since most information on the Internet today is free, intellectual property owners have little incentive to make valuable information accessible through the network. There are many potential providers who could sell information on the Internet and many potential consumers for that information. What is missing is an electronic commerce mechanism that links the merchants and the consumers. NetBill is a business model, set of protocols, and software implementation allowing consumers to pay owners and retailers of information. While NetBill will enable a market economy in information, it is still expected that there will be an active exchange of free information.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of the ATP-binding domain of vaccinia virus thymidine kinase. (1990)

Although small in size (20 kDa), the vaccinia virus (VV) thymidine kinase protein (EC 2.7.1.21 TK) is a relatively complex enzyme which must contain domains involved in binding both substrates (ATP and thymidine) and a feedback inhibitor (dTTP), as well as sequences directing the association of individual protein monomers into a functional tetrameric enzyme. Alignment of predicted amino acid sequences of the thymidine kinase genes from a variety of sources was used to identify highly conserved regions as a first step toward locating potential regions housing essential domains. A conserved domain (domain I) near the amino terminus of VV TK protein had characteristics consistent with a nucleotide-binding site. Analysis of the nucleotide substrate specificity of VV TK indicated that ATP acts as the major phosphate donor for thymidine phosphorylation while GTP, CTP, and UTP were inefficient substrates. Site-directed mutagenesis was performed on domain I to generate 11 mutant enzymes. Comparison of the wild-type and mutant proteins with regard to enzyme activity revealed that two of the mutant enzymes, T18 and S19, exhibited enhanced enzyme activity (3.73-fold and 1.35-fold, respectively) relative to the control. The other mutations introduced led to greatly reduced levels of enzyme activity which correlated with a reduced or altered ability of the mutant enzymes to bind ATP as determined by ATP-agarose affinity chromatography. Wild-type VV TK bound to an ATP affinity column could also be eluted with dTTP. Glycerol gradient separation of wild-type TK in the presence or absence of dTTP indicated that dissociation of the tetrameric complex was not the means by which enzymatic inhibition was achieved. Taken together, these results suggest that (i) domain I (amino acids 11-22) of the VV TK corresponds to the ATP-binding site, and (ii) that dTTP is able to interfere with ATP binding, either directly or indirectly, and thereby inhibit enzymatic activity without dissociating the native enzyme.
Genetic bases of hypertriglyceridemic phenotypes (2011)

Compared to other complex traits, genetic variants account for a high proportion of HTG diagnoses. By tallying the number of HTG risk alleles, it is possible to discriminate between individuals with HTG and normolipidemia, particularly in those with extreme scores. Future directions include finding the missing genetic component and determining whether genetic profiling can help with diagnosis or personalized treatment advice.
Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications (2007)

Pemetrexed is a new-generation antifolate, approved for the treatment of mesothelioma and non-small cell lung cancer, currently being evaluated for the treatment of a variety of other solid tumors. This review traces the history of antifolates that led to the development of pemetrexed and describes the unique properties of this agent that distinguish it from other antifolates. These include (a) its very rapid conversion to active polyglutamate derivatives in cells that build to high levels and are retained for long intervals to achieve prolonged and potent inhibition of its major target enzyme thymidylate synthase, (b) its high affinity for three folate transporters, and (c) its marked sensitivity to the level of physiologic folates in cells. The latter results in the unique and paradoxical finding that when transport mediated by the major folate transporter (the reduced folate carrier) is impaired, pemetrexed activity is preserved. This is due to concurrent contraction of competing cellular physiologic folates and utilization of a novel second transport carrier for which pemetrexed has high affinity, recently identified as the proton-coupled folate transporter (PCFT). Laboratory studies are reviewed that raise the possibility of new approaches to the use of folic acid supplementation in clinical regimens with pemetrexed.