gebhart/patrepeval huggingface dataset:
Abstract 77: MicroRNA-34a Accelerates Aging in Vascular Smooth Muscle Cells (SMCs) Isolated from Transgenic Mice Overexpressing Nox1 in SMCs (2013)

Background: Aging increases cardiovascular morbidity. Aging in vascular smooth muscle cells (VSMC) induces cell senescence, leading to impaired vasodilation with decreased vascular compliance, increased inflammation and oxidative stress. MicroRNA-34a (miR-34a) has been reported as a biomarker of aging. Methods and Results: After screening for a group of miRs, there was a &gt; 2 fold of miR-34a in aortic SMCs isolated from transgenic mice overexpressing Nox1 in SMCs (Nox-1 SMCs). Therefore, we hypothesized that miR34 contributes to VSMC aging. TaqMan miR assay confirmed an increased miR-34a by 2.1 fold in young NOX-1 SMCs (passage 3-7) with an increase by 5.25 fold in activity of senescence-associated β-galactosidase (SA-β-Gal ) compared to WT. miR-34a in old NOX-1 and WT SMCs (passage 14-16) was increased by 3.8 fold and 2.1 fold, respectively, compared to young SMCs (both P&lt; 0.01 ). There was 1.8 fold more miR-34a detected in old NOX-1 vs. old WT SMCs. SA-β-Gal positive cells accounted for 0.8±1% and 4±1.3% in young WT and NOX-1 SMCs (P&lt;0.01), and 5±1.5% and 32±5% in old WT and NOX-1 SMCs (P &lt;0.005). After transfection with miR-34a inhibitor, mature miR-34a was decreased by 75% and SA-β-Gal activity by 58% in old NOX-1 cells with parallel changes in the protein expression for Gamma-H2AX( a DNA damage marker) and p21( an activator for cell senescence). Moreover, phosphatase nuclear targeting subunit (PNUTS, a recently identified anti-age protein and direct miR-34a target) was not changed in young NOX-1 SMCs but reduced by 78% in old NOX-1 SMCs. Interestingly, nuclear factor (erythroid-derived 2)-like 2 (Nrf2, a key transcription factor for antioxidant genes) mRNA and protein were decreased by 55% and 32% in old NOX-1 SMCs (P&lt;0.01 and 0.05). Nrf2 activator tert-butylhydroquinone (tBHQ) reduced miR-34a from 2.9±0.4 to 1.8±0.2 fold in those cells. Conclusion: Increased NOX-1 in SMCs induces miR-34a that accelerates SMC senescence. The pathway may involve downregulation of Nrf2 and increased P21 through P53 pathway. This provides potential targets for protecting against vascular aging.
Total Syntheses of Natural Pseurotins A, F2, and Azaspirene (2004)

Abstract We describe the total syntheses of natural pseurotins A and F2, inhibitors of chitin synthase, both of which possess an unusual 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione ring system. The total syntheses of these spiro-hetereocyclic natural products feature: 1) a stereoselective preparation of two segments, i.e., a 2,3-dihydroxylated heptenal derivative and a highly functionalized γ-lactone, each from d-glucose, 2) the connection of the two segments via an aldol-type carbon–carbon bond formation, 3) spirocyclic ring formation from the aldol adduct through convenient 3(2H)-furanone formation, 4) the transformation of a spirocyclic γ-lactone into a γ-lactam hemiaminal derivative, and 5) conversion of the benzyl substituent in the γ-lactam ring into a benzoyl group via a cyclic enamide followed by m-CPBA oxidation in the final stage of the total synthesis. In the initial stage, the quaternary spiro-carbon center in the target molecules was efficiently constructed by a stereochemically exclusive vinyl Grignard addition to the d-glucose-derived 3-ulose. Furthermore, the preparation of the γ-lactone included a stereo- and regioselective Cu(I)-mediated benzyl Grignard addition to aldehyde. We have also completed the total synthesis of a structurally related novel angiogenesis inhibitor, azaspirene, using the analogous reaction sequence.
A convergent, flexible synthesis of 1,3-dienes (2002)

1,3-Dienes were prepared from 1,4-ketoxanthates, obtained by the radical addition reaction of an S-(2-oxoalkyl) xanthate to a terminal olefin, through the DBU induced thermal elimination of sulfur dioxide from the derived 2-sulfolenes.
Ultrasound triggered mRNA delivery to dendritic cells—Towards an in vivo cancer vaccination strategy (2017)

