gebhart/patrepeval huggingface dataset:
Hydrogen sulfide (H2S) releasing agents: chemistry and biological applications (2014)

Hydrogen sulfide (H2S) is a newly recognized signaling molecule with very potent cytoprotective actions. The fields of H2S physiology and pharmacology have been rapidly growing in recent years, but a number of fundamental issues must be addressed to advance our understanding of the biology and clinical potential of H2S in the future. Hydrogen sulfide releasing agents (also known as H2S donors) have been widely used in these fields. These compounds are not only useful research tools, but also potential therapeutic agents. It is therefore important to study the chemistry and pharmacology of exogenous H2S and to be aware of the limitations associated with the choice of donors used to generate H2S in vitro and in vivo. In this review we summarized the developments and limitations of currently available donors including H2S gas, sulfide salts, garlic-derived sulfur compounds, Lawesson's reagent/analogs, 1,2-dithiole-3-thiones, thiol-activated donors, photo-caged donors, and thioamino acids. Some biological applications of these donors were also discussed.
Information Processing in Medical Imaging Meeting (IPMI) (1993)

Abstract : Welcome to the thirteenth IPMI. As attendees here in beautiful northern Arizona, you are part of a tradition extending back to the early days of digital imaging. This conference holds a special place in the hearts of many longtime IPMI-goers. No other conference in our field can provide the spirited interactions and the stimulation that occur regularly at this one. To the IPMI veterans, we say welcome back, and thanks for continuing to make our conference the unique event it is. To first-time attendees, we extend a special welcome and an invitation to join the fray, to contribute your insights and criticisms of the ideas offered here. Let's all join in the give and take that lend vitality and excitement to our endeavors.
Cloning of a DNA fragment encoding a heme-repressible hemoglobin-binding outer membrane protein from Haemophilus influenzae (1996)

Haemophilus influenzae is able to use hemoglobin as a sole source of heme, and heme-repressible hemoglobin binding to the cell surface has been demonstrated. Using an affinity purification methodology, a hemoglobin-binding protein of approximately 120 kDa was isolated from H. influenzae type b strain HI689 grown in heme-restricted but not in heme-replete conditions. The isolated protein was subjected to N-terminal amino acid sequencing, and the derived amino acid sequence was used to design corresponding oligonucleotides. The oligonucleotides were used to probe a Southern blot of EcoRI-digested HI689 genomic DNA. A hybridizing band of approximately 4.2 kb was successfully cloned into pUC19. Using a 1.9-kb internal BglII fragment of the 4.2-kb clone as a probe, hybridization was seen in both typeable and nontypeable H. influenzae but not in other bacterial species tested. Following partial nucleotide sequencing of the 4.2-kb insert, a putative open reading frame was subcloned into an expression vector. The host Escherichia coli strain in which the cloned fragment was expressed bound biotinylated human hemoglobin, whereas binding of hemoglobin was not detected in E. coli with the vector alone. In conclusion, we hypothesize that the DNA fragment encoding an approximately 120-kDa heme-repressible hemoglobin-binding protein mediates one step in the acquisition of hemoglobin by H. influenzae in vivo.
1992 AAAI Robot Exhibition and Competition (1993)

The first Robotics Exhibition and Competition sponsored by the Association for the Advancement of Artificial Intelligence was held in San Jose, California, on 14-16 July 1992 in conjunction with the Tenth National Conference on AI. This article describes the history behind the competition, the preparations leading to the competition, the threedays during which 12 teams competed in the three events making up the competition, and the prospects for other such competitions in the future.
The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice (2008)

During dietary fat-induced development of obesity and insulin resistance, we found substantial changes in gene expression in the small intestine, indicating modulations of biological processes, especially related to lipid metabolism. Moreover, we found differential expression of potential signaling molecules that can provoke systemic effects in peripheral organs by influencing their metabolic homeostasis. Many of these fat-modulated genes could be linked to obesity and/or insulin resistance. Together, our data provided various leads for a causal role of the small intestine in the etiology of obesity and/or insulin resistance.
Nonablative Laser Skin Resurfacing using a 1540 nm Erbium Glass Laser (2002)

