bluuebunny/crossref_metadata_2025 huggingface dataset:
A note on prefixes of regular languages
Authors: Seiferas Joel I.
Published: June 2010

Hopcroft and Ullman (problem 3.10 [1]) pose the amusing question of whether the "first third" of a regular language L, FIRST-THIRD(L) = {x| x is a prefix of a member of L of length 3|x|}, is necessarily regular. To see that it is, we can adapt of 1-way deterministic finite-state acceptor (an FA, for short) for L to get a 2-way non-deterministic finite-state acceptor with endmarkers for FIRST-THIRD(L). This acceptor behaves like the FA on x until it reaches the right endmarker, and then it uses another pass over x at half speed to behave like the FA on some nondeterministically chosen continuation of length 2|x|. That such an acceptor accepts a regular language follows from an argument similar to that of Shepherdson for deterministic acceptors [2].
The Analytical Chemistry of Drug Monitoring in Athletes
Authors: Bowers Larry D.
Published: June 2010

The detection and deterrence of the abuse of performance-enhancing drugs in sport are important to maintaining a level playing field among athletes and to decreasing the risk to athletes’ health. The World Anti-Doping Program consists of six documents, three of which play a role in analytical development: The World Anti-Doping Code, The List of Prohibited Substances and Methods, and The International Standard for Laboratories. Among the classes of prohibited substances, three have given rise to the most recent analytical developments in the field: anabolic agents; peptide and protein hormones; and methods to increase oxygen delivery to the tissues, including recombinant erythropoietin. Methods for anabolic agents, including designer steroids, have been enhanced through the use of liquid chromatography/tandem mass spectrometry and gas chromatography/combustion/isotope-ratio mass spectrometry. Protein and peptide identification and quantification have benefited from advances in liquid chromatography/tandem mass spectrometry. Incorporation of techniques such as flow cytometry and isoelectric focusing have supported the detection of blood doping.
Characterization of Nanomaterials by Physical Methods
Authors: Rao C.N.R. , Biswas Kanishka
Published: June 2010

Much progress in nanoscience and nanotechnology has been made in the past few years thanks to the increased availability of sophisticated physical methods to characterize nanomaterials. These techniques include electron microscopy and scanning probe microscopies, in addition to standard techniques such as X-ray and neutron diffraction, X-ray scattering, and various spectroscopies. Characterization of nanomaterials includes the determination not only of size and shape, but also of the atomic and electronic structures and other important properties. In this article we describe some of the important methods employed for characterization of nanostructures, describing a few case studies for illustrative purposes. These case studies include characterizations of Au, ReO3, and GaN nanocrystals; ZnO, Ni, and Co nanowires; inorganic and carbon nanotubes; and two-dimensional graphene.
Polymers for Drug Delivery Systems
Authors: Liechty William B. , Kryscio David R. , Slaughter Brandon V. , Peppas Nicholas A.
Published: June 2010

Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery.
Unit Operations of Tissue Development: Epithelial Folding
Authors: Zartman Jeremiah J. , Shvartsman Stanislav Y.
Published: June 2010

The development of multicellular organisms relies on a small set of construction techniques—assembly, sculpting, and folding—that are spatially and temporally regulated in a combinatorial manner to produce the diversity of tissues within the body. These basic processes are well conserved across tissue types and species at the level of both genes and mechanisms. Here we review the signaling, patterning, and biomechanical transformations that occur in two well-studied model systems of epithelial folding to illustrate both the complexity and modularity of tissue development. In particular, we discuss the possibility of a spatial code specifying morphogenesis. To decipher this code, engineers and scientists need to establish quantitative experimental systems and to develop models that address mechanisms at multiple levels of organization, from gene sequence to tissue biomechanics. In turn, quantitative models of embryogenesis can inspire novel methods for creating synthetic organs and treating degenerative tissue diseases.
Chemical Engineering Education: A Gallimaufry of Thoughts
Authors: Bird R. Byron
Published: June 2010

To discuss various facets of chemical engineering education, I proceed step by step through my own education and career. In this way, I touch on various points concerning the operation of the educational system that may be of interest to others.
Catalytic Conversion of Renewable Biomass Resources to Fuels and Chemicals
Authors: Serrano-Ruiz Juan Carlos , West Ryan M. , Dumesic James A.
Published: June 2010

Lignocellulosic biomass is renewable and cheap, and it has the potential to displace fossil fuels in the production of fuels and chemicals. Biomass-derived carboxylic acids are important compounds that can be used as platform molecules for the production of a variety of important chemicals on a large scale. Lactic acid, a prototypical biomass derivative, and levulinic acid, an important chemical feedstock produced by hydrolysis of waste cellulosic materials, can be upgraded using bifunctional catalysts (those containing metal and acid sites), which allows the integration of several transformations (e.g., oxygen removal and C–C coupling) in a single catalyst bed. This coupling between active sites is beneficial in that it reduces the complexity and cost of the biomass conversion processes. Deoxygenation of biomass derivatives is a requisite step for the production of fuels and chemicals, and strategies are proposed to minimize the consumption of hydrogen from an external source during this process.
Biofuels: Biomolecular Engineering Fundamentals and Advances
Authors: Li Han , Cann Anthony F. , Liao James C.
Published: June 2010

