gebhart/patrepeval huggingface dataset:
Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information (2017)

A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography.
Functional TCR T cell screening using single-cell droplet microfluidics (2018)

Adoptive T cell transfer, in particular TCR T cell therapy, holds great promise for cancer immunotherapy with encouraging clinical results. However, finding the right TCR T cell clone is a tedious, time-consuming, and costly process. Thus, there is a critical need for single cell technologies to conduct fast and multiplexed functional analyses followed by recovery of the clone of interest. Here, we use droplet microfluidics for functional screening and real-time monitoring of single TCR T cell activation upon recognition of target tumor cells. Notably, our platform includes a tracking system for each clone as well as a sorting procedure with 100% specificity validated by downstream single cell reverse-transcription PCR and sequencing of TCR chains. Our TCR screening prototype will facilitate immunotherapeutic screening and development of T cell therapies.
Structural requirements of tetracycline-Tet repressor interaction: determination of equilibrium binding constants for tetracycline analogs with the Tet repressor (1991)

We used the Tn10-encoded Tet repressor, which has a highly specific binding capacity for tetracycline, to probe contacts between the drug and protein by chemical interference studies of the antibiotic. For that purpose, the equilibrium association constants of modified tetracyclines with the Tet repressor and Mg2+ cations were determined quantitatively. The results confirm the previous notion that Mg2+ probably binds with the oxygens at positions 11 and 12 and is absolutely required for protein-drug recognition. Modifications were introduced at positions seven, six, five, and four of the drug, and anhydrotetracycline was also studied. Substitutions or eliminations of functions at these positions influenced binding to the Tet repressor up to 35-fold. The introduction of an azido function at position seven in 7-azidotetracycline and epimerization of the substituents at position four in 4-epitetracycline lead to a 2- or 25-fold reduction, respectively, of Tet repressor affinity in those compounds. Anhydrotetracycline bound about 35-fold more strongly than tetracycline did, indicating that the oxygen at position 11 may be involved in Tet repressor recognition. This increased binding is in contrast to the lower antibiotic activity of anhydrotetracycline and indicates that the Tet repressor and ribosomes recognize the drug differently.
A Novel Allelic Variant of the Human TSG-6 Gene Encoding an Amino Acid Difference in the CUB Module (2002)

Tumor necrosis factor-stimulated gene-6 (TSG-6) encodes a 35-kDa protein, which is comprised of contiguous Link and CUB modules. TSG-6 protein has been detected in the articular joints of osteoarthritis (OA) patients, with little or no constitutive expression in normal adult tissues. It interacts with components of cartilage matrix (e.g. hyaluronan and aggrecan) and thus may be involved in extracellular remodeling during joint disease. In addition, TSG-6 has been found to have anti-inflammatory properties in models of acute and chronic inflammation. Here we have mapped the human TSG-6 gene to 2q23.3, a region of chromosome 2 linked with OA. A single nucleotide polymorphism was identified that involves a non-synonymous G --> A transition at nucleotide 431 of the TSG-6 coding sequence, resulting in an Arg to Gln alteration in the CUB module (at residue 144 in the preprotein). Molecular modeling of the CUB domain indicated that this amino acid change might lead to functional differences. Typing of 400 OA cases and 400 controls revealed that the A(431) variant identified here is the major TSG-6 allele in Caucasians (with over 75% being A(431) homozygotes) but that this polymorphism is not a marker for OA susceptibility in the patients we have studied. Expression of the Arg(144) and Gln(144) allotypes in Drosophila Schneider 2 cells, and functional characterization, showed that there were no significant differences in the ability of these full-length proteins to bind hyaluronan or form a stable complex with inter-alpha-inhibitor.
Bromodomain and Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype (2006)

