gebhart/patrepeval huggingface dataset:
Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8–mediated apoptosis and down-regulation of c-FLIP protein (2003)

Depsipeptide is in clinical trials for chronic lymphocytic leukemia (CLL) on the basis of earlier observations demonstrating selective in vitro activity in CLL. We sought to determine the relationship of histone H3 and H4 acetylation, inhibition of histone deacetylase, and apoptosis observed in CLL cells to justify a pharmacodynamic end point in these clinical trials. We demonstrate that in vitro depsipeptide induces histone H3 and H4 acetylation and histone deacetylase enzyme inhibition at concentrations corresponding to the LC50 (concentration producing 50% cell death) for cultured CLL cells (0.038 microM depsipeptide). The changes in histone acetylation are lysine specific, involving H4 K5, H4 K12, and H3 K9, and to a lesser extent H4 K8, but not H4 K16 or H3 K14. Depsipeptide-induced apoptosis is caspase dependent, selectively involving the tumor necrosis factor (TNF) receptor (extrinsic pathway) initiating caspase 8 and effector caspase 3. Activation of caspase 8 was accompanied by the down-regulation of cellular FLICE-inhibitory protein (c-FLIP, I-FLICE) without evidence of Fas (CD95) up-regulation. Changes in other apoptotic proteins, including Bcl-2, Bax, Mcl-1, and X-linked inhibitor of apoptosis (XIAP), were not observed. Our results demonstrate a relationship between target enzyme inhibition of histone deacetylase, histone H3 and H4 acetylation, and apoptosis involving the TNF-receptor pathway of apoptosis that is not used by other therapeutic agents in CLL. These data suggest use of histone H3 and H4 acetylation, inhibition of histone deacetylase, and down-regulation of FLIP as pharmacodynamic end points for further evaluation of this drug in patients.
Theoretical Phase Diagrams of Polymer/Clay Composites:  The Role of Grafted Organic Modifiers (2000)

We combine a density functional theory (DFT) with a self-consistent field model (SCF) to calculate the phase behavior of thin, oblate colloidal particles that are coated with surfactants and dispersed in a polymer melt. These coated particles represent organically modified clay sheets. By integrating the two methods, we can investigate the effect of the surfactants' characteristics (grafting density ρgr and length Ngr) and the polymer−surfactant interaction energy on the polymer−clay phase diagram. Depending on the values of these critical parameters and the clay volume fraction, φ, the system can be in an isotropic or nematic phase (which corresponds to an exfoliated composite). The system can also form a smectic, crystal, columnar, or "house-of-cards" plastic solid, as well as a two-phase (immiscible) mixture. Using this model, we isolate conditions that lead to the stabilization of the homogeneous, exfoliated phases (the isotropic and nematic regions) and to the narrowing of the immiscible two-phase regions.
Synchronization of OFDM systems over frequency selective fading channels (2002)

A joint initial frame synchronization and initial channel estimation algorithm for OFDM systems is developed, and its performance with carrier frequency offset and with additive white Gaussian noise in frequency selective channels is evaluated. Transmission of a short pre-frame synchronization burst is proposed and slow fading is assumed, so that the channel can be considered time invariant for the duration of the synchronization burst.
A Pore-forming protein with a protease-activated trigger (1994)

alpha-Hemolysin (alpha HL) is a 293 amino acid pore-forming toxin, which is secreted as a water-soluble monomer by Staphylococcus aureus. By forming a hexameric pore, alpha HL damages the plasma membranes of target cells. Previous studies established that alpha HL proteins with nicks near the midpoint of a central glycine-rich loop are held together by a domain-domain interaction and are hemolytically active. In contrast, alpha HL proteins comprising two alpha HL truncation mutants that overlap in the central loop have no or greatly reduced pore-forming activity, even though the two chains again form a tight complex. Based on these findings, overlap mutants have now been designed that are activated when redundant amino acids in the loop are removed by proteases. Further, the identity of the activating enzyme can be specified by additional mutagenesis of the protease recognition site in the overlap sequence. Mutants of alpha HL that are activated by tumor-associated proteases might be useful components of immunotoxins.
Approximate density functional theory as a practical tool in molecular energetics and dynamics (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTApproximate density functional theory as a practical tool in molecular energetics and dynamicsTom. ZieglerCite this: Chem. Rev. 1991, 91, 5, 651–667Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/cr00005a001https://doi.org/10.1021/cr00005a001research-articleACS PublicationsRequest reuse permissionsArticle Views4524Altmetric-Citations2149LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries. (1990)

