gebhart/patrepeval huggingface dataset:
Crystal structure of a human CD3-ε/δ dimer in complex with a UCHT1 single-chain antibody fragment (2004)

The alpha/beta T cell receptor complex transmits signals from MHC/peptide antigens through a set of constitutively associated signaling molecules, including CD3-epsilon/gamma and CD3-epsilon/delta. We report the crystal structure at 1.9-A resolution of a complex between a human CD3-epsilon/delta ectodomain heterodimer and a single-chain fragment of the UCHT1 antibody. CD3-epsilon/delta and CD3-epsilon/gamma share a conserved interface between the Ig-fold ectodomains, with parallel packing of the two G strands. CD3-delta has a more electronegative surface and a more compact Ig fold than CD3-gamma; thus, the two CD3 heterodimers have distinctly different molecular surfaces. The UCHT1 antibody binds near an acidic region of CD3-epsilon opposite the dimer interface, occluding this region from direct interaction with the TCR. This immunodominant epitope may be a uniquely accessible surface in the TCR/CD3 complex, because there is overlap between the binding site of the UCHT1 and OKT3 antibodies. Determination of the CD3-epsilon/delta structure completes the set of TCR/CD3 globular ectodomains and contributes information about exposed CD3 surfaces.
Acquired Resistance Mutations to ALK Inhibitors Identified by Single Circulating Tumor Cell Sequencing in ALK -Rearranged Non–Small-Cell Lung Cancer (2019)

Our results highlight the genetic heterogeneity and clinical utility of CTCs to identify therapeutic resistance mutations in <i>ALK</i>-rearranged patients. Single CTC sequencing may be a unique tool to assess heterogeneous resistance mechanisms and help clinicians for treatment personalization and resistance options to ALK-targeted therapies.
Synthesis and Structure−Activity Relationships of Parasiticidal Thiosemicarbazone Cysteine Protease Inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi (2004)

We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds that were effective against the enzymes and the parasites but also some compounds that were parasiticidal despite a lack of activity against the proteases. Several compounds were effective in killing all tested parasites. These promising lead compounds were tested for general toxicity in mice, and only one produced observable toxicity after 62 h. Our results suggest that thiosemicarbazones represent validated drug leads that kill several species of protozoan parasites through the inhibition of cysteine proteases as well as other novel targets.
BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance (2011)

Since the initial discovery that a subset of patients with cutaneous melanoma harbor BRAF mutations, substantial research has been focused on determining the pathologic consequences of BRAF mutations, optimizing diagnostic techniques to identify these mutations, and developing therapeutic interventions to inhibit the function of this target in mutation-bearing tumors. Recently, advances have been made which are revolutionizing the standard of care for patients with BRAF mutant melanoma. This paper provides an overview on the pathogenic ramifications of mutant BRAF signaling, the latest molecular testing methods to detect BRAF mutations, and the most recent clinical data of BRAF pathway inhibitors in patients with melanoma and BRAF mutations. Finally, emerging mechanisms of resistance to BRAF inhibitors and ways of overcoming this resistance are discussed.
Intelligent web services (2002)

to mankind, and this universe is evolving. Many people now see Web Services as the next generation in the Web’s evolution. In the traditional Web model, the main activity is browsing: users follow hypertext links. In the Web Services model, the main activity is remote procedure calling: users invoke preprepared tasks that facilitate some useful activity. Examples of Web Services include services supporting
Palladium-Catalyzed Enantioselective C-3 Allylation of 3-Substituted-1H-Indoles Using Trialkylboranes (2006)

We have developed a new enantioselective C-3 allylation of 3-substituted indoles using allyl alcohol and trialkylboranes. Asymmetric syntheses of 3,3-disubstituted indolines and indolenines in enantiomeric excesses up to 90% have been achieved using the bulky borane 9-BBN-C6H13 as the promoter of the reaction. The dependence of the selectivity on the nature of the borane suggests that the boron reagent has a role beyond promoting ionization of the allyl alcohol. A protocol for oxidation of indolenines to oxindoles has also been developed and led to a formal synthesis of (-)-phenserine.
The elements of stem cell self-renewal: a genetic perspective (2003)

Every day, the body produces billions of new blood cells. Each of these is derived from a rare cell in the bone marrow called the hematopoietic stem cell (HSC). Because most mature blood cells have a limited lifespan, the ability of HSCs to self-renew and replenish the mature cell compartment is critical to sustaining life. While great progress has been made in isolating HSCs and defining their functional and phenotypic characteristics, the molecular mechanisms that regulate their self-renewal remain a mystery. Over the last few years, alterations in HSC frequency and self-renewal capacity in transgenic and knock-out mice have led to the identification of novel mediators of HSC homeostasis in vivo. These genetically modified mice have revealed that maintenance of survival, proliferation, quiescence, and normal telomere length all contribute to the self-renewal of HSCs. They also highlight the need to test in context of the normal microenvironment the role of signaling molecules such as Notch and Wnt, which have emerged recently as important regulators of HSC self-renewal. The emerging picture these data provide of the regulation of self-renewal in HSCs has provided a better understanding of the basic biology of stem cells and holds promise for designing strategies to improve bone marrow transplantation.
An Adolescent with Increased Plasma Methylmalonic Acid and Total Homocysteine (2017)

