gebhart/patrepeval huggingface dataset:
Molecular basis of ALS and FTD: implications for translational studies / Molekularna osnova ALS-a i FTD-a: implikacije za translacijska istraživanja (2015)

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The cause is unknown and no effective treatment currently exists. For ALS, there is only a drug Riluzole and a promising substance arimoclomol. The overlap between ALS and FTD occurs at clinical, genetic, and pathological levels. The majority of ALS cases are sporadic (SALS) and a subset of patients has an inherited form of the disease, familial ALS (FALS), with a common SOD1 mutation, also present in SALS. A few of the mutant genes identified in FALS have also been found in SALS. Recently, hexanucleotide repeat expansions in C9ORF72 gene were found to comprise the largest fraction of ALS- and FTD-causing mutations known to date. TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, has been identified as the pathological protein of FALS, SALS and, less frequently, FTD. The less frequent TDP-43 pathology in other forms of familial FTD has been linked to a range of mutations in GRN, FUS/TLS, rarely VCP, and other genes. TDP-43 and FUS/TLS have striking structural and functional similarities, most likely implicating altered RNA processing as a major event in ALS pathogenesis. The clinical overlap of the symptoms of FTD and ALS is complemented by overlapping neuropathology, with intracellular inclusions composed of microtubule-associated protein tau, TDP-43 and less frequently FUS, or unknown ubiquitinated proteins. Furthermore, new therapeutic approaches continue to emerge, by targeting SOD1, TDP-43 or GRN proteins. This review addresses new advances that are being made in our understanding of the molecular mechanisms of both diseases, which may eventually translate into new treatment options.
Development of mobile inspection robot for rescue activities: MOIRA (2004)

In this paper we introduce our developed prototype mobile inspection robot for rescue activities named MOIRA. The robot consists of multi links and the four directions of each link are equipped with small crawlers. Due to the structural features, MOIRA has the following features. (a) MOIRA can go into the debris even if there is a restraint from the four directions (up-side, down-side, right-side and left side). (b) MOIRA does not have a concept of the four directions. That is, MOIRA can be operated even if the robot sideslips without any recover actions.
Chemical Attenuation of Plasmodium berghei Sporozoites Induces Sterile Immunity in Mice (2008)

Radiation and genetic attenuation of Plasmodium sporozoites are two approaches for whole-organism vaccines that protect against malaria. We evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. Sporozoites were treated with the DNA sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits Plasmodium falciparum growth in vitro. Here we show that treatment of Plasmodium berghei sporozoites with centanamycin impaired parasite function both in vitro and in vivo. The infection of hepatocytes by sporozoites in vitro was significantly reduced, and treated parasites showed arrested liver stage development. Inoculation of mice with sporozoites that were treated in vitro with centanamycin failed to produce blood stage infections. Furthermore, BALB/c and C57BL/6 mice vaccinated with treated sporozoites were protected against subsequent challenge with wild-type sporozoites. Our findings demonstrate that chemically attenuated sporozoites could be a viable alternative for the production of an effective liver stage vaccine for malaria.
Rheoencephalographic and Other Studies of Betahistine in Humans: I. The Cerebral and Peripheral Circulatory Effects of Single Doses in Normal Subjects (1975)

Two groups of six young normal male subjects were studied by an improved form of rheoencephalography (intracranial rheoncephalography), by photoplethysmography, and by impedance plethysmography to investigate the possible effects of single doses of betahistine hydrochloride (SERC) and placebo on the normal human cranial, cerebral, scalp, and calf circulations. Two subjects participated in both groups. The results of the two studies were similar and were combined for this presentation. One subject reported slight transient faintness and visual blurring after 20 mg of the drug. No other adverse or side effects were encountered. The results show that the drug causes definite, strong, reproducible, and dose-related responses in the studied circulations, typically those of decreases in their waveform amplitudes and pulse propagation times. Betahistine hydrochloride thus acts as a potent cerebral and peripheral microcirculatory vasodilator in normal humans when given orally. Split-dose studies indicate that responses followed each dose and that the second response was superimposed on the first. The value of using betahistine hydrochloride in overlapping doses is suggested. Atypical cranial, cerebral, scalp, and calf amplitude increases were found in some high-dosage (16-mg) trials. These increases may indicate that betahistine hydrochloride can also act as an arterial vasodilator in sufficiently high dosage, but they equally may indicate that sufficiently profound microcirculatory vasodilatation can elicit secondary arterial circulatory increases.
Elastic and viscoelastic effects in rubber/air acoustic band gap structures: A theoretical and experimental study (2008)

