gebhart/patrepeval huggingface dataset:
Crystal structures of hydrates of simple inorganic salts. III. Water-rich aluminium halide hydrates: AlCl3·15H2O, AlBr3·15H2O, AlI3·15H2O, AlI3·17H2O and AlBr3·9H2O (2014)

Water-rich aluminium halide hydrate structures are not known in the literature. The highest known water content per Al atom is nine for the perchlorate and fluoride. The nonahydrate of aluminium bromide, stable pentadecahydrates of aluminium chloride, bromide and iodide, and a metastable heptadecahydrate of the iodide have now been crystallized from low-temperature solutions. The structures of these hydrates were determined and are discussed in terms of the development of cation hydration spheres. The pentadecahydrate of the chloride and bromide are isostructural. In AlI(3) · 15H2O, half of the Al(3+) cations are surrounded by two complete hydration spheres, with six H2O in the primary and 12 in the secondary. For the heptadecahydrate of aluminium iodide, this hydration was found for every Al(3+).
An advancement in single cell genomics allows for T cell population analysis at high resolution (2019)

Abstract Progress in our understanding of immunology and cancer immunotherapies requires a comprehensive view of immune cell behavior and the interactions of these cells with their environment. Recent technological innovations have facilitated the combination of cell-surface protein, transcriptome, immune repertoire, and antigen specificity measurements from the same single cells, providing thorough and high-throughput lymphocyte characterization. Using the 10x Genomics Single Cell Immune Profiling Solution with Feature Barcoding technology along with oligo-conjugated antibodies and peptide-MHC (pMHC) Dextramers®, we performed multi-omic characterization of PBMCs from cytomegalovirus (CMV) seronegative and seropositive patients. Next generation sequencing libraries were made following the 10x Genomics workflows, where transcriptome and immune repertoire libraries are generated alongside libraries from DNA barcodes conjugated to antibodies or pMHC. Full length, paired TCRα/β sequences with specificity to known CMV antigens were identified in the seropositive donor, but not in the seronegative donor. Interestingly, a large Epstein Barr Virus (EBV) pMHC specific T cell expansion was identified in the CMV seronegative donor, suggesting an active EBV response. Moreover, the combination of transcriptomic and cell surface protein information resulted in an increase in resolution of cell type identification. This multi-omic workflow allowed the identification of enriched amino acid motifs within the TCR sequences that contained novel and known CDR3 amino acid sequences specific to CMV. These technological advancements provide new biological insights that are critical for progress in the field.
Modified Cyclodextrin Sulphates(mCDS11) have Potent Inhibitory Activity against HIV and High Oral Bioavailability (1994)

Modified cyclodextrin sulphate (mCDS) in which lipophilic groups were introduced to cyclodextrin sulphate (CDS) was synthesized and proved more inhibitory to the replication of HIV-1 and HIV-2 than CDS or dextran sulphate (DS). The anti-coagulant activity of mCDS was lower than that of DS. Cyclodextrin phosphate (CDP) showed anti-HIV activity similar to that of CDS, and its anti-coagulant activity was even lower than that of mCDS. Flow cytometric analysis suggested that the mechanism of the anti-HIV-1 action of CDS, mCDS, and CDP is based on inhibition of HIV-1 binding to the cells. The peak blood concentration after oral administration of mCDS11(potassium tris[6-benzylthio-6-deoxy]-β-cyclodextrin hexadecasulphate) to rabbits was about 1000 times higher than the concentration showing anti-HIV activity. The retention time in the blood was also long (blood half-life: 4 h). These results point to the potential usefulness of oral mCDS administration in the prophylaxis and/or therapy of HIV infections.
Effects of intracavernous administration of selective antagonists of alpha(1)-adrenoceptor subtypes on erection in anesthetized rats and dogs. (2000)