The biological production of fuels from renewable sources has been regarded as a feasible solution to the energy and environmental problems in the foreseeable future. Recently, the biofuel product spectrum has expanded from ethanol and fatty acid methyl esters (biodiesel) to other molecules, such as higher alcohols and alkanes, with more desirable fuel properties. In general, biosynthesis of these fuel molecules can be divided into two phases: carbon chain elongation and functional modification. In addition to natural fatty acid and isoprenoid chain elongation pathways, keto acid-based chain elongation followed by decarboxylation and reduction has been explored for higher alcohol production. Other issues such as metabolic balance, strain robustness, and industrial production process efficiency have also been addressed. These successes may provide both scientific insights into and practical applications toward the ultimate goal of sustainable fuel production.
Transcutaneous Immunization: An Overview of Advantages, Disease Targets, Vaccines, and Delivery Technologies
Authors: Karande Pankaj , Mitragotri Samir
Published: June 2010

Skin is an immunologically active tissue composed of specialized cells and agents that capture and process antigens to confer immune protection. Transcutaneous immunization takes advantage of the skin immune network by inducing a protective immune response against topically applied antigens. This mode of vaccination presents a novel and attractive approach for needle-free immunization that is safe, noninvasive, and overcomes many of the limitations associated with needle-based administrations. In this review we will discuss the developments in the field of transcutaneous immunization in the past decade with special emphasis on disease targets and vaccine delivery technologies. We will also briefly discuss the challenges that need to be overcome to translate early laboratory successes in transcutaneous immunization into the development of effective clinical prophylactics.
Dicarboxylate carrier-mediated glutathione transport is essential for reactive oxygen species homeostasis and normal respiration in rat brain mitochondria
Authors: Kamga Christelle K. , Zhang Shelley X. , Wang Yang
Published: June 2010

Glutathione transport into mitochondria is mediated by oxoglutarate (OGC) and dicarboxylate carrier (DIC) in the kidney and liver. However, transport mechanisms in brain mitochondria are unknown. We found that both carriers were expressed in the brain. Using cortical mitochondria incubated with physiological levels of glutathione, we found that butylmalonate, a DIC inhibitor, reduced mitochondrial glutathione to levels similar to those seen in mitochondria incubated without extramitochondrial glutathione (59% of control). In contrast, phenylsuccinate, an OGC inhibitor, had no effect (97% of control). Additional experiments with DIC and OGC short hairpin RNA in neuronal-like PC12 cells resulted in similar findings. Significantly, DIC inhibition resulted in increased reactive oxygen species (ROS) content in and H2O2release from mitochondria. It also led to decreased membrane potential, increased basal respiration rates, and decreased phosphorus-to-oxygen (P/O) ratios, especially when electron transport was initiated from complex I. Accordingly, we found that DIC inhibition impaired complex I activity, but not those for complexes II and III. This impairment was not associated with dislodgment of complex subunits. These results suggest that DIC is the main glutathione transporter in cortical mitochondria and that DIC-mediated glutathione transport is essential for these mitochondria to maintain ROS homeostasis and normal respiratory functions.
Epidermal growth factor reduces autophagy in intestinal epithelium and in the rat model of necrotizing enterocolitis
Authors: Maynard Andrew A. , Dvorak Katerina , Khailova Ludmila , Dobrenen Holly , Arganbright Kelly M. , Halpern Melissa D. , Kurundkar Ashish R. , Maheshwari Akhil , Dvorak Bohuslav
Published: June 2010

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Epidermal growth factor (EGF) is one of the most promising candidates in NEC prophylaxis. Autophagy regulates cell homeostasis, but uncontrolled activation of autophagy may lead to cellular injury. The aim was to evaluate the effects of EGF on intestinal autophagy in epithelial cells and in the rat NEC model and measure autophagy in NEC patients. Intestinal epithelial cells (IEC-6) and the rat NEC model were used to study the effect of EGF on intestinal autophagy. Protein levels of Beclin 1 and LC3II were measured in the intestinal epithelium in both in vivo and in vitro models. Ultrastructural changes in intestinal epithelium were studied by electron microscopy. Expression of Beclin 1, LC3II, and p62 protein was evaluated in biopsies from NEC patients. Autophagy was induced in IEC-6 cells and inhibited by adding EGF into the culture. In the rat NEC model, EGF treatment of NEC reduced expression of Beclin 1 and LC3II in ileal epithelium. Morphologically, typical signs of autophagy were observed in the epithelium of the NEC group, but not in the EGF group. A strong signal for Beclin 1 and LC3II was detected in the intestine from patients with NEC. Autophagy is activated in the intestinal epithelium of NEC patients and in the ileum of NEC rats. Supplementation of EGF blocks intestinal autophagy in both in vivo and in vitro conditions. Results from this study indicate that EGF-mediated protection against NEC injury is associated with regulation of intestinal autophagy.
Intravenous or luminal amino acids are insufficient to maintain pancreatic growth and digestive enzyme expression in the absence of intact dietary protein
Authors: Baumler Megan D. , Koopmann Matthew C. , Thomas Diana D. H. , Ney Denise M. , Groblewski Guy E.
Published: June 2010

