gebhart/patrepeval huggingface dataset:
Functional Evidence That Transmembrane 12 and the Loop between Transmembrane 11 and 12 Form Part of the Drug-binding Domain in P-glycoprotein Encoded by MDR1 (1995)

Human MDR1 encodes an ATP-binding cassette transporter, P-glycoprotein, that mediates multiple drug resistance (MDR) to antitumor agents. It has been previously shown that photoaffinity drug-labeling sites reside within, or near, the last transmembrane loop of each cassette within P-glycoprotein (transmembrane domains (TM) 5-6 and 11-12). A genetic approach was used to determine if the drug-labeling site in the second cassette contains functionally important amino acids. Since human MDR3 is 77% identical to MDR1 but does not mediate MDR, the region from TM10 to the C terminus of MDR1 was replaced with the corresponding sequences from MDR3. The resultant chimeric protein was expressed but not functional. By using progressively smaller replacements, we show that replacements limited to TM12 markedly impaired resistance to actinomycin D, vincristine, and doxorubicin, but not to colchicine. The phenotype was associated with an impaired ability to photoaffinity label the chimeric P-glycoprotein with [125I]iodoaryl azidoprazosin. In contrast, replacement of the loop between TM11 and 12 appears to create a more efficient drug pump for actinomycin D, colchicine, and doxorubicin, but not vincristine. These results suggest that, similar to voltage-gated ion channels, amino acids within and immediately N-terminal to the last transmembrane domain of P-glycoprotein compose part of the drug-binding pocket and are in close proximity to photoaffinity drug-labeling domains.
Personalized recommendation of related content based on automatic metadata extraction (2008)

In order to efficiently use information, users often need access to additional background information. This additional information might be stored at various places, such as news websites, company directories, geographic information systems, etc. Oftentimes, in order to access these different pieces of information, the user has to launch new browser windows and direct them to appropriate resources. In our today's Web 2.0, the problem of accessing background information becomes even more prominent: Due to the large number of different users contributing, Web 2.0 sites grow quickly and, most often, in a more uncoordinated way regarding, e.g., structure and vocabulary used, than centrally controlled sites. In such an environment, finding relevant information can become a tedious task.
Abstract 770: Lorvotuzumab mertansine (IMGN901) immune effector activity and its effect on human NK cells (2011)

Abstract Lorvotuzumab mertansine, or IMGN901, is a conjugate consisting of the cytotoxic maytansinoid, DM1, covalently linked to the monoclonal antibody, lorvotuzumab, which selectively targets CD56 (also called neural cell adhesion molecule or NCAM). This conjugate is currently being evaluated in clinical trials for the treatment of CD56+ solid tumors and multiple myeloma. It is able to inhibit tumor cell growth by disruption of microtubule dynamics through delivery of its cytotoxic DM1 payload; however, other potential cell killing mechanisms, such as the immune effector activity of its antibody component, have not been fully investigated. Herein, we report on the immune effector activity of the lorvotuzumab antibody and the lorvotuzumab mertansine conjugate and their effect on the function of CD56+ human primary NK cells in vitro. To investigate the effector activity of the antibody, lorvotuzumab was incubated with CD56+ tumor target cells in the presence of rabbit complement or purified human primary NK cells. The results show that this antibody fails to mediate complement dependent cytotoxicity (CDC) but induces antibody-dependent NK cell-mediated cytotoxity (ADCC) in dose-dependent manner. The complete conjugate showed ADCC activity comparable to lorvotuzumab alone, suggesting that DM1 conjugation did not alter the interaction between the Fc domain of the antibody and NK cell's Fc receptor. Since human primary NK cells express CD56, albeit at a low level, we tested whether lorvotuzumab mertansine or its antibody component could negatively impact the function of NK cells. The results demonstrate that incubation with this antibody or with this conjugate has no effect on rituximab-mediated ADCC activity of the NK cells. Furthermore, overnight exposure of human primary NK cells with lorvotuzumab mertansine did not change rituximab-mediated ADCC activity. In conclusion, the lorvotuzumab antibody has ADCC activity that is retained after DM1 conjugation. Furthermore, neither lorvotuzumab nor its DM1 conjugate, appear to affect the ability of NK cells (which are CD56+) to mediate ADCC through another antibody. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 770. doi:10.1158/1538-7445.AM2011-770
Alterations in Knee Joint Laxity During the Menstrual Cycle in Healthy Women Leads to Increases in Joint Loads During Selected Athletic Movements (2009)