BACKGROUND A variety of laser systems have recently become available that allow for selective dermal remodeling without disruption of the epidermal surface. Modest clinical improvement in mild to moderate photoinduced facial rhytides with minimal morbidity is typical of these nonablative lasers, providing a significant advantage over traditional ablative laser systems. OBJECTIVE To determine the clinical and histologic effects of a novel 1540 nm erbium glass laser on facial rhytides. METHODS Patients with mild to moderate periorbital and perioral rhytides received a series of three monthly treatments with a 1540-nm erbium-doped phosphate glass laser by a single operator. Photographic and clinical evaluations were independently conducted by the patient and a masked medical observer at each treatment visit and at 1, 3, and 6 months following the final treatment session. Skin biopsies were obtained for histologic analysis by a board-certified dermatopathologist at baseline, immediately following laser irradiation, and at one and six months post-treatment. RESULTS Slow, progressive clinical improvement of rhytides was noted in all patients after each treatment and continued throughout the extended follow-up period. Side effects of treatment were limited to transient erythema and edema immediately following laser irradiation. No serious adverse effects were noted. Histologic skin changes were not apparent until several months following treatment, when an increase in dermal collagen was noted. CONCLUSIONS The nonablative 1540 nm erbium glass laser system with contact cooling produces gradual clinical and histologic improvement in mild to moderate facial rhytides with minimal risk of serious adverse sequelae.
Synthesis of Optically Active Imidazolines, Azapenams, Dioxocyclams, and Bis-dioxocyclams (1997)

Optically active 4-methyl-4-carbomethoxy-Δ2-imidazoline was efficiently synthesized on a multigram scale. Photolysis with (methoxymethylcarbene)chromium complex produced the optically active azapenam in good yield and with high stereoselectivity. Acid-catalyzed dimerization followed by reduction produced the corresponding optically active dioxocyclam in good yield. Using a bis-carbene complex, an optically active bis-dioxocyclam was produced in excellent yield.
Parallel magnetic resonance imaging (2007)

Parallel imaging has been the single biggest innovation in magnetic resonance imaging in the last decade. The use of multiple receiver coils to augment the time consuming Fourier encoding has reduced acquisition times significantly. This increase in speed comes at a time when other approaches to acquisition time reduction were reaching engineering and human limits. A brief summary of spatial encoding in MRI is followed by an introduction to the problem parallel imaging is designed to solve. There are a large number of parallel reconstruction algorithms; this article reviews a cross-section, SENSE, SMASH, g-SMASH and GRAPPA, selected to demonstrate the different approaches. Theoretical (the g-factor) and practical (coil design) limits to acquisition speed are reviewed. The practical implementation of parallel imaging is also discussed, in particular coil calibration. How to recognize potential failure modes and their associated artefacts are shown. Well-established applications including angiography, cardiac imaging and applications using echo planar imaging are reviewed and we discuss what makes a good application for parallel imaging. Finally, active research areas where parallel imaging is being used to improve data quality by repairing artefacted images are also reviewed.
Promiscuous Behavior of HPV16E6 Specific T Cell Receptor Beta Chains Hampers Functional Expression in TCR Transgenic T Cells, Which Can Be Restored in Part by Genetic Modification (2010)

Background : T cell receptor gene transfer is a promising strategy to treat patients suffering from HPV induced malignancies. Therefore we isolated the TCR α β open reading frames of an HPV16E6 specific CTL clone and generated TCR transgenic T cells. In general low level expression of the transgenic TCR in recipient human T cells is observed as well as the formation of mixed TCRs dimers. Here we addressed both issues employing three different expression platforms. Methods : We isolated the HVP16E6 specific TCR α and TCR β open reading frames and retrovirally transduced human T cells with either wild-type (wt), or codon-modified (cm) chains to achieve enhanced TCR expression levels, or used codon-modification in combination with cysteinization (cmCys) of TCRs to facilitate preferential pairing of the introduced TCR α and TCR β chains. Results : Careful analysis of recipient T cells carrying the HPV16E6 TCR β and endogenous TCR chains revealed the transgenic TCRβ chain to behave very promiscuously. Further analysis showed that the percentage of tetramer positive T cells in codon-modified/cysteinized TCR transgenic T cells was four-fold higher compared to wild-type and two-fold higher compared to codon-modification only. Functional activity, as determined by IFN- γ production, was high in cmCysTCR transgenic T cells, where it was low in cm and wt TCR transgenic T cells. Recognition of endogenously processed HPV16E6 antigen by cmCysTCR transgenic T cells was confirmed in a cytotoxicity assay. Conclusions : Promiscuous behavior of the HPV16E6 specific TCR β chain can in part be forced back into specific action in TCR transgenic T cells by codon modification in combination with the inclusion of an extra cysteine in the TCR chains.
Activation of L-Citramalate Hydrolyase from Clostridium tetanomorphum (1969)