CONSIDER 1. Describe the metabolites that are increased in inherited intracellular vitamin B 12 (cobalamin) defects. 2. Explain the clinical and biochemical findings in vitamin B 12 deficiency. 3. List potential causes of vitamin B 12 deficiency.
Engineered Nanomaterials for Biophotonics Applications: Improving Sensing, Imaging, and Therapeutics (2003)

Advances in chemistry and physics are providing an expanding array of nanostructured materials with unique and powerful optical properties. These nanomaterials provide a new set of tools that are available to biomedical engineers, biologists, and medical scientists who seek new tools as biosensors and probes of biological fluids, cells, and tissue chemistry and function. Nanomaterials are also being used to develop optically controlled devices for applications such as modulated drug delivery as well as optical therapeutics. This review discusses applications that have been successfully demonstrated using nanomaterials including semiconductor nanocrystals, gold nanoparticles, gold nanoshells, and silver plasmon resonant particles.
Design and Synthesis of a Conformationally Restricted Trans Peptide Isostere Based on the Bioactive Conformations of Saquinavir and Nelfinavir (2001)

The design and synthesis of a new peptide isostere which contains a trans alkene core is described. The key step involves a Wadsworth-Emmons reaction between chiral aldehyde (2S)-9a and chiral phosphonate 7 under base-sensitive conditions to give a chiral enone (2R)-24a which was reduced to afford the desired trans alkene isosteres (2R,5R)-6a and (2R,5S)-6b (Scheme 6). A potential application of this isostere in the synthesis of HIV protease inhibitors is also discussed.
Smad7 protects against acute kidney injury by rescuing tubular epithelial cells from the G1 cell cycle arrest (2017)

Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored. Here, we report that Smad7 protects against AKI by rescuing the G1 cell cycle arrest of tubular epithelial cells (TECs) in ischemia/reperfusion-induced AKI in mice in which Smad7 gene is disrupted or restored locally into the kidney. In Smad7 gene knockout (KO) mice, more severe renal impairment including higher levels of serum creatinine and massive tubular necrosis was developed at 48 h after AKI. In contrast, restored renal Smad7 gene locally into the kidney of Smad7 KO mice protected against AKI by promoting TEC proliferation identified by PCNA+ and BrdU+ cells. Mechanistic studies revealed that worsen AKI in Smad7 KO mice was associated with a marked activation of TGF-β/Smad3-p21/p27 signaling and a loss of CDK2/cyclin E activities, thereby impairing TEC regeneration at the G1 cell cycle arrest. In contrast, restored Smad7 locally into the kidneys of Smad7 KO mice protected TECs from the G1 cell cycle arrest and promoted TEC G1/S transition via a CDK2/cyclin E-dependent mechanism. In conclusion, Smad7 plays a protective role in AKI. Blockade of TGF-β/Smad3-p21/p27-induced G1 cell cycle arrest may be a key mechanism by which Smad7 treatment inhibits AKI. Thus, Smad7 may be a novel therapeutic agent for AKI.
Physiological and pathological tremors and rhythmic central motor control (2000)

In recent years there has been increasing interest in oscillatory neural activity in the CNS and in the role that such activity may have in motor control. It is thought that physiological tremor may be a manifestation in the periphery of such central oscillatory activity and that some pathological tremors are the result of derangement of these oscillators. This review re-evaluates both early and recent studies on physiological and pathological tremors and other peripheral oscillations in order to gain a new perspective on the nature and function of their central progenitors. This approach, namely using tremor as a 'window' into the function of central oscillations, is particularly suited to human investigations because of the obvious limitations of direct central recording. It is argued that physiological tremor is likely to be multifactorial in origin, with contributions not only from CNS 10-Hz range oscillatory activity, but also from motor unit firing properties, mechanical resonances and reflex loop resonances. Different origins are likely to dominate under different conditions. While some pathological tremors appear to arise as a distortion of central or peripheral components of physiological tremor, others arise de novo, such as the pathological oscillation of 3- to 6-Hz parkinsonian tremor. CNS oscillations outside the 10-Hz range are also found to modulate limb activity in normal individuals, and oscillatory activity exists in other motor systems such as eye movements. Finally, it is shown how studies of peripheral oscillations may help develop hypotheses on the role of CNS oscillations in motor control, including the proposed 'binding' function of synchronized oscillations and the possibility that motor signals could be coded by frequency of modulating oscillation as well as by synaptic connectivity.
Transparent Hardware Management of Stacked DRAM as Part of Memory (2014)

