bluuebunny/crossref_metadata_2025 huggingface dataset:
The maternal legacy of Basques in northern navarre: New insights into the mitochondrial DNA diversity of the Franco‐Cantabrian area
Authors: Cardoso Sergio , Alfonso‐Sánchez Miguel A. , Valverde Laura , Odriozola Adrian , Pérez‐Miranda Ana M. , Peña José A. , de Pancorbo Marian M.
Published: May 2011

Autochthonous Basques are thought to be a trace from the human population contraction that occurred during the Last Glacial Maximum, based mainly on the salient frequencies and coalescence ages registered for haplogroups V, H1, and H3 of mitochondrial DNA in current Basque populations. However, variability of the maternal lineages still remains relatively unexplored in an important fraction of the Iberian Basque community. In this study, mitochondrial DNA diversity in Navarre (North Spain) was addressed for the first time. To that end, HVS‐I and HVS‐II sequences from 110 individuals were examined to identify the most relevant lineages, including analysis of coding region SNPs for the refinement of haplogroup assignment. We found a prominent frequency of subhaplogroup J1c (11.8%) in Navarre, coinciding with previous studies on Basques. Subhaplogroup H2a5, a putative autochthonous Basque lineage, was also observed in Navarre, pointing to a common origin of current Basque geographical groups. In contrast to other Basque subpopulations, comparative analyses at Iberian and European scales revealed a relevant frequency of subhaplogroup H3 (10.9%) and a frequency peak for U5b (15.5%) in Navarre. Furthermore, we observed low frequencies for maternal lineages HV0 and H1 in Navarre relative to other northern Iberian populations. All these findings might be indicative of intense genetic drift episodes generated by population fragmentation in the area of the Franco‐Cantabrian refuge until recent times, which could have promoted genetic microdifferentiation between the different Basque subpopulations. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Juvenile hormone changes associated with diapause induction, maintenance, and termination in the beet webworm, Loxostege sticticalis (lepidoptera: pyralidae)
Authors: Jiang Xingfu , Huang Shaohong , Luo Lizhi
Published: May 2011

At 22°C and under a long‐day photoperiod of L:D 16:8, all the last fifth instar Loxostege sticticalis larvae undergo prepupal stage and pupate without diapause. Under a short‐day photoperiod of L:D 12:12, in contrast, they all enter diapause with approximately 36 days diapause maintenance and then terminate diapause spontaneously, although only 44% of the larvae terminated diapause successfully. Changes in hemolymph juvenile hormone (JH I) titers of diapause‐destined larvae across diapause induction, maintenance and termination were examined using HPLC, and were compared with those of non‐diapause‐destined larvae from the fifth instar through pupation. JH I titer of the earliest fifth instar diapause‐destined larvae remained at a high level with a peak of 220.4 ng/ml, though it decreased continuously to a minimum of 69.0 ng/ml on day 5 in the fifth instar when the larvae stopped feeding to enter diapause. During the diapause maintenance, JH I titer of the mature larvae increased significantly and maintained a high level until day 31 in prepupae. JH I titer declined and fluctuated at low level from 5 days before pupation. In contrast, JH I titer of both the fifth instar non‐diapause‐destined larvae and prepupae remained and fluctuated at low level consistently, as well as decreased before pupation. These results indicate that diapause induction and maintenance in this species might be a consequence of high JH, whereas diapause termination can be attributed to low JH titer, which was in agreement with the hormonal regulation observed in many other larval‐diapausing insects. © 2011 Wiley Periodicals, Inc.
Feasibility of complex coronary and peripheral interventions by trans‐radial approach using large sheaths
Authors: Coroleu Santiago F. , Burzotta Francesco , Fernández‐Gómez Carlos , Tommasino Antonella , Giammarinaro Maura , Coluccia Valentina , Noi Paola Di , Schiavoni Giovanni , Trani Carlo
Published: May 2011

Background: Trans‐radial approach (TRA) reduces vascular access‐site complications but has some technical limitations. Usually, TRA procedures are performed using 5 Fr or 6 Fr sheaths, whereas complex interventions requiring larger sheaths are approached by trans‐femoral access. Methods: During 4 years, at two Institutions with high TRA use, we have attempted to perform selected complex coronary or peripheral interventions by TRA using sheaths larger than 6 Fr. Clinical and procedural data were prospectively collected. Attempt to place a 7 Fr or 8 Fr sheath (according to the planned strategy of the procedure) was performed after 5–6 Fr sheath insertion, administration of intra‐arterial nitrates and radial artery angiography. Late (>3 months) patency of the radial artery was checked (by angiography in the case of repeated procedures or by palpation + reverse Allen test). Results: We collected 60 patients in which TRA large sheath insertion was attempted. The large sheath (87% 7 Fr, 13% 8 Fr) was successfully placed in all cases. Most of the procedures were complex coronary interventions (bifurcated or highly thrombotic or calcific chronic total occlusive lesions), whereas 8.3% were carotid interventions. Procedural success rate was 98.3% (1 failure to reopen a chronic total occlusion). No access‐site related complication occurred. In 57 (95%) patients, late radial artery patency was assessed and showed patency in 90% of the cases, the remaining patients having asymptomatic collateralized occlusion. Conclusions: In selected patients, complex percutaneous interventions requiring 7–8 Fr sheaths can be successfully performed by RA approach without access‐site clinical consequences. © 2011 Wiley Periodicals, Inc.
Perioperative rupture of the LIMA graft leading to cardiogenic shock, emergency angiography, and stenting with a polytetrafluoroethylene‐covered stent
Authors: Yeow Wen‐Loong , Edwards Mark , Yong Gerald
Published: May 2011

