gebhart/patrepeval huggingface dataset:
Aggregation of Mutant Cu/Zn Superoxide Dismutase Proteins in a Culture Model of ALS (1997)

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene underlie some familial cases of amyotrophic lateral sclerosis (FALS), a neurodegenerative disorder characterized by loss of cortical, brainstem, and spinal motor neurons. To investigate the mechanisms responsible for the toxicity of mutant enzyme, SOD-1 cDNAs bearing mutations found in FALS patients (mSOD) were expressed in cultured spinal motor neurons, dorsal root ganglion (DRG) and hippocampal neurons. Many features of motor neuron disease seen in humans with FALS and in transgenic mouse models were reproduced, including preferential susceptibility of motor neurons to toxicity of mSOD. Abnormal cytoplasmic aggregation of mSOD protein was observed in mSOD-expressing motor neurons, but never in neurons expressing SODwt enzyme, and was followed by evidence of apoptotic cell death. Such aggregates were not observed in nonvulnerable neuronal populations expressing mSOD (DRG or hippocampal neurons). Aggregation of SOD-1 may contribute significantly to the death of motor neurons expressing mutations associated with FALS-1 and the mechanisms leading to aggregation may pertain to the specific vulnerability of motor neurons in this disease.
Cyclohexylcarbamic Acid 3‘- or 4‘-Substituted Biphenyl-3-yl Esters as Fatty Acid Amide Hydrolase Inhibitors:  Synthesis, Quantitative Structure−Activity Relationships, and Molecular Modeling Studies (2004)

Fatty acid amide hydrolase (FAAH) is a promising target for modulating endocannabinoid and fatty acid ethanolamide signaling, which may have important therapeutic potential. We recently described a new class of O-arylcarbamate inhibitors of FAAH, including the cyclohexylcarbamic acid biphenyl-3-yl ester URB524 (half-maximal inhibitory concentration, IC(50) = 63 nM), which have significant anxiolytic-like properties in rats. In the present study, by introducing a selected group of substituents at the meta and para positions of the distal phenyl ring of URB524, we have characterized structure-activity profiles for this series of compounds and shown that introduction of small polar groups in the meta position greatly improves inhibitory potency. Most potent in the series was the m-carbamoyl derivative URB597 (4i, IC(50) = 4.6 nM). Furthermore, quantitative structure-activity relationship (QSAR) analysis of an extended set of meta-substituted derivatives revealed a negative correlation between potency and lipophilicity and suggested that small-sized substituents may undertake polar interactions with the binding pocket of the enzyme. Docking studies and molecular dynamics simulations, using the crystal structure of FAAH, indicated that the O-biphenyl scaffold of the carbamate inhibitors can be accommodated within a lipophilic region of the substrate-binding site, where their folded shape mimics the initial 10-12 carbon atoms of the arachidonyl moiety of anandamide (a natural FAAH substrate) and methyl arachidonyl fluorophosphonate (a nonselective FAAH inhibitor). Moreover, substituents at the meta position of the distal phenyl ring can form hydrogen bonds with atoms located on the polar section of a narrow channel pointing toward the membrane-associated side of the enzyme. The structure-activity characterization reported here should help optimize the pharmacodynamic and pharmacokinetic properties of this class of compounds.
Purification and Characterization of Two Aldehyde Dehydrogenases from Pseudomonas aeruginosa (1977)

Two soluble aldehyde dehydrogenases isoenzymes have been purified and separated from extracts of a paraffin‐assimilating bacterium, Pseudomonas aeruginosa. The first one, obtained at an estimated purity of 20% (spec. act. with butanal 0.33 kat/kg) was NAD‐dependent. It was rapidly inactivated at pH 8.6 but was efficiently protected by NAD. It had a molecular weight of 225000 and presented a high affinity for aldehydes of short and middle chain lengths. The second enzyme, obtained in a nearly homogenous state (spec. act. with pentanal 0.62 kat/kg) was NADP‐dependent. It was activated by ions, in particular potassium ions, and had a good affinity for aldehydes of higher chain lengths. Both enzymes were stabilized by thiols and glycerol and were inactivated by reagents of sulfhydryl groups. These enzymes are ‘constitutive’ and their physiological function is uncertain. When the bacteria were grown on n ‐paraffin a new membrane‐bound NAD‐dependent aldehyde dehydrogenase activity was produced.
Modeling and Data for Thermal Conductivity of Ultrathin Single-Crystal SOI Layers at High Temperature (2006)

