gebhart/patrepeval huggingface dataset:
Association of Vibrio cholerae mutants with the intestinal mucosa of infant mice. (1981)

Scanning electron microscopy (SEM) was used to observe the nature of association of mutant strains of Vibrio cholerae to infant mouse intestinal segments. Parental strain Inaba CA 401 was compared to the following mutant phenotypes: nonchemotactic, nonchemotactic reduced motility, flagellated nonmotile, nonflagellated nonmotile, and mucin nonutilizing. The virulence of the different strains was determined by oral-intra-gastric inoculation of seven-day-old mice. Localization of the parental strain during the course of infection in the patent gut of infant mice was followed by the fluorescent antibody (FA) technique. The highly virulent parental strain rapidly penetrated intervillus spaces in the upper and lower regions of the small intestine. By SEM the organism also associated markedly with the mucosal surface of intestinal segments. However, the vibrios were associated predominately with the intestinal mucin rather than the epithelial cell surfaces of villi. Nonchemotactic vibrios retained full virulence and ability to associate with the mucosa. The nonchemotactic strain with a reduced rate of motility was partially deficient in these properties. Nonmotile vibrios of either type were markedly reduced in both properties. The mucin nonutilizing strain associated normally but was weakly virulent. Low virulence of this strain may be due to a reduced ability of the organisms to multiply in the mucin.
Bismuth- and lithium-loaded plastic scintillators for gamma and neutron detection(Conference Presentation) (2016)

Plastic scintillators are widely deployed for ionizing radiation detection, as they can be fabricated in large sizes, for high detection efficiency. However commercial plastics are limited in use for gamma spectroscopy, since their photopeak is too weak, due to low Z, and they are also limited in use for neutron detection, since proton recoils are indistinguishable from other ionizing radiation absorption events in standard plastics. We are working on scale up and production of transparent plastic scintillators based on polystyrene (PS) with high loading of bismuth metallorganics for gamma spectroscopy, and with lithium metallorganics for neutron detection. When activated with standard organic fluors, PS scintillators containing 8 wt% bismuth provide energy resolution of 11% at 662 keV. A PS plastic formulation including 1.3 wt% lithium-6 provides a neutron capture peak at 525 keVee, with 11% resolution for the capture peak and 90% efficiency for thermal neutron capture in 2mm thickness. Acknowledgements This work was performed under the auspices of the U.S. DOE by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344, and has been supported by the US DOE National Nuclear Security Administration, Defense Nuclear Nonproliferation Research and Development under Contract No. DE-AC03-76SF00098
Thermal management of power electronics using thermoelectric coolers (2002)

Many high power electronic devices, such as power amplifies and multiprocessors, operate at high temperatures close to or at the edge of their reliability, which could severely impact performance and operating lifetime. These devices thus need cooling to improve performance and reliability. Conventional thermal management techniques, most of which are discussed, are not well suited to the specific problem of cooling discrete or localized heat dissipating devices since they generally cool the whole board. Moreover, these techniques have difficulty dealing with the large heat fluxes associated with the high density packaging of power devices. The specific problem of spot cooling of power devices can be very effectively solved by using the combination of diamond substrates and a thermoelectric cooler. The highest power components would be mounted directly on a diamond substrate (ideally the top substrate of the cooler) allowing the cooler/diamond combination to maintain the temperature of the device from a few degrees to tens of degrees below that of the substrate on which the cooler is mounted (diamond or any other high thermal conductivity material). This will allow the device to operate at a low enough temperature to increase both reliability and clockspeed. It has been determined that the highest cooling power densities will be achieved with thin film coolers with cooler leg lengths on the order of 20 to 50 microns. The results of a solid state power amplifier (MMIC) cooled using a diamond/cooler combination are presented and discussed.
Studies on lipid biosynthesis and cholesterol content of liver and serum lipoproteins in rats fed various phthalate esters (1978)