A model of proliferative human restenosis was developed in domestic pigs by using deep injury to the coronary arterial media. Metal wire coils were delivered percutaneously to the coronary arteries of 11 pigs with an oversized, high-pressure (14 atm) balloon and were left in place for times ranging from 28 to 70 days. During placement, the balloon expanded the coils and delivered them securely within the arterial lumen. Light microscopic examination of the vessels confirmed fracture of the internal elastic lamina by the coil. An extensive proliferative response occurred in 10 of the 11 pigs and was associated with a luminal area narrowing of at least 50% in all but one pig. The histopathologic features of the proliferative response were identical to those observed in human cases of restenosis after angioplasty. Immunohistochemical studies confirmed the prominence of smooth muscle cells in the proliferative tissue. A similar response was obtained in two of five porcine coronary arteries in which balloon inflation only was performed, without coil implant. This model is practical and inexpensive and closely mimics the proliferative portion of human restenosis both grossly and microscopically. Thus, it may be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures.
Highly accurate sigmoidal fitting of real-time PCR data by introducing a parameter for asymmetry (2008)

The five-parameter sigmoidal models outperform the established four-parameter model with high statistical significance. The estimation of essential PCR parameters such as PCR efficiency, threshold cycles and initial template fluorescence is more robust and has smaller variance. The model is implemented in the qpcR package for the freely available statistical R environment. The package can be downloaded from the author's homepage.
Biochemical Characterization of Acyl Carrier Protein (AcpM) and Malonyl-CoA:AcpM Transacylase (mtFabD), Two Major Components ofMycobacterium tuberculosis Fatty Acid Synthase II (2001)

Malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase (MCAT) is an essential enzyme in the biosynthesis of fatty acids in all bacteria, including Mycobacterium tuberculosis. MCAT catalyzes the transacylation of malonate from malonyl-CoA to activated holo-ACP, to generate malonyl-ACP, which is an elongation substrate in fatty acid biosynthesis. To clarify the roles of the mycobacterial acyl carrier protein (AcpM) and MCAT in fatty acid and mycolic acid biosynthesis, we have cloned, expressed, and purified acpM and mtfabD (malonyl-CoA:AcpM transacylase) from M. tuberculosis. According to the culture conditions used, AcpM was produced in Escherichia coli in two or three different forms: apo-AcpM, holo-AcpM, and palmitoylated-AcpM, as revealed by electrospray mass spectrometry. The mtfabD gene encoding a putative MCAT was used to complement a thermosensitive E. coli fabD mutant. Expression and purification of mtFabD resulted in an active enzyme displaying strong MCAT activity in vitro. Enzymatic studies using different ACP substrates established that holo-AcpM constitutes the preferred substrate for mtFabD. In order to provide further insight into the structure-function relationship of mtFabD, different mutant proteins were generated. All mutations (Q9A, R116A, H194A, Q243A, S91T, and S91A) completely abrogated MCAT activity in vitro, thus underlining the importance of these residues in transacylation. The generation and characterization of the AcpM forms and mtFabD opens the way for further studies relating to fatty acid and mycolic acid biosynthesis to be explored in M. tuberculosis. Since a specific type of FabD is found in mycobacterial species, it represents an attractive new drug target waiting to be exploited.
Reverse Genetics Demonstrates that Proteolytic Processing of the Ebola Virus Glycoprotein Is Not Essential for Replication in Cell Culture (2002)