Simulations of the temperature field in silicon-on-insulator (SOI) and strained-Si transistors can benefit from experimental data and modeling of the thin silicon layer thermal conductivity at high temperatures. This paper develops algebraic expressions to account for the reduction in thermal conductivity due to the phonon-boundary scattering for pure and doped silicon layers and presents the experimental data for 50-nm-thick single-crystal silicon layers at high temperatures. The model applies to the temperature range of 300-1000 K for silicon layer thicknesses from 10 nm to 1 mum (and even bulk), which agrees well with the experimental data. In addition, the algebraic model has an excellent agreement with both the experimental data and predictions of thin-film thermal conductivity based on thermal conductivity integral and Boltzmann transport equation. The analytical thermal modeling and ISE-TCAD electrothermal simulations confirm that both the electrical and thermal performances of SOI transistor can be largely affected if the reduced thermal conductivity of the silicon due to phonon boundary scattering is not properly taken into consideration
Control of Erythropoietin Secretion by Doxycycline or Mifepristone in Mice Bearing Polymer-Encapsulated Engineered Cells (1999)

Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete mouse erythropoietin (Epo) in response to stimulation by doxycycline or mifepristone. Engineered cells were introduced into AN69 hollow fibers, which were implanted in the peritoneal cavity or recipient mice. Animals receiving doxycycline or mifepristone showed stable polyhemia and increased serum Epo concentrations over a 6-month observation period, whereas animals not receiving the inducer drug had normal hematocrits. Epo secretion could be switched on and off, depending on the presence of doxycycline in the drinking water. In contrast, polyhemia was hardly reversible after subcutaneous injections of mifepristone. These data show that a permanent and regulated systemic delivery of a therapeutic protein can be obtained by the in vivo implantation of engineered allogeneic cells immunoprotected in membrane polymers.
Early events in DNA replication require cyclin E and are blocked by p21CIP1. (1995)

Using immunodepletion of cyclin E and the inhibitor protein p21WAF/CIP1, we demonstrate that the cyclin E protein, in association with Cdk2, is required for the elongation phase of replication on single-stranded substrates. Although cyclin E/Cdk2 is likely to be the major target by which p21 inhibits the initiation of sperm DNA replication, p21 can inhibit single-stranded replication through a mechanism dependent on PCNA. While the cyclin E/Cdk2 complex appears to have a role in the initiation of DNA replication, another Cdk kinase, possibly cyclin A/Cdk, may be involved in a later step controlling the switch from initiation to elongation. The provision of a large maternal pool of cyclin E protein shows that regulators of replication are constitutively present, which explains the lack of a protein synthesis requirement for replication in the early embryonic cell cycle.
PPAR_19481_Teszt_1105 (2021)

PPAR_19481_Teszt_1105
Milling of submicron channels on gold layer using double charged arsenic ion beam (2004)

The capability of using a focused ion beam (FIB) for milling of submicron channel structures on a gold layer is investigated. A double-charged arsenic (As2+) FIB is adopted to assess the effect of the dwell time on the final profiles of the milled structures. A single-pass milling, which creates relatively shallow microchannels, is conducted in order to estimate the corresponding milling yields. The condition to provide a uniform ion flux in milling is first studied. The procedure on conducting the milling experiment is then presented. The atomic force microscope (AFM) is applied for measuring the profiles of the milled channels. Based on the AFM measurements, the milling yields have been estimated and compared with the sputtering yields predicted by a more sophisticated numerical simulation. The milling yield for the relatively shallow microchannels presently considered has been discovered to be roughly equal to the predicted normal-incidence sputtering yield. Consistence has also been found as the present findings have been compared with other channel milling studies, which had used different ion beams and target materials. FIB milling has been shown to be an effective tool for making submicron channels in gold layers.
Selective and reversible inhibitors of ubiquitin-specific protease 7: a patent evaluation (WO2013030218) (2014)