A 58‐year‐old man underwent an elective coronary bypass graft for severe four‐vessel stenosis. Cardiogenic shock developed just after coronary bypass grafting with a left internal mammary artery (LIMA) to left anterior descending (LAD) artery and superficial venous graft to 1st and 2nd obtuse marginal (OM1/OM2) arteries the posterior descending artery (PDA) was too small to graft. Despite significant inotropes and an intra‐aortic balloon pump, the patient deteriorated in intensive care unit with cardiogenic shock and ventricular arrhythmia. Urgent coronary angiography revealed a rupture or torn LIMA graft with extravasation of contrast into the left pleural cavity. There was no distal LIMA to LAD flow probably due to graft thrombosis. Revascularisation was performed on the severe ostial native LAD stenosis with a drug eluting stent. The rupture graft was then stented with a polytetrafluoroethylene‐covered stent, which stopped the bleeding, and latter, led to total graft thrombosis. The patient improved significantly and supportive inotropes could be weaned down. At 11 month follow‐up, the patient had mild left ventricular dysfunction, widely patent ostial LAD stent and thrombosed LIMA graft. © 2011 Wiley Periodicals, Inc.
A single center experience with same‐day transradial‐PCI patients: A contrast with published guidelines
Authors: Gilchrist Ian C. , Rhodes Denise A. , Zimmerman Helen E.
Published: May 2011

Objectives: Our goal was to compare recently published Consensus Statement from the SCAI/ACC on appropriateness for same‐day PCI with patient characteristics from a real‐world same‐day PCI experience in the United States. Background: Recent practice statement published by the SCAI /ACC in 2009 describes patients suitable for outpatient PCI procedures. Whether this practice statement reflects actual real‐world practice in the setting of advances in transradial catheterization needs further exploration. Methods: Pre‐existing, deidentified, quality assurance data from 100 sequential patients undergoing transradial PCI, and same‐day discharge were compared with criteria in SCAI/ACC statement on outpatient PCI. Each had been identified post‐PCI as uncomplicated and therefore eligible for same day discharged. Specific attention was placed on whether the patients carried any exclusion to same‐day discharge. Results: One hundred six procedures were recorded in 100 patients including 11 women and 89 men, median age 62 (55,71) years all with stable ischemia. Early follow up was done for medication compliance. None were readmitted nor had post‐PCI complications. Only 15% met appropriateness criteria for same‐day discharge. Older age, distance from the hospital, greater than simple PCI, and the need for specific antiplatelet therapy represented the dominant contraindications to discharge. Conclusions: Using transradial approaches and structured early follow up by advance practice nurses, same‐day discharge can be accomplished successfully in a broad range of patients outside of those suggested by the SCAI/ACC 2009 Consensus Document. Confirmation of these results could result in shorter hospitalizations for US patients and align advances in catheterization technology to optimize heath care delivery. © 2011 Wiley Periodicals, Inc.
Hybrid therapy for interrupted aortic arch with aortopulmonary window in a low birth weight infant
Authors: Lin Ming‐Chih , Wang Chung‐Chi , Fu Yun‐Ching
Published: May 2011

Interrupted aortic arch (IAA) is rarely associated with aortopulmonary window. Single‐stage total correction is the preferred therapeutic option. When total correction is unfeasible, staged repair could be the therapeutic choice. Here, we presented a low birth weight infant who underwent bilateral pulmonary arteries banding and stenting ductus arteriosus by hybrid procedure. Hybrid procedure avoids long‐term central line insertion and guarantees ductal flow. It also avoids the side effects from prostaglandin infusion. © 2011 Wiley Periodicals, Inc.
Quantifying the Electronic Effects of Carbohydrate Hydroxy Groups by Using Aminosugar Models
Authors: Pedersen Christian M. , Olsen Jacob , Brka Azra B. , Bols Mikael
Published: May 2011

Methyl amino‐deoxy‐glycosides with α‐ and β‐gluco, α‐galacto, or α‐manno stereochemistry with the amino functionality in each of the four possible non‐anomeric positions have been synthesized and their pKa values determined by titration. These model compounds were chosen because they are the amino derivatives of the most common glycosyl acceptors. From this study it was possible to evaluate the electron density at each of the given positions in the carbohydrate and compare them. Some general trends were observed: The basicity of the amino groups decreases in the order 6‐NH2>3‐NH2>2‐NH2>4‐NH2 (referring to the position). The basicity of a of an amino‐deoxy‐sugar generally increases when one or more substituents on the sugar ring are axial. The basicity decreases when the amine is antiperiplanar to an oxygen atom. These findings are in agreement with the observations obtained from glycosylation chemistry and the regioselective protection of sugars.
Multistep Oligometal Complexation of the Macrocyclic Tris(N2O2) Hexaoxime Ligand
Authors: Akine Shigehisa , Sunaga Shuichi , Nabeshima Tatsuya
Published: May 2011