Ebola virus, a prime example of an emerging pathogen, causes fatal hemorrhagic fever in humans and in nonhuman primates. Identification of major determinants of Ebola virus pathogenicity has been hampered by the lack of effective strategies for experimental mutagenesis. Here we exploit a reverse genetics system that allows the generation of Ebola virus from cloned cDNA to engineer a mutant Ebola virus with an altered furin recognition motif in the glycoprotein (GP). When expressed in cells, the GP of the wild type, but not of the mutant, virus was cleaved into GP1 and GP2. Although posttranslational furin-mediated cleavage of GP was thought to be an essential step in Ebola virus infection, generation of a viable mutant Ebola virus lacking a furin recognition motif in the GP cleavage site demonstrates that GP cleavage is not essential for replication of Ebola virus in cell culture.
Room-Temperature Ionic Liquids and Composite Materials: Platform Technologies for CO2 Capture (2009)

Clean energy production has become one of the most prominent global issues of the early 21st century, prompting social, economic, and scientific debates regarding energy usage, energy sources, and sustainable energy strategies. The reduction of greenhouse gas emissions, specifically carbon dioxide (CO(2)), figures prominently in the discussions on the future of global energy policy. Billions of tons of annual CO(2) emissions are the direct result of fossil fuel combustion to generate electricity. Producing clean energy from abundant sources such as coal will require a massive infrastructure and highly efficient capture technologies to curb CO(2) emissions. Current technologies for CO(2) removal from other gases, such as those used in natural gas sweetening, are also capable of capturing CO(2) from power plant emissions. Aqueous amine processes are found in the vast majority of natural gas sweetening operations in the United States. However, conventional aqueous amine processes are highly energy intensive; their implementation for postcombustion CO(2) capture from power plant emissions would drastically cut plant output and efficiency. Membranes, another technology used in natural gas sweetening, have been proposed as an alternative mechanism for CO(2) capture from flue gas. Although membranes offer a potentially less energy-intensive approach, their development and industrial implementation lags far behind that of amine processes. Thus, to minimize the impact of postcombustion CO(2) capture on the economics of energy production, advances are needed in both of these areas. In this Account, we review our recent research devoted to absorptive processes and membranes. Specifically, we have explored the use of room-temperature ionic liquids (RTILs) in absorptive and membrane technologies for CO(2) capture. RTILs present a highly versatile and tunable platform for the development of new processes and materials aimed at the capture of CO(2) from power plant flue gas and in natural gas sweetening. The desirable properties of RTIL solvents, such as negligible vapor pressures, thermal stability, and a large liquid range, make them interesting candidates as new materials in well-known CO(2) capture processes. Here, we focus on the use of RTILs (1) as absorbents, including in combination with amines, and (2) in the design of polymer membranes. RTIL amine solvents have many potential advantages over aqueous amines, and the versatile chemistry of imidazolium-based RTILs also allows for the generation of new types of CO(2)-selective polymer membranes. RTIL and RTIL-based composites can compete with, or improve upon, current technologies. Moreover, owing to our experience in this area, we are developing new imidazolium-based polymer architectures and thermotropic and lyotropic liquid crystals as highly tailorable materials based on and capable of interacting with RTILs.
Effects of rHuEpo on cellular proliferation and endothelin-1 production in cultured endothelial cells (1995)

rHuEpo directly stimulates EC proliferation as a competence factor, and it also accelerates endothelin-1 production in association with stimulation of DNA and protein syntheses by EC.
Phase 1b Randomized Study of Antidote-Controlled Modulation of Factor IXa Activity in Patients With Stable Coronary Artery Disease (2008)

This is the first experience of an RNA aptamer drug-antidote pair achieving inhibition and active restoration of factor IXa activity in combination with platelet-directed therapy in stable coronary artery disease. The preliminary clinical safety and predictable pharmacodynamic effects form the basis for ongoing studies in patients undergoing elective revascularization procedures.
Controlling the Activities of the Diiron Centre in Bacterial Monooxygenases: Lessons from Mutagenesis and Biodiversity (2015)