Recent technology advancements allow for the integration of large memory structures on-die or as a die-stacked DRAM. Such structures provide higher bandwidth and faster access time than off-chip memory. Prior work has investigated using the large integrated memory as a cache, or using it as part of a heterogeneous memory system under management of the OS. Using this memory as a cache would waste a large fraction of total memory space, especially for the systems where stacked memory could be as large as off-chip memory. An OS managed heterogeneous memory system, on the other hand, requires costly usage-monitoring hardware to migrate frequently-used pages, and is often unable to capture pages that are highly utilized for short periods of time. This paper proposes a practical, low-cost architectural solution to efficiently enable using large fast memory as Part-of-Memory (PoM) seamlessly, without the involvement of the OS. Our PoM architecture effectively manages two different types of memory (slow and fast) combined to create a single physical address space. To achieve this, PoM implements the ability to dynamically remap regions of memory based on their access patterns and expected performance benefits. Our proposed PoM architecture improves performance by 18.4% over static mapping and by 10.5% over an ideal OS-based dynamic remapping policy.
Three Different Fates for Phosphinidenes Generated by Photocleavage of Phospha-Wittig Reagents ArPPMe3 (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThree Different Fates for Phosphinidenes Generated by Photocleavage of Phospha-Wittig Reagents ArPPMe3Shashin Shah, M. Cather Simpson, Rhett C. Smith, and John D. ProtasiewiczView Author Information Department of Chemistry Case Western Reserve University Cleveland, Ohio 44106-7708 Cite this: J. Am. Chem. Soc. 2001, 123, 28, 6925–6926Publication Date (Web):June 20, 2001Publication History Received6 March 2001Published online20 June 2001Published inissue 1 July 2001https://pubs.acs.org/doi/10.1021/ja015767lhttps://doi.org/10.1021/ja015767lrapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1651Altmetric-Citations102LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Carbon,Photochemical reactions,Photodissociation,Precursors,Redox reactions Get e-Alerts
A multicarrier allocation (MCA) scheme for variable-rate 3Gwireless systems (2000)

High spectral efficiency and flexible data rate access are the main focus of future wireless networks. Multiple channel allocation schemes have the potential of achieving this goal. By assigning multiple slots and/or multiple carriers to one user, it is possible to provide a flexible data rate with quite low complexity. In this article we propose a simple allocation scheme where each user is assigned a fixed group of carriers. These carriers are adaptively used depending on the interference situation within the system. The system performance in terms of average throughput is investigated for two different types of allocation schemes: a fully centralized scheme and a distributed one that uses frequency diversity as a mean of improving the user link quality. The obtained results show that both schemes improve the system throughput over single carrier allocation without affecting the capacity of the system in terms of number of users per cell.
Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT2R and cytoskeletal dysregulation (2015)

Patients with organ failure of vascular origin have increased circulating haematopoietic stem cells and progenitors (HSC/P). Plasma levels of angiotensin II (Ang-II), are commonly increased in vasculopathies. Hyperangiotensinemia results in activation of a very distinct Ang-II receptor set, Rho family GTPase members, and actin in bone marrow endothelial cells (BMEC) and HSC/P, which results in decreased membrane integrin activation in both BMEC and HSC/P, and in HSC/P de-adhesion and mobilization. The Ang-II effect can be reversed pharmacologically and genetically by inhibiting Ang-II production or signalling through BMEC AT2R, HSCP Ang-II receptor type 1 (AT1R)/AT2R or HSC/P RhoA, but not by interfering with other vascular tone mediators. Hyperangiotensinemia and high counts of circulating HSC/P seen in sickle cell disease (SCD) as a result of vascular damage, is significantly decreased by Ang-II inhibitors. Our data define for the first time the role of Ang-II HSC/P traffic regulation and redefine the haematopoietic consequences of anti-angiotensin therapy in SCD.
Non-peptide δ opioid agonists and antagonists (Part II) (1999)

A continuing effort in the development of non-peptide δ opioid agonists and antagonists has been seen in the last two years. The first non-peptide δ opioid antagonist naltrindole has represented for years the starting point for the design of novel potent and selective δ opioid ligands. Several research groups are still working on the framework of this prototype and have produced a large number of new derivatives with different in vitro and in vivo pharmacological activities. The discovery of TAN-67, BW373U86 and SNC 80 stimulated other lines of research aimed at synthesising analogues with better δ opioid agonist profile and suitable in vivo activity. Chemically unrelated compounds have also been disclosed deriving from the structural comparison of previously identified ligands. These studies have given further insights about the key determinants for the selective interaction with the δ opioid receptor (DOR). The availability of these tool compounds has allowed significant progression in the understanding of the pharmacology associated with the DOR. In addition to the possible use of selective δ opioid agonists as safe and effective pain relief agents, other interesting activities of possible clinical interest have been disclosed e.g., antiviral, cardioprotective and diuretic activity. Furthermore, many scientific reports confirmed the interesting pharmacological activities associated to the selective blockade of the DOR with antagonists e.g., immunosuppression and prevention of substance abuse. This review will focus on the above research activities, highlighting the most relevant literature and patent reports of the last two years. The medicinal chemistry and the competitive scenario related to non-peptide δ opioid ligands will be considered. Emphasis on the therapeutic potential of selective δ opioid ligands will also be discussed throughout the present review.
Robust Structured Light Coding for 3D Reconstruction (2007)