We previously reported that rats receiving total parenteral nutrition (TPN) undergo significant pancreatic atrophy characterized by reduced total protein and digestive enzyme expression due to a lack of intestinal stimulation by nutrients (Baumler MD, Nelson DW, Ney DM, Groblewski GE. Am J Physiol Gastrointest Liver Physiol 292: G857–G866, 2007). Essentially identical results were recently reported in mice fed protein-free diets (Crozier SJ, D'Alecy LG, Ernst SA, Ginsburg LE, Williams JA. Gastroenterology 137: 1093–1101, 2009), provoking the question of whether reductions in pancreatic protein and digestive enzyme expression could be prevented by providing amino acids orally or by intravenous (IV) infusion while maintaining intestinal stimulation with fat and carbohydrate. Controlled studies were conducted in rats with IV catheters including orally fed/saline infusion or TPN-fed control rats compared with rats fed a protein-free diet, oral amino acid, or IV amino acid feeding, all with oral carbohydrate and fat. Interestingly, neither oral nor IV amino acids were sufficient to prevent the pancreatic atrophy seen for TPN controls or protein-free diets. Oral and IV amino acids partially attenuated the 75–90% reductions in pancreatic amylase and trypsinogen expression; however, values remained 50% lower than orally fed control rats. Lipase expression was more modestly reduced by a lack of dietary protein but did respond to IV amino acids. In comparison, chymotrypsinogen expression was induced nearly twofold in TPN animals but was not altered in other experimental groups compared with oral control animals. In contrast to pancreas, protein-free diets had no detectable effects on jejunal mucosal villus height, total mass, protein, DNA, or sucrase activity. These data underscore that, in the rat, intact dietary protein is essential in maintaining pancreatic growth and digestive enzyme adaptation but has surprisingly little effect on small intestinal mucosa.
Oncogenic engagement of the Met receptor is sufficient to evoke angiogenic, tumorigenic, and metastatic activities in rat intestinal epithelial cells
Authors: Bernier Jimmy , Chababi Walid , Pomerleau Véronique , Saucier Caroline
Published: June 2010

The deregulation of Met/hepatocyte growth factor (HGF) receptor tyrosine kinase signaling constitutes a common event in colorectal cancers. However, the physiopathological functions of such a deregulation remain poorly understood. In the present study, we investigated the role of the deregulation of Met receptor in the neoplastic transformation of intestinal epithelial cells. To do so, the normal, well-established and characterized rat intestinal epithelial IEC-6 cells were transduced with a retrovirus carrying the oncogenic constitutive active form of Met receptor, Tpr-Met. Herein, we show that compared with control IEC-6 cells, Tpr-Met-IEC-6 cells exhibit enhanced proliferation, loss of growth-contact inhibition, cell morphological alterations, actin cytoskeletal reorganization, loss of E-cadherin expression and anchorage-independent growth. Moreover, Tpr-Met-IEC-6 cells are conferred the capacity to produce the proangiogenic factor VEGF and to reduce the potent antiangiogenic factor thrombospondin-1. Of significance, Tpr-Met-IEC-6 cells are endowed with the ability to elicit angiogenic responses and to form tumors and metastases in vivo. Hence, our study demonstrates for the first time that the sole oncogenic engagement of Met receptor in normal intestinal epithelial cells is sufficient to induce a wide array of cancerous biological processes that are fundamental to the initiation and malignant progression of colorectal cancers.
Diabetic KK-Aymice are highly susceptible to oxidative hepatocellular damage induced by acetaminophen
Authors: Kon Kazuyoshi , Ikejima Kenichi , Okumura Kyoko , Arai Kumiko , Aoyama Tomonori , Watanabe Sumio
Published: June 2010

Despite pathophysiological similarities to alcoholic liver disease, susceptibility to acetaminophen hepatotoxicity in metabolic syndrome-related nonalcoholic steatohepatitis (NASH) has not been well elucidated. In this study, therefore, we investigated acetaminophen-induced liver injury in KK-Aymice, an animal model of metabolic syndrome. Twelve-week-old male KK-Ayand C57Bl/6 mice were injected intraperitoneally with 300 or 600 mg/kg acetaminophen, and euthanized 6 h later. Liver histology was assessed, and hepatic expression of 4-hydroxy-2-nonenal was detected by immunohistochemistry. Levels of reduced glutathione were determined spectrophotometrically. Phosphorylation of c-Jun NH2-terminal kinase (JNK) was analyzed by Western blotting. Hepatocytes were isolated from both strains by collagenase perfusion, and cell death and oxidative stress were measured fluorometrically by use of propidium iodide and 5-(and-6)-chloromethyl-2′7′-dichloro-dihydrofluorescein diacetate acetyl ester, respectively. Acetaminophen induced more severe necrosis and apoptosis of hepatocytes in KK-Aymice than in C57Bl/6 mice and significantly increased serum alanine aminotransferase levels in KK-Aymice. Acetaminophen-induction of 4-hydroxy-2-nonenal in the liver was potentiated, whereas the levels of reduced glutathione in liver were lower in KK-Aymice. Acetaminophen-induced phosphorylation of JNK in the liver was also enhanced in KK-Aymice. Exposure to 20 μM tert-butyl hydroperoxide did not kill hepatocytes isolated from C57Bl/6 mice but induced cell death and higher oxidative stress in hepatocytes from KK-Aymice. These results demonstrated that acetaminophen toxicity is increased in diabetic KK-Aymice mainly due to enhanced oxidative stress in hepatocytes, suggesting that metabolic syndrome-related steatohepatitis is an exacerbating factor for acetaminophen-induced liver injury.
MARCKS-related peptide modulates in vivo the secretion of airway Muc5ac
Authors: Foster W. Michael , Adler Kenneth B. , Crews Anne L. , Potts Erin N. , Fischer Bernard M. , Voynow Judith A.
Published: June 2010

