gebhart/patrepeval huggingface dataset:
Inhibitors of Protein-Disulfide Isomerase Prevent Cleavage of Disulfide Bonds in Receptor-bound Glycoprotein 120 and Prevent HIV-1 Entry (2002)

We previously reported that monoclonal antibodies to protein-disulfide isomerase (PDI) and other membrane-impermeant PDI inhibitors prevented HIV-1 infection. PDI is present at the surface of HIV-1 target cells and reduces disulfide bonds in a model peptide attached to the cell membrane. Here we show that soluble PDI cleaves disulfide bonds in recombinant envelope glycoprotein gp120 and that gp120 bound to the surface receptor CD4 undergoes a disulfide reduction that is prevented by PDI inhibitors. Concentrations of inhibitors that prevent this reduction and inhibit the cleavage of surface-bound disulfide conjugate prevent infection at the level of HIV-1 entry. The entry of HIV-1 strains differing in their coreceptor specificities is similarly inhibited, and so is the reduction of gp120 bound to CD4 of coreceptor-negative cells. PDI inhibitors also prevent HIV envelope-mediated cell-cell fusion but have no effect on the entry of HIV-1 pseudo-typed with murine leukemia virus envelope. Importantly, PDI coprecipitates with both soluble and cellular CD4. We propose that a PDI.CD4 association at the cell surface enables PDI to reach CD4-bound virus and to reduce disulfide bonds present in the domain of gp120 that binds to CD4. Conformational changes resulting from the opening of gp120-disulfide loops may drive the processes of virus-cell and cell-cell fusion. The biochemical events described identify new potential targets for anti-HIV agents.
Fine-Grained Multithreading Support for Hybrid Threaded MPI Programming (2010)

As high-end computing systems continue to grow in scale, recent advances in multi- and many-core architectures have pushed such growth toward more dense architectures, that is, more processing elements per physical node, rather than more physical nodes themselves. Although a large number of scientific applications have relied so far on an MPI-everywhere model for programming high-end parallel systems; this model may not be sufficient for future machines, given their physical constraints such as decreasing amounts of memory per processing element and shared caches. As a result, application and computer scientists are exploring alternative programming models that involve using MPI between address spaces and some other threaded model, such as OpenMP, Pthreads, or Intel TBB, within an address space. Such hybrid models require efficient support from an MPI implementation for MPI messages sent from multiple threads simultaneously. In this paper, we explore the issues involved in designing such an implementation. We present four approaches to building a fully thread-safe MPI implementation, with decreasing levels of critical-section granularity (from coarse-grain locks to fine-grain locks to lock-free operations) and correspondingly increasing levels of complexity. We present performance results that demonstrate the performance implications of the different approaches.
A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations (2001)

A common method for the application of distance constraints in molecular simulations employing Cartesian coordinates is the SHAKE procedure for determining the Lagrange multipliers regarding the constraints. This method relies on the linearization and decoupling of the equations governing the atomic coordinate resetting corresponding to each constraint in a molecule, and is thus iterative. In the present study, we consider an alternative method, M-SHAKE, which solves the coupled equations simultaneously by matrix inversion. The performances of the two methods are compared in simulations of the pure solvents water, dimethyl sulfoxide, and chloroform. It is concluded that M-SHAKE is significantly faster than SHAKE when either (1) the molecules contain few distance constraints (solvent), or (2) when a high level of accuracy is required in the application of the constraints. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 501–508, 2001
Inositol Hexakisphosphate Is Bound in the ADAR2 Core and Required for RNA Editing (2005)

We report the crystal structure of the catalytic domain of human ADAR2, an RNA editing enzyme, at 1.7 angstrom resolution. The structure reveals a zinc ion in the active site and suggests how the substrate adenosine is recognized. Unexpectedly, inositol hexakisphosphate (IP6) is buried within the enzyme core, contributing to the protein fold. Although there are no reports that adenosine deaminases that act on RNA (ADARs) require a cofactor, we show that IP6 is required for activity. Amino acids that coordinate IP6 in the crystal structure are conserved in some adenosine deaminases that act on transfer RNA (tRNA) (ADATs), related enzymes that edit tRNA. Indeed, IP6 is also essential for in vivo and in vitro deamination of adenosine 37 of tRNAala by ADAT1.
Noninvasive Monitoring of Tumors (2008)

