gebhart/patrepeval huggingface dataset:
Direct electro-deposition of graphene from aqueous suspensions (2011)

We describe the direct electro-chemical reduction of graphene oxide to graphene from aqueous suspension by applying reduction voltages exceeding -1.0 to -1.2 V. The conductivity of the deposition medium is of crucial importance and only values between 4-25 mS cm(-1) result in deposition. Above 25 mS cm(-1) the suspension de-stabilises while conductivities below 4 mS cm(-1) do not show a measurable deposition rate. Furthermore, we show that deposition can be carried out over a wide pH region ranging from 1.5 to 12.5. The electro-deposition process is characterised in terms of electro-chemical methods including cyclic voltammetry, quartz crystal microbalance, impedance spectroscopy, constant amperometry and potentiometric titrations, while the deposits are analysed via Raman spectroscopy, infra-red spectroscopy, X-ray photoelectron spectroscopy and X-ray diffractometry. The determined oxygen contents are similar to those of chemically reduced graphene oxide, and the conductivity of the deposits was found to be ∼20 S cm(-1).
Expression of IL‐15RA or an IL‐15/IL‐15RA fusion on CD8+ T cells modifies adoptively transferred T‐cell function in cis (2009)

IL-15 and IL-15 receptor alpha (IL-15RA) play a significant role in multiple aspects of T-cell biology. However, given the evidence that IL-15RA can present IL-15 in trans, the functional capacity of IL-15RA expressed on CD8(+) T cells to modify IL-15 functions in cis is currently unclear. In the current study, we explore the functional consequences of IL-15RA, expression on T cells using a novel method to transfect naive CD8(+) T cells. We observed that RNA nucleofection led to highly efficient, non-toxic, and rapid manipulation of protein expression levels in unstimulated CD8(+) T cells. We found that transfection of unstimulated CD8(+) T cells with IL-15RA RNA led to enhanced viability of CD8(+) T cells in response to IL-15. Transfection with IL-15RA enhanced IL-15-mediated phosphorylation of STAT5 and also promoted IL-15-mediated proliferation in vivo of adoptively transferred naïve CD8(+) T cells. We demonstrated that IL-15RA can present IL-15 via cis-presentation on CD8(+) T cells. Finally, we showed that transfection with a chimeric construct linking IL-15 to IL-15RA cell autonomously enhances the viability and proliferation of primary CD8(+) T cells and cytotoxic potential of antigen-specific CD8(+) T cells. The clinical implications of the current study are discussed.
Human Papillomavirus Type 6b Virus-Like Particles Are Able To Activate the Ras-MAP Kinase Pathway and Induce Cell Proliferation (2001)

The initial step in viral infection is the attachment of the virus to the host cell via an interaction with its receptor. We have previously shown that a receptor for human papillomavirus is the alpha6 integrin. The alpha6 integrin is involved in the attachment of epithelial cells with the basement membrane, but recent evidence suggests that ligation of many integrins results in intracellular signaling events that influence cell proliferation. Here we present evidence that exposure of A431 human epithelial cells to human papillomavirus type 6b L1 virus-like particles (VLPs) results in a dose-dependent increase in cell proliferation, as measured by bromodeoxyuridine incorporation. This proliferation is lost if VLPs are first denatured or incubated with a monoclonal antibody against L1 protein. The MEK1 inhibitor PB98059 inhibits the VLP-mediated increase in cell proliferation, suggesting involvement of the Ras-MAP kinase pathway. Indeed, VLP binding results in rapid phosphorylation of the beta4 integrin upon tyrosine residues and subsequent recruitment of the adapter protein Shc to beta4. Within 30 min, the activation of Ras, Raf, and Erk2 was observed. Finally, the upregulation of c-myc mRNA was observed at 60 min. These data indicate that human papillomavirus type 6b is able to signal cells via the Ras-MAP kinase pathway to induce cell proliferation. We hypothesize that such a mechanism would allow papillomaviruses to infect hosts more successfully by increasing the potential pool of cells they are able to infect via the initiation of proliferation in resting keratinocyte stem and suprabasal cells.
Implication of phagosome-lysosome fusion in restriction of Mycobacterium avium growth in bone marrow macrophages from genetically resistant mice (1993)