In a mouse model of neutrophil elastase-induced bronchitis that exhibits goblet cell metaplasia and inflammation, we investigated the effects of intratracheal instillation of the MANS peptide, a peptide identical to the NH2 terminus of the myristoylated alanine-rich C kinase substrate (MARCKS) on mucin protein airway secretion, inflammation, and airway reactivity. To induce mucus cell metaplasia in the airways, male BALB/c mice were treated repetitively with the serine protease, neutrophil elastase, on days 1, 4, and 7. On day 11, when goblet cell metaplasia was fully developed and profiles of proinflammatory cytokines were maximal, the animals were exposed to aerosolized methacholine after intratracheal instillation of MANS or a missense control peptide (RNS). MANS, but not RNS, attenuated the methacholine-stimulated secretion of the major respiratory mucin protein, Muc5ac (50% reduction). Concurrently, elastase-induced proinflammatory cytokines typically recovered in bronchoalveolar lavage (BAL), including KC, IL-1β, IL-6, MCP-1, and TNFα, were reduced by the MANS peptide (mean levels decreased 50–60%). Secondary to the effects of MANS on mucin secretion and inflammation, mechanical lung function by forced oscillation technique was characterized with respect to airway reactivity in response to cumulative aerosol stimulation with serotonin. The MANS peptide was also found to effectively attenuate airway hyperresponsiveness to serotonin in this airway hypersecretory model. Collectively, these findings support the concept that even in airway epithelia remodeled with goblet cell metaplasia and in a state of mucin hypersecretion, exogenous attenuation of function of MARCKS protein via the MANS peptide decreases airway mucin secretion, inflammation, and hyperreactivity.
The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito
Authors: Schepel Stephen A. , Fox Andrew J. , Miyauchi Jeremy T. , Sou Tiffany , Yang Jason D. , Lau Kenneth , Blum Austin W. , Nicholson Linda K. , Tiburcy Felix , Nachman Ronald J. , Piermarini Peter M. , Beyenbach Klaus W.
Published: June 2010

In the past, we have used the kinins of the cockroach Leucophaea (the leucokinins) to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti . Now using the kinins of Aedes (the aedeskinins), we have found that in isolated Aedes Malpighian tubules all three aedeskinins (1 μM) significantly 1) increased the rate of fluid secretion (V̇S), 2) hyperpolarized the basolateral membrane voltage (Vbl), and 3) decreased the input resistance (Rin) of principal cells, consistent with the known increase in the Cl−conductance of the paracellular pathway in Aedes Malpighian tubules. Aedeskinin-III, studied in further detail, significantly increased V̇Swith an EC50of 1.5 × 10−8M. In parallel, the Na+concentration in secreted fluid significantly decreased, and the K+concentration significantly increased. The concentration of Cl−remained unchanged. While the three aedeskinins triggered effects on Vbl, Rin, and V̇S, synthetic kinin analogs, which contain modifications of the COOH-terminal amide pentapeptide core sequence critical for biological activity, displayed variable effects. For example, kinin analog 1578 significantly stimulated V̇Sbut had no effect on Vbland Rin, whereas kinin analog 1708 had no effect on V̇Sbut significantly affected Vbland Rin. These observations suggest separate signaling pathways activated by kinins. One triggers the electrophysiological response, and the other triggers fluid secretion. It remains to be determined whether the two signaling pathways emanate from a single kinin receptor via agonist-directed signaling or from a differentially glycosylated receptor. Occasionally, Malpighian tubules did not exhibit a detectable response to natural and synthetic kinins. Hypothetically, the expression of the kinin receptor may depend on developmental, nutritional, and/or reproductive signals.
Reduced fasting-induced activation of hypothalamic arcuate neurons is associated with hyperleptinemia and increased leptin sensitivity in obese mice
Authors: Becskei Csilla , Lutz Thomas A. , Riediger Thomas
Published: June 2010

