gebhart/patrepeval huggingface dataset:
Folding intermediates are involved in genetic diseases? (1995)

Recent experimental data show that some human genetic diseases are due to mutations in proteins which influence their trafficking and lead to retaining of proteins in the endoplasmic reticulum or their unproper processing. In this paper a hypothesis is proposed that these mutations are connected with an incomplete protein folding, blocking it at the stage of the kinetic molten globule or even earlier. If so, the specific drugs against these diseases may be ligands and other factors which facilitate the correct protein folding.
Role of phospholipase Cγ at fertilization and during mitosis in sea urchin eggs and embryos (1999)

It is well known that stimulation of egg metabolism after fertilization is due to a rise in intracellular free calcium concentration. In sea urchin eggs, this first calcium signal is followed by other calcium transients that allow progression through mitotic control points of the cell cycle of the early embryo. How sperm induces these calcium transients is still far from being understood. In sea urchin eggs, both InsP3 and ryanodine receptors contribute to generate the fertilization calcium transient, while the InsP3 receptor generates the subsequent mitotic calcium transients. The identity of the mechanisms that generate InsP3 after fertilization remains an enigma. In order to determine whether PLCgamma might be the origin of the peaks of InsP3 production that punctuate the first mitotic cell cycles of the fertilized sea urchin egg, we have amplified by RT-PCR several fragments of sea urchin PLCgamma containing the two SH2 domains. The sequence shares similarities with SH2 domains of PLCgamma from mammals. One fragment was subcloned into a bacterial expression plasmid and a GST-fusion protein was produced and purified. Antibodies raised to the GST fusion protein demonstrate the presence of PLCgamma protein in eggs. Microinjection of the fragment into embryos interferes with mitosis. A related construct made from bovine PLCgamma also delayed or prevented entry into mitosis and blocked or prolonged metaphase. The bovine construct also blocked the calcium transient at fertilization, in contrast to a tandem SH2 control construct which did not inhibit either fertilization or mitosis. Our data indicate that PLCgamma plays a key role during fertilization and early development.
Inhibitory Effects of Japanese Herbal Medicines Sho-saiko-to and Juzen-taiho-to on Nonalcoholic Steatohepatitis in Mice (2014)

Although Japanese herbal medicines (JHMs) are widely used in Japan, only a few studies have investigated their effects on nonalcoholic steatohepatitis (NASH). In the present study, we examined the effect of 4 kinds of JHMs [sho-saiko-to (TJ-9), inchin-ko-to (TJ-135), juzen-taiho-to (TJ-48), and keishi-bukuryo-gan (TJ-25)] on a mouse model of NASH. Db/db mice were divided into 6 groups: control diet (control), methionine- and choline-deficient diet (MCD), and MCD diet supplemented with TJ-9, TJ-135, TJ-48, and TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively). All mice were sacrificed after 4 weeks of treatment, and biochemical, pathological, and molecular analyses were performed. Serum alanine aminotransferase levels and liver histology, including necroinflammation and fibrosis, were significantly alleviated in the TJ-9 and TJ-48 groups compared with the MCD group. The expression level of transforming growth factor (TGF)-β1 mRNA in the liver was significantly suppressed by TJ-48. Although the differences were not statistically significant, the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were lower, and those of peroxisome proliferators-activated receptor (PPAR)γ were higher in the TJ-9 and/or TJ-48 groups than in the MCD group. Similarly, even though the results were not statistically significant, malondialdehyde levels in liver tissues were lower in the TJ-9 and TJ-48 groups than in the MCD group. We showed that JHMs, especially TJ-9 and TJ-48, inhibited the necroinflammation and fibrosis in the liver of a mouse model of NASH, even though the mechanisms were not fully elucidated. Further studies are needed in the future to investigate the possibility of clinical application of these medicines in the treatment for NASH.
Anticipating, measuring, and minimizing MEMS mirror scan error to improve laser scanning microscopy's speed and accuracy (2017)

