gebhart/patrepeval huggingface dataset:
High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1 (2000)

Recently, the human ATP-binding cassette transporter-1 (ABC1) gene has been demonstrated to be mutated in patients with Tangier disease. To investigate the role of the ABC1 protein in an experimental in vivo model, we used gene targeting in DBA-1J embryonic stem cells to produce an ABC1-deficient mouse. Expression of the murine Abc1 gene was ablated by using a nonisogenic targeting construct that deletes six exons coding for the first nucleotide-binding fold. Lipid profiles from Abc1 knockout (-/-) mice revealed an approximately 70% reduction in cholesterol, markedly reduced plasma phospholipids, and an almost complete lack of high density lipoproteins (HDL) when compared with wild-type littermates (+/+). Fractionation of lipoproteins by FPLC demonstrated dramatic alterations in HDL cholesterol (HDL-C), including the near absence of apolipoprotein AI. Low density lipoprotein (LDL) cholesterol (LDL-C) and apolipoprotein B were also significantly reduced in +/- and -/- compared with their littermate controls. The inactivation of the Abc1 gene led to an increase in the absorption of cholesterol in mice fed a chow or a high-fat and -cholesterol diet. Histopathologic examination of Abc1-/- mice at ages 7, 12, and 18 mo demonstrated a striking accumulation of lipid-laden macrophages and type II pneumocytes in the lungs. Taken together, these findings demonstrate that Abc1-/- mice display pathophysiologic hallmarks similar to human Tangier disease and highlight the capacity of ABC1 transporters to participate in the regulation of dietary cholesterol absorption.
Increasing efficiency of high-NA metasurface lenses (Conference Presentation) (2017)

Diffractive optical devices based on dielectric metasurfaces have recently attracted significant attention. Small size, low weight, planar form factor, and potential for low-cost manufacturing using semiconductor fabrication techniques are some of the main features that make metasurfaces ideal candidates for implementation of low-cost miniaturized optical systems. However, to become competitive for practical applications, metasurfaces should also offer specifications (e.g. efficiency, bandwidth, and wavefront error) comparable to their refractive counterparts. We have recently demonstrated diffraction-limited metasurface lenses with high efficiency using high refractive index nano-posts. Low numerical aperture (NA) metasurface lenses have more than 90% focusing efficiency, but the efficiency of the lenses with NA>0.5 decreases with increasing NA and drops to ~40% for NA=0.9, thus resulting in a trade-off between the NA and efficiency. Here we identify the main physical origin of this trade-off as the low transmission of large diameter nano-posts for transverse-magnetic (TM) polarized light incident at large angles, and show that the low transmission is caused by the excitation of undesired high order modes in these nano-posts. To overcome this issues, we present a novel approach for evaluating different metasurface designs in implementation of high NA metasurface components. The approach is based on adiabatic approximation of aperiodic metasurfaces by periodic gratings, and considers the effect of large deflection angles. Using the proposed design approach, we experimentally demonstrate more than 75% focusing efficiency for metasurface lenses with NA=0.7, and more than 70% deflection efficiency for 50-degree beam deflectors for unpolarized light at 915 nm.
Developmental control of CD8+ T cell–avidity maturation in autoimmune diabetes (2005)

The progression of immune responses is generally associated with an increase in the overall avidity of antigen-specific T cell populations for peptide-MHC. This is thought to result from preferential expansion of high-avidity clonotypes at the expense of their low-avidity counterparts. Since T cell antigen-receptor genes do not mutate, it is puzzling that high-avidity clonotypes do not predominate from the outset. Here we provide a developmental basis for this phenomenon in the context of autoimmunity. We have carried out comprehensive studies of the diabetogenic CD8 T cell population that targets residues 206-214 of the beta cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(206-214)) and undergoes avidity maturation as disease progresses. We find that the succession of IGRP(206-214)-specific clonotypes with increasing avidities during the progression of islet inflammation to overt diabetes in nonobese diabetic mice is fueled by autoimmune inflammation but opposed by systemic tolerance. As expected, naive high-avidity IGRP(206-214)-specific T cells respond more efficiently to antigen and are significantly more diabetogenic than their intermediate- or low-avidity counterparts. However, central and peripheral tolerance selectively limit the contribution of these high-avidity T cells to the earliest stages of disease without abrogating their ability to progressively accumulate in inflamed islets and kill beta cells. These results illustrate the way in which incomplete deletion of autoreactive T cell populations of relatively high avidity can contribute to the development of pathogenic autoimmunity in the periphery.
Tuning Thermoresponsive Properties of Cationic Elastin-like Polypeptides by Varying Counterions and Side-Chains (2017)