Fasting increases c-Fos expression in neuropeptide Y (NPY) neurons of the hypothalamic arcuate nucleus (ARC) in lean, but not in hyperleptinemic mice with late-onset obesity (LOO). Although obesity is associated with leptin resistance, we hypothesized that under fasting conditions, leptin sensitivity might be restored and that hyperleptinemia may counteract the neuronal response to fasting. We investigated whether the reduced fasting response of ARC neurons in LOO is paralleled by an increase in leptin sensitivity, as measured by leptin-induced STAT-3 phosphorylation. To assess leptin's role in the modulation of the fasting-induced ARC activation, we investigated c-Fos responses and hormone and metabolite levels in hyperleptinemic diet-induced obese (DIO) and in leptin-deficient ob/ob mice. Leptin induced a stronger STAT-3 phosphorylation in fasted LOO and lean mice than in ad libitum-fed animals. Similar to LOO, hyperleptinemic DIO mice showed no c-Fos response after fasting, while ob/ob mice showed a stronger response than lean control mice. Mimicking hyperleptinemia by repeated leptin injections in lean mice during fasting attenuated the fasting-induced c-Fos expression. Our findings indicate that high leptin levels prevent the fasting-induced activation of ARC neurons in mice. Moreover, leptin sensitivity is dynamic in obese subjects and depends on the feeding status. During short-term increases in leptin sensitivity, e.g., during fasting, leptin signaling appears to be effective, even in hyperleptinemic obesity. As reflected by the blockade of the fasting-induced ARC activation, fasting seems to interfere with the responsiveness of the ARC to signals related to the status of energy intake.
Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states
Authors: Hasek Barbara E. , Stewart Laura K. , Henagan Tara M. , Boudreau Anik , Lenard Natalie R. , Black Corey , Shin Jeho , Huypens Peter , Malloy Virginia L. , Plaisance Eric P. , Krajcik Rozlyn A. , Orentreich Norman , Gettys Thomas W.
Published: June 2010

Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0°C vs. 1.5°C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ ∼0.75) vs. controls (RQ ∼0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.
Effects of exercise training on airway responsiveness and airway cells in healthy subjects
Authors: Scichilone Nicola , Morici Giuseppe , Zangla Daniele , Chimenti Laura , Davì Eva , Reitano Simona , Paternò Alessandra , Santagata Roberta , Togias Alkis , Bellia Vincenzo , Bonsignore Maria Rosaria
Published: June 2010

Airway responsiveness to methacholine (Mch) in the absence of deep inspirations (DIs) is lower in athletes compared with sedentary individuals. In this prospective study, we tested the hypothesis that a training exercise program reduces the bronchoconstrictive effect of Mch. Ten healthy sedentary subjects (M/F: 3/7; mean ± SD age: 22 ± 3 yr) entered a 10-wk indoor rowing exercise program on rowing ergometer and underwent Mch bronchoprovocation in the absence of DIs at baseline, at weeks 5 and 10, as well as 4–6 wk after the training program was completed. Exercise-induced changes on airway cells and markers of airway inflammation were also assessed by sputum induction and venous blood samples. Mean power output during the 1,000 m test was 169 ± 49 W/stroke at baseline, 174 ± 49 W/stroke at 5 wk, and 200 ± 60 W/stroke at 10 wk of training ( P < 0.05). The median Mch dose used at baseline was 50 mg/ml (range 25–75 mg/ml) and remained constant per study design. At the pretraining evaluation, the percent reduction in the primary outcome, the inspiratory vital capacity (IVC) after inhalation of Mch in the absence of DIs was 31 ± 13%; at week 5, the Mch-induced reduction in IVC was 22 ± 19%, P = 0.01, and it further decreased to 15 ± 11% at week 10 ( P = 0.0008). The percent fall in IVC 4–6 wk after the end of training was 15 ± 11% ( P = 0.87 vs. end of training). Changes in airway cells were not associated with changes in airway responsiveness. Our data show that a course of exercise training can attenuate airway responsiveness against Mch inhaled in the absence of DIs in healthy subjects and suggest that a sedentary lifestyle may favor development of airways hyperresponsiveness.
A Critique of the Critical Cochlea: Hopf—a Bifurcation—Is Better Than None
Authors: Hudspeth A. J. , Jülicher Frank , Martin Pascal
Published: June 2010

The sense of hearing achieves its striking sensitivity, frequency selectivity, and dynamic range through an active process mediated by the inner ear's mechanoreceptive hair cells. Although the active process renders hearing highly nonlinear and produces a wealth of complex behaviors, these various characteristics may be understood as consequences of a simple phenomenon: the Hopf bifurcation. Any critical oscillator operating near this dynamic instability manifests the properties demonstrated for hearing: amplification with a specific form of compressive nonlinearity and frequency tuning whose sharpness depends on the degree of amplification. Critical oscillation also explains spontaneous otoacoustic emissions as well as the spectrum and level dependence of the ear's distortion products. Although this has not been realized, several valuable theories of cochlear function have achieved their success by incorporating critical oscillators.
Paired Associative Stimulation Induces Change in Presynaptic Inhibition of Ia Terminals in Wrist Flexors in Humans
Authors: Lamy Jean-Charles , Russmann Heike , Shamim Ejaz A. , Meunier Sabine , Hallett Mark
Published: June 2010

Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments ( experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1and D2 inhibitions methods; experiment 2) and postactivation depression ( experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals.
A Comparison of Sleeplike Slow Oscillations in the Hippocampus Under Ketamine and Urethane Anesthesia
Authors: Sharma Arjun V. , Wolansky Trish , Dickson Clayton T.
Published: June 2010