The transmission of acoustic waves through centimeter-scale elastic and viscoelastic two-dimensional silicone rubber/air phononic crystal structures is investigated theoretically and experimentally. We introduce a finite difference time domain method for two-dimensional elastic and viscoelastic composite structures. Elastic fluid-solid phononic crystals composed of a two-dimensional array of cylindrical air inclusions in a solid rubber matrix, as well as an array of rubber cylinders in an air matrix, are shown to behave similarly to fluid-fluid composite structures. These systems exhibit very wide band gaps in their transmission spectra that extend to frequencies in the audible range of the spectrum. This effect is associated with the very low value of the transverse speed of sound in rubber compared to that of the longitudinal polarization. The difference in transmission between elastic and viscoelastic rubber/air crystals results from attenuation of transmission over a very wide frequency range, leaving only narrow passing bands at very low frequencies. These phononic crystals demonstrate the practical design of elastic or viscoelastic solid rubber/air acoustic band gap sound barriers with small dimensions.
Resonantly laser-driven plasma waves for electron acceleration (1995)

A method for generating large-amplitude nonlinear plasma waves, which utilizes an optimized train of independently adjustable, intense laser pulses, is analyzed in one dimension both theoretically and numerically (using both Maxwell-fluid and particle-in-cell codes). Optimal pulse widths and interpulse spacings are computed for pulses with either square or finite-rise-time sine shapes. A resonant region of the plasma wave phase space is found where the plasma wave is driven most efficiently by the laser pulses. The width of this region, and thus the optimal finite-rise-time laser pulse width, was found to decrease with increasing background plasma density and plasma wave amplitude, while the nonlinear plasma wavelength, and thus the optimal interpulse spacing, increases. Also investigated are damping of the wave by trapped background electrons and the sensitivities of the resonance to variations in the laser and plasma parameters. Resonant excitation is found to be superior for electron acceleration to either beat-wave or single-pulse excitation because comparable plasma-wave amplitudes may be generated at lower plasma densities, reducing electron-phase detuning, or at lower laser intensities, reducing laser-plasma instabilities. Practical experimental methods for producing the required pulse trains are discussed.
p53-induced Gene 3 Mediates Cell Death Induced by Glutathione Peroxidase 3 (2012)

Expression of glutathione peroxidase 3 (GPx3) is down-regulated in a variety of human malignancies. Both methylation and deletion of GPx3 gene underlie the alterations of GPx3 expression in prostate cancer. A strong correlation between the down-regulation of GPx3 expression and progression of prostate cancer and the suppression of prostate cancer xenografts in SCID mice by forced expression of GPx3 suggests a tumor suppression role of GPx3 in prostate cancer. However, the mechanism of GPx3-mediated tumor suppression remains unclear. In this report, GPx3 was found to interact directly with p53-induced gene 3 (PIG3). Forced overexpression of GPx3 in prostate cancer cell lines DU145 and PC3 as well as immortalized prostate epithelial cells RWPE-1 increased apoptotic cell death. Expression of GPx3(x73c), a peroxidase-negative OPAL codon mutant, in DU145 and PC3 cells also increased cell death. The induced expression of GPx3 in DU145 and PC3 cells resulted in an increase in reactive oxygen species and caspase-3 activity. These activities were abrogated by either knocking down PIG3 or mutating the PIG3 binding motif in GPx3 or binding interference from a peptide corresponding to PIG3 binding motif in GPx3. In addition, UV-treated RWPE-1 cells underwent apoptotic death, which was partially prevented by knocking down GPx3 or PIG3, suggesting that GPx3-PIG3 signaling is critical for UV-induced apoptosis. Taken together, these results reveal a novel signaling pathway of GPx3-PIG3 in the regulation of cell death in prostate cancer.
THE EFFECT OF GENITAL PROLAPSE ON VOIDING (1999)

