gebhart/patrepeval huggingface dataset:
Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene (1998)

Two mouse mutations gyro (Gy) and hypophosphatemia (Hyp) are mouse models for X-linked hypophosphatemic rickets and have been shown to be deleted for the 5' and 3' end of the mouse homolog of PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome; formerly called PEX), respectively. In addition to the metabolic disorder observed in Hyp mice, male Gy mice are sterile and show circling behavior and reduced viability. The human SMS (spermine synthase) gene maps approximately 39 kb upstream of PHEX and is transcribed in the same direction. To elucidate the complex phenotype of Gy mice, we characterized the genomic region upstream of Phex. By establishing the genomic structure of mouse Sms, a 160-190 kb deletion was shown in Gy mice, which includes both Phex and Sms. There are several pseudogenes of SMS / Sms in man and mouse. Northern analysis revealed three different Sms transcripts which are absent in Gy mice. Measurement of polyamine levels revealed a marked decrease in spermine in liver and pancreas of affected male Gy mice. Analysis of brain tissue revealed no gross or histological abnormalities. Gy provides a mouse model for a defect in the polyamine pathway, which is known to play a key role in cell proliferation.
Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor‐specific fluorescent ligands (2008)

Quantitation of circulating tumor cells (CTCs) can provide information on the stage of a malignancy, onset of disease progression and response to therapy. In an effort to more accurately quantitate CTCs, we have synthesized fluorescent conjugates of 2 high-affinity tumor-specific ligands (folate-AlexaFluor 488 and DUPA-FITC) that bind tumor cells >20-fold more efficiently than fluorescent antibodies. Here we determine whether these tumor-specific dyes can be exploited for quantitation of CTCs in peripheral blood samples from cancer patients. A CTC-enriched fraction was isolated from the peripheral blood of ovarian and prostate cancer patients by an optimized density gradient centrifugation protocol and labeled with the aforementioned fluorescent ligands. CTCs were then quantitated by flow cytometry. CTCs were detected in 18 of 20 ovarian cancer patients (mean 222 CTCs/ml; median 15 CTCs/ml; maximum 3,118 CTCs/ml), whereas CTC numbers in 16 gender-matched normal volunteers were negligible (mean 0.4 CTCs/ml; median 0.3 CTCs/ml; maximum 1.5 CTCs/ml; p < 0.001, chi(2)). CTCs were also detected in 10 of 13 prostate cancer patients (mean 26 CTCs/ml, median 14 CTCs/ml, maximum 94 CTCs/ml) but not in 18 gender-matched healthy donors (mean 0.8 CTCs/ml, median 1, maximum 3 CTC/ml; p < 0.0026, chi(2)). Tumor-specific fluorescent antibodies were much less efficient in quantitating CTCs because of their lower CTC labeling efficiency. Use of tumor-specific fluorescent ligands to label CTCs in peripheral blood can provide a simple, accurate and sensitive method for determining the number of cancer cells circulating in the bloodstream.
The DOE Bioenergy Research Centers: History, Operations, and Scientific Output (2015)

Over the past 7 years, the US Department of Energy’s Office of Biological and Environmental Research has funded three Bioenergy Research Centers (BRCs). These centers have developed complementary and collaborative research portfolios that address the key technical and economic challenges in biofuel production from lignocellulosic biomass. All three centers have established a close, productive relationship with DOE’s Joint Genome Institute (JGI). This special issue of Bioenergy Research samples the breadth of basic science and engineering work required to underpin a diverse, sustainable, and robust biofuel industry. In this report, which was collaboratively produced by all three BRCs, we discuss the BRC contributions over their first 7 years to the development of renewable transportation fuels. We also highlight the BRC research published in the current issue and discuss technical challenges in light of recent progress.
Preparation and Surface Characterization of Polymer Nanoparticles Designed for Incorporation into Hybrid Materials (2007)

