gebhart/patrepeval huggingface dataset:
Callipeltoside A: Total Synthesis, Assignment of the Absolute and Relative Configuration, and Evaluation of Synthetic Analogues (2002)

The total synthesis of the novel antitumor agent callipeltoside A, as well as several analogues, is accomplished and allows assignment of the stereochemistry not previously established. A convergent strategy is employed wherein the target is dissected into three units-the core macrolactone, the sugar callipeltose, and a cyclopropyl bearing chain. The strategy for the synthesis of the macrolactone derives from employment of diastereoselective aldol reactions that emanate from an 11 carbon piece. The stereochemistry of the latter derives from the chiral pool and two asymmetric reactions-a ketone reduction using CBS-oxazaborolidine and a Pd catalyzed asymmetric allylic alkylation (AAA). The novelty of the latter protocol is its control of regioselectivity as well as absolute configuration. The trisubstituted olefin is generated using an alkene-alkyne coupling to create a trisubustituted olefin with complete control of geometry. The excellent chemo- and regioselectivity highlights the synthetic potential of this new ruthenium catalyzed process. The macrolactonization employs in situ formation of an acylketene generated by the thermolysis of a m-dioxolenone. Two strategies evolved for attachment of the side chain-one based upon olefination and a second upon olefin metathesis. The higher efficiency of the latter makes it the method of choice. A novel one pot olefin metathesis-Takai olefination protocol that should be broadly applicable is developed. The sugar is attached by a glycosylation by employing the O-trichloroacetimidate. This route provided both C-13 epimers of the macrolactone by using either enantiomeric ligand in the Pd AAA reaction. It also provided both trans-chlorocyclopropane diastereomers of callipeltoside A which allows the C-20 and C-21 configuration to be established as S and R, respectively. The convergent nature of the synthesis in which the largest piece, the macrolatone, require only 16 linear steps imparts utility to this strategy for the establishment of the structure-activity relationship. Initial biological testing demonstrates the irrelevance of the chloro substituent and the necessity of the sugar.
Performance of Alternate Blowing Agents to Chlorofluorocarbons in RIM Structural and Elastomeric Polyurethane Foams (1990)

On examine l'utilisation d'eau comme gonflant dans les mousses de polyurethannes lors du moulage par injection des reactifs. On etudie les techniques de mise en œuvre et les proprietes physiques
Picturing the body in spatial neglect (2013)

Spatial neglect-a syndrome in which there is asymmetric perception, orienting, or response associated with functional disability(1)-has a potentially devastating effect on self-care and safety after stroke. Still, it frequently goes unrecognized.(2) How is this possible? A tremendously disabling disorder should be easy to detect. In this issue of Neurology(®), Rousseaux et al.(3) present a study that may give us an inkling of the problem: we may be assessing the eyes, but not the body.
Zapożyczenia czeskie w słowniku Pfula : terminologia naukowa (2015)