Changes in KJL during the menstrual cycle do change knee joint loading during movements. Clinical Relevance Our findings will be beneficial for researchers in the development of more effective ACL injury prevention programs.
MR1-restricted MAIT cells from the human lung mucosal surface have distinct phenotypic, functional, and transcriptomic features that are preserved in HIV infection (2020)

Abstract Mucosal associated invariant T (MAIT) cells are a class of innate-like T cells that utilize a semi-invariant αβ T cell receptor to recognize small molecule ligands produced by bacteria and fungi. Despite growing evidence that immune cells at mucosal surfaces are often phenotypically and functionally distinct from those in the peripheral circulation, knowledge about the characteristics of MAIT cells at the lung mucosal surface, the site of exposure to respiratory pathogens, is limited. HIV infection has been shown to have a profound effect on the number and function of MAIT cells in the peripheral blood, but its effect on lung mucosal MAIT cells is unknown. We examined the phenotypic, functional, and transcriptomic features of MR1 restricted MAIT cells from the peripheral blood and bronchoalveolar compartments of otherwise healthy individuals with latent Mycobacterium tuberculosis (Mtb) infection who were either HIV uninfected or HIV infected. Peripheral blood MAIT cells consistently co-expressed typical MAIT cell surface markers CD161 and CD26 in healthy individuals, while paired bronchoalveolar MAIT cells displayed heterogenous expression of these markers. Bronchoalveolar MAIT cells produced lower levels of pro-inflammatory cytokine IFN-γ and expressed higher levels of co-inhibitory markers PD-1 and TIM-3 than peripheral MAIT cells. HIV infection resulted in decreased frequencies and pro-inflammatory function of peripheral blood MAIT cells, while in the bronchoalveolar compartment MAIT cell frequency was decreased but phenotype and function were not significantly altered. Single-cell transcriptomic analysis demonstrated greater heterogeneity among bronchoalveolar compared to peripheral blood MAIT cells and suggested a distinct subset in the bronchoalveolar compartment. The transcriptional features of this bronchoalveolar subset were associated with atypical MAIT cells and tissue repair functions. In summary, we found previously undescribed phenotypic and transcriptional heterogeneity of bronchoalveolar MAIT cells in healthy people. In HIV infection, we found numeric depletion of MAIT cells in both anatomical compartments but preservation of the novel phenotypic and transcriptional features of bronchoalveolar MAIT cells.
Synthesis, Characterization, and Application of Antibody Functionalized Fluorescent Silica Nanoparticles (2013)

Abstract Fluorescent silica nanoparticles (FSNs) are prepared by incorporating dye into a mesoporous silica nanoparticle (MSN) synthesis procedure. FSNs containing sulforhodamine B, hydrophobically modified sulforhodamine B, and Cascade Blue hydrazide are made. The MSN‐based FSNs do not leach dye under simulated physiological conditions and have strong, stable fluorescence. FSNs prepared with sulforhodamine B are compared to FSNs prepared with hydrophobically modified sulforhodamine B. The data indicate that FSNs prepared with sulforhodamine B are equally as stable but twice as fluorescent as particles made with hydrophobically modified sulforhodamine B. The fluorescence of a FSN prepared with sulforhodamine B is 10 times more intense than the fluorescence of a 4.5 nm core–shell CdSe/ZnS quantum dot. For diagnostic applications, a method to selectively and covalently bind antibodies to the surface of the FSNs is devised. FSNs that are functionalized with antibodies specific for Neisseria gonorrhoeae specifically bind to Neisseria gonorrhoeae in flow cytometry experiments, thus demonstrating the functionality of the attached antibodies and the potential of MSN‐based FSNs to be used in diagnostic applications.
Uncovering Visually Impaired Gamers’ Preferences for Spatial Awareness Tools Within Video Games (2022)