A critical unanswered question about mixed lineage leukemia (MLL) is how specific MLL fusion partners control leukemia phenotype. The MLL-cyclic AMP-responsive element binding protein-binding protein (CBP) fusion requires both the CBP bromodomain and histone acetyltransferase (HAT) domain for transformation and causes acute myelogenous leukemia (AML), often preceded by a myelodysplastic phase. We did domain-swapping experiments to define whether unique specificities of these CBP domains drive this specific MLL phenotype. Within MLL-CBP, we replaced the CBP bromodomain or HAT domain with P300/CBP-associated factor (P/CAF) or TAF(II)250 bromodomains or the P/CAF or GCN5 HAT domains. HAT, but not bromodomain, substitutions conferred enhanced proliferative capacity in vitro but lacked expression of myeloid cell surface markers normally seen with MLL-CBP. Mice reconstituted with domain-swapped hematopoietic progenitors developed different disease from those with MLL-CBP. This included development of lymphoid disease and lower frequency of the myelodysplastic phase in those mice developing AML. We conclude that both the CBP bromodomain and HAT domain play different but critical roles in determining the phenotype of MLL-CBP leukemia. Our results support an important role for MLL partner genes in determining the leukemia phenotype besides their necessity in leukemogenesis. Here, we find that subtleties in MLL fusion protein domain specificity direct cells toward a specific disease phenotype.
Rhenium-selenium-chlorine solid phases: cluster excision and core substitution reactions of molecular species (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRhenium-selenium-chlorine solid phases: cluster excision and core substitution reactions of molecular speciesOmar M. Yaghi, Michael J. Scott, and R. H. HolmCite this: Inorg. Chem. 1992, 31, 23, 4778–4784Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/ic00049a013https://doi.org/10.1021/ic00049a013research-articleACS PublicationsRequest reuse permissionsArticle Views488Altmetric-Citations64LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Ischaemia induced alternans of action potential duration in the intact-heart: dependence on coronary flow, preload and cycle length (1993)

Clinical and experimental evidence relate action potential duration (APD) alternans to ischaemic heart disease and ventricular arrhythmias. The present investigation was performed to study the quantitative relationship between APD alternans and the degree of ischaemia, loading conditions and cycle length (CL) in an intact heart. Monophasic action potentials (MAP) were simultaneously recorded by contact electrodes from two left (LV) and one right ventricular (RV) sites in 20 Langendorff-perfused rabbit hearts. The preparations were subjected to global ischaemia at flow rates ranging from 40% of normal flow to complete cessation of flow. Pacing was performed at either constant or regularly changing CL. The magnitude of APD alternans was expressed as beat-to-beat differences in action potential duration of two consecutive MAPs. During normal perfusion, neither very fast pacing at a CL of 200 ms nor periodical rate switches resulted in persistent APD alternans. Pacing at a constant CL of 800 ms did not induce APD alternans at complete cessation of flow for 6 min. However, alternans developed progressively at a constant CL of 400 ms after 2.8 +/- 0.3 min of complete ischaemia at the pre-loaded LV, and after 4.6 +/- 0.4 min at the unloaded RV (P < 0.01). The reduction of preload at the LV from 15 to 5 mmHg end-diastolic pressure delayed development of APD alternans from 2.8 +/- 03 min to 4.3 +/- 0.4 min (P < 0.05) at 400 ms CL. Following graded underperfusion of 40%, 20% and 10% of initial flow, persistent APD alternans developed in relation to the degree of flow reduction and increased progressively with duration of ischaemia. APD alternans at the LV always preceded the onset of APD alternans at the RV. In experiments with identical flow rates the shortest CL of 200 ms resulted in the greatest and earliest initiation of APD alternans compared to the longer CL (P < 0.01, P < 0.001). An increase in CL from 400 to 800 ms immediately abolished APD alternans, generated by the shorter CL, at any time during the 6 min period of complete ischaemia. Similarly, increasing the cycle length from 200 or 400 to 600 ms eliminated APD alternans up to 6 min of ischaemia and significantly reduced its magnitude between 7 and 10 min within a few beats. We conclude that persistent APD alternans is a characteristic findings in the rabbit heart during global ischaemia4 It is a sensitive parameter of the severity of ischaemia and depends.(ABSTRACT TRUNCATED AT 400 WORDS)
Synthesis of Doxorubicin Conjugates Through Hydrazone Bonds to Melanotransferrin P97 (2003)

Abstract Through hydrazone bonds, three doxorubicin-p97 conjugates 5, 9, 12 are synthesized using adipic dihydrazine, 4-(4-N-maleimidophenyl)-butyric acid hydrazine 6 and adipic acid mono hydrazine 10 as linkers. These are potential agents for treating brain tumors.
Vaccine-induced CD8+ T-cell responses to MAGE-3 correlate with clinical outcome in patients with melanoma. (2003)

There was a correlation between vaccine-induced CD8+ T-cell responses to melanoma-associated antigens and improved clinical outcome, but the correlation depended on the antigen against which the response is directed. The only significant correlation was with responses to MAGE-3.
HCP: A Flexible CNN Framework for Multi-Label Image Classification (2015)

