gebhart/patrepeval huggingface dataset:
The Economic Burden of Dry Eye Disease in the United States: A Decision Tree Analysis (2010)

DED poses a substantial economic burden on the payer and on the society. These findings may provide valuable information for health plans or employers regarding budget estimation.
cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. (1986)

The amino acid sequences deduced from cDNA clones of human lamin A and lamin C show identity between these two lamins except for an extra 9.0-kDa carboxyl-terminal tail that is present only in lamin A. Both lamins A and C contain an alpha-helical domain of approximately 360 residues that shows striking homology to a corresponding alpha-helical rod domain that is the structural hallmark of all intermediate filament proteins. However, the lamin alpha-helical domain is 14% larger than that of the intermediate filament proteins. In addition to the extensive homology to intermediate filament proteins as reported [McKeon, F., Kirschner, M. & Caput, D. (1986) Nature (London) 319, 463-468], a different 82-amino acid residue stretch at the carboxyl terminus of lamin A has been deduced and verified by amino acid sequencing. This region contains sequence homology to amino- and carboxylterminal domains of type I and type II epidermal keratins. Implications of the presence of these and other domains in lamins A and C for the assembly of the nuclear lamina are discussed.
miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs (2002)

Gemin3 is a DEAD-box RNA helicase that binds to the Survival of Motor Neurons (SMN) protein and is a component of the SMN complex, which also comprises SMN, Gemin2, Gemin4, Gemin5, and Gemin6. Reduction in SMN protein results in Spinal muscular atrophy (SMA), a common neurodegenerative disease. The SMN complex has critical functions in the assembly/restructuring of diverse ribonucleoprotein (RNP) complexes. Here we report that Gemin3 and Gemin4 are also in a separate complex that contains eIF2C2, a member of the Argonaute protein family. This novel complex is a large approximately 15S RNP that contains numerous microRNAs (miRNAs). We describe 40 miRNAs, a few of which are identical to recently described human miRNAs, a class of small endogenous RNAs. The genomic sequences predict that miRNAs are likely to be derived from larger precursors that have the capacity to form stem-loop structures.
Synthesis of 5,6‐dimethoxyquinazolin‐2(1H)‐ones (1986)

Abstract Synthesis of 5,6‐dimethoxyquinazolin‐2(1 H )‐one derivatives was the subject of investigations leading to the preparation of title compounds 11, 13, 14 and 26 . Target quinazolines 1 were synthesized in three ways; the route starting from o ‐vanillin via the intermediacy of 6‐amino‐2,3‐dimethoxyacetophenone ( 19 ) was used for most of the preparative work. The unexpected formation of an acid‐labile dimer of 13 was discovered and solid state 13 C nmr was used for structural assignment. The 5‐methoxy substituent in these systems shows anomalous spectral characteristics and, in one case, was cleaved in acid media to 22 .
Role of the Sp Family of Transcription Factors in the Ontogeny of Growth Hormone Receptor Gene Expression (1999)

The growth hormone (GH) receptor is essential for the actions of growth hormone on postnatal growth and metabolism. GH receptor transcripts are characterized by the presence of disparate 5'-untranslated exons. Factors regulating the expression of the GC rich L2 transcript of the murine GH receptor gene have hitherto remained unidentified. To characterize the mechanisms regulating expression of the L2 transcript, primer extension and ribonuclease protection assays were used to identify transcription start sites in RNA from liver of adult mice. Transient transfection experiments revealed that 2.0 kilobase pairs of the L2 5'-flanking sequence exhibited promoter activity in BNL CL.2 (mouse liver) cells, CV-1 (monkey kidney) cells, and HRP.1 trophoblasts. Deletional analysis localized a major regulatory region to within 75 base pairs of the 5' transcription start site. Sequence analysis revealed that the region contained consensus binding sites for the Sp family of transcription factors. Standard gel shift and supershift analysis using liver nuclear extracts established that Sp1 and Sp3 bound this regulatory element. Transfection of wild type but not mutant decoy oligonucleotides into BNL CL.2 cells decreased the activity of the L2 promoter. Overexpression of Sp1 and Sp3 protein in Drosophila Schneider cells established that Sp3 is more potent than Sp1 in transactivating the L2 promoter. Co-transfection experiments further established that Sp1 antagonizes the activity of Sp3 to transactivate the L2 promoter. Western blot analysis of liver nuclear extracts revealed that the levels of Sp3 increase significantly after birth, suggesting a role for the Sp family of transcription factors in controlling the fetal to postnatal increase in GH receptor gene expression.
Photon antibunching in the fluorescence of a single dye molecule trapped in a solid (1992)