Abstract The effect of various phthalate ester plasticizers on lipid metabolism in rats was studied in vivo and in vitro. Di‐2‐ethylhexyl phthalate (DEHP) and di‐n‐butyl phthalate (DBP) inhibited (30–70%) hepatic sterologenesis from 14 C‐acetate and 14 C‐mevalonate in liver minces from rats fed the phthalates at a level of 2.5 mmoles/100 g of chow diet for 21 days; inhibition of 14 C‐acetate incorporation into phospholipids, triglycerides, and steryl esters was reduced (35–70%) by DEHP and DBP feeding. In addition, serum cholesterol was lowered ca. 14 mg/dl with dietary DEHP or DBP but not with dimethyl phthalate (DMP). Hepatic total cholesterol levels were reduced significantly (31%, P&lt;0.001) by DMP but not by DBP or DEHP. In other studies with DEHP fed at the 0.5% level in chow diets (1.3 mmoles/100 g), the incorporation (esterification) of 3 H‐oleate into di‐ and triglycerides was reduced ca. 40%. Furthermore, the addition of DEHP (2%, 5 mmoles/100 g) to a semisynthetic diet containing 10% fat (hydrogenated coconut oil) resulted in changes in serum lipoprotein composition. The percentage of serum cholesterol in LDL rose from 22% to 34% while that in HDL fell from 78% to 66%; these changes occurred without net changes in serum cholesterol levels. Possible mechanisms for the inhibitory effect of phthalates on hepatic lipid biosynthesis are discussed.
Supplementary Tables S1-S6 from Predictive Biomarkers for Adjuvant Capecitabine Benefit in Early-Stage Triple-Negative Breast Cancer in the FinXX Clinical Trial (2023)

&lt;p&gt;Supplementary Table S1 includes biological description of the 30 custom genes, Supplementary Tables S2-S3 show patient characteristics, Supplementary Table S4 shows biological classification of the study cohort, Supplementary Tables S5-6 show survival analysis and interaction tests for selected genes and metagenes&lt;/p&gt;
Relationship between the Antigenic Topography and the Structure of Human Growth Hormone* (1990)

Monoclonal antibodies (MAb) to human GH (hGH) were used to correlate the antigenic topography of the hormone with its structure. Competition experiments performed in a solid phase RIA system allowed us to measure the reactivity toward the MAb of the following hGH derivatives: hGH 20K (a natural variant lacking residues 32-46), hGH selectively modified in His or Met residues, hGH with the C and/or N-terminal disulfide bond reduced and carbamidomethylated, and hGH cleaved between residues 142-143. Results indicated that fragment 32-46 participates in the structure of epitopes EB1/EB3 and that the C-terminal bridge is located in epitope 10D6, whereas opening of both disulfide bridges alters the entire hGH antigenic surface. His-151 and Met-170 were placed in epitopes NA71 and AC8, respectively, whereas His-18 and Met-14 would be involved in the hGH antigenic domain formed by overlapping epitopes 3C11, 10C1, and HG3. MAb AE5, AE12, and AC3 define a flexible hGH region related to sequence 134-150; the respective epitopes show high conformational mobility induced by modifications in other regions of the molecule. Binding of the different hGH derivatives to lactogenic receptors from female rat liver gave some insights on the localization of the hormone-binding site. Epitopes EB1/EB3 and 10D6 were discarded because there was not a direct correlation between their drastic immunological alterations and the binding properties of the respective hGH derivatives. In the same way, epitopes AE5, AE12, and AC3 were excluded from the hGH-binding domain because a disruption in those sites did not affect the hGH interaction with receptors. We conclude that the hGH structure defined by epitopes 3C11, 10C1, and HG3 is probably related to the binding properties of the hormone.
Predicting Odor Pleasantness from Odorant Structure: Pleasantness as a Reflection of the Physical World (2007)

Although it is agreed that physicochemical features of molecules determine their perceived odor, the rules governing this relationship remain unknown. A significant obstacle to such understanding is the high dimensionality of features describing both percepts and molecules. We applied a statistical method to reduce dimensionality in both odor percepts and physicochemical descriptors for a large set of molecules. We found that the primary axis of perception was odor pleasantness, and critically, that the primary axis of physicochemical properties reflected the primary axis of olfactory perception. This allowed us to predict the pleasantness of novel molecules by their physicochemical properties alone. Olfactory perception is strongly shaped by experience and learning. However, our findings suggest that olfactory pleasantness is also partially innate, corresponding to a natural axis of maximal discriminability among biologically relevant molecules.
Specific mutations in the estrogen receptor change the properties of antiestrogens to full agonists. (1995)

