gebhart/patrepeval huggingface dataset:
Noble metal ionic catalysts: correlation of increase in CO oxidation activity with increasing effective charge on Pd ion in Pd ion substituted Ce1−xMxO2−δ(M = Ti, Zr and Hf) (2008)

Pd ion substituted Ce1-xMxO2-delta (M = Ti, Zr, Hf) have been prepared by a single step solution combustion method. Two atom% Pd ion substitution in the title compounds is confirmed by X-ray diffraction (XRD) and Pd ion charge state and redox properties have been determined by X-ray photoelectron spectroscopy (XPS) and H2/TPR studies. While Pd ion in CeO2 (Ce0.98Pd0.02O2-delta) showed higher catalytic activity for CO oxidation than Pd metal impregnated over CeO2, further increase in the catalytic activity is observed with Pd ion in Ce1-xTi(Hf)xO2 and a decrease in the activity with Pd ion in Ce1-xZrxO2. Effective charge on Pd ion could be varied by its substitution in these solid solutions Ce1-xMxO2 (M = Ti, Zr & Hf) and also in TiO2 compared to Pd ion in PdO. Effective positive charge on Pd ion is determined from the core level binding energy shift of Pd(3d5/2) peak with respect to Pd metal. Rate of CO oxidation increased and activation energy decreased with increase in effective charge on the Pd ion in the Pd ion substituted fluorites.
A randomized, double-blind study on efficacy and safety of sepranolone in premenstrual dysphoric disorder (2021)

Women with premenstrual dysphoric disorder (PMDD) experience mood symptoms related to the increase in progesterone and the neuroactive steroid allopregnanolone. Our hypothesis is that allopregnanolone is the symptom provoking factor. The rationale for the present study was to treat PMDD patients with the GABA<sub>A</sub> receptor modulating steroid antagonist, sepranolone (isoallopregnanolone). Patients (n = 206) with PMDD from 12 European centers were randomized in a parallel double-blind study and treated with placebo, sepranolone 10 mg and 16 mg. Patients administered sepranolone subcutaneously every 48 h during the 14 premenstrual days of three consecutive menstrual cycles. After obtaining informed consent, the PMDD diagnosis was confirmed according to DSM-5 and verified with two menstrual cycles of daily symptom ratings using the Daily Record of Severity of Problems (DRSP) scale in an eDiary. Inclusion and exclusion criteria stipulated that the women should be essentially healthy, not pregnant, have no ongoing psychiatric disorder or take interfering medications, and have regular menstrual cycles. The study's primary endpoint was the Total symptom score (Sum21, the score for all 21 symptom questions in the DRSP). In the prespecified statistical analysis the average score of the 5 worst premenstrual days in treatment cycles 2 and 3 were subtracted from the corresponding average score in the two diagnostic cycles. The treatment effects were tested using analysis of variance in a hierarchal order starting with the combined active sepranolone treatments vs. placebo. The prespecified analysis of Sum21 showed a large treatment effect of all three treatments but no statistically significant difference to placebo. However, the ratings of distress showed a significant treatment effect of sepranolone compared to placebo (p = 0.037) and the ratings of impairment showed a trend to greater treatment effect of sepranolone compared to placebo. Many women with PMDD had symptoms during a longer period than the late luteal phase. It has previously been shown that 9 premenstrual days may be more representative for comparison of PMDD symptom periods than the 5 worst premenstrual days. A post hoc analysis was undertaken in the per protocol population investigating the treatment effect during 9 premenstrual days in the third treatment cycle. The Sum21 results of this analysis showed that the sepranolone 10 mg was significantly better than placebo (p = 0.008). Similar significant treatment effects were found for the impairment and distress scores. A significantly larger number of individuals experienced no or minimal symptoms (Sum21 <42 points) with the 10 mg sepranolone treatment compared to placebo (p = 0.020). The results indicate that there is an attenuating effect by sepranolone on symptoms, impairment, and distress in women with PMDD especially by the 10 mg dosage. Sepranolone was well tolerated, and no safety concerns were identified.
Amino Acid Metabolic Origin as an Evolutionary Influence on Protein Sequence in Yeast (2009)

