bluuebunny/crossref_metadata_2025 huggingface dataset:
Breaking Bat
Authors: Aguilar Isaac-Cesar , Kagan David
Published: January 2013

The sight of a broken bat in Major League Baseball can produce anything from a humorous dribbler in the infield to a frightening pointed projectile headed for the stands. Bats usually break at the weakest point, typically in the handle. Breaking happens because the wood gets bent beyond the breaking point due to the wave sent down the bat created by the collision with the ball.1 The kind of wood that is used plays a role in the manner in which the bat breaks—-its “failure mode.” We report on a simple experiment to compare the breaking strength and failure modes of ash and maple dowels. The results illustrate some of the features of breaking bats under game conditions.
Converging or Diverging Lens?
Authors: Branca Mario
Published: January 2013

Why does a lens magnify? Why does it shrink objects? Why does this happen? The activities that we propose here are useful in helping us to understand how lenses work, and they show that the same lens can have different magnification capabilities. A converging lens can also act as a diverging lens.
Optimal Ski Jump
Authors: Rębilas Krzysztof
Published: January 2013

Consider a skier who goes down a takeoff ramp, attains a speed V, and jumps, attempting to land as far as possible down the hill below (Fig. 1). At the moment of takeoff the angle between the skier's velocity and the horizontal is α. What is the optimal angle α that makes the jump the longest possible for the fixed magnitude of the velocity V? Of course, in practice, this is a very sophisticated problem; the skier's range depends on a variety of complex factors in addition to V and α. However, if we ignore these and assume the jumper is in free fall between the takeoff ramp and the landing point below, the problem becomes an exercise in kinematics that is suitable for introductory-level students. The solution is presented here.
Measuring the Effectiveness of Simulations in Preparing Students for the Laboratory
Authors: Paetkau Mark , Bissonnette Dan , Taylor Colin
Published: January 2013

Computer simulations (we use the word liberally here to include applets, animations, apps, etc.) have been making steady progress as teaching tools. Large collections of simulations, created by individuals1,2 and by groups,3 are freely available. More recently, research on the effectiveness of simulations as teaching tools, particularly focused on the teaching of concepts, has been an area of interest.4,5 We have been using simulations at Thompson Rivers University (TRU) to help prepare students for the physics lab for the past five years. In work by others, simulations were used in the pre-laboratory work to prepare students on a conceptual level.6 In our case the simulations are used to help prepare students for the experimental aspect. The current work focuses on students' need to take data in the lab and how students can be prepared to efficiently obtain that data.
Pharmaceutical Innovation Gets a Little Help from New Friends
Authors: Munos Bernard H.
Published: January 2013

The U.S. National Center for Advancing Translational Science and its partners set out to remove the roadblocks that are slowing pharmaceutical innovation.
Remaking the Brain with Stem Cells
Authors: Baker Aaron B.
Published: January 2013

A new cell-based therapy in monkeys shows potential for treating Parkinson’s disease.
Fragmenting Malignant Melanoma
Authors: Bettegowda Chetan
Published: January 2013

Catastrophic chromosomal abnormalities are associated with poor prognosis in malignant melanoma.
Antimicrobial Effects of Stem Cells
Authors: Calfee Carolyn S.
Published: January 2013

Mesenchymal stem cells show benefit in an ex vivo perfused human lung model of bacterial acute lung injury.
Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus
Authors: Perlman Stanley , Zhao Jincun
Published: January 2013

A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in
mBio
, Müller et al. described several important differences between the two viruses [M. A. Müller et al.,
mBio
3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor-2 (hACE2). These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.
Microbial Composition of Human Appendices from Patients following Appendectomy
Authors: Guinane Caitriona M. , Tadrous Amany , Fouhy Fiona , Ryan C. Anthony , Dempsey Eugene M. , Murphy Brendan , Andrews Emmet , Cotter Paul D. , Stanton Catherine , Ross R. Paul
Published: January 2013

The human appendix has historically been considered a vestige of evolutionary development with an unknown function. While limited data are available on the microbial composition of the appendix, it has been postulated that this organ could serve as a microbial reservoir for repopulating the gastrointestinal tract in times of necessity. We aimed to explore the microbial composition of the human appendix, using high-throughput sequencing of the 16S rRNA gene V4 region. Seven patients, 5 to 25 years of age, presenting with symptoms of acute appendicitis were included in this study. Results showed considerable diversity and interindividual variability among the microbial composition of the appendix samples. In general, however,
Firmicutes
was the dominant phylum, with the majority of additional sequences being assigned at various levels to
Proteobacteria
,
Bacteroidetes
,
Actinobacteria
, and
Fusobacteria
. Despite the large diversity in the microbiota found within the appendix, however, a few major families and genera were found to comprise the majority of the sequences present. Interestingly, also, certain taxa not generally associated with the human intestine, including the oral pathogens
Gemella
,
Parvimonas
, and
Fusobacterium
, were identified among the appendix samples. The prevalence of genera such as
Fusobacterium
could also be linked to the severity of inflammation of the organ. We conclude that the human appendix contains a robust and varied microbiota distinct from the microbiotas in other niches within the human microbiome. The microbial composition of the human appendix is subject to extreme variability and comprises a diversity of biota that may play an important, as-yet-unknown role in human health.

