gebhart/patrepeval huggingface dataset:
Exploratory study of the effect of one week of orally administered CNSA-001 (sepiapterin) on CNS levels of tetrahydrobiopterin, dihydrobiopterin and monoamine neurotransmitter metabolites in healthy volunteers (2019)

Tetrahydrobiopterin (BH<sub>4</sub>) is a cofactor for the enzymes tyrosine hydroxylase and tryptophan hydroxylase, the rate-limiting enzymes in the production of the neurotransmitters, dopamine and serotonin, respectively, in the central nervous system (CNS). Administration of BH<sub>4</sub> is used clinically within the management of persons with genetic BH<sub>4</sub> deficiencies, but the BH<sub>4</sub> molecule does not cross the blood-brain barrier sufficiently. CNSA-001 is a pharmaceutical preparation of sepiapterin, a natural precursor of BH<sub>4</sub> that induced larger increases in plasma BH<sub>4</sub> compared with administration of the same doses of BH<sub>4</sub> itself in healthy volunteers in a randomized trial. Here, we report the effects of 7 days of once-daily treatment with CNSA-001 60 mg/kg (<i>n</i> = 6) or placebo (<i>n</i> = 2) on metabolites of the BH<sub>4</sub> synthetic pathway and on biomarkers of the serotonin (5-hydroxyindoleacetic acid [5-HIAA]) and dopamine (homovanillic acid [HVA]) pathways in cerebrospinal fluid (CSF) in subjects from this trial. There were no notable changes in any metabolite in placebo-treated subjects. Administration of CNSA-001 increased mean BH<sub>4</sub> from 18.1 (SD 3.0) to 35.1 (10.0) nmol/L, and of dihydrobiopterin (BH<sub>2</sub>) from 2.1 (0.3) to 7.9 (1.5) nmol/L. Overall, administration of CNSA-001 had little effect on mean levels (pre- vs. post-treatment) of 5-HIAA (76.1 [SD 29.8] vs. 70.1 [23.1] nmol/L) or HVA (177.2 [66.5] vs. 184.8 [35.3]) nmol/L. One subject with low 5-HIAA and HVA at baseline responded with approximately three-fold increases in CNS levels of these metabolites after CNSA-001 treatment, with post-treatment levels within the range of those seen in other subjects. Administration of CNSA-001 60 mg/kg markedly increased levels of BH<sub>4</sub> in the CNS of healthy volunteers, with apparently little overall effect in CNS levels of already normal key neurotransmitter metabolites.
Albumin, steroid hormones and the origin of vertebrates (2002)

Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and various phytochemicals and xenobiotics that bind to receptors for steroids and other lipophilic hormones. Despite albumin's low affinity (K(d) approximately 10(-4) M to 10(-6) M) for these lipophilic compounds, the high concentration of albumin in serum makes this protein a major carrier of steroids and lipophilic hormones and a regulator of their access to receptors. Albumin also functions as a sink for xenobiotics, diminishing the binding of xenobiotics to hormone receptors and other cellular proteins. This protects animals from endocrine disruption by xenobiotics. We propose that these properties of albumin were important in protochordates and primitive vertebrates, such as jawless fish, about 600 to 530 million years ago, just before and during the Cambrian period. It is at that time that the ancestral receptors of adrenal and sex steroids - androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins - arose in multicellular animals. Albumin regulated access of steroids to their receptors, as well as protecting animals from endocrine disruptors, such as phytochemicals, fungal chemicals and phenolics, and other chemicals formed at hydrothermal vents by geochemical processes. Thus, animals in which albumin expression was high had a selective advantage in regulating the steroid response and avoiding endocrine disruption by xenobiotics.
A Technical Word- and Term-Translation Aid Using Noisy Parallel Corpora across Language Groups (1997)