The metabolic cycle of Saccharomyces cerevisiae consists of alternating oxidative (respiration) and reductive (glycolysis) energy-yielding reactions. The intracellular concentrations of amino acid precursors generated by these reactions oscillate accordingly, attaining maximal concentration during the middle of their respective yeast metabolic cycle phases. Typically, the amino acids themselves are most abundant at the end of their precursor's phase. We show that this metabolic cycling has likely biased the amino acid composition of proteins across the S. cerevisiae genome. In particular, we observed that the metabolic source of amino acids is the single most important source of variation in the amino acid compositions of functionally related proteins and that this signal appears only in (facultative) organisms using both oxidative and reductive metabolism. Periodically expressed proteins are enriched for amino acids generated in the preceding phase of the metabolic cycle. Proteins expressed during the oxidative phase contain more glycolysis-derived amino acids, whereas proteins expressed during the reductive phase contain more respiration-derived amino acids. Rare amino acids (e.g., tryptophan) are greatly overrepresented or underrepresented, relative to the proteomic average, in periodically expressed proteins, whereas common amino acids vary by a few percent. Genome-wide, we infer that 20,000 to 60,000 residues have been modified by this previously unappreciated pressure. This trend is strongest in ancient proteins, suggesting that oscillating endogenous amino acid availability exerted genome-wide selective pressure on protein sequences across evolutionary time.
Water-Soluble Carbon Nanoparticles Improve Seed Germination and Post-Germination Growth of Lettuce under Salinity Stress (2020)

Seed germination is a critical developmental phase for seedling establishment and crop production. Increasing salinity stress associated with climatic change can pose a challenge for seed germination and stand establishment of many crops including lettuce. Here, we show that water soluble carbon nanoparticles (CNPs) can significantly promote seed germination without affecting seedling growth. Twenty-seven varieties of lettuce (Lactuca sativa) were screened for sensitivity to germination in 150 and 200 mM NaCl, and six salt-sensitive varieties (Little Gem, Parris Island, Breen, Butter Crunch, Muir, and Jericho) were selected and primed with 0.3% soluble carbon nanoparticles. Pretreatment with CNPs significantly improved seed germination under 150 mM NaCl and high temperature. CNP treatment slightly inhibited the elongation of primary roots but promoted lateral root growth and accumulation of chlorophyll content of seedlings grown under salt stress. Despite different lettuce varieties exhibiting a distinct response to nanoparticle treatments, results from this study indicate that soluble nanoparticles can significantly improve lettuce seed germination under salinity stress, which provide fundamental evidence on the potential of nanoparticles in agricultural application to improve crop yield and quality under stressful conditions.
Hydrodynamic considerations for spring-driven autoinjector design (2023)

In recent years, significant progress has been made in the studies of the spring-driven autoinjector, leading to an improved understanding of this device and its interactions with tissue and therapeutic proteins. The development of simulation tools that have been validated against experiments has also enhanced the prediction of the performance of spring-driven autoinjectors. This paper aims to address critical hydrodynamic considerations that impact the design of spring-driven autoinjectors, with a specific emphasis on sloshing and cavitation. Additionally, we present a framework that integrates simulation tools to predict the performance of spring-driven autoinjectors and optimize their design. This work is valuable to the pharmaceutic industry, as it provides crucial insights into the development of spring-driven autoinjectors and therapeutic proteins. This work can also enhance the efficacy and safety of the delivery of therapeutic proteins, ultimately improving patient outcomes.
D-106 Cellular immune correlates analysis of an HIV-1 pre- exposure prophylaxis trial (2016)

The majority of HIV exposures do not result in an established systemic infection. Preexposure Prophylaxis (PrEP) trials provide the right subjects with sufficient numbers to investigate mechanisms of resistance. We leveraged the global iPrEx PrEP trial to query T cell mediated mechanisms of resistance. We compared those who remained HIV-1 seronegative (HESN) to those who became infected during the trial with the variables of HIV-specific IFN-γ T cell responses, frequency and phenotypes of activated T cells and HLA MHC class I genotypes. HIV-specific IFN-γ responses were more frequent in HESN when compared to matched pre-infection samples from those who became infected. Logistic regression analyses suggested a reduced infection risk was associated with a Vif-specific response Hazard Ratio = 0.36, 95% CI: 0.19 to 0.66. In pilot analyses of T cell activation, the frequency of CD38+HLA-DR+ CD8+ T cells was greater in those who seroconverted relative to those that remained uninfected (1.30% vs. 0.82%, respectively, P = 0.005). HLA-B15 showed the strongest association with infection outcomes among all others. HLA-B15 allele frequency in HESN was 0.0392 in HESN and 0.1961 in those who became infected. HLA-B15 and was also associated with lower T cell response frequency. PrEP studies provide the naturalistic setting to assess the immune fingerprint of HIV resistance in HESN, providing the right control group, sufficient subject numbers and clinical outcomes to associate infection risk. We found Vif-specific T cell responses and lower T cell activation was associated with reduced infection risk while Protease responses, greater frequencies of activated T cells, and having the HLA-B15 Class I MHC allele was associated with increased HIV infection risk.
Interfering with the Dimerization of the ErbB Receptors by Transmembrane Domain-Derived Peptides Inhibits Tumorigenic Growth in Vitro and in Vivo (2016)