IMPORTANCE
There are currently limited data available on the microbial composition of the human appendix. It has been suggested, however, that it may serve as a “safe house” for commensal bacteria that can reinoculate the
gut at
need. The present study is the first comprehensive view of the microbial composition of the appendix as determined by high-throughput sequencing. We have determined that the human appendix contains a wealth of microbes, including members of 15 phyla. Important information regarding the associated bacterial diversity of the appendix which will help determine the role, if any, the appendix microbiota has in human health is presented.
Human Claudin-8 and -14 Are Receptors Capable of Conveying the Cytotoxic Effects of Clostridium perfringens Enterotoxin
Authors: Shrestha Archana , McClane Bruce A.
Published: January 2013

Clostridium perfringens
enterotoxin (CPE) contributes to several important human gastrointestinal (GI) diseases. This toxin and its derivatives are also being explored for translational applications, i.e., cancer therapy or drug delivery. Some, but not all, members of the 24-member claudin (Cldn) family of mammalian tight junction proteins can serve as CPE receptors. Among the human Cldns (hCldns), hCldn-3 and -4 are known to convey CPE sensitivity when expressed by fibroblast transfectants. However, other Cldns are also reportedly expressed in the intestines, where they might contribute to natural CPE-mediated GI disease, and in other organs, where they might react with CPE-based therapeutics. Therefore, the current study assessed whether two additional hCldns beside hCldn-3 and -4 are also functional CPE receptors. Using Cldn-expressing transfectants, hCldn-8 and -14 were shown to convey CPE-mediated cytotoxicity at pathophysiologically relevant concentrations of this toxin, although ~2-to-10-fold less efficiently than hCldn-4. Site-directed mutagenesis then demonstrated that the N
146
residue in hCldn-14 and the S
151
residue in hCldn-8 are largely responsible for modulating the weaker CPE binding properties of hCldn-8 and -14 versus hCldn-4, which broadens understanding of Cldn:CPE binding interactions. Since Cldn-8 and -14 are reportedly expressed in mammalian intestines, the current results support the possibility that these two hCldns contribute to natural CPE-mediated gastrointestinal disease and could be CPE-based therapeutic targets for cancers overexpressing those claudins. However, these results also suggest caution during therapeutic use of CPE, which might trigger toxic side effects in normal human tissues producing hCldn-8 or -14, as well as in those producing hCldn-3 or -4.

IMPORTANCE
Clostridium perfringens
enterotoxin (CPE) is responsible for the gastrointestinal symptoms of the second-most-common bacterial food-borne illness and is also being explored for use as a cancer therapeutic or for increasing drug delivery. Until now, the only known human CPE receptors were claudin-3 and -4. This work shows that human claudin-8 and -14 can also bind CPE and convey cytotoxicity, although slightly less efficiently than claudin-3 and -4. The claudin-8 and -14 residues responsible for this weaker CPE binding were identified, shedding new light on CPE:claudin interactions.
Recurrent hamstring muscle injury: applying the limited evidence in the professional football setting with a seven-point programme
Authors: Brukner Peter , Nealon Andrew , Morgan Christopher , Burgess Darren , Dunn Andrew
Published: January 2013

Recurrent hamstring injuries are a major problem in sports such as football. The aim of this paper was to use a clinical example to describe a treatment strategy for the management of recurrent hamstring injuries and examine the evidence for each intervention. A professional footballer sustained five hamstring injuries in a relatively short period of time. The injury was managed successfully with a seven-point programme—biomechanical assessment and correction, neurodynamics, core stability, eccentric strengthening, an overload running programme, injection therapies and stretching/relaxation. The evidence for each of these treatment options is reviewed. It is impossible to be definite about which aspects of the programme contributed to a successful outcome. Only limited evidence is available in most cases; therefore, decisions regarding the use of different treatment modalities must be made by using a combination of clinical experience and research evidence.
A user's guide to performance of the best shoulder physical examination tests
Authors: Myer Cortney A , Hegedus Eric J , Tarara Daniel Thomas , Myer Daniel M
Published: January 2013

Background

This article provides clinicians with a user's guide on the performance of the shoulder physical examination tests most supported by current evidence from a recent systematic review published in theBritish Journal of Sports Medicine.