Technical-term translation represents one of the most difficult tasks for human translators since (1) most translators are not familiar with terms and domain-specific terminology and (2) such terms are not adequately covered by printed dictionaries. This paper describes an algorithm for translating technical words and terms from noisy parallel corpora across language groups. Given any word which is part of a technical term in the source language, the algorithm produces a ranked candidate match for it in the target language. Potential translations for the term are compiled from the matched words and are also ranked. We show how this ranked list helps translators in technical-term translation. Most algorithms for lexical and term translation focus on Indo-European language pairs, and most use a sentence-aligned clean parallel corpus without insertion, deletion or OCR noise. Our algorithm is language- and character-set-independent, and is robust to noise in the corpus. We show how our algorithm requires minimum preprocessing and is able to obtain technical-word translations without sentence-boundary identification or sentence alignment, from the English–Japanese awk manual corpus with noise arising from text insertions or deletions and on the English–Chinese HKUST bilingual corpus. We obtain a precision of 55.35% from the awk corpus for word translation including rare words, counting only the best candidate and direct translations. Translation precision of the best-candidate translation is 89.93% from the HKUST corpus. Potential term translations produced by the program help bilingual speakers to get a 47% improvement in translating technical terms.
MEMS Helmholtz coils for magnetic resonance imaging (2005)

Miniature coils for magnetic resonance imaging and spectroscopy are demonstrated. A rectangular Helmholtz arrangement based on a pair of substrates separated by spherical alignment spacers is investigated. An optimal geometry is developed using simple theory and verified by numerical analysis. Prototypes are fabricated using silicon substrates shaped by anisotropic etching to form a trough to hold an internal sample and pits for use as alignment features, and carrying Cu/Au conductors fabricated by electroplating. Q values of 11 are obtained, and devices containing an internal proton source are developed for use as fiducial markers in H-1 magnetic resonance imaging at 1.5 T. Magnetic resonance spectroscopy is also performed on the internal source, with a SNR of approximate to 85.
Unfolding of Proteins and Long Transient Conformations Detected by Single Nanopore Recording (2007)

We study the electrophoretic blockades due to entries of partially unfolded proteins into a nanopore as a function of the concentration of the denaturing agent. Short and long pore blockades are observed by electrical detection. Short blockades are due to the passage of completely unfolded proteins, their frequency increases as the concentration of the denaturing agent increases, following a sigmoidal denaturation curve. Long blockades reveal partially folded conformations. Their duration increases as the proteins are more folded. The observation of a Vogel-Fulcher law suggests a glassy behavior.
Inhibition of the Immunoproteasome Subunit LMP7 with ONX 0914 Ameliorates Graft-versus-Host Disease in an MHC-Matched Minor Histocompatibility Antigen–Disparate Murine Model (2015)

In the current study we evaluated the effects of immunoproteasome inhibition using ONX 0914 (formerly PR-957) to ameliorate graft-versus-host disease (GVHD). ONX 0914, an LMP7-selective epoxyketone inhibitor of the immunoproteasome, has been shown to reduce cytokine production in activated monocytes and T cells and attenuate disease progression in mouse models of rheumatoid arthritis, colitis, systemic lupus erythematosus, and, more recently, encephalomyelitis. Inhibition of LMP7 with ONX 0914 in the B10.BR→CBA MHC-matched/minor histocompatibility antigen (miHA)-disparate murine blood and marrow transplant (BMT) model caused a modest but significant improvement in the survival of mice experiencing GVHD. Concomitant with these results, in vitro mixed lymphocyte cultures revealed that stimulator splenocytes, but not responder T cells, treated with ONX 0914 resulted in decreased IFN-γ production by allogeneic T cells in both MHC-disparate (B10.BR anti-B6) and miHA-mismatched (B10.BR anti-CBA) settings. In addition, a reduction in the expression of the MHC class I-restricted SIINFEKL peptide was observed in splenocytes from transgenic C57BL/6-Tg(CAG-OVA)916Jen/J mice exposed to ONX 0914. Taken together, these data support that LMP7 inhibition in the context of BMT modulates allogeneic responses by decreasing endogenous miHA presentation and that the consequential reduction in allogeneic stimulation and cytokine production reduces GVHD development.
Enhancingmda-7/IL-24 therapy in renal carcinoma cells by inhibiting multiple protective signaling pathways using sorafenib and by Ad.5/3 gene delivery (2010)