Niniejsza praca ukazuje rozwój zapożyczeń czeskich, a właściwie terminologii naukowej pochodzenia czeskiego w języku górnołużyckim od połowy XIX wieku aż po czasy współczesne. Podstawę ekscerpcji materiału stanowił wydany w 1866 roku Łužiski serbski słownik Křesćana Bohuwěra Pfula. Analizą objęte zostały hasła kwalifikowane przez samego leksykografa jako bohemizmy (łącznie 1494 wyrazy hasłowe), które następnie zostały porównane z materiałem zawartym w późniejszych słownikach górnołużyckich oraz w górnołużyckim korpusie tekstowym HOTKO (w pojedynczych przypadkach również w innych tekstach źródłowych). Takie podejście pozwoliło w pełni pokazać losy zapożyczeń czeskich w górnołużycczyźnie. Jednocześnie dało choćby częściową odpowiedź na pytanie, dlaczego niektóre zapożyczenia nie utrzymały się w języku, a pośrednio pozwoliło także pokazać rozwój górnołużyckiej terminologii naukowej w ogóle. Zebrany materiał został podzielony na dwie grupy: terminologię naukową i słownictwo ogólne. Niniejsza rozprawa stanowi pierwszą część opracowania zagadnienia rozwoju zapożyczeń czeskich w języku górnołużyckim. Z 432 terminów pochodzenia czeskiego zachowało się do dziś 132, czyli 30%. Najwięcej utrzymało się nazw geograficznych (13 z 22 zapożyczeń) i zoologicznych (39 z 74 zapożyczeń), tj. odpowiednio 59% i około 53% wszystkich przejętych nazw geograficznych i zoologicznych. Następne w kolejności są nazwy geologiczne (9 z 26, czyli około 35%), terminy z zakresu literatury, mitologii, sztuki i architektury (13 z 38, czyli ponad 34%), nazwy botaniczne (20 z 59, czyli około 34%), terminy matematyczne (5 z 19, czyli ponad 26%), terminy z różnych dyscyplin naukowych (6 z 27, czyli ponad 22%), a także terminy lingwistyczne (3 z 14, czyli ponad 21%), anatomiczne i medyczne (10 z 48, czyli ponad 20%) oraz fizyczne i astronomiczne (3 z 15, czyli 20%). W mniejszym stopniu zachowały się nazwy chemiczne (10 z 70, czyli ponad 14%) i terminy filozoficzne (1 z 11, czyli 9%). Nie utrzymał się żaden termin z zakresu prawa. Wiele z zachowanych bohemizmów występuje jako terminy samodzielne, pozostałe jako synonimy innych nazw, np. internacjonalizmów lub germanizmów. Część z nich notowana jest w słownikach jako przestarzałe, niektóre zaś należy chyba uznać za takie ze względu na fakt, że jako ostatnie rejestrują je pojedyncze słowniki z lat pięćdziesiątych ubiegłego wieku.
Cryogenic stabilization of high vapor pressure samples for surface analysis under ultrahigh vacuum conditions (1999)

A novel form of ultrahigh vacuum (UHV) cryogenic stabilization has been used to obtain high-resolution x-ray photoelectron spectroscopy (XPS) data from a complex amine, 1,8-bis(dimethylamino)naphthalene, whose solid phase exhibited at room temperature an unacceptably high rate of sublimation. Protonated versions of the amine exhibit hydrogen bonding. Electron spectroscopy for chemical analysis chemical shifts can be used to describe the strength and asymmetry of hydrogen bonding formed in proton sponge complexes. Analyzing the binding energy shifts of N (1s) induced by the presence of this hydrogen bonding required obtaining corresponding XPS spectra from the nonprotonated (reference) sample, but the reference sample sublimes under even moderate vacuum conditions. The combined results suggest that other high vapor pressure materials, particularly those that were previously considered to be too corrosive for routine analysis, can be cryogenically stabilized for surface analysis under similar UHV conditions.
AER: Adaptive energy efficient routing protocol for network of flying robots monitoring over disaster hit area (2012)

In large scale disasters like earth quake it is necessary to undertake post disaster mitigation activities abruptly in order to for reduce damage and for early post-disaster rehabilitation and reconstruction. This paper proposes a design framework for an optimal control strategy to efficiently perform surveillance over a wide disaster hit area using a network of flying robots to determine the extent of damage promptly. The main focus of the paper is to develop an adaptive and energy efficient routing strategy with less power dissipation and delay compared to traditional routing algorithms. This protocol efficiently determines the best route by taking account of the residual energy, signal strength and various environmental factors. Simulation results show that the proposed routing scheme achieves much higher performance than the classical routing protocols.
Protection against Anoikis and Down-regulation of Cadherin Expression by a Regulatable β-Catenin Protein (2002)