We report the synthesis of methionine-containing recombinant elastin-like polypeptides (ELPs) of different lengths that contain periodically spaced methionine residues. These ELPs were chemoselectively alkylated at all methionine residues to give polycationic derivatives. Some of these samples were found to possess solubility transitions in water, where the temperature of these transitions varied with ELP concentration, nature of the methionine alkylating group, and nature of the sulfonium counterions. These studies show that introduction and controlled spacing of methionine sulfonium residues into ELPs can be used as a means both to tune their solubility transition temperatures in water using a variety of different parameters and to introduce new side-chain functionality.
Interactive programming environments (1984)

article Free Access Share on Interactive programming environments Authors: David R. Barstow McGraw-Hill McGraw-HillView Profile , Howard E. Shrobe McGraw-Hill McGraw-HillView Profile , Erik Sandewall McGraw-Hill McGraw-HillView Profile , Stephen W. Smoliar View Profile Authors Info & Claims ACM SIGSOFT Software Engineering NotesVolume 9Issue 4July 1984 pp 56–58https://doi.org/10.1145/1012339.1012342Published:01 July 1984Publication History 17citation339DownloadsMetricsTotal Citations17Total Downloads339Last 12 Months48Last 6 weeks4 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Assessment of ventricular contractile state and function in patients with univentricular heart. (1989)

To elucidate the ventricular contractile state and function in patients with univentricular heart, the ventricular volume, mass, ejection phase index, and wall stress were evaluated with biplane ventriculography and pressure measurement in 41 patients: 18 with left ventricular (LV) type (age, 6.4 +/- 6.1 years) and 23 with right ventricular (RV) type (age, 5.7 +/- 4.1 years), and data from patients with univentricular heart were compared with data from 19 normal control subjects (age, 7.2 +/- 4.3 years). Although the end-diastolic and end-systolic volumes were significantly greater in both types of univentricular heart than in the normal control group, the volumes for the LV and RV type patients did not differ from each other. The ejection fraction (EF) was depressed in both patient types of univentricular heart and was significantly (p less than 0.005) lower in the RV type than in the LV type patients (0.56 +/- 0.05 for LV type, 0.50 +/- 0.07 for RV type, and 0.64 +/- 0.03 for the control group). The ventricular mass was larger in both patient types of univentricular heart than in that of the control group, whereas the ratio of ventricular mass to end-diastolic volume was significantly (p less than 0.001) lower in the RV type patients than in the LV type patients and the control group (0.79 +/- 0.18 g/ml for LV type, 0.51 +/- 0.10 for RV type, and 0.82 +/- 0.13 for control group). End-systolic stress was significantly elevated in both types of univentricular heart (241 +/- 45 for LV type, 328 +/- 52 for RV type, and 205 +/- 26 kdynes/cm2 for the control group) and significantly (p less than 0.001) greater in the RV type than in the LV type patients. There was a significant inverse correlation (p less than 0.001) between end-systolic stress and the ratio of mass to end-diastolic volume in all the patients. In 27 patients (12 patients for LV type, 15 for RV type) the mean normalized systolic ejection rate corrected for heart rate (MNSERc) clearly fell below the 95% confidence limit of the normal end-systolic stress-MNSERc relation. The end-systolic stress:end-systolic volume ratio was also significantly depressed in both patient types of univentricular heart (3.49 +/- 1.77 for LV type, 4.07 +/- 2.13 for RV type, and 7.20 +/- 1.32 for the control group). In these variables, however, there were no significant differences between LV and RV type patients of univentricular heart.(ABSTRACT TRUNCATED AT 400 WORDS)
Electromagnetic excitation of nano-carbon in vacuum (2005)