We describe a method to speed up microelectromechanical system (MEMS) mirror scanning by > 20x, while also improving scan accuracy. We use Landweber deconvolution to determine an input voltage which would produce a desired output, based on the measured MEMS impulse response. Since the MEMS is weakly nonlinear, the observed behavior deviates from expectations, and we iteratively improve our input to minimize this deviation. This allows customizable MEMS angle vs. time with <1% deviation from the desired scan pattern. We demonstrate our technique by optimizing a point scanning microscope's raster patterns to image mammal submandibular gland and pollen at ~10 frames/s.
Reassembly of lipid-protein complexes of pulmonary surfactant. Proposed mechanism of interaction. (1983)

We studied the interaction at 37 degrees C between a major apolipoprotein of pulmonary surfactant and 11 mixtures of lipids. The experiments were carried out in the presence of either 3 mM Ca2+ or 10 mM EDTA. The amount of apolipoprotein associated with lipid was independent of Ca2+. However the binding was sensitive to the percentage of gel-state lipid in the vesicles, and the amount of apolipoprotein in the recombinant lipoprotein complex decreased as the percentage of fully saturated phospholipid was reduced. Maximum association of the apolipoprotein occurred with lipid vesicles containing 85% 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 15% 1,2-dipalmitoyl-sn-glycero-3-phospho-1-glycerol or 1,2-dipalmitoyl-sn-glycerol. Fluorescence measurements on the apolipoprotein indicated that the tryptophan side chains were in a relatively hydrophobic environment, and that the wavelength of maximum fluorescence emission was not changed upon the binding of lipid. The results suggest that the principal mode of interaction between the apolipoprotein and lipids of surfactant is hydrophobic bonding. The most extensive binding occurs with lamellar lipids in a gel that would be expected to have inhomogeneities in packing density due to the presence of acidic phospholipids or other glycerolipids. The role of Ca2+ in this interaction has not been fully determined. Although it is not needed to effect the binding of the lipids and the apolipoprotein, it does influence the physical state of the complex, and possibly the stoichiometry of lipid to protein. Some of the processes mediated by Ca2+ in this interaction may be analogous to those observed in membrane fusion. Thus, Ca2+ probably causes segregation of the lamellar phospholipids into domains, inducing vesicular disruption and fusion. This lipid aggregates about hydrophobic sites on the protein, thereby forming high molecular weight reassembly complexes.
Risk Based Mobile Access Control (RiBMAC) policy framework (2011)

Mobile devices are increasingly being deployed by enterprises, governments, and the military. Protecting sensitive data that will invariably reside on them is critical. Mobile devices cannot be protected by physical security the same way as stationary systems. Therefore, they must deploy strong internal protection mechanisms for access control. Policies for access control must be driven by context and risk in the environmental in which they operate. This is inherently different from traditional policy models that focus on the multi-user access control. We propose the Risk Based Mobile Access Control (RiBMAC) policy framework for mobile device access control. It uses risk factor abstractions to break down the complexity in the specification, management and evaluation of risk based policies. Its agent-centric approach can effectively integrate a large number of onboard sensors and risk assessment components in different hardware and operational configurations. RiBMAC is a simple yet powerful policy framework that is expressive, practical and scalable. RiBMAC, in conjunction with the appropriate enforcement mechanisms, can greatly improve security for tactical mobile devices.
An Antagonist Mutant IL-15/Fc Promotes Transplant Tolerance (2006)

Immunochemistry studies demonstrated that prolonged graft survival was accompanied by reduced intragraft mononuclear cell infiltration and pro-inflammatory cytokine gene expression in the mIL-15/Fc treated recipients. Moreover, parallel experiments employing a mutated nonlytic IgG2a Fc demonstrate that the Fc portion of mIL-15/Fc contributes to the overall efficacy of the molecule in vivo.
Lidocaine Analgesia for Removal of Wound Vacuum-Assisted Closure Dressings (2012)

