gebhart/patrepeval huggingface dataset:
Defective Reticuloendothelial System Fc-Receptor Function in Systemic Lupus Erythematosus (1979)

To determine whether reticuloendothelial-system immunospecific Fc-receptor function is abnormal in patients with systemic lupus erythematosus, we studied the clearance of IgG-sensitized 51Cr-labeled erythrocytes by these splenic macrophage membrane receptors in 15 untreated patients. Fc-specific clearance rates were strikingly abnormal in 13 of 15 patients (half-times ranging from 80 to 2256 minutes, P less than 0.001 as compared to controls). Abnormal clearances correlated with immune-complex levels (as measured by the C1q-binding assay) and with disease activity. C1q-binding activity and anti-DNA titers also correlated with disease activity. The correlations of C3, C4, CH50 and factor B with abnormal clearance and disease activity were weaker or nonexistent. The significant correlations among clearance, disease activity and C1q-binding activity suggest that the defect in Fc-receptor function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue deposition and damage.
Oxidation of DNA Hairpins by Oxoruthenium(IV):  Effects of Sterics and Secondary Structure (1996)

The effects of steric hindrance on the oxidation of DNA by polypyridyl oxoruthenium(IV) complexes have been investigated. The complexes oxidize DNA by activation either of the 1' ribose C-H bond or by oxo transfer to the guanine nucleobase. A method is presented for determining the relative rates of activation of individual sites from the dependence of the extent of cleavage on the oxidant concentration. This analysis shows that hybridization of the labeled strand to its complement attenuates the rate of oxidation of guanine more effectively than the rate of sugar oxidation. Accordingly, higher ratios of guanine/sugar oxidation are observed in single strands. Among the individual guanine residues, however, the relative reactivities are not altered by hybridization; a similar result is obtained for sugar oxidation. This result implies that sequence-dependent chemical reactivity is partly responsible for the different extents of cleavage observed within the sequence. The ability of hybridization to protect guanine from oxidation is also apparent in hairpin studies, where the stem guanines are much less reactive than the loop guanines, and altered sugar conformations in the loop lead to modulated reactivity. Finally, a set of sterically differentiated complexes shows greater steric effects for oxidation of guanine compared to oxidation of sugar, as expected from the relative rates of the single strand and duplexes.
Sources of linearity degradation in LINC transmitters for hybrid and outphasing combiners (2004)

The LINC (linear amplification using non linear components) is a potential candidate as a transmitter system for providing both high linearity and high efficiency. In this paper, we review all the origins of linearity degradation in LINC transmitters for both matched and outphasing combiners and group them into three main sources. We first show that the linearity degradation in the LINC transmitter with an outphasing combiner is inherent to the combiner structure. We further show the impact of phase and amplitude imbalance in the two LINC branches on the transmitter linearity. Finally the filtering effect on the linearity in the LINC transmitter is studied. Extensive simulations using the advanced design system (ADS) software with CDMA signals (7 dB of peak-to-average) have been carried out and results are presented to validate the approach used in each case studied.
Securing frame communication in browsers (2009)

Many Web sites embed third-party content in frames, relying on the browser's security policy to protect against malicious content. However, frames provide insufficient isolation in browsers that let framed content navigate other frames. We evaluate existing frame navigation policies and advocate a stricter policy, which we deploy in the open-source browsers. In addition to preventing undesirable interactions, the browser's strict isolation policy also affects communication between cooperating frames. We therefore analyze two techniques for interframe communication between isolated frames. The first method, fragment identifier messaging, initially provides confidentiality without authentication, which we repair using concepts from a well-known network protocol. The second method, &lt;code&gt;postMessage&lt;/code&gt;, initially provides authentication, but we discover an attack that breaches confidentiality. We propose improvements in the &lt;code&gt;postMessage&lt;/code&gt; API to provide confidentiality; our proposal has been standardized and adopted in browser implementations.
Rhodopsin self-associates in asolectin liposomes (2006)