Discussion

A description of clinical shoulder tests is provided with explanations on exact testing procedures and complimentary photographs.
Methodological variations and their effects on reported medication administration error rates
Authors: McLeod Monsey Chan , Barber Nick , Franklin Bryony Dean
Published: January 2013

Background

Medication administration errors (MAEs) are a problem, yet methodological variation between studies presents a potential barrier to understanding how best to increase safety. Using the UK as a case-study, we systematically summarised methodological variations in MAE studies, and their effects on reported MAE rates.

Methods

Nine healthcare databases were searched for quantitative observational MAE studies in UK hospitals. Methodological variations were analysed and meta-analysis of MAE rates performed using studies that used the same definitions. Odds ratios (OR) were calculated to compare MAE rates between intravenous (IV) and non-IV doses, and between paediatric and adult doses.

Results

We identified 16 unique studies reporting three MAE definitions, 44 MAE subcategories and four different denominators. Overall adult MAE rates were 5.6% of a total of 21 533 non-IV opportunities for error (OE) (95% CI 4.6% to 6.7%) and 35% of a total of 154 IV OEs (95% CI 2% to 68%). MAEs were five times more likely in IV than non-IV doses (pooled OR 5.1; 95% CI 3.5 to 7.5). Including timing errors of ±30 min increased the MAE rate from 27% to 69% of 320 IV doses in one study. Five studies were unclear as to whether the denominator included dose omissions; omissions accounted for 0%–13% of IV doses and 1.8%–5.1% of non-IV doses.

Conclusions

Wide methodological variations exist even within one country, some with significant effects on reported MAE rates. We have made recommendations for future MAE studies; these may be applied both within and outside the UK.
A novel approach to improving emergency department consultant response times
Authors: Soong Christine , High Sasha , Morgan Matthew W , Ovens Howard
Published: January 2013

Background

Emergency department (ED) overcrowding is a threat to patient safety and public health. Availability of specialty consultation to the ED may contribute to overcrowding. We implemented a novel intervention using education, goal setting and real-time performance feedback to improve time to admission for patients referred to general internal medicine (GIM).

Methods

Using a time-series design, we examined the effects of a quality improvement intervention on ED wait-times in an academic medical centre. The multifaceted approach included a didactic session for GIM housestaff on medicine triage principles and methods; setting a goal to have disposition decisions and, where appropriate, admission order within 4 h of consultation request; and providing personal data feedback on their performance on this metric to GIM housestaff during their rotation on the inpatient teaching service over a 1-year period. We compared time from consultation request to disposition decision and overall ED length of stay (LOS) for all patients referred to GIM during the intervention period (February 2011–February 2012) with data from the control period (January 2010–January 2011).

Results

Mean time from GIM consultation request to admission order entry decreased by 92 min (SD, 5, p<0.05) from 321min in the control period to 229 min in the intervention period. Overall ED LOS for GIM patients decreased by 59 min (SD, 14, p<0.05) for admitted patients from 1022 min in the control period to 963 min in the intervention period, and by 40 min (SD, 13, p<0.05) for all patients referred to GIM. GIM staffing and patient characteristics remained stable across the two periods.

Discussion

ED throughput for admitted medical patients improved with a quality improvement initiative involving education, goal setting and performance feedback.
Breast cancer stem cells: an update
Authors: Iqbal Jabed , Chong Pek Yoon , Tan Puay Hoon
Published: January 2013

Breast cancer is a significant cause of morbidity and mortality in women with a high incidence of recurrence or treatment failure. Growing evidence suggests that cancer stem cells (CSCs) most likely contribute to tumour progression, spread and therapy failure. However, despite extensive research and the tremendous clinical potential of such cells in possible therapeutic management, the real nature of CSCs remains an enigma. In this review, we discuss the fundamental properties and molecular target of CSCs and focus on recent advances regarding the identification of CSC markers with emphasis on breast cancer and the underlying molecular mechanism of CSC phenotypes. We also discuss experimental evidence of targeting molecular pathways in order to modulate breast CSC behaviour in tumourigenesis and the controversies associated with it that potentially weaken the CSC model in breast cancer and other cancers as well.
Childhood emotional functioning and the developmental origins of cardiovascular disease risk
Authors: Appleton Allison A , Loucks Eric B , Buka Stephen L , Rimm Eric , Kubzansky Laura D
Published: January 2013

Background

Dysregulated emotional functioning has been linked with higher cardiovascular disease (CVD) risk among adults. Early life experiences may influence the development of adulthood CVD, but few studies have examined whether potential damaging effects of dysregulated emotional function begin earlier in life. Therefore, we examined associations of child emotional functioning and the 10-year risk of developing CVD in midlife.

Methods

We studied 377 adult offspring (mean age=42.2) of Collaborative Perinatal Project participants, a US cohort of pregnant women enrolled in 1959–1966. Three measures of child emotional functioning derived from psychologist ratings of behaviour at 7 years of age were examined: distress proneness, attention and inappropriate self-regulation. Adulthood 10-year CVD risk was calculated with the validated Framingham general CVD risk algorithm. Gender-specific multiple regression models assessed associations of childhood emotion and adulthood CVD risk independent of covariates measured across the life course. Potential mediators of the associations were also examined.