During sleep and anesthesia, a slow (≤1 Hz) synchronized rhythmic fluctuation of the network activity in the neocortex (nCTX) is prominent. This rhythm, called the slow oscillation (SO), corresponds to sequences of neuronal activity and inactivity (UP and DOWN states) in local and extended networks. Recently, this network pattern has also been described in the hippocampus (HPC) and, interestingly, it shows a dynamic correlation with ongoing SO in the nCTX. However, because of its transient nature during both sleep and urethane anesthesia, studying the SO in the HPC is difficult. Ketamine anesthesia is known to induce a uniform and continuous SO state in the nCTX, but its effects on HPC activity and HPC–nCTX interplay are unknown. Using multisite local field potential recordings, we investigated the effects of ketamine anesthesia on HPC activity and its relation to concurrent nCTX activity. We directly compared the spectral content and spatial distribution of laminar potentials and current source density (CSD) under ketamine to urethane anesthesia. Ketamine evoked stable bouts of SO in the HPC that had a peak frequency of 1.77 ± 0.08 Hz, slightly higher than that of urethane: 1.17 ± 0.07 Hz. Laminar voltage and CSD profiles of SO were highly correlated across ketamine and urethane anesthesia, although a higher degree of HPC–nCTX coherence at SO frequencies appeared under ketamine as opposed to urethane. In addition, activity in the gamma bandwidth (30–40 Hz) made up 4.7% of the power spectrum under ketamine, but accounted for only 2.0% of the power spectrum in urethane. Although some differences exist, the SO under ketamine anesthesia appears highly similar to that under urethane.
Acute Tension Pneumothorax Following Cardiac Herniation after Pneumonectomy
Authors: Steinmann Daniel , Rohr Eva , Kirschbaum Andreas
Published: June 2010

A tension pneumothorax is one of the main causes of cardiac arrest in the initial postoperative period after thoracic surgery. Tension pneumothorax and cardiac herniation must be taken into account in hemodynamically unstable patients after pneumonectomy. We report an unusual case of successful treatment of acute tension pneumothorax following cardiac herniation and intrathoracic bleeding after pneumonectomy.
Mechanical and Fracture Behaviors of Elastomer‐Rich Thermoplastic Polyolefin/SiCp Nanocomposites
Authors: Liao Cheng Zhu , Tjong Sie Chin
Published: June 2010

Elastomer‐rich thermoplastic polyolefin (ETPO) resin containing 70 wt% maleated styrene‐ethylene‐butadiene‐styrene (SEBS‐g‐MA) and 30 wt% polypropylene and its nanocomposites filled with 1–5 wt% SiC nanoparticles (SiCp) were fabricated using extrusion and injection molding techniques. The mechanical and thermal behaviors of ETPO and its nanocomposites were investigated. Tensile measurements showed that the SiCp additions lead to reductions in both tensile stiffness and strength of ETPO. However, Izod impact and EWF measurements indicated that the impact strength and fracture toughness of ETPO improve substantially with increasing SiCp content. This demonstrated that SiC nanoparticles toughen the ETPO blend effectively. Furthermore, SiCp additions were found to improve the thermal resistance of ETPO blend considerably.
Role of Reaction and Factors of Carbon Nanotubes Growth in Chemical Vapour Decomposition Process Using Methane—A Highlight
Authors: VM Sivakumar , Mohamed Abdul Rahman , Abdullah Ahmad Zuhairi , Chai Siang-Piao
Published: June 2010

One of the remarkable achievements in the field of nanotechnology is Carbon Nanotubes (CNT) synthesis. Since their discovery in 1991 by Iijima, CNTs have attracted much attention across the world. The CNTs are broadly classified into single‐walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs). The most distinguished features of SWNTs and MWNTs are their electrical, mechanical, chemical, and electronic properties which in turn find their potential applications in almost all fields of science, engineering, and technology. Based on the previous research studies to till date, chemical vapour deposition (CVD) is considered to be the simplest method with high energy efficiency and precise control of reaction parameters compared to other different methods for synthesizing CNTs. Since production of CNTs is becoming the most important factor in the applications point of view, most industries today are opting for the CVD technique.
This paper reviewed the synthesis of CNT by CVD especially focusing on methane CVD. Various parameters influencing the reaction and CNT growth were also discussed. A detailed review was made over the different types of CVD process, influence of metal, supports, metal‐support interaction, effect of promoters, and reaction parameters role in CNTs growth.
Synthesis of High‐Yield Gold Nanoplates: Fast Growth Assistant with Binary Surfactants
Authors: Wang Changshun , Kan Caixia , Zhu Jiejun , Zeng Xiaoling , Wang Xiangfu , Li Hongchen , Shi Daning
Published: June 2010