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
The Distribution of YKL-40 in Osteoarthritic and Normal Human Articular Cartilage (1999)

YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive staining for YKL-40 was in general low in normal cartilage. The present findings, together with previous observations, suggests that YKL-40 may be of importance in cartilage remodelling/degradation of osteoarthritic joints.
Oxindole-3-spiropyrrolidines and -piperidines. Synthesis and local anesthetic activity (1976)

The synthesis and local anesthetic properties of five 1-dealkyloxindole-3-spiropyrrolidines and six 1-dealkyloxindole-3-spiropiperidines are described. The compounds studied include members of all five possible positional isomers of the two classes of spirooxindoles; all showed local anesthetic activity by the rat sciatic nerve block method. The coincidence of the least variability in the relative positions of basic nitrogen, amide carbonyl, and aromatic ring (compounds 1 and 6) with lowest normalized toxicity is noteworthy.
Conditional Expression in the Malaria Mosquito Anopheles stephensi With Tet-On and Tet-Off Systems (2004)

We report successful conditional gene expression in the malaria vector, Anopheles stephensi, on the basis of binary systems consisting of gene driver and responder transgenic lines generated by Minos-mediated germline transformation. An A. gambiae tissue-specific enhancer derived from a serpin (SRPN10) gene was utilized to control the temporal and spatial expression of doxycycline (dox)-sensitive transcriptional regulators in the driver lines. The "Tet-Off" driver utilized the tetracycline-controlled transcriptional activator (tTA) that is unable to bind and activate transcription from tetracycline operators (TetO) in the presence of dox; the "Tet-on" driver utilized the reverse tTA (rtTA) that, conversely, binds and activates TetO operators in the presence of dox. The responder lines carried insertions encompassing a LacZ reporter gene, cis-regulated by a TetO-P-element hybrid promoter. The progeny of crosses between driver and responder lines expressed beta-galactosidase under dual, tissue-specific and dox-mediated regulation. In adult rtTA/TetOPlacZ progeny, dox treatment rapidly induced beta-galactosidase activity throughout the midgut epithelium and especially in malaria parasite-invaded epithelial cells. Transactivator-dependent, dox-mediated regulation was observed in hemocytes and pericardial cells using both systems. Conditional tissue-specific regulation is a powerful tool for analyzing gene function in mosquitoes and potentially for development of strategies to control disease transmission.
Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human (2000)

The cloned vanilloid receptor VR1 has attracted recent attention as a molecular integrator of painful stimuli on primary sensory neurons. The existence of vanilloid-sensitive neurons in the brain is, however, controversial. In this study, we have used an antibody and a complementary RNA probe to explore the distribution of neurons that express VR1 in rat and in certain areas of human brain. In the rat, we observed VR1-expressing neurons throughout the whole neuroaxis, including all cortical areas (in layers 3 and 5), several members of the limbic system (e.g., hippocampus, central amygdala, and both medial and lateral habenula), striatum, hypothalamus, centromedian and paraventricular thalamic nuclei, substantia nigra, reticular formation, locus coeruleus, cerebellum, and inferior olive. VR1-immunopositive cells also were found in the third and fifth layers of human parietal cortex. Reverse transcription-PCR performed with rat VR1-specific primers verified the expression of VR1 mRNA in cortex, hippocampus, and hypothalamus. In the central nervous system, neonatal capsaicin treatment depleted VR1 mRNA from the spinal nucleus of the trigeminal nerve, but not from other areas such as the inferior olive. The finding that VR1 is expressed not only in primary sensory neurons but also in several brain nuclei is of great importance in that it places VRs in a much broader perspective than pain perception. VRs in the brain (and putative endogenous vanilloids) may be involved in the control of emotions, learning, and satiety, just to name a few exciting possibilities.
Renal Na/H exchanger NHE-3 and Na-PO4 cotransporter NaPi-2 protein expression in glucocorticoid excess and deficient states. (1998)

