gebhart/patrepeval huggingface dataset:
Development of a Scalable Asymmetric Process for the Synthesis of GLYT1 Inhibitor BI 425809 (Iclepertin) (2023)

A robust and scalable synthesis process for BI 425809 (Iclepertin), a GLYT1 inhibitor with potential therapeutic properties for the treatment of central nervous system disorders, was developed and implemented on a multikilogram scale. Key aspects of the process include the efficient asymmetric synthesis of intermediate 3-((1R,5R)-3-azabicyclo[3.1.0]hexan-1-yl)-5-(trifluoromethyl)isoxazole·HCl from raw materials readily available in bulk and the synthesis of (R)-5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)benzoic acid through a novel Rh-catalyzed asymmetric hydrogenation.
Abstract 2877: Perifosine alone and in combination with antimetabolites interferes with NF-kB pathway activation in colon cancer cell lines (2012)

Abstract Background: Perifosine, a novel, first-in-class, oral Akt inhibitor, in combination with the antimetabolite Capecitabine is currently in Phase III clinical trials for the treatment of refractory advanced colorectal cancer. We have shown previously that Perifosine in combination with antimetabolites displayed synergistic cytotoxicity and apoptosis in colon cancer and other cell lines [1]. Constitutive NF-kB activation is frequently observed in colorectal cancer and, moreover, is associated with resistance to chemotherapy [2]. Hence we analysed, wether downregulation of the NF-kB pathway contributes to Perifosine mechanism of action and to the observed synergism with antimetabolites in colon cancer cell lines. Methods: Cellular NF-kB activation in nuclear extracts was measured by the TransAm NF-kB p65 ELISA (Active Motif, USA) monitoring binding of NF-kB to its response element. To allow for higher throughput of NF-kB pathway analysis a monoclonal SW620 colon cancer cell line ectopically expressing a NF-kB response element driven reporter gene (Promega, USA) was established. Cellular cytotoxicity and apoptosis assays as well as western blotting were performed according to standard procedures. The analysis of drug combinations was conducted by CalcuSyn software (Biosoft, UK) [3]. Results: Perifosine pretreatment decreased TNFα-induced NF-kB activation in SW620 cells in both independent assay sytems with IC50 values of about 7-10 µM. This effect seems to be specific, since the results were not mimicked by cytotoxic effects of Perifosine. Some of the antimetabolites alone upregulated NF-kB activity in the reporter gene assay. In the presence of these antimetabolites Perifosine was still capable to downregulate NF-kB activity. Conclusions: In summary, these results demonstrate that downregulation of the NF-kB pathway may contribute to the mechanism of action of Perifosine. Moreover, cotreatment with Perifosine has the potential to interfere with the development of antimetabolite resistance due to NF-kB activation in colon cancer. Further experiments addressing Perifosine's mechanism of action in combination with antimetabolites in gastric cancer cell lines are ongoing. References [1] Aicher et al. (2010), Perifosine in combination with antimetabolites induces synergistic effects on cytotoxicity and apoptosis in human colon, multiple myeloma, breast, renal, and liver tumor cell lines. AACR-NCI-EORTC International Conference, Berlin, Germany. [2] Sakamoto and Maeda (2010), Expert. Opin. Ther. Targets 14, 593-601 [3] Chou (2006), Pharmacological Reviews 58, 621-681 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2877. doi:1538-7445.AM2012-2877
How to Get the Best Gas Separation Membranes from State-of-the-Art Glassy Polymers (2022)

Herein we focus on fundamental polymer science factors in membrane-based gas separation to open another chapter on this important topic. Realistically thinking about nanometer and angstrom scale matrix attributes that are translatable into higher performance thin glassy polymer asymmetric membrane layers in practical large-scale devices is crucial. Such thinking should be guided by expertise in both polymer and membrane communities to advance the state-of-the-art. Polymer structures, membrane morphologies, and effects of operating conditions are discussed here by using specific examples to illustrate key issues. Rubbery polymers are not the focus of this discussion since they lack diffusive discrimination for size-similar penetrants, which glassy polymers provide and make them the focus here. Four scalable subtopics guide necessary thinking: (i) plasticization, (ii) antiplasticization, (iii) dual-mode transport involving saturation of unrelaxed free volume, and (iv) nonuniform free volume and stress profiles in thin skin glassy polymer asymmetric or composite membranes. Furthermore, using these subtopics in the context of macromolecular science, we discuss issues needed to expand the state-of-the-art in gas separation membranes.
Improved cell sensitivity and longevity in a rapid impedance‐based toxicity sensor (2009)

