gebhart/patrepeval huggingface dataset:
Therapy of leishmaniasis: Superior efficacies of liposome-encapsulated drugs (1978)

Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.
Regulation of Reticuloendothelial Iron Transporter MTP1 (Slc11a3) by Inflammation (2002)

Acute and chronic inflammation cause many changes in total body iron metabolism including the sequestration of iron in phagocytic cells of the reticuloendothelial system. This change in iron metabolism contributes to the development of the anemia of inflammation. MTP1, the duodenal enterocyte basolateral iron exporter, is also expressed in the cells of the reticuloendothelial system (RES) and is likely to be involved in iron recycling of these cells. In this study, we use a lipopolysaccharide model of the acute inflammation in the mouse and demonstrate that MTP1 expression in RES cells of the spleen, liver, and bone marrow is down-regulated by inflammation. The down-regulation of splenic expression of MTP1 by inflammation was also observed in a Leishmania donovani model of chronic infection. The response of MTP1 to lipopolysaccharide (LPS) requires signaling through the LPS receptor, Toll-like receptor 4 (TLR4). In mice lacking TLR4, MTP1 expression is not altered in response to LPS. In addition, mice lacking tumor necrosis factor-receptor 1a respond appropriately to LPS with down-regulation of MTP1, despite hyporesponsiveness to tumor necrosis factor-alpha signaling, suggesting that this cytokine may not be required for the LPS effect. We hypothesize that the iron sequestration in the RES system that accompanies inflammation is because of down-regulation of MTP1.
Characterization of carbon nanotubes by Raman spectroscopy (2008)

Application of Raman spectroscopy to analyse carbon nanotubes has been presented. Having a mixture of various carbon nanotube samples, one can easily distinguish, in a quick experiment, presence of singlewalled, doublewalled and multiwalled carbon nanotubes (SWCNT, DWCNT, MWCNT, respectively). The so-called G-line is a characteristic feature of the graphitic layers and corresponds to the tangential vibration of carbon atoms. Another characteristic mode is a typical sign of defective graphitic structures (D-line). A comparison of the intensity ratios of these two peaks gives a measure of the quality of the bulk samples. In addition, there is a third mode, named the radial breathing mode (RBM) which is very sensitive to the diameter of SWCNT and DWCNT. Additional option is application of Raman microscopy for mapping analysis and depth profiling to view the changes of intensity in various directions in the sample.
CHEMICAL SPECIFICITY IN GENETICAL DIFFERENCES OF TASTE SENSITIVITY (1949)

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
Tuning the Temperature Response of Branched Poly(N-isopropylacrylamide) Prepared by RAFT Polymerization (2008)

Reversible addition-fragmentation chain transfer (RAFT) polymerization in the presence of a compound capable of both reversible chain transfer through a thiocarbonylthio moiety and propagation via a vinyl group led to highly branched copolymers by a method analogous to self-condensing vinyl copolymerization. An acryloyl trithiocarbonate prepared by copper-catalyzed azide-alkyne cycloaddition was copolymerized with N-isopropylacrylamide (NIPAM) in ratios selected to tune the distribution and length of branches in the resulting thermoresponsive polymers. The degree of branching increased with chain transfer agent (CTA) concentration, as proven by NMR spectroscopy, size exclusion chromatography, and viscometry. Retention of the thiocarbonylthio compound during the polymerization was evidenced by successful chain extension of a branched N-isopropylacrylamide (PNIPAM) macroCTA by RAFT polymerization of N,N-dimethylacrylamide. The branched polymers led to reduced lower critical solution temperatures as compared to linear PNIPAM, an effect attributed primarily to an increased contribution of hydrophobic end groups. End group cleavage by radical-induced reduction resulted in an increased transition temperature more similar to that expected for linear PNIPAM.
A new method of three‐dimensional coronary artery reconstruction from X‐ray angiography: Validation against a virtual phantom and multislice computed tomography (2007)

The developed method for coronary artery reconstruction from conventional angiography images provides the geometry of coronary arteries in the 3D space.
Phototherapy Reduces the Number of Epidermal and CGRP-positive Dermal Nerve Fibres (2004)

