gebhart/patrepeval huggingface dataset:
Synthesis, SAR, and Series Evolution of Novel Oxadiazole-Containing 5-Lipoxygenase Activating Protein Inhibitors: Discovery of 2-[4-(3-{(R)-1-[4-(2-Amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915) (2015)

The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and potent inhibition of LTB4 synthesis in human whole blood (IC50 < 100 nM). Optimization of binding and functional potencies, as well as physicochemical properties resulted in the identification of compound 69 (BI 665915) that demonstrated an excellent cross-species drug metabolism and pharmacokinetics (DMPK) profile and was predicted to have low human clearance. In addition, 69 was predicted to have a low risk for potential drug-drug interactions due to its cytochrome P450 3A4 profile. In a murine ex vivo whole blood study, 69 demonstrated a linear dose-exposure relationship and a dose-dependent inhibition of LTB4 production.
Bis(phosphane oxide) Adducts of Rh2(MTPA)4 — Kinetics and Chirality Discrimination (2004)

Abstract The symmetrical bis(phosphane oxide) 1 and its chiral derivatives 2 and 3 form a variety of adduct species with the dirhodium complex [Rh−Rh] which can be identified by low‐temperature 1 H and 31 P NMR spectroscopy by using varying [Rh−Rh] :ligand ratios. The asymmetric bis(phosphane oxide) 3 shows a distinct preference for binding through the Ph 2 P=O (P a ) as compared to the t Bu(Ph)P=O (P b ) functionality due to the bulky tert ‐butyl group. The chiral bis(phosphane oxides) 2 and 3 form complex mixtures of various adduct species. Nevertheless, it is possible to monitor enantiomeric compositions from various NMR signal duplications at 213 K and even at room temperature or slightly elevated temperatures. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)
Thermal modeling and management in ultrathin chip stack technology (2002)

This paper presents a thermal modeling for power management of a new three-dimensional (3-D) thinned dies stacking process. Besides the high concentration of power dissipating sources, which is the direct consequence of the very interesting integration efficiency increase, this new ultra-compact packaging technology can suffer of the poor thermal conductivity (about 700 times smaller than silicon one) of the benzocyclobutene (BCB) used as both adhesive and planarization layers in each level of the stack. Thermal simulation was conducted using three-dimensional (3-D) FEM tool to analyze the specific behaviors in such stacked structure and to optimize the design rules. This study first describes the heat transfer limitation through the vertical path by examining particularly the case of the high dissipating sources under small area. First results of characterization in transient regime by means of dedicated test device mounted in single level structure are presented. For the design optimization, the thermal draining capabilities of a copper grid or full copper plate embedded in the intermediate layer of stacked structure are evaluated as a function of the technological parameters and the physical properties. It is shown an interest for the transverse heat extraction under the buffer devices dissipating most the power and generally localized in the peripheral zone, and for the temperature uniformization, by heat spreading mechanism, in the localized regions where the attachment of the thin die is altered. Finally, all conclusions of this analysis are used for the quantitative projections of the thermal performance of a first demonstrator based on a three-levels stacking structure for space application.
Prevention of Type 2 Diabetes Mellitus (2003)

