gebhart/patrepeval huggingface dataset:
Targeting &#945;v&#946;3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides (2010)

The outstanding physio-pathological role played by integrin receptors in living subjects motivates the enormous interest shown by scientists worldwide for this topic. More than twenty years of research has spanned across the structural and functional elucidation of these proteins and over their antagonism-based biomedical applications. The proof-of concept stage, aimed at identifying potent inhibitors, covered a decade of studies, and paved the way for a more advanced era of research where these antagonist molecules were thrown into the deep end of applicative studies. This review intends to summarize the major efforts conducted thus far and focuses on the design, synthesis and biomedical applications of cyclic RGD-containing alpha(v)beta(3) integrin antagonists, in both their small and macromolecular formats. In particular, Chapters 1 and 2 offer a comprehensive outlook on the rational basis for the design of integrin inhibitors, Chapter 3 chronicles the biological and medical applications of monofunctional RGD integrin ligands both in their monomeric and multimeric asset, and Chapter 4 illustrates the potential of RGD-based multifunctional systems in molecular medicine.
Chronotropic Incompetence and Its Contribution to Exercise Intolerance in Older Heart Failure Patients (2006)

Brubaker, Peter H. PhD; Joo, Kee-Chan PhD; Stewart, Kathryn P. RDMS; Fray, Brittney MS; Moore, Brian MS; Kitzman, Dalane W. MDAuthor Information
JAPANESE SECURITY AND PEACE REGIME ON THE KOREAN PENINSULA (2000)

The sharp rise of North Korea’s threat to Japan’s security in recent years has prompted Japan to play a more active role in the uncertain peace-building effort on the Korean peninsula. Indeed, Tokyo has adopted a multifaceted security policy toward the management of problems associated with a divided Korea. On the one hand, it has committed itself as a major underwriter of the Korean Peninsula Energy Development Organization (KEDO) and is a supporter of the Four-Party Peace Talks and other multilateral confidence and security building efforts in the region. On the other hand, Tokyo has also strengthened its long-standing bilateral military ties with Washington, sought ways to cooperate with Seoul on security matters, and unilaterally instituted measures to beef up its defense capabilities. In fact, Japan’s trilateral cooperation with the United States and South Korea on diplomatic as well as military measures has limited North Korea’s ability to exploit the inevitable differences in national priorities among the three democratic countries. The continuation and deepening of this cooperation should help in convincing Pyongyang that it needs to moderate its confrontational behavior. This should in turn increase the prospect of establishing a stable peace regime on the Korean peninsula. Japan has vital security interests at stake in Korea, and it would be to Japan’s advantage to see the establishment of a stable peace regime on the Korean peninsula. In fact, Japan in recent years has played an active role in the uncertain peace-building effort between North Korea on the one side and South Korea and the United States on the other. Japan has committed itself as a key financial sponsor of the Korean Peninsula Energy Development Organization (KEDO) and is a supporter of the Four-Party Peace Talks and other multilateral confidence and security building efforts in the region. However, Japan has hedged these more optimistic bets by strengthening its long-standing bilateral military alliance with the United States, seeking ways to cooperate with South Korea on security matters, and unilaterally beefing up its own defense capabilities in case that things go very wrong on the Korean peninsula. On the whole, this multifaceted Japanese security policy has had a positive impact on the maintenance of regional stability in Northeast Asia and the ongoing effort to build a permanent peace on the Korean peninsula. In particular, Japan’s trilateral cooperation with the United States and South Korea on diplomatic as well as military measures has limited North Korea’s ability to exploit the inevitable differences in national priorities among the three democratic countries. The continuation and deepening of this cooperation should prompt North Korea to make a realistic appraisal of its strategic options and moderate its bellicose behavior. This in turn should increase the prospect of creating a stable peace regime on the Korean peninsula.
A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon γ antibody, in patients with moderate to severe Crohn’s disease (2006)

