gebhart/patrepeval huggingface dataset:
Development of a novel class of B-RafV600E-selective inhibitors through virtual screening and hierarchical hit optimization (2012)

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-Raf(V600E) mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we describe the development of novel B-Raf(V600E) selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC(50) values were identified as B-Raf(V600E) inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC(50) values with selectivity for B-Raf(V600E)in vitro and exclusive cytotoxicity against B-Raf(V600E) harboring cancer cells.
An 18F-Labeled PSMA Ligand for PET/CT of Prostate Cancer: First-in-Humans Observational Study and Clinical Experience with 18F-JK-PSMA-7 During the First Year of Application (2019)

In preclinical trials, the recently developed tracer 2-methoxy-<sup>18</sup>F-DCFPyL (<sup>18</sup>F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of <sup>18</sup>F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. <b>Methods:</b> In an Institutional Review Board-approved pilot study, the initial clinical utility of PET/CT imaging with <sup>18</sup>F-JK-PSMA-7 was directly compared with <sup>68</sup>Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer. The 2 PSMA tracers were administered to each patient less than 3 wk apart. Next, we analyzed the data of 75 consecutive patients who had undergone clinical <sup>18</sup>F-JK-PSMA-7 PET/CT imaging for tumor localization of biochemical recurrence (BCR). <b>Results:</b> The pilot study in 10 patients who were examined with both PSMA tracers demonstrated that <sup>18</sup>F-JK-PSMA-7 was at least equivalent to <sup>68</sup>Ga-PSMA-11. All unequivocally <sup>68</sup>Ga-PSMA-11-positive lesions could be also detected using <sup>18</sup>F-JK-PSMA-7, and in 4 patients additional suspected PSMA-positive lesions were identified (1 patient changed from PSMA-negative to PSMA-positive). In patients with BCR (after prostatectomy or radiotherapy), the capacity of <sup>18</sup>F-JK-PSMA-7 PET/CT to detect at least one PSMA-positive lesion was 84.8%. The prostate-specific antigen (PSA)-stratified detection rate of <sup>18</sup>F-JK-PSMA-7 after prostatectomy varied among 54.5% (6/11 patients; PSA < 0.5 μg/L), 87.5% (14/16 patients; PSA 0.5-2 μg/L), and 90.9% (20/22 patients; PSA > 2 μg/L). <b>Conclusion:</b> The tracer <sup>18</sup>F-JK-PSMA-7 was found to be safe and clinically useful. We demonstrated that <sup>18</sup>F-JK-PSMA-7 was not inferior when directly compared with <sup>68</sup>Ga-PSMA-11 in a pilot study but indeed identified additional PSMA-avid suspected lesions in oligometastasized patients with BCR. In a subsequent analysis of a clinical cohort of BCR patients, <sup>18</sup>F-JK-PSMA-7 was useful in tumor localization. <sup>18</sup>F-JK-PSMA-7 is recommended for future prospective trials.
Cytosolic and nuclear caspase-8 have opposite impact on survival after liver resection for hepatocellular carcinoma (2013)

Assessment of TRAIL-receptor expression patterns may have therapeutic implications for the use of TRAIL receptor agonists in HCC therapy. Tumor-specific nuclear localisation of caspase-8 in HCC suggests an apoptosis-independent function of caspase-8 and correlates with patient survival.
8B.02 (2015)

Objective: It is well known that congestive heart failure (CHF) is characterized by an increased adrenergic tone and by an impaired baroreflex sympathetic and vagal control. In recent years have been developed additional therapeutic options, baroreflex activation therapy (BAT), capable to antagonize the sympathetic overactivity. It has been reported in CHF patients a significant reduction in muscle sympathetic nerve activity (MSNA) after 6 months BAT. Whether the effects on sympathetic and clinical variables were maintained chronically is unknown. Design and method: Eleven CHF patients (NYHA class III, left ventricular ejection fraction < 40%, with optimized and stable medical therapy and no active resinchronization therapy) have been evaluated at baseline and after 6 and 24 months BAT follow-up. During each step we collected clinical parameters, HYHA class, six-minute hall walk distance (6MHW), quality of life from the Minnesota Living with Heart Failure Questionnaire score (QOL), LVEF (3D echo), B-type natriuretic peptide (BNP), estimated glomerular filtration rate (eGFR), MSNA by microneurography, and baro reflex sensitivity (variated Kienbaum's method). Results: Two patients died during long-term follow-up (pneumoniae and acute HF). In the surviving 9 the beneficial effects observed at 6 months (MSNA -28%; BRS +100%; 6MWD +22.7%; LVEF +10%; QOL +37.2%) were maintained 21.5 ± 4.2 months (MSNA -31.6%,p < 0.001; BRS +100%,p < 0.001; 6MWD +19%,p = 0.01; LVEF +2.4%,p < 0.01; QOL +42.7%p < 0.01). A slight but not significant reduction was observed in blood pressure, heart rate, BNP and eGFR values. Hospitalization was not necessary after BAT. Conclusions: BAT provides long-term reduction in sympathetic activity and improvement in baroreflex sensitivity. This is accompanied by an improvement in clinical status, quality of life and functional capacity and by a reduction in rates of hospitalization.
Full transmission and reflection of waves propagating through a maze of disorder (2016)