We show that the photoreceptor rhodopsin (Rh) can exist in the membrane as a dimer or multimer using luminescence resonance energy transfer and FRET methods. Our approach looked for interactions between Rh molecules reconstituted into asolectin liposomes. The low receptor density used in the measurements ensured minimal receptor crowding and artifactual association. The fluorescently labeled Rh molecules were fully functional, as measured by their ability to activate the G protein transducin. The luminescence resonance energy transfer measurements revealed a distance of 47-50 Angstroms between Rh molecules. The measured efficiency of FRET between receptors was close to the theoretical maximum possible, indicating nearly quantitative Rh-Rh association. Together, these results provide compelling evidence that Rh spontaneously self-associates in membranes.
Permeability of blood-brain barrier to various sized molecules (1985)

We studied disruption of the blood-brain barrier (BBB) by acute hypertension and a hyperosmolar solution. The goals were to determine whether 1) disruption of the BBB occurs primarily in arteries, capillaries, or veins, and 2) transport of different-sized molecules is homogeneous or size dependent. Sprague-Dawley rats were studied using intravital fluorescent microscopy of pial vessels and fluorescein-labeled dextrans (FITC-dextran, mol wt = 70,000, 20,000, and 4,000 daltons). The site of disruption was determined by the appearance of microvascular leaky sites. Transport of different-sized molecules was calculated from clearance of FITC-dextran. During gradual hypertension and osmotic disruption, all leaky sites were venular. Rapid hypertension produced venular leaky sites and, in some experiments, diffuse arteriolar extravasation of FITC-dextran. Clearance of different-sized molecules was homogeneous during acute hypertension. In contrast, clearance of molecules during osmotic disruption was size dependent. The findings suggest that 1) venules and veins are the primary sites of disruption following acute hypertension and a hyperosmolar solution; 2) transport of different-sized molecules is homogeneous following acute hypertension, which suggests a vesicular mechanism; and 3) transport following hyperosmolar disruption is size dependent, which suggests that hyperosmolar disruption may involve formation of pores as well as vesicular transport.
Reduction of heterocycles with nickel-aluminum alloy (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of heterocycles with nickel-aluminum alloyGeorge LunnCite this: J. Org. Chem. 1987, 52, 6, 1043–1046Publication Date (Print):March 1, 1987Publication History Published online1 May 2002Published inissue 1 March 1987https://pubs.acs.org/doi/10.1021/jo00382a013https://doi.org/10.1021/jo00382a013research-articleACS PublicationsRequest reuse permissionsArticle Views1212Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Chinese free antiretroviral treatment program: challenges and responses (2007)

To respond to the HIV/AIDS epidemic in China, the National Center for AIDS/STD Control and Prevention established the Division of Treatment and Care in late 2001. The pilot for the National Free ART Program began in Henan Province in 2002, and the program fully began in 2003. Treatment efforts initially focused on patients infected through illicit blood and plasma donation in the mid-1990s and subsequently expanded to include HIV-infected injection drug users, commercial sex workers, pregnant women, and children. The National Free ART Database was established in late 2004, and includes data on current patients and those treated before 2004. Over 31 000 adult and pediatric patients have been treated thus far. Challenges for the program include integration of drug treatment services with ART, an under-resourced health care system, co-infections, stigma, discrimination, drug resistance, and procurement of second-line ART. The merging of national treatment and care, epidemiologic, and drug resistance databases will be critical for a better understanding of the epidemic, for earlier identification of patients requiring ART, and for improved patient follow-up. The Free ART Program has made considerable progress in providing the necessary care and treatment for HIV-infected people in China and has strong government support for continued improvement and expansion.
X-ray Crystallography Reveals a Reduced Substrate Complex of UDP-Galactopyranose Mutase Poised for Covalent Catalysis by Flavin, (2009)

The flavoenzyme uridine 5'-diphosphate galactopyranose mutase (UGM or Glf) catalyzes the interconversion of UDP-galactopyranose and UDP-galactofuranose. The latter is a key building block for cell wall construction in numerous pathogens, including Mycobacterium tuberculosis. Mechanistic studies of UGM suggested a novel role for the flavin, and we previously provided evidence that the catalytic mechanism proceeds through a covalent flavin-galactose iminium. Here, we describe 2.3 and 2.5 A resolution X-ray crystal structures of the substrate-bound enzyme in oxidized and reduced forms, respectively. In the latter, C1 of the substrate is 3.6 A from the nucleophilic flavin N5 position. This orientation is consistent with covalent catalysis by flavin.
Discovery and characterization of small molecule Rac1 inhibitors (2017)