Results

Women had 31% higher CVD risk per SD increase in childhood distress proneness (p=0.03) and 8% reduced risk per SD increase in attention (p=0.09). For men, each SD increase in childhood distress proneness was associated with 17% higher CVD risk (p=0.02). Associations were partly explained by adulthood body mass index and depressive symptoms in women but not in men. Inappropriate self-regulation was not associated with CVD risk.

Conclusions

Several aspects of childhood emotional functioning was associated with adulthood CVD risk, particularly for women. As such, primary prevention of CVD may be associated with addressing early life emotional functioning.
How does progress towards the MDG 4 affect inequalities between different subpopulations? Evidence from Nepal
Authors: Nguyen Kim-Huong , Jimenez-Soto Eliana , Morgan Alison , Morgan Chris , Hodge Andrew
Published: January 2013

Background

Few previous studies have examined non-wealth-based inequalities in child mortality within developing countries. This study estimates changes in under-5-year-olds  and neonatal mortality in Nepal across a range of subnational levels, which allows us to assess the degree of equity in Nepal's progress towards Millennium Development Goal 4.

Methods

Direct estimates of under-5-year-olds and neonatal death rates were generated for 1990–2005 using three Demographic and Health Surveys and two Living Standards Surveys by the following levels: national, rural/urban location, ecological region, development region, ethnicity and wealth. Absolute and relative inequalities were measured by rate differences and rate ratios, respectively. Additionally, wealth-related inequality was calculated using slope and relative indexes of inequality and concentration indices.

Results

Estimates suggest that while most rates of under-5-year-olds and neonatal mortality have declined across the different equity markers, leading to a downward trend in absolute inequalities, relative inequalities appear to have remained stable over time. The decline in absolute inequalities is strongest for under-5-year-olds’ mortality, with no statistically significant trend in either relative or absolute inequalities found for neonatal mortality. A possible increase in inequalities, at least in relative terms, was found across development regions, where death rates remain high in the mid-western region.

Conclusions

By 2015, our estimates suggest that more than 65% of deaths of under-5-year-olds will occur in the neonatal period, with stable trends in neonatal mortality inequalities. These findings along with the fact that health outcomes for neonates are more highly dependent on health systems, suggest further equitable reductions in under-5-year-olds mortality will require broad health-system strengthening, with a focus on the improvement of healthcare services provided for mothers and newborns. Other inequities suggest continued special attention for vulnerable subpopulations is warranted, particularly to overcome social exclusion and financial barriers to care in urban areas.
Trajectories of socioeconomic inequalities in health, behaviours and academic achievement across childhood and adolescence
Authors: Howe Laura D , Lawlor Debbie A , Propper Carol
Published: January 2013

Background

Socioeconomic inequalities are a key policy challenge. Studies to date have not taken a unified approach to assess how socioeconomic inequalities in health, behaviour and educational attainment change as children age.

Methods

We examined maternal education inequalities in multiple offspring health, behavioural and educational outcomes and how these changed across childhood and adolescence in the Avon Longitudinal Study of Parents and Children, a cohort born in 1991/1992 in South-West England (N=5560–11 463).

Results

Inequalities were observed for some health measures (blood pressure (BP), height, cholesterol, bone mineral density (BMD) and fat-mass (females)) but not in other measures (parent-assessed child health, triglycerides, fat-mass (males), high-density lipoprotein-cholesterol, C reactive protein). The strongest health inequality was systolic BP (mean difference comparing highest to lowest maternal education −0.28 SD (95% CI −0.35 to −0.20), approximately 2.6 mm Hg. Wide inequalities, similar in magnitude to BP, were observed for behavioural outcomes. Even greater inequalities were observed for offspring academic achievement (mean difference comparing highest to lowest maternal education 1.43 SD (95% CI 1.37 to 1.50), a difference of 22%). For all behavioural outcomes and some health indicators, inequality was stable over childhood. For some outcomes (BP, BMD and most education outcomes), inequality narrowed as children got older. Only for height and attainment in English tests was there evidence of widening inequalities with age.

Conclusions

Our results suggest that within this cohort, maternal education inequalities in offspring health, behaviour and educational attainment are established in childhood but do not increase up to adolescence. Maternal education inequalities in behaviour and educational attainment were considerably larger than in health measures.
Current trends in endovascular management of traumatic cerebrovascular injury
Authors: Kansagra Akash P , Cooke Daniel L , English Joey D , Sincic Ryan M , Amans Matthew R , Dowd Christopher F , Halbach Van V , Higashida Randall T , Hetts Steven W
Published: January 2013

Background

The role of catheter angiography in the diagnosis and management of traumatic cerebrovascular injury has evolved rapidly with advances in CT and MR angiography and continued development of endovascular techniques.