The purpose of this study was to gain an understanding of why phototherapy relieves itching. Skin samples (3 mm punch biopsies) from non-inflamed gluteal skin of 10 patients undergoing phototherapy were compared before and after 20 treatments. All the cutaneous nerve fibres here visualized by antibodies against PGP 9.5, sensory nerve fibres by antibodies against calcitonin gene-related peptide (CGRP) and capsaicin-sensitive primary nociceptive afferents by antibodies against VR1-receptor. Following treatment, the number of PGP 9.5-positive nerve fibres in the epidermis was reduced from 193 +/- 52 to 102 +/- 34 (p < 0.0001) and the number of CGRP-immunoreactive nerve fibres, which occurred only in dermis, was reduced from 28 +/- 15 to 22 +/- 7 (p = 0.04). The VR1-immunoreactive nerve fibres, some of them containing immunoreactivity to CGRP, were not affected. The success of phototherapy in combating itch may at least partly be linked with the reduction in the number of epidermal nerve fibres. The reduction in the number of CGRP-immunoreactive nerve fibres in the dermis may contribute to the beneficial effects of UV irradiation on the inflammatory process.
Pharmacokinetics and pharmacodynamics of DSTA4637A: A novel THIOMAB™ antibody antibiotic conjugate against Staphylococcus aureus in mice (2016)

DSTA4637A, a novel THIOMAB™ antibody antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as a potential therapy against S. aureus infections. Structurally, TAC is composed of an anti-S. aureus antibody linked to a potent antibiotic, dmDNA31. The goal of the current study was to characterize the pharmacokinetics (PK) of TAC in mice, assess the effect of S. aureus infection on its PK, and evaluate its pharmacodynamics (PD) by measuring the bacterial load in various organs at different timepoints following TAC treatment. Plasma concentrations of 3 analytes, total antibody (TAb), antibody-conjugated dmDNA31 (ac-dmDNA31), and unconjugated dmDNA31, were measured in these studies. In non-infected mice (target antigen absent), following intravenous (IV) administration of a single dose of TAC, systemic concentration-time profiles of both TAb and ac-dmDNA31 were bi-exponential and characterized by a short distribution phase and a long elimination phase as expected for a monoclonal antibody-based therapeutic. Systemic exposures of both TAb and ac-dmDNA31 were dose proportional over the dose range tested (5 to 50 mg/kg). In a mouse model of systemic S. aureus infection (target antigen present), a single IV dose of TAC demonstrated PK behavior similar to that in the non-infected mice, and substantially reduced bacterial load in the heart, kidney, and bones on 7 and 14 d post dosing. These findings have increased our understanding of the PK and PK/PD of this novel molecule, and have shown that at efficacious dose levels the presence of S. aureus infection had minimal effect on TAC PK.
Molecular correlates of the M‐current in cultured rat hippocampal neurons (2002)

M-type K(+) currents (I(K(M))) play a key role in regulating neuronal excitability. In sympathetic neurons, M-channels are thought to be composed of a heteromeric assembly of KCNQ2 and KCNQ3 K(+) channel subunits. Here, we have tried to identify the KCNQ subunits that are involved in the generation of I(K(M)) in hippocampal pyramidal neurons cultured from 5- to 7-day-old rats. RT-PCR of either CA1 or CA3 regions revealed the presence of KCNQ2, KCNQ3, KCNQ4 and KCNQ5 subunits. Single-cell PCR of dissociated hippocampal pyramidal neurons gave detectable signals for only KCNQ2, KCNQ3 and KCNQ5; where tested, most also expressed mRNA for the vesicular glutamate transporter VGLUT1. Staining for KCNQ2 and KCNQ5 protein showed punctate fluorescence on both the somata and dendrites of hippocampal neurons. Staining for KCNQ3 was diffusely distributed whereas KCNQ4 was undetectable. In perforated patch recordings, linopirdine, a specific M-channel blocker, fully inhibited I(K(M)) with an IC(50) of 3.6 +/- 1.5 microM. In 70 % of these cells, TEA fully suppressed I(K(M)) with an IC(50) of 0.7 +/- 0.1 mM. In the remaining cells, TEA maximally reduced I(K(M)) by only 59.7 +/- 5.2 % with an IC(50) of 1.4 +/- 0.3 mM; residual I(K(M)) was abolished by linopirdine. Our data suggest that KCNQ2, KCNQ3 and KCNQ5 subunits contribute to I(K(M)) in these neurons and that the variations in TEA sensitivity may reflect differential expression of KCNQ2, KCNQ3 and KCNQ5 subunits.
Diagnosis and Management of Epithelial Ovarian Cancer (2006)