Abstract The soluble diiron monooxygenases (SDIMOs) are a diverse group of bacterial enzymes that possess a deeply buried binuclear iron centre that forms an oxo‐diferryl (Fe IV ) intermediate that is capable of oxygenating a wide range of unfunctionalised hydrocarbons and other hydrophobic organic molecules, ranging in size from methane to diaromatics such as naphthalene and substituted biphenyls. In the environment, these enzymes are important in bioremediation of hydrocarbons and chlorinated hydrocarbons and in mitigation of the greenhouse effect due to methane, and also have numerous potential applications in synthetic organic chemistry. In this review we consider how both natural variations among the enzymes and an increasing body of evidence from mutagenesis studies cast light on how the protein controls the size of substrates that can access the active site, the precision of regio‐ and stereoselectivity and the oxidising power of the active centre.
A novel architecture and coexistence method to provide global access to/from Bluetooth WPANs by IEEE 802.11 WLANs (2003)

Bluetooth is a radio technology for wireless personal area networking (WPAN) operating in the 2.4 GHz ISM frequency band. We introduce a novel Bluetooth architecture (BlueStar) whereby selected Bluetooth devices, called Bluetooth wireless gateways (BWGs), are also IEEE 802.11 enabled so that these BWGs could serve as ingress/egress points to/from the IEEE 802.11 wireless network and thus provide access to WANs such as the Internet. We propose mitigating interference between Bluetooth and IEEE 802.11 by employing a hybrid approach of adaptive frequency hopping (AFH) and Bluetooth carrier sense (BCS) of the channels. AFH labels channels as "bad" or "good", and Bluetooth devices only access those channels in the "good" state, whereas BCS is used to avoid collision by sensing the channel prior to any transmission. By combining AFH and BCS, we minimize the effect of the worst-case interference scenario wherein both a Bluetooth and an IEEE 802.11 interface are colocated in a single device. BlueStar enables Bluetooth devices, in either a piconet or a scatternet, to access the WAN through the BWG without the need for any fixed Bluetooth access points, while utilizing the widely deployed base of IEEE 802.11 networks. We define the protocol stack employed by BlueStar as well as indicate how BWGs efficiently manage their capacity allocation through different systems. We also mathematically derive an upper bound on the number of BWGs needed in a scatternet so that uninterrupted access to all Bluetooth devices could be provided.
Cytotoxic Activity of Some AnatolianSalvia. Extracts and Isolated Abietane Diterpenoids (2008)

Salvia hypargeia. Fisch. et Mey. (Lamiaceae) root extract, among 16 Salvia. extracts, showed the highest activity against the human ovarian cancer cell line. Bioactivity-guided fractionation of this plant extract has yielded four abietane-type diterpenes [5,6-didehydro-7-hydroxytaxodone (1), 14-deoxycoleon U (= 6-hydroxysalvinolone) (2), demethylcryptojaponol (3), and salvicanaric acid (4)] two triterpenes (lupeol and lupeol-3-acetate), and a fatty acid mixture consisting mainly of palmitic acid (51.6%) and palmitoleic acid (6.4%). Compounds 2 and 3 were found to be active against A2780 human ovarian cancer cell line with IC50 values of 3.9 and 1.2 μ g/mL, respectively, and the fatty acid composition was the most active part of the extract (IC50 = 0.6 μ g/mL).
Deep neural networks are easily fooled: High confidence predictions for unrecognizable images (2015)

Deep neural networks (DNNs) have recently been achieving state-of-the-art performance on a variety of pattern-recognition tasks, most notably visual classification problems. Given that DNNs are now able to classify objects in images with near-human-level performance, questions naturally arise as to what differences remain between computer and human vision. A recent study [30] revealed that changing an image (e.g. of a lion) in a way imperceptible to humans can cause a DNN to label the image as something else entirely (e.g. mislabeling a lion a library). Here we show a related result: it is easy to produce images that are completely unrecognizable to humans, but that state-of-the-art DNNs believe to be recognizable objects with 99.99% confidence (e.g. labeling with certainty that white noise static is a lion). Specifically, we take convolutional neural networks trained to perform well on either the ImageNet or MNIST datasets and then find images with evolutionary algorithms or gradient ascent that DNNs label with high confidence as belonging to each dataset class. It is possible to produce images totally unrecognizable to human eyes that DNNs believe with near certainty are familiar objects, which we call “fooling images” (more generally, fooling examples). Our results shed light on interesting differences between human vision and current DNNs, and raise questions about the generality of DNN computer vision.
Stability of performance on the Hopkins Verbal Learning Test (1995)

