gebhart/patrepeval huggingface dataset:
Factors associated with adherence to highly active antiretroviral therapy in homeless or unstably housed adults living with HIV (2009)

The aim of this study is to investigate adherence to highly active antiretroviral therapy (HAART) in persons living with HIV/AIDS (PLWHA) who are homeless or unstably housed. We evaluated homeless or unstably housed PLWHA (n=644) in three US cities were enrolled in the Housing and Health Study. Using baseline data and controlling for gender, race, age, and education, we examined associations between self-reported two- and Seven-day adherence and access to healthcare, mental health, substance use, and attitudes toward HIV medical therapy. Of the 644 participants, 358 (55%) were currently on HAART. For two-day adherence, 280 (78%) reported missing no prescribed doses (100% adherence), and for seven-day adherence, 291 (81%) reported > or =90% adherence. Logistic regression analyses indicated being younger, not having health insurance, and drug use were associated with missing > or =1 dose over the past two days. Scoring lower on SF-36 mental component summary scale and having greater risk of depression (CES-D) and stress (Perceived Stress Scale) were associated with poorer adherence for both two- and seven-day outcomes. Negative attitudes toward HIV treatment were also associated with lower adherence. Adherence to HIV medications in this population is similar to other groups. Coexisting problems of access to healthcare, higher risk of mental health problems, along with poorer attitudes toward treatment are associated with increased likelihood of missing doses. Comprehensive models of HIV care that include a continuum of medical and social services are essential for treating this population.
Amine oxidation and the chemistry of quinone imines. Part II. 2,5-Di-methoxy-4-t-butylaniline (1972)

The oxidation of 2,5-dimethoxy-4-t-butylaniline (1) by alkaline ferricyanide or silver oxide gives 2,2′,5,5′-tetramethoxy-4,4′-di-t-butylazobenzene (2) and 3,8-dimethoxy-2,7-di-t-butylphenazine (3). Chromatographic separation of the oxidation products on neutral alumina gives rise to six other products, including three N-aryl-p-quinone imines (4), (6), and (7), a tetrameric product (5), and a phenoxazone (8). Evidence is presented for the structures of these compounds, and their origin is discussed.The formation of the phenazine (3) provides clear evidence for the cyclisation of an intermediate N-aryl-o-quinone di-imine (11) under these conditions. Isolation of the debutylated quinone imine (7) substantiates assumptions made in the previous paper.
Resonant-optical-cavity photoconductive switch with 05% conversion efficiency and 10W peak power (2006)

We report a new photoconductive switch having an average output power of 44 μW, an instantaneous bandwidth of ∼300 GHz, an output pulse width of ∼2.2 ps, a peak output power of ≈1.0 W, and an optical-to-electrical conversion efficiency of ∼0.5% when pumped by a palm-sized mode-locked free-space laser at λ=780.6 nm with an average power of 8.7 mW and an optical pulse width of ∼−230 fs. The switch is made from an ErAs:GaAs epitaxial layer inside a resonant optical cavity and coupled to a planar three-turn square spiral antenna.
Limitation of Excessive Extracellular Matrix Turnover May Contribute to Survival Benefit of Spironolactone Therapy in Patients With Congestive Heart Failure (2000)

In patients with CHF, high baseline serum levels of markers of cardiac fibrosis synthesis are significantly associated with poor outcome and decrease during spironolactone therapy. The benefit from spironolactone was associated with higher levels of collagen synthesis markers. These results suggest that limitation of the excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with CHF.
Nitrated Fatty Acids: Endogenous Anti-inflammatory Signaling Mediators (2006)

