gebhart/patrepeval huggingface dataset:
The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation (2008)

The crystal structure of the high-affinity Escherichia coli MetNI methionine uptake transporter, a member of the adenosine triphosphate (ATP)-binding cassette (ABC) family, has been solved to 3.7 angstrom resolution. The overall architecture of MetNI reveals two copies of the adenosine triphosphatase (ATPase) MetN in complex with two copies of the transmembrane domain MetI, with the transporter adopting an inward-facing conformation exhibiting widely separated nucleotide binding domains. Each MetI subunit is organized around a core of five transmembrane helices that correspond to a subset of the helices observed in the larger membrane-spanning subunits of the molybdate (ModBC) and maltose (MalFGK) ABC transporters. In addition to the conserved nucleotide binding domain of the ABC family, MetN contains a carboxyl-terminal extension with a ferredoxin-like fold previously assigned to a conserved family of regulatory ligand-binding domains. These domains separate the nucleotide binding domains and would interfere with their association required for ATP binding and hydrolysis. Methionine binds to the dimerized carboxyl-terminal domain and is shown to inhibit ATPase activity. These observations are consistent with an allosteric regulatory mechanism operating at the level of transport activity, where increased intracellular levels of the transported ligand stabilize an inward-facing, ATPase-inactive state of MetNI to inhibit further ligand translocation into the cell.
A three-dimensional thiophene-annulated perylene bisimide as a fullerene-free acceptor for a high performance polymer solar cell with the highest PCE of 8.28% and a VOC over 1.0 V (2018)

PSCs based on <bold>BPT-S</bold> achieved the PCE of 8.28%, which is the highest value based on S-annulated PBIs acceptors so far.
Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis (2003)

Gene therapy approaches involving vascular endothelial growth factor (VEGF) to promote therapeutic angiogenesis are under consideration for conditions ranging from ischemic heart disease to nonhealing skin ulcers. Here we make the surprising observation that the transgenic delivery of VEGF to the skin results in a profound inflammatory skin condition with many of the cellular and molecular features of psoriasis, including the characteristic vascular changes, epidermal alterations, and inflammatory infiltrates. Even longstanding psoriatic disease remains dependent on the transgenic VEGF in this model because it can be effectively reversed by the addition of VEGF Trap, a potent VEGF antagonist. Previous attempts to faithfully replicate the psoriatic phenotype through the transgenic delivery of epidermal keratinocyte growth factors or inflammatory mediators generated phenotypes with only partial resemblance to human psoriasis, leaving unanswered questions about the etiology of this disease. The ability of transgenic VEGF to induce a psoriasiform phenotype suggests a new etiology and treatment approach for this disease and further substantiates emerging concerns about possible proinflammatory adverse effects that might be associated with therapeutic attempts to deliver VEGF.
Turning Brain into Blood: A Hematopoietic Fate Adopted by Adult Neural Stem Cells in Vivo (1999)

Stem cells are found in various organs where they participate in tissue homeostasis by replacing differentiated cells lost to physiological turnover or injury. An investigation was performed to determine whether stem cells are restricted to produce specific cell types, namely, those from the tissue in which they reside. After transplantation into irradiated hosts, genetically labeled neural stem cells were found to produce a variety of blood cell types including myeloid and lymphoid cells as well as early hematopoietic cells. Thus, neural stem cells appear to have a wider differentiation potential than previously thought.
Combinatorial Organic Synthesis of Highly Functionalized Pyrrolidines: Identification of a Potent Angiotensin Converting Enzyme Inhibitor from a Mercaptoacyl Proline Library (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCombinatorial Organic Synthesis of Highly Functionalized Pyrrolidines: Identification of a Potent Angiotensin Converting Enzyme Inhibitor from a Mercaptoacyl Proline LibraryMartin M. Murphy, John R. Schullek, Eric M. Gordon, and Mark A. GallopCite this: J. Am. Chem. Soc. 1995, 117, 26, 7029–7030Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/ja00131a037https://doi.org/10.1021/ja00131a037research-articleACS PublicationsRequest reuse permissionsArticle Views502Altmetric-Citations158LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
Tyrosinase mutants are capable of prodrug activation in transfected nonmelanotic cells. (2000)