The estrogen receptor (ER) stimulates transcription of target genes by means of its two transcriptional activation domains, AF-1 in the N-terminal part of the receptor and AF-2 in its ligand-binding domain. AF-2 activity is dependent upon a putative amphipathic alpha-helix between residues 538 and 552 in the mouse ER. Point mutagenesis of conserved hydrophobic residues within this region reduces estrogen-dependent transcriptional activation without affecting hormone and DNA binding significantly. Here we show that these mutations dramatically alter the pharmacology of estrogen antagonists. Both tamoxifen and ICI 164,384 behave as strong agonists in HeLa cells expressing the ER mutants. In contrast to the wild-type ER, the mutant receptors maintain nuclear localization and DNA-binding activity after ICI 164,384 treatment. Structural alterations in AF-2 caused by gene mutations such as those described herein or by estrogen-independent signaling pathways may account for the insensitivity of some breast cancers to tamoxifen treatment.
Statistical fusion of surface labels provided by multiple raters (2010)

Studies of the size and morphology of anatomical structures rely on accurate and reproducible delineation of the structures, obtained either by human raters or automatic segmentation algorithms. Measures of reproducibility and variability are vital aspects of such studies and are usually acquired using repeated scans and repeated delineations (in the case of human raters). Methods exist for simultaneously estimating the true structure and rater performance parameters from multiple segmentations and have been demonstrated on volumetric images. In this work, we extend the application of previous methods onto two-dimensional surfaces parameterized as triangle meshes. Label homogeneity is enforced using a Markov random field formulated with an energy that addresses the challenges introduced by the surface parameterization. The method was explored using both simulated raters and surface labels obtained from an atlas registration. Simulated raters are computed using a global error as well as a novel and more realistic boundary error model. We study the impact of raters and their accuracy based on both models, and show how effectively this method estimates the true segmentation on simulated and real surfaces.
Very large area 20cm × 20cm flat panel phototubes using ALD microchannel plates (2015)

Novel borosilicate microcapillary array MCPs have been employed build large area (20 cm × 20 cm) flat panel phototube detectors. Design of the 20 cm sealed tube assembly comprises of a borosilicate entrance window, a proximity focused bialkali photocathode, a pair of MCPs, and a strip-line readout anode. Micro-capillary arrays have been processed to function as microchannel plates (MCPs) using atomic layer deposition (ALD) to produce the conductive and secondary emissive layers. Using borosilicate micro-capillary substrates has advantages over traditional MCPs, including the ability to be produced in large robust formats (20cm), low intrinsic background (<;0.06 events cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> sec <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> ), high open area ratios (up to 85%), and stable gain during >7 C cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> charge extraction after preconditioning (vacuum bake and burn-in). The gain, pulse height distribution, imaging performance are equivalent, or better than conventional MCPs. The flat panel design employs a brazed ceramic walled enclosure with a hot indium seal and a transfer photocathode. We have achieved >20% quantum efficiency and good gain uniformity over the 20cm field of view, spatial resolution of <;1 cm and obtained event timing accuracy of close to 100ps FWHM.
MEMBRANE LIPID OXIDATION IN A MUCROSOMAL FRACTION OF RED HAKE MUSCLE (1980)

A microsomal fraction which catalyzes the oxidation of the membrane lipid in the presence of NADH and Fe has been isolated from the muscle of red hake. Unlike other microsomal membrane systems previously reported which prefer, and in some cases require, NADPH, very little lipid oxidation is observed with NADPH in the fish muscle system. The enzymic nature of the reaction is indicated by the preference of NADH versus NADPH, the inhibitory effect of high concentrations of NADH, and the loss of the activity of the system upon heating. The effect of temperature on production of TBA-reactive substances and the loss of NADH from the reaction medium was followed. There is a sharp decline in production of TBA-reactive substances between 6°C and 0°C. Phosphate buffer was shown to inhibit the oxidation compared to histidine buffer at low concentrations of ADP. High concentrations of ADP were inhibitory to the lipid peroxidation system when histidine was used as buffer.
Author response: Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment (2017)