The treatment of non–small-cell lung cancer has made limited but clinically significant progress during the past two decades of clinical research. Through carefully designed clinical trials, investigators have identified several chemotherapeutic drugs to combat this disease. Many questions have been asked and answered. Which combinations work best? How frequently should they be given and for how long? And which patients should be treated?1 Nonetheless, such advances have been limited, and the prognosis for patients with advanced disease remains grim.Despite the modest results achieved with conventional cytotoxic chemotherapeutic agents, the past several decades of basic cancer research have started to . . .
Simplified processing for high spectral efficiency wireless communication employing multi-element arrays (1999)

We investigate robust wireless communication in high-scattering propagation environments using multi-element antenna arrays (MEAs) at both transmit and receive sites. A simplified, but highly spectrally efficient space-time communication processing method is presented. The user's bit stream is mapped to a vector of independently modulated equal bit-rate signal components that are simultaneously transmitted in the same band. A detection algorithm similar to multiuser detection is employed to detect the signal components in white Gaussian noise (WGN). For a large number of antennas, a more efficient architecture can offer no more than about 40% more capacity than the simple architecture presented. A testbed that is now being completed operates at 1.9 GHz with up to 16 quadrature amplitude modulation (QAM) transmitters and 16 receive antennas. Under ideal operation at 18 dB signal-to-noise ratio (SNR), using 12 transmit antennas and 16 receive antennas (even with uncoded communication), the theoretical spectral efficiency is 36 bit/s/Hz, whereas the Shannon capacity is 71.1 bit/s/Hz. The 36 bits per vector symbol, which corresponds to over 200 billion constellation points, assumes a 5% block error rate (BLER) for 100 vector symbol bursts.
A phase I single dose escalation trial of ch806 in patients with advanced tumors expressing the 806 antigen (2006)

13028 Background: Ch806 is a chimeric antibody (mAb) that binds to a unique epitope only exposed on a transitional untethered form of the Epidermal Growth Factor Receptor (EGFR), and the de2–7 EGFR, but not exposed on wtEGFR. Immunohistochemistry (IHC) studies have demonstrated that the 806 antigen is not detected in any normal human tissue, but is highly expressed in a broad range of epithelial cancers, and in gliomas. Preclinial studies have shown that ch806 has potent anti-tumor activity in xenograft models expressing amplified EGFR or de2–7 EGFR, and is internalized into tumor cells. Methods: The primary objective of this first in man study was to determine the toxicity of increasing single doses of c806. The secondary objectives were to characterize the biodistribution, pharmacokinetics (pK) and tumor uptake of In-111 ch806, to determine human antibody responses (HACA), and to document tumour responses to ch806. Patients with advanced or metastatic disease whose tumors expressed the 806 antigen by IHC received a single infusion of 111 In-labelled ch806. 111 In-ch806 was administered as a single, 1 hour infusion at dose levels of of 5 mg/m 2 , 10 mg/m 2 , 20 mg/m 2 and 40 mg/m 2 . Results: 7 patients (1 at 5mg/m 2 dose and 2 each at 10, 20 and 40 mg/m 2 doses) have been entered into the study: squamous cell lung (2), colorectal (1), squamous cell anus (1), mesothelioma (1), squamous cell larynx (1) and squamous cell skin with lung metastasis (1). Patients had a median age 66 (range 49–75) and median of 1.5 (range 0–4) prior oncological treatment regimens. No significant toxicities were observed. The biodistribution of ch806 showed excellent targeting of tumour sites in all patients. There was no evidence of any normal tissue uptake of ch806. PK analysis showed comparable Cl at all dose levels (mean ± SD: 34.6 ± 5.0 mL/hr), no normal tissue saturable compartment, and dose dependent Cmax and AUC. HACA analysis is ongoing. One patient had a reduction in size of cervical lymphadenopathy on study, and progressive pulmonary disease at study completion. There was 1 patient with SD and 6 with PD at study completion. Conclusion: ch806 was very well tolerated and targeted a wide range of tumour types with no normal tissue uptake, which is markedly different to other mAbs that target wtEGFR. No significant financial relationships to disclose.
Control of the out-of-plane curvature in SU-8 compliant microstructures by exposure dose and baking times (2007)

