gebhart/patrepeval huggingface dataset:
High Breakdown Point Conditional Dispersion Estimation with Application to S & P 500 Daily Returns Volatility (1998)

We show that quasi-maximum likelihood (QML) estimators for conditional dispersion models can be severely affected by a small number of outliers such as market crashes and rallies, and we propose new estimation strategies (the two-stage Hampel estimators and two-stage S-estimators) resistant to the effects of outliers and study the properties of these estimators. We apply our methods to estimate models of the conditional volatility of the daily returns of the S&P 500 Cash Index series. In contrast to QML estimators, our proposed method resists outliers, revealing an informative new picture of volatility dynamics during typical daily market activity.
A comparison of the attitudes of obstetricians and family physicians toward obstetric practice, training, and hospital privileges of family physicians. (1990)

Responses of national samples of 329 residency-trained family physicians and 237 obstetricians were studied to determine the attitudes of family physicians and obstetricians toward the practice of obstetrics by family physicians. The attitudes of obstetricians and family physicians varied greatly, and the attitudes of obstetricians toward obstetric care provided by family physicians tended to become less supportive following the time of the obstetricians' training. In particular, obstetricians felt strongly that family physicians were inadequately trained to provide uncomplicated obstetric care. These negative attitudes were reflected in obstetricians' opinions regarding hospital obstetric privileges for family physicians. From a list of 11 obstetric privileges, obstetricians indicated that residency-trained family physicians should be granted a mean of 2.2 privileges, while family physicians who currently practice obstetrics indicated a mean of 6.6 (P less than .001). Family physicians who felt well supported by obstetricians during their obstetric training were more likely to develop positive attitudes toward obstetric practice than those who were not well supported. Both obstetricians and family physicians indicated that the adequacy of maternity care in rural areas would decline if family physicians withdrew from maternity care. There was strong agreement that rising malpractice premiums may soon force family physicians to stop delivering babies. This study concludes that there are vast differences among obstetricians and family physicians in perceptions regarding obstetric practice by family physicians which may adversely affect such practice.
Recurrent Glioblastomas Reveal Molecular Subtypes Associated with Mechanistic Implications of Drug-Resistance (2015)

Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemness-related genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6) in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprograming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.
What can a clock mutation in mice tell us about bipolar disorder? (2007)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Dendrimers as Biopharmaceuticals: Synthesis and Properties (2008)

Two general aspects which need to be considered for the successful application of dendrimers for biomedical purposes are their availability at an acceptable cost and their suitability as regards their pharmacodynamic and pharmacokinetic properties. These two aspects are covered in this review. In the first part, synthetic strategies for the preparation of dendrimers are outlined and emphasis is given to recent work on methodologies whose aim is the development of more efficient routes to dendrimers in terms of the materials used for their synthesis as well as in terms of the procedures required for their purification. These include procedures involving double-stage and double exponential synthesis, orthogonal coupling strategies, self-assembly and solid-phase approaches, as well as particularly useful synthetic protocols such as those used in "click chemistry". The second part of the review deals with the way in which the size, chemical constitution and physicochemical properties of dendrimers used for drug delivery may affect pharmacodynamic and pharmacokinetic parameters which are important considerations for drug bioavailability. This is illustrated by an overview of examples from recent work involving non-steroidal anti-inflammatory drugs, anticancer drugs and antibacterials.
Regulatory T cells in skin (2017)

Foxp3<sup>+</sup> CD4<sup>+</sup> regulatory T (Treg) cells are a subset of immune cells that function to regulate tissue inflammation. Skin is one of the largest organs and is home to a large proportion of the body's Treg cells. However, relative to other tissues (such as the spleen and gastrointestinal tract) the function of Treg cells in skin is less well defined. Here, we review our understanding of how Treg cells migrate to skin and the cellular and molecular pathways required for their maintenance in this tissue. In addition, we outline what is known about the specialized functions of Treg cells in skin. Namely, the orchestration of stem cell-mediated hair follicle regeneration, augmentation of wound healing, and promoting adaptive immune tolerance to skin commensal microbes. A comprehensive understanding of the biology of skin Treg cells may lead to novel therapeutic approaches that preferentially target these cells to treat cutaneous autoimmunity, skin cancers and disorders of skin regeneration.
Three‐Dimensional Programmable Assembly by Untethered Magnetic Robotic Micro‐Grippers (2014)