A number of toxicity sensors for testing field water using a range of eukaryotic cell types have been proposed, but it has been difficult to identify sensors with both appropriate sensitivity to toxicants and the potential for long-term viability. Assessment of bovine pulmonary artery endothelial cell (BPAEC) monolayer electrical impedance with electric cell-substrate impedance sensing (ECIS) showed promise in a previous systematic evaluation of toxicity sensor technologies. The goal of the study reported here was to improve toxicant responsiveness and field portability of this cell-based toxicity sensor. A variety of human cells, non-human mammalian cells, and non-mammalian vertebrate cells were screened for sensitivity to 12 waterborne industrial chemicals. The results of this assessment show that bovine lung microvessel endothelial cell (BLMVEC) monolayers and iguana heart (IgH-2) cell monolayers could detect nine out of the 12 waterborne industrial chemicals, an improvement over the seven chemicals previously detected using BPAEC monolayers. Both the BLMVEC and IgH-2 cell monolayers were tested for their ability for long-term survival on the ECIS test chips in a laboratory environment. Both cell lines were able to maintain high impedance readings on the ECIS electrodes for 37 days, a key trait in developing a field-portable toxicity sensor for water. Cell line optimization has greatly contributed to the on-going development of a field-portable cell-based biosensor that detects with sensitivity a wide range of waterborne toxicants.
Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis (2012)

瞄准：为了对 decapentaplegic (SMAD ) 识别并且描绘果蝇母亲， 3 依赖者在与 Helicobacter hepaticus 跟随感染的有免疫力的房间人口变化(H。hepaticus ) 。方法：SMAD3-/-(n = 19 ) 并且大肠炎抵抗的 SMAD3+/-(n = 24 ) 老鼠(年龄的 8-10 wk ) 感染 H。在有免疫力的房间人口的 hepaticus 和变化[T 淋巴细胞，生来的杀手(NK ) 房间， T 规章的房间] 在 0 d， 3 d， 7 d 和用流动 cytometry 感染以后的 28 d 在怒气和 mesenteric 淋巴节点(MsLNs ) 被测量。在 T 淋巴细胞和 granzyme B+ 房间的遗传型依赖者变化也用 immunohistochemistry 在近似冒号织物在 28 d 以后被估计。结果：当以前观察了， SMAD3-/- ，然而并非 SMAD3+/- 老鼠，发达大肠炎，在 4 wk 达到顶点感染以后。在 T 房间子集的重要变化都没在任何时间点在怒气或在在遗传型之间的 MsLNs 被观察。然而， CD4+ 和 CD8+/CD62Llo 房间，一张受动器 T 淋巴细胞人口，以及 NK 房间(NKp46/DX5+) 在在 7 d 和 28 d 的 SMAD3-/- 老鼠的 MsLNs 是显著地更高的感染以后。在冒号， CD3+ 房间的一个更高的数字在与在基线的 SMAD3+/ 老鼠相比的 SMAD3-/- 是在场的，它显著地没在感染期间变化。然而， granzyme B+ 房间的数字， cytolytic 淋巴细胞的一个标记，显著地在 SMAD3-/- 鼠标增加了与两只 SMAD3+/- 老鼠相比并且到基线值感染以后的 28 d。这与在这些动物的更严重的大肠炎开发一致。结论：数据建议在 SMAD3 发信号的缺点增加危险性到 H。通过受动器淋巴细胞的异常激活或 dysregulation 的导致 hepaticus 的大肠炎。
Joint AP On/Off and User-Centric Clustering for Energy-Efficient Cell-Free Massive MIMO Systems (2022)

