gebhart/patrepeval huggingface dataset:
Concurrent V(D)J recombination and DNA end instability increase interchromosomal trans -rearrangements in ATM-deficient thymocytes (2013)

During the CD4(-)CD8(-) (DN) stage of T-cell development, RAG-dependent DNA breaks and V(D)J recombination occur at three T-cell receptor (TCR) loci: TCRβ, TCRγ and TCRδ. During this stage, abnormal trans-rearrangements also take place between TCR loci, occurring at increased frequency in absence of the DNA damage response mediator ataxia telangiectasia mutated (ATM). Here, we use this model of physiologic trans-rearrangement to study factors that predispose to rearrangement and the role of ATM in preventing chromosomal translocations. The frequency of DN thymocytes with DNA damage foci at multiple TCR loci simultaneously is increased 2- to 3-fold in the absence of ATM. However, trans-rearrangement is increased 10 000- to 100 000-fold, indicating that ATM function extends beyond timely resolution of DNA breaks. RAG-mediated synaptic complex formation occurs between recombination signal sequences with unequal 12 and 23 base spacer sequences (12/23 rule). TCR trans-rearrangements violate this rule, as we observed similar frequencies of 12/23 and aberrant 12/12 or 23/23 recombination products. This suggests that trans-rearrangements are not the result of trans-synaptic complex formation, but they are instead because of unstable cis synaptic complexes that form simultaneously at distinct TCR loci. Thus, ATM suppresses trans-rearrangement primarily through stabilization of DNA breaks at TCR loci.
SENSE phase‐constrained magnitude reconstruction with iterative phase refinement (2007)

Conventional sensitivity encoding (SENSE) reconstruction is based on equations in the complex domain. However, for many MRI applications only the magnitude is relevant. If there exists an estimate of the underlying phase information, a magnitude-only phase-constrained reconstruction can help to improve the conditioning of the SENSE reconstruction problem. Consequently, this reduces g-factor-related noise enhancement. In previous attempts at phase-constrained SENSE reconstruction, image quality was hampered by strong aliasing artifacts resulting from inadequate phase estimates and high sensitivity to phase errors. If a full-resolution phase image is used, a significant reduction in aliasing errors and better noise properties compared to SENSE can be obtained. An iterative scheme that improves the phase estimate to better approximate the phase is presented. The mathematical framework of the new approach is provided together with comparisons of conventional SENSE, phase-constrained SENSE, and the new phase-refinement method. Both theory and experimental verification demonstrate significantly better noise performance at high reduction factors, i.e., close to the theoretical limit. For applications that need only magnitude data, an iterative phase-constrained SENSE reconstruction can provide substantial SNR improvement over SENSE reconstruction and less artifacts than phase-constrained SENSE.
Mining interesting locations and travel sequences from GPS trajectories (2009)

The increasing availability of GPS-enabled devices is changing the way people interact with the Web, and brings us a large amount of GPS trajectories representing people's location histories. In this paper, based on multiple users' GPS trajectories, we aim to mine interesting locations and classical travel sequences in a given geospatial region. Here, interesting locations mean the culturally important places, such as Tiananmen Square in Beijing, and frequented public areas, like shopping malls and restaurants, etc. Such information can help users understand surrounding locations, and would enable travel recommendation. In this work, we first model multiple individuals' location histories with a tree-based hierarchical graph (TBHG). Second, based on the TBHG, we propose a HITS (Hypertext Induced Topic Search)-based inference model, which regards an individual's access on a location as a directed link from the user to that location. This model infers the interest of a location by taking into account the following three factors. 1) The interest of a location depends on not only the number of users visiting this location but also these users' travel experiences. 2) Users' travel experiences and location interests have a mutual reinforcement relationship. 3) The interest of a location and the travel experience of a user are relative values and are region-related. Third, we mine the classical travel sequences among locations considering the interests of these locations and users' travel experiences. We evaluated our system using a large GPS dataset collected by 107 users over a period of one year in the real world. As a result, our HITS-based inference model outperformed baseline approaches like rank-by-count and rank-by-frequency. Meanwhile, when considering the users' travel experiences and location interests, we achieved a better performance beyond baselines, such as rank-by-count and rank-by-interest, etc.
The Essential Schizosaccharomyces pombe gpi1 Gene Complements a Bakers' Yeast GPI Anchoring Mutant and is Required for Efficient Cell Separation (1997)