Convolutional Neural Network (CNN) has demonstrated promising performance in single-label image classification tasks. However, how CNN best copes with multi-label images still remains an open problem, mainly due to the complex underlying object layouts and insufficient multi-label training images. In this work, we propose a flexible deep CNN infrastructure, called Hypotheses-CNN-Pooling (HCP), where an arbitrary number of object segment hypotheses are taken as the inputs, then a shared CNN is connected with each hypothesis, and finally the CNN output results from different hypotheses are aggregated with max pooling to produce the ultimate multi-label predictions. Some unique characteristics of this flexible deep CNN infrastructure include: 1) no ground-truth bounding box information is required for training; 2) the whole HCP infrastructure is robust to possibly noisy and/or redundant hypotheses; 3) the shared CNN is flexible and can be well pre-trained with a large-scale single-label image dataset, e.g., ImageNet; and 4) it may naturally output multi-label prediction results. Experimental results on Pascal VOC 2007 and VOC 2012 multi-label image datasets well demonstrate the superiority of the proposed HCP infrastructure over other state-of-the-arts. In particular, the mAP reaches 90.5% by HCP only and 93.2% after the fusion with our complementary result in [44] based on hand-crafted features on the VOC 2012 dataset.
The Evolution of Bacterial Transformation: Sex With Poor Relations (1997)

Bacteria are the only organisms known to actively take up DNA and recombine it into their genomes. While such natural transformation systems may provide many of the same benefits that sexual reproduction provides eukaryotes, there are important differences that critically alter the consequences, especially when recombination's main benefit is reducing the mutation load. Here, analytical and numerical methods are used to study the selection of transformation genes in populations undergoing deleterious mutation. Selection for transformability depends on the shape of the fitness function against mutation. If the fitness function is linear, then transformation would be selectively neutral were it not for the possibility that transforming cells may take up DNA that converts them into nontransformable cells. If the selection includes strong positive (synergistic) epistasis, then transformation can be advantageous in spite of this risk. The effect of low quality DNA (from selectively killed cells) on selection is then studied analytically and found to impose an additional cost. The limited data available for real bacterial populations suggest that the conditions necessary for the evolution of transformation are unlikely to be met, and thus that DNA uptake may have some function other than recombination of deleterious mutations.
Molecular Basis of Buspirone's Anxiolytic Action (1991)

Buspirone has been available in the United States for over four years for the treatment of anxiety. It was anticipated this drug would offer certain advantages over the established benzodiazepines. In contrast to diazepam, early studies found no evidence for the interaction of buspirone with GABAergic mechanisms. Behavioural, electrophysiological and receptor binding experiments gradually led to the idea that buspirone owes much of its anxiolytic activity to its ability to attenuate central 5-hydroxytryptamine neurotransmission. Specifically, it appears to act as an agonist at presynaptic 5-HT1A receptors, particularly in the raphe nuclei. Although buspirone also shows an affinity for dopamine D2 receptors, where it seems to behave as an antagonist, there is much doubt that this effect is related to its anxiolytic action. Even though buspirone and the benzodiazepines do not obviously share a common mode of action, the possibility is discussed that there is an underlying common mechanism of responsible for their antianxiety effects.
New restriction enzymes discovered from Escherichia coli clinical strains using a plasmid transformation method (2003)

The presence of restriction enzymes in bacterial cells has been predicted by either classical phage restriction-modification (R-M) tests, direct in vitro enzyme assays or more recently from bacterial genome sequence analysis. We have applied phage R-M test principles to the transformation of plasmid DNA and established a plasmid R-M test. To validate this test, six plasmids that contain BamHI fragments of phage lambda DNA were constructed and transformed into Escherichia coli strains containing known R-M systems including: type I (EcoBI, EcoAI, Eco124I), type II (HindIII) and type III (EcoP1I). Plasmid DNA with a single recognition site showed a reduction of relative efficiency of transformation (EOT = 10(-1)-10(-2)). When multiple recognition sites were present, greater reductions in EOT values were observed. Once established in the cell, the plasmids were subjected to modification (EOT = 1.0). We applied this test to screen E.coli clinical strains and detected the presence of restriction enzymes in 93% (14/15) of cells. Using additional subclones and the computer program, RM Search, we identified four new restriction enzymes, Eco377I, Eco585I, Eco646I and Eco777I, along with their recognition sequences, GGA(8N)ATGC, GCC(6N)TGCG, CCA(7N)CTTC, and GGA(6N)TATC, respectively. Eco1158I, an isoschizomer of EcoBI, was also found in this study.
Theoretical analysis of acetyltriazene and the mechanistic implications of its reaction with acid (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTheoretical analysis of acetyltriazene and the mechanistic implications of its reaction with acidJudy L. Ozment, Ann M. Schmiedekamp, Laurie A. Schultz-Merkel, Richard H. Smith Jr., and Christopher J. MichejdaCite this: J. Am. Chem. Soc. 1991, 113, 2, 397–405Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/ja00002a003https://doi.org/10.1021/ja00002a003research-articleACS PublicationsRequest reuse permissionsArticle Views88Altmetric-Citations15LEARN 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-Alertsclose Get e-Alerts
Simultaneous utilization of glucose, xylose and arabinose in the presence of acetate by a consortium of Escherichia coli strains (2012)

