gebhart/patrepeval huggingface dataset:
Structural Characterization of a Novel Cbl Phosphotyrosine Recognition Motif in the APS Family of Adapter Proteins (2005)

The Cbl adapter proteins typically function to down-regulate activated protein tyrosine kinases and other signaling proteins by coupling them to the ubiquitination machinery for degradation by the proteasome. Cbl proteins bind to specific tyrosine-phosphorylated sequences in target proteins via the tyrosine kinase-binding (TKB) domain, which comprises a four-helix bundle, an EF-hand calcium-binding domain, and a non-conventional Src homology-2 domain. The previously derived consensus sequence for phosphotyrosine recognition by the Cbl TKB domain is NXpY(S/T)XXP (X denotes lesser residue preference), wherein specificity is conferred primarily by residues C-terminal to the phosphotyrosine. Cbl is recruited to and phosphorylated by the insulin receptor in adipose cells through the adapter protein APS. APS is phosphorylated by the insulin receptor on a C-terminal tyrosine residue, which then serves as a binding site for the Cbl TKB domain. Using x-ray crystallography, site-directed mutagenesis, and calorimetric studies, we have characterized the interaction between the Cbl TKB domain and the Cbl recruitment site in APS, which contains a sequence motif, RA(V/I)XNQpY(S/T), that is conserved in the related adapter proteins SH2-B and Lnk. These studies reveal a novel mode of phosphopeptide interaction with the Cbl TKB domain, in which N-terminal residues distal to the phosphotyrosine directly contact residues of the four-helix bundle of the TKB domain.
The Relevance of Crystal Forms in the Pharmaceutical Field: Sword of Damocles or Innovation Tools? (2022)

This review is aimed to provide to an "educated but non-expert" readership and an overview of the scientific, commercial, and ethical importance of investigating the crystalline forms (polymorphs, hydrates, and co-crystals) of active pharmaceutical ingredients (API). The existence of multiple crystal forms of an API is relevant not only for the selection of the best solid material to carry through the various stages of drug development, including the choice of dosage and of excipients suitable for drug development and marketing, but also in terms of intellectual property protection and/or extension. This is because the physico-chemical properties, such as solubility, dissolution rate, thermal stability, processability, etc., of the solid API may depend, sometimes dramatically, on the crystal form, with important implications on the drug's ultimate efficacy. This review will recount how the scientific community and the pharmaceutical industry learned from the catastrophic consequences of the appearance of new, more stable, and unsuspected crystal forms. The relevant aspects of hydrates, the most common pharmaceutical solid solvates, and of co-crystals, the association of two or more solid components in the same crystalline materials, will also be discussed. Examples will be provided of how to tackle multiple crystal forms with screening protocols and theoretical approaches, and ultimately how to turn into discovery and innovation the purposed preparation of new crystalline forms of an API.
EVALUATION OF MICROPOROUS POLYSACCHARIDE HEMOSPHERES AS A NOVEL HEMOSTATIC AGENT IN OPEN PARTIAL NEPHRECTOMY: FAVORABLE EXPERIMENTAL RESULTS IN THE PORCINE MODEL (2004)

MPH provided rapid, effective and durable hemostasis in the porcine open partial nephrectomy model. Additional experimental and clinical evaluation is warranted to define the role of MPH assisted partial nephrectomy in humans.
Editorial: Survey and Experimental Analysis of Event Detection Techniques for Twitter (2016)

Twitter's popularity as a source of up-to-date news and information is constantly increasing. In response to this trend, numerous event detection techniques have been proposed to cope with the rate and volume of Twitter data streams. Although most of these works conduct some evaluation of the proposed technique, a comparative study is often omitted. In this paper, we present a survey and experimental analysis of state-of-the-art event detection techniques for Twitter data streams. In order to conduct this study, we define a series of measures to support the quantitative and qualitative comparison. We demonstrate the effectiveness of these measures by applying them to event detection techniques as well as to baseline approaches using real-world Twitter streaming data.
Searching for the Optimal Donor for Allogenic Adipose-Derived Stem Cells: A Comprehensive Review (2022)

