gebhart/patrepeval huggingface dataset:
Binding Interactions with the Complementary Subunit of Nicotinic Receptors (2013)

The agonist-binding site of nicotinic acetylcholine receptors (nAChRs) spans an interface between two subunits of the pentameric receptor. The principal component of this binding site is contributed by an α subunit, and it binds the cationic moiety of the nicotinic pharmacophore. The other part of the pharmacophore, a hydrogen bond acceptor, has recently been shown to bind to the complementary non-α subunit via the backbone NH of a conserved Leu. This interaction was predicted by studies of ACh-binding proteins and confirmed by functional studies of the neuronal (CNS) nAChR, α4β2. The ACh-binding protein structures further suggested that the hydrogen bond to the backbone NH is mediated by a water molecule and that a second hydrogen bonding interaction occurs between the water molecule and the backbone CO of a conserved Asn, also on the non-α subunit. Here, we provide new insights into the nature of the interactions between the hydrogen bond acceptor of nicotinic agonists and the complementary subunit backbone. We studied both the nAChR of the neuromuscular junction (muscle-type) and a neuronal subtype, (α4)2(β4)3. In the muscle-type receptor, both ACh and nicotine showed a strong interaction with the Leu NH, but the potent nicotine analog epibatidine did not. This interaction was much attenuated in the α4β4 receptor. Surprisingly, we found no evidence for a functionally significant interaction with the backbone carbonyl of the relevant Asn in either receptor with an array of agonists.
Identifying biomarkers specific to bone metastases in castrate-resistant prostate cancer. (2014)

5092 Background: Castrate-resistant prostate cancer (CRPC) has a propensity to metastasize to bone. There is evidence to suggest a differential response to treatment in bone versus visceral metastases. We sought to identify molecular targets specific to CRPC bone metastases. Methods: Liver (n=19), lymph node (n=68), and bone metastases (n=20) from 54 CRPC patients were laser capture microdissected to identify biomarkers using Agilent Expression Arrays. Tissue microarrays (TMAs) were used to validate the differential expression of proteins of interest in bone (n=117) and visceral (n=65) metastases. Prosaposin (PSAP) was evaluated in serial serum samples from men who presented with localized, recurrent, and metastatic disease. Results: Gene Set Enrichment and Ingenuity Pathway Analyses identified pathways that were altered between bone and visceral metastases (q<0.05): 1) Epithelial mesenchymal transition (ZEB1/2, SNAI1/2, TGFB1, VIM), 2) Survival (BAD, BAX), 3) Innate immune response (CNN2, COL4A1, CCL14, FPR1, TLR4, MMP9, SERPINF1) and 4) Osteomimetic (POSTN, SPP1, RUNX2, DKK1, DMP1, IBSP, THBS3). Based on TMAs, both nuclear and cytoplasmic Twist were higher in bone than in visceral metastases (p<0.01). Nuclear Twist and SLUG were associated with fibroblast-like epithelial cells, suggesting that a subset of nuclear-Twist positive CRPC cells in the bone have high metastatic potential. BCL-2 and MCL-1 survival proteins have been shown to be decreased in CRPC bone metastases. Here we show that BAX and BAD are overexpressed. Moreover, we validated the increased expression of osteomimetic proteins and determined that serum PSAP (which has been associated with disease progression) is elevated in patients who developed bone metastases. Conclusions: Heterogeneity of CRPC metastases both within and between patients is an obstacle in determining the appropriate treatment regimen for each patient. However, our data highlight that differential response to therapy could also be based on the site of metastasis. We have identified biomarkers that differentiate bone from visceral metastases that may represent new therapeutic targets for CRPC bone metastases.
Aboveground, belowground biomass and nutrients pool in <i>Salicornia brachiata</i> at coastal area of India: interactive effects of soil characteristics (2018)