We prepared water dispersions of poly(n-butyl methacrylate-st-butyl acrylate) crosslinked core-shell nanoparticles functionalized with different amounts of trimethoxisilane (TMS) groups in the outer shell. The purpose of the TMS groups is to chemically bind the rubbery particles to a nanostructured silica network, using sol-gel copolymerization. Here, we present nanoparticles containing 13 mol % and 30 mol % of TMS groups in the outer shell and compare their surface morphology with particles that do not contain TMS. The particles are prepared by a two-step seeded emulsion polymerization technique at neutral pH. In the first step, we obtained crosslinked seed particles (44 nm in diameter) by a batch process. In the second step, we used a semi-continuous emulsion polymerization technique under starved feed conditions to obtain monodispersed particles of controlled composition and size (ca. 100 nm in diameter). Fluorescence decay measurements were performed in situ on the dispersions, using a pair of cationic dyes adsorbed onto the surface of the nanoparticles: rhodamine 6G as the energy transfer donor and malachite green carbinol hydrochloride as the acceptor. The kinetics of Förster resonance energy transfer (FRET) between the dyes is sensitive to the donor-acceptor distance, allowing us to obtain the binding distribution of the dyes at the nanoparticle surface. For the unmodified nanoparticles, we found a dye distribution that corresponds to an average interface thickness of delta = (5.2 +/- 0.2) nm. For the samples containing 13 mol % and 30 mol % of TMS groups in the outer shell we obtained broader interfaces, with widths of delta = (6.2 +/- 0.2) nm and delta = (6.5 +/- 0.1) nm respectively. This broadening of the distribution with the surface modification is interpreted in terms of the increase in free volume of the shell caused by the TMS groups. Finally, we studied the effect of temperature on the water-polymer interface fuzziness, in order to evaluate the accessibility of the TMS groups during the sol-gel synthesis of nanostructured hybrid materials.
The social subject in biographical interpretive methods: emotional, mute, creative, divided (2004)

This chapter asks questions about the conceptualisation of the ontology of the social subject that informs biographical methods of research. This chapter was conceived after the author’s experience of listening to the accounts of war trauma counsellors in Kosovo. This reminded the author that the origins of psychoanalysis remain entirely relevant today for the understanding that the social subject is always and everywhere simultaneously a psychological subject. Within this view, emotionality is the crucial foundation of all true mentality, dreaming the rudiments of all creativity. However, these functions may be attacked and may be damaged by the trauma of social and political terror, upheaval, displacement and dislocation. Biographical research has the potential to grasp the complicated relationship between psychological and the social subject more than any other method of research, only if it embraces an ontology of deep subjectivity such as psychoanalysis purposes. Some of the topics discussed in this chapter are: emotionality, dreaming and trauma; mind and emotional experience; and social strategy, creativity and dreaming.
Time-resolved phase-change recording mark formation with zinc oxide near-field optical active layer (2015)

In this paper, an optical active thin film of zinc oxide (ZnOx) nano-composites exploited for the enhancement of optical signals in an ultra-high density recording scheme has been demonstrated. Via the electron microscope investigation, the results display randomly distributed crystalline nanograins in the ZnOx thin films. Optical disks with the ZnOx nanostructured thin films show that the carrier-to-noise ratio (CNR) above 25 dB can be obtained at the mark trains of 100 nm, while the optimal writing power is reduced as a function of the increasing thickness of the ZnOx films. Furthermore, by conducting a series of the optical pump–probe experiments, the optical responses of recording marks on as-deposited phase-change Ge2Sb2Te5 (as-GST) recording layers present that the highly contrast bright recording bits can be acquired with the existence of the ZnOx nanostructured thin films, providing prospective potentials in future data storage and optoelectronic devices.
Tautomerism of Histidine 64 Associated with Proton Transfer in Catalysis of Carbonic Anhydrase (2007)