Mobile sub‐millimeter micro‐robots have demonstrated untethered motion and transport of cargo in remote, confined or enclosed environments. However, limited by simple design and actuation, they lack remotely‐actuated on‐board mechanisms required to perform complex tasks such as object assembly. A flexible patterned magnetic material which allows internal actuation, resulting in a mobile micro‐gripper which is driven and actuated by magnetic fields, is introduced here. By remotely controlling the magnetization direction of each micro‐gripper arm, a gripping motion which can be combined with locomotion for precise transport, orientation, and programmable three‐dimensional assembly of micro‐parts in remote environments is demonstrated. This allows the creation of out‐of‐plane 3D structures and mechanisms made from several building blocks. Using multiple magnetic materials in each micro‐gripper, the addressable actuation of gripper teams for parallel, distributed operation is also demonstrated. These mobile micro‐grippers can potentially be applied to 3D assembly of heterogeneous meta‐materials, construction of medical devices inside the human body, the study of biological systems in micro‐fluidic channels, 3D micro‐device prototyping or desktop micro‐factories.
Effect of Cerivastatin on Endothelial Dysfunction and Aortic CD36 Expression in Diabetic Hyperlipidemic Rats (2004)

A mutation of the CD36 gene that encodes a fatty acid transporter has been reported to play a role in insulin resistance in spontaneously hypertensive rat (SHR). Statins reduce circulating cholesterol and triglyceride concentrations. The objective of this study was to determine the role of CD36 and the significance of statin therapy in insulin-resistance syndromes. We determined the isometric relaxation induced by acetylcholine or lecithinized superoxide dismutase (SOD) in aortas obtained from Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of insulin resistance and dyslipidemia, and normal control (Long Evans Tokushima Otsuka; LETO) rats with or without cerivastatin treatment. We also determined the effect of cerivastatin on aortic expression of CD36 and PPARgamma. The CD36 genotype and microsatellite markers on chromosome 4 were also determined. The relaxation induced by acetylcholine and lecithinized SOD were attenuated in OLETF rats but restored by a low dose of cerivastatin without significant changes in serum cholesterol. These relaxations were also restored by a high dose of cerivastatin with significant reductions in serum cholesterol and triglyceride. Cerivastatin increased the aortic expression of CD36 and PPARgamma mRNA in both LETO and OLETF rats. However, the basal level of CD36 mRNA and the increase in CD36 mRNA in response to cerivastatin were significantly lower in OLETF rats than in LETO rats. Although the abnormal CD36 genotype reported in SHR was not found in OLETF rats, the microsatellite markers of D4Rat151 and D4Rat115 differed between OLETF and LETO rats. In conclusion, insulin resistance in OLETF rats may be partially due to an altered expression of CD36. Increased aortic expression of CD36 in response to cerivastatin could explain the reduction in serum triglyceride concentrations with statin therapy and may have pronounced beneficial effects in insulin-resistance syndromes.
Preference Programming for Configuration (2001)

Preference programming provides a new paradigm for expressing (default) decisions, preferences between decisions, and search strategies in a declarative and unified way and for embedding them in a constraint and rule language. Business experts can thus directly specify preferences and search directives in form of rules without needing to program search strategies as required by constraint programming based configuration tools. Preference programming allows to describe preferences between individual decisions, as well as groups of decisions and decision rules. There can be dynamic (or context-dependent) preferences, inconsistent preferences, and meta-preferences. Following [Brewka, 1989; Junker, 1997], preferences constrain the order in which decisions are made during search. It is possible to enumerate all configurations or to focus search to preferred configurations, which respect the default choices and preferences of the user.
Variable insurance premium for safer driving: A survey result (2011)

Driving involves a risk of having accidents, of which insurance companies cover the financial consequences. They would prefer their customers to drive safer. A survey was carried out to study drivers' reactions on variable insurance premiums. An in-car device would record the driving behaviour and send an aggregated report, calculating the reward based on total distance, distance less in risky conditions (nighttime, speeding) or environments (urban, extraurban). According to the survey, 27% of the drivers is willing to change to an insurance with a variable rate, and that this hardly depends on the final reward, but it depends more the driver himself. Approximately 25% indicates to change the driving behaviour due to the variable premium. Finally, drivers are not simply choosing the cheapest insurance, but value some elements (e.g., reward for total mileage) more than others (e.g., reward for urban mileage).
Development of spontaneous multisystem autoimmune disease and hypersensitivity to antibody‐induced inflammation in Fcγ receptor IIa–transgenic mice (2005)

The presence of enhanced passive and induced autoimmunity, as well as the emergence of spontaneous autoimmune disease at 20-45 weeks of age, suggest that FcgammaRIIa is a very important factor in the pathogenesis of autoimmune inflammation and a possible target for therapeutic intervention.
On the Hilbert-Huang transform data processing system development (2004)