Abstract As the global epidemic of type 2 diabetes continues unabated with the associated increasing socioeconomic burden, attention is increasingly turning to the important issue of prevention. Type 2 diabetes is one part of the broader medical paradigm associated with cardiovascular disease—the metabolic syndrome. Population‐directed prevention is aimed at reducing the risk factor burden in both the general population and susceptible communities or ethnic groups. To date, there has been limited attention paid to dealing with the foreseen epidemic of type 2 diabetes. Targeted prevention involves higher intensity intervention strategies aimed at subjects with impaired glucose tolerance and impaired fasting glucose (prediabetes). There are now four major studies investigating lifestyle intervention in subjects with impaired glucose tolerance and all have shown significant reduction in progression to type 2 diabetes. Over the last 20 years there have been a number of targeted pharmacological intervention studies in subjects reported, with mixed results. Recently troglitazone, acarbose, and metformin have been shown to reduce progression to diabetes. There are now large targeted studies underway, examining the possible prevention of diabetes with ramipril, rosiglitazone, nateglinide, valsartan, and insulin. Whether lifestyle strategies or pharmacological intervention will also reduce cardiovascular outcomes is unknown. Possible but speculative mechanisms for diabetes prevention with pharmacological interventions are discussed. Many other issues remain to be addressed and these are the following: (1) How best to implement risk factor reduction (behavioral modification) in the population at large, in susceptible communities and ethnic groups? (2) How to achieve and maintain lifestyle changes targeted at prediabetic subjects? (3) What is the long‐term value and safety of pharmacological treatment of otherwise asymptomatic prediabetic subjects? (4) Are there benefits of combination therapies with lifestyle and pharmacological interventions in prediabetic individuals? (5) What are the socioeconomic costs and benefits, including cardiovascular protection, of implementing diabetes prevention programs?
Figure S8 from AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-x<sub>L</sub>, Induces Tumor Regression in Hematologic Cancer Models without Dose-limiting Thrombocytopenia (2023)

&lt;p&gt;Figure S8&lt;/p&gt;
Method for radiometric calibration of an endoscope's camera and light source (2008)

An endoscope is a commonly used instrument for performing minimally invasive visual examination of the tissues inside the body. A physician uses the endoscopic video images to identify tissue abnormalities. The images, however, are highly dependent on the optical properties of the endoscope and its orientation and location with respect to the tissue structure. The analysis of endoscopic video images is, therefore, purely subjective. Studies suggest that the fusion of endoscopic video images (providing color and texture information) with virtual endoscopic views (providing structural information) can be useful for assessing various pathologies for several applications: (1) surgical simulation, training, and pedagogy; (2) the creation of a database for pathologies; and (3) the building of patient-specific models. Such fusion requires both geometric and radiometric alignment of endoscopic video images in the texture space. Inconsistent estimates of texture/color of the tissue surface result in seams when multiple endoscopic video images are combined together. This paper (1) identifies the endoscope-dependent variables to be calibrated for objective and consistent estimation of surface texture/color and (2) presents an integrated set of methods to measure them. Results show that the calibration method can be successfully used to estimate objective color/texture values for simple planar scenes, whereas uncalibrated endoscopes performed very poorly for the same tests.
Radiofrequency echographic multi-spectrometry for the in-vivo assessment of bone strength: state of the art—outcomes of an expert consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) (2019)

New approaches for improved bone strength and fracture risk estimations are needed for a better management of osteoporotic patients. In this context, REMS represents a valuable approach for osteoporosis diagnosis and fracture risk prediction.
Digital Beamforming Algorithm for 5G Low-SHF Band Massive MIMO (2019)

Towards furthering the industrial revolution, the concept of a new cellular network began to be drawn up around 2010 as the fifth generation (5G) mobile wireless communication system. One of the main differences between the fourth generation (4G) mobile communication system Long Term Evolution (LTE) and 5G new radio (NR) is the frequency bands utilized. 5G NR assumes higher frequency bands. Effective utilization of the higher frequency bands needs to resolve the technical issue of the larger path-loss. Massive multiple-input multiple-output (Massive MIMO) beamforming (BF) technology contributes to overcome this problem, hence further study of Massive MIMO BF for each frequency band is necessary toward high-performance and easy implementation. In this paper, then, we propose a Massive MIMO method with fully-digital BF based on two-tap precoding for low super high frequency (SHF) band downlink (DL) transmissions (called as Digital FBCP). Additionally, three intersite coordination algorithms for Digital FBCP are presented for multi-site environments and one of the three algorithms is enhanced. It is shown that Digital FBCP achieves better throughput performance than a conventional algorithm with one-tap precoding. Considering performance of intersite coordination as well, it is concluded that Digital FBCP can achieve around 5 Gbps in various practical environments.
Successful nelarabine and venetoclax treatment of a relapsed/refractory mediastinal myeloid sarcoma with clonal TCR rearrangement (2021)