Abstract Citramalate hydrolyase (mesaconase) is inactivated by oxygen and can be reactivated by incubating the two protein components (Components I and II) with a reducing agent and ferrous ion in the absence of oxygen. Optimal conditions for the activation of the enzyme have been determined by the use of purified preparations of the two components, and the specificity of the reducing agent and ferrous ion requirements has been investigated. Several mercaptans and dithionite are effective in varying degrees as reducing agents. Three mercaptans, 2-mercaptoethanol, 2-mercaptoethylamine, and homocysteine, are fully effective at pH 8 and at a low Fe2+ concentration, whereas other mercaptans are maximally effective only when the pH and the Fe2+ level are increased. Ferrous ion is essential for activation of the enzyme and cannot be replaced by other divalent cations. Manganous ion inhibits activation. Evidence has been obtained that reduction of Component II by a mercaptan is the first rate-limiting step in the activation process. Reduction of Component II is a slow process, requiring about 45 min at 37° to reach completion under specific conditions. The degree of reduction appears to depend on the mercaptan concentration. Reduction is fully reversible by exposure to oxygen. Component II, either oxidized or reduced, is strongly inhibited by exposure to iodoacetate, whereas Component I is insensitive to iodoacetate. Ferrous ion is not involved in reduction of Component II by mercaptans, but is essential for the interaction of the protein components to form a catalytically active complex. The formation of the active complex from Component I and reduced Component II, in the presence of mercaptoethanol and ferrous ion, requires about 15 min at 37° and 45 min at 25° to reach completion under specific conditions. At temperatures below about 15°, full activation is not achieved, but a stable activity level is reached that varies linearly with temperature. At 0°, this level is about 50% of maximal activity when Component II is limiting and about 80% when Component I is limiting. The effect of temperature on the activity level is irreversible in the sense that raising the temperature increases activity whereas lowering the temperature has no effect. The pH of the activation solution also markedly affects the extent of active complex formation; at 37°, the final activity level increases sharply between pH 6.5 and 7.5, and approaches a maximal value at pH 8.0 and above. These and other results are interpreted to indicate the existence of two conformational states or more of Component II and several types of complexes of the two components. The stability of the conformational states and the complexes is postulated to vary with temperature and pH of the activation solution.
Transfer of genes into hematopoietic cells using recombinant DNA viruses. (1985)

The ability of recombinant DNA viruses to transfer genes into hematopoietic cells has been explored. A recombinant simian virus 40 (SV40) in which the early region had been replaced with the chloramphenicol acetyltransferase (CAT) gene driven by the promoter from Rous sarcoma virus (RSV), was constructed. This virus transferred the CAT gene more efficiently into mouse and human bone marrow cells and into the K562, MEL, and WEHI hematopoietic tissue culture cell lines, than the classical calcium phosphate DNA transfer procedure, as shown by assay for CAT activity 48 hr after infection. Recombinant SV40 virions were also shown to be capable of stably transforming Chinese hamster ovary cells by use of an early region recombinant containing the methotrexate-resistant dihydrofolate reductase (DHFR) gene driven by the RSV promoter. The entire DHFR transcriptional unit could be detected in the genome of transformed cells that were also shown to be resistant to methotrexate. A recombinant adenovirus stock containing the neomycin-resistance gene driven by the SV40 early promoter was used to infect the K562 and MEL hematopoietic cell lines to resistance to the antibiotic G418. Transformation frequency was 10- to 100-fold higher than that obtained with calcium phosphate-precipitated DNA. Most or all of the recombinant adenovirus genome was integrated as 1-3 copies in the transformed cells. These studies show the feasibility of using DNA viruses for introduction of new genetic material into hematopoietic cells.
Mesenchymal progenitor cells in human umbilical cord blood (2000)