The ability of the host to resist infection to a variety of intracellular pathogens, including mycobacteria, is strongly dependent upon the expression of the Bcg gene. Mouse strains which express the resistance phenotype (Bcgr) restrict bacterial growth, whereas susceptible strains (Bcgs) allow bacterial growth. Expression of the Bcg allele is known to influence the priming of host macrophages (M phi s) for bactericidal function. In the present work, bone marrow-derived M phi s from congenic BALB/c (Bcgs) and C.D2 (BALB/c.Bcgr) mice were infected with the virulent strain Mycobacterium avium TMC 724 to define the mechanism involved in growth restriction of M. avium. By combining CFU measurements and ultrastructural analyses, we show that growth of this bacterium is restricted in marrow M phi s from resistant mice. Using acid phosphatase as a lysosomal marker, we provide evidence that the hydrolytic activity of M phi s, as measured by the capacity of lysosomes to fuse with and transfer active hydrolytic enzymes to phagosomes in which M. avium resides, is an expression of the Bcg gene and that this phenomenon is a key antibacterial activity responsible for growth restriction of M. avium: (i) the percentage of phagosome-lysosome fusions was twice as high in Bcgr M phi s as in Bcgs M phi s, and (ii) the percentage of intact viable bacteria residing in acid phosphatase-negative phagosomes was twice as low in Bcgr M phi s as in the Bcgs counterparts. These differences are not due to a lower activity of the enzyme in Bcgr M phi s. The mechanism by which the Bcg gene exerts control over the phagolysosomal fusion is discussed.
Angiotensin-(1-7) improves the post-ischemic function in isolated perfused rat hearts (2002)

We evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) on post-ischemic function in isolated hearts from adult male Wistar rats perfused according to the Langendorff technique. Local ischemia was induced by coronary ligation for 15 min. After ischemia, hearts were reperfused for 30 min. Addition of angiotensin II (Ang II) (0.20 nM, N = 10) or Ang-(1-7) (0.22 nM, N = 10) to the Krebs-Ringer perfusion solution (KRS) before the occlusion did not modify diastolic or systolic tension, heart rate or coronary flow (basal values for Ang-(1-7)-treated hearts: 0.72 +/- 0.08 g, 10.50 +/- 0.66 g, 216 +/- 9 bpm, 5.78 +/- 0.60 ml/min, respectively). During the period of occlusion, the coronary flow, heart rate and systolic tension decreased (values for Ang-(1-7)-treated hearts: 2.83 +/- 0.24 ml/min, 186 +/- 7 bpm, 6.95 +/- 0.45 g, respectively). During reperfusion a further decrease in systolic tension was observed in control (4.95 +/- 0.60 g) and Ang II-treated hearts (4.35 +/- 0.62 g). However, in isolated hearts perfused with KRS containing Ang-(1-7) the further reduction of systolic tension during the reperfusion period was prevented (7.37 +/- 0.68 g). The effect of Ang-(1-7) on the systolic tension was blocked by the selective Ang-(1-7) antagonist A-779 (2 nM, N = 9), by the bradykinin B2 antagonist HOE 140 (100 nM, N = 10), and by indomethacin pretreatment (5 mg/kg, ip, N = 8). Pretreatment with L-NAME (30 mg/kg, ip, N = 8) did not change the effect of Ang-(1-7) on systolic tension (6.85 +/- 0.61 g). These results show that Ang-(1-7) at low concentration (0.22 nM) improves myocardial function (systolic tension) in ischemia/reperfusion through a receptor-mediated mechanism involving release of bradykinin and prostaglandins.
A Novel LSD1 Inhibitor T-3775440 Disrupts GFI1B-Containing Complex Leading to Transdifferentiation and Impaired Growth of AML Cells (2016)

Dysregulation of lysine (K)-specific demethylase 1A (LSD1), also known as KDM1A, has been implicated in the development of various cancers, including leukemia. Here, we describe the antileukemic activity and mechanism of action of T-3775440, a novel irreversible LSD1 inhibitor. Cell growth analysis of leukemia cell lines revealed that acute erythroid leukemia (AEL) and acute megakaryoblastic leukemia cells (AMKL) were highly sensitive to this compound. T-3775440 treatment enforced transdifferentiation of erythroid/megakaryocytic lineages into granulomonocytic-like lineage cells. Mechanistically, T-3775440 disrupted the interaction between LSD1 and growth factor-independent 1B (GFI1B), a transcription factor critical for the differentiation processes of erythroid and megakaryocytic lineage cells. Knockdown of LSD1 and GFI1B recapitulated T-3775440-induced transdifferentiation and cell growth suppression, highlighting the significance of LSD1-GFI1B axis inhibition with regard to the anti-AML effects of T-3775440. Moreover, T-3775440 exhibited significant antitumor efficacy in AEL and AMKL xenograft models. Our findings provide a rationale for evaluating LSD1 inhibitors as potential treatments and indicate a novel mechanism of action against AML, particularly AEL and AMKL. Mol Cancer Ther; 16(2); 273-84. ©2016 AACR.
Density Estimation (2004)