Cell-free massive multiple-input multiple-output systems are expected to provide faster and more robust connections to user equipments (UEs) by cooperation of a massive number of distributed access points (APs). Energy efficiency (EE) is becoming an important indicator to design and operate networks; to improve EE, use of sleep-mode of APs (SMA), also called AP switch on/off, for selected APs has been investigated. Although previous works analyze the performance of SMA in the presence of user-centric clustering (UCC), these two techniques are assumed to not affect each other. In this paper, we propose a new greedy combining algorithm (GCA), where SMA and UCC work alternately to obtain better performance, and show its superiority over a conventional algorithm. Example simulations show that GCA can achieve 44% higher total EE for 8 UEs and 59% for 16 UEs with 64 APs. Additionally, GCA also provides higher minimum spectral efficiency thanks to its structure of the algorithm.
Precise Evaluation of Angstrom‐Ordered Mixed Interfaces in Solution‐Processed OLEDs by Neutron Reflectometry (2014)

The interfaces between hole-transporting polymer (TFB) and the emitting small molecules (CBP: Ir(ppy)3) in OLEDs are investigated using neutron reflectometry. The interface with the evaporated CBP: Ir(ppy)3 layer is clear. On the other hand, the interface with the spin-coated CBP: Ir(ppy)3 layer is broad, and the CBP: Ir(ppy)3 disperses into the TFB layer. The mixing ratio of CBP is larger than that of Ir(ppy)3. The influences of the interfaces on the hole only device characteristics are investigated. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Effects of Nitrogen and Plasma Power on Electrochemical Properties of Boron-Doped Diamond Electrodes Grown by MPCVD (2002)

The influences of nitrogen addition and the attenuation of microwave power during microwave plasma-assisted chemical vapor deposition (MPCVD) of diamond films on electrochemical properties of the grown films were investigated. Although diamond films grown in the presence of a small amount of nitrogen did not contain sp2 carbon and appeared to be normally deposited films, the electrical and electrochemical properties were different from films grown under an atmosphere without nitrogen. Especially, the potential windows of diamond films grown in the presence of nitrogen at low microwave power were very wide and extended to 3.6 V in sulfuric acid solution, which is comparable to the widest value of the potential window of diamond electrodes reported till now. It was also found that the attenuation of the plasma power during MPCVD by itself was effective in the expansion of the potential window because of the defect-free growth of diamond crystals.
ChemInform Abstract: Peri‐ and Stereoselectivity Effects in the Intramolecular (2 + 2) Cycloaddition Reaction of Phenylsulfonyl‐Substituted Allenes. (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.
Fabrication of Surface Plasmon-Polariton Couplers and Waveguide Devices (2009)

Described here is holographic stepping-lithography fabrication of grating couplers and waveguide platforms for efficient surface plasmon-polariton (SPP) excitation on metallic structures. These methods provide consistent coupling with design flexibility and high efficiency for various SPP nanophotonic devices.
High-transfer-rate 4.7-GB DVD-RAM (2003)

Showed the feasibility of 4.7-GB DVD-RAM media for 5/spl times/ recording. In order to maintain compatibility with current 2/spl times/ drives, we reduced jitter in both 2/spl times/ and 5/spl times/ recording. The most important design concept is to control the crystal growth velocity and crystal nucleation frequency: the former should be reduced and the latter increased. To control these values, we prepared a medium having a Ge-Sb-Te recording film and a nucleation promoting film. It showed jitter lower than 10% in both 2/spl times/ and 5/spl times/ recording.
Laser Demonstrations of Rare-Earth Ions in Low-Phonon Chloride and Sulfide Crystals (2000)

Laser results are summarized for the low-phonon hosts KPb 2 Cl 5 and CaGa 2 S 4 . Radiative quantum efficiencies were determined in KPb 2 Cl 5 :Dy 3+ directly from emission spectra in order to accurately determine its long-wavelength potential. The results indicate that room-temperature laser action should be possible to near 9 µm in this host.
Interactions between the intestinal microflora, diet and diarrhoea, and their influences on piglet health in the immediate post-weaning period (2003)