The imidazole (15)N signals of histidine 64 (His(64)), involved in the catalytic function of human carbonic anhydrase II (hCAII), were assigned unambiguously. This was accomplished by incorporating the labeled histidine as probes for solution NMR analysis, with (15)N at ring-N(delta1) and N(epsilon2), (13)Cat ring-Cepsilon1, (13)C and (15)N at all carbon and nitrogen, or (15)N at the amide nitrogen and the labeled glycine with (13)C at the carbonyl carbon. Using the pH dependence of ring-(15)N signals and a comparison between experimental and simulated curves, we determined that the tautomeric equilibrium constant (K(T)) of His(64) is 1.0, which differs from that of other histidine residues. This unique value characterizes the imidazole nitrogen atoms of His(64) as both a general acid (a) and base (b): its epsilon2-nitrogen as (a) releases one proton into the bulk, whereas its delta1-nitrogen as (b) extracts another proton from a water molecule within the water bridge coupling to the zinc-bound water inside the cave. This accelerates the generation of zinc-bound hydroxide to react with the carbon dioxide. Releasing the productive bicarbonate ion from the inside separates the water bridge pathway, in which the next water molecules move into beside zinc ion. A new water molecule is supplied from the bulk to near the delta1-nitrogen of His(64). These reconstitute the water bridge. Based on these features, we suggest here a catalytic mechanism for hCAII: the tautomerization of His(64) can mediate the transfers of both protons and water molecules at a neutral pH with high efficiency, requiring no time- or energy-consuming processes.
Safety and Tolerability of Omecamtiv Mecarbil During Exercise in Patients With Ischemic Cardiomyopathy and Angina (2014)

Doses of omecamtiv mecarbil producing plasma concentrations previously shown to increase systolic function were well tolerated during exercise in these study patients with ischemic cardiomyopathy and angina. There was no indication that treatment increased the likelihood of myocardial ischemia in this high-risk population. (Pharmacokinetics [PK] and Tolerability of Intravenous [IV] and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina; NCT00682565).
Secure communication in frequency selective channels with fade-avoiding subchannel usage (2014)

The random nature of fading channels is an enabling factor for achieving secrecy against eavesdropping. By considering the channel frequency selectivity, we propose an adaptive transmission scheme in which the faded subchannels of the legitimate channel are not used for conveying information. Thus, capacity reduction in legitimate channel is minimized while causing a reduction of the eavesdropper channel capacity proportional to the unused subchannels. Besides improving communication secrecy with the intelligent subchannel usage, populating the unused subchannels with artificially-generated noise that further disturbs the eavesdropper's reception is proposed. Since each receiver has its own channel state information (CSI) but not other's, eavesdroppers cannot discard the distortion which is integrated into the transmitted signal as a function of the legitimate pair's CSI. Positive secrecy capacity and outage probabilities are provided as well as error performance example in a communication scenario. It is showed that while careful usage of the subchannels in frequency selective channels improves the secrecy, introducing the fade-filling noise creates an error floor for the malicious nodes.
Modelling the Exhaust Gas Recirculation Mass Flow Rate in Modern Diesel Engines (2016)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;The intrinsic model accuracy limit of a commonly used Exhaust Gas Recirculation (EGR) mass flow rate model in diesel engine air path control is discussed in this paper. This EGR mass flow rate model is based on the flow of a compressible ideal gas with unchanged specific heat ratio through a restriction cross-area within a duct. A practical identification procedure of the model parameters is proposed based on the analysis of the engine data and model structure. This procedure has several advantages which include simplicity, low computation burden and low engine test cost. It is shown that model tuning requires only an EGR valve sweep test at a few engine steady state operating points. It is also shown that good model accuracy can be achieved when the control variables of other air path devices, e.g. the vane position of a Variable Geometry Turbocharger (VGT) and the torque demand of an Electric Turbo Assist (ETA), are kept constant during the EGR valve sweep test used to tune the model. Two different diesel engines are used in this work to demonstrate the model tuning procedure and the model validation results. Both engines are equipped with a high pressure external EGR system and a VGT. One of the engines has a relatively new air system device - an ETA. The model validation results of both engines show good model accuracy not only at steady state engine operating points but also during engine transients.&lt;/div&gt;&lt;/div&gt;
Response from the authors (2006)