The invention described in this review (WO2013030218) relates to compounds based on the quinazolin-4-one scaffold, their process of preparation and applications to inhibit the ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme (DUB), which is considered a potentially important new drug target for treating cancer and immunological disorders. Data are presented indicating that these small-molecule compounds are useful as selective and reversible inhibitors of USP7 in vitro and also in a cellular context, although the panel of other enzymes tested was limited. The synthesis strategy allows for the generation of a considerable variety of compounds, although similar properties of selective USP7 inhibition were reported for other related compound classes, thereby increasing the complexity of the patenting process. However, structural patterns that contribute to the selectivity of USP7 and other DUB enzyme inhibition are starting to emerge. Practical implications involve the treatment of cancer, neurodegenerative diseases, immunological disorders, diabetes, bone and joint diseases, cardiovascular diseases and viral and bacterial infections. The quality of these findings and a comparison to other compound classes with similar properties, as well as the potential for further development toward clinical exploitation are discussed.
Limitations and Late Complications of Third-Generation Automatic Cardioverter-Defibrillators (1995)

Despite the major diagnostic and therapeutic advantages of tiered-therapy ICDs, a significant proportion of patients continue to experience hardware-related complications or receive inappropriate shocks.
EcoTILLING for the identification of allelic variants of melon eIF4E, a factor that controls virus susceptibility (2007)

This study shows the applicability of EcoTILLING in Cucumis spp., but given the conservation of eIF4E, new candidate genes should probably be considered to identify new sources of resistance to plant viruses. Part of the methodology described here could alternatively be used in TILLING experiments that serve to generate new eIF4E alleles.
Peptide synthesis. Part 7. Solid-phase synthesis of conotoxin G1 (1985)

The neurotoxin conotoxin G1 from Conus geographus has been synthesised by a solid-phase method using fluorenylmethoxycarbonylamino acids and a polar, poly(dimethylacrylamide)-based support. The two disulphide bridges were formed selectively by differential protection of cysteine residues using S-acetamidomethyl and S-t-butylsulphenyl groups.
Alternative Pathway Activation of Complement by Shiga Toxin Promotes Exuberant C3a Formation That Triggers Microvascular Thrombosis (2011)

Shiga toxin (Stx)-producing E.coli O157:H7 has become a global threat to public health; it is a primary cause of diarrhea-associated hemolytic uremic syndrome (HUS), a disorder of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure with thrombi occluding renal microcirculation. In this study, we explored whether Stx triggers complement-dependent microvascular thrombosis in in vitro and in vivo experimental settings of HUS. Stx induced on human microvascular endothelial cell surface the expression of P-selectin, which bound and activated C3 via the alternative pathway, leading to thrombus formation under flow. In the search for mechanisms linking complement activation and thrombosis, we found that exuberant complement activation in response to Stx generated an increased amount of C3a that caused further endothelial P-selectin expression, thrombomodulin (TM) loss, and thrombus formation. In a murine model of HUS obtained by coinjection of Stx2 and LPS and characterized by thrombocytopenia and renal dysfunction, upregulation of glomerular endothelial P-selectin was associated with C3 and fibrin(ogen) deposits, platelet clumps, and reduced TM expression. Treatment with anti-P-selectin Ab limited glomerular C3 accumulation. Factor B-deficient mice after Stx2/LPS exhibited less thrombocytopenia and were protected against glomerular abnormalities and renal function impairment, indicating the involvement of complement activation via the alternative pathway in the glomerular thrombotic process in HUS mice. The functional role of C3a was documented by data showing that glomerular fibrin(ogen), platelet clumps, and TM loss were markedly decreased in HUS mice receiving C3aR antagonist. These results identify Stx-induced complement activation, via P-selectin, as a key mechanism of C3a-dependent microvascular thrombosis in diarrhea-associated HUS.
Marked Disparity Between Trabecular and Cortical Bone Loss with Age in Healthy Men (1984)