Abstract The present study determined the plant biomass (aboveground and belowground) of Salicornia brachiata from six different salt marshes distributed in Indian coastal area over one growing season (September 2014–May 2015). The nutrients concentration and their pools were estimated in plant as well as soil. Belowground biomass in S. brachiata was usually lower than the aboveground biomass. Averaged over different locations, highest biomass was observed in the month of March (2.1 t ha −1 ) followed by May (1.64 t ha −1 ), February (1.60 t ha −1 ), November (0.82 t ha −1 ) and September (0.05 t ha −1 ). The averaged aboveground to belowground ratio was 12.0. Aboveground and belowground biomass were negatively correlated with pH of soil, while positively with soil electrical conductivity. Further, there were positive relationships between organic carbon and belowground biomass; and available sodium and aboveground biomass. The nutrient pools in aboveground were always higher than to belowground biomass. Aboveground pools of carbon (543 kg ha −1 ), nitrogen (48 kg ha −1 ), phosphorus (4 kg ha −1 ), sodium (334 kg ha −1 ) and potassium (37 kg ha −1 ) were maximum in the month of March 2015. Bioaccumulation and translocation factors for sodium of S. brachiata were more than one showing tolerance to salinity and capability of phytoremediation for the saline soil.
Characterization of Micelle Formation by the Single Amino Acid-Based Surfactants Undecanoic L-Isoleucine and Undecanoic L-Norleucine in the Presence of Diamine Counterions with Varying Chain Lengths (2023)

The binding of linear diamine counterions with different methylene chain lengths to the amino-acid-based surfactants undecanoic L-isoleucine (und-IL) and undecanoic L-norleucine (und-NL) was investigated with NMR spectroscopy. The counterions studied were 1,2-ethylenediamine, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, and 1,6-diaminohexane. These counterions were all linear diamines with varying spacer chain lengths between the two amine functional groups. The sodium counterion was studied as well. Results showed that when the length of the counterion methylene chain was increased, the surfactants’ critical micelle concentrations (CMC) decreased. This decrease was attributed to diamines with longer methylene chains binding to multiple surfactant monomers below the CMC and thus acting as templating agents for the formation of micelles. The entropic hydrophobic effect and differences in diamine counterion charge also contributed to the size of the micelles and the surfactants’ CMCs in the solution. NMR diffusion measurements showed that the micelles formed by both surfactants were largest when 1,4-diaminobutane counterions were present in the solution. This amine also had the largest mole fraction of micelle-bound counterions. Finally, the und-NL micelles were larger than the und-IL micelles when 1,4-diaminobutane counterions were bound to the micelle surface. A model was proposed in which this surfactant formed non-spherical aggregates with both the surfactant molecules’ hydrocarbon chains and n-butyl amino acid side chains pointing toward the micelle core. The und-IL micelles, in contrast, were smaller and likely spherically shaped.
Determining the Robot-to-Robot Relative Pose Using Range-only Measurements (2007)

In this paper we address the problem of determining the relative pose of pairs robots that move on a plane while measuring the distance to each other. We show that the minimum number of distance measurements required for the 3 degrees of freedom robot-to-robot transformation to become locally observable is 3. Furthermore, we prove that the maximum number of possible solutions in this case is 6, while a minimum of 5 distance measurements is necessary in order to uniquely determine the robots' relative pose. Finally, we present efficient algorithms for computing all possible solutions and evaluate the validity of our theoretical results both in simulation and experimentally.
Bad news for taxpayers as SARS targets property developments (2009)

Gross-income came under scrutiny again, this time to the detriment of the tax-payer, in a recent judgement where property developers used interest-free loans to build retirement dwellings for clients.
SWCNT–porphyrin nano-hybrids selectively activated by ultrasound: an interesting model for sonodynamic applications (2020)