Adipose-derived stem cells comprise several clinically beneficial qualities that have been explored in basic research and have motivated several clinical studies with promising results. After being approved in the European Union, UK, Switzerland, Israel, and Japan, allogeneic adipose-derived stem cells (darvadstrocel) have been recently granted a regenerative medicine advanced therapy (RMAT) designation by US FDA for complex perianal fistulas in adults with Crohn’s disease. This huge scientific step is likely to impact the future spread of the indications of allogeneic adipose-derived stem cell applications. The current knowledge on adipose stem cell harvest describes quantitative and qualitative differences that could be influenced by different donor conditions and donor sites. In this comprehensive review, we summarize the current knowledge on the topic and propose donor profiles that could provide the optimal initial quality of this living drug, as a starting point for further applications and studies in different pathological conditions.
Total Synthesis of an Immunosuppressive Glycolipid, (<i>2S,3S,4R</i>)-1-<i>O</i>- (α-<scp>d</scp>-Galactosyl)-2- tetracosanoylamino-1,3,4-nonanetriol (2005)

[reaction: see text] A practical and efficient total synthesis of (2S,3S,4R)-1-O-(alpha-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonanetriol, OCH 1b, a potential therapeutic candidate for Th1-mediated autoimmune diseases, is described. The synthesis incorporates direct alkylation onto epoxide 5 and stereospecific halide ion catalyzed alpha-glycosidation reaction. A key intermediate 10 was obtained in only eight steps and 37% overall yield from commercially available d-arabitol 2, and the total synthesis of 1b was accomplished in 12 steps and 19% overall yield. This method will enable the synthesis of a variety of phytosphingolipids, especially that with the shorter sphingosine side chain than 1a, in a highly stereoselective manner.
Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease (2020)

In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.
Effects of Angiotensin II Receptor Blockers on the Relationships Between Ambulatory Blood Pressure and Anti-Hypertensive Effects, Autonomic Function, and Health-Related Quality of Life (2009)

The aim of the present study was to examine the relationships between the anti-hypertensive effects, autonomic function, and health-related quality of life (HRQOL) following treatment of hypertensive subjects with angiotensin receptor blockers (ARBs) in hypertensives. Nineteen patients with hypertension were assigned randomly to daily treatment with ARBs. After 16 weeks of treatment, blood pressure (BP) and 24 h the ratio of low frequency to high frequency component (LF/HF), an index of sympathovagal balance were decreased by ARBs. The HRQOL scores improved during the study. In this study, ARB therapy was associated with an improvement in BP, autonomic function, and HRQOL.
Data from Cyclin-Dependent Kinase–Mediated Phosphorylation Plays a Critical Role in the Oncogenic Functions of PELP1 (2023)

&lt;div&gt;Abstract&lt;p&gt;Estrogen receptor (ER) signaling plays an important role in breast cancer progression, and ER functions are influenced by coregulatory proteins. PELP1 (proline-, glutamic acid–, and leucine-rich protein 1) is a nuclear receptor coregulator that plays an important role in ER signaling. Its expression is deregulated in hormonal cancers. We identified PELP1 as a novel cyclin-dependent kinase (CDK) substrate. Using site-directed mutagenesis and &lt;i&gt;in vitro&lt;/i&gt; kinase assays, we identified Ser&lt;sup&gt;477&lt;/sup&gt; and Ser&lt;sup&gt;991&lt;/sup&gt; of PELP1 as CDK phosphorylation sites. Using the PELP1 Ser&lt;sup&gt;991&lt;/sup&gt; phospho-specific antibody, we show that PELP1 is hyperphosphorylated during cell cycle progression. Model cells stably expressing the PELP1 mutant that lack CDK sites had defects in estradiol (E2)–mediated cell cycle progression and significantly affected PELP1-mediated oncogenic functions &lt;i&gt;in vivo&lt;/i&gt;. Mechanistic studies showed that PELP1 modulates transcription factor E2F1 transactivation functions, that PELP1 is recruited to pRb/E2F target genes, and that PELP1 facilitates ER signaling cross talk with cell cycle machinery. We conclude that PELP1 is a novel substrate of interphase CDKs and that its phosphorylation is important for the proper function of PELP1 in modulating hormone-driven cell cycle progression and also for optimal E2F transactivation function. Because the expression of both PELP1 and CDKs is deregulated in breast tumors, CDK-PELP1 interactions will have implications in breast cancer progression. Cancer Res; 70(18); 7166–75. ©2010 AACR.&lt;/p&gt;&lt;/div&gt;
Humanised monoclonal antibodies neutralise pertussis toxin by receptor blockade and reduced retrograde trafficking (2018)

