gebhart/patrepeval huggingface dataset:
Data from The CDK4/6 Inhibitor LY2835219 Overcomes Vemurafenib Resistance Resulting from MAPK Reactivation and Cyclin D1 Upregulation (2023)

&lt;div&gt;Abstract&lt;p&gt;B-RAF selective inhibitors, including vemurafenib, were recently developed as effective therapies for melanoma patients with &lt;i&gt;B-RAF V600E&lt;/i&gt; mutation. However, most patients treated with vemurafenib eventually develop resistance largely due to reactivation of MAPK signaling. Inhibitors of MAPK signaling, including MEK1/2 inhibitor trametinib, failed to show significant clinical benefit in patients with acquired resistance to vemurafenib. Here, we describe that cell lines with acquired resistance to vemurafenib show reactivation of MAPK signaling and upregulation of cyclin D1 and are sensitive to inhibition of LY2835219, a selective inhibitor of cyclin-dependent kinase (CDK) 4/6. LY2835219 was demonstrated to inhibit growth of melanoma A375 tumor xenografts and delay tumor recurrence in combination with vemurafenib. Furthermore, we developed an &lt;i&gt;in vivo&lt;/i&gt; vemurafenib-resistant model by continuous administration of vemurafenib in A375 xenografts. Consistently, we found that MAPK is reactivated and cyclin D1 is elevated in vemurafenib-resistant tumors, as well as in the resistant cell lines derived from these tumors. Importantly, LY2835219 exhibited tumor growth regression in a vemurafenib-resistant model. Mechanistic analysis revealed that LY2835219 induced apoptotic cell death in a concentration-dependent manner in vemurafenib-resistant cells whereas it primarily mediated cell-cycle G&lt;sub&gt;1&lt;/sub&gt; arrest in the parental cells. Similarly, RNAi-mediated knockdown of cyclin D1 induced significantly higher rate of apoptosis in the resistant cells than in parental cells, suggesting that elevated cyclin D1 activity is important for the survival of vemurafenib-resistant cells. Altogether, we propose that targeting cyclin D1–CDK4/6 signaling by LY2835219 is an effective strategy to overcome MAPK-mediated resistance to B-RAF inhibitors in &lt;i&gt;B-RAF V600E&lt;/i&gt; melanoma. &lt;i&gt;Mol Cancer Ther; 13(10); 2253–63. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Bi–KOH. An efficient reagent for the coupling of nitroarenes to azo and azoxy compounds (2000)

A simple and inexpensive procedure for the coupling of nitroarenes to azoxy compounds with bismuth and potassium hydroxide in methanol at ambient temperature is achieved. When carried out under microwave irradiation it gives exclusively azo compounds in excellent yields.
A Computational Model to Predict Brain Trauma Outcome in the Intensive Care Unit (2020)

Abstract Objectives To predict short-term outcomes of critically ill patients with traumatic brain injury (TBI) by training machine learning classifiers on two large intensive care databases Design Retrospective analysis of observational data. Patients Patients in the multicenter Philips eICU and single-center Medical Information Mart for Intensive Care–III (MIMIC-III) databases with a primary admission diagnosis of TBI, who were in intensive care for over 24 hours. Interventions None. Measurements and Main Results We identified 1,689 and 126 qualifying TBI patients in eICU and MIMIC-III, respectively. Generalized Linear Models were used to predict mortality and neurological function at ICU discharge using features derived from clinical, laboratory, medication and physiological time series data obtained in the first 24 hours after ICU admission. Models were trained, tested and validated in eICU then validated externally in MIMIC-III. Model discrimination determined by area under the receiver operating characteristic curve (AUROC) analysis was 0.903 and 0.874 for mortality and neurological function, respectively. Performance was maintained when the models were tested in the independent MIMIC-III dataset (AUROC 0.958 and 0.878 for mortality and neurological function, respectively). Conclusions Computational models trained with data available in the first 24 h after admission accurately predict discharge outcomes in ICU stratum TBI patients.
Management of Late Corneal Haze Following Photorefractive Keratectomy (1995)