The Schizosaccharomyces pombe gpi1+ gene was cloned by complementation of the Saccharomyces cerevisiae gpi1 mutant, which has temperature-sensitive defects in growth and glycosyl phosphatidylinositol (GPI) membrane anchoring of protein, and which is defective in vitro in the first step in GPI anchor assembly, the formation of N-acetylglucosaminyl phosphatidylinositol (GlcNAc-PI). S. pombe gpi1+ encodes a protein with 29% identity to amino acids 87–609 of the S. cerevisiae protein, and is the functional homolog of the S. cerevisiae Gpi1 protein, for it restores [3H]inositol-labelling of protein and in vitro GlcNAc-PI synthetic activity to both S. cerevisiae gpi1 and gpi1::URA3 cells. Disruption of gpi1+ is lethal. Haploid Δgpi1+::his7+ spores germinate, but proceed through no more than three rounds of cell division, many cells ceasing growth as binucleate, septate cells with thickened septa. These results indicate that GPI synthesis is an essential function in fission yeast, and suggest that GPI anchoring is also required for completion of cytokinesis. The nucleotide sequence reported will appear in the GenBank Nucleotide Sequence database under the Accession Number U77355.©1997 John Wiley & Sons, Ltd.
Outcome of intraarterial urokinase for acute vascular occlusion. (1991)

Intraarterial urokinase (IAUK) was administered to 33 patients on 40 occasions for the treatment of acute extremity ischemia and long-term patency was assessed. Lysis was successful in 39 of the 40 cases (95%). Occlusive thrombus was cleared in 12 of 13 patients with native artery occlusion (7 complete, 5 partial), 8 of 9 with autologous vein grafts (5 complete, 3 partial), and in all 18 patients with synthetic grafts (17 complete, 1 partial). The primary cumulative patency following successful IAUK was 100% for native arteries and 47% for synthetic grafts at 12 months, and 23% for autologous grafts at 9 months. The difference in rethrombosis rate between autologous vein (67%) and native artery (0%) was significant (p = 0.02) as was the difference between infrainguinal prosthetic grafts (63%) and native artery (p = 0.025). IAUK is most effective for the treatment of native artery occlusion, but is significantly less effective for thrombosed infrainguinal autologous vein or synthetic grafts due to the likelihood of reocclusion, despite the high immediate success rate. For autologous vein grafts, lysis is frequently incomplete and patency rapidly deteriorates regardless of adjunctive therapy to relieve the underlying obstruction.
Identification of New Epitopes from Four Different Tumor-Associated Antigens: Recognition of Naturally Processed Epitopes Correlates with HLA-A∗0201-Binding Affinity (2001)

Forty-two wild-type and analogue peptides derived from p53, carcinoembryonic Ag, Her2/neu, and MAGE2/3 were screened for their capacity to induce CTLs, in vitro, capable of recognizing tumor target lines. All the peptides bound HLA-A*0201 and two or more additional A2 supertype alleles with an IC(50) of 500 nM or less. A total of 20 of 22 wild-type and 9 of 12 single amino acid substitution analogues were found to be immunogenic in primary in vitro CTL induction assays, using normal PBMCs and GM-CSF/IL-4-induced dendritic cells. These results suggest that peripheral T cell tolerance does not prevent, in this system, induction of CTL responses against tumor-associated Ag peptides, and confirm that an HLA class I affinity of 500 nM or less is associated with CTL epitope immunogenicity. CTLs generated by 13 of 20 of the wild-type epitopes, 6 of 9 of the single, and 2 of 5 of the double substitution analogues tested recognized epitopes generated by endogenous processing of tumor-associated Ags and expressed by HLA-matched cancer cell lines. Further analysis revealed that recognition of naturally processed Ag was correlated with high HLA-A2.1-binding affinity (IC(50) = 200 nM or less; p = 0.008), suggesting that high binding affinity epitopes are frequently generated and can be recognized as a result of natural Ag processing. These results have implications for the development of cancer vaccines, in particular, and for the process of epitope selection in general.
Experimental photoimmunotherapy of hepatic metastases of colorectal cancer with a 17.1A chlorin(e6) immunoconjugate. (2000)