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States. Although there has been a statistically significant improvement in 5-year survival, in 2005 more than 16,000 women were expected to die of this disease. To date, there is no reliable method to screen for ovarian cancer; therefore, the majority of cases are diagnosed with advanced disease. For early ovarian cancer, appropriate surgical staging and adjuvant chemotherapy for selected cases will result in survival rates of 90-95%. For advanced ovarian cancer, survival depends primarily on the success of the initial surgical procedure. Patients with complete cytoreduction to microscopic disease are often cured with adjuvant chemotherapy. There is growing evidence that these patients with microscopic residual disease are excellent candidates for intraperitoneal chemotherapy, and this mode of chemotherapy delivery may be their best opportunity for cure. Patients with optimal cytoreduction also may benefit from intraperitoneal chemotherapy, but cure is less likely. For patients with suboptimal cytoreduction, intravenous chemotherapy with a combination of carboplatin and paclitaxel is the current standard therapy. Most of these patients will experience recurrence of the cancer, with small chance of cure. Salvage chemotherapy is important in ovarian cancer because many patients respond to several salvage regimens. Because of the high response rate of ovarian cancer, even after relapse, it is probably better to consider 10-year survival as the ideal end point. Finally, new biologic agents, in combination with traditional surgery and chemotherapy, may result in further improvement in survival for patients with ovarian cancer.
Engineering of Saccharomyces cerevisiae for Efficient Anaerobic Alcoholic Fermentation of l -Arabinose (2007)

For cost-effective and efficient ethanol production from lignocellulosic fractions of plant biomass, the conversion of not only major constituents, such as glucose and xylose, but also less predominant sugars, such as l-arabinose, is required. Wild-type strains of Saccharomyces cerevisiae, the organism used in industrial ethanol production, cannot ferment xylose and arabinose. Although metabolic and evolutionary engineering has enabled the efficient alcoholic fermentation of xylose under anaerobic conditions, the conversion of l-arabinose into ethanol by engineered S. cerevisiae strains has previously been demonstrated only under oxygen-limited conditions. This study reports the first case of fast and efficient anaerobic alcoholic fermentation of l-arabinose by an engineered S. cerevisiae strain. This fermentation was achieved by combining the expression of the structural genes for the l-arabinose utilization pathway of Lactobacillus plantarum, the overexpression of the S. cerevisiae genes encoding the enzymes of the nonoxidative pentose phosphate pathway, and extensive evolutionary engineering. The resulting S. cerevisiae strain exhibited high rates of arabinose consumption (0.70 g h(-1) g [dry weight](-1)) and ethanol production (0.29 g h(-1) g [dry weight](-1)) and a high ethanol yield (0.43 g g(-1)) during anaerobic growth on l-arabinose as the sole carbon source. In addition, efficient ethanol production from sugar mixtures containing glucose and arabinose, which is crucial for application in industrial ethanol production, was achieved.
Stereoselektive Synthese von 2′‐O‐(2‐Methoxyethyl)ribonucleosiden: Nachbargruppenbeteiligung der Methoxyethoxy‐Gruppe bei der Ribosylierung von Heterocyclen (1996)