The piglet is subjected to many environmental, behavioural and dietary stresses immediately after weaning, and the intestinal microenvironment of the newly weaned pig is particularly precarious. With weaning comes a major change in diet that requires and induces significant changes in the types and numbers of micro-organisms residing in the gastrointestinal tract, as well as in the physiology’ and functionality of the tract. Given these circumstances, it is not surprising that the newly weaned pig is highly susceptible to enteric disease. The balance between development of a “healthy intestinal microflora or the establishment of bacterial intestinal disease can he easily tipped toward disease expression (Aumaitre et al, 1995; Nabuurs, 1995). This chapter briefly describes the basic intestinal microflora present during the post-weaning period, specific enteric diseases that can occur at this time, and some potential precipitating dietary factors. Particular emphasis is placed on Escherichia coli and its involvement in the condition known as post weaning colibacillosis (PWC), since this is the most common cause of intestinal disease in the newly-weaned pig. The role of dietary fibre in altering susceptibility to PWC receives special attention.
Systemin triggers an increase of cytoplasmic calcium in tomato mesophyll cells: Ca2+ mobilization from intra‐ and extracellular compartments (1998)

We show here that, within 1–2 min of application, systemin triggers a transient increase of cytoplasmic free calcium concentration ([Ca 2+ ] c ) in cells from Lycopersicon esculentum mesophyll. The systemin‐induced Ca 2+ increase was slightly but not significantly reduced by L‐type Ca 2+ channel blockers (nifedipine, verapamil and diltiazem) and the Ca 2+ chelator [ethylene glycol tetraacetic acid (EGTA)], whereas inorganic Ca 2+ channel blockers (LaCl 3 , CdCl 2 and GdCl 3 ) and compounds affecting the release of intracellular Ca 2+ from the vacuole (ruthenium red, LiCl, neomycin) strongly reduced the systemin‐induced [Ca 2+ ] c increase. By contrast, no inhibitory effect was seen with the potassium and chloride channel blockers tested. Unlike systemin, other inducers of proteinase inhibitor (PI) and of wound‐induced protein synthesis, such as jasmonic acid (JA) and bestatin, did not trigger an increase of cytoplasmic Ca 2+ . The systemin‐induced elevation of cytoplasmic Ca 2+ which might be an early step in the systemin signalling pathway, appears to involve an influx of extracellular Ca 2+ simultaneously through several types of Ca 2+ permeable channels, and a release of Ca 2+ from intracellular stores sensitive to blockers of inositol 1,4,5‐triphosphate (IP 3 )‐ and cyclic adenasine 5’‐diphosphoribose (cADPR)‐mediated Ca 2+ release.
Switching boundary geometry and the control of single-phase inverters (1989)

A geometric approach to switching power converter control design is investigated for the single-phase voltage-sourced inverter. A method for deriving switching boundaries based on steady-state trajectories of the asymptotic model is presented as a generalization of the DC-DC converter case. It is shown that for an elliptical switching boundary, it is possible to produce sinusoidal output without any time-varying reference signal. The nonlinear feedback control law derived provides two degrees of freedom for adjustment of steady-state performance. Simulation and experimental results for the proposed controller are summarized. >
Curing and heat transfer in polyurethane reaction molding (1978)

Abstract Temperature measurements were made on the adiabatic polymerization of three urethane systems; two casting formulations, one thermoplastic and the other thermosetting, and a commercial reaction injection molding (RIM) formulation with a 10 second gel time. The data were found to fit a simple nth order overall kinetic expression. These kinetic and heat of reaction results were used to model heat transfer in a 3.8 cm diameter cylinder with an isothermal wall. Experimental temperature profiles for the two casting urethanes were in good agreement with predictions. The kinetic data on the RIM material was used to model temperature profiles1 in 3 and 6 mm thick plaque molds. Experimental measurements of temperature near the mold center agreed with the model. Temperatures measured near the wall were higher due to failure of the isothermal wall assumption.
Further Characterization of CD34‐Low/Negative Mouse Hematopoietic Stem Cells (1999)