The proerectile properties of three novel alpha(1)-adrenoceptor (alpha(1)-ADR) antagonists with different profiles of selectivity for the alpha(1)-ADR subtypes have been evaluated in anesthetized rats and dogs on intracavernous (IC) injection, in comparison with prazosin and phentolamine. In rats, the tested compounds decreased blood pressure (BP) and increased IC pressure (ICP), as well as the ratio ICP/BP. Rec 15/2841 (alpha(1a)- plus alpha(1L)-ADR-selective antagonist) and Rec 15/2615 (alpha(1b)-ADR selective) were the most potent compounds. The ICP/BP ratios calculated after injection of Rec 15/3039 (alpha(1d)-ADR selective) were not markedly different from those observed after vehicle injection. Prazosin and phentolamine proved poorly active, their main effect being hypotension. Approximate ED(25) values (dose of compound in micrograms inducing 25% increase of ICP/BP ratio) were Rec 15/2615 (22 microgram/kg)>= Rec 15/2841 (29 microgram/kg) > prazosin (136 microgram/kg) > phentolamine (1298 microgram/kg) > Rec 15/3039 (9600 microgram/kg). Submaximal stimulation of the cavernous nerve elicited an ICP rise whose amplitude was not altered by Rec compounds. In contrast, prazosin and phentolamine decreased this ICP rise. All compounds but 15/3039 induced significant increase of the ICP/BP ratio in dogs. Rec 15/2615 proved to be the most interesting compound, inducing significant increases of ICP/BP at doses practically devoid of effects on BP. The rank order of potency in dog in increasing the ICP/BP ratio was similar to that observed in rats. Only at the highest doses tested, all compounds, except Rec 15/3039, decreased the ICP rise elicited by submaximal stimulation of the cavernous nerve. Our data demonstrate that the alpha(1b)- and alpha(1L)-ADR subtypes are functionally relevant for the erectile function in these models, and that alpha(1b)- and/or alpha(1L)-ADR subtypes selective antagonists could represent a real advantage in erectile dysfunction therapy.
Identification of Potential Broad‐Spectrum Peptidomimetic Antivirals Active Against Zika Virus (2018)

Zika virus (ZIKV) has recently been the cause of major epidemics in South American countries especially Brazil. ZIKV has been identified as the cause of microcephaly in the fetuses of pregnant women and the Guillain‐Barre Syndrome, and to date, no therapeutics or vaccines are available against ZIKV infection. Previously, we reported the anti‐ZIKV activity of Heat Shock Protein (HSP) 70‐Interacting Peptide (HIP), a cell‐permeable hairpin peptide derived from the domain I of nonstructural protein 5A of hepatitis C virus (HCV). These results implicate the HSP70 family members in the pathogenesis of ZIKV, identify the HSP70 family proteins as potential host therapeutic targets against ZIKV, and present the HIP as a potential therapeutic agent with significant anti‐ZIKV activity. In this study, we performed rigorous in silico analyses to identify potential peptidomimetic compounds that mimic the binding of the HIP to HSP70. Through particle swarm optimization via SwarmDock, binding solutions were generated from crystal structures of HSP70 nucleotide binding domain (NBD) and NS5A Domain I. The highest‐ranked residue interactions were mapped through visualization software, which identified a common binding region at a pocket at the C‐terminus. Subsequent modeling at this pocket was used to generate a HIP‐binding model, independently confirmed through docking of HIP to HSP70‐NBD in AutoDock Vina. Virtual high‐throughput screening of a diverse compound library against the binding pocket identified putative leads. We are currently assessing the antiviral activity of the lead compounds in our cell culture model of ZIKV infection. Subsequently, the best leads will be optimized to achieve greater antiviral activity. As HIP also blocks HCV, the targeting of HSP70 may represent a broad‐spectrum approach for future antivirals. Targeting ZIKV and other Flaviviruses through host proteins provides a therapeutic target that avoids selection of resistant viral particles. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Hydrogenation of Carbon Dioxide to Methanol by Using a Homogeneous Ruthenium–Phosphine Catalyst (2012)

Einfach effizient: Die homogene katalytische Hydrierung von CO2 zu Methanol gelingt mit einem Rutheniumphosphankomplex unter milden Reaktionsbedingungen (siehe Schema; HNTf2=Bis(trifluormethan)sulfonimid). Dies ist das erste Beispiel einer CO2-Hydrierung zu Methanol mit einem einzelnen, molekular definierten homogenen Katalysator. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 2628: Genome-wide sequencing identifies ATM as a pancreatic cancer susceptibility gene (2012)