Mutations in several components of a bacterial ribosome are shown to broadly decrease antibiotic and stress sensitivity, and readily accessible reversion mutations allow these ribosomal mutations to serve as stepping stones to high level antibiotic resistance.
Identification of Botanical Viral Entry Inhibitors for SARS‐CoV‐2 (2022)

The examination of biodiversity across the world has historically been a critical part of drug development and led to the discovery of common medications for many medical issues including pain management, cancer, heart disease, and infections. During the SARS‐CoV‐2 pandemic, the use of natural supplements in the United States has increased. The efficacy of these natural products to prevent SARS‐CoV‐2 infection and the safety of their use remains unexplored; therefore, more research must be done to determine which supplements have antiviral properties. The Quave Natural Product Library (QNPL) is a collection of over 2,000 botanical and fungal extracts and includes the 40 most used natural supplements in the United States. Collection of the biological samples for the library requires field expeditions to areas throughout the world with high levels of biodiversity. Each of these extracts were tested in a SARS‐CoV‐2 pseudotyped virus system to determine which extracts inhibit viral entry, specifically the virus spike protein binding to host cells ACE2 receptors. Mammalian cell cytotoxicity assays were run in parallel. Evaluation of 1,887 extracts and 18 single compounds from the QNPL against SARS‐CoV‐2 identified. 317 extracts derived from 134 species across 76 families (1 lichen, 2 fungi, 73 plant families) exhibited ≥50% inhibition activity in the wild type spike pseudotyped model at 20 µg/mL. Of these bioactive extracts, 129 extracts derived from 95 plant species exhibited ≥85% inhibition activity and ≤15% cytotoxicity in the wild‐type model. Once these 129 extracts were identified, an interesting pattern emerged indicating many hits were from species that are known to be cardiotoxic due to rich composition of cardiac glycosides. For further selection and testing, we reviewed each extract and consulted the literature to eliminate extracts with those properties or similar compounds, which narrowed down our interest to 8 extracts. These extracts were further validated in a concentration‐response assay in a pseudotyped virus model. The EC 50 values of the top 3 extracts were all under 10 µg/mL. These 3 extracts all exhibited activity (≥85% inhibition activity) in the wildtype and variant pseudotyped models. Testing in live SARS‐CoV‐2 confirmed antiviral activity from 2 of 3 extracts, Plant A flowers and Plant B roots. Further chemical characterization of the major metabolites of these two hits was performed using MS/MS fragmentation data compared with the literature, in silico prediction, and web‐based databases. The results revealed phenylpropanoids, flavonoids, triterpenes, glycosidic terpenes, and fatty acids as the major chemical classes. The next steps of this study seek to identify and isolate purified bioactive compounds to further understand their role in SARS‐CoV‐2 inhibition.
Anti-viral agents: potential utility in exacerbations of asthma (2013)

Asthma is the most common chronic respiratory disease and its prevalence is on the increase. Respiratory viral infections in early life have been suggested to increase the risk of development of asthma in later life and virus infection remains the single greatest precipitant of asthma exacerbations. The development of effective anti-viral treatments remains a key target for therapeutic intervention. Here we discuss the role of respiratory viral infection in asthma exacerbation and highlight current and potential anti-viral agents and their mechanisms of action.
The Missing Beginning of ‚The Dialogue of a Man and His Ba‘: P. Amherst III and the History of the ‚Berlin Library‘ (2003)

Article The Missing Beginning of ‚The Dialogue of a Man and His Ba‘: P. Amherst III and the History of the ‚Berlin Library‘ was published on January 1, 2003 in the journal Zeitschrift für Ägyptische Sprache und Altertumskunde (volume 130, issue 1).
A low-cost wear-leveling algorithm for block-mapping solid-state disks (2012)