To define age-related changes in bone mineral content in normal men, we measured radial (proximal and distal) and vertebral bone mineral content in 62 men aged 30 to 92 years. Radial bone mineral content (largely cortical bone) was measured by single photon absorptiometry, and trabecular vertebral content (T12, L1 to L3) by computed tomography. Radial bone mineral content fell gradually (2% to 3.4% per decade) with age, but vertebral trabecular content fell more rapidly (12% per decade). Body size was not associated with the rate of bone loss from the distal radial and vertebral sites, but men with lower surface areas lost bone more rapidly at the predominantly cortical proximal radial site. The fact that radial cortical bone mineral content falls much less rapidly than vertebral trabecular content with age and is also associated with surface area indicates that trabecular and cortical bone compartments may be independently modulated. Age-related bone loss should not be considered a homogeneous process.
The Catalysis of Nuclear Reactions by mu Mesons (1956)

In the course of a recent experiment involving the stopping of negative K mesons in a 10-inch liquid hydrogen bubble chamber, an interesting new reaction was observed to take place. The chamber is traversed by many more negative {mu} mesons than K mesons, so that in the last 75,000 photographs, approximately 2500 {mu}{sup -} decays at rest have been observed. In the same pictures, several hundred {pi}{sup -} mesons have been observed to disappear at rest, presumably by one of the ''Panofsky reactions''. For tracks longer than 10 cm, it is possible to distinguish a stopping {mu} meson from a stopping {pi} meson by comparing its curved path (in a field of 11,000 gauss) with that of a calculated template. In addition to the normal {pi}{sup -} and {mu}{sup -} stoppings, we have observed 15 cases in which what appears (from curvature measurement) to be a {mu}{sup -} meson comes to rest in the hydrogen, and then gives rise to a secondary negative particle of 1.7 cm range, which in turn decays by emitting an electron. (A 4.1-Mev {mu} meson from {pi} - {mu} decay has a range of 1.0 cm.) The energy spectrum of the electrons from these 15 secondary particles looks remarkably like that of the {mu} meson. There are four electrons in the energy range 50 to 55 Mev, and none higher; the other electrons have energies varying from 50 Mev to 13 Mev. The most convincing proof that the primary particle actually comes to rest, and does not--for example--have a large resonant cross section for scattering at a residual range of 1.7 cm, is the following: In five of the 15 special events, there is a large gap between the last bubble of the primary track and the first bubble of the secondary track. This gap is a real effect, and not merely a statistical fluctuation in the spacing of the bubbles, since in some cases the tracks form a letter X, and in another case the secondary track is parallel to the primary, but displaced transversely by about 1 mm at the end of the primary. These real gaps appear also (although perhaps less frequently) between some otherwise normal-looking {mu}{sup -} endings and the subsequent decay electron; they are thought to be the distance traveled by the small neutral mesic atom.
Health Maintenance System (HMS) Hardware Research, Design, and Collaboration (2010)

The Space Life Sciences division (SLSD) concentrates on optimizing a crew member's health. Developments are translated into innovative engineering solutions, research growth, and community awareness. This internship incorporates all those areas by targeting various projects. The main project focuses on integrating clinical and biomedical engineering principles to design, develop, and test new medical kits scheduled for launch in the Spring of 2011. Additionally, items will be tagged with Radio Frequency Interference Devices (RFID) to keep track of the inventory. The tags will then be tested to optimize Radio Frequency feed and feed placement. Research growth will occur with ground based experiments designed to measure calcium encrusted deposits in the International Space Station (ISS). The tests will assess the urine calcium levels with Portable Clinical Blood Analyzer (PCBA) technology. If effective then a model for urine calcium will be developed and expanded to microgravity environments. To support collaboration amongst the subdivisions of SLSD the architecture of the Crew Healthcare Systems (CHeCS) SharePoint site has been redesigned for maximum efficiency. Community collaboration has also been established with the University of Southern California, Dept. of Aeronautical Engineering and the Food and Drug Administration (FDA). Hardware disbursements will transpire within these communities to support planetary surface exploration and to serve as an educational tool demonstrating how ground based medicine influenced the technological development of space hardware.
Intermittent hypoxia is a key regulator of cancer cell and endothelial cell interplay in tumours (2008)