We have previously reported that in adult mouse bone marrow, CD34low/- c-kit+ Sca-1+ lineage markers negative (Lin-) (CD34-KSL) cells represent hematopoietic stem cells with long-term marrow repopulating ability whereas CD34+ c-kit+ Sca-1+ Lin- (CD34+KSL) cells are progenitors with short-term reconstitution capacity. To further characterize cells in those two populations, relative expression of various genes were examined by reverse transcriptase polymerase chain reaction (RT-PCR). In CD34-KSL cells, none of the genes studied was found to be expressed with the exception of GATA-2, IL-1R alpha, IL-2R gamma, AIC-2B, c-kit, EPO-R, and c-mpl. In contrast, expression of GATA-1 and all cytokine receptor genes examined except IL-2R beta, IL-7R alpha and IL-9R alpha were found in CD34+KSL. The difference between these two populations was also shown in single cell culture analysis of these cells. When cells were clone-sorted and cultured in the presence of SCF, IL-3 and EPO, CD34-KSL cells required much more time to undergo the first cell division than CD34+KSL cells. Dormancy and random fashion of cell division by CD34-KSL cells were also evident by the analysis of the second cell division, which was found to be delayed and unsynchronous compared with CD34+KSL cells. Clonal culture analysis showed that CD34-KSL cells were more potent in proliferation and multilineage differentiation capacities than CD34+KSL cells. In a paired-daughter cell experiment, 75% of CD34-KSL and 50% of CD34+KSL paired-daughter-derived colonies were nonidentical with wide variety of lineage combinations. Taken together, these data support our previous notion that CD34-KSL cells are at higher rank in hematopoietic hierarchy than CD34+KSL cells. In addition, our results using highly enriched stem cell population directly obtained from mouse bone marrow support the proposed stochastic nature of lineage commitment.
Road Risk Modeling and Cloud-Aided Safety-Based Route Planning (2015)

This paper presents a safety-based route planner that exploits vehicle-to-cloud-to-vehicle (V2C2V) connectivity. Time and road risk index (RRI) are considered as metrics to be balanced based on user preference. To evaluate road segment risk, a road and accident database from the highway safety information system is mined with a hybrid neural network model to predict RRI. Real-time factors such as time of day, day of the week, and weather are included as correction factors to the static RRI prediction. With real-time RRI and expected travel time, route planning is formulated as a multiobjective network flow problem and further reduced to a mixed-integer programming problem. A V2C2V implementation of our safety-based route planning approach is proposed to facilitate access to real-time information and computing resources. A real-world case study, route planning through the city of Columbus, Ohio, is presented. Several scenarios illustrate how the "best" route can be adjusted to favor time versus safety metrics.
Changes in the Metabolism of Dihydrotestosterone in the Hyperplastic Human Prostate* (1983)

It has been well established that hyperplastic human prostatic tissue is characterized by a 3- to 4-fold elevation in the content of dihydrotestosterone (DHT) compared to that in normal prostatic tissue. However, the exact mechanism responsible for DHT accumulation has not been established. One hypothesis for the abnormal elevation of DHT content in hyperplastic prostatic tissue is that changes occur in the tissue itself which shift the overall balance of androgen metabolism favoring the increased accumulation of DHT. To test this hypothesis, the metabolic activities that produce and remove DHT were determined in a series of normal as well hyperplastic human prostates. The results of these studies demonstrated that in each of the eight separate hyperplastic prostatic tissues assayed, there was a significant increase in 5 alpha-reductase activity producing DHT concomitant with significant decreases in the 3 alpha- and 3 beta-hydroxysteroid oxidoreductase reductase and 17 beta-hydroxysteroid oxidoreductase oxidase activities removing DHT. These specific alterations result in a major shift in the overall balance of androgen metabolism which favors an increase in the net formation of DHT in hyperplastic prostatic tissue. Such a shift in androgen metabolism is, therefore, at least one mechanism for the well documented increase in DHT content found in hyperplastic human prostatic tissue.
Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis (2023)

As one of the most successful human pathogens, <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a novel glutamine metabolism antagonist, JHU083, inhibits <i>Mtb</i> proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days post-infection, and reduced lung pathology. JHU083 treatment also initiates earlier T-cell recruitment, increased proinflammatory myeloid cell infiltration, and a reduced frequency of immunosuppressive myeloid cells when compared to uninfected and rifampin-treated controls. Metabolomics analysis of lungs from JHU083-treated <i>Mtb</i>-infected mice revealed reduced glutamine levels, citrulline accumulation suggesting elevated NOS activity, and lowered levels of quinolinic acid which is derived from the immunosuppressive metabolite kynurenine. When tested in an immunocompromised mouse model of <i>Mtb</i> infection, JHU083 lost its therapeutic efficacy suggesting the drug's host-directed effects are likely to be predominant. Collectively, these data reveal that JHU083-mediated glutamine metabolism inhibition results in dual antibacterial and host-directed activity against tuberculosis.