Myeloid sarcomas represent a heterogeneous group of diseases with a tumoral presentation of acute myeloid leukemia. The clinical presentation of these hematologic cancers is typically aggressive and thus rapidly fatal in the absence of treatment, which relies on intensive chemotherapy that is sometimes followed by allogeneic hematopoietic stem-cell transplant (AHSCT). However, the global treatment strategy for these lesions is currently not well established. We report the case of a patient presenting with a highly refractory mediastinal myeloid sarcoma with uncommon morphologic and phenotypic characteristics and a clonal TCR rearrangement. The patient's disease was progressive despite multiple courses of intensive chemotherapy and a combination of nelarabine and venetoclax finally led to a complete metabolic response consolidated by an AHSCT. This treatment regimen, which has never been reported before, was very well tolerated especially on the neurologic and hematologic levels. This case underlines the clinical, histologic and molecular heterogeneity of what is called myeloid sarcoma and the importance of next-generation sequencing analysis of the tumor mass with both myeloid and lymphoid panels to better classify this rare entity and identify therapeutic targets.
LC-MS/MS Assay Validation for a New Immune Modulator, JHL45, and its Major Metabolite in Plasma: Application to Pharmacokinetic Studies in Rats (2009)

JHL45, a novel immune modulator for anti-atopic dermatitis and allergic airway disease, was synthesized from decursin isolated from Angelica gigas. In order to conduct a pharmacokinetic study of JHL45, an analytical method, ideally one that uses a minimal amount of biological sample must first be validated. In this study, a HPLC-MS/MS method was developed and validated for the quantification of JHL45 and its major metabolite, (+)-decursinol, from 10 <TEX>${\mu}L$</TEX> of rat plasma. JHL45 was stable under the analysis conditions, and intra- and inter-day accuracies exceeded 90.06%, with a precision variability <TEX>${\leq}$</TEX> 13.16% for each analyte. The mean values for Cmax, AUC8h, half-life of JHL45 in rats after intravenous administration of 5 mg/kg JHL45 were 24.59 μg/mL, 10.02 <TEX>${\mu}g{\cdot}h/mL$</TEX>, and 1.88 h, respectively. The validated method herein will be useful for further pharmacokinetic studies of JHL45, as well as in preclinical and clinical phases.
Sorption and swelling of poly(DL‐lactic acid) and poly(lactic‐co‐glycolic acid) in supercritical CO2: An experimental and modeling study (2008)

Abstract Tissue engineering scaffolds require a controlled pore size and structure to host tissue formation from cell populations. Supercritical carbon dioxide (scCO 2 ) processing can be used to form porous scaffolds in which the escape of CO 2 from a plasticized polymer melt generates gas bubbles that shape the pores. The process is difficult to control with respect to changes in final pore size, porosity, and interconnectivity, while the solubility of CO 2 in the polymers strongly affects the foaming process. An in‐depth understanding of polymer CO 2 interaction will enable a successful scaffold processing. Amorphous poly( DL ‐lactic acid) (P DL LA) and poly(lactic acid‐ co ‐glycolic acid) (PLGA) polymers are attractive candidates for fabricating scaffolds. In this study, CO 2 sorption and swelling isotherms at 35 °C and up to 200 bar on a variety of homo‐ and copolymers of lactic acid and glycolic acids are presented. Sorption is measured through a gravimetric technique using a suspension microbalance and swelling by visualization. The obtained results are modeled using the Sanchez‐Lacombe equation of state. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 483–496, 2008
Anti-biased RF MEMS varactor topology for 20&#x2013;25 dB linearity enhancement (2010)

A new topology for significantly improving the linearity of RF MEMS varactors is reported in this paper. A single MEMS varactor subject to a low frequency noise and/or modulating signal is the main structure under consideration. The key idea is to separate the single varactor into two varactors in parallel, which are anti-biased. This leads to out-of-phase vibration of the two beams under the influence of the low-frequency noise and/or modulating signal, which eventually leads to a nearly constant capacitance value of the entire topology. The effectiveness of the new method is demonstrated by both measured results from fabricated RF MEMS varactors and simulated results using a large-signal model of MEMS varactor in Agilent's Advanced Design System (ADS). Both experimental and simulated results indicate an improvement of 20-25 dB compared to the conventional design when the varactors are biased close to their pull-in voltage and the low-frequency signal is close to their self-resonant frequency. This underlines the potential of the proposed topology in high-power RF MEMS circuits.
Evolution of Single-Use Urologic Endoscopy: Benchtop and Initial Clinical Assessment of a New Single-Use Flexible Cystoscope (2021)

