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We establish the existence of standing waves with one pulse, multiple spikes and transition layers in the nonlinear reaction-diffusion systemu(t) = f(u, w) + u(xx), w(t) = epsilon(2) g(u, w) + w(xx), x is an element of R,where e >...
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We establish the existence of standing waves with one pulse, multiple spikes and transition layers in the nonlinear reaction-diffusion systemu(t) = f(u, w) + u(xx), w(t) = epsilon(2) g(u, w) + w(xx), x is an element of R,where e > 0 is a small parameter, f(u, w) = 0 has three branches u = h(1) (w), u = h(2)(w) and u = h(3) (W) on an interval of to and g(u, w) = 0 intersects u = h(1) (w) once and u = h(3)(w) at most once. We use a different method to prove the existence of a single pulse. The existence of multiple spikes and transition layers is a new result. The new method is a topological shooting plan consisting of various shooting arguments. The main technical advance of this plan is that it provides a setup for proving the existence of not only a single pulse, but also multiple spikes and transition layers. The proof of the existence of spikes and transition layers involves more delicate estimates in order to assure the existence of certain types of solutions necessary in the topological shooting arguments. A two-dimensional topological shooting principle and another elementary topological principle are applied in the shooting arguments. (C) 2004 Elsevier Inc. All rights reserved.
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An efficient and sensitive method has been established for simultaneous determination of 653 pesticides in teas by GC/MS and HPLC/MS/MS. The method involved extraction with acetonitrile followed by cleanup using Cleanert-TPT SPE a...
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An efficient and sensitive method has been established for simultaneous determination of 653 pesticides in teas by GC/MS and HPLC/MS/MS. The method involved extraction with acetonitrile followed by cleanup using Cleanert-TPT SPE and subsequent identification and quantitation of 490 pesticides by GC/MS and 448 pesticides by HPLC/MS/ MS. The LODs for pesticides determined by GC/MS were between 1.0 and 500 microg/kg, and those determined by HPLC/MS/MS were between 0.03 and 4820 microg/kg. At the low fortification levels of 0.01-100 microg/kg, the average recoveries of 94% of the pesticides determined by GC/MS were between 60 and 120%, 77% of which had an RSD below 20%. For 91% of pesticides determined by HPLC/MS/MS, the average recoveries were between 60 and 120%, 76% of which had an RSD below 20%. The paper also reports a novel SPE column, Cleanert TPT, which comprised graphitized carbon black (PestiCarb), polyamine silica, and amide polystyrene for purifying the tea samples. The results indicated good repeatiblity and reproducibility.
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Copy number variation (CNV) is a source of genetic diversity in humans. Numerous CNVs are being identified with various genome analysis platforms, including array comparative genomic hybridization (aCGH), single nucleotide polymor...
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Copy number variation (CNV) is a source of genetic diversity in humans. Numerous CNVs are being identified with various genome analysis platforms, including array comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) genotyping platforms, and next-generation sequencing. CNV formation occurs by both recombination-based and replication-based mechanisms and de novo locus-specific mutation rates appear much higher for CNVs than for SNPs. By various molecular mechanisms, including gene dosage, gene disruption, gene fusion, position effects, etc., CNVs can cause Mendelian or sporadic traits, or be associated with complex diseases. However, CNV can also represent benign polymorphic variants. CNVs, especially gene duplication and exon shuffling, can be a predominant mechanism driving gene and genome evolution.
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Copy number variation (CNV) is a source of genetic diversity in humans. Numerous CNVs are being identified with various genome analysis platforms, including array comparative genomic hybridization (aCGH), single nucleotide polymor...
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Copy number variation (CNV) is a source of genetic diversity in humans. Numerous CNVs are being identified with various genome analysis platforms, including array comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) genotyping platforms, and next-generation sequencing. CNV formation occurs by both recombination-based and replication-based mechanisms and de novo locus-specific mutation rates appear much higher for CNVs than for SNPs. By various molecular mechanisms, including gene dosage, gene disruption, gene fusion, position effects, etc., CNVs can cause Mendelian or sporadic traits, or be associated with complex diseases. However, CNV can also represent benign polymorphic variants. CNVs, especially gene duplication and exon shuffling, can be a predominant mechanism driving gene and genome evolution.