Increasing knowledge on the crucial role of dendritic cells (DCs) in the initiation of immunity has launched a new field in cancer immunotherapy: DC vaccination. By loading patient’s DCs with tumor antigens and injecting them as a vaccine, antitumor immune responses can be induced. This project aims to use theranostic mRNA-loaded MBs for ultrasound-guided, ultrasound-triggered antigen-loading of DCs within the lymph nodes in vivo. mRNA-loaded MBs were prepared by attaching mRNA-lipid complexes to lipid MBs via avidin-biotin linkages. MBs loaded with mRNA encoding a tumor antigen (ovalbumin, OVA) were used to sonoporate murine DCs in vitro. These mRNA-sonoporated DCs were then used as therapeutic vaccines in E.G7-OVA-bearing mice. In vitro mRNA-sonoporation of murine DCs revealed transfection efficiencies up to 27%. The potential of this technique was further assessed in vivo by vaccinating E.G7-OVA-bearing mice with sonoporated DCs. When mRNA-sonoporated DCs were used, tumor growth was significantly reduced and even regressed in 30% of the animals. Moreover, rechallenge with tumor cells did not lead to tumor growth, indicating long-lasting immunological protection. A CEUS study in dogs showed the MBs rapidly drained to the lymph nodes after sc injection. Moreover, this revealed detailed information on the lymphatic anatomy.
Prevention and Treatment of Obesity, Insulin Resistance, and Diabetes by Bile Acid–Binding Resin (2006)

Bile acid-binding resins, such as cholestyramine and colestimide, have been clinically used as cholesterol-lowering agents. These agents bind bile acids in the intestine and reduce enterohepatic circulation of bile acids, leading to accelerated conversion of cholesterol to bile acids. A significant improvement in glycemic control was reported in patients with type 2 diabetes whose hyperlipidemia was treated with bile acid-binding resins. To confirm the effect of such drugs on glucose metabolism and to investigate the underlying mechanisms, an animal model of type 2 diabetes was given a high-fat diet with and without colestimide. Diet-induced obesity and fatty liver were markedly ameliorated by colestimide without decreasing the food intake. Hyperglycemia, insulin resistance, and insulin response to glucose, as well as dyslipidemia, were markedly and significantly ameliorated by the treatment. Gene expression of the liver indicated reduced expression of small heterodimer partner, a pleiotropic regulator of diverse metabolic pathways, as well as genes for both fatty acid synthesis and gluconeogenesis, by treatment with colestimide. This study provides a molecular basis for a link between bile acids and glucose metabolism and suggests the bile acid metabolism pathway as a novel therapeutic target for the treatment of obesity, insulin resistance, and type 2 diabetes.
Figure S1-11 from Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors (2023)

&lt;p&gt;Supplementary Figure S1-11&lt;/p&gt;
Implications of an audible third heart sound in evaluating cardiac function. (1993)

We prospectively compared auscultatory findings of third heart sounds with radionuclide ventriculographic analysis of systolic and diastolic function. Cardiac auscultation was done to detect an S3 in patients referred for radionuclide ventriculographic analysis of ventricular function. Of 49 adult men with the diagnosis of chronic, nonvalvular heart failure who were referred for the evaluation of heart failure, 22 (45%) at the time of the ventriculography had an S3 present on examination. For the entire study group, the radionuclide ventriculography-derived ejection fraction was 33% +/- 19.5 (mean +/- SD) with a range of 6% to 74%. The peak ejection rate was 2.05 +/- 1.09 end-diastolic volume per second with a range of 0.30 to 4.56. The peak filling rate was 1.97 +/- 1.07 end-diastolic volume per second with a range of 0.44 to 3.94, and the time to peak filling rate was 0.18 +/- 0.11 per second with a range of 0.05 to 0.61. The presence of an S3 was associated with a reduced ejection fraction and also with impaired diastolic function as determined by the peak filling rate. The sensitivity and specificity for the S3 in detecting abnormal systolic function (ejection fraction < 50%) were 51% and 90%, respectively, with a positive predictive value of 95% and a negative predictive value of only 32%. For an ejection fraction of less than 30%, the S3 had a sensitivity and specificity of 78% and 88%. The presence of an S3 was highly predictive of an abnormal ejection fraction. The absence of an S3, however, is not uncommon in patients with a mildly impaired ejection fraction.
ChemInform Abstract: Purine and 1‐Deazapurine Ribonucleosides and Deoxyribonucleosides: Synthesis and Biological Activity. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
<title>Optical elements derived from stretched glass</title> (1993)