Lower urinary tract symptoms are common in women with genital prolapse. Voiding difficulty, bladder outlet obstruction and occult stress incontinence may coexist and they are associated with prolapse. Detrusor instability and urethral hypermobility also correlate with the degree of prolapse but impaired detrusor contractility and intrinsic sphincter deficiency do not. In women with severe prolapse ring pessary reduction of prolapse during urodynamics is useful to determine symptomatic and occult conditions.
Cognate interactions between helper T cells and B cells. II. Dissection of cognate help by using a class II-restricted, antigen-specific, IL-2-dependent helper T cell clone. (1989)

In order to determine the involvement of T-B cell contact vs lymphokine production in mediating B cell cycle entry and progression, Th cell clones "defective" in lymphokine production were cloned. Th-3.1 is one such clone that required IL-2 to produce significant levels of IL-4 and IFN-gamma. Unlike conventional Th clones, Th-3.1 induced B cell proliferation only in the presence of Ag and IL-2. In contrast to the absolute requirement of IL-2 for Th-3.1-induced B cell proliferation, IL-2 was not required for the formation of stable Th-3.1-B cell conjugates or Th-3.1-induced B cell entry into the G1 phase of the cell cycle. In the absence of IL-2 and under conditions that promoted Th-B cell interactions, Th-3.1 induced 10 to 20% of resting B cells to enter G1. B cell entry into the cell cycle was not inhibited by anti-lymphokine mAb or promoted by exogenous lymphokines, suggesting that endogenous lymphokine activity was not required for Th-3.1-induced G0 to G1 transition. The data suggested that the IL-2-independent induction of B cells into G1 by Th-3.1 was a cell contact-dependent event. Direct proof that Th-3.1-B cell contact was necessary for B cell cycle entry was provided by comparative in situ analysis of the RNA synthetic activity and the RNA content of B cells that were in physical contact with Th-3.1 or not in contact with Th-3.1. In situ autoradiography of RNA synthesis illustrated that a high frequency of B cells in contact with Th-3.1 expressed heightened RNA synthetic activity, whereas "bystander" B cells were less frequently induced into cycle. In situ laser cytometry of B cell size and total RNA content showed that B cells in physical contact with Th-3.1 had a higher RNA content and were larger than "bystander" B cells present in the same microcultures. This model system has allowed the dissection of T cell help into IL-2-dependent and IL-2-independent phases. Early cell contact-dependent events and B cell cycle progression into G1 were IL-2 independent, whereas the production of lymphokines (IL-4, IFN-gamma) by Th-3.1 and Th-3.1-induced B cell proliferation was IL-2 dependent.
Adult Rat Hepatocyte Cultures As The Cellular Component Of An Artificial Hybrid Liver (1984)