Stereoselective Synthesis of 2′‐ O ‐(2‐Methoxythyl)ribonucleosides: Neighboring‐Group Participation of the Methoxythoxy Group in the Ribosylation Step A new access to 2′‐ O ‐(2‐methoxyethyl)ribonucleosides, building blocks for second‐generation antisense oligonucleotides, is presented. The influence of various reaction parameters on the coupling reaction of 2‐ O ‐(2‐methoxyethyl)‐ D ‐ribose derivatives with heteroaromatic bases as the key step was investigated, and reaction conditions were optimized with regard to formation of the desired β‐ D ‐anomers. With Sn 2+ salts as promotors in polar solvents, these β‐ D ‐anomers were formed with a high degree of steroselectivity.
White Adipocyte Vascular Endothelial Growth Factor: Regulation by Insulin (2002)

White adipose tissue from rats was examined for insulin- responsive vascular endothelial growth factor 165 (VEGF) secretion and mRNA expression. When separated into it constituent fat vs. stromal-vascular cells using collagenase digestion methods, only the adipocytes (or whole fat tissue) responded to physiological insulin concentrations by doubling VEGF release over 4 and 24 h in culture. Adipocyte VEGF mRNA expression increased similarly. Several adipose depots were tested. Although omental fat cells had the highest rates of VEGF release, the differences were not significant. Insulin-stimulated VEGF release was mediated in part via PI3K, but not PKC. Additional hormones/agents were tested, including steroids, leptin, an adenosine analog, and norepinephrine. Only the latter compound increased VEGF production, and this effect was mediated by adenylate cyclase. Adjusting the incubation glucose concentration between 0–20 mm did not alter adipocyte VEGF release. An experimental mimic of hypoxia, CoCl2, also increased adipocyte VEGF, and this effect was additive with 100 nm insulin. These studies demonstrate that physiological insulin concentrations stimulate VEGF formation and expression in cultured rodent white adipocytes. Although the biological significance of this observation remains to be determined, if white adipocyte-derived VEGF has paracrine or systemic endocrine actions, these might hypothetically impact on adipose expansion or the vascular comorbidities of obesity.
Metabotropic glutamate receptors: Phosphorylation and receptor signaling (2007)

Metabotropic glutamate receptors (mGluRs) play important roles in neurotransmission, neuronal development, synaptic plasticity, and neurological disorders. Recent studies have revealed a sophisticated interplay between mGluRs and protein kinases: activation of mGluRs regulates the activity of a number of kinases, and direct phosphorylation of mGluRs affects receptor signaling, trafficking, and desensitization. Here we review the emerging literature on mGluR phosphorylation, signaling, and synaptic function.
Scalable Distributed Communication\nArchitectures to Support Advanced\nMetering Infrastructure in Smart Grid (2012)

In this paper, we investigate the scalability of three communication architectures for advanced metering infrastructure (AMI) in smart grid. AMI in smart grid is a typical cyber-physical system (CPS) example, in which large amount of data from hundreds of thousands of smart meters are collected and processed through an AMI communication infrastructure. Scalability is one of the most important issues for the AMI deployment in smart grid. In this study, we introduce a new performance metric, accumulated bandwidth distance product (ABDP), to represent the total communication resource usages. For each distributed communication architecture, we formulate an optimization problem and obtain the solutions for minimizing the total cost of the system that considers both the ABDP and the deployment cost of the meter data management system (MDMS). The simulation results indicate the significant benefits of the distributed communication architectures over the traditional centralized one. More importantly, we analyze the scalability of the total cost of the communication system (including MDMS) with regard to the traffic load on the smart meters for both the centralized and the distributed communication architectures. Through the closed form expressions obtained in our analysis, we demonstrate that the total cost for the centralized architecture scales linearly as O(λN), with N being the number of smart meters, and λ being the average traffic rate on a smart meter. In contrast, the total cost for the fully distributed communication architecture is O(λ⅔N⅔), which is significantly lower.
Regulation of human tissue kallikrein-related peptidase expression by steroid hormones in 32 cell lines (2008)