Haemopoiesis is sustained by two main cellular components, the haematopoietic cells (HSCs) and the mesenchymal progenitor cells (MPCs). MPCs are multipotent and are the precursors for marrow stroma, bone, cartilage, muscle and connective tissues. Although the presence of HSCs in umbilical cord blood (UCB) is well known, that of MPCs has been not fully evaluated. In this study, we examined the ability of UCB harvests to generate in culture cells with characteristics of MPCs. Results showed that UCB-derived mononuclear cells, when set in culture, gave rise to adherent cells, which exhibited either an osteoclast- or a mesenchymal-like phenotype. Cells with the osteoclast phenotype were multinucleated, expressed TRAP activity and antigens CD45 and CD51/CD61. In turn, cells with the mesenchymal phenotype displayed a fibroblast-like morphology and expressed several MPC-related antigens (SH2, SH3, SH4, ASMA, MAB 1470, CD13, CD29 and CD49e). Our results suggest that preterm, as compared with term, cord blood is richer in mesenchymal progenitors, similar to haematopoietic progenitors.
Kupffer Cells May Autoregulate Interleukin 1 Production by Producing Interleukin 1 Inhibitor and Prostaglandin E2 (1988)

Rat Kupffer cells stimulated with bacterial lipopolysaccharide (LPS) produced high levels of interleukin 1 (IL-1), as determined by thymocyte proliferation assay. Indomethacin revealed a dose-dependent augmentation in IL-1 production, in parallel with a dose-dependent reduction in prostaglandin E2 production by Kupffer cells. The addition of exogenous prostaglandin E2, dibutyryl cAMP, or isoproterenol led to a dose-dependent suppression of IL-1 production. The supernatant from LPS-stimulated Kupffer cells also contained factors that inhibited IL-1-induced thymocyte proliferation. Upon gel filtration, two inhibitory peaks, at apparent MW of 27,000 and 6000, were obtained. The latter but not the former fraction also affected interleukin 2 (IL-2)-induced thymocyte proliferation. Increasing amounts of IL-1 overcame the inhibitory activity derived from the 27,000 MW fractions. These results suggest to us that prostaglandin E2 and IL-1 inhibitor released by Kupffer cells may be involved in negative self-control in regulating IL-1 production and its action.
Tau Paired Helical Filaments from Alzheimer's Disease Brain and Assembled in Vitro Are Based on β-Structure in the Core Domain (2004)

Tau protein, a neuronal microtubule-associated protein, forms insoluble fibers ("paired helical filaments") in Alzheimer's disease and other tauopathies. Conflicting views on the structure of the fibers have been proposed recently, ranging from mainly alpha-helical structure to mainly beta-sheet, or a mixture of mostly random coil and beta-sheet. We have addressed this issue by studying tau fibers immunopurified from Alzheimer brain tissue by a conformation-specific antibody and comparing them with fibers reassembled from recombinant tau or tau constructs in vitro, using a combination of electron microscopy and spectroscopic methods. Brain-derived fibers and reassembled fibers both exhibit a typical twisted appearance when examined by electron microscopy. The soluble tau protein is a natively unfolded protein dominated by random coil structure, whereas Alzheimer PHFs and reassembled fibers show a shift toward an increase in the level of beta-structure. The results support a model in which the repeat domain of tau (which lies within the core of PHFs) adopts an increasing level of beta-structure during aggregation, whereas the N- and C-terminal domains projecting away from the PHF core are mostly random coil.
Preparation and mechanical properties of polypropylene‐clay hybrids using a maleic anhydride‐modified polypropylene oligomer (1998)