A macrocyclic oxime ligand H6L, which has an O6 cavity surrounded by three N2O2 chelate sites, was synthesized and the multistep oligometal complexation behavior was investigated. Upon complexation with zinc(II), the H6L ligand afforded two kinds of hexanuclear complexes, L2Zn6 then LZn6. Each of the complexation steps proceeded highly efficiently. In the latter complex, a Zn3(μ3‐OH) unit was incorporated into the trimetalated ligand, LZn3. The integrated N2O2 chelate coordination sites provide a unique environment for a homometallic complex. The different nature of the peripheral N2O2 sites and the central O6 site is particularly suitable for the selective formation of heterometallic complexes. Complexation with the zinc(II) ion in the presence of alkaline earth (Ca and Ba) or rare earth (La, Eu, Lu) metal ions afforded the heterotetranuclear complexes LZn3M (M=Ca, Ba, La, Eu, Lu), in which zinc(II) and ion M occupied the N2O2 and O6 sites, respectively. Titration experiments showed that the heterometallic complexes LZn3Ca and LZn3Ba were converted into the homometallic complex LZn6 whereas LZn3La was not. As a result, the binding affinity in the central O6 site of the LZn3 unit is apparently in the order of Ca2+, Ba2+<Zn3(μ3‐OH)<La3+. This difference in the affinities of metal ions as well as the ionic sizes makes the novel conversion efficient, particularly in the case of the three‐step conversion from H6L to H2LZn2Ba, LZn3Ba, then LZn6.
Trafficking of drug candidates relevant for sports drug testing: Detection of non‐approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet
Authors: Thevis Mario , Geyer Hans , Thomas Andreas , Schänzer Wilhelm
Published: May 2011

Identifying the use of non‐approved drugs by cheating athletes has been a great challenge for doping control laboratories. This is due to the additional complexities associated with identifying relatively unknown and uncharacterized compounds and their metabolites as opposed to known and well‐studied therapeutics. In 2010, the prohibited drug candidates and gene doping substances AICAR and GW1516, together with the selective androgen receptor modulator (SARM) MK‐2866 were obtained by the Cologne Doping Control Laboratory from Internet suppliers and their structure, quantity, and formulation elucidated. All three compounds proved authentic as determined by liquid chromatography—high resolution/high accuracy (tandem) mass spectrometry and comparison to reference material. While AICAR was provided as a colourless powder in 100 mg aliquots, GW1516 was obtained as an orange/yellow suspension in water/glycerol (150 mg/ml), and MK‐2866 (25 mg/ml) was shipped dissolved in polyethylene glycol (PEG) 300. In all cases, the quantified amounts were considerably lower than indicated on the label. The substances were delivered via courier, with packaging identifying them as containing ‘amino acids’ and ‘green tea extract’, arguably to circumvent customs control. Although all of the substances were declared ‘for research only’, their potential misuse in illicit performance‐enhancement cannot be excluded; moreover sports drug testing authorities should be aware of the facile availability of black market copies of these drug candidates. Copyright © 2011 John Wiley & Sons, Ltd.
High dosage of aripiprazole‐induced dysphagia
Authors: Lin Ta‐Wei , Lee Bo‐Shyan , Liao Yi‐Cheng , Chiu Nan‐Ying , Hsu Wen‐Yu
Published: May 2011

Background:

Dysphagia as a main manifestation of extrapyramidal symptoms is an uncommon adverse effect of second‐generation antipsychotics.

Method:

We present a 54‐year‐old drug‐naïve patient with schizophrenia, who developed dysphagia with aripiprazole 30 mg daily treatment.

Results:

This is the first case report on aripiprazole‐induced dysphagia. We discuss the risk factors that led to dysphagia in this case.

Conclusion:

Aripiprazole‐induced dysphagia is rare, and it is important to beaware that it does occur with high‐dosage treatment. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Human mesenchymal stem cells respond to native but not oxidized damage associated molecular pattern molecules from necrotic (tumor) material
Authors: Lotfi Ramin , Eisenbacher Judith , Solgi Ghasem , Fuchs Karin , Yildiz Tatjana , Nienhaus Christian , Rojewski Markus T. , Schrezenmeier Hubert
Published: May 2011

Necrosis is a characteristic feature of advanced solid tumors. Released necrotic factors, also referred to as damage associated molecular patterns (DAMPs), are known to critically impact the tumor microenvironment by enhancing angiogenesis or influencing the immune response. We have recently shown that DAMPs can act as chemoattractants and activators of granulocytes. We demonstrate that necrotic material from both normal and tumor cells promotes proliferation and trafficking of human mesenchymal stem cells (MSCs). We characterize the protein high mobility group box 1 (HMGB1) as a crucial member of DAMPs within necrotic material. In addition, we show that DAMPs interfere with expression of indoleamine 2, 3‐dioxygenase (IDO) in MSCs. The biological activity of necrotic material toward MSCs is abolished once these DAMPs are oxidized. MSCs found within tumor tissue can act as immunoregulatory cells and are able to promote tumor metastasis, thus playing a crucial role within the tumor microenvironment. Here, we reveal DAMPs to be crucial factors in the setting of MSC biology within the tumor microenvironment. The tumor microenvironment is characterized by reducing and hypoxic conditions that protect DAMPs from oxidation. Based on our results, oxidizing conditions should be considered for therapeutic approaches that target the tumor microenvironment.
SASPase regulates stratum corneum hydration through profilaggrin‐to‐filaggrin processing
Authors: Matsui Takeshi , Miyamoto Kenichi , Kubo Akiharu , Kawasaki Hiroshi , Ebihara Tamotsu , Hata Kazuya , Tanahashi Shinya , Ichinose Shizuko , Imoto Issei , Inazawa Johji , Kudoh Jun , Amagai Masayuki
Published: May 2011