Human tissue kallikrein-related peptidases(KLK), which are secreted serine proteases, are encoded by 15 genes located on chromosome 19q 13.4. Previous studies have shown that KLK expression is regulated by steroid hormones and many KLKs are dysregulated in hormone dependent malignancies. Some KLKs are proposed biomarkers for these cancers. We have characterized KLK hormonal regulation patterns using a large number of human cell lines. KLK levels were quantified in supernatants from 32 cell lines, each subjected to four hormonal stimulations (dexamethasone, norgestrel, dihydrotestosterone or estradiol), using ELISAs. Cell lines included breast, prostate, ovarian, lung, pancreatic, colon, and cervical cancer cells, T-lymphocytes, keratinocytes and non-cancerous epithelial breast cell line. KLKs were regulated in several cell lines not previously studied, such as keratinocytes (KLK 5, 6, and 7), ovarian cancer (KLK 5 and 9) and cervical cancer (KLK 3, 5, 6, 7,8, 10, 11, and 13) cells. Many KLKs were regulated by the synthetic glucocorticoid dexamethasone; specifically, KLK 5, 6, 8, 10, and 11 were upregulated in several breast cancer lines and downregulated in several cervical cancer lines. Knowledge of KLK hormonal regulation patterns will help to shed further light on their potential use as biomarkers and therapeutic targets for hormone-related malignancies.
General versus Specific Actions of Mild-Moderate Hypothermia in Attenuating Cerebral Ischemic Damage (2007)

Mild or moderate hypothermia is generally thought to block all changes in signaling events that are detrimental to ischemic brain, including ATP depletion, glutamate release, Ca(2+) mobilization, anoxic depolarization, free radical generation, inflammation, blood-brain barrier permeability, necrotic, and apoptotic pathways. However, the effects and mechanisms of hypothermia are, in fact, variable. We emphasize that, even in the laboratory, hypothermic protection is limited. In certain models of permanent focal ischemia, hypothermia may not protect at all. In cases where hypothermia reduces infarct, some studies have overemphasized its ability to maintain cerebral blood flow and ATP levels, and to prevent anoxic depolarization, glutamate release during ischemia. Instead, hypothermia may protect against ischemia by regulating cascades that occur after reperfusion, including blood-brain barrier permeability and the changes in gene and protein expressions associated with necrotic and apoptotic pathways. Hypothermia not only blocks multiple damaging cascades after stroke, but also selectively upregulates some protective genes. However, most of these mechanisms are addressed in models with intraischemic hypothermia; much less information is available in models with postischemic hypothermia. Moreover, although it has been confirmed that mild hypothermia is clinically feasible for acute focal stroke treatment, no definite beneficial effect has been reported yet. This lack of clinical protection may result from suboptimal criteria for patient entrance into clinical trials. To facilitate clinical translation, future efforts in the laboratory should focus more on the protective mechanisms of postischemic hypothermia, as well as on the effects of sex, age and rewarming during reperfusion on hypothermic protection.
Effective Methods for Introducing Some Aryl and Heteroaryl Substituent onto 1-Azaazulene Nuclei (2005)

Introduction of aryl and heteroaryl groups onto 1-azaazulene ring was achieved by addition-elimination reaction and Suzuki coupling.Reaction of 2-chloro-1-azaazulenes with 2-aryllithium and 2-heteroaryllithium followed by dehydrogenation with o-chloranil gave 8-aryl-and 8-heteroaryl-2-chloro-1-azaazulene in good yields.Suzuki coupling of 3-iodo-1-azaazulenens with phenylboronic acid in the presence of Pd catalyst afforded 3-phenyl-1-azaazulenes in excellent yield.Suzuki coupling of 2-bromo-1-azaazulenes with phenylboronic acid gave 2-phenyl-1-azaazulenes.Suzuki coupling of 2,3-dibromo-1-azaazulene with phenylboronic acid preferentially occurred at C-2. Reaction of 3-iodo-1-azaazulene with bis(pinacolato)diboron produced 3,3'-bis(1-azaazulene) derivative.
Industrial Excimer Lasers: Issues And Answers (1988)

Industrial applications of excimer lasers are expanding rapidly. This trend has led to the evolution of a new generation of excimer lasers designed specifically for industrial usage. This paper reviews some of the issues which need to be addressed in the development of such a laser. Included are market considerations, technology related items and issues related to the laser configuration.