This paper provides a practical description of density estimation based on kernel methods. An important aim is to encourage practicing statisticians to apply these methods to data. As such, reference is made to implementations of these methods in R, S-PLUS and SAS.
Polarization mode dispersion emulator (2002)

We investigate a new technique to realistically emulate polarization mode dispersion. We demonstrate that 15 sections of polarization-maintaining fiber with randomly rotatable connections emulates an almost ideal Maxwellian differential group delay (DGD) distribution, whereas fixed connections is inadequate.
Antiviral Drug Resistance of Human Cytomegalovirus (2010)

The study of human cytomegalovirus (HCMV) antiviral drug resistance has enhanced knowledge of the virological targets and the mechanisms of antiviral activity. The currently approved drugs, ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), target the viral DNA polymerase. GCV anabolism also requires phosphorylation by the virus-encoded UL97 kinase. GCV resistance mutations have been identified in both genes, while FOS and CDV mutations occur only in the DNA polymerase gene. Confirmation of resistance mutations requires phenotypic analysis; however, phenotypic assays are too time-consuming for diagnostic purposes. Genotypic assays based on sequencing provide more rapid results but are dependent on prior validation by phenotypic methods. Reports from many laboratories have produced an evolving list of confirmed resistance mutations, although differences in interpretation have led to some confusion. Recombinant phenotyping methods performed in a few research laboratories have resolved some of the conflicting results. Treatment options for drug-resistant HCMV infections are complex and have not been subjected to controlled clinical trials, although consensus guidelines have been proposed. This review summarizes the virological and clinical data pertaining to HCMV antiviral drug resistance.
Toward two-dimensional self-organization of nanostructures using wafer bonding and nanopatterned silicon surfaces (2002)

The structure of ultrathin silicon layers obtained by molecular hydrophobic bonding is investigated. The twist and tilt angles between the two crystals are accurately controlled. The buried Si|Si interface is observed by transmission electron microscopy and by grazing incidence X-ray techniques. For low twist angle values (/spl psi/<5/spl deg/) plane view observations reveal well-defined dislocation networks. Cross-section observations give evidence that the dislocation networks are localized at the bonding interfacial plane with no threading dislocation. Grazing incidence small angle X-ray scattering measurements confirm the good quality of the bonding interface as well as the quality of the dislocation networks. Grazing incidence X-ray diffraction is also used and shows the long-range order of the periodic strain field in the silicon layer. It shows, especially, the interaction between the dislocations. X-ray reflectivity was employed and estimated that the interfacial thickness (i.e., thickness of the bonding) lower than 1 nm decreases when the twist angle increases. The nanopatterned surface is then investigated by scanning tunneling microscopy and X-ray methods. To validate these substrates for long-range order self-organization, the growth of Si and Ge quantum dots is finally achieved.
The Role of Mitochondrial DNA Copy Number in Mammalian Fertility1 (2010)

Mammalian mitochondrial DNA (mtDNA) is a small, maternally inherited genome that codes for 13 essential proteins in the respiratory chain. Mature oocytes contain more than 150 000 copies of mtDNA, at least an order of magnitude greater than the number in most somatic cells, but sperm contain only approximately 100 copies. Mitochondrial oxidative phosphorylation has been suggested to be an important determinant of oocyte quality and sperm motility; however, the functional significance of the high mtDNA copy number in oocytes, and of the low copy number in sperm, remains unclear. To investigate the effects of mtDNA copy number on fertility, we genetically manipulated mtDNA copy number in the mouse by deleting one copy of Tfam, an essential component of the mitochondrial nucleoid, at different stages of germline development. We show that males can tolerate at least a threefold reduction in mtDNA copy number in their sperm without impaired fertility, and in fact, they preferentially transmit a deleted Tfam allele. Surprisingly, oocytes with as few as 4000 copies of mtDNA can be fertilized and progress normally through preimplantation development to the blastocyst stage. The mature oocyte, however, has a critical postimplantation developmental threshold of 40 000-50 000 copies of mtDNA in the mature oocyte. These observations suggest that the high mtDNA copy number in the mature oocyte is a genetic device designed to distribute mitochondria and mtDNAs to the cells of the early postimplantation embryo before mitochondrial biogenesis and mtDNA replication resumes, whereas down-regulation of mtDNA copy number is important for normal sperm function.
Characterization of human cardiac myosin heavy chain genes. (1989)