Multiple scattering of waves in disordered media is often seen as a nightmare whether it be for communication, imaging, or focusing purposes. The ability to control wave propagation through scattering media is thus of fundamental interest in many domains of wave physics, ranging from optics or acoustics to medical imaging or telecommunications. Thirty years ago, it was shown theoretically that a properly designed combination of incident waves could be fully transmitted through (or reflected by) a disordered medium. Although this remarkable prediction has attracted a great deal of attention, open and closed channels have never been accessed experimentally. Here, we study the propagation of elastic waves through a disordered elastic waveguide. Thereby, we present experimental measurements of the full S-matrix across a disordered elastic wave guide. To that aim, laser-ultrasonic techniques have been used in order to obtain a satisfying spatial sampling of the field at the input and output of the scattering medium. The unitarity of the S-matrix is investigated and the eigenvalues of the transmission matrix are shown to follow the expected bimodal distribution. Full transmission and reflection of waves propagating through disorder are obtained for the first time experimentally. The wave-fields associated to these open and closed channels are imaged within the scattering medium to highlight the interference effects operating in each case.
ChemInform Abstract: Inhibition of α‐Mannosidases by Seven‐Carbon Sugars: Synthesis of Some Seven‐Carbon Analogues of Mannofuranose. (1993)

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.
Gestalt: Unifying fault localization for networked systems (2013)

Researchers have proposed many algorithms for localizing faults in networked systems, but it is unclear which algorithm is best suited for a given network; the performance of these algorithms differs markedly for different networks. We develop a framework that can explain these differences by anatomizing the algorithms into their basic choices and analyzing these choices with respect to six defining characteristics of real networks. Our analysis also reveals that no existing algorithm simultaneously provides good localization accuracy and low computational overhead. Based on our insights, we develop a new algorithm called Gestalt. To perform well across a range of networks, Gestalt combines the good choices of existing algorithms and with a new method to explore the space of possible faults in a way that is both low overhead and robust to noise. We apply it to three real, diverse networks: an email network, a peer-topeer messaging system, and an ISP network. In each case, Gestalt has either significantly higher localization accuracy or an order of magnitude faster running time. For example, when applied to Lync [2], Gestalt localizes faults with the same accuracy as Sherlock [6], while reducing fault localization time from days to 23s on a single system.
Personalized Federated Learning via Convex Clustering (2022)

We propose a parametric family of algorithms for personalized federated learning with locally convex user costs. The proposed framework is based on a generalization of convex clustering in which the differences between different users' models are penalized via a sum-of-norms penalty, weighted by a penalty parameter <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$A$</tex> . The proposed approach enables “automatic” model clustering, without prior knowledge of the hidden cluster structure, nor the number of clusters. Analytical bounds on the weight parameter, that lead to simultaneous personalization, generalization and automatic model clustering are provided. The solution to the formulated problem enables personalization, by providing different models across different clusters, and generalization, by providing models different than the per-user models computed in isolation. We then provide an efficient algorithm based on the Parallel Direction Method of Multipliers (PDMM) to solve the proposed formulation in a federated server-users setting. Numerical experiments corroborate our findings. As an interesting byproduct, our results provide several generalizations to convex clustering.
Diversity of T-cell antigen receptor variable genes used by mycosis fungoides cells. (1992)

The expression of T-cell antigen receptor beta-chain variable genes (V beta) was evaluated in 28 cases of mycosis fungoides. A novel polymerase chain reaction (PCR) technique was used to associate expression of particular V beta genes with monoclonal T-cell populations. In addition, the same biopsies used for PCR analysis were also examined for reactivity with a panel of seven monoclonal antibodies that specifically recognized V beta proteins from four different families. Only three cases clearly stained with the antibodies, a result consistent with a diverse set of V beta genes being used. This was confirmed by PCR analysis, which indicated that V beta genes from many different families were expressed by these tumors. Preferential use of the V beta 8 family, which had been previously use of the V beta 8 family, which had been previously reported for this disease, was not evident among the cases analyzed.
Fish freshness estimation using eye image processing under white and UV lightings (2017)