A novel and simple chemical method was developed to fastly synthesize Au nanoplates with size of micrometers and tens of nanometers in thickness. The synthesis was carried out within 30 minutes by thermal reduction of precursors (HAuCl4) in the presence of binary surfactants Poly(vinylpyrrolidone) (PVP) and cetyltrimethylammonium bromide (CTAB) in ethylene glycol (EG) solution. The presence and concentration of PVP and CTAB in the growth solution play important roles in the fast formation of Au nanoplates. The obtained Au nanoplates exhibit strong surface plasmon absorption in the near‐infrared region (NIR), displaying a considerable dependence on the shape and size. Characterizations by Transmission electron microscope and X‐ray diffraction indicated that the nanoplates are single crystals with (111) planes as two basal surfaces. Explanations for the nuclei formation and crystal growth behind anisotropic Au nanoplates were proposed.
Phase I Dose Finding Studies of Obatoclax (GX15-070), a Small Molecule Pan-BCL-2 Family Antagonist, in Patients with Advanced Solid Tumors or Lymphoma
Authors: Hwang Jimmy J. , Kuruvilla John , Mendelson David , Pishvaian Michael J. , Deeken J.F. , Siu Lillian L. , Berger Mark S. , Viallet Jean , Marshall John L.
Published: June 2010

Purpose: Two phase I, single-agent studies were conducted to determine the dose and regimen of obatoclax, an antagonist of all BCL-2 antiapoptotic proteins, for evaluation in phase II trials. The two studies, GX001 and GX005, evaluated the safety and tolerability of weekly 1-hour and 3-hour infusions of obatoclax, respectively.

Experimental Design: Eligible patients in both studies were adults with solid tumor or lymphoma and performance status 0-1 for whom standard therapies were not appropriate. In the GX001 study an accelerated dose titration design was initially used with subsequent cohorts of three to six patients with 40% dose increments between levels. In the GX005 study three to six patients entered at each dose level with 40% dose increments between levels.

Results: Thirty-five patients were enrolled in studies GX001 (n = 8) and GX005 (n = 27). Clinically significant central nervous system (CNS) toxicity was observed using the 1-hour infusion schedule. The obatoclax maximum tolerated dose (MTD) in GX001 was 1.25 mg/m2 due to these infusional CNS events. The 3-hour infusion schedule studied in GX005 had improved tolerability, and the obatoclax MTD was 20 mg/m2. One patient in GX005 with relapsed non-Hodgkin's lymphoma achieved partial response of 2 months' duration, and one patient with relapsed non-Hodgkin's lymphoma had stable disease for 18 months.

Conclusions: The 1-hour infusion schedule of obatoclax was associated with neuropsychiatric dose-limiting toxicities at relatively low doses (MTD, 1.25 mg/m2). The 3-hour i.v. infusion of obatoclax administered once weekly to patients with solid tumors was better tolerated (MTD, 20 mg/m2), and evidence of clinical activity was observed. Clin Cancer Res; 16(15); 4038–45. ©2010 AACR.
Maladies émergentes transmises par les tiques
Authors: Mutz Ingomar
Published: June 2010

Les infections transmises par les tiques surviennent dans le monde entier et sont bien connues depuis plus d’un siècle. Certaines d’entre elles sont très courantes alors que d’autres sont extrêmement rares. Les techniques modernes de génétique moléculaire (dont une plus grande disponibilité de la réaction en chaîne par polymérase (PCR) (de l’anglais polymerase chain reaction) ont permis la découverte et la classification de nouveaux pathogènes, notamment de l’ordre des rickettsies. Le présent article s’intéresse aux agents viraux, bactériens et protozoaires responsables de maladies chez l’homme. La plupart des morsures de tiques et donc des maladies qui en résultent, surviennent durant la période la plus chaude de l’année. Les réservoirs naturels de ces maladies présentent une grande variation géographique. L’origine d’une morsure de tique n’est pas fiable car elle passe souvent inaperçue. Les maladies transmises par les tiques les plus courantes sont la borréliose de Lyme et l’encéphalite due à un flavivirus. Les infections virales se manifestent le plus souvent par les signes neurologiques de l’encéphalite tandis que les infections causées par les rickettsies se caractérisent par des poussées de fièvre (biphasique), des symptômes systémiques liés à une infection et une éruption cutanée avec présence de pétéchies. Certaines maladies transmises par les tiques peuvent être prévenues par la vaccination, telle que l’encéphalite. Dès les premiers signes cliniques, les infections non virales devraient être traitées très tôt par des antibiotiques afin d’obtenir les meilleurs résultats. Les maladies transmises par les tiques peuvent être fatales. Les taux de mortalité sont variables; ils dépendent de la virulence du pathogène, de l’absence de recours aux mesures préventives ou d’un retard dans le diagnostique et le traitement.
Co-Morbidity in COPD: The Effects of Cardiovascular Drug Therapies
Authors: Suissa Samy
Published: June 2010

Cardiovascular disease is a major co-morbidity in chronic obstructive pulmonary disease (COPD) patients and is a predictor of all-cause mortality. This paper reviews the study design and data analyses of observational studies of cardiovascular drug effects in patients with COPD and evaluates the potential for bias on the validity of their findings. Three recent observational studies of statin use in the setting of COPD show surprisingly high efficacy results which, by their magnitude, demand closer analysis. Such analysis reveals that immortal time and immeasurable time biases likely accounted for dramatic findings of reduced mortality with aggressive treatment for cardiovascular disease. After removing these sources of bias, the effects are mitigated or may disappear entirely. Investigation of methods and results in the statin studies reviewed in this article reveals significant bias that has skewed the results of these early studies. Correcting these methodological flaws with proper statistical analysis may attenuate or even eliminate these apparent benefits.
Case Report of Acute Aortic Dissection during Treatment with Capecitabine for a Late Recurrence of Breast Cancer
Authors: Sclafani Francesco , Carnaghi Carlo , Colombo Piergiuseppe , Bozzarelli Silvia , De Vincenzo Fabio , Rimassa Lorenza , Giorgetti Pier Luigi , Santoro Armando
Published: June 2010