The physical elongation of a phase-separated glass by the application of a pulling stress to the glass above its softening temperature leads to a material with a number of interesting optical properties. This study is concerned with silver halide as the separated phase in an alkali-alumino- borosilicate glass. The initially spherically shaped halide particle is elongated into an elliptical shape by the action of the stretching process. As a consequence, the composite body acquires optical anisotropy exhibited as birefringence and dichroism. Experimental results show how the magnitude of the optical anisotropy can be related to shape anisotropy of the particles and, in turn, to the pulling stress. These results are discussed in terms of a simple polarizability model which adequately explains the results.
Features and distribution of CD8 T cells with human leukocyte antigen class I–specific receptor expression in chronic hepatitis C (2007)

These results support the concept that an accumulation in the liver parenchyma of NKR(+)CD8(+) T cells that have functional alterations could be responsible for liver lesions. They provide novel insights into the complexity of liver-infiltrating CD8(+) T cells in chronic hepatitis C and reveal that distinct subsets of antigen-experienced CD8(+) T cells are differentially sensitive to the pervasive influence of HCV.
Supplementary Tables from TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors (2023)

&lt;p&gt;Supplementary Tables&lt;/p&gt;
Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease (2015)

Oxidants/antioxidants play an important role in cellular homeostasis. The human body has endogenous molecules that work as antioxidants, such as glutathione, superoxide dismutase, peroxidases, and catalase. Exogenous substances in the diet, such as β-carotene, ascorbate, and vitamin E, are vital antioxidants. Of these, vitamin E is likely the most important antioxidant in the human diet, and many studies have been performed to elucidate its role in health and disease. Vitamin E is a family of several compounds, of which α-tocopherol is the most widely known analog. α-Tocopherol exhibits antioxidative property in vitro and inhibits oxidation of low-density lipoprotein cholesterol. In addition, α-tocopherol shows anti-inflammatory activity and modulates expression of proteins involved in the uptake, transport, and degradation of atherogenic lipids. Though α-tocopherol exhibits important antioxidant, anti-inflammatory, and antiatherogenic features in vitro, α-tocopherol supplements have failed to consistently reduce atherosclerosis-related events in human trials. The conflicting results have led to reconsideration of the importance previously given to α-tocopherol and led to interest in other members of vitamin E family, especially γ-tocopherol, which exerts a much more potent antioxidant, anti-inflammatory, and cardioprotective effect than α-tocopherol. This reconsideration has been backed by solid laboratory and clinical research. We suggest that the absence of γ-tocopherol in traditional preparations may be one reason for the lack of consistent salutary effects of vitamin E preparations in clinical trials. This review summarizes our current understanding of tocopherols as antioxidant molecules and emerging evidence of an important role of γ-tocopherol in the pathophysiology of atherosclerosis-related cardiovascular disease.
Photovoltaic maximum power point tracking for mobile applications (2010)

The photovoltaic maximum power point tracking (MPPT) algorithm based on incremental conductance is found to have an error mode which prevents its normal operation under conditions of rapidly changing/oscillating solar input (insolation). An enhancement to the algorithm is investigated and experimentally evaluated. It can be readily added around an existing MPPT algorithm to enable it to be used more reliably in mobile applications.
Gas Turbine Model Scaling (1995)

A dimensional analysis, of both the equations governing boundary-layer flow with heat transfer and of the steady and unsteady boundary conditions, demonstrates that twelve non-geometric, dimensionless parameters are required for the complete similarity of a three-dimensional, compressible, viscous flow with a freestream pressure gradient. The analysis shows that non-dimensional groups describing the machine can be reduced to a function of metal angles and twelve fundamentally derived, dimensionless scaling parameters. The equation describing the rate of local entropy generation caused by fluid friction and heat transfer is also non-dimensionalised. This leads to an estimate of the relative magnitude of entropy generation due to fluid friction and heat transfer. A comparison of the principle operating parameters for a number of existing gas turbine test facilities, designed to model the aerodynamic and heat transfer conditions in real engines, suggests that full modelling of engine boundary-layer phenomena has not been achieved. A semi-empirical, boundary-layer analysis suggests that measured velocity boundary-layer profiles from adiabatic test facilities differ significantly with those from a gas turbine operating at engine gas to wall temperature ratios. Similarly, the analysis established the shape of the velocity boundary-layer to be dependent upon the specific-heat ratio.
A hierarchical block-based modeling methodology for SoC in GENESYS (2003)