The effect of processing conditions on the curvature of SU-8 cantilevers up to 6400 µm long is determined by experimental methods. Our observations suggest that a zero curvature condition can be achieved by controlling the exposure dose and post-exposure baking time for any given SU-8 thickness. The curvature of SU-8 cantilevers processed with different exposure doses and post-exposure baking times has been measured and reveals that the gradient of crosslinking density throughout the SU-8 film is the cause of out-of-plane stress. A general model for the SU-8 cantilever curvature is developed which explains the behavior of SU-8 structures that have been processed with different conditions and can be used to predict the general effect on the SU-8 cantilever curvature for different SU-8 thicknesses and process parameters.
Coding for the Slepian-Wolf problem with turbo codes (2002)

This paper proposes a practical coding scheme for the Slepian-Wolf problem of separate encoding of correlated sources. Finite-state machine (FSM) encoders, concatenated in parallel, are used at the transmit side and an iterative turbo decoder is applied at the receiver. Simulation results of system performance are presented for binary sources with different amounts of correlation. Obtained results show that the proposed technique outperforms by far both an equivalent uncoded system and a system coded with traditional (non-concatenated) FSM coding.
The illusion of robotic life (2012)

This paper describes our approach on the development of the expression of emotions on a robot with constrained facial expressions. We adapted principles and practices of animation from Disney™ and other animators for robots, and applied them on the development of emotional expressions for the EMYS robot. Our work shows that applying animation principles to robots is beneficial for human understanding of the robots' emotions.
Fast switching characteristics of a widely tunable laser transmitter (2003)

We demonstrate a widely tunable laser transmitter that accesses 32 ITU channels with 100-GHz spacing and switches between all channel combinations in less than 45 ns. The compact module uses commercially available electronic components. We investigate the electrical and thermal properties of the laser and the tuning section driver. The experiments show that a low output impedance driver circuit produces faster switching times. Also, temperature variation of the laser limits the wavelength accuracy of the switching. Finally, we present the correlation between switching times and the laser tuning currents.
Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4 (2001)

The syndecans make up a family of transmembrane heparan sulfate proteoglycans that act as coreceptors with integrins and growth factor tyrosine kinase receptors. Syndecan-4 is upregulated in skin dermis after wounding, and, in cultured fibroblasts adherent to the ECM protein fibronectin, this proteoglycan signals cooperatively with beta1 integrins. In this study, we generated mice in which the syndecan-4 gene was disrupted by homologous recombination in embryonic stem cells to test the hypothesis that syndecan-4 contributes to wound repair. Mice heterozygous or homozygous for the disrupted syndecan-4 gene are viable, fertile, and macroscopically indistinguishable from wild-type littermates. Compared with wild-type littermates, mice heterozygous or homozygous for the disrupted gene have statistically significant delayed healing of skin wounds and impaired angiogenesis in the granulation tissue. These results indicate that syndecan-4 is an important cell-surface receptor in wound healing and angiogenesis and that syndecan-4 is haplo-insufficient in these processes.
2-(Purin-6-yl)-2-thiopseudourea Hydrochloride (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2-(Purin-6-yl)-2-thiopseudourea HydrochlorideEugene F. McInerney and Eugene J. KupchikCite this: J. Med. Chem. 1967, 10, 4, 739–740Publication Date (Print):July 1, 1967Publication History Published online1 May 2002Published inissue 1 July 1967https://pubs.acs.org/doi/10.1021/jm00316a053https://doi.org/10.1021/jm00316a053research-articleACS PublicationsRequest reuse permissionsArticle Views37Altmetric-Citations3LEARN 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
Maternal height, pregnancy estriol and birth weight in reference to breast cancer risk in Boston and Shanghai (2005)

Birth weight has been positively associated with breast cancer risk in adult life and is positively associated with the principal pregnancy estrogen estriol. Birth weight is lower among Chinese women than among Caucasian women, but paradoxically, pregnancy estriol levels are higher among the former than the latter. We studied a cohort of 317 Caucasian pregnant women in Boston, MA, and 339 Chinese pregnant women in Shanghai, China. We investigated whether maternal height, which is inversely associated with pregnancy estriol levels, interacts with this hormone in relation to birth weight, thus accommodating the apparently contradictory ecologic and analytic evidence concerning the role of pregnancy estrogens on breast cancer risk in the offspring. In both Boston and Shanghai, there was a positive association of pregnancy estriol with birth weight among taller women, whereas among shorter women the association was essentially null. The relevant interaction terms were highly significant in Boston (p approximately 0.006), whereas in Shanghai, where pregnant women were generally shorter, the interaction term was suggestive (p approximately 0.14). We conclude that maternal height should be considered an important risk factor for breast cancer in the offspring since it is a crucial determinant of birth weight, both directly and through positive interaction with the principal pregnancy estrogen estriol.
Visualizing electronic mail (2003)