Nano-carbon as lighting source is demonstrated in this paper. The characterized nano-radiation from nano-carbon, excited by different lasers in vacuum, is observed when laser intensity is over a threshold. With lower excitation threshold and smaller white light source, nano-carbon is more applicable to be as lighting system than the others in scientific experiments. White light emission of nano-carbon induced by more practicable electromagnetic excitation (microwave) is also demonstrated, which is caused by the faradic heating of the metal substrates, with molecular spectra and better color rendering. Lighting systems comprised of nano-carbon may become one of the considerable directions in optics.
Biotin (2009)

Biotin is a water-soluble vitamin and serves as a coenzyme for five carboxylases in humans. Biotin is also covalently attached to distinct lysine residues in histones, affecting chromatin structure and mediating gene regulation. This review describes mammalian biotin metabolism, biotin analysis, markers of biotin status, and biological functions of biotin. Proteins such as holocarboxylase synthetase, biotinidase, and the biotin transporters SMVT and MCT1 play crucial roles in biotin homeostasis, and these roles are reviewed here. Possible effects of inadequate biotin intake, drug interactions, and inborn errors of metabolism are discussed, including putative effects on birth defects.
Production and characterization of two immunotoxins specific for M5b ANLL leukaemia (1991)

We describe the production and functional characterization of 2 monocytic-cell-lineage-specific immunotoxins constructed with saporin emitoxin (SAP) from Saponaria officinalis. Interest in the production of these immunotoxins, of possible clinical relevance, has been raised by the availability of 2 MAbs of high specificity for circulating monocytes and M5b ANLL, thus envisaging their potential use in bone-marrow purging. SAP emitoxin was selected on the basis of the low cytotoxicity in unconjugated form, as opposed to highly specific cytotoxicity and favourable pharmacokinetical properties in the conjugated form. SPDP conjugation produced immunotoxins which retained serological specificity and protein-synthesis-inhibitory activity. The 2 immunotoxins did not interfere with bone-marrow progenitor-cell growth in a CFU-GM colony assay. On the contrary, they were capable of killing monocytic cells selectively, as demonstrated in phenotypical and functional assays. Thus these 2 novel immunotoxins appear to be promising reagents in purging autologous bone marrow prior to transplantation in patients suffering from monocytic leukaemia.
CDK5 Participates in Amyloid-β Production by Regulating PPARγ Phosphorylation in Primary Rat Hippocampal Neurons (2019)

Cyclin-dependent kinase 5 (CDK5) in adipose tissue mediates peroxisome proliferator-activated receptor γ (PPARγ) phosphorylation at Ser273 to inhibit its activity, causing PPARγ target gene expression changes. Among these, insulin-degrading enzyme (IDE) degrades amyloid-β peptide (Aβ), the core pathological product of Alzheimer's disease (AD), whereas β-amyloid cleavage enzyme 1 (BACE1) hydrolyzes amyloid-β protein precursor (AβPP). Therefore, we speculated that CDK5 activity in the brain might participate in Aβ production, thereby functioning as a key molecule in AD pathogenesis. To confirm this hypothesis, we transduced primary rat hippocampal neurons using CDK5-expressing lentiviral vectors. CDK5 overexpression increased PPARγ Ser273 phosphorylation, decreased IDE expression, increased BACE1 and AβPP expression, increased Aβ levels, and induced neuronal apoptosis. The CDK5 inhibitor roscovitine effectively reversed these CDK5 overexpression-mediated effects. Moreover, silencing of the Cdk5 gene via CDK5 shRNA-expressing lentiviral vectors in primary hippocampal neurons did not exert any protective effect against normal neuronal apoptosis, nor were significant effects observed on Aβ levels, PPARγ phosphorylation, or PPARγ target gene expression in the cells. However, Cdk5 gene silencing exhibited a neuroprotective effect in the Aβ-induced AD neuron model by effectively inhibiting the Aβ-induced neuronal apoptosis, PPARγ phosphorylation, PPARγ expression downregulation, and PPARγ target gene expression changes, and reducing Aβ levels. In conclusion, this study demonstrated that CDK5 played an important role in the pathogenesis of AD. Specifically, CDK5 participated in Aβ production by regulating PPARγ phosphorylation. Targeted therapy against CDK5 could effectively reduce and reverse the neurotoxic effects of Aβ and may represent a novel approach for AD treatment.
Na,K-ATPase β-Subunit Is Required for Epithelial Polarization, Suppression of Invasion, and Cell Motility (2001)