Pertussis toxin (PTx) is a major protective antigen produced by Bordetella pertussis that is included in all current acellular vaccines. Of several well-characterized monoclonal antibodies binding this toxin, the humanised hu1B7 and hu11E6 antibodies are highly protective in multiple in vitro and in vivo assays. In this study, we determine the molecular mechanisms of protection mediated by these antibodies. Neither antibody directly binds the B. pertussis bacterium nor supports antibody-dependent complement cytotoxicity. Both antibodies, either individually or as a cocktail, form multivalent complexes with soluble PTx that bind the FcγRIIb receptor more tightly than antibody alone, suggesting that the antibodies may accelerate PTx clearance via immune complex formation. However, a receptor binding assay and cellular imaging indicate that the main mechanism used by hu11E6 is competitive inhibition of PTx binding to its cellular receptor. In contrast, the main hu1B7 neutralising mechanism appears to be inhibition of PTx internalisation and retrograde trafficking. We assessed the effects of hu1B7 on PTx retrograde trafficking in CHO-K1 cells using quantitative immunofluorescence microscopy. In the absence of hu1B7 or after incubation with an isotype control antibody, PTx colocalizes to organelles in a manner consistent with retrograde transport. However, after preincubation with hu1B7, PTx appears restricted to the membrane surface with colocalization to organelles associated with retrograde transport significantly reduced. Together, these data support a model whereby hu11E6 and hu1B7 interfere with PTx receptor binding and PTx retrograde trafficking, respectively.
Ultra-fine Cu Wiring Surrounded by Electroless-Plated Ni: Effective Structure for High Insulation Reliable Wiring Applicable to Panel Level Fabrication (2017)

Abstract Panel level packages such as 2.1D organic interposer and fan-out packages have been attracting the attention as a low cost substrate technology with high density fine wiring layers which interconnect multiple die set side by side. The Cu trench wirings for these packages are usually fabricated by fine and almost rectangular shaped pattern formation of insulation film followed by Ti/Cu sputtering as a seed layer formation, Cu electroplating and CMP. However, sputtering tends to be difficult to deposit on the side wall of almost rectangular shaped pattern. Another challenge is insulation reliability between ultra-fine wirings because electrochemical migration of Cu ion is one of the most serious problems for ultra-fine wirings. Here, instead of seed sputtering, we applied a Ni electroless plating because electroless plating is appropriate to panel process and Ni has high corrosion resistance. Ni seed was uniformly formed on both side wall and bottom of these rectangular patterns. After Cu electroplating, CMP and Ni selective electroless plating on Cu, Cu trench wiring fully surrounded by Ni in 1.5/1.5 μm of line and space was fabricated which has passed biased HAST over 200 h by suppressing corrosion of wiring.
Metal ion levels after metal-on-metal proximal femoral replacements (2005)

Metal-on-metal hip bearings are being implanted into younger patients. The consequence of elevated levels of potentially carcinogenic metal ions is therefore a cause for concern. We have determined the levels of cobalt (Co), chromium (Cr), titanium (Ti) and vanadium (Va) in the urine and whole blood of patients who had had metal-on-metal and metal-on-polyethylene articulations in situ for more than 30 years. We compared these with each other and with the levels for a control group of subjects. We found significantly elevated levels of whole blood Ti, Va and urinary Cr in all arthroplasty groups. The whole blood and urine levels of Co were grossly elevated, by a factor of 50 and 300 times respectively in patients with loose metal-on-metal articulations when compared with the control group. Stable metal-on-metal articulations showed much lower levels. Elevated levels of whole blood or urinary Co may be useful in identifying metal-on-metal articulations which are loose.
Supplementary Video #7 from Live-Cell Imaging of Invasion and Intravasation in an Artificial Microvessel Platform (2023)

&lt;p&gt;An HMVEC vessel under shear stress (12-15 dyne cm-2) extending an angiogenic sprout towards a cluster of MDA-MB-231 breast cancer cells.&lt;/p&gt;
Refined Solar Sail Force Model with Mission Application (2007)