Abstract Pancreatic ductal adenocarcinoma (PDA) affects over 44,000 people in the United States every year and carries a dismal prognosis, with a 5-year survival rate of just 5%. A subset of these patients (5-10%) report a familial history of the disease. The genetic etiology in these familial cases is poorly defined, with known susceptibility genes, such as: BRCA2, PALB2, CDKN2A, BRCA1, PRSS1 and STK11, accounting for only 10-15% of familial pancreatic cancer. In an effort to identify previously unappreciated pancreatic cancer susceptibility genes, we used next generation sequencing technology to evaluate the whole genome and whole exome sequences of 16 (6 families) and 22 individuals (10 families) respectively. All of these families enrolled into one of the familial pancreatic cancer registries participating in the Pancreatic Cancer Genetic Epidemiology (PacGene) Consortium, all had at least three members with PDA, and DNA was available from at least two affected members in each kindred. Using this approach, we identified heterozygous, inactivating, ATM mutations in two kindreds with familial pancreatic cancer (c.8266A&amp;gt;AT; p.K2756X and c.170G&amp;gt;GA; p.W57X). These mutations were previously reported as disease causing variants in patients with ataxia-telangiectasia, an autosomal recessive condition resulting from bi-allelic deleterious mutations of ATM. Interestingly, heterozygotes of deleterious ATM mutations have an increased risk of breast cancer. However, there have been no previous reports of deleterious ATM mutations in the germline of familial PDA patients. In our study, mutations segregated with disease in both kindreds and tumor analysis demonstrated Loss of heterozygosity (LOH) of the wild-type allele. Sequence analysis of the entire ATM gene in an additional 166 familial pancreatic cancer probands indentified four additional patients with deleterious mutations in the ATM gene (c.3214G&amp;gt;GT; p.E1072X, c.6095G&amp;gt;GA; p.R2032K, IVS41-1G&amp;gt;GT and c.3801delG), while no deleterious mutations were identified in 190 spouse controls (p=0.046). When considering only the mostly severely affected families, those with three or more pancreatic cancer cases, four deleterious mutations were found in 87 families (P=0.009). These results indicate that ATM mutations play an important role in familial pancreatic cancer predisposition and have significant implications in the management of affected individuals and the risk assessment of family members. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2628. doi:1538-7445.AM2012-2628
Ultralow percolation threshold of single walled carbon nanotube-epoxy composites synthesized via an ionic liquid dispersant/initiator (2014)

Uniform dispersion of single walled carbon nanotubes (SWNTs) in an epoxy was achieved by a streamlined mechano-chemical processing method. SWNT-epoxy composites were synthesized using a room temperature ionic liquid (IL) with an imidazolium cation and dicyanamide anion. The novel approach of using ionic liquid that behaves as a dispersant for SWNTs and initiator for epoxy polymerization greatly simplifies nanocomposite synthesis. The material was processed using simple and scalable three roll milling. The SWNT dispersion of the resultant composite was evaluated by electron microscopy and electrical conductivity measurements in conjunction with percolation theory. Processing conditions were optimized to achieve the lowest possible percolation threshold, 4.29 × 10−5 volume fraction SWNTs. This percolation threshold is among the best reported in literature yet it was obtained using a streamlined method that greatly simplifies processing.
Inducible Ig heavy chain switching in an IgM+ Ly-1 B cell line. Evidence for a state of switch commitment. (1988)