beta-Catenin signaling plays a key role in a variety of cellular contexts during embryonic development and tissue differentiation. Aberrant beta-catenin signaling has also been implicated in promoting human colorectal carcinomas as well as a variety of other cancers. To study the molecular and cellular biological functions of beta-catenin in a controlled fashion, we created a regulatable form of activated beta-catenin by fusion to a modified estrogen receptor (ER) ligand binding domain (G525R). Transfection of tissue culture cells with expression vectors encoding this hybrid protein allows the signal transduction function of beta-catenin to be induced by the synthetic estrogen, 4-hydroxytamoxifen, leading to regulated activation of a beta-catenin-lymphocyte enhancer-binding factor-dependent reporter gene as well as induction of endogenous cyclin D1 expression. The activation of ER-beta-catenin signaling rescues RK3E cells from anoikis and correlates with an increased phosphorylation of mitogen-activated protein kinase. The inhibition of anoikis by ER-beta-catenin can be abolished by a mitogen-activated protein kinase pathway inhibitor, PD98059. Evidence is also provided to show that ER-beta-catenin down-regulates cadherin protein levels. These findings support a key role for activated beta-catenin signaling in processes that contribute to tumor formation and progression.
Efficient duty-cycle mismatch compensation in digital transmitter (2014)

This paper presents an efficient mitigation approach for duty cycle mismatch of in-phase and quadrature upconversion signals in digital transmitters. This approach is supported by a mathematical analysis of the baseband equivalent impact of duty cycle mismatch. An efficient digital pre-distortion method is proposed to eliminate the distortion impact. Simulation results show that, for both 64-QAM and 256-QAM modulation schemes, the error-vector-magnitude can be improved from -25.1dB to less than -55dB, which leaves substantial design margin for other non-idealities distorting the transmitted signal.
The synergy of BET inhibitors with aurora A kinase inhibitors in MYCN-amplified neuroblastoma is heightened with functional TP53 (2021)

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared to single agents, these combinations cooperated to decrease levels of N-myc. We treated both TP53-wild type and mutant, MYCN-amplified cell lines with the BETi JQ1 and the AURKAi Alisertib. The combination had improved efficacy in the TP53-WT context, notably driving apoptosis in both genetic backgrounds. JQ1+Alisertib combination treatment of a MYCN-amplified, TP53-null or TP53-restored genetically engineered mouse model of NBL prolonged survival better than either single agent. This was most profound with TP53 restored, with marked tumor shrinkage and apoptosis induction in response to combination JQ1+Alisertib. BETi+AURKAi in MYCN-amplified NBL, particularly in the context of functional TP53, provided anti-tumor benefits in preclinical models. This combination should be studied more closely in a pediatric clinical trial.
Structural Genomics of Pathogenic Protozoa: an Overview (2008)

The Structural Genomics of Pathogenic Protozoa (SGPP) Consortium aimed to determine crystal structures of proteins from trypanosomatid and malaria parasites in a high throughput manner. The pipeline of target selection, protein production, crystallization, and structure determination, is sketched. Special emphasis is given to a number of technology developments including domain prediction, the use of "co-crystallants," and capillary crystallization. "Fragment cocktail crystallography" for medical structural genomics is also described.
Tri‐ tert ‐Butylcyclopropenyl Tetrafluoroborate (2003)

Abstract Tri‐ tert ‐Butylcyclopropenyl tetrafluoroborate reactant: 74.6 g. (0.700 mole) of 1‐chloro‐2,2‐dimethylpropane reactant: 71.7 g. (0.533 mole) of tert ‐butylacetyl chloride intermediate: dineopentyl ketone intermediate: α,α′‐ Dibromodineopentyl ketone intermediate: 20.0 g. (0.120 mole) of di‐ tert ‐butylcyclopropenone product: tri‐ tert ‐butylcyclopropenyl tetrafluoroborate
Discovery of Growth Differentiation Factor 15 as an Erythroblast-Secreted Regulator of Hepcidin with Very High Level Expression in Patients with Thalassemia. (2006)