<b><i>Introduction:</i></b> Office cystoscopy is one of the most frequently performed procedures by a urologist. However, single-use cystoscopes remain quite undeveloped. Ambu<sup>®</sup> has developed single-use broncoscopes, rhinolaryngoscopes, and duodenoscopes. Recently, they released a single-use cystoscope. In this study, we performed a benchtop and an initial clinical assessment of the Ambu aScope™ (4) Cysto (aS4C) single-use cystoscope. <b><i>Materials and Methods:</i></b> Ten new, never-used aS4C single-use cystoscopes were assessed for optical performance, maximal tip flexion, and irrigation flow rate with empty working channel, 365 μm laser fiber, 0.035 in hydrophilic-tipped wire, 1.9F nitinol basket, and a 1.8 mm flexible stent grasper. All cystoscopes were then fully flexed 25 times in each direction, and maximal flexion angles were remeasured with and without instruments. Optical resolution, distortion, and depth of field were measured and compared with our reusable digital flexible cystoscopes. Assessment of clinical use was performed for inpatient bedside procedures using a Likert feedback survey and the NASA Task Load Index. <b><i>Results:</i></b> Maximal upward flexion exceeded 200° and 160° for all working instruments in upward and downward flexion. Downward flexion demonstrated different flexion between instrument groups in pre- and postcycling (<i>p</i> < 0.001). There was no clinical difference between the pre- and postcycling flexion. Flow rate decreased with increasing working instrument size (<i>p</i> < 0.001). The Olympus HD cystoscope resolution was superior at 3 and 5 mm distance, but not at other distances. The Ambu scope was superior to the Olympus SD scope at all distances except 3 mm. The aS4C had higher Likert scale survey scores for clinical use. <b><i>Conclusions:</i></b> The new Ambu single-use cystoscope demonstrates good flexion across instruments and comparable optics with reusable cystoscopes. In addition, initial inpatient bedside use of the aS4C and Monitor system compares favorably with the Olympus reusable cystoscope. Further testing in clinical scenarios such as hematuria, urothelial carcinoma, and operative endoscopy is warranted.
Implications of quantum optics in high harmonic generation (2020)

Effects of extreme nonlinear optics, such as high harmonic generation (HHG), are conventionally modeled with classical electromagnetic fields: both the driving and emitted fields are treated classically. We present the fully quantum electrodynamical theory of extreme nonlinear optics and use it to predict new quantum effects in HHG. The quantum description shows new effects in both the spectral and statistical properties of HHG. We also describe how the HHG process changes in the single-atom regime and discuss experiments that can test our various predictions. Revealing the quantum-optical nature of HHG could lead to novel sources of attosecond light having intrinsically quantum statistics, such as squeezing and entanglement.
Trisomy of chromosome 15 in spontaneous leukemia of AKR mice. (1975)

Karyotypes of spontaneous thymomas of AKR mice were determined by trypsin-Giemsa banding methods. Trisomy of chromosome 15 occurred in 10 of 11 leukemic mice. Seven of the thymomas were predominantly trisomic for chromosome 15, one was trisomic for chromosome 12, and one exhibited multiple trisomies of chromosomes 3, 12, 15, and 17. Trisomy was not found in the norm-l AKR tissues examined.
Es werde Licht – mit Galliumnitrid: der Nobelpreis für Physik 2014 (2014)

Erhebliche Energieeinsparungen sind dank einer einzigen Erfindung möglich: der blauen Leuchtdiode. Die Forschung an GaN-basierte blauen LEDs resultierte nicht nur in einer effizienten weißen Lichtquelle, sondern hat viele weitere Anwendungs- und Forschungsperspektiven eröffnet. Die an der Entwicklung der blauen LED in erster Linie beteiligten Forscher wurden mit dem Nobelpreis für Physik 2014 ausgezeichnet.
Functional Applications of Text Analytics Systems (2022)