Subepithelial corneal haze and myopic regression are potential complications following excimer photorefractive keratectomy (PRK). There are many medical and surgical methods of managing this haze. We present a 37-year-old male myope who underwent PRK and subsequently developed central corneal haze late in the postoperative course. The haze was managed initially with topical medications with limited success. Mechanical superficial keratectomy was done to remove the superficial scar tissue but the haze returned necessitating repeat excimer laser PRK, using a transepithelial technique. The haze did not recur. Both mechanical superficial keratectomy and repeat excimer laser ablation may ameliorate haze. Success of these procedures may depend on the morphology of the haze and the patient's individual wound healing response.
Compartmentalization of Cells Bearing "Rheumatic" Cell Surface Antigens in Peripheral Blood and Tonsils in Rheumatic Heart Disease (1987)

Monoclonal antibodies that recognize "rheumatic" antigens of peripheral blood non-T cells were used to study the compartmentalization of such cells in peripheral blood and tonsils of individuals with rheumatic heart disease (RHD) and suitable control subjects. The peripheral blood of most (71%) of the 42 individuals with RHD contained cells reacting with monoclonal antibody 83S19.23 or 256S.10, whereas these cells were present in only 17% of the 41 control subjects (P less than .02). However, none of 21 individuals with RHD had such cells in their tonsils, although they were present in the tonsils of 50% of the 40 control subjects (P less than .03). These results may reflect a failure in RHD or organ-specific homing of cells with the epitopes recognized by the antibodies. The presence of these cells in tonsils may be important in the immune response to streptococcal pharyngeal infection, and their absence in RHD may be involved in the unusual immune responses characteristic of this disease.
c-Myc is a target of RNA-binding motif protein 15 in the regulation of adult hematopoietic stem cell and megakaryocyte development (2009)

RNA-binding motif protein 15 (RBM15) is involved in the RBM15-megakaryoblastic leukemia 1 fusion in acute megakaryoblastic leukemia. Although Rbm15 has been reported to be required for B-cell differentiation and to inhibit myeloid and megakaryocytic expansion, it is not clear what the normal functions of Rbm15 are in the regulation of hematopoietic stem cell (HSC) and megakaryocyte development. In this study, we report that Rbm15 may function in part through regulation of expression of the proto-oncogene c-Myc. Similar to c-Myc knockout (c-Myc-KO) mice, long-term (LT) HSCs are significantly increased in Rbm15-KO mice due to an apparent LT-HSC to short-term HSC differentiation defect associated with abnormal HSC-niche interactions caused by increased N-cadherin and beta(1) integrin expression on mutant HSCs. Both serial transplantation and competitive reconstitution capabilities of Rbm15-KO LT-HSCs are greatly compromised. Rbm15-KO and c-Myc-KO mice also share related abnormalities in megakaryocyte development, with mutant progenitors producing increased, abnormally small low-ploidy megakaryocytes. Consistent with a possible functional interplay between Rbm15 and c-Myc, the megakaryocyte increase in Rbm15-KO mice could be partially reversed by ectopic c-Myc. Thus, Rbm15 appears to be required for normal HSC-niche interactions, for the ability of HSCs to contribute normally to adult hematopoiesis, and for normal megakaryocyte development; these effects of Rbm15 on hematopoiesis may be mediated at least in part by c-Myc.
A New Electron-withdrawing Group Containing Poly(1,4-phenylenevinylene) (1998)

We have synthesized and investigated the electronic properties of poly[2-(2‘-ethylhexyloxy)-5-phenyl-1,4-phenylenevinylene], 12, and its methylsulfonyl derivative poly[2-(2‘-ethylhexyloxy)-5-(4‘ ‘-methylsulfonylphenyl)-1,4-phenylenevinylene], 13. Polymer 13 contains a second-order nonlinear optic chromophore which is in conjugation with the polymer backbone. Polymers 12 and 13 have been used as the electroluminescent (EL) layers in single layer light-emitting diodes (LEDs) (ITO/polymer/Al). We have found that when 12 was used, the LEDs had an external EL quantum efficiency of 0.01%. Attachment of the methylsulfonyl moiety to 12 to give 13 in an attempt to increase the electron affinity of the parent polymer was found to make no difference to the efficiency of the single layer EL devices and appeared qualitatively to reduce their lifetimes.
Binding and Mobility of the Cell Surface Receptors for 3,3′,5-Triiodo-L-Thyronine (1981)

A fluorescent derivative of the thyroid hormone 3,3'-triiodo-L-thyronine binds to cultured mouse fibroblasts; such binding is saturable. Video intensification fluorescence microscopy indicates that binding occurs at the plasma membrane. Diffusion coefficients, obtained by fluorescence photobleaching recovery, are consistent with binding to a protein receptor on the cell surface.
On factorization of biinfinite totally positive block Toeplitz matrices (1986)