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Corneal angiogenesis is associated with a variety of corneal diseases, and is sometimes vision threatening. In recent years, with the discovery of major pro- and anti-angiogenic factors in the cornea, details of the angiogenic pro...
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Corneal angiogenesis is associated with a variety of corneal diseases, and is sometimes vision threatening. In recent years, with the discovery of major pro- and anti-angiogenic factors in the cornea, details of the angiogenic process are gradually unveiled. Of note, corneal inflammation and neovascularization associated with severe limbal stem cell (LSC) deficiency is a clinically challenging issue in that the condition persists long after the initial insult, and will not improve without transplantation of LSCs. However, to date the molecular mechanism by which LSC transplantation restores corneal avascularity is not fully understood. In addition to discussing major pro-angiogenic factors involved in corneal neovascularization, this review article also focuses on possible molecular mechanisms underlying persistent inflammation and neovascularization following severe LSC deficiency, and anti-angiogenic factors expressed by human limbo-corneal epithelial cells (HLCECs). Most of the recently discovered corneal anti-angiogenic factors belong to extracellular matrix proteins that acquire angio-inhibitory activity only after proper proteolytic processing. Our recent findings showed that the secretion of endostatin (derived from basement membrane collagen XVIII) and restin (from collagen XV) by HLCECs were enhanced when HLCECs were cultivated on amniotic membrane (AM). This adds to the advantage of transplanting ex vivo expanded HLCECs cultivated on AM in that the anti-angiogenic activity of the epithelial cells is augmented in a physiological way. Furthermore, proteomic profiling of HLCECs and human conjunctival epithelial cells (HCECs) identified a 14-3-3 protein (stratifin) preferentially expressed by HLCECs. In addition to functioning as a cell cycle controller, keratinocyte-derived stratifin induces MMPs which are involved in the generation of restin (by MMP-1) and endostatin (by MMP-3). These findings highlight the significance of delicate epithelial-matrix interactions in the maintenance of corneal avascularity.
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Throughout much of the last century insulin served a central role in the advancement of peptide chemistry, pharmacology, cell signaling and structural biology. These discoveries have provided a steadily improved quantity and quali...
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Throughout much of the last century insulin served a central role in the advancement of peptide chemistry, pharmacology, cell signaling and structural biology. These discoveries have provided a steadily improved quantity and quality of life for those afflicted with diabetes. The collective work serves as a foundation for the development of insulin analogs and mimetics capable of providing more tailored therapy. Advancements in patient care have been paced by breakthroughs in core technologies, such as semisynthesis, high performance chromatography, rDNA-biosynthesis and formulation sciences. How the structural and conformational dynamics of this endocrine hormone elicit its biological response remains a vigorous area of study. Numerous insulin analogs have served to coordinate structural biology and biochemical signaling to provide a first level understanding of insulin action. The introduction of broad chemical diversity to the study of insulin has been limited by the inefficiency in total chemical synthesis, and the inherent limitations in rDNA-biosynthesis and semisynthetic approaches. The goals of continued investigation remain the delivery of insulin therapy where glycemic control is more precise and hypoglycemic liability is minimized. Additional objectives for medicinal chemists are the identification of superagonists and insulins more suitable for noninjectable delivery. The historical advancements in the synthesis of insulin analogs by multiple methods is reviewed with the specific structural elements of critical importance being highlighted. The functional refinement of this hormone as directed to improved patient care with insulin analogs of more precise pharmacology is reported. (c) 2007 Wiley Periodicals, Inc.
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Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD(+)). They suppress genome-wide transcripti...
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Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD(+)). They suppress genome-wide transcription, yet upregulate a select set of proteins related to energy metabolism and pro-survival mechanisms, and therefore play a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of sirtuins has been reported for both acute and chronic neurological diseases. The focus of this review is to summarize the latest progress regarding the protective effects of sirtuins, with a focus on SIRT1. We first introduce the distribution of sirtuins in the brain and how their expression and activity are regulated. We then highlight their protective effects against common neurological disorders, such as cerebral ischemia, axonal injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Finally, we analyze the mechanisms underlying sirtuin-mediated neuroprotection, centering on their non-histone substrates such as DNA repair enzymes, protein kinases, transcription factors, and coactivators. Collectively, the information compiled here will serve as a comprehensive reference for the actions of sirtuins in the nervous system to date, and will hopefully help to design further experimental research and expand sirtuins as therapeutic targets in the future.