Sonodynamic therapy (SDT) is an innovative anticancer approach, based on the excitation of a given molecule (usually a porphyrin) by inertial acoustic cavitation that leads to cell death <i>via</i> the production of reactive oxygen species (ROS). This study aims to prepare and characterize nanosystems based on porphyrin grafted carbon nanotubes (SWCNTs), to understand some aspects of the mechanisms behind the SDT phenomenon. Three different porphyrins have been covalently linked to SWCNTs using either Diels-Alder or 1,3-dipolar cycloadditions. ROS production and cell viability have been evaluated upon ultrasound irradiation. Despite the low porphyrin content linked on the SWCNT, these systems have shown high ROS production and high tumour-cell-killing ability. The existence of a PET (photoinduced electron transfer)-like process would appear to be able to explain these observations. Moreover, the demonstrated ability to absorb light limits the impact of side effects due to light-excitation.
P057 All- cause mortality in patients with invasive Candidiasis or candidemia from an interim analysis of a Phase 3 Open-label Study (FURI) (2022)

Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Background There are limited oral treatment options for patients with high-mortality fungal infections such as candidemia or invasive candidiasis who fail currently available antifungals or have an infection caused by resistant organisms. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor with activity against Candida species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of, or with invasive fungal disease refractory to, standard antifungal therapy. We present an interim analysis of all-cause mortality within 30 days post-treatment from the FURI study by fungal disease type for patients with candidemia or invasive candidiasis, who completed therapy up until October 2021. Methods FURI patients are eligible for enrolment if they have proven or probable: severe mucocutaneous candidiasis or invasive candidiasis, or candidemia, with documented evidence of failure, intolerance, or toxicity related to a currently approved standard-of-care antifungal treatment; or patients who cannot receive approved oral antifungal options (eg, due to susceptibility), and continued IV antifungal therapy is clinically undesirable or unfeasible. Patients were followed through 30 days post-treatment for all-cause mortality. Results Out of the 113 patients who completed therapy in the FURI study through October 2021, 56 (50%) had invasive candidiasis or candidemia and were treated with ibrexafungerp. The most common infections in this group were candidemia (15/56, 26.8%), intra-abdominal infection (13/56, 23.2%), and bone infection (10/56, 17.9%). Overall survival within 30 days post-treatment in this group of 56 patients was 94.6%. Of the 56 patients with candidemia or invasive candidiasis, three (5.3%) died within 30 days after completion of treatment with ibrexafungerp, a fourth died at 31 days, a fifth died at 50 days, and a sixth died at 56 days. The mean age of the expired patients was 56 years. All 4 patients had candidemia (3 with C. parapsilosis and 1 with C. albicans), and 2 had intra-abdominal candidiasis, (both with C. glabrata). The average time on therapy with ibrexafungerp was 15.7 days. The mean time to death post-treatment for these patients was 27 days (median, 21 days). In five cases, the deaths were due to causes other than the underlying fungal disease. For the other case, the cause of death was not disclosed. Conclusions Analysis of all-cause mortality in these patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal diseases and limited treatment options.
Acute exercise increases immune responses to SARS CoV-2 in a previously infected man (2021)

Evidence is emerging that exercise and physical activity provides protection against severe COVID-19 disease in patients infected with SARS-CoV-2, but it is not known how exercise affects immune responses to the virus. A healthy man completed a graded cycling ergometer test prior to and after SARS-CoV-2 infection, then again after receiving an adenovirus vector-based COVID-19 vaccine. Using whole blood SARS-CoV-2 peptide stimulation assays, IFN-γ ELISPOT assays, flow cytometry, <i>ex vivo</i> viral-specific T-cell expansion assays and deep T-cell receptor (TCR) β sequencing, we found that exercise robustly mobilized highly functional SARS-CoV-2 specific T-cells to the blood compartment that recognized spike protein, membrane protein, nucleocapsid antigen and the B.1.1.7 α-variant, and consisted mostly of CD3+/CD8+ T-cells and double-negative (CD4-/CD8-) CD3<sup>+</sup> T-cells. The magnitude of SARS-CoV-2 T-cell mobilization with exercise was intensity dependent and robust when compared to T-cells recognizing other viruses (e.g. CMV, EBV, influenza). Vaccination enhanced the number of exercise-mobilized SARS-CoV-2 T-cells recognizing spike protein and the α-variant only. Exercise-mobilized SARS-CoV-2 specific T-cells proliferated more vigorously to <i>ex vivo</i> peptide stimulation and maintained broad TCR-β diversity against SARS-CoV-2 antigens both before and after <i>ex vivo</i> expansion. Neutralizing antibodies to SARS-CoV-2 were transiently elevated during exercise after both infection and vaccination. Finally, infection was associated with an increased metabolic demand to defined exercise workloads, which was restored to pre-infection levels after vaccination. This case study provides impetus for larger studies to determine if these immune responses to exercise can facilitate viral clearance, ameliorate symptoms of long COVID syndrome, and/or restore functional exercise capacity following SARS-CoV-2 infection.
Modelrecoveryanti-windupforcontinuous-timerateand magnitudesaturatedlinearplants ? (2012)