The stratum corneum (SC), the outermost layer of the epidermis, acts as a barrier against the external environment. It is hydrated by endogenous humectants to avoid desiccation. However, the molecular mechanisms of SC hydration remain unclear. We report that skin‐specific retroviral‐like aspartic protease (SASPase) deficiency in hairless mice resulted in dry skin and a thicker and less hydrated SC with an accumulation of aberrantly processed profilaggrin, a marked decrease of filaggrin, but no alteration in free amino acid composition, compared with control hairless mice. We demonstrated that recombinant SASPase directly cleaved a linker peptide of recombinant profilaggrin. Furthermore, missense mutations were detected in 5 of 196 atopic dermatitis (AD) patients and 2 of 28 normal individuals. Among these, the V243A mutation induced complete absence of protease activity in vitro, while the V187I mutation induced a marked decrease in its activity. These findings indicate that SASPase activity is indispensable for processing profilaggrin and maintaining the texture and hydration of the SC. This provides a novel approach for elucidating the complex pathophysiology of atopic dry skin.
Crystallographic and NMR studies on species intermediate between haloalkoxyphosphoranes and alkoxyphosphonium halides
Authors: Yamamoto Yohsuke , Nakao Kumiko , Hashimoto Takeshi , Matsukawa Shiro , Suzukawa Naoyuki , Kojima Satoshi , Akiba Kin‐ya
Published: May 2011

A series of the monocyclic organophosphorus compounds ([o‐OC(CH3)2C6H4]PPh(CH2 Ph)X) bearing a halogen (X = F, Cl, and Br) or a tetrafluoroborate (X = BF4) were synthesized. The solid‐state structures of the bromide, the tetrafluoroborate, and an analogous fluoride ([o‐OC(CF3)2C6H4]PPh(CH2 Ph)F) were determined by single crystal X‐ray crystallography. The geometry of the fluoride was almost an ideal trigonal bipyramid (TBP). On the other hand, the bromide and tetrafluoroborate were essentially phosphonium salts with phosphorane character to some extent for the former. In CD3 CN, the bromide, the chloride, and the tetrafluoroborate were found to exist as phosphonium salts. However, it was suggested that in CDCl3, the bromide and the chloride have structures rapidly equilibrating or averaged between the phosphorane and the phosphonium forms. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:523–530, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20717
Acetyl‐L‐carnitine‐mediated neuroprotection during hypoxia is attributed to ERK1/2‐Nrf2‐regulated mitochondrial biosynthesis
Authors: Hota Kalpana Barhwal , Hota Sunil Kumar , Chaurasia Om Prakash , Singh Shashi Bala
Published: May 2011

Neuronal damage in hypoxia and several neurodegenerative disorders is invariably associated with oxidative damage and mitochondrial dysfunction. Administration of acetyl‐L‐carnitine (ALCAR) on the other hand attenuates neuronal damage, prevents apoptosis, and improves energy status in hypoxic stress through less understood mechanisms. Becasue mitochondrial biogenesis could be a possible mechanism for ALCAR‐induced improvement in bioenergetics in neurons, the present study aimed at exploring signaling pathways of ALCAR‐induced neuroprotection in hypoxia and possible occurrence of mitochondrial biogenesis. To create global hypoxia, adult Sprague–Dawley rats were exposed to a simulated altitude of 7,620 m at standard temperature and humidity conditions. We here demonstrate that administration of ALCAR to hypoxic rats for a period of 2 weeks effectively protected hippocampal neurons from mitochondrial dysfunction, excitotoxicity, and neurodegeneration. ALCAR administration resulted in peroxisome proliferator‐activated receptor γ coactivator‐1α and nuclear respiratory factor‐1‐induced mitochondrial biogenesis, the expression of which was regulated by an extracellular‐related kinase‐nuclear factor erythroid 2‐related factor 2 (ERK‐Nrf2)‐mediated mechanism. Most notably, calcium buffering into nonfunctional mitochondria ameliorated excitotoxicity and improved bioenergetic status of the hippocampal neurons. Together, the data reveal the immense therapeutic potential of ALCAR for the treatment of ischemia, stroke, and other neurodegenerative disorders associated with hypoxic stress and excitotoxicity. © 2011 Wiley Periodicals, Inc.
Inactivation of ventral midline thalamus produces selective spatial delayed conditional discrimination impairment in the rat
Authors: Hembrook Jacqueline R. , Onos Kristen D. , Mair Robert G.
Published: May 2011

The reuniens (Re) and rhomboid (Rh) nuclei are organized to influence activity in distributed limbic networks involving hippocampus and medial prefrontal cortex (mPFC). To elucidate the role of these nuclei in spatial memory we inactivated Re and Rh in rats with the GABAA agonist muscimol and compared effects on two spatial delayed conditional discriminations: delayed nonmatching to position (DNMTP) and varying choice radial maze delayed nonmatching (VC‐DNM). DNMTP is trained in operant chambers and requires rats to choose between the same two levers on all trials. VC‐DNM is trained in automated radial mazes and requires rats to choose between two arms, randomly selected from eight alternatives on each trial. DNMTP is affected by hippocampal and mPFC lesions while VC‐DNM is affected by hippocampal, but not mPFC lesions (Porter et al. (2000) Behav Brain Res 109:69–81). We found evidence of a localized (low dose) effect of ReRh inactivation on DNMTP but not VC‐DNM. This was confirmed by comparison with muscimol injections in an anatomical control site. These results are consistent with evidence that Re and Rh affect measures of spatial working memory that depend on interactions between hippocampus and mPFC, but not measures that depend on hippocampus alone. © 2011 Wiley Periodicals, Inc.
Alcohol effects on simulated driving in frequent and infrequent binge drinkers
Authors: Bernosky‐Smith Kimberly A. , Shannon Erin E. , Roth Alicia J. , Liguori Anthony
Published: May 2011

Objective

Compared with non‐bingers, binge drinkers are more likely to drive while intoxicated. The extent to which binge frequency impacts confidence in driving and subsequent driving impairment is unknown. This study compared the effects of an experimenter‐delivered alcohol binge on subjective impairment and simulated driving ability in female high‐frequency and low‐frequency bingers.