Abstract Iron overload causes considerable morbidity associated with thalassemia due to inappropriate suppression of the iron regulator, hepcidin. One possible explanation for this phenomenon is that protein(s) that are normally secreted into the marrow microenvironment by erythroblasts become endocrine signals in patients with thalassemia due to the myeloproliferative nature of the disease. To test this hypothesis, progenitor and precursor cell transcriptional profiles were generated with Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays using primary erythroblasts cultured from 15 healthy human donors. For this study, informatic analyses were focused upon 54 members of the TGF–B/BMP superfamily. Among the subset of genes identified by this screen, evidence for high-level expression of a gene named growth differentiation factor 15 (GDF15) was discovered in the precursor cell profiles. Quantitative PCR, Western, and ELISA analyses confirmed expression and secretion of GDF15 during erythroblast maturation. GDF15 is an apoptosis-associated protein expressed primarily by the placenta. To determine whether GDF15 serves as a regulator of hepcidin expression, hepcidin expression assays were performed using a human hepatoma cell line (HuH-7). BMP2 and BMP4 were studied for comparison. Addition of BMP2 and BMP4 (range 10,000–500,000 pg/ml) resulted in dosed increases in hepcidin mRNA (5–30 fold). At the concentrations of GDF15 normally found in human blood (500 pg/ml), a 2-fold increase in the expression of hepcidin was measured compared to matched cultures containing no supplemental GDF15. However, GDF15 dosed to levels above 5,000 pg/ml resulted in a significant reduction in hepcidin expression. Next, plasma levels of GDF15 were measured in the peripheral blood of 162 donors (donor groups included healthy controls, sickle-cell syndromes, thalassemia syndromes, and other causes of anemia) to determine whether plasma GDF15 levels are dysregulated in thalassemia. Plasma samples from 21 hereditary hemochromatosis donors provided evidence that significantly elevated GDF15 expression is not associated with iron overload in the absence of erythroid pathology. Compared with mean plasma GDF15 levels of 536±222 pg/ml among the control samples, only patients with thalassemia intermedia, thalassemia major, and HbE-beta thalassemia showed significantly elevated plasma levels of GDF15 (9 donors; mean GDF15 24,600 pg/ml; range 8,980–75,100 pg/ml; p&lt;0.01). Elevated ferritin levels (&gt;370 ug/L) were noted in each of those patients regardless of their transfusion or chelation history. These novel findings suggest that GDF15 is secreted from human erythroblasts, released into the circulation at extremely high levels in thalassemia patients, and contributes to iron overloading in those patients by suppressing hepcidin expression.
Image-Guided Nanosystems for Targeted Delivery in Cancer Therapy (2012)

Current challenges in early detection, limitations of conventional treatment options, and the constant evolution of cancer cells with metastatic and multi-drug resistant phenotypes require novel strategies to effectively combat this deadly disease. Nanomedical technologies are evolving at a rapid pace and are poised to play a vital role in diagnostic and therapeutic interventions - the so-called "theranostics" - with potential to advance personalized medicine. In this regard, nanoparticulate delivery systems can be designed with tumor seeking characteristics by utilizing the inherent abnormalities and leaky vasculature of solid tumors or custom engineered with targeting ligands for more specific tumor drug targeting. In this review we discuss some of the recent advances made in the development of multifunctional polymeric nanosystems with an emphasis on image-guided drug and gene delivery. Multifunctional nanosystems incorporate variety of payloads (anticancer drugs and genes), imaging agents (optical probes, radio-ligands, and contrast agents), and targeting ligands (antibodies and peptides) for multi-pronged cancer intervention with potential to report therapeutic outcomes. Through advances in combinatorial polymer synthesis and high-throughput testing methods, rapid progress in novel optical/radiolabeling strategies, and the technological breakthroughs in instrumentation, such as hybrid molecular and functional imaging systems, there is tremendous future potential in clinical utility of theranostic nanosystems.
Polyhalogenated heterocyclic compounds. Part 47.1 Syntheses of multi-substituted pyridine derivatives from pentafluoropyridine (2001)

A sequence of nucleophilic aromatic substitution and palladium catalysed coupling processes were used to transform pentafluoropyridine into various pyridine derivatives that bear five different functional groups.
Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol. (1992)

A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf PSK stimulation by nerve growth factor (NGF) in PC12 pheochromocytoma cells. Mitogen stimulation of Raf kinase was measured by determination of Raf hyperphosphorylation and activity towards exogenous substrates and both of these events were inhibited in cells expressing M17 Ras. In contrast, tyrosine phosphorylation of a direct substrate of activated tyrosine kinase receptors, phospholipase C-gamma 1 (PLC-gamma 1), was unaffected. These data indicate that tyrosine phosphorylation of PLC-gamma 1 is not sufficient for growth induction in NIH3T3 cells and that Ras mediates signal transfer from activated membrane receptors to Raf kinases in the cytosol. As activated Raf induced differentiation in PC12 cells expressing M17 Ras we conclude that Raf kinase activation may be sufficient to account for this aspect of NGF function.
Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies and redistribute to hundreds of nuclear sites after stress (1995)