While we agree with many of the points Dr. Peleg makes in his letter, there are additional practical considerations. Microbial food safety and thermal processing are expanding bases of knowledge. Governmental regulations and verification of current commercial thermal processes are based on our existing knowledge. While there may be more mathematically accurate models for some data, there is currently insufficient raw data that has been published to estimate their practical importance. In the effort to define more accurately the effects of heat on microbial cell lethality, let us all agree that the primary goal must remain finding math models that more adequately fit the biological data, not the other way around. Putting together a scientific forum where all interested parties can address these deficiencies is probably the best place to start.
On development of 600-850 V 6H-SiC LDMOS transistors using silane-ambient implant anneal (2002)

In this work, we report on development of 600-850 V SiC LDMOSFET's, which for the first time utilize silane-overpressure implant annealing, in comparison to earlier works. A 2-D model using Medici/sup TM/ software from Avant! Corporation was used to optimize the structure, and a modified implant anneal with silane overpressure was used to improve the surface morphology of implanted regions. Further, drain and gate electrode extensions were used to increase the blocking voltage.
Health planning in Pakistan: a case study (1997)

Health planning is an essential function of the state. For it to be successful, a number of conditions need to be satisfied. In particular it needs to be flexible, participative and integrated with other decision processes. Despite some strengths, the health planning system in Pakistan has generally failed to provide the framework to allow such an approach. Links between strategic and operational planning have been weak; decision-making has been very centralized; there has been a lack of functional clarity; the respective roles of bureaucrats and politicians have been unclear; and, links between capital and recurrent budgets and between planning and implementation have been weak. As a result, there is a number of imbalances in the allocation of resources. The introduction of a revised health planning system for Pakistan is discussed. The constraints on such a system and an initial assessment of its success are presented. © 1997 John Wiley & Sons, Ltd.
Critical Role for Hematopoietic Cell Kinase (Hck)-mediated Phosphorylation of Gab1 and Gab2 Docking Proteins in Interleukin 6-induced Proliferation and Survival of Multiple Myeloma Cells (2004)

Interleukin-6 (LI-6) is a known growth and survival factor in multiple myeloma via activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling cascade. In this report we show that Grb2-associated binder (Gab) family adapter proteins Gab1 and Gab2 are expressed by multiple myeloma cells; and that interleukin-6 induces their tyrosine phosphorylation and association with downstream signaling molecules. We further demonstrate that these events are Src family tyrosine kinase-dependent and specifically identify the role of hematopoietic cell kinase (Hck) as a new Gab family adapter protein kinase. Conversely, inhibition of Src family tyrosine kinases by the pyrazolopyrimidine PP2, as in kinase-inactive Hck mutants, significantly reduces IL-6-triggered activation of extracellular signal-regulated kinase and AKT-1, leading to significant reduction of multiple myeloma cell proliferation and survival. Taken together, these results delineate a key role for Hck-mediated phosphorylation of Gab1 and Gab2 docking proteins in IL-6-induced proliferation and survival of multiple myeloma cells and identify tyrosine kinases and downstream adapter proteins as potential new therapeutic targets in multiple myeloma.
State to State to State Dynamics of theD+H2→HD+HReaction: Control of Transition-State Pathways via Reagent Orientation (2006)

The influence of reagent rotation on the dynamics of the D+H2 -->HD+H reaction is studied. The state-resolved differential cross section is measured using the Rydberg-atom scheme in a crossed beam experiment. It is found that the H2 rotation has a strong influence on the results. This effect was traced to the selection of the quantum bottleneck states through reagent orientation, thus suggesting a novel strategy to control the transition-state pathways in direct chemical reactions.
Action of the novel selective thromboxane antagonist (3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbazolepropan oic acid on vascular smooth muscle preparations. (1989)