In this paper we present a new monochromatic pattern for a robust structured light coding based on the spatial neighborhood scheme using the M-array approach. The proposed pattern is robust as it allows a high error rate characterized by an average Hamming distance higher than 6. We tackle the design problem with the definition of a small set of symbols associated to simple geometrical primitives. One of these primitives embeds the local orientation of the pattern. This is helpful while performing the search for the relevant neighborhood during the decoding process. The aim of this work is to use this pattern for the real-time 3-D reconstruction of dynamic scenes, particularly in endoscopic surgery, with fast and reliable detection and decoding stages. Ongoing results are presented to assess both the capabilities of the proposed pattern and the reliable decoding algorithm with projections onto simple 3-D scenes and onto internal structures of a pig abdomen.
The Agrobacterium Ti Plasmids (2014)

Agrobacterium tumefaciens is a plant pathogen with the capacity to deliver a segment of oncogenic DNA carried on a large plasmid called the tumor-inducing or Ti plasmid to susceptible plant cells. A. tumefaciens belongs to the class Alphaproteobacteria, whose members include other plant pathogens (Agrobacterium rhizogenes), plant and insect symbionts (Rhizobium spp. and Wolbachia spp., respectively), human pathogens (Brucella spp., Bartonella spp., Rickettsia spp.), and nonpathogens (Caulobacter crescentus, Rhodobacter sphaeroides). Many species of Alphaproteobacteria carry large plasmids ranging in size from ∼100 kb to nearly 2 Mb. These large replicons typically code for functions essential for cell physiology, pathogenesis, or symbiosis. Most of these elements rely on a conserved gene cassette termed repABC for replication and partitioning, and maintenance at only one or a few copies per cell. The subject of this review is the ∼200-kb Ti plasmids carried by infectious strains of A. tumefaciens. We will summarize the features of this plasmid as a representative of the repABC family of megaplasmids. We will also describe novel features of this plasmid that enable A. tumefaciens cells to incite tumor formation in plants, sense and respond to an array of plant host and bacterial signal molecules, and maintain and disseminate the plasmid among populations of agrobacteria. At the end of this review, we will describe how this natural genetic engineer has been adapted to spawn an entire industry of plant biotechnology and review its potential for use in future therapeutic applications of plant and nonplant species.
Acceleration of fibrinolysis by the N-terminal peptide of alpha 2- plasmin inhibitor (1985)

When blood plasma containing the NH2-terminal 12-residue peptide (N- peptide) of alpha 2-plasmin inhibitor (alpha 2PI; alpha 2-antiplasmin) was clotted in the presence of calcium ions, the N-peptide and alpha 2PI were cross-linked to fibrin by activated coagulation factor XIII. The amount of N-peptide cross-linked to fibrin was proportional to the concentration of N-peptide present in plasma. On the other hand, the amount of alpha 2PI cross-linked to fibrin was decreased by the presence of N-peptide, and the decrease was in reverse relationship to the increase of cross-linking of N-peptide. Spontaneous fibrinolysis or fibrinolysis induced by tissue plasminogen activator was accelerated by the presence of N-peptide, and the acceleration was dependent on the concentrations of N-peptide and directly proportional to inhibition of alpha 2PI cross-linking exerted by N-peptide. The acceleration was more pronounced when the clot was compacted by platelet-mediated clot retraction or by a squeeze. Fibrinolysis of an alpha 2PI-deficient or a factor XIII-deficient plasma clot was not accelerated by N-peptide. These findings were substantiated in a purified system and support the previous proposal that alpha 2PI is cross-linked to fibrin at the glutamine residue that is next to the NH2-terminus of alpha 2PI, and this factor XIII-mediated cross-linking of alpha 2PI is significant in inhibition of physiologically occurring endogenous fibrinolysis.
Marketing in the New Millennium: Emerging Issues and Trends (2012)

Given the focus on marketing research, the present paper combines both the academic and the practitioner perspectives to highlight several issues and emerging trends that will shape the role of marketing research in the new millennium.These include redefinition of marketing researcher, the ongoing nature of marketing research, qualitative research, Internet marketing research, and ethical issues in marketing research.