The ErbB family of tyrosine kinase receptors is a key element in preserving cell growth homeostasis. This family is comprised of four single-transmembrane domain proteins designated ErbB-1-4. Ligand binding initiates dimerization followed by tyrosine phosphorylation and signaling, which when uncontrolled lead to cancer. Accordingly, extensive research has been devoted to finding ErbB-intercepting agents, directed against ErbB-1 and ErbB-2, but so far, no inhibitor has targeted the transmembrane domain (TMD), which is instrumental for receptor dimerization and activation. Moreover, no antitumor agents targeted ErbB-3, which although it cannot generate signals in isolation, its heterodimerization with ErbB-2 leads to the most powerful and oncogenic signaling unit in the ErbB family. Here, to further elucidate the role of the interactions between the TMDs of the ErbB family in cancer, we investigated peptides derived from the TMDs of ErbB-1 and ErbB-2. We then focused on the C-terminal domains (B2C) and their analogue, named B2C-D, that contains both d- and l-amino acids. Both peptides incorporated the distal GXXXG dimerization motif to target the TMD of ErbB-3. Our results revealed that B2C-D is highly active both in vitro and in vivo. It significantly inhibits neuregulin- and EGF-induced ErbB activation, impedes the proliferation of a battery of human cancer cell lines, and retards tumor growth in vivo. Notably, combining low concentrations of B2C-D and gemcitabine chemotherapy completely arrested proliferation of pancreatic cancer cells. Biochemical and in vitro interaction studies suggest direct interference with the assembly of the wild-type ErbB-2-ErbB-3 heterodimer as the underlying mode of action. To the best of our knowledge, this is the first agent to target the TMDs of ErbB to delay tumor growth and signaling.
Probing Coordination Complexes by Carbon Nanotube-Assisted Low-Voltage Paper Spray Ionization Mass Spectrometry (2017)

Fragile transition metal complex ions such as [Cr(H<sub>2</sub>O)<sub>4</sub>Cl<sub>2</sub>]<sup>+</sup>, difficult to be observed by gas-phase spectroscopy, are detected easily with carbon nanotube (CNT)-assisted low-voltage ambient ionization mass spectrometry. Observation of various substituted ions with D<sub>2</sub>O and ROH (R = CH<sub>3</sub>, C<sub>2</sub>H<sub>5</sub>, ...) established the versatility of the technique in detecting diverse species. Ligand substitution occurring in solution was captured by the low-voltage technique. The extreme softness of the technique coupled with nanoscale ion sources enabled the creation of such species. Analysis was extended to other halides as well. The intensity of these fragile ions gradually disappeared at voltages beyond 500 V and are completely absent in standard high-voltage ionization. Detection of inorganic complexes further enhances the scope of low-voltage ionization.
CRISPR-Cas9 Mediated Exonic Disruption for HIV-1 Elimination (2021)

The work was supported by the University of Nebraska Foundation, including donations from the Carol Swarts, M.D. Emerging Neuroscience Research Laboratory, the Margaret R. Larson Professorship, and individual donor support from the Frances and Louie Blumkin Foundation and from Harriet Singer. The research received support from National Institutes of Health grants T32 NS105594, 5R01MH121402, 1R01Al158160, R01 DA054535, PO1 DA028555, R01 NS126089, R01 NS36126, PO1 MH64570, P30 MH062261, and 2R01 NS034239.
Quantum yield determination of photochemical reactions of photochromic compounds in solid films. (1985)