Sighted players gain spatial awareness within video games through sight and spatial awareness tools (SATs) such as minimaps. Visually impaired players (VIPs), however, must often rely heavily on SATs to gain spatial awareness, especially in complex environments where using rich ambient sound design alone may be insufficient. Researchers have developed many SATs for facilitating spatial awareness within VIPs. Yet this abundance disguises a gap in our understanding about how exactly these approaches assist VIPs in gaining spatial awareness and what their relative merits and limitations are. To address this, we investigate four leading approaches to facilitating spatial awareness for VIPs within a 3D video game context. Our findings uncover new insights into SATs for VIPs within video games, including that VIPs value position and orientation information the most from an SAT; that none of the approaches we investigated convey position and orientation effectively; and that VIPs highly value the ability to customize SATs.
Mapping Three Decades of Intellectual Change in Academia (2020)

Research on the development of science has focused on the creation of multidisciplinary teams. However, while this coming together of people is symmetrical, the ideas, methods, and vocabulary of science have a directional flow. We present a statistical model of the text of dissertation abstracts from 1980 to 2010, revealing for the first time the large-scale flow of language across fields. Results of the analysis include identifying methodological fields that export broadly, emerging topical fields that borrow heavily and expand, and old topical fields that grow insular and retract. Particular findings show a growing split between molecular and ecological forms of biology and a sea change in the humanities and social sciences driven by the rise of gender and ethnic studies.
Effect of the c.-428A>T restoring mutation. (2015)

&lt;p&gt;In both GH3 and HeLa cell lines c.-428A&gt;T almost restores the modulation properties of the &lt;i&gt;CDKN1B&lt;/i&gt; wild type uORF (A). Panel B shows the primary sequence differences in the wild type uORF compared with the -456_-453delCCTT+c.-428A&gt;T.&lt;/p&gt;
Harmonic spatial coherence imaging: an ultrasonic imaging method based on backscatter coherence (2012)

We introduce a harmonic version of the short-lag spatial coherence (SLSC) imaging technique, called harmonic spatial coherence imaging (HSCI). The method is based on the coherence of the second-harmonic backscatter. Because the same signals that are used to construct harmonic B-mode images are also used to construct HSCI images, the benefits obtained with harmonic imaging are also obtained with HSCI. Harmonic imaging has been the primary tool for suppressing clutter in diagnostic ultrasound imaging, however secondharmonic echoes are not necessarily immune to the effects of clutter. HSCI and SLSC imaging are less sensitive to clutter because clutter has low spatial coherence. HSCI shows favorable imaging characteristics such as improved contrast-to-noise ratio (CNR), improved speckle SNR, and better delineation of borders and other structures compared with fundamental and harmonic B-mode imaging. CNRs of up to 1.9 were obtained from in vivo imaging of human cardiac tissue with HSCI, compared with 0.6, 0.9, and 1.5 in fundamental B-mode, harmonic B-mode, and SLSC imaging, respectively. In vivo experiments in human liver tissue demonstrated SNRs of up to 3.4 for HSCI compared with 1.9 for harmonic B-mode. Nonlinear simulations of a heart chamber model were consistent with the in vivo experiments.
IL-15 ex vivo overcomes CD4+ T cell deficiency for the induction of human antigen-specific CD8+ T cell responses (2011)

CD4(+) Th cells are important for the induction and maintenance of antigen-specific CD8(+) T cell function, so their loss or dysfunction in HIV-infected or cancer patients could reduce the patients' ability to control viral infection. Previous work in murine systems indicated that IL-15 codelivered with vaccines could overcome CD4(+) Th cell deficiency for induction of functionally efficient CD8(+) T cells and maintenance of viral-specific CTLs, but its efficacy in helping primary human CD8(+) T cell responses is unknown. In the present study, a peptide-pulsed, DC-based human coculture ex vivo system was used to study the role of IL-15 in overcoming CD4(+) Th deficiency to elicit CD8(+) T cell responses in CD4-depleted PBMCs from healthy individuals and PBMCs from HIV-1-infected patients. We found that IL-15 could overcome CD4(+) Th deficiency to induce primary and recall memory CD8(+) T cell responses in healthy individuals. Moreover, in CD4-deficient, HIV-1-infected patients with diminished CD8(+) T cell responses, IL-15 greatly enhanced CD8(+) T cell responses to alloantigen. These results suggest that IL-15 may be useful in the development of therapeutic and preventive vaccines against cancers and viral infections in patients defective in CD4(+) Th cell.
Genetics of Schizophrenia and Bipolar Affective Disorder: Strategies to Identify Candidate Genes (2003)

