gebhart/patrepeval huggingface dataset:
A Little VEGF Goes a Long Way (1996)

Nevertheless, the simplicity of using injections of naked plasmid DNA into skeletal muscle tissue as an effective means to deliver a potent, secreted angiogenesis factor into ischemic peripheral vascular beds is both an exciting and encouraging finding. It is estimated that 150,000 patients per year require lower-limb amputations for ischemic peripheral vascular disease in the United States. The impressive progress being made toward the use of VEGF gene therapy for effective therapeutic angiogenesis in ischemic peripheral vascular disease is truly welcome news for clinicians faced with the task of providing care for those patients suffering from lower-limb vascular insufficiency.
Rational re‐design of the substrate binding site of flavocytochrome P450 BM3 (2000)

Bacillus megaterium P450 BM3 is a fatty acid hydroxylase with selectivity for long chain substrates (C(12)-C(20)). Binding or activity with substrates of chain length <C(12) has not been reported. Rational mutagenesis was used to re-design the enzyme to encourage binding of short chain fatty acids (C(4)-C(10)). We show that wild-type P450 BM3 has activity and weak affinity for substrates as short as butyrate (C(4)). However, turnover/binding of short chain substrates is dramatically increased by introducing a novel substrate carboxylate binding site close to the heme. Mutant L181K shows catalytic efficiency (k(cat)/K(M)) increased >13-fold with butyrate, while the L75T/L181K double mutant has k(cat)/K(M) increased >15-fold with hexanoate and binding (K(d)) improved >28-fold for butyrate. Removing the arginine 47/lysine 51 carboxylate binding motif at the mouth of the active site disfavours binding of all fatty acids, indicating its importance in the initial recognition of substrates.
Wavelength-tunable narrow-linewidth semiconductor fiber-ring laser (2000)

A passive sub-ring was inserted into a semiconductor fiber-ring laser as the Vernier configuration to enable stable lasing spectrum. Wavelength tuning over 20 nm and fine tuning of less than 0.0001 nm were obtained by rotating the polarization controller and adjusting the voltage on the phase modulator, respectively. A narrow linewidth of less than 10 kHz and a sidemode suppression ratio of higher than 35 dB were demonstrated with single longitudinal-mode operation.
Transport of Antisense Across the Blood–Brain Barrier (2004)

Antisense-mediated therapy holds great promise for the treatment of central nervous system (CNS) diseases in which neurodegeneration is linked to over-production of endogenous protein. Administration of antisense therapy could be difficult, however, because peripherally administered antisense would have to cross the blood-brain barrier (BBB) in effective quantities. Several studies have investigated various modifications that can be introduced into antisense molecules to improve their ability to cross the BBB. Recently, two types of unmodified antisense analogs have been shown to effectively cross the BBB and affect CNS function. One of the analogs, a phosphorothioate oligodeoxy-nucleotide (P-ODN) directed against the amyloid β protein, was peripherally administered via iv injection. This analog crosses the BBB via a saturable transport mechanism termed oligonucleotide transport system-1 (OTS-1) (1). Another unmodified P-ODN was also shown to cross the BBB. This P-ODN was directed at methionine enkephalin (Met-Enk), an opiate peptide associated with alcoholism (unpublished results). The second type of unmodified analog shown to cross the BBB is a peptide nucleic acid (PNA) that was directed against the neurotensin receptor NTS-1 in rats and was administered via ip injection (2). Antisense molecules that can cross the BBB would be potential therapeutic agents and useful tools in the elucidation of CNS pathophysiology.
Double patterning of contact array with carbon polymer (2008)

The spacer patterning technique (SPT) is well known as one of the methods expanding the resolution limit and mainly useful for patterning line & space of memory device. Although contact array could be achieved by both spacer patterning technique and double exposure & etch technique (DEET) <sup>1</sup>, the former would be preferable to the latter by the issues of overlay burden and resolution limit of isolated contact. The process procedure for contact array is similar to that for line & space which involves the 1st mask exposure, etch, carbon polymer deposition, the 2nd mask exposure and etch step sequentially. With SPT, it would be possible to realize contact array of 30nm half pitch including 30nm isolated contact as well as line & space of 30nm half pitch.
Newborn screening in the Asia Pacific region (2007)