The action of the thromboxane A2-receptor-antagonist (3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbazo lepropanoic acid (Bay u 3405) on vascular smooth muscle preparations was investigated in vitro. In rabbit aortic rings Bay u 3405 is a potent inhibitor of vasoconstriction produced by thromboxane A2 (TXA2)/PG endoperoxides generated by stimulated human platelets (EC50 1.3 x 10(-6) mol/l), (+/-)-cTA2 (Carbocyclic thromboxane A2 [2 beta(Z),3 alpha-(1E,3R*)-3- (3-hydroxy(1-octenyl)-bicyclo[3.1.1]hept-2-yl-5-heptenoic acid]) (EC50 3.3 x 10(-7) mol/l) and U 46619 (EC50 3.8 x 10(-7) mol/l). In pig circumflex coronary arteries Bay u 3405 was 150 times more potent (EC50 2.6 x 10(-9) mol/l) than in rabbit aorta. In rabbit and rat aorta the concentration-response curves for U 46619 were shifted to the right in a parallel manner and the maximum responses were not suppressed. The Schild-plot yielded a straight line with a slope of 1.14 (rabbit) or 1.29 (rat) and pA2 values of 7.43 and 8.59, respectively. The vasoconstrictive action of other agonists such as KCl, serotonin, histamine, epinephrine, norepinephrine, acetylcholine and angiotensin were not affected. In human platelets inhibition of the TXA2-synthase was seen only at concentrations of Bay u 3405 of 2.4 x 10(-5) mol/l and above. From these findings it is concluded that Bay u 3405 is a potent, competitive TXA2/endoperoxide receptor antagonist in vascular smooth muscle.
Abstract 5801: Unexpected selectivity of histone deacetylase inhibitors in live MDA-MD-231 triple-negative breast cancer cells (2018)

Abstract While inhibition of histone deacetylases (HDAC) is a promising strategy for the treatment of cancer, HDACs do play essential roles in normal cellular function, limiting their use as therapeutic targets. Increasing evidence shows that each of the HDAC isoforms carry out unique biological functions; therefore, by inhibiting a single isoform, one could regulate a focused subset of genes and achieve the desired therapeutic effect and lower toxicity. To investigate this aspect, many isoform-selective inhibitors have been synthesized, characterized for selectivity against recombinant HDACs in biochemical assays, and tested for anti-cancer activity. Despite significant progress, the actual engagement of HDAC isoforms is poorly characterized since methods to determine selectivity of HDAC inhibitors in live cells with unperturbed epigenetic machinery and in vivo are missing. Recently, using a novel photoreactive HDAC probe (PRP), we demonstrated that its isoform selectivity in live breast cancer cells is cell-type dependent, differs from that determined in the biochemical assays, and, in the case of HDAC3, is regulated by phosphorylation by c-Jun N-terminal kinase (JNK). Similar cell-type dependent variability in HDAC isoform selectivity was also observed for other HDAC isoforms. In this report, we extended our photolabeling approach to characterize HDAC isoform selectivity of the commonly used in pre-clinical and clinical research non-selective and selective inhibitors: SAHA, panobinostat, pimelic diphenylamide 106, PCI-34051, and TMP-269. Seven novel PRPs based on the chemical scaffolds of these HDAC inhibitors were synthesized and tested in the biochemical assay and the cell-based photolabeling assay in live triple negative breast cancer cells MDA-MB-231. We found that the cell-based profiles of these PRPs were skewed toward inhibition of HDAC3 irrespective of their biochemical selectivity, chemotypes, or isoform abundance, suggesting that the actual HDAC isoform selectivity and target engagement in live cells is different from that perceived based on the results of the biochemical assay. These studies suggest that a substantial correction in our understanding of the role HDAC isoforms and their inhibitors play in live cells in culture and in vivo may be necessary. Further expansion of these studies to other types of cells and animal tissues ex vivo and in vivo as well as identification of the mechanisms responsible for modulation of HDAC isoform selectivity and target engagement are in progress. Citation Format: Shaimaa M. Aboukhatwa, Thomas W. Hanigan, Jayaprakash Neerasa, Taha Y. Taha, Nathan D. Brown, Eman E. El-Bastawissy, Mohamed A. Elkersh, Tarek F. El-Moselhy, Jonna Frasor, Pavel A. Petukhov. Unexpected selectivity of histone deacetylase inhibitors in live MDA-MD-231 triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5801.
Artificial cells based on biodegradable polymersomes (2003)

The aim of the research that is described in this thesis is to develop biodegradable, biocompatible polymersomes that can serve as a basis for artificial cells. These artificial cells should be able to be delivered to the circulation, interact with specific sites where they perform their function, and biodegrade afterwards.