Tyrosinase has been suggested as a prodrug-converting enzyme for the treatment of melanoma. We hypothesized that tyrosinase expression in transfected nonmelanotic cells can be used in a gene therapy paradigm of prodrug activation. To verify our hypothesis, we used the following tyrosinase variants: (a) a full-length human tyrosinase clone (T); (b) a mutant lacking the COOH-terminal cytoplasmic domain (TdeltaC); (c) a mutant lacking the COOH-terminal transmembrane and cytoplasmic domains (TdeltaTC); and (d) a fusion with the eight COOH-terminal amino acids of lysosome-associated membrane protein-1 (TL). Expression of mutant and wild-type tyrosinases was induced by transfection in nontumorigenic human cells of epithelial origin (293HEK, MCF-10A adenoma, and NHDF-Ad human dermal fibroblasts) as well as in tumor cells (9L gliosarcoma, MCF7 adenocarcinoma, and HT-1080 fibrosarcoma). When compared with the wild-type tyrosinase transfectants, truncated mutant expression resulted in higher mRNA levels that paralleled higher enzyme activity of the truncated mutants. Two model tyrosinase prodrugs, hydroxyphenyl-propanol (HPP) and N-acetyl-4-S-cysteaminylphenol (NAcSCAP) inhibited proliferation and caused cell death of transfected cells in a dose-dependent manner. Effects of prodrug treatment were compared for tumorigenic cells and their nontumorigenic counterparts. Two truncated mutants (TdeltaC and TdeltaTC) showed low endogenous cytotoxicity and efficiently suppressed proliferation and induced cytotoxicity in transfected tumor cells in the presence of NAcSCAP. Overall, these results indicate that the developed tyrosinase mutants hold promise as prodrug activation systems for tumoral gene therapy.
In vitro–expanded human CD4+CD25+ T-regulatory cells can markedly inhibit allogeneic dendritic cell–stimulated MLR cultures (2004)

CD4(+)CD25(+) T-regulatory (Treg) cells have been shown to critically regulate self- and allograft tolerance in several model systems. Studies of human Treg cells have been restricted by the small number present in peripheral blood and their naturally hypoproliferative state. To better characterize Treg suppressor cell function, we determined methods for the isolation and expansion of these cells. Stringent magnetic microbead-based purification was required for potent suppressor cell line generation. Culture stimulation with cell-sized Dynabeads coated with anti-CD3 and anti-CD28 monoclonal antibodies, CD4(+) feeder cells, and interleukin 2, provided for marked expansion in cell number (100-fold), with retention and enhancement of suppressor function. The potent Treg cell lines suppressed proliferation in dendritic cell-driven allo-mixed lymphocyte reaction (MLR) cultures by more than 90%. The Treg-derived suppressor cells functioned early in allo-MLR because expression of activation antigens and accumulation of cytokines was nearly completely prevented. Importantly, cultured Treg cells also suppressed activated and matured dendritic cell-driven responses. These results demonstrate that short-term suppressor cell lines can be generated, and they can express a very potent suppressive activity. This approach will enable more detailed biologic studies of Treg cells and facilitate the evaluation of cultured Treg cells as a novel form of immunosuppressive therapy.
Stable multi-target tracking in real-time surveillance video (2011)

The majority of existing pedestrian trackers concentrate on maintaining the identities of targets, however systems for remote biometric analysis or activity recognition in surveillance video often require stable bounding-boxes around pedestrians rather than approximate locations. We present a multi-target tracking system that is designed specifically for the provision of stable and accurate head location estimates. By performing data association over a sliding window of frames, we are able to correct many data association errors and fill in gaps where observations are missed. The approach is multi-threaded and combines asynchronous HOG detections with simultaneous KLT tracking and Markov-Chain Monte-Carlo Data Association (MCM-CDA) to provide guaranteed real-time tracking in high definition video. Where previous approaches have used ad-hoc models for data association, we use a more principled approach based on a Minimal Description Length (MDL) objective which accurately models the affinity between observations. We demonstrate by qualitative and quantitative evaluation that the system is capable of providing precise location estimates for large crowds of pedestrians in real-time. To facilitate future performance comparisons, we make a new dataset with hand annotated ground truth head locations publicly available.
StreamCloud: An Elastic and Scalable Data Streaming System (2012)