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In studies of the evolution of avian flight there has been a singular preoccupation with unravelling its origin. By contrast, the complex changes in morphology that occurred between the earliest form of avian flapping flight and t...
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In studies of the evolution of avian flight there has been a singular preoccupation with unravelling its origin. By contrast, the complex changes in morphology that occurred between the earliest form of avian flapping flight and the emergence of the flight capabilities of extant birds remain comparatively little explored. Any such work has been limited by a comparative paucity of fossils illuminating bird evolution near the origin of the clade of extant (i.e. 'modern') birds (Aves). Here we recognize three species from the Early Cretaceous of China as comprising a new lineage of basal ornithurine birds. Ornithurae is a clade that includes, approximately, comparatively close relatives of crown clade Aves (extant birds) and that crown clade. The morphology of the best-preserved specimen from this newly recognized Asian diversity, the holotype specimen of Yixianornis grabaui Zhou and Zhang 2001, complete with finely preserved wing and tail feather impressions, is used to illustrate the new insights offered by recognition of this lineage. Hypotheses of avian morphological evolution and specifically proposed patterns of change in different avian locomotor modules after the origin of flight are impacted by recognition of the new lineage. The complete articulated holotype specimen of Yixianornis grabaui, from the Early Cretaceous Jiufotang Formation of Liaoning Province, in north-eastern China, arguably the best-preserved basal ornithurine specimen yet discovered, provides the earliest evidence consistent with the presence of extant avian tail feather fanning.
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We present a new approach to training back-propagation artificial neural nets (BP-ANN) based on regularization and cross-validation and on initialization by a logistic regression (LR) model. The new approach is expected to produce...
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We present a new approach to training back-propagation artificial neural nets (BP-ANN) based on regularization and cross-validation and on initialization by a logistic regression (LR) model. The new approach is expected to produce a BP-ANN predictor at least as good as the LR-based one. We have applied the approach to ten data sets of biomedical interest and systematically compared BP-ANN and LR. In all data sets, taking deviance as criterion, the BP-ANN predictor outperforms the LR predictor used in the initialization, and in six cases the improvement is statistically significant. The other evaluation criteria used (C-index, MSE and error rate) yield variable results, but, on the whole, confirm that, in practical situations of clinical interest, proper training may significantly improve the predictive performance of a BP-ANN.
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Persons with a prosthesis implanted in a cochlea with residual acoustic sensitivity can, in some cases, achieve better speech perception with "hybrid" stimulation than with either acoustic or electric stimulation presented alone. ...
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Persons with a prosthesis implanted in a cochlea with residual acoustic sensitivity can, in some cases, achieve better speech perception with "hybrid" stimulation than with either acoustic or electric stimulation presented alone. Such improvements may involve "across auditory-nerve fiber" processes within central nuclei of the auditory system and within-fiber interactions at the level of the auditory nerve. Our study explored acoustic-electric interactions within feline auditory nerve fibers (ANFs) so as to address two goals. First, we sought to better understand recent results that showed non-monotonic recovery of the electrically evoked compound action potential (ECAP) following acoustic masking (Nourski et al. 2007, Hear. Res. 232:87-103). We hypothesized that post-masking changes in ANF temporal properties and responsiveness (spike rate) accounted for the ECAP results. We also sought to describe, more broadly, the changes in ANF responses that result from prior acoustic stimulation. Five response properties-spike rate, latency, jitter, spike amplitude, and spontaneous activity-were examined. Post-masking reductions in spike rate, within-fiber jitter and across-fiber variance in latency were found, with the changes in temporal response properties limited to ANFs with high spontaneous rates. Thus, our results suggest how non-monotonic ECAP recovery occurs for ears with spontaneous activity, but cannot account for that pattern of recovery when there is no spontaneous activity, including the results from the presumably deafened ears used in the Nourski et al. (2007) study. Finally, during simultaneous (electric+acoustic) stimulation, the degree of electrically driven spike activity had a strong influence on spike rate, but did not affect spike jitter, which apparently was determined by the acoustic noise stimulus or spontaneous activity.
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