The cell adhesion molecule E-cadherin has been implicated in maintaining the polarized phenotype of epithelial cells and suppression of invasiveness and motility of carcinoma cells. Na,K-ATPase, consisting of an alpha- and beta-subunit, maintains the sodium gradient across the plasma membrane. A functional relationship between E-cadherin and Na,K-ATPase has not previously been described. We present evidence that the Na,K-ATPase plays a crucial role in E-cadherin-mediated development of epithelial polarity, and suppression of invasiveness and motility of carcinoma cells. Moloney sarcoma virus-transformed Madin-Darby canine kidney cells (MSV-MDCK) have highly reduced levels of E-cadherin and beta(1)-subunit of Na,K-ATPase. Forced expression of E-cadherin in MSV-MDCK cells did not reestablish epithelial polarity or inhibit the invasiveness and motility of these cells. In contrast, expression of E-cadherin and Na,K-ATPase beta(1)-subunit induced epithelial polarization, including the formation of tight junctions and desmosomes, abolished invasiveness, and reduced cell motility in MSV-MDCK cells. Our results suggest that E-cadherin-mediated cell-cell adhesion requires the Na,K-ATPase beta-subunit's function to induce epithelial polarization and suppress invasiveness and motility of carcinoma cells. Involvement of the beta(1)-subunit of Na,K-ATPase in the polarized phenotype of epithelial cells reveals a novel link between the structural organization and vectorial ion transport function of epithelial cells.
Essential Role for Sphingosine Kinases in Neural and Vascular Development (2005)

Sphingosine-1-phosphate (S1P), an important sphingolipid metabolite, regulates diverse cellular processes, including cell survival, growth, and differentiation. Here we show that S1P signaling is critical for neural and vascular development. Sphingosine kinase-null mice exhibited a deficiency of S1P which severely disturbed neurogenesis, including neural tube closure, and angiogenesis and caused embryonic lethality. A dramatic increase in apoptosis and a decrease in mitosis were seen in the developing nervous system. S1P(1) receptor-null mice also showed severe defects in neurogenesis, indicating that the mechanism by which S1P promotes neurogenesis is, in part, signaling from the S1P(1) receptor. Thus, S1P joins a growing list of signaling molecules, such as vascular endothelial growth factor, which regulate the functionally intertwined pathways of angiogenesis and neurogenesis. Our findings also suggest that exploitation of this potent neuronal survival pathway could lead to the development of novel therapeutic approaches for neurological diseases.
Post-depositional detrital remanent magnetism in reconstituted deep sea sediment (1975)

Evidence of disturbance by benthic burrowing organisms is commonly observed in deep-sea sediment cores but these same cores often possess good magnetic records, especially of field reversals. The natural remanent magnetism (NRM) of these burrowed sediments cannot be a depositional detrital remanence (DRM) but must rather have been acquired at some later time. An experiment was designed to demonstrate that a post-depositional DRM could be acquired in deep-sea sediment in conjunction with sediment disturbance similar to that caused by benthic fauna.
Bone grafts in dentistry (2013)

Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.
PEGylated TNF-Related Apoptosis-Inducing Ligand (TRAIL) Analogues: Pharmacokinetics and Antitumor Effects (2011)