Nitroalkene derivatives of linoleic acid (LNO2) and oleic acid (OA-NO2) are present; however, their biological functions remain to be fully defined. Herein, we report that LNO2 and OA-NO2 inhibit lipopolysaccharide-induced secretion of proinflammatory cytokines in macrophages independent of nitric oxide formation, peroxisome proliferator-activated receptor-gamma activation, or induction of heme oxygenase-1 expression. The electrophilic nature of fatty acid nitroalkene derivatives resulted in alkylation of recombinant NF-kappaB p65 protein in vitro and a similar reaction with p65 in intact macrophages. The nitroalkylation of p65 by fatty acid nitroalkene derivatives inhibited DNA binding activity and repressed NF-kappaB-dependent target gene expression. Moreover, nitroalkenes inhibited endothelial tumor necrosis factor-alpha-induced vascular cell adhesion molecule 1 expression and monocyte rolling and adhesion. These observations indicate that nitroalkenes such as LNO2 and OA-NO2, derived from reactions of unsaturated fatty acids and oxides of nitrogen, are a class of endogenous anti-inflammatory mediators.
Cell Growth-Inhibitory Action of SAGP, an Antitumor Glycoprotein from Streptococcus pyogenes (Su Strain) (1987)

An antitumor acidic glycoprotein (SAGP) from Streptococcus pyogenes (Su strain) inhibited the growth of BALB/3T3 cells in culture in a dose-dependent manner (0.03-10.0 μg/ml). This effect of SAGP was abolished by washing the cells, suggesting that SAGP weakly binds to the cell membrane. The ability of the cells to form colonies was unaffected by three days exposure to SAGP. Cell cycle analysis by flow cytometry revealed an accumulation of SAGP-treated cells in the S-phase. SAGP (3 μg/ml) reduced the incorporation of 3H-thymidine into the cells to approximately half of the control level. These results suggest that SAGP inhibits the growth of target cells by acting on their surface membrane and decreasing the rate of DNA synthesis.
The Economic Impact of COVID-19: Rebuilding the Las Vegas Economy (2020)

This study analyzes the recent trends of monthly visitors to the Las Vegas-ParadiseHenderson, NV metropolitan statistical area (MSA) for the first five months of 2020. In addition, six scenarios for the seven-month period of June through December 2020 estimate the net loss of visitors to Southern Nevada and the impact for the state economy in terms of employment, income, the total value added (contribution to Gross State Product), output sales, and state and local tax revenues. The counter-factual scenario – projecting the regional economy if no COVID-19 outbreak occurred – serves as a baseline scenario that allows measurement of the net economic losses from a significantly reduced number of visitors to Las Vegas due to the coronavirus pandemic. Finally, this study proposes three forecasted recovery paths for the tourism industry in Las Vegas, in terms of the number of predicted visitors for future years.
Design and development of masked therapeutic antibodies to limit off-target effects: Application to anti-EGFR antibodies (2009)

Therapeutic antibodies frequently cause side effects by binding antigen in non-target tissues. Here we demonstrate a novel molecular design of antibodies that addresses this problem by reversibly "masking" antibody complementarity determining regions until they reach diseased tissues containing disease-associated proteases. Specifically, two distinct single-chain Fv (scFv) fragments derived from antibodies against the epidermal growth factor receptor (cetuximab and 425) were fused a protease susceptible linker to their epitopes, which were engineered to encourage intermolecular association. Surface plasmon resonance and flow cytometry were used to confirm that the masked complex poorly interacts with native antigen, whereas protease treatment restores antigen recognition. Minimally, the "masked" scFvs possesses an eight-fold lower association with the epitope compared with the individual scFvs unmasked by proteolytic cleavage. This molecular design may have general utility for targeted release of therapeutic antibodies at disease sites.
Nanoparticle‐based PARACEST agents: the quenching effect of silica nanoparticles on the CEST signal from surface‐conjugated chelates (2012)

Silica nanoparticles of average diameter 53 ± 3 nm were prepared using standard water-in-oil microemulsion methods. After conversion of the surface Si-OH groups to amino groups for further conjugation, the PARACEST agent, EuDOTA-(gly)₄ (-) was coupled to the amines via one or more side-chain carboxyl groups in an attempt to trap water molecules in the inner-sphere of the complex. Fluorescence and ICP analyses showed that approximately 1200 Eu(3+) complexes were attached to each silica nanoparticle, leaving behind excess protonated amino groups. CEST spectra of the modified silica nanoparticles showed that attachment of the EuDOTA-(gly)₄ (-) to the surface of the nanoparticles did not result in a decrease in water exchange kinetics as anticipated, but rather resulted in a complete elimination of the normal Eu(3+) -bound water exchange peak and broadening of the bulk water signal. This observation was traced to catalysis of proton exchange from the Eu(3+) -bound water molecule by excess positively charged amino groups on the surface of the nanoparticles.
Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1. (1986)