Introduction: This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon γ antibody, in patients with moderate to severe Crohn’s disease (CD). Patients and methods: Forty five patients with a CD activity index (CDAI) of 250–450 were randomised in a double blind, placebo controlled, dose escalating fashion to receive single doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) or placebo. By day 29, patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals. Primary objectives were safety and tolerability. Secondary outcomes included assessments of immunogenicity, clinical activity, and potential pharmacodynamic surrogates. Results: Treatment was generally well tolerated. There were slightly more reports of chills, flu-like syndrome, asthenia, nausea, and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab cohorts. Two serious adverse events rated as worsening of CD occurred under fontolizumab. Antibodies to fontolizumab were confirmed in one patient. No differences in clinical activity parameters were noted between any of the active treatment groups and placebo, with the placebo group having a particularly favourable outcome (60% response and 40% remission). By day 29, a more enhanced decrease in median Crohn’s disease endoscopic index of severity (p = 0.02) and serum C reactive protein (p&lt;0.001) was observed in the 4.0 mg/kg (n = 14) fontolizumab cohort compared with placebo (n = 10). Pharmacodynamic effects were observed by immunohistochemistry. Conclusions: Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD. A biological activity of fontolizumab is suggested.
Characterization and selective inhibition of myristoyl-CoA:protein N-myristoyltransferase from Trypanosoma brucei and Leishmania major (2006)

The eukaryotic enzyme NMT (myristoyl-CoA:protein N-myristoyltransferase) has been characterized in a range of species from Saccharomyces cerevisiae to Homo sapiens. NMT is essential for viability in a number of human pathogens, including the fungi Candida albicans and Cryptococcus neoformans, and the parasitic protozoa Leishmania major and Trypanosoma brucei. We have purified the Leishmania and T. brucei NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and specific peptide substrates. A number of inhibitory compounds that target NMT in fungal species have been tested against the parasite enzymes in vitro and against live parasites in vivo. Two of these compounds inhibit TbNMT with IC50 values of <1 microM and are also active against mammalian parasite stages, with ED50 (the effective dose that allows 50% cell growth) values of 16-66 microM and low toxicity to murine macrophages. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against infectious diseases including African sleeping sickness and Nagana.
Depth plane adaptive integral imaging using a varifocal liquid lens array (2015)

This paper proposes an enhanced integral imaging system with an electrically controllable image plane to address the issue of the limited depth problem in integral imaging. For implementation of the variable image plane, a varifocal liquid lens array and driving device are adopted instead of an ordinary solid lens array. The position of the central depth plane is varied by adjusting the focal length of the lens array. The proposed system enables matching between the object position and depth plane electrically, and thus an object moving from 5.15 to 11.72 cm is clearly displayed with this method.
An Enzymic Analysis of NADPH Production and Consumption in Candida utilis (1983)

Candida utilis CBS 621 was grown in chemostat cultures at D = 0.1 h-1 on glucose, xylose, gluconate, acetate, or ethanol as the growth-limiting substrate with ammonia or nitrate as the nitrogen source and analysed for NADPH-producing and NADPH-consuming enzyme activities. Nitrate and nitrite reductases were strictly NADPH-dependent. For all carbon sources, growth with nitrate resulted in elevated levels of HMP pathway enzymes. NADP+-linked isocitrate dehydrogenase did not vary significantly with the NADPH requirement for biosynthesis. Growth on ethanol strongly enhanced activity of NADP+-linked aldehyde dehydrogenase. Neither NADP+-linked malic enzyme nor transhydrogenase activities were detectable under any of the growth conditions. The absence of transhydrogenase was confirmed by the enzyme profiles of cells grown on mixtures of glucose and formate. It is concluded that the HMP pathway and possibly NADP+-linked isocitrate dehydrogenase are the major sources of NADPH in Candida utilis.
Targeted Delivery of Drugs and DNA with Liposomes (1993)