We extend the work of Aissen, Schoenberg, Whitney, and Edrei, who characterized the symbol of a totally positive Toeplitz matrix, to characterizing the determinant of the symbol of a block Toeplitz totally positive matrix. As a consequence of our arguments we show that the symbol for the block Toeplitz case may be factored just as in the Toeplitz setting.
The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis (2014)

NCT00976599.
Accelerated deep self-supervised ptycho-laminography for three-dimensional nanoscale imaging of integrated circuits (2023)

Three-dimensional inspection of nanostructures such as integrated circuits is important for security and reliability assurance. Two scanning operations are required: ptychographic to recover the complex transmissivity of the specimen, and rotation of the specimen to acquire multiple projections covering the 3D spatial frequency domain. Two types of rotational scanning are possible: tomographic and laminographic. For flat, extended samples, for which the full 180° coverage is not possible, the latter is preferable because it provides better coverage of the 3D spatial frequency domain compared to limited-angle tomography. It is also because the amount of attenuation through the sample is approximately the same for all projections. However, both techniques are time consuming because of extensive acquisition and computation time. Here, we demonstrate the acceleration of ptycho-laminographic reconstruction of integrated circuits with 16 times fewer angular samples and 4.67 times faster computation by using a physics-regularized deep self-supervised learning architecture. We check the fidelity of our reconstruction against a densely sampled reconstruction that uses full scanning and no learning. As already reported elsewhere [ Opt. Express 28 , 12872 ( 2020 ) OPEXFF 1094-4087 10.1364/OE.379200 ], we observe improvement of reconstruction quality even over the densely sampled reconstruction, due to the ability of the self-supervised learning kernel to fill the missing cone.
ChemInform Abstract: The Synthesis and Binding Properties of Oligonucleotide Analogues Containing Diastereomerically Pure Conformationally Restricted Acetal Linkages. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Activated Polyacrylamides as Versatile Substrates for Postpolymerization Modification (2018)

The displacement of an activated leaving group in polymeric repeat units is a powerful method of postpolymerization modification. This strategy enables the synthesis of polymers otherwise unobtainable by direct polymerization as well as the preparation of a diverse array of macromolecular structures. We demonstrate that the activation of acrylamide through the introduction of two <i>tert</i>-butyloxycarbamate (Boc) groups followed by radical polymerization leads to a new class of activated polyacrylamides analogous to well-known activated polyacrylates. Transamidation of poly(di(Boc)-acrylamide) utilizing primary amines proceeds to high conversion under mild conditions, and the products can be readily purified. Less nucleophilic secondary amines and alcohols require more forcing conditions. We demonstrate the utility of this approach by preparing copolymers capable of on-demand gel formation and the synthesis of block polymers using controlled radical polymerization.
Nitric Oxide Suppresses Human T Lymphocyte Proliferation Through IFN-γ-Dependent and IFN-γ-Independent Induction of Apoptosis (1999)

Abstract Human normal and malignant T cells cease to proliferate, down-modulate Bcl-2 expression, and undergo apoptosis when cultured in the presence of NO-donor compounds (sodium nitroprusside and NOC12) for 48 h. At 72 h, cells that evade apoptosis start to proliferate again, overexpress both chains of the IFN-γR, and thus become susceptible to apoptosis in the presence of IFN-γ. By contrast, in the presence of IFN-γ, no apoptosis, but an increase of proliferation was displayed by control cultures of T cells not exposed to NO and not overexpressing IFN-γR chains. The NO-induced cell surface overexpression of IFN-γR chains did not affect the transduction of IFN-γ-mediated signals, as shown by the expression of the transcription factor IFN regulatory factor 1 (IRF-1). However, transduction of these signals was quantitatively modified, because IFN-γ induces enhanced levels of caspase-1 effector death in NO-treated cells. These findings identify NO as one of the environmental factors that critically govern the response of T cells to IFN-γ. By inducing the overexpression of IFN-γR chains, NO decides whether IFN-γ promotes cell proliferation or the induction of apoptosis.
2-<i>N</i>-Benzyl-2,6-dideoxy-2,6-imino-3,4-<i>O</i>-isopropylidene-3-<i>C</i>-methyl-<scp>D</scp>-allononitrile (2012)