A non-destructive method of estimating the freshness of fish is required for appropriate price setting and food safety. In particular, for determining the possibility of eating raw fish (sashimi), freshness estimation is critical. We studied such an estimation method by capturing images of fish eyes and performing image processing using the temporal changes of the luminance of pupil and iris. To detect subtle non-visible changes of these features, we used UV (375 nm) light illumination in addition to visible white light illumination. Polarization and two-channel LED techniques were used to remove strong specular reflection from the cornea of the eye and from clear-plastic wrap used to cover the fish to maintain humidity. Pupil and iris regions were automatically detected separately by image processing after the specular reflection removal process, and two types of eye contrast were defined as the ratio of mean and median pixel values of each region. Experiments using 16 Japanese dace (Tribolodon hakonensis) at 23℃ and 85% humidity for 24 hours were performed. The eye contrast of raw fish increase non-linearly in the initial period and then decreased; however, that of frozen-thawed fish decreased linearly throughout 24 hours, regardless of the lighting. Interestingly, the eye contrast using UV light showed a higher correlation with time than that using white light only in the case of raw fish within the early 6- hour period postmortem. These results show the possibility of estimating fish freshness in the initial stage when fish are eaten raw using white and UV lightings.
Neurokinin-1 Receptor Signalling Impacts Bone Marrow Repopulation Efficiency (2013)

Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R) deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1(-/-)) showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1 (-/-), Tac4 (-/-) and Tac1 (-/-)/Tac4 (-/-) mice) repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment.
Large-scale assembly of highly stretchable and conductive polydopamine-generated poly (ethylene terephthalate)/ polyurethane fabric through the self-assembly intercalation strategy for superior sensing (2022)

Smart wearable electronic devices with superb sensing performance have aroused superb attention in recent years. However, designing an admirable strain sensor with the excellent balance between superior sensitivity and excellent stretchability remains a major challenge. Herein, we developed a conductive polydopamine-coated poly (ethylene terephthalate)/polyurethane fabric as the wearable strain sensor with the layered generating structure and the cooperative effect of carboxylated carbon nanotubes and reduced graphene oxide via self-assembly intercalation process. Obviously, the cooperative conductive effect of conductive fillers endowed the fabric with a superb integration of tunable strain sensitivity (0–265.48), outstanding electromechanical performance, great stretchability (0–220%), excellent heating performance, and long-term stability and repeatability under different strains over 2500 cycles. Especially, the as-prepared sensor was used for the detection of tiny body movements and vigorous human motions, indicating its further impressive prospect in wearable smart electronics. Therefore, such the proposed sensor with the layered generating structure exhibited remarkable potential for developing the flexible wearable electronic device of integrated sensing property and excellent electromechanical performance.
Phase equilibria and structural investigations in the Ni-poor part of the system Al–Ge–Ni (2012)

The ternary phase diagram Al-Ge-Ni was investigated between 0 and 50 at.% Ni by a combination of differential thermal analysis (DTA), powder- and single-crystal X-ray diffraction (XRD), metallography and electron probe microanalysis (EPMA). Ternary phase equilibria and accurate phase compositions of the equilibrium phases were determined within two partial isothermal sections at 400 and 700 °C, respectively. The two binary intermediate phases AlNi and Al<sub>3</sub>Ni<sub>2</sub> were found to form extended solid solutions with Ge in the ternary. Three new ternary phases were found to exist in the Ni-poor part of the phase diagram which were designated as τ<sub>1</sub> (oC24, CoGe<sub>2</sub>-type), τ<sub>2</sub> (at approximately Al<sub>67.5</sub>Ge<sub>18.0</sub>Ni<sub>14.5</sub>) and τ<sub>3</sub> (cF12, CaF<sub>2</sub>-type). The ternary phases show only small homogeneity ranges. While τ<sub>1</sub> was investigated by single crystal X-ray diffraction, τ<sub>2</sub> and τ<sub>3</sub> were identified from their powder diffraction pattern. Ternary phase reactions and melting behaviour were studied by means of DTA. A total number of eleven invariant reactions could be derived from these data, which are one ternary eutectic reaction, six transition reactions, three ternary peritectic reactions and one maximum. Based on the measured DTA values three vertical sections at 10, 20 and 35 at.% Ni were constructed. Additionally, all experimental results were combined to a ternary reaction scheme (Scheil diagram) and a liquidus surface projection.
Power-Efficient Dimensionality Reduction for Distributed Channel-Aware Kalman Tracking Using WSNs (2009)