Objective

To identify the modern spectrum of traumatic arterial injury encountered during catheter neuroangiography and to examine current patterns of endovascular treatment.

Methods

Records of trauma patients undergoing catheter neuroangiography over a 4 year period at two high volume centers were retrospectively reviewed. The sample comprised 100 separate arterial lesions that were classified according to mechanism, location, acuity, and endovascular treatment. Follow-up imaging and clinical notes were reviewed to identify procedural complications.

Results

Of 100 arterial lesions, 81% were related to blunt trauma. Distribution of lesions by location was 42% intracranial, 39% cervical, and 19% extracranial. The most common injuries were pseudoaneurysm (38%), fistula (29%), and dissection (19%). In total, 41% of lesions underwent endovascular treatment, with trends favoring treatment of non-acute, penetrating, non-cervical, and high grade lesions. Therapy involved coil embolization for 89% of treated lesions. There were a total of two immediate neurovascular complications and one delayed neurovascular complication; one of these resulted in a permanent neurological deficit.

Conclusions

Our experience in a large cohort of patients suggests that a relatively high proportion of traumatic arterial lesions identified by catheter angiography are treated by endovascular means, with a low rate of immediate and delayed neurovascular complications.
Genetic and ecological differences between two Utah endemics: US federally threatenedTownsendia apricaand its close congener,T. jonesiivar.lutea(Asteraceae)
Authors: Lipsen Linda P.J. , Lee Christopher , Whitton Jeannette
Published: January 2013

We used genetic data from isozymes, along with soil analysis and ecological niche models to characterize two rare, morphologically similar Utah endemic Townsendias (Asteraceae). Townsendia aprica Welsh & Reveal and Townsendia jonesii (Beaman) Reveal var. lutea S.L. Welsh are herbaceous perennials endemic to adjacent areas of the Colorado Plateau region in southern Utah. Both are rare (T. aprica is listed as threatened under the Endangered Species Act, USA), and the validity of recognizing them as separate has been questioned. Populations of both taxa were scored for nine informative isozyme loci. High levels of genetic variation were found in each, with little variation among populations within taxa and low but significant divergence estimated between the taxa (FST= 0.119). Neighbor-joining analysis revealed two moderately supported clusters of populations corresponding to the two taxa. Characteristics of the soils on which the two taxa occur differed significantly in percentage sand (higher for T. aprica), percentage clay, and CaCO3(both higher for T. jonesii var. lutea). Furthermore, ecological niche modeling using 19 climatic variables suggests that the two taxa occupy distinct niches. Taken together, these results support recognition of the two taxa as distinct, and suggest that they are equally imperiled based on their genetic and ecological features.
Growth of largemouth bass in a dynamic estuarine environment: an evaluation of the relative effects of salinity, diet, and temperature
Authors: Glover David C. , DeVries Dennis R. , Wright Russell A.
Published: January 2013

Some freshwater fishes occur regularly in estuarine areas that experience spatial and seasonal variation in marine influence. These dynamic abiotic and biotic conditions potentially influence food consumption and growth. We found that effects of an estuarine environment on the growth of largemouth bass (Micropterus salmoides) in Alabama's Mobile–Tensaw River Delta depended on body size, distance from the marine source, and amount of freshwater inflow. Incremental growth analyses demonstrated that young largemouth bass (<age-3) grew more rapidly downstream in the estuarine environment declining with distance upstream; this relationship was reversed for older fish with faster growth in fresher, upstream areas. The magnitude of freshwater inflow influenced the relationship between age-specific growth and proximity to Mobile Bay. Bioenergetics simulations suggest that interactions among size-specific metabolic cost of salinity, maximum water temperature, and spatial differences in both salinity and prey energetic content can explain these growth patterns. The cost–benefit of the estuarine environment to largemouth bass is not only dynamic seasonally, but also changes ontogenetically because of shifts in salinity tolerance and prey use.
INTERACTIONS OF ELECTROMAGNETIC RADIATION WITH BOSE–EINSTEIN CONDENSATES: MANIPULATING ULTRA–COLD ATOMS WITH LIGHT
Authors: CATTANI FEDERICA , KIM ARKADY , LISAK MIETEK , ANDERSON DAN
Published: January 2013

A review of models describing the interactions of ultra-cold atoms and laser light is given. Both semi-classical and fully quantum models are presented with particular attention given to the introduction of local field effects. Some possible effects of self-localization and guiding, consequences of such interactions, are discussed.
NOVEL VOLTAGE-MODE CASCADABLE ALL-PASS SECTIONS EMPLOYING GROUNDED PASSIVE COMPONENTS
Authors: MAHESHWARI SUDHANSHU , MOHAN JITENDRA , CHAUHAN DURG SINGH
Published: January 2013