The aim of this paper is to propose a refined mathematical model for describing the acceleration experienced by a&#13;&#13;\nsolar sail. Unlike the conventional model characterized by constant coefficients, the force coefficients of the sail are&#13;&#13;\nnow assumed to depend on the light incidence angle, the sail surface roughness, and the sun–sail distance. The new&#13;&#13;\nmodel is elaborated with the support of experimental data that show how the main variable affecting the force&#13;&#13;\ncoefficients is the light incidence angle. To emphasize the differences between the refined force model with respect to&#13;&#13;\nthe conventional one, a comparison is established through the analysis of a circle-to-circle interplanetary rendezvous&#13;&#13;\nproblem between coplanar orbits. The problem is solved using an indirect approach and the optimal steering law is approximated in polynomial form. A number of optimal trajectories toward Mars and Venus are simulated and the&#13;&#13;\nresults obtained are discussed as a function of the dimensionless sail loading parameter and the sail surface&#13;&#13;\nroughness.
Active M-ary sequential hypothesis testing (2010)

This paper considers a generalized sequential hypothesis testing problem in which a decision maker not only can sequentially trade off the sensing cost with the declaration precision, but also can exert control over the sensed information. Here, the decision maker's action impacts the sensing cost as well as outcome. Numerically solving an appropriate DP, it is shown that the sensing outcome has a dual role: (1) it immediately reduces the uncertainty in the decision maker's belief; and (2) it shapes the future belief via Bayes' rule. This paper focuses on sufficient conditions rendering the optimal sensing actions independent of the current and future belief vector, and reducing the problem to a classical (passive) hypothesis testing problem.
Evaluation of the safety and efficacy of micronized halofantrine in the treatment of semi-immune patients with acute,<i>Plasmodium falciparum</i>malaria (1996)

The efficacy of the standard formulation of halofantrine hydrochloride has been compromised by the formulation's irregular bio-availability. A micronized preparation of the drug has now been evaluated in the treatment of malaria in northern Tanzania. Overall, 100 patients with mild to moderate Plasmodium falciparum malaria were recruited and treated with the preparation over 18 h. Those weighing > 40 kg were each given three, 500-mg doses and those weighing less were given roughly equivalent doses/kg. The 95 evaluable patients were all successfully treated, with a mean fever-clearance time of 22.5 h (range 4-76 h) and a mean parasite-clearance time of 35.6 h (range 15-66 h). There were no relapses. Abdominal pain was the commonest adverse event reported (22 cases). A single patient died suddenly in the recovery phase; the cause of this event was not determined. Further studies are required to evaluate the pharmacokinetics of the halofantrine formulation under field conditions.
ChemInform Abstract: Efficient and Selective Azidation of per‐O‐Acetylated Sugars Using Ultrasound Activation: Application to the One‐Pot Synthesis of 1,2,3‐Triazole Glycosides. (2015)

Abstract An inexpensive, simple, and highly efficient process is developed for the selective anomeric azidation of protected sugars using ultrasound activation and an of iron catalyst.
Learning Compositional Visual Concepts with Mutual Consistency (2018)

Compositionality of semantic concepts in image synthesis and analysis is appealing as it can help in decomposing known and generatively recomposing unknown data. For instance, we may learn concepts of changing illumination, geometry or albedo of a scene, and try to recombine them to generate physically meaningful, but unseen data for training and testing. In practice however we often do not have samples from the joint concept space available: We may have data on illumination change in one data set and on geometric change in another one without complete overlap. We pose the following question: How can we learn two or more concepts jointly from different data sets with mutual consistency where we do not have samples from the full joint space? We present a novel answer in this paper based on cyclic consistency over multiple concepts, represented individually by generative adversarial networks (GANs). Our method, ConceptGAN, can be understood as a drop in for data augmentation to improve resilience for real world applications. Qualitative and quantitative evaluations demonstrate its efficacy in generating semantically meaningful images, as well as one shot face verification as an example application.
Similarity-Aware Network Embedding with Self-Paced Learning (2019)

Network embedding, which aims to learn low-dimensional vector representations for nodes in a network, has shown promising performance for many real-world applications, such as node classification and clustering. While various embedding methods have been developed for network data, they are limited in their assumption that nodes are correlated with their neighboring nodes with the same similarity degree. As such, these methods can be suboptimal for embedding network data. In this paper, we propose a new method named SANE, short for Similarity-Aware Network Embedding, to learn node representations by explicitly considering different similarity degrees between connected nodes in a network. In particular, we develop a new framework based on self-paced learning by accounting for both the explicit relations (i.e., observed links) and implicit relations (i.e., unobserved node similarities) in network representation learning. To justify our proposed model, we perform experiments on two real-world network data. Experiments results show that SNAE outperforms state-of-the-art embedding models on the tasks of node classification and node clustering.
flvi-1, a common integration domain of feline leukemia virus in naturally occurring lymphomas of a particular type (1990)