Administration of pharmacologic doses of glucocorticoid in vivo increases renal proximal tubule apical membrane Na/H exchange and decreases Na/PO4 cotransport activity (1). Current data suggest that the NHE-3 and NaPi-2 proteins mediate significant fractions of proximal tubule apical membrane Na/H exchange and Na/PO4 cotransport, respectively. This study examines whether glucocorticoid excess or deficiency affects NHE-3 and NaPi-2 protein abundance and the intrarenal distribution of these transporters. Protein abundance of NHE-3 and NaPi-2 in control rats was compared to rats rendered glucocorticoid-deficient by bilateral adrenalectomy, and to rats receiving pharmacologic doses of dexamethasone using immunoblots and immunohistochemistry. Adrenalectomy had modest effects on NHE-3 protein abundance, but dexamethasone administration to either adrenalectomized or sham-operated rats significantly increased NHE-3 protein abundance in both the proximal tubule and thick ascending limb, but not the thin descending limb. Adrenalectomy increased NaPi-2 protein abundance in the proximal tubule, whereas dexamethasone administration dramatically suppressed NaPi-2 protein on the apical membrane in both adrenalectomized and sham-operated animals. No significant reciprocal increase in subapical NaPi-2 staining was seen in the dexamethasone-treated rats. The present study shows that glucocorticoids regulate proximal tubule apical membrane Na/H exchange and NaPi cotransport by changes in protein abundance of NHE-3 and NaPi-2, respectively.
RNA interference and its current application in mammals. (2004)

It is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. It is also expected that RNAi might one day be used to treat human diseases.
Evaluation of the Sites of Opioid Influence on Anterior Pituitary Hormone Secretion Using a Quaternary Opiate Antagonist (1991)

Studies were conducted to determine the effects of a potent narcotic antagonist, nalmefene methyliodide, which does not cross the blood-brain barrier (BBB), on the secretion of anterior pituitary hormones and on the anterior pituitary hormonal response to morphine sulfate. Since the localization of opiate receptor responses to inside or outside the BBB depended upon the relative ability of nalmefene HCl and nalmefene methyliodide to penetrate the BBB, initial studies were conducted to document that nalmefene methyliodide does not block opiate receptors inside the central nervous system. While nalmefene HCl blocked morphine-induced antinociceptive responses at doses as low as 10 micrograms/kg, nalmefene methyliodide was ineffective in this regard at doses as high as 500 micrograms/kg. The luteinizing hormone (LH) suppression and prolactin (PRL) secretion induced by morphine was blocked by both nalmefene HCl and its methyliodide analogue, indicating that the opioid receptor type which mediates both responses is located outside the BBB. We observed that basal PRL levels were reduced by nalmefene HCl but not by nalmefene methyliodide indicating that basal PRL secretion is influenced by opioid neurons inside the BBB. While nalmefene HCl blocked morphine-induced suppression of thyroid-stimulating hormone (TSH) release, nalmefene methyliodide was less effective, suggesting that opiate-induced TSH suppression may be mediated by receptors located both within and outside the BBB. Nalmefene HCl caused a growth hormone (GH)-secretory response by itself, but nalmefene HCl and nalmefene methyliodide were ineffective in blocking morphine-induced GH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Silicon-on-insulator optical intensity modulatorbased on waveguide-vanishing effect (1996)

A silicon-on-insulator (SOI) optical intensity modulator has been proposed and fabricated, and is based on the large cross-section singlemode rib waveguide condition, the waveguide-vanishing effect and the free-carrier plasma dispersion effect. In the modulator the SOI technique uses silicon and silicon dioxide thermal bonding and back-polishing. The insertion loss of the device is measured to be 3.65 dB at a wavelength of 1.3 µm. The modulation depth is 96% at an injection current of 45 mA. Response time is ~160 ns.
Systemic tumor necrosis factor α mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor α–transgenic mice (2004)