The success of blood spot newborn screening in the USA led to early screening efforts in parts of the Asia Pacific Region in the mid-1960s. While there were early screening leaders in the region, many of the countries with depressed and developing economies are only now beginning organized screening efforts. Four periods of screening growth in the Asia Pacific region were identified. Beginning in the 1960s, blood spot screening began in New Zealand and Australia, followed by Japan and a cord blood screening programme for G6PD deficiency in Singapore. In the 1980s, established programmes added congenital hypothyroidism and new programmes developed in Taiwan, Hong Kong, China (Shanghai), India and Malaysia. Programmes developing in the 1990s built on the experience of others developing more rapidly in Korea, Thailand and the Philippines. In the 2000s, with limited funding support from the International Atomic Energy Agency, there has been screening programme development around detection of congenital hypothyroidism in Indonesia, Mongolia, Sri Lanka, Myanmar and Pakistan. Palau has recently contracted with the Philippine newborn screening programme. There is little information available on newborn screening activities in Nepal, Cambodia, Laos and the other Pacific Island nations, with no organized screening efforts apparent. Since approximately half of the births in the world occur in the Asia Pacific Region, it is important to continue the ongoing implementation and expansion efforts so that these children can attain the same health status as children in more developed parts of the world and their full potential can be realized.
The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma (1990)

Gastric cancer remains a disease with a very poor prognosis, and there is no safe and effective form of therapy for advanced disease. Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo, and that blockade of gastrin receptors can prolong survival in xenografted nude mice. We have thus performed a randomized, controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma. Proglumide had no overall effect on survival (Mantel-Cox statistic = 0.5, P = 0.48). The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group. No significant difference was seen with proglumide, which has a relatively low affinity with the gastrin receptor and also has partial agonist activity. Drugs that are far more specific and potent gastrin receptor antagonists are becoming available, which may have a greater effect on survival, and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy.
Metabolism and bioavailability oftrans-resveratrol (2005)

Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a polyphenolic compound accounting to the stilbene class. Most stilbenes in plants act as antifungal phytoalexins, compounds that are usually synthesized only in response to infection or injury. Resveratrol has been detected in trees, in a few flowering plants, in peanuts, and in grapevines. The major dietary sources of resveratrol include grapes, wine, peanuts, and peanut products. Numerous in vitro studies describe different biological effects of resveratrol. The major impacts are the antioxidative, anti-inflammatory, and estrogenic effects as well as anticancer and chemopreventive activities. In order to reveal information on absorption, metabolism, and the consequent bioavailability of resveratrol, different research approaches were performed, including in vitro, ex vivo, and in vivo models, all of which are considered in this review. Summarizing the data, resveratrol is absorbed and metabolized. Around 75% of this polyphenol are excreted via feces and urine. The oral bioavailability of resveratrol is almost zero due to rapid and extensive metabolism and the consequent formation of various metabolites as resveratrol glucuronides and resveratrol sulfates. The potential biologic activity of resveratrol conjugates should be considered in future investigations.
Use of diagnostic neutral losses for structural information on unknown aromatic metabolites: an experimental and theoretical study (2008)

This work presents the use of neutral losses (NL) for the identification of compounds related to the metabolism of tyrosine. The mass spectra of all the studied compounds, recorded at several collision energies, are compared. The fragmentation mechanism of protonated molecules, MH(+), is explained by combining collision-induced dissociation (CID) mass spectra and density functional theory (DFT) calculations. The results show that the first fragmentation is the elimination from MH(+) of a neutral molecule including a functional group of the linear chain. Three primary neutral losses are observed: 17 u (NH(3)), 18 u (H(2)O) and 46 u (H(2)O+CO) characterizing amino, hydroxyl and carboxylic functions on the linear chain. The presence and abundance of ions corresponding to these losses are dependent on (i) the position of the functional group on the linear chain, (ii) the initial localisation of the protonating hydrogen, and (iii) the substitution of the aromatic ring. For compounds including a functional group on the benzylic carbon atom, the investigation of the other functions requires the knowledge of secondary fragmentations. Among these secondary fragmentations we have retained the loss of NH(3) from [MH-18u](+) and the loss of ketene from [MH-17u](+). Experimentally these fragmentations are detected using losses of 35 u and 59/73 u. In other words, NL35 identifies hydroxy and amino compounds and NL 46 and/or NL59/73 identify carboxylic acids. The search for characteristic neutral losses is used for the analysis of compounds in a mixture and the analysis of biological fluid. We show that selective search of several neutral losses allows also the unambiguous differentiation of isomers and gives the opportunity to identify compounds in biological fluids.
Synthesis and Structural Properties of Novel Tricyclic 15-membered Azalides (2009)

Starting from 3-decladinosyl-9a,11-cyclic carbamates of 15 membered azalide, strained tricyclic aglycone derivatives were prepared.The bridging 5-membered hemiketal ring was obtained by intramolecular ketalization of intermediary 3-keto derivative, whereas 5-membered ether derivatives were obtained by intramolecular Williamson-type displacement.In case of 12-O-alkyl derivatives complete diastereoslective formation of ethers was observed, while unsubstituted compound gave diastereomeric mixture.NMR analysis was used to confirm the structures of new tricyclic azalide compounds.
Removal of cytokines and activated complement components in an experimental model of continuous plasma filtration coupled with sorbent adsorption (1998)