The monoclonal antibody UCHL1 identified an antigen present on most thymocytes, a subpopulation of resting T cells within both the CD4 and CD8 subsets, and on mature activated T cells. The UCHL1 determinant is also present on cells of the myeloid lineage, but not normal B cells or NK cells. Functionally, UCHL1 identifies a subpopulation of T cells which proliferates maximally to soluble antigen and provides maximum help for PWM-stimulated immunoglobulin synthesis. In contrast, the UCHL1- cells do not induce immunoglobulin synthesis and do not proliferate in the presence of soluble antigen, although both the UCHL1- and the UCHL1+ fractions of T cells proliferate well in the presence of PHA. By standard immunoprecipitation techniques and SDS page, the antigen recognized by UCHL1 was found to have a molecular weight of 180,000-185,000. Preclearing experiments using antibodies identifying the leucocyte common antigen, LCA, and the lymphocyte function-associated antigen, LFA-1, which have similar molecular weights to UCHL1, showed that the UCHL1 determinant is not biochemically related to these antigens.
Carbon nanotube Schottky diode and directionally dependent field-effect transistor using asymmetrical contacts (2005)

We demonstrate the fabrication and operation of a carbon nanotube (CNT) based Schottky diode by using a Pd contact (high-work-function metal) and an Al contact (low-work-function metal) at the two ends of a single-wall CNT. We show that it is possible to tune the rectification current-voltage (I-V) characteristics of the CNT through the use of a back gate. In contrast to standard back gate field-effect transistors (FET) using same-metal source drain contacts, the asymmetrically contacted CNT operates as a directionally dependent CNT FET when gated. While measuring at source-drain reverse bias, the device displays semiconducting characteristics whereas at forward bias, the device is nonsemiconducting.
The therapeutic potential of modulators of the Hedgehog-Gli signaling pathway. (2002)

The discovery of small molecules that act as agonists and antagonists of the Hedgehog-Gli signaling pathway, which plays important roles in the embryo and adult, opens a new avenue for the treatment of diseases caused by aberrant suppression or activation of this complex pathway.
Transcriptional Modulation of the Immune Response by Peroxisome Proliferator-Activated Receptor-α Agonists in Autoimmune Disease (2009)

Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists have been shown to have a therapeutic benefit in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). In this study, we investigated the mechanism by which the PPARalpha agonist gemfibrozil induces immune deviation and protects mice from EAE. We demonstrated that treatment with gemfibrozil increases expression of the Th2 transcription factor GATA-3 and decreases expression of the Th1 transcription factor T-bet in vitro and directly ex vivo. These changes correlated with an increase in nuclear PPARalpha expression. Moreover, the protective effects of PPARalpha agonists in EAE were shown to be partially dependent on IL-4 and to occur in a receptor-dependent manner. PPARalpha was demonstrated, for the first time, to regulate the IL-4 and IL-5 genes and to bind the IL-4 promoter in the presence of steroid receptor coactivator-1, indicating that PPARalpha can directly transactivate the IL-4 gene. Finally, therapeutic administration of PPARalpha agonists ameliorated clinically established EAE, suggesting that PPARalpha agonists may provide a treatment option for immune-mediated inflammatory diseases.
Occludin-deficient Embryonic Stem Cells Can Differentiate into Polarized Epithelial Cells Bearing Tight Junctions (1998)