We have determined whether an adenovirus that comprises the tail and shaft domains of a serotype 5 virus and the knob domain of a serotype 3 virus expressing MDA-7/IL-24, Ad.5/3-mda-7, more effectively infects and kills renal carcinoma cells (RCCs) compared to a serotype 5 virus, Ad.5-mda-7. RCCs are a tumor cell type that generally does not express the receptor for the type 5 adenovirus; the coxsackie and adenovirus receptor (CAR). Ad.5/3-mda-7 infected RCCs to a much greater degree than Ad.5-mda-7. MDA-7/IL-24 protein secreted from Ad.5/3-mda-7-infected RCCs induced MDA-7/IL-24 expression and promoted apoptosis in uninfected "bystander" RCCs. MDA-7/IL-24 killed both infected and bystander RCCs via CD95 activation. Knockdown of intracellular MDA-7/IL-24 in uninfected RCCs blocked the lethal effects of conditioned media. Infection of RCC tumors in one flank, with Ad.5/3-mda-7, suppressed growth of infected tumors and reduced the growth rate of uninfected tumors implanted on the opposite flank. The toxicity of the serotype 5/3 recombinant adenovirus to express MDA-7/IL-24 was enhanced by combined molecular or small molecule inhibition of MEK1/2 and PI3K; inhibition of mTOR, PI3K and MEK1/2; or use of the multi-kinase inhibitor sorafenib. In RCCs, combined inhibition of cytoprotective cell signaling pathways enhanced the MDA-7/IL-24-induction of CD95 activation, with greater mitochondrial dysfunction due to loss of MCL-1 and BCL-XL expression, and tumor cell death. Treatment of RCC tumors in vivo with sorafenib also enhanced Ad.5/3-mda-7 toxicity and prolonged animal survival. Future combinations of these approaches hold promise for developing a more effective therapy for kidney cancer.
Luminescent Quantum Dots (2011)

Luminescent quantum dots have emerged over the last 25 years in a wide variety of research fields. This proceeding will discuss the synthesis of quantum dots, their structural properties, and ultrafast carrier dynamics. Additionally we will highlight the utilization of quantum dots in photovoltaics, solid-state lighting, and as fluorescent biological probes.
The Association of Epstein–Barr Virus with Smooth-Muscle Tumors Occurring after Organ Transplantation (1995)

Smooth-muscle tumors that developed after organ transplantation contained clonal EBV, suggesting that the virus has a role in the development of these neoplastic lesions.
Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction (2000)

These results indicate that in men with erectile dysfunction low free testosterone may correlate independently of age with the impaired relaxation of cavernous endothelial and corporeal smooth muscle cells to a vasoactive challenge. These findings give clinical support to the experimental knowledge of the importance of androgens in regulating smooth muscle function in the penis.
Single‐fiber electromyography in limb and facial muscles in muscle‐specific kinase antibody and acetylcholine receptor antibody myasthenia gravis (2005)

We examined the findings from single-fiber electromyography in extensor digitorum communis (EDC) and orbicularis oculi (OOc) in 13 myasthenia gravis (MG) patients with muscle-specific kinase antibodies (MuSK-MG) and 12 MG patients with acetylcholine receptor antibodies (AChR-MG) with similar clinical scores. More than 70% of AChR-MG patients had abnormal jitter in both EDC and OOc, but the majority of MuSK-MG patients had normal jitter in EDC despite abnormal jitter in OOc. These findings demonstrate clear differences between the neurophysiology of MuSK-MG and AChR-MG.
Robot-assisted surgical systems: a new era in laparoscopic surgery (2002)

The introduction of laparoscopic surgery offers clear advantages to patients; to surgeons, it presents the challenge of learning new remote operating techniques quite different from traditional operating. Telemanipulation, introduced in the late 1990s, was a major advance in overcoming the reduced dexterity introduced by laparoscopic techniques. This paper reviews the development of robotic systems in surgery and their role in the operating room of the future.
Measurement of the absolute fluorescence quantum yield of rhodamine B solution using a dual-beam thermal lens technique (1996)