This presentation is divided into three parts: long-circulating liposomes, immunoliposomes and gene transfer with liposomes. The mechanism of action for the poly(ethylene glycol)-phospholipid conjugates to prolong the circulation time of liposomes can be understood on the basis of steric barrier activity imposed by the flexible PEG chains on the liposome surface. The action of ganglioside GM1, on the other hand, probably involves specific interactions with serum protein(s). Immunoliposomes can efficiently bind with the target only if the target is readily accessible and the liposomes stay in the circulation for a relatively long period of time. Coating the liposome surface with PEG chains or GM1 enhances the target binding of immunoliposomes, except when PEG of greater than 5000 dalton is used. In this case, immunoliposome binding to the target is sterically hindered by the long PEG chains. To overcome the problem, antibody molecule is conjugated to the distal end of the PEG chain. This approach works well except that the liver uptake of immunoliposomes is somewhat enhanced. For the delivery of DNA into cells, a novel cationic amphiphile (DC-chol) is synthesized and is now used in clinical trials of gene therapy for melanoma. Current effort is concentrated on the means to enhance the level and duration of transgene expression.
Growth of endothelial cell on the surface of intravascular stent material:Bionic construction of bioactive extracellular matrix (2009)

冠状动脉内置入药物涂层支架显著解决了支架内再狭窄,但是,支架内晚期及超晚期血栓带来新的难题加快支架内皮化,预防血栓形成成为研究的关键.目的:观察内皮细胞在经刻蚀并构建仿生的生物活性表面,整合细胞外基质成分的金属钛表面的生长情况.设计、时间及地点:对比观察,于2007-08/2009-01在西南交通大学先进材料与技术教育部重点实验室完成.材料:成年杂交犬6只,体质量15-20kg,纯钛(99.997...
Screening for Breast Cancer: Systematic Evidence Review Update for the US Preventive Services Task Force (2009)

BACKGROUND: This systematic review is an update of evidence since the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation on breast cancer screening. PURPOSE: To determine the effectiveness of mammography screening in decreasing breast cancer mortality among average-risk women age 40 to 49 and 70 and older; the effectiveness of clinical breast examination (CBE) and breast self examination (BSE); and harms of screening. DATA SOURCES: Cochrane Controlled Trials Registry and Database of Systematic Reviews (4th Quarter 2008), MEDLINE® (January 2001 to December 2008), reference lists, and Web of Science® for published studies; Breast Cancer Surveillance Consortium for screening mammography data. STUDY SELECTION: Randomized controlled trials with breast cancer mortality outcomes for screening effectiveness; multiple study designs and data sources for harms. DATA EXTRACTION: Investigators abstracted relevant data and rated study quality using established criteria. DATA SYNTHESIS: Mammography screening reduces breast cancer mortality by 15% for women age 39 to 49 (relative risk 0.85; 95% CrI 0.75 to 0.96; 8 trials); data are lacking for age ≥70. Radiation exposure from mammography is low. Patient adverse experiences are common, transient, and do not impact screening practices. Estimates of overdiagnosis vary from 1% to 10%. Younger women have more false positive mammograms and additional imaging, but fewer biopsies than older women. Trials of CBE are ongoing; for BSE, trials showed no reductions in mortality but increased benign biopsies. LIMITATIONS: Studies of older women, digital mammography, and MRI are lacking. CONCLUSIONS: Mammography screening reduces breast cancer mortality for women age 39 to 69; data are insufficient for older women. False positive mammograms and additional imaging are common. No benefit has been shown for CBE or BSE.
Discretized streams (2013)

Many "big data" applications must act on data in real time. Running these applications at ever-larger scales requires parallel platforms that automatically handle faults and stragglers. Unfortunately, current distributed stream processing models provide fault recovery in an expensive manner, requiring hot replication or long recovery times, and do not handle stragglers. We propose a new processing model, discretized streams (D-Streams), that overcomes these challenges. D-Streams enable a parallel recovery mechanism that improves efficiency over traditional replication and backup schemes, and tolerates stragglers. We show that they support a rich set of operators while attaining high per-node throughput similar to single-node systems, linear scaling to 100 nodes, sub-second latency, and sub-second fault recovery. Finally, D-Streams can easily be composed with batch and interactive query models like MapReduce, enabling rich applications that combine these modes. We implement D-Streams in a system called Spark Streaming.
Nonunion of the humerus after failure of surgical treatment (2000)