Methods

Female drinkers were assigned to high‐frequency (n = 30) or low‐frequency (n = 30) binge groups based on their Alcohol Use Questionnaire responses. At 30‐min intervals within a 2‐h period, participants received either a placebo drink (n = 15 per group) or a 0.2 g/kg dose of alcohol (n = 15 per group; cumulative dose 0.8 g/kg). Self‐reported impairment, driving confidence, and simulated driving were then measured.

Results

Self‐reported confidence in driving was significantly lower after alcohol than after placebo in low‐frequency but not high‐frequency bingers. Self‐reported impairment and collisions during simulated driving were significantly greater after alcohol than after placebo in both low‐frequency and high‐frequency bingers.

Conclusions

The impairing effects of a single alcohol binge on driving ability in women are not influenced by binge frequency. However, high binge frequency may be associated with a less cautious approach to post‐binge driving. Copyright © 2011 John Wiley & Sons, Ltd.
Observations of cardiac beating behaviors of wild‐type and mutant Drosophilae with optical coherence tomography
Authors: Tsai Meng‐Tsan , Chang Feng‐Yu , Lee Cheng‐Kuang , Chi Ting‐Ta , Yang Kai‐Min , Lin Lian‐Yu , Wu June‐Tai , Yang C. C.
Published: May 2011

Time‐resolved optical coherence tomography (OCT) scanning images of wild‐type and mutant fruit flies (Drosophila melanogaster), illustrating the heartbeat patterns for evaluating their cardiac functions, are demonstrated. Based on the heartbeat patterns, the beat rate and the relative phase between the first two heart segments can be evaluated. The OCT scanning results of mutant flies with impaired proteasome function in cardiac muscles show irregular heartbeat patterns and systematically decreased average beat rates, when compared with the regular patterns of ∼4.97 beats/s in average beat rate of the wild‐type. In both wild‐type and proteasome mutant flies, the beatings at different locations in the same heart segment are essentially synchronized. However, between different heart segments, although the beating in the second segment shows a lag in phase behind that of the first segment in a wild‐type, in a proteasome mutant, the beating in the second segment becomes significantly leading that of the first segment. Besides the comparison between the wild‐type and proteasomal mutant flies, the influences of using different methods for immobilizing flies during OCT scanning on the heart functions are demonstrated. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins
Authors: Forti Flavio , Boechi Leonardo , Estrin Dario A. , Marti Marcelo A.
Published: May 2011

The ubiquitous heme proteins perform a wide variety of tasks that rely on the subtle regulation of their affinity for small ligands like O2, CO, and NO. Ligand affinity is characterized by kinetic association and dissociation rate constants, that partially depend on ligand migration between the solvent and active site, mediated by the presence of internal cavities or tunnels. Different computational methods have been developed to study these processes which can be roughly divided in two strategies: those costly methods in which the ligand is treated explicitly during the simulations, and the free energy landscape of the process is computed; and those faster methods that use prior computed Molecular Dynamics simulation without the ligand, and incorporate it afterwards, called implicit ligand sampling (ILS) methods. To compare both approaches performance and to provide a combined protocol to study ligand migration in heme proteins, we performed ILS and multiple steered molecular dynamics (MSMD) free energy calculations of the ligand migration process in three representative and well theoretically and experimentally studied cases that cover a wide range of complex situations presenting a challenging benchmark for the aim of the present work. Our results show that ILS provides a good description of the tunnel topology and a reasonable approximation to the free energy landscape, while MSMD provides more accurate and detailed free energy profile description of each tunnel. Based on these results, a combined strategy is presented for the study of internal ligand migration in heme proteins. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Efficiency of tabu‐search‐based conformational search algorithms
Authors: Grebner Christoph , Becker Johannes , Stepanenko Svetlana , Engels Bernd
Published: May 2011

Efficient conformational search or sampling approaches play an integral role in molecular modeling, leading to a strong demand for even faster and more reliable conformer search algorithms. This article compares the efficiency of a molecular dynamics method, a simulated annealing method, and the basin hopping (BH) approach (which are widely used in this field) with a previously suggested tabu‐search‐based approach called gradient only tabu search (GOTS). The study emphasizes the success of the GOTS procedure and, more importantly, shows that an approach which combines BH and GOTS outperforms the single methods in efficiency and speed. We also show that ring structures built by a hydrogen bond are useful as starting points for conformational search investigations of peptides and organic ligands with biological activities, especially in structures that contain multiple rings. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Implementation and evaluation of a docking‐rescoring method using molecular footprint comparisons
Authors: Balius Trent E. , Mukherjee Sudipto , Rizzo Robert C.
Published: May 2011

