gebhart/patrepeval huggingface dataset:
Binding of selected iodothyronine analogues to receptor sites of isolated rat hepatic nuclei. High correlation between structural requirements for nuclear binding and biological activity (1975)

The limited capacity, high affinity binding of 35 iodothyronine analogues by rat liver nuclei has been examined in an in vitro system. The in vitro nuclear binding of all the analogues tested was highly correlated with their published thyromimetic potencies in the intact animals. Binding and biological activity are greater for 3'-mono-than 3',5'-di-substituted iodothyronines. A 4'-hydroxyl group is essential, but the 3' substituent can be several halogen or non-halogen groups for which the distal conformation is preferred. The ether linkage can be replaced equally well by a methylene or sulfur group. The presence of both 3 and 5 groups which are limited to halogens or small alkyl groups are necessary for the maintenance of significant activity. Halogen-free iodothyronines have very low, but significant activity both in vitro and in vivo. The data provide information on the structural requirements for thyroid hormone action and further support the physiological relevance of the nuclear sites.
Carbon dioxide absorption by hydroxyalkyl amidines impregnated into mesoporous silica: the effect of pore morphology and absorbent loading (2013)

Hydroxyalkyl amidine (HAM) derivatives react with CO2 in a quantitative manner under dry conditions near room temperature, and then release it at a moderate temperature of approximately 60 °C. In the present study, HAM compounds were impregnated into porous silica particles to obtain solid CO2 sorbents. This process produced a large surface area for reaction between CO2 and the absorbents for enhanced CO2 capture efficiency. Several types of mesoporous silicas that differed in pore size, pore volume, and particle size and shape were investigated in order to identify the optimum processing parameters for preparation of hybrid materials with the best possible CO2 capture performance. The amount of HAMs loaded into the silica was optimized so as to retain the open porous structure for efficient transport of gas molecules, while providing a large surface area of reactive material. We have demonstrated that HAM-loaded silica could be used as an effective CO2 filter for dilute gas mixtures such as air.
Functionally distinct isoforms of the CRE-BP DNA-binding protein mediate activity of a T-cell-specific enhancer. (1992)

Expression of the CD3 delta gene of the T-cell receptor (TCR) complex is regulated by a T-cell-specific enhancer. A highly conserved 40-bp motif (element delta A) within the CD3 delta enhancer is responsible for mediating its activity and specificity. Element delta A exhibits sequence similarities to the cyclic AMP response element (CRE) but does not respond to changes in the level of cyclic AMP. Using the delta A element as a probe, we have isolated three cDNA clones encoding three distinct protein isoforms, products of differential splicing and alternate promoter usage of the CRE-BP gene. These isoforms share the DNA binding and dimerization domains at the C terminus of the protein but differ at their N termini. In transfection assays, their activities as transcription regulators differ: CRE-BP2 is a potent activator, CRE-BP3 is a weak activator, and CRE-BP1 is transcriptionally inert. Mutations in the basic region of the CRE-BP1 protein which abrogate its ability to bind DNA render this protein a dominant repressor of the delta A enhancer. Antibodies to the CRE-BP protein interact specifically with the ubiquitous and predominantly T-cell-restricted nuclear complexes that bind to the delta A element and suggest the presence of this protein in homo- and heterodimeric complexes. Since the delta A motif is also present in the enhancer and promoter of the TCR alpha and beta genes, the CRE-BP isoforms may mediate expression of other members of the CD3/TCR complex during T-cell development.
Synthesis and Anticonvulsant Activities of (R)-N-(4′-Substituted)benzyl 2-Acetamido-3-methoxypropionamides (2009)

The structure-activity relationship (SAR) for the N-benzyl group in the clinical antiepileptic agent (R)-lacosamide [(R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-3] has been explored. Forty-three compounds were prepared and then evaluated at the National Institute of Neurological Disorders and Stroke Anticonvulsant Screening Program for seizure protection in the maximal electroshock (MES) and subcutaneous Metrazol models. Comparing activities for two series of substituted aryl regioisomers (2', 3', 4') showed that 4'-modified derivatives had the highest activity. Significantly, structural latitude existed at the 4'-site. The SAR indicated that nonbulky 4'-substituted (R)-3 derivatives exhibited superb activity, independent of their electronic properties. Activities in the MES test of several compounds were comparable with or exceeded that of (R)-3 and surpassed the activities observed for the traditional antiepileptic agents phenytoin, phenobarbital, and valproate.
Decreased Survival of B Cells of HIV-viremic Patients Mediated by Altered Expression of Receptors of the TNF Superfamily (2004)