As the number of electronic messages continues to grow, information visualization tools become increasingly important to support users in the complexity of managing the large amount of information they receive. This paper presents a visualization approach to support e-mail browsing as well as querying. A new clustering mechanism is presented which, based on the hierarchical nature of domain names, provides an automatic classification of electronic messages. This representation is combined with a temporal visualization that supports browsing, Boolean searching and threading operations.
Abstract 4331: Advantages of polyacetal polymer-based antibody drug conjugates employing cysteine bioconjugation. (2013)

Abstract The application of polymers to antibody drug conjugate (ADC) design and preparation can provide numerous advantages, including 1) significantly higher capacity for drug payload; 2) utilization of alternative payloads not suitable for direct conjugation approaches; 3) improvement of physicochemical properties of resulting ADCs; 4) utilization of protein recognition scaffolds beyond the commonly used IgGs; and 5) improvements in PK and biodistribution. Herein we present results of a novel, biodegradable polyacetal polymer-based conjugation system to create next-generation ADCs. The basis of this new conjugation system is a hydrophilic, fully biodegradable polyacetal carrier (PHF or poly(1-hydroxymethylethylene hydroxymethylformal) modified with chemically orthogonal linkers. One linker is used to covalently attach a targeting moiety (mAb or alternative) via cysteine conjugation, while a second, chemically distinct linker is used to attach a drug payload and to control the mechanism and rate of drug release. Previously we have reported highly efficacious polyacetal ADCs prepared by utilizing random lysine modification. In this report we present an alternative cysteine-based bioconjugation strategy. Conventional, direct drug-cysteine linked ADCs are destabilized due to loss of inter-chain disulfide bridges. In contrast, the polyacetal polymer conjugated via cysteines in the antibody hinge region stabilizes the resulting ADCs through the formation of inter-chain bridge structures. To demonstrate the benefits of this approach, we prepared Her-2 targeted ADCs with protein recognition scaffolds ranging in size from 15 kDa to 150 kDa, all targeting the Her-2 antigen, and bearing an anti-tubulin agent as the drug payload. ADCs were highly active and selective in vitro in Her-2 expressing cell lines. These polyacetal cysteine-based ADCs exhibited prolonged plasma and tumor exposure in the Her-2 expressing BT474 mouse xenograft model and tumor-specific accumulation. The ADCs were well-tolerated, and resulted in 100% tumor-free survivors. Citation Format: Alex Yurkovetskiy, Natalya Bodyak, Mao Yin, Joshua Thomas, Patrick Conlon, Cheri Stevenson, Alex Uttard, Liu Qin, Dmitry Gumerov, Elena Ter-Ovaneysan, Michael DeVit, Timothy B. Lowinger. Advantages of polyacetal polymer-based antibody drug conjugates employing cysteine bioconjugation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4331. doi:10.1158/1538-7445.AM2013-4331
Studies on Imidazole Compounds. I. A Synthesis of Imidazoles with Functional Groups in the 2-Position (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on Imidazole Compounds. I. A Synthesis of Imidazoles with Functional Groups in the 2-PositionReuben G. JonesCite this: J. Am. Chem. Soc. 1949, 71, 2, 383–386Publication Date (Print):February 1, 1949Publication History Published online1 May 2002Published inissue 1 February 1949https://pubs.acs.org/doi/10.1021/ja01170a002https://doi.org/10.1021/ja01170a002research-articleACS PublicationsRequest reuse permissionsArticle Views1146Altmetric-Citations69LEARN 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
Effects of recombinant human interleukin-3 in patients with relapsed small-cell lung cancer treated with chemotherapy: a dose-finding study. (1992)

This study demonstrates that rhIL-3 can be safely administered after chemotherapy on an outpatient basis. rhIL-3 is tolerated well at doses up to 8 micrograms/kg/d and is biologically active in patients after myelosuppressive chemotherapy.
mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer (2016)

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer. Cancer Res; 76(23); 6911-23. ©2016 AACR.