A docking‐rescoring method, based on per‐residue van der Waals (VDW), electrostatic (ES), or hydrogen bond (HB) energies has been developed to aid discovery of ligands that have interaction signatures with a target (footprints) similar to that of a reference. Biologically useful references could include known drugs, inhibitors, substrates, transition states, or side‐chains that mediate protein‐protein interactions. Termed footprint similarity (FPS) score, the method, as implemented in the program DOCK, was validated and characterized using: (1) pose identification, (2) crossdocking, (3) enrichment, and (4) virtual screening. Improvements in pose identification (6–12%) were obtained using footprint‐based (FPSVDW+ES) vs. standard DOCK (DCEVDW+ES) scoring as evaluated on three large datasets (680–775 systems) from the SB2010 database. Enhanced pose identification was also observed using FPS (45.4% or 70.9%) compared with DCE (17.8%) methods to rank challenging crossdocking ensembles from carbonic anhydrase. Enrichment tests, for three representative systems, revealed FPSVDW+ES scoring yields significant early fold enrichment in the top 10% of ranked databases. For EGFR, top FPS poses are nicely accommodated in the molecular envelope defined by the reference in comparison with DCE, which yields distinct molecular weight bias toward larger molecules. Results from a representative virtual screen of ca. 1 million compounds additionally illustrate how ligands with footprints similar to a known inhibitor can readily be identified from within large commercially available databases. By providing an alternative way to rank ligand poses in a simple yet directed manner we anticipate that FPS scoring will be a useful tool for docking and structure‐based design. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Acceleration of the GAMESS‐UK electronic structure package on graphical processing units
Authors: Wilkinson Karl A. , Sherwood Paul , Guest Martyn F. , Naidoo Kevin J.
Published: May 2011

The approach used to calculate the two‐electron integral by many electronic structure packages including generalized atomic and molecular electronic structure system‐UK has been designed for CPU‐based compute units. We redesigned the two‐electron compute algorithm for acceleration on a graphical processing unit (GPU). We report the acceleration strategy and illustrate it on the (ss|ss) type integrals. This strategy is general for Fortran‐based codes and uses the Accelerator compiler from Portland Group International and GPU‐based accelerators from Nvidia. The evaluation of (ss|ss) type integrals within calculations using Hartree Fock ab initio methods and density functional theory are accelerated by single and quad GPU hardware systems by factors of 43 and 153, respectively. The overall speedup for a single self consistent field cycle is at least a factor of eight times faster on a single GPU compared with that of a single CPU. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
The syntheses and in vitro biotransformation studies of [14C]apixaban, a highly potent, selective, efficacious and orally bioavailable inhibitor of blood coagulation Factor Xa
Authors: Maxwell Brad D. , Tran Scott B. , Chen Shiang‐Yuan , Zhang Donglu , Chen Bang‐Chi , Zhang Huiping , Bonacorsi Samuel J.
Published: May 2011

Apixaban is a potent inhibitor of blood coagulation Factor Xa in the late stages of development. [14C]apixaban was synthesized with the 14C label in the two different lactam ring systems within the molecule for various in vitro and in vivo metabolism studies. A nine‐step synthesis of [14C]apixaban, 10, with the label in the central lactam ring was completed in 14% overall yield. A second synthesis of [14C]apixaban, 14, with the 14C label in the outer lactam ring was completed in three steps in a 14% overall yield. No significant differences were observed between the metabolite profiles of 10 and 14, [14C]apixaban, from both rat and human hepatocyte or microsomal incubations. Copyright © 2011 John Wiley & Sons, Ltd.
Prevalence and clinical significance of hepatitis D virus co‐infection in patients with chronic hepatitis B in Korea
Authors: Kim Hyoung Su , Kim Sung Jun , Park Hye Won , Shin Woon Geon , Kim Kyung Ho , Lee Jin Heon , Kim Hak Yang , Jang Myoung Kuk
Published: May 2011

Hepatitis D virus (HDV) infection can cause severe acute and chronic liver disease in patients infected with hepatitis B virus (HBV). Despite the significant decline in the global HDV infection, it remains a major health concern in some countries. This study aimed to investigate the prevalence and clinical features of HDV co‐infection in patients with chronic HBV infection in Korea, where HBV infection is endemic. Nine hundred forty patients [median age, 48 (18–94) years; men, 64.5%] infected chronically with HBV were enrolled consecutively. All patients who were positive for hepatitis B surface antigen (HBsAg) for at least 6 months and were tested for anti‐HDV. A portion of the HDV delta antigen was amplified, sequenced, and subjected to molecular and phylogenetic analysis using sera from the patients who were anti‐HDV positive. Clinical features and virologic markers were evaluated. Inactive HBsAg carriers, chronic hepatitis B, cirrhosis and hepatocellular carcinoma accounted for 29.5%, 44.7%, 17.9%, and 8.0%, respectively. Only three patients were positive for anti‐HDV, corresponding to a 0.32% positive rate. All patients who were positive for anti‐HDV were inactive HBsAg carriers. HDV RNA could be amplified by PCR from the sera of two patients. Phylogenetic analysis showed that both carried HDV genotype 1. In conclusion, the prevalence of HDV infection is very low (0.32%) in Korea. All HDVs were genotype 1 and detected in inactive HBsAg carriers. Therefore, HDV co‐infection may not have a significant clinical impact in Korean patients with chronic HBV infection. J. Med. Virol. 83:1172–1177, 2011. © 2011 Wiley‐Liss, Inc.
Reversible inhibition of hydrogen peroxide elimination by calcium in brain mitochondria
Authors: Tretter Laszlo , Biagioni Angeli Emanuela , Ardestani Mohammad Reza , Goracci Gianfrancesco , Adam‐Vizi Vera
Published: May 2011