Human immunodeficiency virus (HIV) infection leads to numerous perturbations of B cells through mechanisms that remain elusive. We performed DNA microarray, phenotypic, and functional analyses in an effort to elucidate mechanisms of B cell perturbation associated with ongoing HIV replication. 42 genes were up-regulated in B cells of HIV-viremic patients when compared with HIV-aviremic and HIV-negative patients, the majority of which were interferon (IFN)-stimulated or associated with terminal differentiation. Flow cytometry confirmed these increases and indicated that CD21(low) B cells, enhanced in HIV-viremic patients, were largely responsible for the changes. Increased expression of the tumor necrosis factor (TNF) superfamily (TNFSF) receptor CD95 correlated with increased susceptibility to CD95-mediated apoptosis of CD21(low) B cells, which, in turn, correlated with HIV plasma viremia. Increased expression of BCMA, a weak TNFSF receptor for B lymphocyte stimulator (BLyS), on CD21(low) B cells was associated with a concomitant reduction in the expression of the more potent BLyS receptor, BAFF-R, that resulted in reduced BLyS binding and BLyS-mediated survival. These findings demonstrate that altered expression of genes associated with IFN stimulation and terminal differentiation in B cells of HIV-viremic patients lead to an increased propensity to cell death, which may have substantial deleterious effects on B cell responsiveness to antigenic stimulation.
Separating key management from file system security (1999)

No secure network file system has ever grown to span the Internet. Existing systems all lack adequate key management for security at a global scale. Given the diversity of the Internet, any particular mechanism a file system employs to manage keys will fail to support many types of use.We propose separating key management from file system security, letting the world share a single global file system no matter how individuals manage keys. We present SFS, a secure file system that avoids internal key management. While other file systems need key management to map file names to encryption keys, SFS file names effectively contain public keys, making them self-certifying pathnames. Key management in SFS occurs outside of the file system, in whatever procedure users choose to generate file names.Self-certifying pathnames free SFS clients from any notion of administrative realm, making inter-realm file sharing trivial. They let users authenticate servers through a number of different techniques. The file namespace doubles as a key certification namespace, so that people can realize many key management schemes using only standard file utilities. Finally, with self-certifying pathnames, people can bootstrap one key management mechanism using another. These properties make SFS more versatile than any file system with built-in key management.
Effect of Antioxidants on Oxidative Modification of LDL (1991)

Human low density lipoprotein (LDL) with a molecular mass of 2.5 million contains on average 1300 molecules of polyunsaturated fatty acids (PUFAs) bound in the different lipid classes. The predominant antioxidant in LDL is alpha-tocopherol, with an average of 6 molecules in each LDL particle. The other substances with potential antioxidant activity are: gamma-tocopherol, beta-carotene, alpha-carotene, lycopene, cryptoxanthin, cantaxanthin, phytofluene and ubiquinol-10. Each is present in amounts of only 1/20th to 1/300th of that of alpha-tocopherol. If LDL is exposed to oxidative conditions (Cu++ ions, macrophages) a lag phase precedes the oxidation of PUFAs. During the lag phase the antioxidants disappear with alpha-tocopherol the first to go and beta-carotene the last. The lag phase, which can readily be determined, is an index of the oxidation resistance of LDL. If LDL is loaded with vitamin E in vitro its oxidation resistance increases linearly with its alpha-tocopherol content according to the equation, y = kx+a. The same relationship is applicable if the alpha-tocopherol content of LDL is increased by taking oral vitamin E. Daily doses of 150, 225, 800 and 1200 IU RRR-alpha-tocopherol increased the LDL alpha-tocopherol on average to 138%, 158%, 144% and 215% of the initial value, the oxidation resistance being increased to 118%, 156%, 135% and 175%, respectively. The efficiency of vitamin E-dependent (= k) and the vitamin independent (= a) oxidation resistance seem to be subject specific with strong individual variation.(ABSTRACT TRUNCATED AT 250 WORDS)
Ageing induced vascular smooth muscle cell senescence in atherosclerosis (2015)

Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis.
Surface differentiation antigens of human mammary epithelial cells carried on the human milk fat globule. (1977)

Rabbit antibodies against components of the human milk fat globule bind specifically to normal human breast epithelial cells and cell lines derived from breast carcinomas, as well as to the outer surface of the human milk fat globule. Variation in indirect immunofluorescence staining in both intensity per cell and percentage of cells stained is observed for the different brest cell lines. Cells derived from other epithelial and other ectodermal tissues, fetal fibroblasts, cells of the blood buffy coat, and even fibroblasts of the breast itself do not bind the antibodies. This suggests that these antibodies are detecting cell-type-specific antigens. These normal breast epithelial cell antigens are on the cell surface and their expression is stable in long-term cultured cell lines, even after much chromosomal variation in a given line. By affinity chromatography, three distinct antigenic components can be isolated from the milk fat globule, one of which contains carbohydrate. These differentiation antigens of the human breast epithelial cell are not only useful as specific cell-type markers, but also can provide a tool to study the role of the cell surface in normal and neoplastic mammary development.
Potassium Bicarbonate Reduces Urinary Nitrogen Excretion in Postmenopausal Women (1997)