Multilevel flash memory cells double or even triple storage density, producing affordable solid-state disks for end users. However, flash lifetime is becoming a critical issue in the popularity of solid-state disks. Wear-leveling methods can prevent flash-storage devices from prematurely retiring any portions of flash memory. The two practical challenges of wear-leveling design are implementation cost and tuning complexity. This study proposes a new wear-leveling design that features both simplicity and adaptiveness. This design requires no new data structures, but utilizes the intelligence available in sector-translating algorithms. Using an on-line tuning method, this design adaptively tunes itself to reach good balance between wear evenness and overhead. A series of trace-driven simulations show that the proposed design outperforms a competitive existing design in terms of wear evenness and overhead reduction. This study also presents a prototype that proves the feasibility of this wear-leveling design in real solid-state disks.
The cysteine residue of glial fibrillary acidic protein is a critical target for lipoxidation and required for efficient network organization (2018)

The type III intermediate filament protein glial fibrillary acidic protein (GFAP) contributes to the homeostasis of astrocytes, where it co-polymerizes with vimentin. Conversely, alterations in GFAP assembly or degradation cause intracellular aggregates linked to astrocyte dysfunction and neurological disease. Moreover, injury and inflammation elicit extensive GFAP organization and expression changes, which underline reactive gliosis. Here we have studied GFAP as a target for modification by electrophilic inflammatory mediators. We show that the GFAP cysteine, C294, is targeted by lipoxidation by cyclopentenone prostaglandins (cyPG) in vitro and in cells. Electrophilic modification of GFAP in cells leads to a striking filament rearrangement, with retraction from the cell periphery and juxtanuclear condensation in thick bundles. Importantly, the C294S mutant is resistant to cyPG addition and filament disruption, thus highlighting the critical role of this residue as a sensor of oxidative damage. However, GFAP C294S shows defective or delayed network formation in GFAP-deficient cells, including SW13/cl.2 cells and GFAP- and vimentin-deficient primary astrocytes. Moreover, GFAP C294S does not effectively integrate with and even disrupts vimentin filaments in the short-term. Interestingly, short-spacer bifunctional cysteine crosslinking produces GFAP-vimentin heterodimers, suggesting that a certain proportion of cysteine residues from both proteins are spatially close. Collectively, these results support that the conserved cysteine residue in type III intermediate filament proteins serves as an electrophilic stress sensor and structural element. Therefore, oxidative modifications of this cysteine could contribute to GFAP disruption or aggregation in pathological situations associated with oxidative or electrophilic stress.
Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle. (1998)

In this study we analyzed the expression of aquaporin-4 (AQP4) in mammalian skeletal muscle. Immunohistochemical experiments revealed that affinity-purified AQP4 antibodies stained selectively the sarcolemma of fast-twitch fibers. By immunogold electron microscopy, little or no intracellular labeling was detected. Western blot analysis showed the presence of two immunopositive bands with apparent molecular masses of 30 and 32 kD specifically present in membrane fraction of a fast-twitch rat skeletal muscle (extensor digitorum longus, EDL) and not revealed in a slow-twitch muscle (soleus). PCR Southern blot experiments resulted in a selective amplification in EDL of a 960-bp cDNA fragment encoding for the full-length rat form of AQP4. Functional experiments carried out on isolated skeletal muscle bundle fibers demonstrated that the osmotic response is faster in EDL than in soleus fibers isolated from the same rat. These results provide for the first time evidence for the expression of an aquaporin in skeletal muscle correlated to a specific fiber-type metabolism. Furthermore, we have analyzed AQP4 expression in skeletal muscle of mdx mice in which a decreased density of orthogonal arrays of particles, a typical morphological feature of AQP4, has been reported. Immunofluorescence experiments showed a marked reduction of AQP4 expression suggesting a critical role in the membrane alteration of Duchenne muscular dystrophy.
Large-scale RNAi screen of G protein-coupled receptors involved in larval growth, molting and metamorphosis in the red flour beetle (2011)

The results from our study revealed the physiological roles of some GPCRs in T. castaneum. These findings could help in development of novel pesticides targeting these GPCRs.