In the present work, the Ca2+ dependence of mitochondrial H2O2 elimination was investigated. Mitochondria isolated from guinea pig brain were energized by glutamate and malate and incubated with micromolar concentrations of Ca2+ in the presence of ADP, preventing permeability transition pore formation. After the completion of Ca2+ uptake, mitochondria were challenged with H2O2 (5 μM), then at various time points residual H2O2 was determined using the Amplex red method and compared with that in mitochondria incubated with H2O2 without Ca2+ addition. Dose‐dependent inhibition of H2O2 elimination by Ca2+ was detected, which was prevented by the Ca2+‐uptake inhibitor Ru 360. Stimulation of Ca2+ release from Ca2+ ‐loaded mitochondria by a combined addition of Ru 360 and Na+ decreased the Ca2+‐evoked inhibition of H2O2 removal. After Ca2+ uptake (50 μM), mitochondrial aconitase activity was found to be decreased, which was partially attributable to the impaired elimination of endogenously produced reactive oxygen species. We found that the effects of Ca2+ and H2O2 on the activity of aconitase were additive. These results confirm that Ca2+ inhibits elimination of H2O2 in mitochondria and demonstrate that this effect is concentration dependent and reversible. The phenomenon described here can play a role in the modulation of ROS handling under conditions involving excessive cellular Ca2+ load. © 2011 Wiley‐Liss, Inc.
The “B Space” of mitochondrial phosphorylation
Authors: Chinopoulos Christos
Published: May 2011

It was recently shown that, in progressively depolarizing mitochondria, the F0‐F1 ATP synthase and the adenine nucleotide translocase (ANT) may change directionality independently from each other (Chinopoulos et al. [2010] FASEB J. 24:2405). When the membrane potentials at which these two molecular entities reverse directionality, termed reversal potential (Erev), are plotted as a function of matrix ATP/ADP ratio, an area of the plot is bracketed by the Erev_ATPase and the Erev_ANT, which we call “B space”. Both reversal potentials are dynamic, in that they depend on the fluctuating values of the participating reactants; however, Erev_ATPase is almost always more negative than Erev_ANT. Here we review the conditions that define the boundaries of the “B space”. Emphasis is placed on the role of matrix substrate‐level phosphorylation, because during metabolic compromise this mechanism could maintain mitochondrial membrane potential and prevent the influx of cytosolic ATP destined for hydrolysis by the reversed F0‐F1 ATP synthase. © 2011 Wiley‐Liss, Inc.
An insight into the mechanism of CEC separation of template analogues on a norepinephrine‐imprinted monolith
Authors: Huang Bao‐Yu , Chen Yu‐Cheng , Liu Chuen‐Ying
Published: May 2011

A monolith molecularly imprinted polymer (MIP) column was prepared from template (−)‐norepinephrine, functional monomer (itaconic acid), and a cross‐linker (either ethylene glycol dimethacrylate or divinylbenzene) in porogen N,N‐dimethylformamide. Understanding the molecular recognition of a template using an MIP seems feasible. However, it is hard to explain the recognition properties of their analogues on an MIP. The separation mechanism was investigated with the addition of charged surfactants, native and derivatised β‐cyclodextrin (β‐CD), achiral crown ether, etc. to determine the retention behaviour of the template analogues. The addition of organic modifiers and the adjustment of separation conditions were used to manipulate the selectivity. No chiral recognition was observed under most of the test conditions except the experiment with the charged β‐CD on the divinylbenzene‐MIP column. The different experimental conditions led to differences in the mobilities of the analytes and resulted in remarkable enantiomeric separation of the template. We confirmed the presence of mixed‐mode selectivity of the stationary phase based on hydrogen bonding, hydroelectric and hydrophobic interactions, and the electrophoretic mode.
Method for removing hypopharyngeal salivary bypass tubes
Authors: Kejner Alexandra E. , Rosenthal Eben L.
Published: May 2011

Objective:

To describe a novel method for the removal of the salivary bypass tube (SBT) that precludes the need for extraction under general anesthesia.

Study Design:

Retrospective case series.

Methods/Technique:

Patients who had undergone laryngectomy/laryngopharyngectomy with subsequent development of pharyngocutaneous fistula and intraoperative placement of a salivary bypass tube were included in this series. The tubes were removed at the bedside or in clinic utilizing a Fogarty‐type method over a Foley catheter.

Results:

Three patients underwent removal of hypopharyngeal salivary bypass tubes 1 to 2 weeks after placement. Inflation of the Foley catheter within the lumen of the salivary bypass tube facilitated successful removal without the need for additional procedures. All three patients required only topical anesthetic and tolerated the procedure with minimal discomfort.

Conclusions:

Compared to current methods, this technique is cost‐effective and time‐efficient while not compromising patient safety or comfort. Laryngoscope, 2011
Chain‐Length‐Dependent Termination in Radical Polymerization of Acrylates
Authors: Barth Johannes , Buback Michael , Russell Gregory T. , Smolne Sebastian
Published: May 2011

The technique of SPPLP EPR, which is single‐pulse pulsed‐laser polymerization (SPPLP) in conjunction with electron paramagnetic resonance (EPR) spectroscopy, is used to carry out a detailed investigation of secondary (chain‐end) radical termination of acrylates. Measurements are performed on methyl acrylate, n‐butyl acrylate, and dodecyl acrylate in bulk and in toluene solution at −40 °C. The reason for the low temperature is to avoid formation of mid‐chain radicals (MCRs), a complicating factor that has imparted ambiguity to the results of previous studies of this nature. Consistent with these previous studies, composite‐model behavior for chain‐length‐dependent termination (CLDT) rate coefficients, $k_{{\rm t}}^{i,i} $, is found in this work. However, lower and more reasonable values of αs, the exponent for variation of $k_{{\rm t}}^{i,i} $ at short chain lengths, are found in the present study. Most likely this is because of the absence of MCRs, thereby validating the methodology of this work. Family‐type termination behavior is observed, with the following average parameter values adequately describing all results, regardless of acrylate or the presence of toluene: αs  = 0.79, αl = 0.21 (long chains) and ic ≈ 30 (crossover chain length). All indications are that these values carry over to termination of acrylate chain‐end radicals at higher, more practical temperatures. Further, these values largely make sense in terms of what is understood about the physical meaning of the parameters. Variation of the rate coefficient for termination between monomeric radicals, $k_{{\rm t}}^{{\rm 1,1}} $, is found to be well described by the simple Smoluchowski and Stokes–Einstein equations. This allows easy prediction of $k_{{\rm t}}^{{\rm 1,1}} $ for different alkyl acrylates, solvent, and temperature. Through all this the unrivalled power of SPPLP EPR for measuring and understanding (chain‐length‐dependent) termination rate coefficients shines through.