Stability of performance on the Hopkins Verbal Learning Test (HVLT) was assessed in 45 healthy elderly subjects over a 9-month period. Stability coefficients were moderate but statistically significant for total recall (r = 0.50), true-positive recognitions (r = 0.66), and false-positive errors (r = 0.42). These correlations are comparable to test-retest correlations reported for other clinical tests of verbal memory (e.g., Logical Memory subtest of the Wechsler Memory Scale-Revised, California Verbal Learning Test) and are sufficient for its clinical use.
Adeno-associated viral vector delivers cardiac-specific and hypoxia-inducible VEGF expression in ischemic mouse hearts (2004)

It has been shown that the adeno-associated virus (AAV) vector can deliver the VEGF gene efficiently into the ischemic mouse myocardium. However, the AAV genomes can be found in extracardiac organs after intramyocardial injection. To limit unwanted VEGF expression in organs other than the heart, we tested the use of the cardiac myosin light chain 2v (MLC-2v) promoter and the hypoxia-response element to mediate cardiac-specific and hypoxia-inducible VEGF expression. An AAV vector, MLCVEGF, with 250 bp of the MLC-2v promoter and nine copies of the hypoxia-response element driving VEGF expression, was constructed. Gene expression was studied in vitro by infection of rat cardiomyocytes, rat skeletal myocytes, and mouse fibroblasts with the vector and in vivo by direct injection of the vector into normal and ischemic mouse hearts. With MLCVEGF infection, VEGF expression was higher in cardiomyocytes than the other two cell lines and was hypoxiainducible. VEGF expression was also higher in ischemic hearts than in normal hearts. No VEGF expression was detectable in organs with detectable MLCVEGF vectors other than the heart. MLCVEGF-injected ischemic hearts had more capillaries and small vessels around the injection site, smaller infarct size, and better cardiac function than the negative controls. Hence, MLCVEGF can mediate cardiac-specific and hypoxia-inducible VEGF expression, neoangiogenesis, infarct-size reduction, and cardiac functional improvement.
Prevalence of acne and its impact on the quality of life in school-aged adolescents in Malaysia (2009)

Facial acne is a common disorder and appears to have a considerable impact on quality of life among adolescents. The above findings should alert health care professionals and the school authorities to actively identify, manage and educate adolescents with facial acne.
Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins (1998)

Using an in vitro randomization and functional selection procedure, we have identified three novel classes of exonic splicing enhancers (ESEs) recognized by human SF2/ASF, SRp40, and SRp55, respectively. These ESEs are functional in splicing and are highly specific. For SF2/ASF and SRp55, in most cases, only the cognate SR protein can efficiently recognize an ESE and activate splicing. In contrast, the SRp40-selected ESEs can function with either SRp40 or SRp55, but not with SF2/ASF. UV cross-linking/competition and immunoprecipitation experiments showed that SR proteins recognize their cognate ESEs in nuclear extract by direct and specific binding. A motif search algorithm was used to derive consensus sequences for ESEs recognized by these SR proteins. Each SR protein yielded a distinct 5- to 7-nucleotide degenerate consensus. These three consensus sequences occur at higher frequencies in exons than in introns and may thus help define exon-intron boundaries. They occur in clusters within regions corresponding to naturally occurring, mapped ESEs. We conclude that a remarkably diverse set of sequences can function as ESEs. The degeneracy of these motifs is consistent with the fact that exonic enhancers evolved within extremely diverse protein coding sequences and are recognized by a small number of SR proteins that bind RNA with limited sequence specificity.