Solid tumours are complex structures in which the interdependent relationship between tumour and endothelial cells modulates tumour development and metastasis dissemination. The tumour microenvironment plays an important role in this cell interplay, and changes in its features have a major impact on tumour growth as well as on anticancer therapy responsiveness. Different studies have shown irregular blood flow in tumours, which is responsible for hypoxia and reoxygenation phases, also called intermittent hypoxia. Intermittent hypoxia induces transient changes, the impact of which has been underestimated for a long time. Recent in vitro and in vivo studies have shown that intermittent hypoxia could positively modulate tumour development, inducing tumour growth, angiogenic processes, chemoresistance, and radioresistance. In this article, we review the effects of intermittent hypoxia on tumour and endothelial cells as well as its impacts on tumour development.
Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation (2002)

The plasma membrane of cells is composed of lateral heterogeneities, patches and microdomains. These membrane microdomains or lipid rafts are enriched in glycosphingolipids and cholesterol and have been implicated in cellular processes such as membrane sorting and signal transduction. In this study we investigated the importance of lipid raft formation in the innate immune recognition of bacteria using biochemical and fluorescence imaging techniques. We found that receptor molecules that are implicated in lipopolysaccharide (LPS)-cellular activation, such as CD14, heat shock protein (hsp) 70, 90, Chemokine receptor 4 (CXCR4), growth differentiation factor 5 (GDF5) and Toll-like receptor 4 (TLR4), are present in microdomains following LPS stimulation. Lipid raft integrity is essential for LPS-cellular activation, since raft-disrupting drugs, such as nystatin or MCD, inhibit LPS-induced TNF-alpha secretion. Our results suggest that the entire bacterial recognition system is based around the ligation of CD14 by bacterial components and the recruitment of multiple signalling molecules, such as hsp70, hsp90, CXCR4, GDF5 and TLR4, at the site of CD14-LPS ligation, within the lipid rafts.
Dual Growth Factor Delivery Using Biocompatible Core–Shell Microcapsules for Angiogenesis (2013)

An optimized electrodropping system produces homogeneous core-shell microcapsules (C-S MCs) by using poly(L-lactic-co-glycolic acid) (PLGA) and alginate. Fluorescence imaging clearly shows the C-S domain in the MC. For release control, the use of high-molecular-weight PLGA (HMW 270 000) restrains the initial burst release of protein compared to that of low-MW PLGA (LMW 40 000). Layer-by-layer (LBL) assembly of chitosan and alginate on MCs is also useful in controlling the release profile of biomolecules. LBL (7-layer) treatment is effective in suppressing the initial burst release of protein compared to no LBL (0-layer). The difference of cumulative albumin release between HMW (7-layer LBL) and LMW (0-layer LBL) PLGA is determined to be more than 40% on day 5. When dual angiogenic growth factors (GFs), such as platelet-derived GF (PDGF) and vascular endothelial GF (VEGF), are encapsulated separately in the core and shell domains, respectively, the VEGF release rate is much greater than that of PDGF, and the difference of the cumulative release percentage between the two GFs is about 30% on day 7 with LMW core PLGA and more than 45% with HMW core PLGA. As for the angiogenic potential of MC GFs with human umbilical vein endothelial cells (HUVECs), the fluorescence signal of CD31+ suggests that the angiogenic sprout of ECs is more active in MC-mediated GF delivery than conventional GF delivery, and this difference is significant, based on the number of capillary branches in the unit area. This study demonstrates that the fabrication of biocompatible C-S MCs is possible, and that the release control of biomolecules is adjustable. Furthermore, MC-mediated GFs remain in an active form and can upregulate the angiogenic activity of ECs.
In Vivo Rat Model of Preeclampsia (2006)

Preeclampsia is characterized by the clinical triad of new hypertension, proteinuria, and edema after 20 wk of gestation. Recent evidence suggests that disturbances in angiogenic factors (such as vascular endothelial growth factor and placental growth factor) signaling and endothelial health may play a major role in the pathogenesis of preeclampsia. Exogenous administration of soluble fms-like tyrosine kinase-1 (sFlt-1; a circulating anti-angiogenic protein) results in a preeclampsia-like phenotype in rats. This chapter describes the methods we use in our laboratory to create the sFlt-1 induced-rat model of preeclampsia.