Background: Cardiovascular toxicity is amongst the most clinically relevant side effects of antitumoral treatments. Moreover, the potential association between anticancer drugs and vascular damage is well known since chemotherapeutics, such as fluoropyrimidines, were introduced into clinical practice. Case: A 77-year-old woman treated with capecitabine for late recurrence of breast cancer developed life-threatening toxicity shortly after receiving the second cycle of therapy. Although a history of cardiovascular disease was not reported, the imaging procedures performed upon admission to the hospital showed the unpredicted appearance of an acute aortic dissection of the abdominal aorta. Conclusion: The absence of risk factors in the woman’s history, timing of the dissection and associated life-threatening toxicities that developed, as well as the pathological findings are consistent with the vascular toxicity described in experimental models for fluoropyrimidines. Combined with all these are circumstances supporting a probable cause-effect correlation between the chemotherapy and the dramatic vascular events that occurred.
Anti-Tumour Activity of Fotemustine and Protons in Combination with Bevacizumab
Authors: Korićanac Lela B. , Žakula Jelena J. , Petrović Ivan M. , Valastro Lucia M. , Cirrone Giuseppe A.P. , Cuttone Giacomo , Ristić-Fira Aleksandra M.
Published: June 2010

Background: Metastatic melanoma is one of the most aggressive tumours and is also very resistant to current therapeutic approaches. The aim of this investigation was the in vitro study of the anti-proliferative effects of fotemustine (FM; 100 and 250 µM), bevacizumab (5 µg/ml) and proton irradiation (12 and 16 Gy) on resistant HTB140 human melanoma cells. Methods: Viability was estimated by sulphorhodamine B assay, while cell proliferation was analyzed by 5-bromo-2-deoxyuridine assay. Cell cycle distribution and apoptosis were examined using flow cytometry. Results: Cell viability and proliferation were reduced after all applied treatments. The level of apoptosis significantly increased after treatment with FM, protons or a combination of all agents, while the apoptotic index ranged from 1.2 to 9.2. Proton irradiation, as well as combined treatment with bevacizumab and protons or 100 µM FM, bevacizumab and protons, have reduced melanoma cell proliferation through the induction of G1 phase arrest. Single FM (250 µM) or bevacizumab treatment and their combination, as well as the joint application of these 2 agents with protons, reduced cell proliferation and provoked G2 phase accumulation. Conclusion: The analyzed treatments reduced cell viability and proliferation, triggered G1 or G2 cell cycle phase accumulation and stimulated apoptotic cell death.
Type 2 Diabetes in Octogenarians Is Associated with Decreased Low Molecular Weight Adiponectin
Authors: Graessler Juergen , Gruber Matthias , Radke Rolf-Bernd , Kopprasch Steffi , Schwarz Peter E.H. , Kamke Wolfram , Bornstein Stefan R. , Fischer Sabine
Published: June 2010

Background: Adiponectin circulates in the blood in three different multimer isoforms, of which the high molecular weight form (HMW) is presumed to mediate insulin sensitivity. We examined whether adiponectin oligomer distribution is associated with aging and type 2 diabetes (T2D) in octogenarians without characteristic features of metabolic syndrome. Methods: The study included 154 octogenarians (58 men, 96 women), 24 normoglycemic middle-aged controls (11 men, 13 women; mean age 44 years), and 33 middle-aged individuals (14 men, 19 women; mean age 55 years) with T2D. Based on oral glucose tolerance test 62 octogenarians had normal, 63 impaired glucose tolerance, and 29 octogenarians had newly detected T2D. Serum adiponectin multimer isoforms were measured after overnight fast by enzyme-linked immunosorbent assays. Results:Compared to the normoglycemic middle-aged control group, male normoglycemic octogenarians revealed significantly higher total adiponectin and all adiponectin isoforms. The same was true for females with the exception of low molecular weight (LMW) adiponectin, which was not statistically higher in octogenarians. Male and female octogenarians with T2D had significantly higher levels of total, HMW, and middle molecular weight (MMW) adiponectin, but not LMW adiponectin, than middle-aged individuals with T2D. Female, but not male, octogenarians revealed significantly lower total adiponectin than normoglycemic octogenarians. Compared with normoglycemic octogenarians, male and female octogenarians with T2D were characterized by significantly lower LMW adiponectin. In male and female octogenarians, total adiponectin and all multimer isoforms were directly correlated with HDL cholesterol. LMW adiponectin in octogenarians of both sexes was inversely correlated with glucose level at 2-hour oral glucose tolerance test. Conclusions: Serum levels of total adiponectin as well as its HMW and MMW isoforms were significantly higher in octogenarians with normoglycemia or T2D than in corresponding middle-aged control groups. In male and female octogenarians without metabolic syndrome, T2D was associated with lower LMW adiponectin, while the HMW and MMW isoforms were not statistically different.