The low stability and fast clearance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are the main obstacles to its implementation as an antitumor agent. Here, we attempted to improve its pharmacokinetic and pharmacodynamic profiles by using PEGylation. N-terminal PEGylated TRAIL (PEG-TRAIL) was synthesized using 2, 5, 10, 20, and 30 kDa PEG. Antitumor effect assessments in HCT116 tumor bearing nude mice showed that all PEG-TRAIL analogues efficiently suppressed mean tumor growth, with mean tumor growth inhibition (TGI) values (5K-, 20K-, 30K-PEG-TRAIL) of 43.5, 61.7, and 72.3%, respectively. In particular, 30K-PEG-TRAIL was found to have antitumor efficacy for five days after a single administration (1 mg/mouse, i.p.). The different antitumor effects of these PEG-TRAIL analogues were attributed to augmented pharmacokinetics and metabolic resistance. All analogues were found to have higher metabolic stabilities in rat plasma, extended pharmacokinetic profiles, and greater circulating half-lives (3.9, 5.3, 6.2, 12.3, and 17.7 h for 2, 5, 10, 20, and 30K-PEG-TRAIL, respectively, versus 1.1 h for TRAIL, i.p.) in ICR mice. Our findings suggest that TRAIL derivatized with PEG of an appropriate M(w) might be useful antitumor agent with protracted activity.
The Biological Action of Choriogonadotropin Is Not Dependent on the Complete Native Quaternary Interactions between the Subunits (1999)

Human CG (hCG) is a member of the glycoprotein hormone family characterized by a heterodimeric structure consisting of a common alpha-subunit noncovalently bound to a hormone-specific beta-subunit. The two subunits are highly intertwined and only the heterodimer is functional, implying that the quaternary structure is critical for biological activity. To assess the dependence of the bioactivity of hCG on the heterodimeric interactions, alpha- and beta-subunits bearing mutations that prevent assembly were covalently linked to form a single chain hCG. Receptor binding and signal transduction of these analogs were tested and their structural integrity analyzed using a panel of monoclonal antibodies (mAbs). These included dimer-specific mAbs, which react with at least four different epitope sites on the hormone, and some that react only with the free beta-subunit. We showed that there was significant loss of quaternary and tertiary structure in several regions of the molecule. This was most pronounced in single chains that had one of the disulfide bonds of the cystine knot disrupted in either the alpha- or beta-subunit. Despite these structural changes, the in vitro receptor binding and signal transduction of the single chain analogs were comparable to those of the nonmutated single chain, demonstrating that not all of the quaternary configuration of the hormone is necessary for biological activity.
Hedgehog Signaling Regulates Bladder Cancer Growth and Tumorigenicity (2012)

The role of Hedgehog (HH) signaling in bladder cancer remains controversial. The gene encoding the HH receptor and negative regulator PATCHED1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1 functioning as a classic tumor suppressor gene, loss-of-function mutations in the remaining copy of PTCH1 are not commonly found. Here, we provide direct evidence for a critical role of HH signaling in bladder carcinogenesis. We show that transformed human urothelial cells and many urothelial carcinoma cell lines exhibit constitutive HH signaling, which is required for their growth and tumorigenic properties. Surprisingly, rather than originating from loss of PTCH1, the constitutive HH activity observed in urothelial carcinoma cell lines was HH ligand dependent. Consistent with this finding, increased levels of HH and the HH target gene product GLI1 were found in resected human primary bladder tumors. Furthermore, on the basis of the difference in intrinsic HH dependence of urothelial carcinoma cell lines, a gene expression signature was identified that correlated with bladder cancer progression. Our findings therefore indicate that therapeutic targeting of the HH signaling pathway may be beneficial in the clinical management of bladder cancer.
Auditory Detection of a Noise Signal (1960)

Measurements of the detectability of a noise signal in noise are reported in this paper. Parameters of the noise signal such as the band width, duration, and center frequency are investigated. The results are compared with an optimum-detection model. For some constant detectability the equation generated by the model and one constant, an attenuation factor, closely fit the experimental data over the major range of the experimental parameters. The major area of discrepancy between model and data is the shape of the psycho-physical function. Implications of the data for the critical-band mechanism are also discussed.