We have isolated and analyzed the structure of the genes coding for the alpha and beta forms of the human cardiac myosin heavy chain (MYHC). Detailed analysis of four overlapping MYHC genomic clones shows that the alpha-MYHC and beta-MYHC genes constitute a total length of 51 kilobases and are tandemly linked. The beta-MYHC-encoding gene, predominantly expressed in the normal human ventricle and also in slow-twitch skeletal muscle, is located 4.5 kilobases upstream of the alpha-MYHC-encoding gene, which is predominantly expressed in normal human atrium. We have determined the nucleotide sequences of the beta form of the MYHC gene, which is 100% homologous to the cardiac MYHC cDNA clone (pHMC3). It is unlikely that the divergence of a few nucleotide sequences from the cardiac beta-MYHC cDNA clone (pHMC3) reported in a MYHC cDNA clone (pSMHCZ) from skeletal muscle is due to a splicing mechanism. This finding suggests that the same beta form of the cardiac MYHC gene is expressed in both ventricular and slow-twitch skeletal muscle. The promoter regions of both alpha- and beta-MYHC genes, as well as the first four coding regions in the respective genes, have also been sequenced. The sequences in the 5'-flanking region of the alpha- and beta-MYHC-encoding genes diverge extensively from one another, suggesting that expression of the alpha- and beta-MYHC genes is independently regulated.
2‘-Deoxyisoguanosine Adopts More than One Tautomer To Form Base Pairs with Thymidine Observed by High-Resolution Crystal Structure Analysis (1998)

The questions of whether different tautomeric forms of nucleic acid bases exist to any significant extent in DNA, or what their possible roles in mutation may be, are under intense scrutiny. 2'-Deoxyisoguanosine (iG) has been suggested to have a propensity to adopt the enol form. Isoguanine (also called 2-hydroxyadenine) can be found in oxidatively damaged DNA generated from treating DNA with a Fenton-type reactive oxygen-generating system and is known to cause mutation. We have analyzed the three-dimensional structure of the DNA dodecamer d(CGC[iG]AATTTGCG) (denoted iG-DODE) by X-ray crystallography and NMR. The crystal structure of the iG-DODE complexed with the minor groove binder Hoechst 33342, refined to 1.4 A resolution, showed that the two independent iG.T base pairs in the dodecamer duplex adopt different (one in Watson-Crick and the other in wobble) conformations. The high-resolution nature of the structure also affords unprecedented clear information about the conformation and interactions of the Hoechst drug. The Hoechst 33342 binds in the narrow minor groove at the iGAATT site, with the N-methylpiperazine ring near the iG4.T21 base pair. Three hydrogen bonds are found between the NH of the Hoechst ligand and T-O2 DNA atoms. In solution, the two iG.T base pairs in iG-DODE predominantly are in the wobble form at 2 degreesC. At higher temperatures, another duplex form (likely involving the enol form of iG) is in slow exchange with the keto form and becomes significantly populated, reaching approximately 40% at 40 degreesC. Our data support the conclusion that iG pairs with T in a Watson-Crick configuration to a significant extent at physiological temperature (37 degreesC), which may explain the facile incorporation rate of T across from an iG during in vitro DNA replication.
Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease (2010)

This interventional study provides Class II evidence that atomoxetine (target dosage = 80 mg/day) is not efficacious in improving clinically significant depression in PD.
Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis (1997)

Steroidogenesis begins with the metabolism of cholesterol to pregnenolone by the inner mitochondrial membrane cytochrome P450 side-chain cleavage (P450scc) enzyme. The rate of steroid formation, however, depends on the rate of cholesterol transport from intracellular stores to the inner mitochondrial membrane and loading of P450scc with cholesterol. In previous in vitro studies, we demonstrated that a key element in the regulation of cholesterol transport is the mitochondrial peripheral-type benzodiazepine receptor (PBR). We also showed that the polypeptide diazepam binding inhibitor (DBI), an endogenous PBR ligand, stimulates cholesterol transport and promotes loading of cholesterol to P450scc in vitro, and that its presence is vital for hCG-induced steroidogenesis by Leydig cells. Based on these data and the observations that i) the mitochondrial PBR binding and topography are regulated by hormones; ii) the 18-kDa PBR protein is functionally coupled to the mitochondrial contact site voltage-dependent anion channel protein; iii) the 18-kDa PBR protein is a channel for cholesterol, as shown by molecular modeling and in vitro reconstitution studies; iv) targeted disruption of the PBR gene in steroidogenic cells dramatically reduces the ability of the cells to transport cholesterol in the mitochondria and produce steroids; v) endocrine disruptors, with known anisteroidogenic effect, inhibit PBR ligand binding; and vi) in vivo reduction of adrenal PBR expression results in reduced circulating glucocorticoid levels, we conclude that PBR is an indispensable element of the steroidogenic machinery.
Radiofrequency catheter ablation for atrial fibrillation (1995)