Photoimmunotherapy (using a monoclonal antibody-targeted photosensitizer and red light) may be a strategy to overcome the limitations inherent in photodynamic therapy of liver tumors. The aims of this study were (a) to test the efficacy of selective treatment of hepatic metastases of colorectal cancer in an orthotopic murine xenograft using the murine monoclonal antibody 17.1A conjugated to the photosensitizer chlorin(e6), and (b) to compare the tumor response after the same light dose was delivered at two different fluence rates. Based on previous biodistribution studies that had shown that the photoimmunoconjugate with a polyanionic charge had both a higher absolute tumor chlorin(e6) content and a greater tumor:normal liver ratio than those obtained with a photoimmunoconjugate bearing a polycationic charge, mice were treated 3 h after i.v. injection of the polyanionic 17.1A chlorin(e6) conjugate or unconjugated photosensitizer. Red light was delivered into the liver tumor by an interstitial fiber, and tumor response end points were total tumor weight in the short term and survival in the long term. There was a highly significant reduction (<20% of controls; P = 0.0035) in the weight of the tumors in the mice treated with photoimmunotherapy, and the median survival increased from 62.5 to 102 days (P = 0.015). Photodynamic therapy with free chlorin(e6) produced a smaller decrease in tumor weight and a smaller extension of survival, neither of which were statistically significant. A comparison of photoimmunotherapy with 10 J of light delivered at 30 or 300 mW showed that the higher fluence rate prolonged survival significantly more than the lower fluence rate. This may have been because the high fluence rate gave a contribution of laser-induced hyperthermia to the photodamage. Correlation studies showed that the amount of normal liver remaining at necropsy correlated best with survival. Photoimmunotherapy shows efficacy in destroying liver tumors, and future studies should maximize selectivity to minimize the destruction of normal liver.
Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: Reagents for tumor immunotherapy (1996)

Studies in melanoma patients have revealed that self proteins can function as targets for tumor-reactive cytotoxic T lymphocytes (CTL). One group of self proteins MAGE, BAGE, and GAGE are normally only expressed in testis and placenta, whilst another group of CTL recognized proteins are melanocyte-specific differentiation antigens. In this study we have investigated whether CTL can be raised against a ubiquitously expressed self protein, mdm-2, which is frequently overexpressed in tumors. The observation that T-cell tolerance is self major histocompatibility complex-restricted was exploited to generate CTL specific for an mdm-2 derived peptide presented by nonself major histocompatibility complex class I molecules. Thus, the allo-restricted T-cell repertoire of H-2d mice was used to isolate CTL specific for the mdm100 peptide presented by allogeneic H-2Kb class I molecules. In vitro, these CTL discriminated between transformed and normal cells, killing specifically Kb-positive melanoma and lymphoma tumors but not Kb-expressing dendritic cells. In vivo, the CTL showed antitumor activity and delayed the growth of melanoma as well as lymphoma tumors in H-2b recipient mice. These experiments show that it is possible to circumvent T-cell tolerance to ubiquitously expressed self antigens, and to target CTL responses against tumors expressing elevated levels of structurally unaltered proteins.
A comparative analysis of standard and alternative antidepressants in the treatment of human immunodeficiency virus patients (1996)