The promyelocytic leukemia protein fused to the retinoic acid receptor alpha in t(15;17) acute promyelocytic leukemia, the primary biliary cirrhosis autoantigen, Sp100, as well as the incompletely characterized protein NDP55, are co-localized in specific immunohistochemically defined nuclear domains (ND10), which are potential equivalents of ultrastructurally defined nuclear bodies. We investigated whether the distribution of these proteins depends on environmental conditions and whether ND10 correlate with nuclear bodies. Certain nuclear bodies and ND10 react in a similar way and share antigens. Interferon exposure doubled the number of ND10 and increased the frequency of nuclear bodies, whereas herpes simplex virus infection or heat shock modify both. Redistribution of ND10-associated proteins to hundreds of small sites throughout the chromatin was inducible by stress in the form of heat shock and exposure to Cd++ ions. The change of distribution was rapid and independent of protein synthesis, and thus not part of the classical heat shock response. The very rapid redistribution of these proteins after heat shock, together with the development of ND10 upon interferon activation, raises the possibility that ND10 represent storage sites of certain matrix proteins readily accessible throughout the chromatin in response to stress or other effectors that induce global nuclear changes.
Exploring Social Posterior Collapse in Variational Autoencoder for Interaction Modeling (2021)

Multi-agent behavior modeling and trajectory forecasting are crucial for the safe navigation of autonomous agents in interactive scenarios. Variational Autoencoder (VAE) has been widely applied in multi-agent interaction modeling to generate diverse behavior and learn a low-dimensional representation for interacting systems. However, existing literature did not formally discuss if a VAE-based model can properly encode interaction into its latent space. In this work, we argue that one of the typical formulations of VAEs in multi-agent modeling suffers from an issue we refer to as social posterior collapse, i.e., the model is prone to ignoring historical social context when predicting the future trajectory of an agent. It could cause significant prediction errors and poor generalization performance. We analyze the reason behind this under-explored phenomenon and propose several measures to tackle it. Afterward, we implement the proposed framework and experiment on real-world datasets for multi-agent trajectory prediction. In particular, we propose a novel sparse graph attention message-passing (sparse-GAMP) layer, which helps us detect social posterior collapse in our experiments. In the experiments, we verify that social posterior collapse indeed occurs. Also, the proposed measures are effective in alleviating the issue. As a result, the model attains better generalization performance when historical social context is informative for prediction.
Identification of a Novel Pharmacophore for Peptide Toxins Interacting with K+ Channels (2005)

KappaM-conotoxin RIIIK blocks TSha1 K+ channels from trout with high affinity by interacting with the ion channel pore. As opposed to many other peptides targeting K+ channels, kappaM-RIIIK does not possess a functional dyad. In this study we combine thermodynamic mutant cycle analysis and docking calculations to derive the binding mode of kappaM-conotoxin RIIIK to the TSha1 channel. The final model reveals a novel pharmacophore, where no positively charged side chain occludes the channel pore. Instead the positive-charged residues of the toxin form a basic ring; kappaM-RIIIK is anchored to the K+ channel via electrostatic interactions of this basic ring with the loop and pore helix residues of the channel. The channel amino acid Glu-354 is likely to be a fundamental determinant of the selectivity of kappaM-RIIIK for the TSha1 channel. The Cgamma-OH of Hyp-15 is in contact with the carbonyls of the selectivity filter, disturbing the charge distribution pattern necessary for the coordination of K+ ions. This novel, experimentally based pharmacophore model proves the existence of diverse binding modes of peptidic toxins to K+ channels and underlines the role of intermolecular electrostatic interactions involving channel loop side chains in determining the selectivity of toxins for specific K+ channel types.