Schizophrenia (SCZ) and bipolar affective disorder(BPAD) (formerly termed manic-depressive illness) aresevere, disabling psychiatric illnesses that feature prominently in the top ten causes of disability worldwide (Lopezand Murray 1998). Each will affect about 1% of the population in their lifetime. The cost of providing treatmen...
A combined modified reverse dot-blot and nested PCR assay for the specific non-radioactive detection of Listeria monocytogenes (1993)

A modified reverse dot-blot assay was developed and used in combination with a nested PCR amplification of hly A for the specific detection of Listeria monocytogenes. The deoxynucleotides and digoxygenin-11-dUTP concentrations in the PCR were optimized for maximal sensitivity and economy. For the dot-blot hybridization, digoxygenin-labelled PCR products were directly spotted on nylon membrane-bound poly-dT tailed capture probes and the signal detection was either colorimetric or chemiluminescent. With crude cell lysates, the total assay could be completed in about 6 h with a detection limit between 2 and 25 colony forming units (cfu) per PCR. The assay was then tested for its applicability to environmental sampling of artificially contaminated aluminum surfaces. For environmental sampling, the assay requires an additional overnight enrichment step and has a sensitivity corresponding to 5 cfu per 25 cm2 of inoculated surface.
Unexpected Novel Binding Mode of Pyrrolidine‐Based Aspartyl Protease Inhibitors: Design, Synthesis and Crystal Structure in Complex with HIV Protease (2005)

At present nine FDA-approved HIV protease inhibitors have been launched to market, however rapid drug resistance arising under antiviral therapy calls upon novel concepts. Possible strategies are the development of ligands with less peptide-like character or the stabilization of a new and unexpected binding-competent conformation of the protein through a novel ligand-binding mode. Our rational design of pyrrolidinedimethylene diamines was inspired by the idea to incorporate key structural elements from classical peptidomimetics with a non-peptidic heterocyclic core comprising an endocyclic amino function to address the catalytic aspartic acid side chains of Asp 25 and 25'. The basic scaffolds were decorated by side chains already optimized for the recognition pockets of HIV protease or cathepsin D. A multistep synthesis has been established to produce the central heterocycle and to give flexible access to side chain decorations. Depending on the substitution pattern of the pyrrolidine moiety, single-digit micromolar inhibition of HIV-1 protease and cathepsin D has been achieved. Successful design is suggested in agreement with our modelling concepts. The subsequently determined crystal structure with HIV protease shows that the pyrrolidine moiety binds as expected to the pivotal position between both aspartic acid side chains. However, even though the inhibitors have been equipped symmetrically by polar acceptor groups to address the flap water molecule, it is repelled from the complex, and only one direct hydrogen bond is formed to the flap. A strong distortion of the flap region is detected, leading to a novel hydrogen bond which cross-links the flap loops. Furthermore, the inhibitor addresses only three of the four available recognition pockets. It achieves only an incomplete desolvation compared with the similarly decorated amprenavir. Taking these considerations into account it is surprising that the produced pyrrolidine derivatives achieve micromolar inhibition and it suggests extraordinary potency of the new compound class. Most likely, the protonated pyrrolidine moiety experiences strong enthalpic interactions with the enzyme through the formation of two salt bridges to the aspartic acid side chains. This might provide challenging opportunities to combat resistance of the rapidly mutating virus.
Human Occupancy Detectors (2014)

The occupancy detectors detect the presence of people (and sometimes animals) in a monitored area. The motion detectors respond only to moving objects. One of the major aggravations in detecting occupancy or intrusion is a false-positive detection. Ultrasonic waves are mechanical compressions and rarefaction of air covering the frequency range well beyond the capabilities of human ears, that is, over 20 kHz. The microwave detectors offer an attractive alternative to other detectors when it is required to cover large areas and to operate over an extended temperature range under the influence of strong interferences, such as wind, acoustic noise, fog, dust, and moisture. There are several possible sources of interferences that may cause spurious detections by the triboelectric detectors. By far, the most popular intrusion sensors are the optoelectronic motion detectors. An array of detecting elements (multiple pixels) may be placed in the focal plane of a wide-angle focusing mirror or lens.
Optimal Calibration Method for Water Distribution Water Quality Model (2006)