Text analytics consist of the statistics about a text element, which includes the word count, the word histogram, and the word frequency histogram. Most text documents of value are related to other—sometimes many other—documents, and so analytics describing the relative frequency of terms in a document compared to its peers are important for defining key words (tagging, labeling, indexing), search-responsive terms (query terms), and compressed versions of the documents (key words, summary, etc.).This clearly written text explains the functional applications of search, translation, optimization, and learning with regard to text analytics. Generation of analytics is aided by a hybrid, ensemble, or other combinatorial approach in which two or more effective analytic processes are used simultaneously, and their outputs combined to form a better “consensus”. Additional value to the preservation of the information is provided through these methods. Also, since they encompass capabilities of two or more knowledge-generating systems, they can create a “superset” of access points to the data generated. The book also describes the role of functional approaches in the testing and configuration of these systems.
Evaluation of the antibody response in pigs vaccinated against Streptococcus suis capsular type 2 using a double-antibody sandwich enzyme-linked immunosorbent assay. (1994)

A double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was standardized for the detection of specific antibodies following vaccination with Streptococcus suis capsular type 2 bacterins. No statistically significant increase of antibody titers was detected in vaccinated piglets compared to the nonvaccinated control group, even if a minority of piglets demonstrated an important postvaccinal response. Three of four vaccinated sows showed a low antibody response to vaccine and specific immunity was detected in piglets of only one litter of these three sows. Passive protection studies showed that none of the sera from vaccinated piglets were protective for mice whereas serum obtained from hyperimmunized pigs gave protection.
Temperature-Induced Molecular Reorganization in Thin Films and on Surfaces as Observed by Grazing Incidence Infrared Spectroscopy (1985)

With the use of a thermostated grazing incidence reflection (GIR) infrared cell, spectra of organic monolayers and thin polymer films have been obtained as a function of temperature. Results indicate that insight into the mechanism of molecular reorganization which often occurs at elevated temperatures can be obtained through thermal cycling experiments. In particular, studies of ultrathin poly(methylmethacrylate) [PMMA] films as a function of temperature reveal the onset of molecular segmental motion known to occur at the glass transition temperature, T g (∼100°C). Similarly, in Langmuir-Blodgett (L-B) monolayers of cadmium arachidate (CdA), GIR measurements indicate that a two-stage disordering process occurs with increasing temperature. Pretransitional disordering of the hydrocarbon tails may be a contributing factor to the onset of the thermal melting point.
Bimorphisms and synchronous grammars (2014)

We tend to think of the study of language as proceeding by characterizing the strings and structures of a language, and we think of natural language processing as using those structures to build systems of utility in manipulating the language. But many language-related problems are more fruitfully viewed as requiring the specification of a relation between two languages, rather than the specification of a single language. We provide a synthesis and extension of work that unifies two approaches to such language relations: the automata-theoretic approach based on tree transducers that transform trees to their counterparts in the relation, and the grammatical approach based on synchronous grammars that derive pairs of trees in the relation. In particular, we characterize synchronous tree-substitution grammars and synchronous tree-adjoining grammars in terms of bimorphisms, which have previously been used to characterize tree transducers. In the process, we provide new approaches to formalizing the various concepts: a metanotation for describing varieties of tree automata and transducers in equational terms; a rigorous formalization of tree-adjoining and tree-substitution grammars and their synchronous counterparts, using trees over ranked alphabets; and generalizations of tree-adjoining grammar allowing multiple adjunction.
Reconstruction of binary-data-page thick holograms for an arbitrarily oriented reference beam (1981)

The readout of a page of binary data from a holographic memory utilizing a thick recording material is treated for arbitrary angular positioning of the reference beam. The diffraction efficiency associated with each bit in the data page is calculated. Histograms showing the distribution of the diffracted powers and thus the fidelity of reconstruction for example cases are presented.