These studies suggest an efficient removal of cytokines in continuous plasmafiltration with sorbent adsorption. The binding of alpha2-macroglobulin, a carrier of cytokines in plasma, might be a additional mechanism in the removal of cytokines from plasma.
Palmitate Diet-induced Loss of Cardiac Caveolin-3: A Novel Mechanism for Lipid-induced Contractile Dysfunction (2013)

Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate), and MCT diet (21% medium-chain triglycerides, no palmitate). We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.
On the nature of antibody combining sites: Unusual structural features that may confer on these sites an enhanced capacity for binding ligands (1990)

A detailed analysis of the structural aspects of antibody-antigen interactions has been made possible by the availability of X-ray structures for three complexes of antilysozyme Fabs to lysozyme (reviewed by Davies et al.: J. Biol. Chem. 263:10541-10544, 1988.) Examination of the antigen-contacting residues in the three antilysozyme Fabs reveals the occurrence of a large number of aromatics, particularly tyrosines, and the absence of apolar, aliphatic residues. Calculation of the frequency of occurrence of the various amino acid types reveals that tyrosines are three times, and histidines and asparagines eight times, more likely to be found in the complementarity-determining regions than in the framework of the variable domains. Analysis of the solvent accessibility of the residues in Fvs (the modules containing variable domains of the light and heavy chains) of known three-dimensional structure indicates that tyrosines and tryptophans are more exposed when they occur in the complementarity-determining regions than when in the framework. Furthermore, many more of the asparagines in the complementarity-determining regions than in the framework are buried. These asparagines appear to have a structural role in that they hydrogen-bond through their side chains to other side chains and, even more so, to the protein backbone. The stabilizing effect of the asparagines, plus the rigidity of the framework, may serve to allow the greater exposure of the aromatic residues to solvent. In view of the greater potential contribution of aromatic side chains to the total binding energy, these results suggest that antibody combining sites have structural features that make them especially suited for interacting with ligands.
Chirality Transfer in Au-Catalyzed Cyclization Reactions of Monoallylic Diols: Selective Access to Specific Enantiomers Based on Olefin Geometry (2011)

The gold(I)-catalyzed cyclization of monoallylic diols to form tetrahydropyrans is shown to be highly stereoselective when chiral allylic alcohols are employed. Substrates that differ only in olefin geometry provide enantiomeric products from formal S(N)2' reactions in high yields with excellent chirality transfer. The allylic alcohol stereochemistry also efficiently controls the facial selectivity when the substrates include additional stereocenters.
Detection of Bordetella pertussis associated with the alveolar macrophages of children with human immunodeficiency virus infection (1991)

In humans, infection with Bordetella pertussis is considered to be localized to an epithelial surface. However, an intracellular state in cultured cells and in the macrophages of infected animals has been shown. By using indirect immunofluorescence with a monoclonal antibody, it was found that 3 of 20 bronchoalveolar lavage specimens from children with human immunodeficiency virus infection had B. pertussis associated with pulmonary alveolar macrophages. None of the cultures from the patients grew B. pertussis. The B. pertussis appeared to be intracellular.
Simultaneous Detection of 15 Human Cytokines in a Single Sample of Stimulated Peripheral Blood Mononuclear Cells (2003)

Cytokines secreted by cells of the immune system can alter the behavior and properties of immune or other cells. At a site of inflammation, sets of cytokines interact with immune cells, and their combined effect is often more important than the function of one isolated component. Conventional techniques, such as enzyme-linked immunosorbent assays, generally require large quantities of cells to characterize a complete cytokine profile of activated lymphocytes. The Bio-Plex system from Bio-Rad Laboratories combines the principle of a sandwich immunoassay with the Luminex fluorescent-bead-based technology. We developed a multiplex cytokine assay to detect different cytokines simultaneously in culture supernatant of human peripheral blood mononuclear cells stimulated with antigen and with mitogen. Fifteen human cytokines (interleukin 1alpha [IL-1alpha], IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-18, gamma interferon, and tumor necrosis factor alpha) were validated with a panel of healthy individuals, rheumatoid arthritis patients, and juvenile idiopathic arthritis patients. Comparing the multiplex assay with a regular enzyme-linked immunosorbent assay technique with this donor panel resulted in correlation coefficients for all cytokines ranging from 0.75 to 0.99. Intra-assay variance proved to be less then 10%, whereas interassay variability ranged between 10 and 22%. This multiplex system proved to be a powerful tool in the quantitation of cytokines. It will provide a more complete picture in differences between activated lymphocyte cytokine profiles from healthy individuals and those from patients with chronic inflammatory diseases.
La televisió americana i el dilema digital (Conferència extraordinària a Barcelona) (1999)