Estimation of nonstationary dynamical processes is of paramount importance in various applications including target tracking and navigation. The goal of this paper is to perform such tasks in a distributed fashion, using data collected at power-limited sensors which either communicate with a fusion center (FC) over noisy links, or, communicate with each other over nonideal channels in an ad hoc setting. In FC-based wireless sensor networks (WSNs) with a prescribed power budget, linear dimensionality reducing operators which account for the sensor-to-FC channel are derived per sensor to minimize the mean-square error (MSE) of Kalman filtered state estimates formed at the FC. Using these operators and state predictions fed back from the FC online, sensors reduce the dimensionality of their local innovation sequences and communicate them to the FC where tracking estimates are corrected. Analytical and numerical results advocate that the novel channel-aware distributed tracker outperforms competing alternatives. In ad hoc WSNs deployed to perform distributed tracking, one sensor broadcasts reduced-dimensionality data per time slot, according to a prespecified transmission order. The dimensionality reducing operators employed by the broadcasting sensor are selected to meet its transmit-power budget, while minimizing the state estimation MSE of the sensor with the lowest receiving SNR. Based on the received reduced-dimensionality data from the broadcasting sensor, every sensor in range performs the MSE optimal tracking. Corroborating distributed target tracking simulations based on distance-only observations illustrate that the novel scheme provides sensors with accurate estimates at affordable communication cost.
Time-domain evidence for an excitonic insulator (2013)

Time- and angle-resolved photoemission spectroscopy with a high–harmonic- generation source is used to classify the potential excitonic insulator 1T-TiSe2 and the reference Peierls-Mott insulator 1T-TaS2 on the basis of the melting times of “spectroscopic order parameters”.
Blind Verification of Elevated Platelet Autoantibodies in Serum of Schizophrenic Patients – Part I: Young Subjects (2009)

In the adult schizophrenic patients, the PAA blood test remains valid for patients who were hospitalized for less than 3 years. Drug treatment, length of disease and age can be assumed to reduce the PAA level considerably.
FAA's CAT III Feasibility Program: Status and Accomplishments (1995)

The FAA has been conducting a Category III (CAT III)
feasibility program. This paper reviews both planning
and technical aspects of the program. The background
and schedule for the CAT III program is summarized,
includmg the relationship to the FAA’s Local Area
Augmentation System (LAAS) and Wide Area
Augmentation System (WAAS) programs. Results and
insights gamed from four of the CAT III flight test
campaigns are summarized, and several major remaining
work areas for CAT III feasibility are discussed.
Studies on Isoniazid Derivatives through a Medicinal Chemistry Approach for the Identification of New Inhibitors of Urease and Inflammatory Markers (2019)

A library of thiosemicarbazide derivatives of isoniazid 3-27, was synthesized and evaluated for their anti-inflammatory and urease inhibition activities, by using in vitro bioassays. Among these compounds 9, 10, 12, 21, and 26 were identified as new derivatives. Prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) and infections caused by Helicobacter pylori (ureolytic bacteria), are the two most significant causes of gastric and peptic ulcers. We focused on the identification of the dual inhibitors of inflammation and urease enzyme. Compound 23 was identified as the best dual inhibitor of inflammation (ROS; IC<sub>50</sub> = 12.3 µg/mL), and urease enzyme inhibition activity (IC<sub>50</sub> = 22.4 µM). Many of these compounds showed comparable activities to the standard anti-inflammatory drug (ibuprofen, IC<sub>50</sub> = 11.2 µg/mL) and urease inhibitor (thiourea/acetohydraoxamic acid, IC<sub>50</sub> = 21.1/20.3 µM). Compound 12 was found to be the most potent urease inhibitor (IC<sub>50</sub> = 12.3 µM) and good inhibitor of inflammation (IC<sub>50</sub> = 27.7 µg/mL). Compounds 19, 11, 13, 9, 17, 10, and 16, were also found to be potent inhibitors of urease. Cytotoxicity was also evaluated and all the compounds were found to be non-cytotoxic, except compound 18 and the parent drug isoniazid (IC<sub>50</sub> = 29.5 and 28.5 µM, respectively).
MultiText Legal Experiments at TREC 2007. (2007)

For the legal track we used the Wumpus search engine and investigated several methods that have proven successful in other domains, including cover density ranking and Okapi BM25 ranking. In addition to the traditional bag-of-words model we used boolean terms and character 4-grams. Pseudo-relevance feedback was e ected using logistic regression on character 4-grams. Some runs speci cally excluded documents returned by the boolean query so as to increase the number of such documents in the pool. While our runs were all marked as manual, this was only because the process was not fully automated and several tuning parameters were set after we viewed the data; no data-speci c tuning was performed in conguring the system for our runs. Our best performing runs used a combination of all of the above-mentioned techniques.