Many applications in several domains such as telecommunications, network security, large-scale sensor networks, require online processing of continuous data flows. They produce very high loads that requires aggregating the processing capacity of many nodes. Current Stream Processing Engines do not scale with the input load due to single-node bottlenecks. Additionally, they are based on static configurations that lead to either under or overprovisioning. In this paper, we present StreamCloud, a scalable and elastic stream processing engine for processing large data stream volumes. StreamCloud uses a novel parallelization technique that splits queries into subqueries that are allocated to independent sets of nodes in a way that minimizes the distribution overhead. Its elastic protocols exhibit low intrusiveness, enabling effective adjustment of resources to the incoming load. Elasticity is combined with dynamic load balancing to minimize the computational resources used. The paper presents the system design, implementation, and a thorough evaluation of the scalability and elasticity of the fully implemented system.
Localizing Parts of Faces Using a Consensus of Exemplars (2013)

We present a novel approach to localizing parts in images of human faces. The approach combines the output of local detectors with a nonparametric set of global models for the part locations based on over 1,000 hand-labeled exemplar images. By assuming that the global models generate the part locations as hidden variables, we derive a Bayesian objective function. This function is optimized using a consensus of models for these hidden variables. The resulting localizer handles a much wider range of expression, pose, lighting, and occlusion than prior ones. We show excellent performance on real-world face datasets such as Labeled Faces in the Wild (LFW) and a new Labeled Face Parts in the Wild (LFPW) and show that our localizer achieves state-of-the-art performance on the less challenging BioID dataset.
Protein chaperones: a composition of matter review (2008 – 2013) (2014)

For Hsp90, there has been considerable creativity in the discovery of novel pharmacophores that fall outside the three initially discovered scaffolds (i.e., ansamycins, resorcinols and purines). Nonetheless, much of the patent literature appears to build on previously reported structure activity relationship through slight modifications of Hsp90 inhibitor space by finding weaknesses in existing patents. The major goal of future development of Hsp90 inhibitors is not necessarily identifying better molecules but rather understanding how to rationally use these agents in the clinic. The development of Hsp70 inhibitors has lagged behind. It will require a more concerted effort from the drug discovery community in order to begin to realize the potential of this target.
Human Breath Emissions of VOCs (1999)

The medical community has long recognized that humans exhale volatile organic compounds (VOCs). Several studies have quantified emissions of VOCs from human breath, with values ranging widely due to variation between and within individuals. The authors have measured human breath concentrations of isoprene and pentane. The major VOCs in the breath of healthy individuals are isoprene (12-580 ppb), acetone (1.2-1,880 ppb), ethanol (13-1,000 ppb), methanol (160-2,000 ppb) and other alcohols. In this study, we give a brief summary of VOC measurements in human breath and discuss their implications for indoor concentrations of these compounds, their contributions to regional and global emissions budgets, and potential ambient air sampling artifacts. Though human breath emissions are a negligible source of VOCs on regional and global scales (less than 4% and 0.3%, respectively), simple box model calculations indicate that they may become an important (and sometimes major) indoor source of VOCs under crowded conditions. Human breath emissions are generally not taken into account in indoor air studies, and results from this study suggest that they should be.
Molecular Dissection of Mammalian RNA Polymerase II Transcriptional Termination (2008)

Transcriptional termination of mammalian RNA polymerase II (Pol II) is an essential but little-understood step in protein-coding gene expression. Mechanistically, termination by all DNA-dependent RNA polymerases can be reduced to two steps, namely release of the RNA transcript and release of the DNA template. Using a simple nuclear fractionation procedure, we have monitored transcript and template release in the context of both natural and artificial Pol II terminator sequences. We describe the timing and relationship between these events and in so doing establish the roles of the poly(A) signal, cotranscriptional RNA cleavage events, and 5'-3' exonucleolytic RNA degradation in the mammalian Pol II termination process.
Overtaking vehicle detection using implicit optical flow (2002)