The correlation between fluorescence photons emitted by an optically pumped single molecule of pentacene in a p-terphenyl host has been investigated at short times. The correlation function shows photon antibunching, a unique feature of a nonclassical radiation field, which decreases if two molecules rather than one are pumped at the same time. The peculiarities of the correlation function for a three-level molecule are discussed and the theoretical description outlined.
Structural and kinetic modifications of aldose reductase by S-nitrosothiols (2001)

Modification of aldose reductase (AR) by the nitrosothiolsS-nitroso-N-acetyl penicillamine (SNAP) and N-(β-glucopyranosyl)-N2-acetyl-S-nitrosopenicillamide (glyco-SNAP) resulted in a 3–7-fold increase in its kcat and a 25–40-fold increase in its Km for glyceraldehyde. In comparison with the native protein, the modified enzyme was less sensitive to inhibition by sorbinil and was not activated by SO2−4 anions. The active-site residue, Cys-298, was identified as the main site of modification, because the site-directed mutant in which Cys-298 was replaced by serine was insensitive to glyco-SNAP. The extent of modification was not affected by Pi or O2, indicating that it was not due to spontaneous release of nitric oxide (NO) by the nitrosothiols. Electrospray ionization MS revealed that the modification reaction proceeds via the formation of an N-hydroxysulphenamide-like adduct between glyco-SNAP and AR. In time, the adduct dissociates into either nitrosated AR (AR-NO) or a mixed disulphide between AR and glyco-N-acetylpenicillamine (AR-S-S-X). Removal of the mixed-disulphide form of the protein by lectin-column chromatography enriched the preparation in the high-Km–high-kcat form of the enzyme, suggesting that the kinetic changes are due to the formation of AR-NO, and that the AR-S-S-X form of the enzyme is catalytically inactive. Modification of AR by the non-thiol NO donor diethylamine NONOate (DEANO) increased enzyme activity and resulted in the formation of AR-NO. However, no adducts between AR and DEANO were formed. These results show that nitrosothiols cause multiple structural and functional changes in AR. Our observations also suggest the general possibility that transnitrosation reactions can generate both nitrosated and thiolated products, leading to non-unique changes in protein structure and function.
Ion-responsive alginate based macroporous injectable hydrogel scaffolds prepared by emulsion templating (2013)

Ion-responsive biocompatible macroporous hydrogels with a well-defined highly interconnected open porous structure were synthesised using oil-in-water (o/w) high internal phase emulsion (HIPE) templating. Methacrylate-modified alginate was crosslinked in the continuous minority water phase and the oil internal phase removed to produce macroporous hydrogel monoliths. The physical dimensions, pore and pore throat size as well as water uptake of the alginate polyHIPE hydrogel can be controllably tuned by ion-responsive behaviour towards Ca<sup>2+</sup> ions. The ionic crosslinks formed are fully reversible and be dissolved using sodium citrate to remove Ca<sup>2+</sup> ions through chelation. The polyHIPE hydrogels possess mechanical properties with storage moduli up to 20 kPa and are biocompatible as shown by cytotoxicity assays. The hydrogel can be extruded through a hypodermic needle causing it to break into small pieces (about 1 to 3 mm in diameter) while retaining the interconnected pore morphology after injection. Furthermore, these hydrogel fragments can be reformed into a coherent scaffold under mild conditions using an alginate solution containing Ca<sup>2+</sup> ions.
What goes up (from heart to brain) must calm down (from brain to heart)! : Studies on the interaction between baroreceptor activity and cortical excitability (1995)

published
Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer (2005)

Bone morphogenetic proteins (BMPs) are an integral component of the TGFbeta superfamily, responsible for regulation of cell proliferation, differentiation, migration and programmed cell death in a variety of cell types. The BMPs transduce their signals directly through the SMAD family of proteins but they also have been reported to interact with the MAPK and Erk pathways. Inactivation of the BMP pathway genes has been implicated as important in several cancers. Recent work has shown that BMP3b is epigenetically inactivated in cancer and suggests that BMP6 can be epigenetically inactivated. We investigated whether BMP6 is epigenetically inactivated in cell lines and whether BMP3b and BMP6 are epigenetically inactivated in non-small-cell lung cancer (NSCLC). We also studied the relationship between BMP methylation and k-ras mutation. Here, we demonstrate that the BMP3b and BMP6 genes are common targets of epigenetic inactivation in NSCLC, and that they are significantly more likely to be concurrently inactivated (P=0.009). Furthermore, this coinactivation of BMP3b and BMP6 is significantly associated with mutation of k-ras codon 12 in lung cancer (P=0.003); those with a k-ras mutation were six times more likely to have concurrent methylation of these BMP loci. Hence, these data suggest that concurrent inactivation of the BMP and activation of the Ras signalling pathways are important in lung carcinogenesis.
A rapid procedure for extracting genomic DNA from leukocytes (1991)