Aberrant activation of Rho GTPase Rac1 has been observed in various tumor types, including pancreatic cancer. Rac1 activates multiple signaling pathways that lead to uncontrolled proliferation, invasion and metastasis. Thus, inhibition of Rac1 activity is a viable therapeutic strategy for proliferative disorders such as cancer. Here we identified small molecule inhibitors that target the nucleotide-binding site of Rac1 through in silico screening. Follow up in vitro studies demonstrated that two compounds blocked active Rac1 from binding to its effector PAK1. Fluorescence polarization studies indicate that these compounds target the nucleotide-binding site of Rac1. In cells, both compounds blocked Rac1 binding to its effector PAK1 following EGF-induced Rac1 activation in a dose-dependent manner, while showing no inhibition of the closely related Cdc42 and RhoA activity. Furthermore, functional studies indicate that both compounds reduced cell proliferation and migration in a dose-dependent manner in multiple pancreatic cancer cell lines. Additionally, the two compounds suppressed the clonogenic survival of pancreatic cancer cells, while they had no effect on the survival of normal pancreatic ductal cells. These compounds do not share the core structure of the known Rac1 inhibitors and could serve as additional lead compounds to target pancreatic cancers with high Rac1 activity.
New pharmacological strategies to restore hearing and treat tinnitus (2004)

Recent advances in molecular pharmacology of the cochlea have lead to a much better understanding of the physiology, and especially the pathophysiology, of the sensorineural structures of the organ of Corti. Knowledge of the intimate molecular mechanisms of cellular dysfunction is of considerable use in the development of new therapeutic strategies. Herein, we summarize the mechanisms of sensory hair cell death after various injuries. Based on these molecular mechanisms, we propose novel therapeutic strategies to restore hearing. In addition to permanent hearing loss, exposure to noise or ototoxic drugs also induces tinnitus. We thus review recent findings obtained from a behavioral model of tinnitus in rats. In addition to providing evidence for the site and mechanism of generation of tinnitus induced by salicylate, these results support the idea that targeting cochlear N-methyl-D-aspartate receptors may represent a promising therapeutic strategy for treating tinnitus.
Bioartificial matrices for therapeutic vascularization (2009)

Therapeutic vascularization remains a significant challenge in regenerative medicine applications. Whether the goal is to induce vascular growth in ischemic tissue or scale up tissue-engineered constructs, the ability to induce the growth of patent, stable vasculature is a critical obstacle. We engineered polyethylene glycol-based bioartificial hydrogel matrices presenting protease-degradable sites, cell-adhesion motifs, and growth factors to induce the growth of vasculature in vivo. Compared to injection of soluble VEGF, these matrices delivered sustained in vivo levels of VEGF over 2 weeks as the matrix degraded. When implanted subcutaneously in rats, degradable constructs containing VEGF and arginine-glycine-aspartic acid tripeptide induced a significant number of vessels to grow into the implant at 2 weeks with increasing vessel density at 4 weeks. The mechanism of enhanced vascularization is likely cell-demanded release of VEGF, as the hydrogels may degrade substantially within 2 weeks. In a mouse model of hind-limb ischemia, delivery of these matrices resulted in significantly increased rate of reperfusion. These results support the application of engineered bioartificial matrices to promote vascularization for directed regenerative therapies.
Nonionic Triblock and Star Diblock Copolymer and Oligomeric Surfactant Syntheses of Highly Ordered, Hydrothermally Stable, Mesoporous Silica Structures (1998)