固体中におけるホトクロミック化合物の光反応量子収率を評価する新しい方法を提案し,実際の実験結果からこの方法の妥当性について検討した。この方法は,試料に照射した反応光の透過光量の時間変化を測定し,以下の解析式を用いて光反応量子収率を算出するものである。試料としては,耐久性に優れたホトクロミック化合物であるα,α,δ-トリメチル-δ-(2,5-ジメチル-3-フリル)フルギドをポリメタクリル酸メチルに分散させたフィルムを用いた。このフルギドの光消色反応について測定を行ない,その結果を上記の解析式を用いて解析した結果,光消色反応量子収率を正確に求めることができた。T℃における量子取率φは,30～80℃の温度範囲で以下のように表わすことができた。φ=4.8×10-4T+0.039
Di- and Polyalkali Metal Derivatives of Heterofunctionally Substituted Organic Molecules (1977)

Treatment of a wide variety of organic molecules with two or more molar equivalents of strongly basic alkali metal reagents affords di- or polyalkali metal derivatives which readily condense with electrophilic reagents to afford synthetically useful compounds. This review describes the preparation and subsequent chemistry of such multiple metal compounds derived from mono-, di-, and polyketones, ß-ketoesters, ylides, carboxylic acids, carboxamides, imides, sulfonamides, sulfones, sulfoxides, nitriles, oximes, hydrazones, azines, alcohols, thiols, ethers, amines, and certain sulfur-containing heterocyclic compounds. 1. Introduction 2. Diketones, Ketoaldehydes, and Related Compounds 2.1. Alkylation Reactions 2.2. Condensation Reactions with Aldehydes and Ketones 2.3. Aroylation and Acylation Reactions 2.4. Other Addition Reactions 3. ß-Ketoesters 4. Metalation of Ylides 5. Carboxylic Acids 6. Carboxamides 7. Imides 8. Sulfonamides 9. Sulfones and Sulfoxides 10. Nitriles 11. Oximes, Hydrazones, and Azines 12. Alcohols, Thiols, Ethers, and Sulfides 13. Amines 14. Miscellaneous Heterocyclic Compounds 15. Addenda
Stuttered and fluent speech production: An ALE meta‐analysis of functional neuroimaging studies (2005)

This study reports an activation likelihood estimation (ALE) meta-analysis of imaging studies of chronic developmental stuttering in adults. Two parallel meta-analyses were carried out: (1) stuttered production in the stutterers; (2) fluent production in the control subjects. The control subjects' data replicated previous analyses of single-word reading, identifying activation in primary motor cortex, premotor cortex, supplementary motor area, Rolandic operculum, lateral cerebellum, and auditory areas, among others. The stuttering subjects' analysis showed that similar brain areas are involved in stuttered speech as in fluent speech, but with some important differences. Motor areas were over-activated in stuttering, including primary motor cortex, supplementary motor area, cingulate motor area, and cerebellar vermis. Frontal operculum, Rolandic operculum, and anterior insula showed anomalous right-laterality in stutterers. Auditory activations, due to hearing one's own speech, were essentially undetectable in stutterers. The phenomenon of efference copy is proposed as a unifying account of the pattern activation revealed within this ALE meta-analysis. This provides the basis for a stuttering system model that is testable and should help to advance the understanding and treatment of this disorder.
Genetics and Biology of Alcoholism, Banbury Report No. 33. Edited by C. Robert Cloninger and Henry Begleiter. Cold Spring Harbor Laboratory Press, New York. 1990. (1991)

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Rapid determination of plasmid‐carrying yeast cells by using an imaging sensor system (1991)

A novel imaging sensor system for the determination of plasmid carrying yeast cells was developed. The sensor system consisted of an Silicon Intensifier Target (SIT) video camera, a fluorescent microscope, and a personal computer system equipped with an image memory board. This system was based on the fact that the membrane integrity of only plasmid-carrying cells is lost following cell growth in 5-fluoro-orotic acid (5-FOA) containing medium, and consequently these target cell can be stained with fluorescent probes and detected. In this study, plasmid-carrying cells were detected and their fraction determined in a mixture of both plasmid-carring and plasmid-free cells. A good correlation was observed between the values determined by this sensor system and the conventional method in the 30%-80% range, and one assay was possible within 4 h. This sensor system could be used for the monitoring of plasmid-carrying fraction in recombinant yeast cells during cultivation.
Intracellular distribution of bis-allylic deuterated linoleic acid into the lipidome of human keratinocytes (2023)