We have developed a rapid procedure based on standard protocols to isolate DNA from leukocytes. The procedure yields 100 Âµg to 150 Âµg from 5 ml of blood. The DNA produced is of good quality (fig. 1) and is suitable for restriction enzyme digestion or PCR amplification.
Synthetic Expanded Porphyrin Chemistry (2003)

Expanded porphyrins are synthetic analogues of the porphyrins, and differ from these and other naturally occurring tetrapyrrolic macrocycles by containing a larger central core with a minimum of 17 atoms, while retaining the extended conjugation features that are a hallmark of these quintessential biological pigments. The result of core expansion is to produce systems with novel spectral and electronic features, interesting and, often unprecedented, cation-coordination properties, and, in many cases, an ability to bind anions in certain protonation states. Also adding to the appeal of expanded porphyrins is their central role in addressing issues of aromaticity. In many cases, they also display structural features, such as decidedly nonplanar "figure-eight" motifs, that have no antecedents in the chemistry of porphyrins or related macrocyclic compounds. In this Review, the various synthetic approaches now being employed to produce expanded porphyrins as well as their various applications-related aspects are discussed.
Calcium Chloride and Sodium Phosphate in Neonatal Parenteral Nutrition Containing TrophAmine (2012)

The data can provide a guide for compounding neonatal PN solutions containing TrophAmine, CaCl, and NaPhos. More studies are needed to determine the long-term effects of substituting CaCl for CaGlu in PN solutions for neonates. Substituting CaCl and NaPhos for CaGlu and KPhos significantly decreases Al concentrations in PN and potential Al exposure of neonatal patients.
ChemInform Abstract: Chemistry of Polynuclear Metal Complexes with Bridging Carbene or Carbyne Ligands. Part 77. Reactions of Iron‐Molybdenum Compounds with Alkynes; Crystal Structures of (MoFe(μ‐C(C6H4Me‐4)C(CHMe)CH2C(Me)C(Me))(CO)4(η‐C5H5)), (MoFe(μ‐C(C6H4Me‐4)C(CHMe)CH2)(CO)5(η‐C5H5)), and (MoFe(μ‐C(C6H4Me‐4)C(CH2PMe3)CHMe)(CO)5(η‐C5H5)). (1988)

Abstract The title reactions are outlined in the scheme.
Effect of Benzalkonium Chloride on Transscleral Drug Delivery (2005)

The results of this study demonstrate that BAK may improve the ocular penetration of a drug in a transscleral drug delivery system without producing toxic reactions.
A Comparison of Enalapril with Hydralazine–Isosorbide Dinitrate in the Treatment of Chronic Congestive Heart Failure (1991)

The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.
Diabetes in pregnancy (1985)

There are three key goals in current management of the diabetic pregnancy. Normal diabetes control before conception and during the first trimester in an attempt to reduce the incidence of congenital abnormalities. This implies that all diabetic women of childbearing age should have counseling before pregnancy. Routine use of new techniques such as home blood glucose monitoring, intensified conventional insulin regimens, or an insulin infusion pump for maintenance of tight metabolic control both before and during pregnancy. Delay in delivery of the baby until the due date, assuming good diabetes control and normal antepartum monitoring of the fetus, to reduce the incidence of macrosomatia, decrease the rate of cesarean section, and decrease neonatal mortality. The current outlook for the pregnant woman with diabetes is an optimistic one. Until recently, most women with diabetes were told that they should avoid pregnancy. Sterilization was often suggested as a means of contraception. Unfortunately, some women are still getting that message from their physician. This is unacceptable, as it is obvious that diabetes is no longer a barrier to pregnancy. Most women with diabetes can now consider the possibility of pregnancy and know that they have a reasonable chance of having a healthy child. Furthermore, new developments in diabetes care continue and should lead to an even brighter future for this group of patients. New advances in treatment, such as implantable insulin pumps, glucose sensors, and islet cell transplants, are just over the horizon. With these developments, a woman with diabetes will be freed from the intensive regimen she must now practice to achieve a successful pregnancy.
Adult Cardiac Sca-1-positive Cells Differentiate into Beating Cardiomyocytes (2004)