The dual-beam thermal lens technique has been found to be very\neffective for the measurement of fluorescence quantum yields of dye solutions. The\nconcentration-dependence of the quantum yield of rhodamine B in methanol is\nstudied here using this technique. The observed results are in line with the\nconclusion that the reduction in the quantum yield in the quenching region is\nessentially due to the non-radiative relaxation of the absorbed energy. The thermal\nlens has been found to become abberated above 40 mW of pump laser power.\nThis low value for the upper limit of pump power is due to the fact that the medium\nis a resonantly absorbing one.
A Minimally Invasive 64-Channel Wireless μECoG Implant (2014)

<?Pub Dtl=""?> Emerging applications in brain–machine interface systems require high-resolution, chronic multisite cortical recordings, which cannot be obtained with existing technologies due to high power consumption, high invasiveness, or inability to transmit data wirelessly. In this paper, we describe a microsystem based on electrocorticography (ECoG) that overcomes these difficulties, enabling chronic recording and wireless transmission of neural signals from the surface of the cerebral cortex. The device is comprised of a highly flexible, high-density, polymer-based 64-channel electrode array and a flexible antenna, bonded to 2.4 mm × 2.4 mm CMOS integrated circuit (IC) that performs 64-channel acquisition, wireless power and data transmission. The IC digitizes the signal from each electrode at 1 kS/s with 1.2 μV input referred noise, and transmits the serialized data using a 1 Mb/s backscattering modulator. A dual-mode power-receiving rectifier reduces data-dependent supply ripple, enabling the integration of small decoupling capacitors on chip and eliminating the need for external components. Design techniques in the wireless and baseband circuits result in over 16× reduction in die area with a simultaneous 3× improvement in power efficiency over the state of the art. The IC consumes 225 μW and can be powered by an external reader transmitting 12 mW at 300 MHz, which is over 3× lower than IEEE and FCC regulations.
Prefrontal cortex dysfunction in clinical depression (1994)

Abstract The role of specific brain regions in the pathophysiology of clinical depression is poorly understood. However, one brain area, the prefrontal cortex, is emerging as likely being directly involved in clinical depression. The authors review accepted clinical diagnostic criteria for depression and show how these relate to the behavioral changes seen after prefrontal cortex damage in man and other animals. Information from structural (MRI, CT) and functional imaging (SPECT, PET) is then examined for direct evidence of prefrontal cortex abnormalities in clinically depressed subjects. Functional imaging studies, with few exceptions, demonstrate prefrontal lobe hypometabolism in primary and secondary depression, with severity of depression often correlating with the degree of frontal inactivity. These studies imply that dysfunction of the prefrontal cortex, particularly with respect to its role in modulating limbic activity, could conceivably produce many of the symptoms seen in clinical depression. Viewing clinical depression as a disease involving dysfunction of the prefrontal cortex and connected brain regions may prove helpful in both the clinical management of depression and in clarifying future avenues for research. Depression 2:59–72 (1994). © 1994 Wiley‐Liss, Inc.
New Helper Cells and Matched Early Region 1-Deleted Adenovirus Vectors Prevent Generation of Replication-Competent Adenoviruses (1998)

The presence of replication-competent adenoviruses (RCAs) in batches of replication-defective adenovirus (Ad) vectors is a major problem for the application of these vectors in gene therapy. RCAs are generated by recombination between sequences in the Ad vector and homologous Ad sequences in the helper cells, resulting in the acquisition by the vector of early region 1. To prevent the formation of RCAs, we have developed helper cell lines, which we named PER, and matched Ad vectors that do not have sequence overlap. PER cells contain the Ad serotype 5 (Ad5) E1A- and E1B-encoding sequences (Ad5 nucleotides 459-3510) under the control of the human phosphoglycerate kinase (PGK) promoter. We demonstrate that PER cells synthesize high levels of the Ad5 E1A and E1B proteins. The yields from PER cells of E1-deleted Ads are similar to those obtained from earlier helper cells, such as 911 and 293 cells. Propagation of matched Ad vectors, which lack Ad5 nucleotides 459-3510, in one of the PER clones, PER.C6, does not result in the generation of RCAs, in contrast to propagation in 293 cells. We conclude that the combination of PER.C6 cells and nonoverlapping E1-deleted adenoviral vectors eliminates the problem of RCA generation by homologous recombination, and allows cost-effective production of safe, clinical-grade batches of recombinant Ad vectors.
Separation and Identification of Mucins and Their Glycoforms (2000)