Conferncia extraordinria a Barcelona.Les Brown La televisi americana i el dilema digital (Conferncia extraordinria a Barcelona) Les BrownL'era digital de la televisi americana es va obrir oficialment fa pocs dies, l'1 de novembre, quan 42 emissores de televisi situades a diverses parts del pas van comenar a transmetre des dels nous canals terrestres.Feia molt poc que els nous televisors digitals es trobaven a les botigues, i a ms a uns preus altssims, de manera que el pblic que ha vist aquestes primeres transmissions -totes en televisi d'alta definici-segurament ha estat menys nombrs que les persones que omplen aquesta sala.Per es tracta d'una situaci com la de l'ou i la gallina.Ja l'hem vista altres vegades amb tecnologies noves, inclosa la mateixa televisi.D'aqu a un any la majoria d'emissores del pas estaran transmetent per les noves freqncies digitals i alhora amb el sistema analgic habitual.Segons les investigacions d'algunes de les principls empreses consultores, d'aqu a uns 20 anys, ms o menys el 90% de les cases dels Estats Units tindran televisor digital.Si s aix, la televisi digital s'haur endarrerit almenys una dotzena d'anys respecte del que s'havia proposat el president Clinton: segons el seu programa, la transformaci completa al sistema digital -amb la fi de la transmissi analgica-s'hauria d'haver assolit l'any 2006.
Hierarchical Database Screenings for HIV-1 Reverse Transcriptase Using a Pharmacophore Model, Rigid Docking, Solvation Docking, and MM−PB/SA (2005)

In this work, an efficient strategy was presented to search drug leads for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) using hierarchical database screenings, which included a pharmacophore model, multiple-conformation rigid docking, solvation docking, and molecular mechanics-Poisson-Boltzmann/surface area (MM-PB/SA) sequentially. Encouraging results were achieved in searching a refined available chemical directory (ACD) database: the enrichment factor after the first three filters was estimated to be 25-fold; the hit rate for all the four filters was predicted to be 41% in a control test using 37 known HIV-1 non-nucleoside reverse transcriptase inhibitors; 10 out of 30 promising solvation-docking hits had MM-PB/SA binding free energies better than -6.8 kcal/mol and the best one, HIT15, had -17.0 kcal/mol. In conclusion, the hierarchical multiple-filter database searching strategy is an attractive strategy in drug lead exploration.
A Crosslinked HA-Based Hydrogel Ameliorates Dry Eye Symptoms in Dogs (2013)

Keratoconjunctivitis sicca, commonly referred to as dry eye or KCS, can affect both humans and dogs. The standard of care in treating KCS typically includes daily administration of eye drops to either stimulate tear production or to hydrate and lubricate the corneal surface. Lubricating eye drops are often applied four to six times daily for the life of the patient. In order to reduce this dosing regimen yet still provides sufficient hydration and lubrication, we have developed a crosslinked hydrogel based on a modified, thiolated hyaluronic acid (HA), xCMHA-S. This xCMHA-S gel was found to have different viscosity and rheologic behavior than solutions of noncrosslinked HA. The gel was also able to increase tear breakup time in rabbits, indicating a stabilization of the tear film. Further, in a preliminary clinical study of dogs with KCS, the gel significantly reduced the symptoms associated with KCS within two weeks while only being applied twice daily. The reduction of symptoms combined with the low dosing regimen indicates that this gel may lead to both improved patient health and owner compliance in applying the treatment.
Molecular cloning of a possible cysteine proteinase predominantly expressed in osteoclasts. (1994)

Osteoclasts are multinucleate giant cells playing key roles in bone resorption. These cells solubilize mineralized bone matrix by means of acid and protease action; however, the precise mechanism of this process is not well known. Recently, we succeeded in the isolation of pure osteoclasts from rabbit bones and constructed a cDNA library. Using a differential screening procedure, two genes expressed predominantly in osteoclasts compared with spleen cells were isolated (Tezuka, K., Sato, T., Kamioka, H., Nijweide, P. J., Tanaka, K., Matsuo, T., Ohta, M., Kurihara, N., Hakeda, Y., and Kumegawa, M. (1992) Biochem. Biophys. Res. Commun. 186, 911-917). One of them, OC-2, was found to encode a possible cysteine proteinase structurally related to cathepsins L and S. By in situ hybridization, OC-2 was confirmed to be expressed in osteoclasts in vivo. By Northern blot analysis, OC-2 was highly and preferentially expressed in osteoclasts compared with other tissues such as kidney, liver, spleen, and lung. The predominant expression of OC-2 in osteoclasts may suggest that OC-2 encodes a protein, possibly a cysteine proteinase, that plays an important role in osteoclastic bone resorption.