A locus in feline DNA, termed flvi-1, which may play an important role in the natural induction of lymphomas by feline leukemia virus (FeLV) was identified. Examination of a bank of 21 naturally occurring FeLV-positive feline lymphomas revealed that FeLV proviral integration occurs at flvi-1 in four independent tumors (19%). Independent integrations occurred within a 2.4-kilobase region of flvi-1, the probability of which by random chance can be estimated as 10(-16). Several lines of evidence, including sequence analysis of the long terminal repeat, demonstrated that proviruses integrated at flvi-1 are exogenously acquired and are oriented in the same transcriptional direction with respect to the locus. Molecularly cloned flvi-1 did not hybridize with probes representing several previously described proviral integration domains or with probes representing 10 oncogenes. The natural feline lymphomas examined in this study were heterogeneous with respect to tissue of origin, cell type, and number of monoclonal proviral integrations. The four tumors in which flvi-1 is interrupted were classified as members of a phenotypic subgroup containing seven lymphomas, i.e., at least four (57%) of seven lymphomas of this type contained FeLV proviral integration at flvi-1. Members of this phenotypic subgroup are non-T-cell lymphomas isolated from the spleen and contain an average of three proviruses, compared with an average of eight among all of the tumors examined. The small number of proviral integrations in tumors of this subgroup suggests that an early proviral integration event into flvi-1 can induce malignant change.
Openflow-controlled optical packet switching network with advanced handling of network dynamics (2014)

We have experimentally demonstrated Openflow-controlled optical packet switching network, while also proposed and demonstrated an advanced Openflow control mechanism to handle the network dynamics with prompt response.
IMMU-05. CCR2+ MYELOID-DERIVED SUPPRESSOR CELLS FROM MURINE GLIOMAS ARE SOURCED FROM THE BONE MARROW, SUPPRESS T CELL ACTIVATION, AND MIGRATE TO CCL2 (2021)

Abstract INTRODUCTION Mounting evidence suggests infiltrating immune-suppressive cells contribute to immune checkpoint inhibitor resistance and poor survival in Glioblastoma (GBM) patients. We have previously shown glioma-associated monocytic-myeloid derived suppressor cells (M-MDSCs) express chemokine receptors CCR2 and CX3CR1. Genetic and pharmacologic targeting of CCR2 promoted sequestration of M-MDSCs in the bone marrow and, in combination with PD-1 blockade, slowed progression of KR158 and 005GSC murine gliomas. This combination treatment also enhanced infiltration of IFNg-producing T cells that were less exhausted. Although CCR2+/CX3CR1+ cells display surface markers indicative of bone marrow-derived M-MDSCs, additional studies are needed to formally establish the source of these cells and to determine if they exhibit an immune-suppressive phenotype as well as migrate to the CCR2 ligands, CCL2 and/or CCL7. OBJECTIVE Evaluate the source, migration, and immune suppressive function of CCR2+/CX3CR1+ myeloid cells from glioma bearing mice. METHODS To identify the source of CCR2+/CX3CR1+ myeloid cells, chimeric wild type mice harboring bone marrow cells from transgenic CCR2WT/RFP/CX3CR1WT/GFP mice were generated. CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from either wild-type or CCR2WT/RFP/CX3CR1WT/GFP naïve and glioma-bearing mice in order to evaluate their immune suppressive phenotype and ability to migrate to CCL2 and CCL7. RESULTS CCR2+/CX3CR1+ cells are present in glioma isolates from chimeric mice, indicative of a bone marrow-derived cell population, and are detectable within the tumor microenvironment as early as 3 days post orthotopic implantation of KR158 cells; these cells accumulate as tumors increase in size (r=0.7605, p=0.007). CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor bearing mice suppress CD8+ T cell production of IFNg and migrate to CCL2 more efficiently than CCL7. CONCLUSION CCR2+/CX3CR1+ cells from glioma bearing mice are derived from the bone marrow and represent an immune suppressive population that migrates to CCL2.