System-on-a-chip (SoC) designs promise to play a dominant role in the future of gigascale integrated (GSI) systems. Existing chip modeling tools based on technology parameters for projecting physical performance are ill suited for projecting the performance of SoC designs. A new modeling methodology for heterogeneous SoCs has been developed for a technology based simulation tool (GENESYS). The hierarchical block modeling methodology mimics the structure of a SoC design by partitioning the chip into blocks as is typical of megacell based design methodologies. The new model allows for exploration of the impact of technology choices on SoC performance for a wide variety of designs. An example SoC is simulated showing improved accuracy of the heterogeneous compared to the homogeneous model. A percentage error of 18.6% for the die size calculation in the homogeneous model is reduced to 3% with the heterogeneous modeling. In addition, the scaling characteristics of the example SoC are shown for the ITRS technology generations. Results show that the same design implemented in 35 nm technology could achieve a factor of 6 increase in clock frequency while operating at less than 1 W on a 5 mm/sup 2/ die.
Uterus autotransplantation in cynomolgus macaques: intraoperative evaluation of uterine blood flow using indocyanine green (2011)

ICG fluorescence angiography can be used for simple evaluation of real-time blood flow conditions in the anastomosed uterine artery, vein and uterine area and can facilitate the success rate of uterus transplantation.
Synthesis and cellular evaluation of click-chemistry probes to study the biological effects of alpha, beta-unsaturated carbonyls (2022)

Humans are commonly exposed to α,β-unsaturated carbonyls as both environmental toxins (e.g. acrolein) and therapeutic drugs (e.g. dimethylfumarate, DMFU, a front-line drug for the treatment of multiple sclerosis and psoriasis). These compounds undergo rapid Michael addition reactions with amine, imidazole and thiol groups on biological targets, with reaction at protein Cys residues being a major reaction pathway. However, the cellular targets of these species (the 'adductome') are poorly understood due to the absence of readily identifiable tags or reporter groups (chromophores/fluorophores or antigens) on many α,β-unsaturated carbonyls. Here we report a 'proof of concept' study in which we synthesize novel α,β-unsaturated carbonyls containing an alkyne function introduced at remote sites on the α,β-unsaturated carbonyl compounds (e.g. one of the methyl groups of dimethylfumarate). The presence of this tag allows 'click-chemistry' to be used to visualize, isolate, enrich and characterize the cellular targets of such compounds. The probes show similar selectivity and reactivity to the parent compounds, and compete for cellular targets, yielding long-lived (stable) adducts that can be visualized in intact cells (such as primary human coronary artery smooth muscle cells), and extracted and enriched for subsequent target analysis. It is shown using this approach that dimethylfumarate forms adducts with multiple intracellular targets including cytoskeletal, organelle and nuclear species, with these including the rate-limiting glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This approach should be amenable to use with multiple α,β-unsaturated carbonyls and a wide variety of targets containing nucleophilic sites.
A Direct and Selective Syntheses of α,α-Dichloro- and α-Chloro-ethyl Ketones by the Reaction of Alkyl Carboxylates with 1,1-Dichloroethyllithium (2000)

Abstract 1,1-Dichloroethyllithium (5), generated by treating 1,1-dichloroethane (4) with lithium diisopropylamide (LDA) or n-butyllithium, reacted with alkyl carboxylates to afford the corresponding α,α-dichloro- or α-monochloro-ethyl ketones selectively in good to high yields. According to the above alkylation method, synthetic intermediates of Taxol, optically active α,α-dichloroethyl polyoxyketone 2 and α-chloroethyl polyoxyketone 3, were respectively synthesized from optically active methyl polyoxycarboxylate 1 in good yields.
Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro. (1987)