Irreversible cellular damage occurs in acute hepatic failure and end-stage cirrhosis, resulting in severely impaired liver functions. These functions can be regained when sufficient hepatocyte regeneration occurs or a suitable donor organ is available for transplantation. The presence of phenolic compounds, free fatty acids, ammonia and mercaptans in high concentrations in the serum of patients with hepatic coma is well established (Zieve, 1981). Removal of these products requires their detoxification by oxidation and conjugation reactions, converting lipophilic metabolites into more hydrophilic compounds that can be excreted into bile and urine. Recent developments in membrane plasmapheresis (Asanuma et al., 1980; Inoue et al., 1981), haemoperfusion (Chang, 1972; Silk and Williams, 1978), or haemodialysis and haemofiltration (Knell, 1981), have improved the prognosis for hepatic failure according to some experimental and clinical trials, but the detoxifying functions of the liver cell, particularly the ones related with glucuronisation, sulphation, transmethylation and cytochrome P450 (together with NADPH-cytochrome P450 reductase) are still difficult to replace. Although the introduction of cyclosporin A has substantially controlled the immunological rejection in liver transplants (Starzl et al., 1981), the scarcity of cadaver livers free of disease necessitates alternative solutions. The development of active enzymaticKeywordsFace SheetHepatic ComaArtificial LiverTissue Culture MediumArtificial Liver SupportThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Technological and economic potential of poly(lactic acid) and lactic acid derivatives (1995)

Lactic acid has been an intermediate-volume specialty chemical (world production ~ 40,000 tons/yr) used in a wide range of food processing and industrial applications. Lactic acid has the potential of becoming a very large volume, commodity-chemical intermediate produced from renewable carbohydrates for use as feedstocks for biodegradable polymers, oxygenated chemicals, plant growth regulators, environmentally friendly 'green' solvents, and specialty chemical intermediates. The recent announcements of new development-scale plants for producing lactic acid and polymer intermediates by major U.S. companies, such as Cargill, Ecochem (DuPont/ConAgra), and Archer Daniels Midland, attest to this potential.
Effect of Polymer Hydration State on In-Gel Immunoassays (2015)

Applications as diverse as drug delivery and immunoassays require hydrogels to house high concentration macromolecular solutions. Yet, thermodynamic partitioning acts to lower the equilibrium concentration of macromolecules in the hydrogel, as compared to the surrounding liquid phase. For immunoassays that utilize a target antigen immobilized in the hydrogel, partitioning hinders introduction of detection antibody into the gel and, consequently, reduces the in-gel concentration of detection antibody, adversely impacting assay sensitivity. Recently, we developed a single-cell targeted proteomic assay with polyacrylamide gel electrophoresis of single cell lysates followed by an in-gel immunoassay. In the present work, we overcome partitioning that both limits analytical sensitivity and increases consumption of costly detection antibody by performing the immunoassay step after dehydrating the antigen-containing polyacrylamide gel. Gels are rehydrated with a solution of detection antibody. We hypothesized that matching the volume of detection antibody solution with the hydrogel water volume fraction would ensure that, at equilibrium, the detection antibody mass resides in the gel and not in the liquid surrounding the gel. Using this approach, we observe (compared with antibody incubation of hydrated gels): (i) 4-11 fold higher concentration of antibody in the dehydrated gels and in the single-cell assay (ii) higher fluorescence immunoassay signal, with up to 5-fold increases in signal-to-noise-ratio and (iii) reduced detection antibody consumption. We also find that detection antibody signal may be less well-correlated with target protein levels (GFP) using this method, suggesting a trade-off between analytical sensitivity and variation in immunoprobe signal. Our volume-matching approach for introducing macromolecular solutions to hydrogels increases the local in-gel concentration of detection antibody without requiring modification of the hydrogel structure, and thus we anticipate broad applicability to hydrogel-based assays, diagnostics, and drug delivery.
PENILE ERECTILE FUNCTION AFTER PERMANENT RADIOACTIVE SEED IMPLANTATION FOR TREATMENT OF PROSTATE CANCER (2001)

The rate of potency preservation after brachytherapy is high, although a decrease occurs from 3 to 6 years. Pretreatment erectile dysfunction as well as higher implant dose are associated with greater impotency.
[Research on laser spectrum detecting technology based on static Mach-Zehnder interferometer]. (2009)