In this paper two approaches are given for anti-windup design for nonlinear control systems with linear plants subject to limitations both in the magnitude and the rate of variation of the control input. Both approaches are based on the so-called Model Recovery Anti-windup (MRAW) framework. The first approach is built by treating the rate+magnitude saturation as a single dynamic nonlinearity, while in the second one, the dynamic compensator dynamics is extended with extra states to treat the two saturations separately. Both approaches lead to global stability with exponentially stable plants and local stability in all other cases. For both approaches, stability and performance guarantees are proven, numerical recipes are given and the relative merits are comparatively highlighted on a simulation example.
China's Science Funding (2011)

This year marks the 25th anniversary of the National Natural Science Foundation of China (NSFC), the largest funding agency for basic research in the country. On this occasion, the leadership of the NSFC and the Chinese Ministry of Finance arranged for the NSFC to be reviewed by an International Evaluation Committee (IEC), which sets a new precedent for China. Part of the motivation for this review was a desire on the part of the Chinese government to determine how well their extensive efforts to boost the support of scientific research measure up to international standards. Apart from logistical arrangements, the IEC was completely independent in its operations. An “evidence-based review” (that is, an overview with extensive data) was carefully prepared by China's National Center for Science and Technology Evaluation. We were also given access to anyone with whom we wanted to speak, including those critical of the present Chinese research culture. Both the evidence-based review and the full report, with our comments and recommendations, are accessible online ( www.nsfc.gov.cn/english/13rp/index.html ). The process and results of this report should be useful not only for China but also for many other nations striving to produce a merit-based culture for science.
Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning (2018)

Substantial rates of fetal loss plague all in vitro procedures involving embryo manipulations, including human-assisted reproduction, and are especially problematic for mammalian cloning where over 90% of reconstructed nuclear transfer embryos are typically lost during pregnancy. However, the epigenetic mechanism of these pregnancy failures has not been well described. Here we performed methylome and transcriptome analyses of pig induced pluripotent stem cells and associated cloned embryos, and revealed that aberrant silencing of imprinted genes, in particular the retrotransposon-derived RTL1 gene, is the principal epigenetic cause of pregnancy failure. Remarkably, restoration of RTL1 expression in pig induced pluripotent stem cells rescued fetal loss. Furthermore, in other mammals, including humans, low RTL1 levels appear to be the main epigenetic cause of pregnancy failure.
Structure of the LKB1-STRAD-MO25 Complex Reveals an Allosteric Mechanism of Kinase Activation (2009)

The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate-activated protein kinase (AMPK). LKB1 activity is regulated by the pseudokinase STRADalpha and the scaffolding protein MO25alpha through an unknown, phosphorylation-independent, mechanism. We describe the structure of the core heterotrimeric LKB1-STRADalpha-MO25alpha complex, revealing an unusual allosteric mechanism of LKB1 activation. STRADalpha adopts a closed conformation typical of active protein kinases and binds LKB1 as a pseudosubstrate. STRADalpha and MO25alpha promote the active conformation of LKB1, which is stabilized by MO25alpha interacting with the LKB1 activation loop. This previously undescribed mechanism of kinase activation may be relevant to understanding the evolution of other pseudokinases. The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function.
Separation of intrinsic and parasitic MOSFET parameters using a multiple built-in Kelvin test structure (2002)