This paper presents two new first-order voltage-mode (VM) cascadable all-pass (AP) sections, employing two differential voltage current conveyors (DVCCs) and three grounded passive components. Both circuits possess high input and low output impedance, which makes them easily cascadable. Non-ideality aspects and parasitic effects are also studied. As an application, a quadrature oscillator is designed using the proposed circuit. The proposed circuits are verified through PSPICE simulations using 0.5 μm CMOS parameters.
INTERFERENCE OF MULTI-MODE GAUSSIAN STATES AND "NON APPEARANCE" OF QUANTUM CORRELATIONS
Authors: OLIVARES STEFANO
Published: January 2013

We theoretically investigate bilinear, mode-mixing interactions involving two modes of uncorrelated multi-mode Gaussian states. In particular, we introduce the notion of "locally the same states" (LSS) and prove that two uncorrelated LSS modes are invariant under the mode mixing, i.e. the interaction does not lead to the birth of correlations between the outgoing modes. We also study the interference of orthogonally polarized Gaussian states by means of an interferometric scheme based on a beam splitter, rotators of polarization and polarization filters.
DERIVING AN ELECTRIC CIRCUIT EQUIVALENT MODEL OF CELL MEMBRANE PORES IN ELECTROPORATION
Authors: MORSHED B. I. , SHAMS M. , MUSSIVAND T.
Published: January 2013

Electroporation is the formation of reversible pores in cell membranes under a brief pulse of high electric field. Dynamics of pore formation during electroporation suggests that the transmembrane potential would settle approximately at the threshold transmembrane potential and the transmembrane resistance would decrease significantly from the state of relaxation. The current electric circuit equivalent models for electroporation containing time-invariant, static and passive components are unable to capture the pore dynamics. A biophysically-inspired electric circuit equivalent model containing dynamic components for membrane pores has been derived using biological parameters. The model contains a voltage-controlled resistor driven by a two-stage cascaded integrator that is activated through a voltage-gated switch. Simulation results with the derived model showed higher accuracy compared to a commonly used model, where the transmembrane resistance decreased million-fold at the onset of electroporation and the transmembrane potential settled at 99.5% of the critical transmembrane potential, thus enabling improved dynamic behavior modeling ability of the pores in electroporation. The derived model allows fast and reliable analysis of this biophysical phenomenon and potentially aids in optimization of various parameters involved in electroporation.
Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH2-terminal (sites 2 + 2a) phosphorylation
Authors: Friedrichsen Martin , Birk Jesper B. , Richter Erik A. , Ribel-Madsen Rasmus , Pehmøller Christian , Hansen Bo Falck , Beck-Nielsen Henning , Hirshman Michael F. , Goodyear Laurie J. , Vaag Allan , Poulsen Pernille , Wojtaszewski Jørgen F. P.
Published: January 2013

Type 2 diabetes is characterized by reduced muscle glycogen synthesis. The key enzyme in this process, glycogen synthase (GS), is activated via proximal insulin signaling, but the exact molecular events remain unknown. Previously, we demonstrated that phosphorylation of Thr308 on Akt (p-Akt-Thr308), Akt2 activity, and GS activity in muscle were positively associated with insulin sensitivity. Here, in the same study population, we determined the influence of several upstream elements in the canonical PI3K signaling on muscle GS activation. One-hundred eighty-one nondiabetic twins were examined with the euglycemic hyperinsulinemic clamp combined with excision of muscle biopsies. Insulin signaling was evaluated at the levels of the insulin receptor, IRS-1-associated PI3K (IRS-1-PI3K), Akt, and GS employing activity assays and phosphospecific Western blotting. The insulin-stimulated GS activity was positively associated with p-Akt-Thr308 ( P = 0.01) and Akt2 activity ( P = 0.04) but not p-Akt-Ser473 or IRS-1-PI3K activity. Furthermore, p-Akt-Thr308 and Akt2 activity were negatively associated with NH2-terminal GS phosphorylation ( P = 0.001 for both), which in turn was negatively associated with insulin-stimulated GS activity ( P < 0.001). We found no association between COOH-terminal GS phosphorylation and Akt or GS activity. Employing whole body Akt2-knockout mice, we validated the necessity for Akt2 in insulin-mediated GS activation. However, since insulin did not affect NH2-terminal phosphorylation in mice, we could not use this model to validate the observed association between GS NH2-terminal phosphorylation and Akt activity in humans. In conclusion, our study suggests that although COOH-terminal dephosphorylation is likely necessary for GS activation, Akt2-dependent NH2-terminal dephosphorylation may be the site for “fine-tuning” insulin-mediated GS activation in humans.
A novel stable isotope tracer method to measure muscle protein fractional breakdown rate during a physiological non-steady-state condition
Authors: Tuvdendorj Demidmaa , Chinkes David L. , Herndon David N. , Zhang Xiao-Jun , Wolfe Robert R.
Published: January 2013