Despite the modest reduction in the overall rate of sugar consumption due to the various deletions that were required to generate the consortium of strains, the approach constitutes a significant improvement in any single-organism approach to utilize sugars found in lignocellulosic hydrolysate in the presence of acetate.
Mesothelin Binding to CA125/MUC16 Promotes Pancreatic Cancer Cell Motility and Invasion via MMP-7 Activation (2013)

Mesothelin (MSLN) and cancer antigen125/mucin 16 (CA125/MUC16) are potential biomarkers for pancreatic cancer (PC) that are co-overexpressed at the invading edges of PC tissues, and their expression correlates with poor survival rates. However, the role of MSLN-MUC16 molecular interaction in PC cell motility and invasion has yet to be elucidated. Using sophisticated bioengineering and molecular biology tools, we report that the binding of MSLN to MUC16 markedly enhances PC cell motility and invasion via the selective induction of matrix metalloproteinase (MMP)-7. MSLN-mediated MMP-7 upregulation in MUC16-expressing PC cells occurs via a p38 MAPK-dependent pathway. Depletion of MMP-7 or inhibition of p38 activity abolishes MSLN-mediated PC motility and invasion. These findings provide a novel perspective on the enhanced invasive potential associated with MSLN and MUC16 co-overexpression, and the mechanism underlying MMP-7 activation in PC invasion and metastasis.
CD4+ T‐regulatory cells: toward therapy for human diseases (2008)

T-regulatory cells (Tregs) have a fundamental role in the establishment and maintenance of peripheral tolerance. There is now compelling evidence that deficits in the numbers and/or function of different types of Tregs can lead to autoimmunity, allergy, and graft rejection, whereas an over-abundance of Tregs can inhibit anti-tumor and anti-pathogen immunity. Experimental models in mice have demonstrated that manipulating the numbers and/or function of Tregs can decrease pathology in a wide range of contexts, including transplantation, autoimmunity, and cancer, and it is widely assumed that similar approaches will be possible in humans. Research into how Tregs can be manipulated therapeutically in humans is most advanced for two main types of CD4(+) Tregs: forkhead box protein 3 (FOXP3)(+) Tregs and interleukin-10-producing type 1 Tregs (Tr1 cells). The aim of this review is to highlight current information on the characteristics of human FOXP3(+) Tregs and Tr1 cells that make them an attractive therapeutic target. We discuss the progress and limitations that must be overcome to develop methods to enhance Tregs in vivo, expand or induce them in vitro for adoptive transfer, and/or inhibit their function in vivo. Although many technical and theoretical challenges remain, the next decade will see the first clinical trials testing whether Treg-based therapies are effective in humans.
Ethidium fluorescence assays. Part 1. Physicochemical studies (1979)

DNA and RNA can be assayed rapidly and very sensitively by exploiting the enhanced fluorescence of ethidium intercalated into duplex regions. By assaying at different pHs and introducing a heating/cooling cycle, a great many physicochemical aspects of DNA and RNA can be studied avoiding the use of radiolabels, and often giving information not otherwise readily obtainable. Studies are described on duplex DNA which involve measurement of extinction coefficients, cross-linking by chemicals, Cot curve analysis as well as estimation of drug-DNA binding constants. The assays can be adapted to investigate multi-stranded nucleic acid structures. The use of co-valently closed circular DNA also allows rapid and extremely sensitive measurements of nicking caused by irradiation or drugs.