One of the main heritage tools used in scientific and engineering data spectrum analysis is the Fourier Integral Transform and its high performance digital equivalent - the fast Fourier transform (FFT). The Fourier view of nonlinear mechanics that had existed for a long time, and the associated FFT (fairly recent development), carry strong a-priori assumptions about the source data, such as linearity and of being stationary. Natural phenomena measurements are essentially nonlinear and nonstationary. A development at the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC), known as the Hilbert-Huang transform (HHT) proposes an approach to the solution for the nonlinear class of spectrum analysis problems. Using the empirical mode decomposition (EMD) followed by the Hilbert transform of the empirical decomposition data (HT) as stated in N.E. Huang et al. (1998), N. E. Huang (1999), and N. E. Huang (2001), the HHT allows spectrum analysis of nonlinear and nonstationary data by using an engineering a-posteriori data processing, based on the EMD algorithm. This results in a non-constrained decomposition of a source real value data vector into a finite set of intrinsic mode functions (IMF) that can be further analyzed for spectrum interpretation by the classical Hilbert transform. This paper describes phase one of the development of a new engineering tool, the HHT data processing system (HHTDPS). The HHTDPS allows applying the HHT to a data vector in a fashion similar to the heritage FFT. It is a generic, low cost, high performance personal computer (PC) based system that implements the HHT computational algorithms in a user friendly, file driven environment. This paper also presents a quantitative analysis for a composite waveform data sample, a summary of technology commercialization efforts and the lessons learned from this new technology development.
Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells (2010)

In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity appear to be particularly promising targets for antigen-specific induction of tolerance without compromising desired protective host immune responses. Several lines of evidence suggest that delivery of antigens to antigen-presenting dendritic cells (DCs) in the steady state (i.e., to immature DCs) may represent a suitable approach to induce antigen-specific T-cell tolerance peripherally. Here, we report that anti-DEC205-mediated delivery of the self-peptide proteolipid protein (PLP)139-151 to DCs ameliorated clinical symptoms in the PLP-induced SJL model of experimental autoimmune encephalomyelitis. Splenocytes from treated mice were anergized to PLP139-151, and IL-17 secretion was markedly reduced. Moreover, we show directly, using transgenic CD4(+) Vβ6(+) TCR T cells specific for PLP139-151, that, under the conditions of the present experiments, these cells also became anergic. In addition, evidence for a CD4(+) T cell-mediated suppressor mechanism was obtained.
Induction of Amphiphilicity in Polymer@Silica Particles: Ceramic Surfactants (2013)

It is shown that, in general, when submicrometer hybrid particles of polymer@silica are subjected to thermal treatment, phase-separated hydrophobicity emerges at particles surface; and that the triggering of hydrophobicity results in particles which show amphiphilic behavior, arranging themselves at water interfaces and stabilizing W/O and O/W emulsions. Many polymer@silica particles show this behavior, and the entrapped polymers include polyethylene Engage, poly(dimethylsiloxane), poly-l-lactic acid, poly(ethylene-block-ethyleneglycol), poly(styrene-co-allyl-achohol), and poly(dimethylesiloxane-block-ethyleneoxide-co-propyleneoxide). The concept is attractive because, by doping the particles with functional molecules, one can get various surfactants from the same treated particle; this is demonstrated with fluorescent probes. It is proposed that the amphiphilic activity is due to Janus heterogeneous distribution of the hydrophobic moieties on the surface.
Structure of in‐serum transfecting DNA–cationic lipid complexes (1997)

Noticeable modifications of in-serum transfection efficiency of dioctadecylamidoglycyl-spermine (DOGS)-DNA complexes are observed, depending on DNA condensation conditions. The structures of the complexes are studied, keeping in mind the variability of lipid polymorphism, by cryo-transmission electron microscopy and X-ray diffraction. By increasing both pH and ionic strength, well-organised lamellar structures with a period of 65 A replace supramicellar aggregates. A relationship between the structures and their in-vitro transfection activity is established. Efficiency in the presence of serum is maintained when a lamellar arrangement is involved.
Serological identification of breast cancer-related antigens from aSaccharomyces cerevisiae surface display library (2005)

A yeast cell surface display technology was used for the isolation and characterization of tumor antigens recognised by autologous or allogeneic breast cancer serum. More than 100 clones recognized by patient serum were isolated using high-through-put fluorescence activated cell sorting. Combined serological and sequence analysis confirmed that a number of proteins known to be overexpressed in breast cancer tissue could be detected. A recently identified small breast epithelial mucin almost exclusively expressed in mammary gland tissue was isolated as a mutated protein variant. Subsequent serological analysis using the yeast expression system for the wild-type and mutant form showed a strong recognition by patient sera, whereas no significant recognition was observed for the respective prokaryotically expressed proteins. The small breast epithelial mucin is present to a large extent in a membrane bound format and might be used for tumor targeting strategies.
Retroviral gene transfer of human adenosine deaminase in murine hematopoietic cells: effect of selectable marker sequences on long-term expression (1991)