Polypropylene-clay hybrids (PPCH) were prepared using a maleic anhydride-modified PP oligomer (PP-MA) as a compatibilizer. PP was melt-blended with organophilic clay which was intercalated with PP-MA. In these PPCHs, the particles of silicate layers were dispersed at the nanometer level. The particles became smaller and were dispersed more uniformly, as the ratio of PP-MA to the clay was increased. The dynamic storage moduli of the PPCHs were higher than that of PP up to 130°C. For example, the modulus of the PPCH with 5 wt % clay and 22 wt % PP-MA was 1.8 times higher compared to that of PP at 80°C. As the dispersibility of the clays was improved, the reinforcement effect of the clays increased. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 67: 87–92, 1998
Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans (2009)

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated that these variants significantly decreased endothelial lipase activity. In addition, a meta-analysis across 5 cohorts demonstrated that the low-frequency Asn396Ser variant is significantly associated with increased HDL-C, while the common Thr111Ile variant is not. Functional analysis confirmed that the Asn396Ser variant has significantly decreased lipase activity both in vitro and in vivo, while the Thr111Ile variant has normal lipase activity. Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C.
Anion Binding within the Cavity of π-Metalated Calixarenes (1997)

The synthesis of a range of bi- and tetrametalated macrocyclic complexes based upon calix[4]arene, p-tert-butylcalix[4]arene and related tetraalkoxy derivatives, of type [{M(L)}2(calixarene-nH)]X4-n and [{M(L)}4(calixarene-2H)]X6 (M = Rh, Ir, Ru; L = Cp*, p-MeC6H4CHMe2; n = 0, 1, 2; X = BF4, CF3SO3, HSO4, I, ReO4, H2PO4, etc., not all combinations) is reported. A related trimetallic calix[5]arene derivative [{Ir(η5-C5Me5)}3(p-tert-butylcalix[5]arene-H)][BF4]5 has also been synthesized. In all cases, the presence of the transition metal centers results in a significant enhancement in the acidity of the hydroxyl functionalities at the calixarene lower rim. For the tri- and tetrametalated derivatives, the host−guest behavior of the calixarene is drastically altered such that anionic guest species are included within the molecular cavity. The function of the new tetrametallic hosts [{Ru(η6-p-MeC6H4CHMe2)}4(η6:η6:η6:η6-C28H22O4)]6+ (15) and [{Ir(η5-C5Me5)}4(η6:η6:η6:η6-C28H22O4)]6+ (16) as anion receptors has been confirmed by X-ray crystal structure investigations upon BF4- (15a, 16a), HSO4- (16c), SO42- (15c), and I- (15d) derivatives, which clearly demonstrate a cooperative effect arising from the arrangement of four metal centers about a common, rigid binding pocket, resulting in anion−host contacts as low as 2.85 Å (BF4···Ccalix). The anion binding properties of host 15 in aqueous solution have also been investigated by 1H NMR titration, giving binding constants in the range 100−550 M-1 for nitrate and halide anions, with the binding constant decreasing in the order Cl- > Br- > I-. Significantly increased binding is observed in nonaqueous media. This novel form of anion complexation contrasts to the formation of weakly bound, van der Waals inclusion complexes commonly observed in calixarene chemistry.
CLINICAL RELEVANCE OF FATIGUE AS A RESIDUAL SYMPTOM IN MAJOR DEPRESSIVE DISORDER (2013)

Residual symptoms of major depressive disorder (MDD) following treatment are increasingly recognized as having a negative impact on the patient because of their association with lack of remission, poorer psychosocial functioning, and a more chronic course of depression. Although the effects of specific residual symptoms have not been as systematically studied, several symptoms, including fatigue, sleep disturbance, anxiety, and concentration difficulties, commonly occur as part of the residual state in MDD. In particular, the relatively high prevalence of residual fatigue suggests that this symptom is not being adequately addressed by standard antidepressant therapies. A review of the clinical relevance of residual fatigue was undertaken, using the published literature with respect to its assessment, neurobiology, and treatment implications. The findings of this review suggest that fatigue is highly prevalent as a residual symptom; its response to treatment is relatively poor or delayed; and the presence of residual fatigue is highly predictive of inability to achieve remission with treatment as well as impaired psychosocial functioning. Recognition of the significant consequences of residual fatigue should reinforce the need for further therapeutic interventions to help reduce the impact of this symptom of MDD.