A new MOSFET test structure built in multiple Kelvin patterns is used to evaluate scaled-down MOSFET characteristics through separation of intrinsic and parasitic parameters. Transistor characteristics and contact resistance of individual MOSFETs are simultaneously measured to clarify the direct correlation between fluctuation of MOSFET characteristics and that of parasitic contact resistance. MOSFET performance without parasitic interconnect resistance can be also measured to define intrinsic current drivability in a MOSFET fully scaled-down to less than sub-half-micrometers dimensions.
Supplementary Data 2 from Uncoupling CD4&lt;sup&gt;+&lt;/sup&gt; TIL-Mediated Tumor Killing from JAK-Signaling in Melanoma (2023)

&lt;p&gt;CD4+ TIL-mediated killing is dependent on MHC Class II expression (TCL#17)&lt;/p&gt;
The <i>MUR1</i> gene of <i>Arabidopsis thaliana</i> encodes an isoform of GDP- <scp>d</scp> -mannose-4,6-dehydratase, catalyzing the first step in the <i>de novo</i> synthesis of GDP- <scp>l</scp> -fucose (1997)

GDP-L-fucose is the activated nucleotide sugar form of L-fucose, which is a constituent of many structural polysaccharides and glycoproteins in various organisms. The de novo synthesis of GDP-L-fucose from GDP-D-mannose encompasses three catalytic steps, a 4,6-dehydration, a 3,5-epimerization, and a 4-reduction. The mur1 mutant of Arabidopsis is deficient in L-fucose in the shoot and is rescued by growth in the presence of exogenously supplied L-fucose. Biochemical assays of the de novo pathway for the synthesis of GDP-L-fucose indicated that mur1 was blocked in the first nucleotide sugar interconversion step, a GDP-D-mannose-4,6-dehydratase. An expressed sequence tag was identified that showed significant sequence similarity to proposed bacterial GDP-D-mannose-4,6-dehydratases and was tightly linked to the mur1 locus. A full-length clone was isolated from a cDNA library, and its coding region was expressed in Escherichia coli. The recombinant protein exhibited GDP-D-mannose-4,6-dehydratase activity in vitro and was able to complement mur1 extracts in vitro to complete the pathway for the synthesis of GDP-L-fucose. All seven mur1 alleles investigated showed single point mutations in the coding region for the 4,6-dehydratase, confirming that it represents the MUR1 gene.
Experimental and Theoretical Analysis of the Steric Tolerance of the Binding Site of Bacterioopsin with the Use of Side-Chain Methyl-Shifted Retinal Analogs (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExperimental and Theoretical Analysis of the Steric Tolerance of the Binding Site of Bacterioopsin with the Use of Side-Chain Methyl-Shifted Retinal AnalogsAngel R. de Lera, Beatriz Iglesias, Jesus Rodriguez, Rosana Alvarez, Susana Lopez, Xavier Villanueva, and Esteve PadrosCite this: J. Am. Chem. Soc. 1995, 117, 31, 8220–8231Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August 1995https://pubs.acs.org/doi/10.1021/ja00136a021https://doi.org/10.1021/ja00136a021research-articleACS PublicationsRequest reuse permissionsArticle Views329Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (3)»Supporting Information Supporting Information Get e-Alerts
Monitoring the microcirculation at the bedside using hand-held imaging microscopes: Automatic tracking of erythrocytes (2015)

In recent years, the development of portable microscopy devices that enable the noninvasive bedside evaluation of the mucosal microcirculation in critically ill patients has expanded the research on this level of the cardiovascular system. Several semi-quantitative scores have been defined to assess the peripheral perfusion, based on videos of the microcirculation. However, they are cumbersome and time-consuming processes, highlighting the need for the development of automated software techniques, to reduce physicians workload and ensure prompt and objective patient evaluation. We developed a rapid, automatic method for the quantitative assessment of erythrocyte velocities in Incident Dark Field (IDF) illumination videos of capillary flow. The technique, based on Kalman filter object tracking, was tested in 35 IDF videos against space-time diagrams, showing high correlation (r = 0.96) and agreement (bias = 3.3 μm/s) with space-time diagrams (STD), below 200 μm/s.