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Morphology Development in Relation to the Ternary Phase Diagram of Biodegradable PDLLA/PCL/PEO Blends
Authors: Buddhiranon Sasiwimon , Kim Namil , Kyu Thein
Published: May 2011

The morphology phase diagram of biodegradable polymer blends of PDLLA, PCL, and PEO is presented and discussed. The phase diagram of PCL/high‐molecular‐weight PDLLA mixtures reveals an hour‐glass phase diagram. Upon lowering the molecular weight of PDLLA, a combined LCST/UCST develops that is intersected by the melting transition curve of PCL. The observed liquid/liquid phase separation and crystal/isotropic phase transition are compared with the theoretical liquidus/solidus curves obtained by solving the combined Flory‐Huggins and phase‐field free energies self‐consistently. A similar study is extended to the binary phase diagrams of PEO/PDLLA and PCL/PEO. Of particular interest is that the prism‐type phase diagram of the ternary blends provides a complete description of the overall phase behavior.

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Tailoring the Degree of Polymerization of Low Molecular Weight Cellulose
Authors: Meiland Marcel , Liebert Tim , Heinze Thomas
Published: May 2011

The degradation of cellulose to lmw samples with $\overline {DP} _{{\rm w}} $ varying from 15 to 130 is investigated. Cellulose samples prepared from the hydrolysis of regenerated cellulose fibers in dilute HCl possess $\overline {DP} _{{\rm w}} $ = 50. Applying homogenous degradation of microcrystalline cellulose in H3PO4 at RT for 3 weeks, samples with $\overline {DP} _{{\rm w}} $ = 35 and a PDI of 1.58 are obtained. Decreasing the hydrolysis temperature to 8 °C results in lmw cellulose with $\overline {DP} _{{\rm w}} $ > 70. Fractionation in DMA/LiCl provides samples with $\overline {DP} _{{\rm w}} $ = 12 to 130, together with a narrow molecular weight distribution. Detailed structural analysis by 2D NMR spectroscopy reveals that the prepared lmw celluloses are suitable as mimics for cellulose.

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Extrusion Foaming of Poly (lactic acid)/Soy Protein Concentrate Blends
Authors: Liu Bo , Jiang Long , Zhang Jinwen
Published: May 2011

Poly(lactic acid) (PLA) and soy protein concentrate (SPC) were compounded using poly(2‐ethyl‐2‐oxazoline) as compatibilizer by twin‐screw extrusion, and the resulting blends were foamed by a chemical blowing agent (CBA) using the same extruder. Effects of foaming temperature and CBA content on cell density and foam density were investigated. Polymeric methylene diphenyl diisocyanate (pMDI) as a co‐compatibilizer was added prior to foaming extrusion and its effects on foam morphology and properties were also studied. The results showed that cell density and foam density were greatly influenced by foaming temperature and CBA content. Using the strong interfacial modifier pMDI in PLA/SPC blends resulted in high‐cell density and low‐foam density when CBA concentration was low.

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Self‐supporting Polymer from a POSS Derivative
Authors: Cheng Chih‐Chia , Yen Ying‐Chieh , Chang Feng‐Chih
Published: May 2011

A new polyhedral oligomeric silsesquioxane macromer, octakis[N‐(6‐aminopyridin‐2‐yl)undecanamide‐10‐dimethyl‐siloxy]silsesquioxane (POSS‐C11‐Py), containing eight diaminopyridine arms, is able to self‐assemble to form a physically crosslinked polymer‐like structure with good mechanical properties (tensile strength = 46.1 MPa, tensile modulus = 0.58 GPa, elongation = 49.3%) through quadruple hydrogen bonding interactions between these arms. POSS‐C11‐Py is the first organic/inorganic supermolecule possessing polymer‐like mechanical properties as a result of self‐complementary interactions, providing a potential route toward the design and fabrication of polymer‐like supramolecular materials.

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Three dimensional modelling of fibrous materials and experimental validation
Authors: Curto J.M.R. , Conceição E.L.T. , Portugal A.T.G. , Simões R.M.S.
Published: May 2011

This article presents a computational model and some simulation results for fibrous materials such as paper. To obtain a better understanding of the influence of fibre properties on the paper structure a novel paper model was developed. This is a physically based model where paper is formed by the sequential deposition of individual fibres. The model intends to capture key papermaking fibre properties like morphology, flexibility, and collapse and process operations such as fibre deposition, network forming or densification. This model is a step forward in transverse paper modelling. In fact, it is a three dimensional model that includes the fibre microstructure, that is, lumen and fibre wall thickness, with a resolution up to 0.05 μm. To test the model validity and predictive capability, laboratory hand sheets were used to study the network formation of an office paper, mainly produced from Eucalyptus globulus bleached Kraft pulp. This paper was characterized via an experimental design that included factors such as raw material and beating degree. The resulting porous structure was characterized and the mechanical performance was assessed. The computational simulation was used to investigate the relative influence of fibre properties such as fibre flexibility, dimensions and collapsibility. The developed multiscale model gave realistic predictions and enabled us to link fibre microstructure and paper properties.