Occludin is the only known integral membrane protein of tight junctions (TJs), and is now believed to be directly involved in the barrier and fence functions of TJs. Occludin-deficient embryonic stem (ES) cells were generated by targeted disruption of both alleles of the occludin gene. When these cells were subjected to suspension culture, they aggregated to form simple, and then cystic embryoid bodies (EBs) with the same time course as EB formation from wild-type ES cells. Immunofluorescence microscopy and ultrathin section electron microscopy revealed that polarized epithelial (visceral endoderm-like) cells were differentiated to delineate EBs not only from wild-type but also from occludin-deficient ES cells. Freeze fracture analyses indicated no significant differences in number or morphology of TJ strands between wild-type and occludin-deficient epithelial cells. Furthermore, zonula occludens (ZO)-1, a TJ-associated peripheral membrane protein, was still exclusively concentrated at TJ in occludin-deficient epithelial cells. In good agreement with these morphological observations, TJ in occludin-deficient epithelial cells functioned as a primary barrier to the diffusion of a low molecular mass tracer through the paracellular pathway. These findings indicate that there are as yet unidentified TJ integral membrane protein(s) which can form strand structures, recruit ZO-1, and function as a barrier without occludin.
A New Route to Isoindole Intermediates (1990)

2-Pivaloylisoindoles 4 were generated from 2-(pivaloylaminomethyl)benzaldehydes 2 under acidic conditions and trapped with N-phenylmaleimide to afford Diels-Alder adducts 5 in good yields.
Predicted and observed effects of antibody affinity and antigen density on monoclonal antibody uptake in solid tumors. (1992)

The uptake and binding of monoclonal antibodies (MAbs) in solid tumors after a bolus i.v. injection are described using a compartmental pharmacokinetic model. The model assumes that MAb permeates into tumor unidirectionally from plasma across capillaries and clears from tumor by interstitial fluid flow and that interstitial antibody-antigen interactions are characterized by the Langmuir isotherm for reversible, saturable binding. Typical values for plasma clearance and tumor capillary permeability of a MAb and for interstitial fluid flow and interstitial volume fraction of a solid tumor were used to simulate the uptake of MAbs at various values of the binding affinity or antigen density for a range of MAb doses. The model indicates that at low doses, an increase in binding affinity may lead to an increase in MAb uptake. On the other hand, at doses approaching saturation of antigen or when uptake is permeation limited, an increase in the binding affinity from moderate to high affinity will have only a small effect on increasing MAb uptake. The model also predicts that an increase in antigen density will greatly increase MAb uptake when uptake is not permeation limited. Our experiments on MAb uptake in melanoma tumors in athymic mice after injection of 20 micrograms MAb (initial plasma concentration, about 120 nM) are consistent with these model-based conclusions. Two MAbs differing in affinity by more than 2 orders of magnitude (3.8 x 10(8) M-1 and 5 x 10(10) M-1) but with similar in vivo antigen densities in M21 melanoma attained similar concentrations in the tumor. Two MAbs of similar affinity but having a 3-fold difference in in vivo antigen density in SK-MEL-2 melanoma showed that the MAb targeted to the more highly expressed antigen attained a higher MAb concentration. We also discuss the model predictions in relation to other experiments reported in the literature. The theoretical and experimental findings suggest that, for high dose applications, efforts to increase MAb uptake in a tumor should emphasize the identification of an abundantly expressed antigen on tumor cells more than the selection of a very high affinity MAb.
MDA-7/IL-24–induced cell killing in malignant renal carcinoma cells occurs by a ceramide/CD95/PERK–dependent mechanism (2009)

Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells. The present studies focused on clarifying the mechanism(s) by which glutathione S-transferase (GST)-MDA-7 altered cell survival of human renal carcinoma cells in vitro. GST-MDA-7 caused plasma membrane clustering of CD95 and the association of CD95 with procaspase-8. GST-MDA-7 lethality was suppressed by inhibition of caspase-8 or by overexpression of short-form cellular FLICE inhibitory protein, but only weakly by inhibition of cathepsin proteases. GST-MDA-7-induced CD95 clustering (and apoptosis) was blocked by knockdown of acidic sphingomyelinase or, to a greater extent, ceramide synthase-6 expression. GST-MDA-7 killing was, in parallel, dependent on inactivation of extracellular signal-regulated kinase 1/2 and on CD95-induced p38 mitogen-activated protein kinase and c-jun NH(2)-terminal kinase-1/2 signaling. Knockdown of CD95 expression abolished GST-MDA-7-induced phosphorylation of protein kinase R-like endoplasmic reticulum kinase. GST-MDA-7 lethality was suppressed by knockout or expression of a dominant negative protein kinase R-like endoplasmic reticulum kinase that correlated with reduced c-jun NH(2)-terminal kinase-1/2 and p38 mitogen-activated protein kinase signaling and maintained extracellular signal-regulated kinase-1/2 phosphorylation. GST-MDA-7 caused vacuolization of LC3 through a mechanism that was largely CD95 dependent and whose formation was suppressed by knockdown of ATG5 expression. Knockdown of ATG5 suppressed GST-MDA-7 toxicity. Our data show that in kidney cancer cells GST-MDA-7 induces ceramide-dependent activation of CD95, which is causal in promoting an endoplasmic reticulum stress response that activates multiple proapoptotic pathways to decrease survival.
Soybean Nodule-Specific Uricase (Nodulin-35) Is Expressed and Assembled into a Functional Tetrameric Holoenzyme in Escherichia coli (1991)