It is the key content of laser warning to reliably and real-time detect the type and characteristic parameters of incident laser. Coherent detection technology detects the information based on the coherence of laser, and is a kind of effective detection technology. In order to detect the incident laser's spectrum, a kind of device for laser detecting and real time spectrum measurement was designed, which measures the laser spectrum on the bases of coherent detecting technology, Fourier optics and optical signal processing. Using compact and static Mach-Zehnder interferometer as the coherent detection components, it can restrain the background light efficiently. The non-scanning mechanical parts allow fast spectrum detection, and narrow laser pulse can be detected. The real-time signal processing is realized by DSP and multi-channel frame subtraction technology to wipe off the background light, detect the laser and measure its spectrum. The result indicates that, using Mach-Zehnder interferometer and multi-channel frame subtraction technology can realize the laser pulse detection, and improve the measuring precision efficiently; 10 ns laser pulse can be detected and the wavelength measuring error is less than 10 nm.
ent-Kaurene Biosynthesis Is Enhanced by Long Photoperiods in the Long-Day Plants Spinacia oleracea L. and Agrostemma githago L (1993)

The effect of photoperiod on ent-kaurene biosynthesis was determined in the long-day (LD) plants spinach (Spinacia oleracea L.) and Agrostemma githago L. Further metabolism of ent-kaurene was blocked by application of the growth retardant tetcyclacis, and ent-kaurene accumulation was measured by isotopic dilution using gas chromatography-selected ion monitoring (GC-SIM) (E. Grosselindemann, J.E. Graebe, D. Stöckl, P. Hedden [1991] Plant Physiol 96: 1099-1104). In spinach, the rate of ent-kaurene accumulation in shoots grown under LD conditions was 3 times higher than in shoots grown under short-day (SD) conditions. ent-Kaurene also accumulated in fully expanded leaves, but at a lower rate than in shoots (15 and 55 pmol g-1 dry weight h-1, respectively). In Agrostemma, ent-kaurene accumulated at a rate 2.5 times higher in plants grown under LD conditions than in those grown under SD conditions. In spinach, enhanced ent-kaurene accumulation was detectable after 1 long day, and with exposure to additional long days, the rate of ent-kaurene accumulation increased further. Conversely, when plants were exposed to LD conditions and then returned to SD conditions, the rate of ent-kaurene accumulation decreased. Following tetcyclacis application, ent-kaurene accumulation was observed in all parts of spinach that were analyzed, but there were large quantitative differences between organs of different ages. As the leaves matured, ent-kaurene biosynthesis declined. Petioles accumulated more ent-kaurene than the corresponding leaf blades. It is concluded that stimulation of ent-kaurene biosynthesis by LD conditions leads to a higher rate of gibberellin biosynthesis, which is essential for stem elongation in rosette plants.
Developmental Regulation of Elastin Production. (1995)

To assess the mechanisms controlling the developmental regulation of tropoelastin expression in vivo, we developed a reverse-transcription-polymerase chain reaction (RT-PCR) assay to detect tropoelastin pre-mRNA as an indicator of ongoing transcription in intact tissue. RNA was isolated from mid-fetal (early-elastogenic), neonatal (peak tropoelastin expression), and adult (very low tropoelastin expression) rat lungs and reverse transcribed, and the cDNA was amplified with intron specific primers. A weak hybridization signal for tropoelastin pre-mRNA was seen in mid-fetal samples, and paralleling the increase in steady-state mRNA levels, a strong signal for pre-mRNA was detected in neonatal samples, indicating transcriptional regulation. Stimulation of fetal lung tropoelastin expression by maternal administration of dexamethasone also led to an increase in pre-mRNA levels. However, signal for tropoelastin pre-mRNA in adult samples was equal to that detected in neonatal samples, even though mRNA levels had dropped about 80-fold. Persistence of tropoelastin transcription in adult tissue was also seen in cell culture models and was verified by nuclear runoff assay. In addition, an RT-PCR assay for alpha 1 (I) procollagen pre-mRNA accurately revealed the known transcriptional regulation of this gene. Our results demonstrate that the induction and maintenance of elastogenesis is controlled by a transcriptional mechanism, whereas, the cessation of tropoelastin expression is controlled by a post-transcriptional mechanism.
Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization (2010)

We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.