The extent to which M. leprae and its products induced suppression of T lymphocyte proliferation in vitro was evaluated. M. leprae antigens suppressed T cell proliferation in response to mitogens and antigens in both lepromatous and tuberculoid patients, as well as controls never exposed to M. leprae or M. leprae endemic areas. Both soluble and particulate fractions of M. leprae were found to suppress proliferation in a dose-dependent manner. The extent of suppression was inversely related to the proliferative response of the donors mononuclear cells to M. leprae. Evidence indicates that M. leprae contains both stimulatory and suppressive molecules for T cells. One such suppressive antigen, Lipoarabinomannan (LAM)-B of M. leprae, also suppressed the proliferative response of tuberculoid patients. Suppression was also observed with the LAM-B of M. tuberculosis. The suppressive effects observed were not due to the toxicity of the antigen. Some of the suppressive activity was mediated by T8+ suppressor cells and was expressed in both lepromatous and tuberculoid patients. We suggest that previous sensitization to M. leprae and other cross-reactive mycobacterial antigens determines the sensitivity of T cells to the suppressive effects of M. leprae antigens.
Teaching Neuro Images : Meningoencephalocele and CSF leak in chronic idiopathic intracranial hypertension (2016)

A 63-year-old woman with epilepsy and chronic headaches was admitted for status epilepticus. A lumbar puncture revealed increased opening pressure of 320 mm H2O and bacterial meningitis. MRI brain demonstrated a partial empty sella, tortuous optic nerve sheaths, flattening of the optic papillae, and numerous prominent arachnoid granulations, consistent with chronic idiopathic intracranial hypertension (IIH), as well as bright CSF signal and brain parenchyma within a left meningoencephalocele (figure, A). A CT cisternogram confirmed communication of the subarachnoid space of the meningoencephalocele with the left sphenoid sinus through a small osseous defect (figure, B). While most CSF leaks are related to trauma, IIH is increasingly recognized as a cause of spontaneous leaks.1,2 While the increased opening pressure may have been due to her acute meningitis, her headache symptoms and MRI findings are suggestive of longstanding intracranial hypertension. Monitoring and medical treatment of IIH must accompany surgical repair to avoid recurrence.2
Microfluidic Glycosyl Hydrolase Screening for Biomass-to-Biofuel Conversion (2010)

The hydrolysis of biomass to fermentable sugars using glycosyl hydrolases such as cellulases and hemicellulases is a limiting and costly step in the conversion of biomass to biofuels. Enhancement in hydrolysis efficiency is necessary and requires improvement in both enzymes and processing strategies. Advances in both areas in turn strongly depend on the progress in developing high-throughput assays to rapidly and quantitatively screen a large number of enzymes and processing conditions. For example, the characterization of various cellodextrins and xylooligomers produced during the time course of saccharification is important in the design of suitable reactors, enzyme cocktail compositions, and biomass pretreatment schemes. We have developed a microfluidic-chip-based assay for rapid and precise characterization of glycans and xylans resulting from biomass hydrolysis. The technique enables multiplexed separation of soluble cellodextrins and xylose oligomers in around 1 min (10-fold faster than HPLC). The microfluidic device was used to elucidate the mode of action of Tm_Cel5A, a novel cellulase from hyperthermophile Thermotoga maritima . The results demonstrate that the cellulase is active at 80 °C and effectively hydrolyzes cellodextrins and ionic-liquid-pretreated switchgrass and Avicel to glucose, cellobiose, and cellotriose. The proposed microscale approach is ideal for quantitative large-scale screening of enzyme libraries for biomass hydrolysis, for development of energy feedstocks, and for polysaccharide sequencing.
A Direct Sulfation Process of a Marine Polysaccharide in Ionic Liquid (2015)

GY785 is an exopolysaccharide produced by a mesophilic bacterial strain Alteromonas infernus discovered in the deep-sea hydrothermal vents. GY785 highly sulfated derivative (GY785 DRS) was previously demonstrated to be a promising molecule driving the efficient mesenchymal stem cell chondrogenesis for cartilage repair. This glycosaminoglycan- (GAG-) like compound was modified in a classical solvent (N,N'-dimethylformamide). However, the use of classical solvents limits the polysaccharide solubility and causes the backbone degradation. In the present study, a one-step efficient sulfation process devoid of side effects (e.g., polysaccharide depolymerization and/or degradation) was developed to produce GAG-like derivatives. The sulfation of GY785 derivative (GY785 DR) was carried out using ionic liquid as a reaction medium. The successful sulfation of this anionic and highly branched heteropolysaccharide performed in ionic liquid would facilitate the production of new molecules of high specificity for biological targets such as tissue engineering or regenerative medicine.