Systemic TNFalpha induces a marked increase in circulating OCPs that is reversible by anti-TNF therapy and may result from their mobilization from bone marrow. Our findings provide a new mechanism whereby TNFalpha stimulates osteoclastogenesis in patients with inflammatory arthritis, suggesting that CD11b+ PBMCs could be used to evaluate a patient's potential for erosive disease and the efficacy of anti-TNF therapy.
Pharmacokinetics of liposomal cisplatin (lipoplatin) in combination with 5-FU in patients with advanced head and neck cancer: first results of a phase III study. (2007)

The pharmacokinetic profile of lipoplatin (in combination with 5-FU) suggests that the liposomal formulation results in a greater body clearance and shorter half life than conventional cisplatin, which confirms the clinical observation of decreased taxicity, especially renal deterioration.
Principles of small molecule activation by metalloenzymes as exemplified by the soluble methane monooxygenase from Methylococcus capsulatus (Bath) * (1997)

Many metalloenzymes activate small molecules in a manner that is unique to natural systems. In this Perspective we discuss the soluble methane monooxygenase protein system from Methylococcus capsulatus (Bath), which uses a mixed-function oxidase to convert methane selectively to methanol. Through a series of biophysical studies, theoretical calculations, synthetic model studies and mechanistic biochemical experiments, the respective roles of the carboxylate-bridged non-heme diiron center and the protein environment in controlling the enzyme mechanism have been delineated. These results are used to identify themes common among metalloenzymes that activate small molecules and to identify future directions for the study of this protein system.
Neuropsychological and psychiatric functioning in sheep farmers exposed to low levels of organophosphate pesticides (2010)

The study aim was to determine whether low level exposure to organophosphate pesticides (OPs) causes neuropsychological or psychiatric impairment. Methodological weaknesses of earlier studies were addressed by: recruiting participants who had retired on ill health grounds; excluding participants with a history of acute poisoning, medical or psychiatric conditions that might account for ill health; and exploring factors which may render some individuals more vulnerable to the effects of OPs than others. Performance on tests of cognition and mood of 127 exposed sheep farmers (67 working, 60 retired) was compared with 78 unexposed controls (38 working, 40 retired) and published test norms derived from a cross section of several thousand adults in the general population. Over 40% of the exposed cohort reported clinically significant levels of anxiety and depression compared to less than 23% of controls. Exposed subjects performed significantly worse than controls and standardisation samples on tests of memory, response speed, fine motor control, mental flexibility and strategy making, even after controlling for the effects of mood. The pattern was similar for both working and retired groups. The cognitive deficits identified cannot be attributed to mood disorder, malingering, a history of acute exposure or genetic vulnerability in terms of PON1(192) polymorphisms. Results suggest a relationship may exist between low level exposure to organophosphates and impaired neurobehavioural functioning and these findings have implications for working practice and for other occupational groups exposed to OPs such as aviation workers and Gulf War veterans.
Preclinical characterization and in vivo imaging studies of an engineered recombinant technetium-99m-labeled metallothionein-containing anti-carcinoembryonic antigen single-chain antibody. (1998)

A recombinant MET containing scFv was successfully expressed, purified and labeled with 99Tc. The stable site-specific labeling of 99Tc, combined with the rapid plasma clearance of the scFv, led to successful early in vivo imaging of xenografted mice.
Dynamics of Person-to-Person Interactions from Distributed RFID Sensor Networks (2010)

Taking advantage of scalability and resolution, this experimental framework allows the monitoring of social interactions, uncovering similarities in the way individuals interact in different contexts, and identifying patterns of super-connector behavior in the community. These results could impact our understanding of all phenomena driven by face-to-face interactions, such as the spreading of transmissible infectious diseases and information.