We have analyzed the pattern of immunoglobulin (Ig) heavy chain isotype secretion in AJ9, a cloned, IgM+ murine B lymphocyte cell line. Upon induction by a variety of lymphokines and polyclonal B-cell activators, AJ9 cells express multiple subclasses of IgG and IgA in addition to IgM. In certain cases, mature isotype is restricted--e.g., IL-5 predominantly elicits production of IgG2 and IgA, a restriction also observed in short-term lymphocyte cultures. In other cases (e.g., anti-IgM plus 8-mercaptoguanosine, a polyclonal B-cell activator) production of mature isotypes is unrestricted. Under optimal conditions, only a low abundance of secreted Ig and low frequency of secreting cells (less than 0.5%) were detected. A serial cloning assay was devised to define the pattern of isotype switching in induced cells and their progeny. We expected to observe a progressive limitation of progeny to expression of single mature isotypes. Surprisingly, nearly all subclones of the induced cells were found to produce a range of mature isotypes. Sequential cloning in basal medium revealed that this induced phenotype persisted for more than a month (greater than 40 generations). Throughout this period, the abundance of mature isotype production remained low, and membrane Ig was exclusively of the IgM isotype. We interpret this induced response to reflect an intermediate state of B-cell differentiation, in which cells become committed to the switching process, but are not adequately stimulated to efficiently complete the process required for expression of mature isotypes. These findings are discussed in regard to the control of the switching process, and their possible relevance to the memory state of B cells.
Addressing key challenges in transportation mode electrification (2016)

Vehicle electrification offers a tremendous potential for greenhouse gas (GHG) reductions in transportation in BC, which account for 24% of total provincial emissions. Battery and drivetrain developments have enabled personal electric vehicles (EVs) to start to penetrate the market, but there remain large opportunities in other parts of the transportation sector. The program of research described in this paper is directed toward exploring these additional opportunities. Bus fleets, and other commercial fleets, present unique challenges and opportunities compared to personal EVs and are being explored in concert with fleet operators. E-bikes enable personal mobility and may also afford health co-benefits that can offer overall financial benefits useful in shaping policy. Comparison between battery-electric and fuel-cell electrified drivetrains is also important to understand the overall round-trip and life-cycle relative efficiencies. These studies are all embedded in a number of modeling frameworks that enable studies of grid-interactions of the vehicles with the grid, in particular taking into account temporally and spatially varying GHG intensities, inter-jurisdictional trading, stochastic planning and operation, and demand response (DR) opportunities. The research is ongoing, so the current paper highlights expected impacts and contributions of the various lines of investigation.
Enhanced Robust Design Simulation and Application to Engine Cycle and Technology Design (2014)

Increases in computing power have enabled designers to efficiently use Monte Carlo simulation to perform robust design analyses of engine systems. Unfortunately, the designer is now faced with the problem of being able to generate more data than he is capable of analyzing or understanding in any tractable manner. Traditional filtered Monte Carlo methods involve creating surrogate model representations (such as Artificial Neural Networks) of a physics based model in order to rapidly generate tens of thousands of model responses as design and technology input parameters are randomly varied within user defined distributions. The downside to this approach is that the designer is often faced with a large design space with which he must perform a significant amount of post processing to arrive at probabilities of meeting design requirements. This research enhances the traditional filtered Monte Carlo robust design approach by regressing surrogate responses of joint confidence intervals for metric responses of interest. Fitting surrogate responses of probabilistic confidence intervals rather than the raw response data changes the problem the engineer is able to answer. Using the new approach the question can be better phrased in terms of the probability of meeting certain requirements. For example, one will be able to ask, “What engine overall pressure ratio is needed to achieve a 90% chance of reaching a 25% reduction in TSFC from the current state of the art?” The more traditional approach does not have the ability to include confidence in the process without significant post-processing. The process will be demonstrated using a two-spool axi-centrifugal turboshaft architecture modeled using the Numerical Propulsion System Simulation (NPSS) program. The new robust design process will be used to demonstrate the probabilistic impacts of both technology and design variables on choosing a cycle that is robust to both growth in mission requirements and changes in anticipated technology levels as the design matures. More specifically, the research will present engine cycle variables including component pressure ratios and temperatures that provide for high probability of meeting notional system level requirements, such as ESFC, under different levels of technology uncertainty. Technology uncertainty will be defined in terms of available material properties and component efficiency.
Abstract 1336: Novel immunotherapeutic activity of JAK and PI3Kδ inhibitors in a model of pancreatic cancer (2015)