The measurement of the fractional breakdown rate (FBR) of muscle proteins during physiological non-steady state of amino acids (AAs) presents some challenges. Therefore, the goal of the present experiment was to modify the bolus stable isotope tracer injection approach to determine both fractional synthesis rate (FSR) and FBR of leg muscle protein during a physiological non-steady state of AAs. The approach uses the traditional precursor-product principle but is modified with the assumption that inward transport of AAs is proportional to their plasma concentrations. The FBR value calculated from the threonine tracer served as a reference to evaluate the validity of the FBR measurement from the phenylalanine tracer, which was under a non-steady-state condition due to the concomitant injection of unlabeled phenylalanine. Plasma phenylalanine concentration increased more than fourfold after the bolus injection, and thereafter it decreased exponentially, whereas the threonine concentration remained stable. FBR values were similar with the two tracers [0.133 ± 0.003 and 0.148 ± 0.003%/h (means ± SE) for the phenylalanine and threonine tracers, respectively, P > 0.05]. In addition, FSR values for the two tracers were similar (0.069 ± 0.002 and 0.067 ± 0.001%/h for the phenylalanine and threonine tracers, respectively, P > 0.05), indicating that the traditional FSR approach can also be used in the non-steady state. Accordingly, net balance (NB) values were similar (−0.065 ± 0.002 and −0.081 ± 0.002%/h for the phenylalanine and threonine tracers, respectively, P > 0.05). This new method of measuring muscle protein FBR during physiological non-steady state gives reliable results and allows simultaneous measurement of muscle protein FSR and thus a calculation of NB.
Reduced mitochondrial ROS, enhanced antioxidant defense, and distinct age-related changes in oxidative damage in muscles of long-lived Peromyscus leucopus
Authors: Shi Yun , Pulliam Daniel A. , Liu Yuhong , Hamilton Ryan T. , Jernigan Amanda L. , Bhattacharya Arunabh , Sloane Lauren B. , Qi Wenbo , Chaudhuri Asish , Buffenstein Rochelle , Ungvari Zoltan , Austad Steven N. , Van Remmen Holly
Published: January 2013

Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus.
Synthesis and Crystal Structure of [MnIII(5-Br-salpn)(DMF)2][B(C6H5)4]
Authors: S Thampidas V. , Basheer Aisha , Shyla Saliny
Published: January 2013

The title compound was synthesized by the reaction between a manganese(II) carboxylate and the tetradentate Schiff base ligand, 5-Br-salpnH2 [N,N′-bis(5-Br-salicylidene)-1,3-diaminopropane] produced in situ. The complex crystallizes in the P21/c space group with unit cell dimensions a=12.37980(10), b=12.60990(10), c=28.9438(3), α=90.00, β=102.0130(10), and γ=90.00. The manganese(III) ion is in a distorted octahedral environment with longer axial bonds.
The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells
Authors: Fernández Massó Julio R. , Oliva Argüelles Brizaida , Tejeda Yelaine , Astrada Soledad , Garay Hilda , Reyes Osvaldo , Delgado-Roche Livan , Bollati-Fogolín Mariela , Vallespí Maribel G.
Published: January 2013

We have demonstrated that the peptide L-2 designed from an alanine scanning of theLimulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-κB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-κB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies.
Bioactive Lipidic Extracts from Octopus (Paraoctopus limaculatus): Antimutagenicity and Antiproliferative Studies
Authors: Moreno-Félix Carolina , Wilson-Sánchez Griselda , Cruz-Ramírez Susana-Gabriela , Velázquez-Contreras Carlos , Plascencia-Jatomea Maribel , Acosta Ana , Machi-Lara Lorena , Aldana-Madrid María-Lourdes , Ezquerra-Brauer Josafat-Marina , Rocha-Alonzo Fernando , Burgos-Hernández Armando
Published: January 2013

Fractions from an organic extract from fresh octopus (Paraoctopus limaculatus) were studied for biological activities such as antimutagenic and antiproliferative properties usingSalmonellatester strains TA98 and TA100 with metabolic activation (S9) and a cancer cell line (B-cell lymphoma), respectively. A chloroform extract obtained from octopus tentacles was sequentially fractionated using thin layer chromatography (TLC), and each fraction was tested for antimutagenic and antiproliferative activities. Organic extract reduced the number of revertants caused by aflatoxin B1showing a dose-response type of relationship. Sequential TLC fractionation of the active extracts produced several antimutagenic and/or antiproliferative fractions. Based on the results obtained, the isolated fractions obtained from octopus contain compounds with chemoprotective properties that reduce the mutagenicity of AFB1and proliferation of cancer cell lines.
HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature
Authors: Saini Neeraj , Hochberg Ephraim P. , Linden Erica A. , Jha Smita , Grohs Heinz K. , Sohani Aliyah R.
Published: January 2013