Although somatic stem cells have been reported to exist in various adult organs, there have been few reports concerning stem cells in the heart. We here demonstrate that Sca-1-positive (Sca-1+) cells in adult hearts have some of the features of stem cells. Sca-1+ cells were isolated from adult murine hearts by a magnetic cell sorting system and cultured on gelatin-coated dishes. A fraction of Sca-1+ cells stuck to the culture dish and proliferated slowly. When treated with oxytocin, Sca-1+ cells expressed genes of cardiac transcription factors and contractile proteins and showed sarcomeric structure and spontaneous beating. Isoproterenol treatment increased the beating rate, which was accompanied by the intracellular Ca(2+) transients. The cardiac Sca-1+ cells expressed oxytocin receptor mRNA, and the expression was up-regulated after oxytocin treatment. Some of the Sca-1+ cells expressed alkaline phosphatase after osteogenic induction and were stained with Oil-Red O after adipogenic induction. These results suggest that Sca-1+ cells in the adult murine heart have potential as stem cells and may contribute to the regeneration of injured hearts.
Preparation of base-modified nucleosides suitable for non-radioactive label attachment and their incorporation into synthetic oligodeoxyribonucleotides (1987)

A very mild and efficient procedure has been developed for the preparation of C-5 substituted deoxyuridines. The substituent carries a masked primary aliphatic amino group. These compounds are readily converted into their phosphoramidites and can be used to prepare oligonucleotides carrying one or more aliphatic amino groups. Fluorescein isothiocyanate coupled to these compounds gives oligonucleotide probes carrying multiple fluorescein labels. These compounds have a free 5'-hydroxy group enabling additional 5'- end radioactive labelling for evaluation of their hybridization characteristics. It was found that oligonucleotides carrying a long (11 atom) linker arm to the fluorescein hybridize more efficiently to mRNA than those carrying a short (4 atom) arm. The long linker arm derivatives are comparable to underivatized oligonucleotides in hybridizing to mRNA.
Quantifying cross-platform engagement through large-scale user alignment (2014)

As online social media becomes prevalent as part of our daily life, it is increasingly common for a user to have accounts on multiple social media platforms. In this work, we present our findings on quantifying the extent of user engagement of different platforms as well as their correlations. The study is conducted based on a large-scale user alignment on 6 major social media platforms. Specifically, we identify both explicit and implicit mentions of social media accounts from the Twitter Decahose stream over a period of 22 months. During the process, we have aligned a total of 21,456,808 Twitter users to their alternative accounts on different platforms. Subsequently, we extract the number of overlapping users between any combination of these social media platforms exhaustively.
Clinical approaches to non-alcoholic fatty liver disease (2014)

Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients.
4-1BB and OX40 Dual Costimulation Synergistically Stimulate Primary Specific CD8 T Cells for Robust Effector Function (2004)

CD40, 4-1BB, and OX40 are costimulatory molecules belonging to the TNF/nerve growth factor superfamily of receptors. We examined whether simultaneous costimulation affected the responses of T cells using several different in vivo tracking models in mice. We show that enforced dual costimulation through 4-1BB and OX40, but not through CD40, induced profound specific CD8 T cell clonal expansion. In contrast, the response of specific CD4 T cells to dual costimulation was additive rather than synergistic. The synergistic response of the specific CD8 T cells persevered for several weeks, and the expanded effector cells resided throughout lymphoid and nonlymphoid tissue. Dual costimulation through 4-1BB and OX40 did not increase BrdU incorporation nor an increase in the number of rounds of T cell division in comparison to single costimulators, but rather enhanced accumulation in a cell-intrinsic manner. Mechanistically speaking, we show that CD8 T cell clonal expansion and effector function did not require T help, but accumulation in (non)lymphoid tissue was predominantly CD4 T cell dependent. To determine whether this approach would be useful in a physiological setting, we demonstrated that dual costimulation mediated rejection of an established murine sarcoma. Importantly, effector function directed toward established tumors was CD8 T cell dependent while being entirely CD4 T cell independent, and the timing of enforced dual costimulation was exquisitely regulated. Collectively, these data suggest that simultaneous dual costimulation through 4-1BB and OX40 induces a massive burst of CD8 T cell effector function sufficient to therapeutically treat established tumors even under immunocompromising conditions.
Sub-1-V CMOS proportional-to-absolute temperature references (2003)

Presents a new all-MOS circuit technique for very-low-voltage proportional-to-absolute temperature (PTAT) references. Optimization of supply scaling below the sum of threshold voltages is based on log companding and implemented by operating the MOSFET in weak inversion. The key design equations for current (μA) and voltage (sub-100 mV) references and their standard deviations (around 5%) are derived by analytical analysis. Two sub-1-V sub-5-μW integrated PTAT references are presented and exhaustively tested for 1.2- and 0.35-μm very large scale integration technologies. Both designs report good agreement between analytical, simulated, and experimental data, exhibiting PSRR(DC)+>60 dB. Hence, the resulting PTAT circuits are suitable for very-low-voltage system-on-a-chip applications in digital CMOS technologies.