Abstract Immunotherapeutic agents are emerging as key components of efficacious multi-agent regimens in cancer. The majority of immunotherapeutic agents developed thus far either attempt to stimulate a more productive anti-tumoral immune response or to inhibit key proteins in the immunosuppressive tumoral milieu. In contrast, agents targeting signal transduction molecules have been largely developed for their ability to impact the proliferative potential of tumor cells directly. Notably, the JAK/STAT and PI3Kδ signaling pathways have been shown to contribute not only to tumor cell proliferation and survival but also to play a crucial role in regulating stromal cells, including immune cells, which are recruited to the tumor microenvironment. Activation of these pathways has been shown to result in the recruitment and expansion of predominantly negative regulatory cells such as myeloid derived suppressor cells and regulatory T cells, suggesting that inhibition of JAK/STAT and PI3Kδ signaling may promote antitumor immunity. Therefore, we have examined the immunotherapeutic potential of selective inhibitors of either JAK or PI3Kδ. We demonstrate that inhibitors of either JAK or PI3Kδ block tumor growth as single agents in the immuno-competent syngeneic PAN02 pancreatic model, which is not driven by oncogenic JAK or PI3K signaling. Tumor growth inhibition is not observed in immunocompromised mice, demonstrating that the anti-tumor effects of these agents require an intact immune system. These agents were tested pairwise with each other and in combination with other immune checkpoint modulators, including an anti-PD-L1 antibody and the IDO1 inhibitor INCB24360. The combinations of JAK inhibition with IDO1 inhibition, PI3Kδ inhibition or PD-1/PD-L1 blockade resulted in enhanced efficacy. Mechanistic studies revealed that the combination of JAK and IDO1 inhibition did not alter the number of infiltrating T cells within the tumor, but instead resulted in a more activated phenotype of the infiltrating T cells, leading to higher levels of IFNγ production. In contrast, combination treatment with regimens that included an inhibitor to PI3Kδ led to a marked increase in the numbers of T cell infiltrates, although the cells were not maximally activated. Further studies to understand the complex cellular responses elicited by these inhibitors may provide the mechanistic rationale to explore JAK or PI3Kδ inhibitor-based immunotherapy combinations in the clinic. Citation Format: Holly K. Koblish, Michael Hansbury, Liang-Chuan S. Wang, Gengjie Yang, Taisheng Huang, Chu-Biao Xue, Yun-Long Li, Eddy Yue, Andrew Combs, Wenqing Yao, Reid Huber, Peggy Scherle. Novel immunotherapeutic activity of JAK and PI3Kδ inhibitors in a model of pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1336. doi:10.1158/1538-7445.AM2015-1336
Electron-paramagnetic-resonance measurements on the di-〈001〉-split interstitial center (R1) in diamond (1996)

Electron-paramagnetic-resonance (EPR) studies in electron-irradiated diamond enriched with 5% $^{13}\mathrm{C}$ have resulted in identification of the di-〈001〉-split interstitial center. It is the isotopic enrichment and the consequent observation of $^{13}\mathrm{C}$ hyperfine satellites that have permitted the structure to be determined more than 30 years after the discovery of the center. Analysis of the $^{13}\mathrm{C}$ hyperfine couplings by a simple molecular orbital calculation shows that the center may be viewed as a biradical consisting of two unpaired electrons, each primarily localized in a nonbonding 2p orbital, on different carbon atoms. The exchange interaction between these electrons results in a spin-triplet ground state which is well separated from the singlet excited state. The zero-field splitting observed in EPR is dipolar in origin and, taken together with the distribution of the unpaired electron population, indicates that the carbon atoms with the nonbonding 2p orbitals are separated by about 2.2 \AA{}. The center has ${\mathrm{\ensuremath{\sigma}}}_{\mathit{h}}$ symmetry. Formation of the di-〈001〉-split interstitial by room temperature irradiation confirms that the interstitial is mobile at this temperature. Identification of this center suggests a 〈001〉-split interstitial configuration for the carbon self-interstitial, a fundamental defect which has so far eluded direct detection. \textcopyright{} 1996 The American Physical Society.
A glimpse under the rim - the composition of microbial biofilm communities in domestic toilets (2009)

For the first time, a molecular fingerprinting and cloning approach was used to monitor the species composition in biofilm samples taken from domestic toilets. Knowledge about the microbial composition of biofilms in domestic toilets is a prerequisite for developing and evaluating strategies for their removal and prevention.