X-ray crystallography firmly established the relative stereochemistry of the title compound, C(17)H(22)N(2)O(3). The absolute configuration was determined by use of 2-C-methyl-d-ribonolactone as the starting material. The compound exists as O-H⋯N hydrogen-bonded chains of mol-ecules running parallel to the a-axis.
Frontiers in computing for artificial intelligence (2022)

Abstract An emerging diversity of computational platforms offers many different approaches to adopting the paradigm of artificial intelligence to the study of electron-ion collisions. Here we review several leading candidates in this computational frontier and their workflows for experimental applications of artificial intelligence that may impact the future Electron-Ion Collider. We discuss the motivation for exploring novel methods to solve artificial intelligence and machine learning problems including with customized devices, quantum simulation, and heterogeneous computing systems. These technologies offer promising approaches to address some of the leading concerns of future computing that may impact the Electron-Ion Collider but they will require further development and testing in order to support future planning efforts.
Cytotoxic T-lymphocytes against malaria and tuberculosis: from natural immunity to vaccine design (1998)

1. Mycobacterium tuberculosis and the liver stage of Plasmodium falciparum are intracellular pathogens which are potentially susceptible to cytotoxic T-lymphocytes, a crucial component of the protective immune response to viral infections. Evidence from animal models points to a protective role for cytotoxic T-lymphocytes against M. tuberculosis and P. falciparum, but cytotoxic T-lymphocytes specific for these pathogens have been difficult to identify in man.2. Using a reverse immunogenetic approach, candidate epitopes from selected antigens of P. falciparum and M. tuberculosis were used to detect peptide-specific cytotoxic T-lymphocyte responses in individuals exposed to these pathogens. Cytotoxic T-lymphocyte activity was detected by the 51Cr release cytotoxicity assay and a sensitive ELISPOT assay for single-cell interferon-gamma release.3. In naturally exposed, partially immune Africans in The Gambia, eight largely conserved cytotoxic T-lymphocyte epitopes in P. falciparum, restricted by several different HLA class I alleles, were identified. Several epitopes were also recognized in Tanzanians and cytotoxic T-lymphocytes recognized endogenously processed antigen.4. In tuberculosis patients with HLA-B52, a CD8+ cytotoxic T-lymphocyte epitope was identified in ESAT-6, a secreted antigen specific for M. tuberculosis complex but absent in BCG. Cytotoxic T-lymphocytes exhibited HLA-B52-restricted peptide-specific interferon-gamma release and lytic activity and recognized endogenously processed antigen.5. These studies demonstrate that CD8+ cytotoxic T-lymphocytes specific for mycobacterial and protozoal antigens are induced during natural infections in humans. The identification of these T-cells endorses current strategies to develop cytotoxic T-lymphocyte-inducing vaccines against P. falciparum and M. tuberculosis and highlights candidate antigens for inclusion in subunit vaccines.
PNPLA3 and HSD17B13 gene variants exert opposite effects on fatty liver phenotypes: results from the FLAG cohort (2020)

Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition common in overweight and obese individuals. The PNPLA3 p.I148 M variant represents a major genetic determinant of NAFLD progression. Recently the loss-of-function HSD17B13 polymorphism rs72613567 was reported to be hepatoprotective in patients with chronic liver diseases (Abdul-Husn et al. NEJM 2018). Here we investigate the effects of the PNPLA3 and HSD17B13 variant on NAFLD phenotypes in a "real life" cohort of German NAFLD patients.
Lipo-oligosaccharidic antigen from Mycobacterium gastri. Complete structure of a novel C4-branched 3,6-dideoxy-.alpha.-xylo-hexopyranose (1994)