A complete nodulin-35 (N-35) cDNA encoding nodule-specific uricase (EC 1.7.3.3) was isolated from a soybean (Glycine max L. var. Prize) nodule cDNA expression library using a previously isolated partial cDNA clone. The N-35 cDNA was expressed in Escherichia coli driven by the lacZ promoter and was found to be functionally active. The uricase activity was detected in the cytoplasmic fraction of E. coli with the same pH optimum and apparent K(m) values as that in the nodules. Because a stop codon is located 15 base pairs upstream of the N-35 initiation codon, it appears that a fusion protein with LacZ was not made, but reinitiation occurred due to the presence of a putative Shine-Dalgarno sequence in the appropriate region. The size of the N-35 polypeptide made in E. coli is identical to that present in soybean nodules and is able to assemble into a tetrameric holoenzyme with the same molecular weight as the native uricase. Thus, the presence of peroxisomes does not appear to be essential for the proper assembly of the holoenzyme in E. coli. These data also indicate that posttranslational modifications or membrane transport are not essential either for the assembly of N-35 into a holoenzyme or for the activity of uricase.
Bifunctional Apoptosis Regulator (BAR), an Endoplasmic Reticulum (ER)-associated E3 Ubiquitin Ligase, Modulates BI-1 Protein Stability and Function in ER Stress (2010)

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates inositol-requiring protein-1 (IRE1), among other ER-associated signaling proteins of the unfolded protein response (UPR) in mammalian cells. IRE1 signaling becomes attenuated under prolonged ER stress. The mechanisms by which this occurs are not well understood. An ER resident protein, Bax inhibitor-1 (BI-1), interacts with IRE1 and directly inhibits IRE1 activity. However, little is known about regulation of the BI-1 protein. We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1. Overexpression of BAR reduced BI-1 protein levels in a RING-dependent manner. Conversely, knockdown of endogenous BAR increased BI-1 protein levels and enhanced inhibition of IRE1 signaling during ER stress. We also found that the levels of endogenous BAR were reduced under prolonged ER stress. Our findings suggest that post-translational regulation of the BI-1 protein by E3 ligase BAR contributes to the dynamic control of IRE1 signaling during ER stress.
Synthesis of flight vehicle guidance and control laws using genetic search methods (1999)

Guidance and control problems in which the system dynamics or the performance measures are discontinuous, non-smooth, or non-convex are difficult to attack with conventional methods. Genetic search techniques can be extremely useful for these types of problems, as genetic methods are not gradient-based and can operate regardless of the complexity of the problem dynamics or performance specifications. In this paper, genetic search methodologies are applied to solving a set of aerospace guidance and control problems. These problems include homing missile guidance, spacecraft reorientation, and advanced aircraft control and guidance logic. The examples presented here demonstrate the advantages of genetic search methods in synthesizing nonlinear guidance and control laws for systems that may be difficult or intractable with conventional approaches.
Neural networks for control and system identification (2003)

A review is presented of the field of neuroengineering as a whole, highlighting the importance of neurocontrol and neuroidentification. Then a description is given of the five major architectures in use today in neurocontrol (in robotics, in particular) and a few areas for future research. The author concludes with comments on neuroidentification.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>