This chapter describes a strategy for the separation and identification of the mucins present in mucous secretions or from cell culture, focusing primarily on those mucins involved in gel formation. At present, the mucins MUC2, MUC5AC, MUC5B, and MUC6 are known to be gel-forming molecules (, , , ). These mucins share common features in that they are oligomeric in nature and consist of a variable number of monomers (subunits) linked in an end-to-end fashion via the agency of disulfide bonds. In addition, their polypeptides comprise regions of dense glycosylation interspersed with “naked” cysteine-rich domains (, , , ).
Increasing cheat robustness of crowdsourcing tasks (2012)

Crowdsourcing successfully strives to become a widely used means of collecting large-scale scientific corpora. Many research fields, including Information Retrieval, rely on this novel way of data acquisition. However, it seems to be undermined by a significant share of workers that are primarily interested in producing quick generic answers rather than correct ones in order to optimise their time-efficiency and, in turn, earn more money. Recently, we have seen numerous sophisticated schemes of identifying such workers. Those, however, often require additional resources or introduce artificial limitations to the task. In this work, we take a different approach by investigating means of a priori making crowdsourced tasks more resistant against cheaters.
Adaptive control of systems with backlash acting on the input (2002)

Two different adaptive controllers for systems with backlash acting on the input are discussed: one in continuous time and one in discrete time. Both schemes are based on a backlash inverse and a linear controller. The unknown plant parameters and the backlash width are estimated. The estimated parameters are used for pole placement design of the controller and for backlash compensation in the backlash inverse. Some analysis of the estimator convergence is done. Simulations of a second order plant show that both schemes give a nice behavior.
Role of cysteines 640, 656, and 661 in steroid binding to rat glucocorticoid receptors. (1992)

The involvement of a vicinally spaced dithiol group in steroid binding to the glucocorticoid receptor has been deduced from experiments with the thiol-specific reagent methyl methanethiolsulfonate and the vicinal dithiol-specific reagent sodium arsenite. The vicinally spaced dithiol appears to reside in the 16-kDa trypsin fragment of the receptor, which is thought to contain 3 cysteines (Cys-640, -656, and -661 of the rat receptor) and binds hormone with an approximately 23-fold lower affinity than does the intact 98-kDa receptor. We now report that the steroid binding specificity of preparations of this 16-kDa fragment and the intact receptor are virtually identical. This finding supports our designation of the 16-kDa fragment as a steroid-binding core domain and validates our continued use of this tryptic fragment in studies of steroid binding. To identify the cysteines which comprise the vicinally spaced dithiol group, and to examine further the role of cysteines in steroid binding, a total of five point mutant receptors were prepared: cysteine-to-serine for each suspected cysteine, cysteine-to-glycine for Cys-656, and the C656,661S double mutant. Unexpectedly, each receptor with a single point mutation still bound steroid. Even the double mutant (C656,661S) bound steroid with wild type affinity. These results suggest that none of these cysteines are directly required either for steroid binding to the glucocorticoid receptor or for heat shock protein 90 association with the receptor. However, the presence of Cys-656 was obligatory for covalent labeling of the receptor by [3H]dexamethasone 21-mesylate. Studies with preparations of the 98 and 16 kDa forms of these mutant receptors revealed both that Cys-656 and -661 comprise the vicinally spaced dithiols reacting with arsenite and that any two of the three thiols could form an intramolecular disulfide after treatment with low concentrations of methyl methanethiolsulfonate. These data, in conjunction with those from experiments on the effects of steric bulk on various receptor functions, support a model for the ligand binding cavity of the receptor that involves all three thiols in a flexible cleft but where thiol-steroid interactions are not essential for binding.