A family of highly ordered mesoporous (20−300 Å) silica structures have been synthesized by the use of commercially available nonionic alkyl poly(ethylene oxide) (PEO) oligomeric surfactants and poly(alkylene oxide) block copolymers in acid media. Periodic arrangements of mescoscopically ordered pores with cubic Im3̄m, cubic Pm3̄m (or others), 3-d hexagonal (P63/mmc), 2-d hexagonal (p6mm), and lamellar (Lα) symmetries have been prepared. Under acidic conditions at room temperature, the nonionic oligomeric surfactants frequently form cubic or 3-d hexagonal mesoporous silica structures, while the nonionic triblock copolymers tend to form hexagonal (p6mm) mesoporous silica structures. A cubic mesoporous silica structure (SBA-11) with Pm3̄m diffraction symmetry has been synthesized in the presence of C16H33(OCH2CH2)10OH (C16EO10) surfactant species, while a 3-d hexagonal (P63/mmc) mesoporous silica structure (SBA-12) results when C18EO10 is used. Surfactants with short EO segments tend to form lamellar mesostructured silica at room temperature. Hexagonal mesoporous silica structures with d(100) spacings of 64−77 Å can be synthesized at 100 °C by using oligomeric nonionic surfactants. Highly ordered hexagonal mesoporous silica structures (SBA-15) with unusually large d(100) spacings of 104−320 Å have been synthesized in the presence of triblock poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide) (PEO−PPO−PEO) copolymers. SBA-15 mesoporous structures have been prepared with BET surface areas of 690−1040 m2/g, pore sizes of 46−300 Å, silica wall thicknesses of 31−64 Å, and pore volumes as large as 2.5 cm3/g. A novel cubic (Im3̄m) cage-structured mesoporous silica structure (SBA-16) with a large cell parameter (a = 176 Å) has been synthesized using triblock copolymers with large PEO segments. The EO/PO ratio of the copolymers can be used to control the formation of the silica mesophase: lowering this ratio of the triblock copolymer moieties promotes the formation of lamellar mesostructured silica, while higher ratios favor cubic mesostructured silica. Cubic mesoporous structures are also obtained when star diblock copolymers are used as structure-directing agents. The calcined ordered mesoporous silicas reported in this paper are thermally stable in boiling water for at least 48 h. The assembly of the inorganic and organic periodic composite materials appears to take place by a hydrogen bonding (S0 H+)(X-I+) pathway. The assembly rate r increases with increasing concentration of [H+] and [Cl-], according to the kinetic expression r = k[H+]0.31[Cl-]0.31.
Characterization of the Structural Requirements for a Carbohydrate Based Anticoagulant with a Reduced Risk of Inducing the Immunological Type of Heparin-associated Thrombocytopenia (1995)

HAT is the most frequent drug induced immune-thrombocytopenia. We recently identified multimolecular PF4/heparin complexes as the major antigen. In order to evaluate the structural requirements for formation of the antigenic complex, we chemically synthesized 13 glucan sulfates and used 5 heparin fractions (2.4-4.8 kD) and a synthesized pentasaccharide, representing the antithrombin III binding sequence of heparin, for further characterize the HAT antigen. In the presence of glucan sulfates and heparin, HAT antibodies caused platelet activation typically at low but not at high concentrations, as measured by 14C-5HT release. The concentration range giving the activation pattern depended on the degree of sulfation (DS) and molecular weight (MW) of the glucan sulfates but not on the type of glycosidic linkage of a polysaccharide. With linear glucan sulfates with a chain length of 35 monosaccharides, the critical DS to form the HAT antigen ranged between 0.60 and 1.20. Glycosidic branched glucan sulfates were able to form the HAT antigen at a lower DS and a lower MW than linear glucan sulfates. Platelet activation by HAT-antibodies in the presence of linear curdlan sulfate fractions was dependent on their MW. At a low concentration (0.01 microM) medium-size fractions (60 kD) caused platelet activation but neither small (12 kD) nor large fractions ( > 150 kD) did. At higher concentrations (2 microM) the opposite reaction pattern was observed. In the case of heparin, the optimal chain length for forming the HAT antigen is a hexadecasaccharide (4.8 kD). Antigen generation decreased with larger and smaller fractions.(ABSTRACT TRUNCATED AT 250 WORDS)
Synthese von Pyrrolen, Pyrazolinen und Pyrazolen über Bis‐en‐hydrazine (1971)