Primary effusion lymphoma (PEL) is a rare extranodal lymphoma that typically presents in a body cavity in the absence of a detectable tumor mass and that occurs predominantly in immunosuppressed individuals. The neoplastic lymphoid cells are frequently infected with human herpes virus 8 (HHV8), also known as Kaposi sarcoma herpes virus (KSHV). We describe two HIV-negative patients who presented with primary effusion lymphoma of B-cell lineage involving the pleural cavity, but whose tumor cells lacked infection by HHV8. We review the English language literature of HHV8-negative PEL of B-cell lineage and compare these lymphomas to HHV8-associated PEL with regard to clinical and pathological characteristics, therapy, and outcome.
Multiscale fragPIN Modularity
Authors: Capobianco Enrico
Published: January 2013

Modularity in protein interactome networks (PINs) is a central theme involving aspects such as the study of the resolution limit, the comparative assessment of module-finding algorithms, and the role of data integration in systems biology. It is less common to study the relationships between the topological hierarchies embedded within the same network. This occurrence is not unusual, in particular with PINs that are considered assemblies of various interactions depending on specialized biological processes. The integrated view offered so far by modularity maps represents in general a synthesis of a variety of possible interaction maps, each reflecting a certain biological level of specialization. The driving hypothesis of this work leverages on such network components. Therefore, subnetworks are generated from fragmentation, a process aimed to isolating parts of a common network source that are here called fragments, from which the acronym fragPIN is used. The characteristics of modularity in each obtained fragPIN are elucidated and compared. Finally, as it was hypothesized that different timescales may underlie the biological processes from which the fragments are computed, the analysis was centered on an example involving the fluctuation dynamics inherent to the signaling process and was aimed to show how timescales can be identified from such dynamics, in particular assigning the interactions based on selected topological properties.
Trabectedin in the Neoadjuvant Treatment of High-Grade Pleomorphic Sarcoma: Report of a Rare Case and Literature Review
Authors: Schuler Markus K. , Richter Stephan , Platzek Ivan , Beuthien-Baumann Bettina , Wieczorek Kathrin , Hamann Christine , Mohm Johannes , Ehninger Gerhard
Published: January 2013

Background. Pleomorphic sarcoma is an aggressive soft tissue sarcoma. In patients with high-risk extremity sarcomas, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery were reported. To our knowledge, this is the first report in the literature of the neoadjuvant use of trabectedin in a patient with high-grade pleomorphic sarcoma, ineligible for standard neoadjuvant combination therapy with an anthracycline-based regimen.Case Presentation. Here we present a 58-year-old White male with a large tumor in the left thigh, but with no signs of metastases. Owing to the history of severe heart attack, three cycles of neoadjuvant trabectedin were administrated to achieve surgically wide margins. After two cycles, an 18F-FDG-PET showed a large proportion of the central tumor area was without metabolic activity. According to RECIST and Choi criteria, the tumor was stable. After the third cycle of trabectedin, the patient underwent a complete resection, which revealed completely necrotic high-grade pleomorphic sarcoma (stage pT2b), with only a small vital area.Conclusion. The present paper on a promising treatment with neoadjuvant trabectedin of patients with high-grade pleomorphic sarcoma might suggest that such treatment approach may provide a greater chance of cure and survival of such patients.
Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of Its Background
Authors: Rajkumar D. S. R. , Faitelson A. V. , Gudyrev O. S. , Dubrovin G. M. , Pokrovski M. V. , Ivanov A. V.
Published: January 2013

In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing.
Concentration Levels and Ecological Risks of Persistent Organic Pollutants in the Surface Sediments of Tianjin Coastal Area, China
Authors: Lu Xiaoxia , Chen Chaoqi , Zhang Shu , Hou Zhen , Yang Junjun
Published: January 2013

Sediments were sampled from different surface water bodies in Tianjin coastal area, China, and persistent organic pollutants (POPs) including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were measured using GC/MS or GC/ECD. The purposes were to investigate the concentration levels of the POPs and to assess their ecological risks. The results showed that all the 16 priority PAHs were detected from the 10 sediments sampled with the total concentrations of the 16 PAHs ranging from 274.06 μg/kg to 2656.65 μg/kg, while the concentrations of the halogenated POPs were generally low except in the Dagu waste discharging river where the total concentrations of 24 OCPs, 35 PCBs, and 14 PBDEs were 3103.36 μg/kg, 87.31 μg/kg, and 13.88 μg/kg, respectively. In the studied sediments, PAHs exhibited risks to benthonic organisms; particularly the concentrations of naphthalene and/or acenaphthene exceeded their probable effect concentrations in several locations. In comparison, only in the Dagu waste discharging river, OCPs exhibited risks with the concentrations of heptachlor epoxide and lindane exceeding their probable effect concentrations. PCBs and PBDEs posed rare risks in the studied area.