Division of Cardiology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Analyzingb→utransitions in semileptonicB¯s→K*+(→Kπ)ℓ−ν¯ℓdecays (2015)

We study the semileptonic decay ${\overline{B}}_{s}\ensuremath{\rightarrow}{K}^{*+}{\ensuremath{\ell}}^{\ensuremath{-}}{\overline{\ensuremath{\nu}}}_{\ensuremath{\ell}}$, which is induced by $b\ensuremath{\rightarrow}u{\ensuremath{\ell}}^{\ensuremath{-}}{\overline{\ensuremath{\nu}}}_{\ensuremath{\ell}}$ transitions at the quark level. We take into account the standard model (SM) operator from $W$-boson exchange as well as possible extensions from physics beyond the SM. The secondary decay ${K}^{*+}\ensuremath{\rightarrow}K\ensuremath{\pi}$ can be used to study a number of angular observables, which are worked out in terms of short-distance Wilson coefficients and hadronic form factors. Our analysis allows for an independent extraction of the Cabibbo-Kobayashi-Maskawa matrix element $|{V}_{ub}|$ and for the determination of certain ratios of ${\overline{B}}_{s}\ensuremath{\rightarrow}{K}^{*}$ form factors. Moreover, a future precision measurement of the forward-backward asymmetry in the ${\overline{B}}_{s}\ensuremath{\rightarrow}{K}^{*+}{\ensuremath{\ell}}^{\ensuremath{-}}{\overline{\ensuremath{\nu}}}_{\ensuremath{\ell}}$ decay can be used to unambiguously verify the left-handed nature of the transition operator as predicted by the SM. We provide numerical estimates for the relevant angular observables and the resulting decay distributions on the basis of available form-factor information from lattice and sum-rule estimates. In addition, we pay particular attention to suitable combinations of angular observables in the decays ${\overline{B}}_{s}\ensuremath{\rightarrow}{K}^{*+}(\ensuremath{\rightarrow}K\ensuremath{\pi}){\ensuremath{\ell}}^{\ensuremath{-}}{\overline{\ensuremath{\nu}}}_{\ensuremath{\ell}}$ and $\overline{B}\ensuremath{\rightarrow}{K}^{*0}(\ensuremath{\rightarrow}K\ensuremath{\pi}){\ensuremath{\ell}}^{+}{\ensuremath{\ell}}^{\ensuremath{-}}$, and find that they provide complementary constraints on the relevant $b\ensuremath{\rightarrow}s$ short-distance coefficients. As a by-product, we perform a SM fit on the basis of selected experimental decay rates in both inclusive and exclusive channels, and hadronic input functions. We find $|{V}_{ub}|=(4.07\ifmmode\pm\else\textpm\fi{}0.20)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}$.
High-Density Lipoprotein–Based Contrast Agents for Multimodal Imaging of Atherosclerosis (2009)

Lipoproteins, natural nanoparticles, have a well-recognized biological role and are highly suitable as a platform for delivering imaging agents. The ease with which both the exterior and interior of the particles can be modified permits the creation of multifunctional nanoparticles for imaging as well as the delivery of therapeutics. Importantly, their endogenous nature may make them biocompatible and biodegradable and allows them to avoid the recognition of the reticuloendothelial system. In particular, high-density lipoproteins (HDL) are of interest, because of their small size they can easily cross the endothelium and penetrate the underlying tissue. We summarize here the progress in establishing HDL as a vector for delivering a variety of diagnostically active materials to vulnerable atherosclerotic plaques in mouse models of atherosclerosis. By loading various types of image-enhancing compounds into either the core or surface of HDL, they can be visualized by different imaging modalities (MRI, CT, optical). By rerouting of HDL away from plaque macrophages, imaging of biological processes in diseases besides atherosclerosis may also be achieved.