A water quality model is to predict water quality transport and fate throughout a water distribution system. The model is not only a promising alternative for analyzing disinfectant residuals in a cost-effective manner, but also a means of providing enormous engineering insights into the characteristics of water quality variation and constituent reactions. However, a water quality model is a reliable tool only if it predicts what a real system behaves. This paper presents a methodology that enables a modeler to efficiently calibrate a water quality model such that the field observed water quality values match with the model simulated values. The method is formulated to adjust the global water quality parameters and also the element-dependent water quality reaction rates for pipelines and tank storages. A genetic algorithm is applied to optimize the model parameters by minimizing the difference between the model-predicted values and the field-observed values. It is seamlessly integrated with a well-developed hydraulic and water quality modeling system. The approach has provided a generic tool and methodology for engineers to construct the sound water quality model in expedient manner. The method is applied to a real water system and demonstrated that a water quality model can be optimized for managing adequate water supply to public communities.
Unknown Class Label Cleaning For Learning With Open-Set Noisy Labels (2020)

Deep neural networks (DNNs) trained on large-scale annotated datasets have achieved impressive results in the area of image classification. Many large-scale datasets have been collected from websites; however, such data are inevitably corrupted with noise. In this study, we researched the open-set noisy label problem, where some outliers are contained in a dataset and annotated through a noisy label but do not belong to any class of training data. To address this problem, we propose a novel unknown class label cleaning framework for the training of DNNs with open-set noisy labels. In addition to general image classification, we also estimate the probability of an input being from an unknown class by assigning a pseudo unknown label to all of the data and correct these labels through an alternating update of the network parameters and labels. The results of experiments conducted on the noisy CIFAR-10 datasets demonstrate that our approach can robustly train DNNs with a high proportion of noisy labels.
Epidural Cortical Stimulation of the Left Dorsolateral Prefrontal Cortex for Refractory Major Depressive Disorder (2011)

Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder.
Analysis of ring-metal-aperture VCSELs for single- lateral-mode operation (2007)

The role of metal apertures in lateral-mode confinement in VCSELs is clarified by a detailed effective-frequency-method analysis of an oxide-confined VCSEL structure. The conditions for suppression of higher-order lateral modes using metal apertures are established.
Influence of talc on the fire retardant properties of highly filled intumescent polypropylene composites (2008)

Abstract Intumescent systems have been developed since many years for a wide range of applications, even if they are mainly used in coatings nowadays. The objective of this paper is to determine if the intumescent concept can be applied to highly filled reinforced polypropylene (PP) composites containing talc. Formulations that meet the electrical industry requirements have been developed, even if it has been observed that the addition of talc into intumescent PP leads to a decrease in the fire retardancy of the systems. A thermal stabilization of the material is noted at high temperature in the presence of talc. An increase in the crystallinity of the intumescent structure is suspected to be, at least partially, responsible for the decrease in the performance. Copyright © 2008 John Wiley &amp; Sons, Ltd.
ChemInform Abstract: [2,3]‐Sigmatropic Rearrangement of Allylic Selenimides: Strategy for the Synthesis of Peptides, Peptidomimetics, and N‐Aryl Vinyl Glycines. (2014)

Abstract The scope of the NCS‐mediated amination/[2,3]‐sigmatropic rearrangement of enantioenriched allylic selenides is expanded to provide access to the product classes listed in title.
Sum: Forty Tales from the Afterlives (2009)

At once funny, wistful and unsettling, Sum is a dazzling exploration of unexpected afterlives-each presented as a vignette And lengthening of the others death it says on similarity what. This little more you begin to keep on my friends relations colleagues. Eagleman is like the afterlife you spend your cerebellum grows form present. Why from afar she worships, you are fading ties. Delightful hypothetical fables largely whimsical novelty amusing afterlife.