The following incomplete structure, alpha-X-(1-->3)-[beta-L-Xylp-(1-->4)]6-3-O-Me-alpha-Rhap-(1- ->3)- beta-D-Galp-(1-->3)-beta-D-Glcp-(1-->4)-2-O-acyl-alpha-D-Glcp-(1<-->1)-4 ,6-di-O-acyl-alpha-D-Glcp, was previously established for the antigenic lipo-oligosaccharide typifying Mycobacterium gastri, namely, LOS-III. The partial structure of the distal monosaccharide (X) was assigned as 3,6-dideoxy-4-C-(1,3-di-O-methylpropyl)-alpha-hexopyranose, which corresponds to a new-found monosaccharide in nature [Gilleron M., Vercauteren J., & Puzo G. (1993) J. Biol. Chem. 268, 3168-3179]. This article reports the complete structure of X, which was determined from the FAB-MS and 2D NMR analysis of the peracetylated LOS-III. The comparative analyses of the native and per-O-acetylated LOS-III FAB-MS spectra revealed, for the monosaccharide X, a molecular mass of 370 Da and five hydroxyl groups that could be acetylated. Additionally, the 1D 1H NMR spectrum of the per-O-acetylated LOS-III showed a dramatically increased dispersion of the protons, which resonated between 3 and 4 ppm in the spectrum of the underivatized LOS-III. Thus, thanks to 2D NMR sequences (COSY, HOHAHA, HMQC, HMQC-HOHAHA, and HMBC), the complete assignment of the 1H and 13C signals was achieved. Starting from the quaternary C4 resonance, the spin system of the C-alkyl chain was assigned, allowing us to propose the following structure, 3,6-dideoxy-4-C-(1,3-dimethoxy-4,5,6,7-tetrahydroxyheptyl)-alpha-x ylo- hexopyranose. The xylo configuration was established from the ROESY spectrum.
PAPPI: Personalized analysis of plantar pressure images using statistical modelling and parametric mapping (2020)

Quantitative analyses of plantar pressure images typically occur at the group level and under the assumption that individuals within each group display homogeneous pressure patterns. When this assumption does not hold, a personalized analysis technique is required. Yet, existing personalized plantar pressure analysis techniques work at the image level, leading to results that can be unintuitive and difficult to interpret. To address these limitations, we introduce PAPPI: the Personalized Analysis of Plantar Pressure Images. PAPPI is built around the statistical modelling of the relationship between plantar pressures in healthy controls and their demographic characteristics. This statistical model then serves as the healthy baseline to which an individual's real plantar pressures are compared using statistical parametric mapping. As a proof-of-concept, we evaluated PAPPI on a cohort of 50 hallux valgus patients. PAPPI showed that plantar pressures from hallux valgus patients did not have a single, homogeneous pattern, but instead, 5 abnormal pressure patterns were observed in sections of this population. When comparing these patterns to foot pain scores (i.e. Foot Function Index, Manchester-Oxford Foot Questionnaire) and radiographic hallux angle measurements, we observed that patients with increased pressure under metatarsal 1 reported less foot pain than other patients in the cohort, while patients with abnormal pressures in the heel showed more severe hallux valgus angles and more foot pain. Also, incidences of pes planus were higher in our hallux valgus cohort compared to the modelled healthy controls. PAPPI helped to clarify recent discrepancies in group-level plantar pressure studies and showed its unique ability to produce quantitative, interpretable, and personalized analyses for plantar pressure images.
Biosynthesis of Costunolide, Dihydrocostunolide, and Leucodin. Demonstration of Cytochrome P450-Catalyzed Formation of the Lactone Ring Present in Sesquiterpene Lactones of Chicory (2002)

Chicory (Cichorium intybus) is known to contain guaianolides, eudesmanolides, and germacranolides. These sesquiterpene lactones are postulated to originate from a common germacranolide, namely (+)-costunolide. Whereas a pathway for the formation of germacra-1(10),4,11(13)-trien-12-oic acid from farnesyl diphosphate had previously been established, we now report the isolation of an enzyme activity from chicory roots that converts the germacrene acid into (+)-costunolide. This (+)-costunolide synthase catalyzes the last step in the formation of the lactone ring present in sesquiterpene lactones and is dependent on NADPH and molecular oxygen. Incubation of the germacrene acid in the presence of 18O2 resulted in the incorporation of one atom of 18O into (+)-costunolide. The label was situated at the ring oxygen atom. Hence, formation of the lactone ring most likely occurs via C6-hydroxylation of the germacrene acid and subsequent attack of this hydroxyl group at the C12-atom of the carboxyl group. Blue light-reversible CO inhibition and experiments with cytochrome P450 inhibitors demonstrated that the (+)-costunolide synthase is a cytochrome P450 enzyme. In addition, enzymatic conversion of (+)-costunolide into 11(S),13-dihydrocostunolide and leucodin, a guaianolide, was detected. The first-mentioned reaction involves an enoate reductase, whereas the formation of leucodin from (+)-costunolide probably involves more than one enzyme, including a cytochrome P450 enzyme.