Retroviral-mediated gene transfer of human adenosine deaminase (hADA) provides a model system for the development of somatic gene therapy as a therapy for diseases of bone marrow-derived cells. We have previously demonstrated that hADA can be observed in all hematopoietic lineages in a minority of mice transplanted with bone marrow cells infected with a simplified retroviral vector, ZipPGK-ADA. Here we report a majority of mice (six of eight) demonstrate expression of hADA in the peripheral blood at least 6 months after transplantation with bone marrow infected with this simplified retroviral vector, which contains no selectable marker. The failure to express hADA in two of eight mice was associated with the absence of the recombinant retroviral provirus in DNA prepared from bone marrow cells of these mice apparently due to failure to efficiently infect the reconstituting hematopoietic stem cell. In an effort to preselect bone marrow stem cells containing proviral integrations, we incorporated the selectable marker neo phosphotransferase (NEO) into a retroviral vector encoding hADA, N2/ZipPGK-ADATKNEO, and used G418 selection of infected bone marrow cells before transplantation. In contrast to the simplified retroviral vector, hADA expression in these recipients was short lived (less than 8 weeks), despite the continued presence of intact provirus in DNA prepared from bone marrow of these mice. To determine whether the preselection of bone marrow using G418 was responsible for the lack of sustained hADA expression, we repeated the infection with the N2/ZipPGK- ADATKNEO vector but omitted the G418 selection step. Again, the majority of recipient mice failed to express hADA long term, although the continued presence of provirus in DNA prepared from peripheral blood cell mononuclear cells was clearly demonstrated. Finally, we demonstrate clonal fluctuation of infected stem cells, and observe a temporal correlation between cessation of expression of hADA and the emergence of a dominant stem cell clone between 14 and 20 weeks posttransplantation in one recipient. These data suggest that inclusion of a second transcriptional unit that includes neo phosphotransferase sequences in this simplified vector is associated with decreased expression of the nonselectable ADA sequences.
Nature of Surface-Induced Nuclear-Spin Relaxation of GaseousHe3 (1969)

Surface-induced spin-lattice relaxation times are reported as a function of temperature for gaseous ${\mathrm{He}}^{3}$ in glass containers. The results are interpreted in terms of a phenomenological theory incorporating distinctly different relaxation processes at low and high temperatures, respectively. The low-temperature mechanism involves ${\mathrm{He}}^{3}$ adsorption on the glass surface, while the high-temperature mechanism (applicable to Pyrex and quartz surfaces) involves permeation of ${\mathrm{He}}^{3}$ into the container material. The latter mechanism can be eliminated by using relatively impermeable aluminosilicate glass containers, and the resulting ${\mathrm{He}}^{3}$ nuclear-spin relaxation times become quite long (&gt;${10}^{5}$ sec) at low gas densities and moderate temperatures. Preliminary experiments using aluminosilicate containers suggest that spin exchange with optically pumped rubidium vapor may lead to sizeable ${\mathrm{He}}^{3}$ nuclear polarization at relatively high densities; in these experiments a ${\mathrm{He}}^{3}$ nuclear-spin relaxation time approaching ${10}^{6}$ sec was observed at 100\ifmmode^\circ\else\textdegree\fi{} C in a 500-Torr ${\mathrm{He}}^{3}$ sample containing rubidium vapor. Phenomenological theory suggests that spin-lattice and spin-spin relaxation times are equal for adsorption-controlled relaxation.
Feedback Regulation of β-Arrestin1 Function by Extracellular Signal-regulated Kinases (1999)

The functions of beta-arrestin1 to facilitate clathrin-mediated endocytosis of the beta2-adrenergic receptor and to promote agonist-induced activation of extracellular signal-regulated kinases (ERK) are regulated by its phosphorylation/dephosphorylation at Ser-412. Cytoplasmic beta-arrestin1 is almost stoichiometrically phosphorylated at Ser-412. Dephosphorylation of beta-arrestin1 at the plasma membrane is required for targeting a signaling complex that includes the agonist-occupied receptors to the clathrin-coated pits. Here we demonstrate that beta-arrestin1 phosphorylation and function are modulated by an ERK-dependent negative feedback mechanism. ERK1 and ERK2 phosphorylate beta-arrestin1 at Ser-412 in vitro. Inhibition of ERK activity by a dominant-negative MEK1 mutant significantly attenuates beta-arrestin1 phosphorylation, thereby increasing the concentration of dephosphorylated beta-arrestin1. Under such conditions, beta-arrestin1-mediated beta2-adrenergic receptor internalization is enhanced as is its ability to bind clathrin. In contrast, if ERK-mediated phosphorylation is increased by transfection of a constitutively active MEK1 mutant, receptor internalization is inhibited. Our results suggest that dephosphorylated beta-arrestin1 mediates endocytosis-dependent ERK activation. Following activation, ERKs phosphorylate beta-arrestin1, thereby exerting an inhibitory feedback control of its function.