Previously we demonstrated that low grade chronic metabolic acidosis exists normally in humans eating ordinary diets that yield normal net rates of endogenous acid production (EAP), and that the degree of acidosis increases with age. We hypothesize that such diet-dependent and age-amplifying low grade metabolic acidosis contributes to the decline in skeletal muscle mass that occurs normally with aging. This hypothesis is based on the reported finding that chronic metabolic acidosis induces muscle protein breakdown, and that correction of acidosis reverses the effect. Accordingly, in 14 healthy postmenopausal women residing in a General Clinical Research Center and eating a constant diet yielding a normal EAP rate, we tested whether correcting their "physiological" acidosis with orally administered potassium bicarbonate (KHCO3; 60-120 mmol/day for 18 days) reduces their urinary nitrogen loss. KHCO3 reduced EAP to nearly zero, significantly reduced the blood hydrogen ion concentration (P < 0.001), and increased the plasma bicarbonate concentration (P < 0.001), indicating that pre-KHCO3, diet-dependent EAP was significantly perturbing systemic acid-base equilibrium, causing a low grade metabolic acidosis. Urinary ammonia nitrogen, urea nitrogen, and total nitrogen levels significantly decreased. The cumulative reduction in nitrogen excretion was 14.1 +/- 12.3 g (P < 0.001). Renal creatinine clearance and urine volume remained unchanged. We conclude that in postmenopausal women, neutralization of diet-induced EAP with KHCO3 corrects their preexisting diet-dependent low grade metabolic acidosis and significantly reduces their urinary nitrogen wasting. The magnitude of the KHCO3-induced nitrogen-sparing effect is potentially sufficient to both prevent continuing age-related loss of muscle mass and restore previously accrued deficits.
PASIC: A processor-A/D converter-sensor integrated circuit (2002)

The design of an integrated smart sensor called PASIC is described. The basic idea is to integrate a 2-D image-sensor array with a linear A/D (analog-to-digital) converter array and a linear processor array in a single chip. The current version of PASIC contains 128 parallel processors with a 128*128-b memory, 128 8-b A/D converters, and a 128*128 photo sensor array. Two 128*8 bidirectional shift registers are used for communication between processor elements and I/O (input/output). A memory-bus organized architecture is used, having been proven as an efficient VLSI architecture for a SIMD (single instruction, multiple data) bit-serial processor array.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors (2014)

The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around -120 to -80 bp, while highly effective sgRNAs targeted from -147 to -89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.
Corporate Renewal and Future Direction at Asia Petroleum Limited (APL) (2012)

The case describes a series of steps taken by the Managing Director (MD) and Chief Executive Officer (CEO) of Asia Petroleum Limited (APL) to implement his corporate renewal plan with twofold objectives: to determine the future direction of the company, and second, to improve current operational performance with a view to satisfy different stakeholders, especially the investors. The option for the future was to convert the current oil transportation business into the power sector. This case is the first part of two parts; case B may be obtained from the author.
Gene therapy in the cardiovascular system: an update (1999)

This update reviews the remarkable progression in several cardiovascular gene transfer domains. The first chemical gene therapy protocols to stimulate angiogenesis in ischemic myocardium are discussed and both the great expectations as well as remaining hurdle are highlighted. In experimental models of restenosis and heart failure gene therapy shows promising results. Important question regarding vector-related limitations and suboptimal in vivo delivery systems will require expeditious attention for gene therapy to become a more widely applicable option in cardiovascular diseases.
Innovations (2000)

Presents new and innovative patents, products, and processes in the industry.
Differentiation and Transplantation of Functional Pancreatic Beta Cells Generated from Induced Pluripotent Stem Cells Derived from a Type 1 Diabetes Mouse Model (2012)