We used the Ilizarov circular external fixator to treat 16 patients with persistent nonunion of the diaphysis of the humerus despite surgical treatment. All patients had pain and severe functional impairment of the affected arm. In ten, nonunion followed intramedullary nailing. We successfully treated these by a closed technique. The nail was left in place and the fracture compressed over it. The fractures of the other six patients had previously been fixed by various methods. We explored these nonunions, removed the fixation devices and excised fibrous tissue and dead bone before stabilising with the Ilizarov fixator. In five patients union was achieved. Bone grafting was not required. In the single patient in whom treatment failed, there had been a severely comminuted open fracture. All except one patient had reduction of pain, and all reported an improvement in function.
Regularities of context-dependent codon bias in eukaryotic genes (2002)

Nucleotides surrounding a codon influence the choice of this particular codon from among the group of possible synonymous codons. The strongest influence on codon usage arises from the nucleotide immediately following the codon and is known as the N1 context. We studied the relative abundance of codons with N1 contexts in genes from four eukaryotes for which the entire genomes have been sequenced: Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana. For all the studied organisms it was found that 90% of the codons have a statistically significant N1 context-dependent codon bias. The relative abundance of each codon with an N1 context was compared with the relative abundance of the same 4mer oligonucleotide in the whole genome. This comparison showed that in about half of all cases the context-dependent codon bias could not be explained by the sequence composition of the genome. Ranking statistics were applied to compare context-dependent codon biases for codons from different synonymous groups. We found regularities in N1 context-dependent codon bias with respect to the codon nucleotide composition. Codons with the same nucleotides in the second and third positions and the same N1 context have a statistically significant correlation of their relative abundances.
Endocrinology of the Amphibian Pineal (1970)

McCord and Allen (1917) found that extracts of mammalian pineal glands contain a potent contracting agent of larval amphibian melanophores. Lerner and his co-workers determined the chemical structure of this principle and named it melatonin. This agent contracts dermal melanophores at a concentration as low as 10−10 g/ml. Both intact and eyeless larval amphibians blanch when placed in the dark, and the melanophore contraction which causes this lightening response is abolished by pinealectomy. The amphibian pineal contains photoreceptive elements similar to those found in the vertebrate lateral eyes, and these elements are inhibited by light but are stimulated in its absence. There is evidence for the presence of both HIOMT and melatonin the amphibian pineal. It has been proposed that the body-blanching response results from a direct stimulation of the pineal under conditions of darkness leading to a release of melatonin into the general circulation which is then responsible for a direct contracting effect on dermal melanophores. The cytophysiological effects of melatonin mimic those that take place in the body-blanching response. Since no other hormone or pharmacological agent duplicates this response, this is strong evidence that melatonin is a hormone that normally regulates body blanching. Other evidence for the support of this hypothesis is presented. Cytological features of both normal and melatonin-induced lightening indicate that the effects of melatonin are at the effector cell level rather than at either the hypothalamus or the pituitary. An inhibition of MSH-release by melatonin is not involved. Melatonin plays a normal role in young larvae to regulate the lightening response that takes place in darkness (the primary chromatic response). Neither melatonin nor the pineal play a role in the later (secondary stage) adaptive background responses of amphibians. As McCord and Allen first noted, the pineal may contain other substances which may have other physiological roles in amphibians as well as other vertebrates. These have been little studied.
Specific branches of hypoglossal nerve to genioglossus muscle as a potential target of selective neurostimulation in obstructive sleep apnea: anatomical and morphometric study (2016)

According to our observations, the optimal selective or supra-selective stimulation of the tongue protractor muscles can be performed on the lateral surface of the GG at roughly equal distance between the mandibular symphysis and the hyoid bone, at a depth of about 0.6 cm above the GG lower border.
Inhibition of IAPP and IAPP(20−29) Fibrillation by Polymeric Nanoparticles (2009)