Polyunsaturated fatty acids (PUFA) are particularly susceptible to free radical-induced lipid peroxidation (LPO). Specific deuteration at bis-allylic positions of PUFA (D-PUFA) has been recently proposed as a way to inhibit the LPO. Here, a high mass resolution untargeted lipidomic analysis protocol was applied to examine the changes in the lipidome of keratinocytes supplemented with bis-allylic deuterated linoleic acid (D2-LA). Incorporation of D2-LA occurs preferentially in membrane phospholipids such as phosphatidylcholine and phosphatidylethanolamine, followed by triglycerides. However, the relative contribution of D2-LA among membrane lipids is highest in cardiolipin (60%) followed by its precursor phosphatidylglycerol (50%). Cardiolipins are enriched in PUFA and exclusively located in mitochondrial membranes, thus representing major targets for lipid peroxidation. These findings indicate that D2-LA supplementation is linked to the preservation of mitochondrial function under oxidative stress. Finally, our study highlights the suitability of high mass resolution lipidomic analysis to investigate lipid metabolism at the level of individual molecular species in stable isotope tracing experiments.
Impairment Mitigation in Optical Communication Systems using Digital Signal Processing (2015)

We examine impairments in optical communications systems (components, subsystems, fiber transmission and optical networking) and show how digital signal processing techniques can alleviate these impairments and provide system margins. Article not available.
Conopeptide ρ-TIA Defines a New Allosteric Site on the Extracellular Surface of the α1B-Adrenoceptor (2012)

The G protein-coupled receptor (GPCR) superfamily is an important drug target that includes over 1000 membrane receptors that functionally couple extracellular stimuli to intracellular effectors. Despite the potential of extracellular surface (ECS) residues in GPCRs to interact with subtype-specific allosteric modulators, few ECS pharmacophores for class A receptors have been identified. Using the turkey β(1)-adrenergic receptor crystal structure, we modeled the α(1B)-adrenoceptor (α(1B)-AR) to help identify the allosteric site for ρ-conopeptide TIA, an inverse agonist at this receptor. Combining mutational radioligand binding and inositol 1-phosphate signaling studies, together with molecular docking simulations using a refined NMR structure of ρ-TIA, we identified 14 residues on the ECS of the α(1B)-AR that influenced ρ-TIA binding. Double mutant cycle analysis and docking confirmed that ρ-TIA binding was dominated by a salt bridge and cation-π between Arg-4-ρ-TIA and Asp-327 and Phe-330, respectively, and a T-stacking-π interaction between Trp-3-ρ-TIA and Phe-330. Water-bridging hydrogen bonds between Asn-2-ρ-TIA and Val-197, Trp-3-ρ-TIA and Ser-318, and the positively charged N terminus and Glu-186, were also identified. These interactions reveal that peptide binding to the ECS on transmembrane helix 6 (TMH6) and TMH7 at the base of extracellular loop 3 (ECL3) is sufficient to allosterically inhibit agonist signaling at a GPCR. The ligand-accessible ECS residues identified provide the first view of an allosteric inhibitor pharmacophore for α(1)-adrenoceptors and mechanistic insight and a new set of structural constraints for the design of allosteric antagonists at related GPCRs.
Mechanical force induces mitochondrial fission (2017)

Eukaryotic cells are densely packed with macromolecular complexes and intertwining organelles, continually transported and reshaped. Intriguingly, organelles avoid clashing and entangling with each other in such limited space. Mitochondria form extensive networks constantly remodeled by fission and fusion. Here, we show that mitochondrial fission is triggered by mechanical forces. Mechano-stimulation of mitochondria - via encounter with motile intracellular pathogens, via external pressure applied by an atomic force microscope, or via cell migration across uneven microsurfaces - results in the recruitment of the mitochondrial fission machinery, and subsequent division. We propose that MFF, owing to affinity for narrow mitochondria, acts as a membrane-bound force sensor to recruit the fission machinery to mechanically strained sites. Thus, mitochondria adapt to the environment by sensing and responding to biomechanical cues. Our findings that mechanical triggers can be coupled to biochemical responses in membrane dynamics may explain how organelles orderly cohabit in the crowded cytoplasm.
Structure and metrology for an analog testability bus (2002)

This paper gives a proposal for an analog testability bus that could be used as the basis for a standard such as IEEE P1149.4. The proposed testability structure is imposed on the I/O pin cells of the analog and mixed technology ICs. It is a superset of the existing IEEE/ANSI 1149.1 testability standard for digital ICs and is intended to cooperate with it. This allows for the testing of interconnect failures such as shorts and opens, the testing of discrete analog components and networks between ICs, and supports the testing of analog functions within the ICs themselves. This paper is a companion to the result of a cooperative effort between AT&T, Ford Motor, Hewlett-Packard, Motorola and the University of Colorado at Colorado Springs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>