Abstract Spezielle cyclische und offenkettige Carbonylverbindungen liefern bei der Umsetzung mit N . N ′‐Dimethyl‐hydrazin über die entsprechenden Bis‐en‐hydrazine 3 als Zwischenstufen bei Säurekatalyse oder Thermolyse N ‐Methyl‐pyrrole. Desgleichen führt die Umsetzung mit Monomethylhydrazin selektiv zu N ‐Methyl‐pyrrolen. Infolge einer Konkurrenzreaktion werden gegebenenfalls Pyrazoline gebildet. Das Pyrazolin‐System kann dabei, falls β‐Eliminierung möglich ist, in das Pyrazol‐ bzw. Pyrazolium‐System umgewandelt werden. — Die Mechanismen der Reaktionen werden diskutiert.
The synthesis of cyclic peptides (2001)

Covering: 1997 to mid-2000.
Decreased Plasma Brain‐Derived Neurotrophic Factor Levels in Patients With Alcohol Dependence (2007)

Changes in the levels of BDNF might play a role in the pathophysiology and inheritance of alcohol dependence.
Endocytosis of heparin-binding protein (CAP37) is essential for the enhancement of lipopolysaccharide-induced TNF-alpha production in human monocytes. (1999)

Heparin-binding protein (HBP), also known as CAP37, is a proteolytically inactive serine protease homologue that is released from activated granulocytes. However, HBP is not a biologically inactive molecule but rather a multifunctional protein with properties that include the enhancement of LPS-induced TNF-alpha production from monocytes. We have previously demonstrated that HBP is internalized in monocytes. In the current study, we hypothesize that HBP is internalized in monocytes via endocytosis, and this internalization is an important mechanism by which HBP enhances LPS-induced TNF-alpha release. Using whole blood from healthy donors and flow cytometry, we found that colchicine (0.1-10 mM), cytochalasin D (1000 microM), NH4Cl (10-50 mM), and bafilomycin A1 (0.1-3 microM) significantly reduced the affinity of FITC-HBP for CD14-positive monocytes. Using isolated human monocytes and ELISA, we found that colchicine (0.1 mM), cytochalasin D (30 and 300 microM), NH4Cl (30 mM), and bafilomycin A1 (1 microM) significantly reduced the effect of HBP (10 microg/ml) to enhance LPS (10 ng/ml)-induced TNF-alpha release after 24 h. These findings demonstrate that internalization of HBP in monocytes is essential for the enhancement of LPS-induced TNF-alpha release. Transport of HBP to an activating compartment depends on intact F-actin polymerization and endosomal acidification, an important mechanism for endosomal protein sorting and trafficking.
Cerebral Blood Flow during Low-flow Hypeithermic Cardiopulmonary Bypass in Baboons (1994)

Although systemic flow is reduced to 20% of full-flow during low-flow CPB, CBF reduced by half is disproportionately preserved relative to systemic flow. Furthermore, there is no time-dependent change in CBF under these low-flow conditions.
Life and death by death receptors (2009)

Death receptors are members of the tumor necrosis factor receptor superfamily characterized by a cytoplasmic region known as the "death domain" that enables the receptors to initiate cytotoxic signals when engaged by cognate ligands. Binding to the ligand results in receptor aggregation and recruitment of adaptor proteins, which, in turn, initiates a proteolytic cascade by recruiting and activating initiator caspases 8 and 10. Death receptors were once thought to primarily induce cytotoxic signaling cascades. However, recent data indicate that they initiate multiple signaling pathways, unveiling a number of nonapoptosis-related functions, including regulation of cell proliferation and differentiation, chemokine production, inflammatory responses, and tumor-promoting activities. These noncytotoxic cascades are not simply a manifestation of inhibiting proapoptotic pathways but are intrinsically regulated by adaptor protein and receptor internalization processes. Insights into these various death receptor signaling pathways provide new therapeutic strategies targeting these receptors in pathophysiological processes.
In vivo axonal transport deficits in a mouse model of fronto-temporal dementia (2014)

In our study, we identified the presence of age-dependent axonal transport deficits beginning at 3 months of age in rTg4510 mice. We correlated these deficits at 3 months to the presence of hyperphosphorylated tau in the brain and the presence within the olfactory epithelium. We observed tau pathology not only in the soma of these neurons but also within the axons and processes of these neurons. Our characterization of axonal transport in this tauopathy model provides a functional time point that can be used for future therapeutic interventions.