Our research group has conducted clinical trials of standard (imipramine, fluoxetine, and sertraline) and alternative antidepressants (dextroamphetamine and testosterone replacement therapy) in the treatment of clinical depression among patients with human immunodeficiency virus (HIV) illness. This report presents secondary analyses of data pooled from these trials with the purpose of comparing the antidepressant efficacy of these various agents. In all trials, a DSM-III-R depressive disorder was the primary criterion for study entry, and each treatment resulted in significant improvement after both 2 and 6 weeks of treatment according to the Hamilton Depression Rating Scale (HDRS). Response rates for standard antidepressants ranged from 70% to 74%, with similar, high response rates found in trials of dextroamphetamine (93%) and testosterone (81%). The response rate of each active drug treatment was superior to that of placebo (33%). Each treatment was well-tolerated in terms of side effects, and there was essentially no effect of any treatment on CD4 cell count. Differences in trial design, entrance criteria, and measurements require that caution be used in interpreting these results; nonetheless, each of the five treatments studied demonstrated strong efficacy and possessed relatively unique benefits, providing health care providers with valuable treatment options in addressing individual needs of patients.
BER performance of turbo-coded PPM CDMA systems on optical fiber (2000)

We obtain upper bounds on the bit error rate (BER) for turbo-coded optical code-division multiple-access (CDMA) systems using pulse position modulation (PPM). We use transfer function bounding techniques to obtain these bounds, so our results correspond to the average bound over all interleavers of a given length. We consider parallel concatenated coding (PCC) schemes that use recursive convolutional codes as constituent codes. We consider systems using an avalanche photodiode (APD), and treat APD noise, thermal noise, and multi-user interference using a Gaussian approximation. We compare the performance of turbo-coded systems with that of BCH-coded systems with soft-decision decoding, and that of concatenated coding systems with outer Reed-Solomon (RS) code and inner convolutional code. We show that turbo-coded systems have better performance than BCH-coded systems. We also show that concatenated systems have better performance than turbo-coded systems when the block length is small and the received laser power is somewhat large.
Mapping Sites of O-GlcNAc Modification Using Affinity Tags for Serine and Threonine Post-translational Modifications (2002)

Identifying sites of post-translational modifications on proteins is a major challenge in proteomics. O-Linked beta-N-acetylglucosamine (O-GlcNAc) is a dynamic nucleocytoplasmic modification more analogous to phosphorylation than to classical complex O-glycosylation. We describe a mass spectrometry-based method for the identification of sites modified by O-GlcNAc that relies on mild beta-elimination followed by Michael addition with dithiothreitol (BEMAD). Using synthetic peptides, we also show that biotin pentylamine can replace dithiothreitol as the nucleophile. The modified peptides can be efficiently enriched by affinity chromatography, and the sites can be mapped using tandem mass spectrometry. This same methodology can be applied to mapping sites of serine and threonine phosphorylation, and we provide a strategy that uses modification-specific antibodies and enzymes to discriminate between the two post-translational modifications. The BEMAD methodology was validated by mapping three previously identified O-GlcNAc sites, as well as three novel sites, on Synapsin I purified from rat brain. BEMAD was then used on a purified nuclear pore complex preparation to map novel sites of O-GlcNAc modification on the Lamin B receptor and the nucleoporin Nup155. This method is amenable for performing quantitative mass spectrometry and can also be adapted to quantify cysteine residues. In addition, our studies emphasize the importance of distinguishing between O-phosphate versus O-GlcNAc when mapping sites of serine and threonine post-translational modification using beta-elimination/Michael addition methods.
Chemical and Photochemical Reductions of Flavin Nucleotides and Analogs* (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical and Photochemical Reductions of Flavin Nucleotides and Analogs*G. K. Radda and Melvin CalvinCite this: Biochemistry 1964, 3, 3, 384–393Publication Date (Print):March 1, 1964Publication History Published online1 May 2002Published inissue 1 March 1964https://pubs.acs.org/doi/10.1021/bi00891a014https://doi.org/10.1021/bi00891a014research-articleACS PublicationsRequest reuse permissionsArticle Views365Altmetric-Citations89LEARN 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
RasGRP, a Ras Guanyl Nucleotide- Releasing Protein with Calcium- and Diacylglycerol-Binding Motifs (1998)

RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has an atypical pair of "EF hands" that bind calcium and a diacylglycerol (DAG)-binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was associated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were absent when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation.
Intermittent blood flow in a murine tumor: radiobiological effects. (1987)

Little is known about how and why hypoxia arises in tumors, i.e., whether hypoxia is a chronic process resulting from diffusion limitations or occurs more acutely due to transient changes in blood perfusion. We have investigated the nature of hypoxia in the murine squamous carcinoma SCC VII using a new fluorescence-activated cell-sorting technique which facilitates isolation of viable tumor cells as a function of their distance from the blood supply. The technique utilizes the DNA binding/diffusion properties of the bisbenzamide fluorochrome Hoechst 33342. This compound has a very short distribution half-life from the blood after i.v. injection but remains bound within tumor cells even after disaggregation, redistributing with a half-life greater than 2 h. Cells can thus be sorted on the basis of their staining intensity (proximity to the blood supply), and varying the Hoechst 33342 administration protocol provides the basis for elucidating transient changes in blood flow that result in acute radiobiological hypoxia. Using this technique, we have demonstrated that acute hypoxia results from transient changes in blood perfusion in 500-mg SCC VII tumors. Independent confirmation of the intermittent blood flow has been obtained using histological techniques.
Valence Band Alignment at Cadmium Selenide Quantum Dot and Zinc Oxide (1010) Interfaces (2008)

A key issue governing efficient electron transfer between two semiconductors is interfacial electronic energy alignment. We address this issue in a model system relevant to quantum-dot-sensitized solar cells, cadmium selenide (CdSe) quantum dots adsorbed on a single crystal zinc oxide (ZnO) (101̅0) surface via 3-mercaptopropionic acid linkers, using ultraviolet photoelectron spectroscopy. The valence band maximum (VBM) of the CdSe quantum dots is found to be located at 1.1 ± 0.1 eV above the VBM of ZnO, nearly independent of the size of the quantum dots (2.1−4.2 nm). This finding suggests that, upon adsorption, there is direct electronic interaction between CdSe quantum dots and the ZnO surface involving CdSe valance bands. Such electronic interaction pins the CdSe valence band to the Fermi level. As a result, varying the quantum dot size mainly tunes the alignment of the conduction band minimum of CdSe with respect to that of the ZnO surface.
In-vitro selection of HIV-1 variants resistant to non-nucleoside reverse transcriptase inhibitors in monocyte-derived macrophages (1997)

Unlike the selection of HIV-1 variants resistant to anti-retroviral drugs in human peripheral blood mononuclear cells and T cell lines, induction of resistance in monocyte-derived macrophages has not been widely studied. Since macrophages serve as a potential HIV-1 reservoir in humans, knowledge of the effect of anti-retroviral drugs on macrophage-tropic HIV-1 isolates may help in the design of a strategy for prolonged suppression of viral replication. In-vitro selection and drug susceptibility testing of macrophage-tropic HIV-1 variants with reduced sensitivity to two non-nucleoside reverse transcriptase inhibitors, atevirdine and delavirdine (both bis-heteroarylpiperazines), is described here. The atevirdine-resistant isolate was cross-resistant to delavirdine, and the delavirdine-resistant isolate was cross-resistant to atevirdine. Interestingly, the atevirdine-resistant isolate, but not the delavirdine-resistant isolate, was also cross-resistant to nevirapin while the inhibition of viral replication of both isolates in macrophages by zidovudine was the same as that in the parental HIV-1 strain. Nucleotide sequence analysis of the resistant macrophage-tropic HIV-1 isolates showed that the atevirdine-induced resistance was due to a single amino acid change at codon 106 and that the delavirdine-induced resistance could be attributed to an amino acid change at codon 236. This study demonstrates that monocyte-derived macrophages can be used to investigate the phenotypic and genotypic acquisition of anti-retroviral drug resistance of macrophage-tropic HIV-1.