The fibrillation process of the islet amyloid polypeptide (IAPP) and its fragment (IAPP(20-29)) was studied by means of Thioflavin T (ThT) fluorescence and transmission electron microscopy in the absence and presence of N-isopropylacrylamide:N-tert-butylacrylamide (NiPAM:BAM) copolymeric nanoparticles. The process was found to be strongly affected by the presence of the nanoparticles, which retard protein fibrillation as a function of the chemical surface properties of the nanoparticles. The NiPAM:BAM ratio was varied from 50:50 to 100:0. The nanoparticles with higher fraction of NiPAM imposed the strongest retardation of IAPP and IAPP(20-29) fibrillation. These particles have the strongest hydrogen bonding capacity due to the less bulky N-isopropyl group and thus less steric hindrance of the hydrogen-bonding groups of the nanoparticle polymer backbone. Kinetic fibrillation data, as monitored by ThT fluorescence and supported by surface plasmon resonance experiments, suggest that the peptide is strongly absorbed onto the surface of the nanoparticles. This interaction reduces the concentration of peptide free in solution available to proceed to fibrillation which results in an increased lag time of fibrillation, observed as a delayed onset of ThT fluorescence increase, plus a reduction of the amount of fibrils formed as indicated by the equilibrium values at the end of the fibrillation reaction. For the fragment (IAPP(20-29)), the presence of nanoparticles changes the mechanism of association from monomers to fibrils, by interfering with early oligomeric species along the fibrillation pathway.
One Week’s Treatment With the Long-Acting Glucagon-Like Peptide 1 Derivative Liraglutide (NN2211) Markedly Improves 24-h Glycemia and α- and β-Cell Function and Reduces Endogenous Glucose Release in Patients with Type 2 Diabetes (2004)

Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabetes. We explored the effect of short-term (1 week) treatment with a GLP-1 derivative, liraglutide (NN2211), on 24-h dynamics in glycemia and circulating free fatty acids, islet cell hormone profiles, and gastric emptying during meals using acetaminophen. Furthermore, fasting endogenous glucose release and gluconeogenesis (3-(3)H-glucose infusion and (2)H(2)O ingestion, respectively) were determined, and aspects of pancreatic islet cell function were elucidated on the subsequent day using homeostasis model assessment and first- and second-phase insulin response during a hyperglycemic clamp (plasma glucose approximately 16 mmol/l), and, finally, on top of hyperglycemia, an arginine stimulation test was performed. For accomplishing this, 13 patients with type 2 diabetes were examined in a double-blind, placebo-controlled crossover design. Liraglutide (6 micro g/kg) was administered subcutaneously once daily. Liraglutide significantly reduced the 24-h area under the curve for glucose (P = 0.01) and glucagon (P = 0.04), whereas the area under the curve for circulating free fatty acids was unaltered. Twenty-four-hour insulin secretion rates as assessed by deconvolution of serum C-peptide concentrations were unchanged, indicating a relative increase. Gastric emptying was not influenced at the dose of liraglutide used. Fasting endogenous glucose release was decreased (P = 0.04) as a result of a reduced glycogenolysis (P = 0.01), whereas gluconeogenesis was unaltered. First-phase insulin response and the insulin response to an arginine stimulation test with the presence of hyperglycemia were markedly increased (P < 0.001), whereas the proinsulin/insulin ratio fell (P = 0.001). The disposition index (peak insulin concentration after intravenous bolus of glucose multiplied by insulin sensitivity as assessed by homeostasis model assessment) almost doubled during liraglutide treatment (P < 0.01). Both during hyperglycemia per se and after arginine exposure, the glucagon responses were reduced during liraglutide administration (P < 0.01 and P = 0.01). Thus, 1 week's treatment with a single daily dose of the GLP-1 derivative liraglutide, operating through several different mechanisms including an ameliorated pancreatic islet cell function in individuals with type 2 diabetes, improves glycemic control throughout 24 h of daily living, i.e., prandial and nocturnal periods. This study further emphasizes GLP-1 and its derivatives as a promising novel concept for treatment of type 2 diabetes.