We describe an optical flow based obstacle detection system for use in detecting vehicles approaching the blind spot of a car on highways and city streets. The system runs at near frame rate (8-15 frames/second) on PC hardware. We will discuss the prediction of a camera image given an implicit optical flow field and comparison with the actual camera image. The advantage to this approach is that we never explicitly calculate optical flow. We will also present results on digitized highway images, and video taken from Navlab 5 while driving on a Pittsburgh highway.
Molecular Basis for Dimethylsulfoxide (DMSO) Action on Lipid Membranes (2006)

Dimethylsulfoxide (DMSO) is an aprotic solvent that has the ability to induce cell fusion and cell differentiation and enhance the permeability of lipid membranes. It is also an effective cryoprotectant. Insights into how this molecule modulates membrane structure and function would be invaluable toward regulating the above processes and for developing chemical means for enhancing or hindering the absorption of biologically active molecules, in particular into or via the skin. We show here by means of molecular simulations that DMSO can induce water pores in dipalmitoyl-phosphatidylcholine bilayers and propose this to be a possible pathway for the enhancement of penetration of actives through lipid membranes. DMSO also causes the membrane to become floppier, which would enhance permeability, facilitate membrane fusion, and enable the cell membrane to accommodate osmotic and mechanical stresses during cryopreservation.
Imatinib Treatment Induces CD5+ B Lymphocytes and IgM Natural Antibodies with Anti-Leukemic Reactivity in Patients with Chronic Myelogenous Leukemia (2011)

Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32), the percentage of bone marrow CD20(+)CD5(+)sIgM(+) lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and -7. All patients with high number of CD20(+)CD5(+)sIgM(+) cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20(+)CD5(+)sIgM(+) lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20(+)CD5(+)sIgM(+) cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response.
Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T‐cell activation (2013)

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T-cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre-)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte-derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome- and transporter associated with Ag processing-dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8⁺ T-cell activation.
Microwave-Specific Enhancement of the Carbon–Carbon Dioxide (Boudouard) Reaction (2013)

The Boudouard reaction, which is the reaction of carbon and carbon dioxide to produce carbon monoxide, represents a simple and straightforward method for the remediation of carbon dioxide in the environment through reduction: CO2(g) + C(s) ⇌ 2CO. However, due to the large positive enthalpy, typically reported to be 172 kJ/mol under standard conditions at 298 K, the equilibrium does not favor CO production until temperatures >700 °C, when the entropic term, −TΔS, begins to dominate and the free energy becomes negative. We have found that, under microwave irradiation to selectively heat the carbon, dramatically different thermodynamics for the reaction are observed. During kinetic studies of the reaction under conditions of flowing CO2, the apparent activation energy dropped from 118.4 kJ/mol under conventional convective heating to 38.5 kJ/mol under microwave irradiation. From measurement of the equilibrium constants as a function of temperature, the enthalpy of the reaction dropped from 183.3 kJ/mol at ∼1100 K to 33.4 kJ/mol at the same temperature under microwave irradiation. This changes the position of the equilibrium so that the temperature at which CO becomes the major product drops from 643 °C in the conventional thermal reaction to 213 °C in the microwave. The observed reduction in the apparent enthalpy of the microwave driven reaction, compared to what is determined for the thermal reaction from standard heats of formation, can be thought of as arising from additional energy being put into the carbon by the microwaves, effectively increasing its apparent standard enthalpy. Mechanistically, it is hypothesized that the enhanced reactivity arises from the interaction of CO2 with the steady-state concentration of electron–hole pairs that are present at the surface of the carbon due to the space-charge mechanism, by which microwaves are known to heat carbon. Such a mechanism is unique to microwave-induced heating and, given the effect it has on the thermodynamics of the Boudouard reaction, suggests that its use may yield energy savings in driving the general class of gas–carbon reactions.