The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs). We generated iPSCs from NOD mouse embryonic fibroblasts or NOD mouse pancreas-derived epithelial cells (NPEs), and applied directed differentiation protocols to differentiate the NOD-iPSCs toward functional pancreatic beta cells. Finally, we investigated whether the NPE-iPSC-derived insulin-producing cells could normalize hyperglycemia in transplanted diabetic mice. The NOD-iPSCs showed typical embryonic stem cell-like characteristics such as expression of markers for pluripotency, in vitro differentiation, teratoma formation, and generation of chimeric mice. We developed a method for stepwise differentiation of NOD-iPSCs into insulin-producing cells, and found that NPE-iPSCs differentiate more readily into insulin-producing cells. The differentiated NPE-iPSCs expressed diverse pancreatic beta cell markers and released insulin in response to glucose and KCl stimulation. Transplantation of the differentiated NPE-iPSCs into diabetic mice resulted in kidney engraftment. The engrafted cells responded to glucose by secreting insulin, thereby normalizing blood glucose levels. We propose that NOD-iPSCs will provide a useful tool for investigating genetic susceptibility to autoimmune diseases and generating a cellular interaction model of T1D, paving the way for the potential application of patient-derived iPSCs in autologous beta cell transplantation for treating diabetes.
Preparation and properties of aromatic polyamides from 2,2′‐bis(p‐aminophenoxy) biphenyl or 2,2′‐bis(p‐aminophenoxy)‐1,1′‐binaphthyl and aromatic dicarboxylic acids (1993)

Abstract New aromatic diamines having kink and crank structures, 2,2′‐bis( p ‐aminophenoxy)biphenyl and 2,2′‐bis( p ‐aminophenoxy)‐1,1′‐binaphthyl, were synthesized by the reaction of p ‐fluoronitrobenzene with biphenyl‐2,2′‐diol and 2,2′‐dihydroxy‐1,1′‐binaphthyl, respectively, followed by catalytic reduction. Biphenyl‐2,2′‐diyl‐ and 1,1′‐binaphthyl‐2,2′‐diyl‐containing aromatic polyamides having inherent viscosities of 0.44–1.18 and 0.26–0.88 dL/g, respectively, were obtained either by the direct polycondensation or low‐temperature solution polycondensation of the diamines with aromatic dicarboxylic acids (or diacid chlorides). These polymers were readily soluble in a variety of organic solvents including N , N ‐dimethylacetamide (DMAc), N ‐methyl‐2‐pyrrolidone (NMP), dimethyl sulfoxide, m ‐cresol, and pyridine. Transparent, pale yellow, and flexible films of these polymers could be cast from the DMAc or NMP solutions. These aromatic polyamides containing biphenyl and binaphthyl units had glass transition temperatures in the range of 215–255 and 266–303°C, respectively. They began to lose weight at ca. 380°C, with 10% weight loss being recorded at about 470°C in air. © 1993 John Wiley &amp; Sons, Inc.
The T Cell Receptor as a Multicomponent Signalling Machine: CD4/CD8 Coreceptors and CD45 in T Cell Activation (1992)

The T cell receptor is a multicomponent signalling machine. The three main components are the hypervariable alpha: beta heterodimer that confers specificity and its attendant invariant chains CD3 gamma, delta, and epsilon and the zeta:zeta or zeta:eta, the CD4 or CD8 coreceptor, and CD45. Each of these components is required for efficient signal transduction, and each has relevant enzymatic activity associated with it. The invariant part of the T cell receptor is associated with the tyrosine kinase p59fyn, the coreceptors are associated with the tyrosine kinase p56lck, and the cytoplasmic domain of CD45 has tyrosine-specific phosphatase activity. Moreover, there is strong evidence that these components interact in the plane of the membrane, and that these interactions are relevant for signal transduction. Finally, changes in the structure of CD45 that occur during differentiation of T cells alter the interactions of these three components of the signal transducing machinery, perhaps accounting for changes in signal transduction that accompany T-cell development in the thymus and the development of immunological memory cells.
Characterization of Fluorosed Human Enamel by Color Reflectance, Ultrastructure, and Elemental Composition (1995)

Mature fluorosed human enamel has been described as a subsurface enamel hypomineralization, with porosity increasing relative to the degree of fluorosis. The purpose of the current study was to quantitatively measure the color of the fluorosed enamel by light reflectance, and to further characterize the enamel by scanning electron microscopy. Teeth with varying degrees of fluorosis were obtained and divided in groups of mild, moderate and severe fluorosis using Dean's index for fluorosis. The color of the labial enamel surface was measured using a Minolta Chroma Meter CR241 (Minolta, Ramsey, N.J., USA). The teeth were further characterized for elemental composition using an energy-dispersive spectrometer, and imaged in both secondary and backscattered electron modes. The results of this study showed that the moderately and severely fluorosed enamel contained an uneven distribution of areas which were more electron-absorbent with a relatively increased carbon content. The changes in the physical characteristics of the teeth could be quantitated by measurements of light reflectance. The color of the teeth was significantly different between groups, with all groups significantly different than normal.