bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Liver Stiffness with Hepatic Expression of Pharmacokinetically Important Genes in Alcoholic Liver Disease
Authors: Theile Dirk , Haefeli Walter Emil , Seitz Helmut Karl , Millonig Gunda , Weiss Johanna , Mueller Sebastian
Published: July 2012

Background

Enhanced drug elimination in alcoholics remains largely indefinable. In contrast, the reduced elimination of drugs in patients with advanced alcoholic liver disease (ALD) is normally owing to hepatic end‐stage disease such as cirrhosis. We here study the mRNA expression of various hepatic drug metabolizing enzymes and transporters in association with liver stiffness (LS) being a novel noninvasive parameter for the assessment of cirrhosis to unravel the dynamic relationship between ALD and determinants of pharmacokinetics such as drug metabolizing enzymes and transporters.

Methods

We quantified mRNA expression levels of various cytochrome P‐450 isoenzymes (CYPs) and drug transporters in 26 liver specimens of chronic alcoholics and 5 controls by quantitative polymerase chain reaction. In addition, liver histology, clinical data, and LS evaluated by transient elastography (Fibroscan) were obtained.

Results

Eighteen patients had a normal or moderate LS < 8 kPa (69.2%), while in the remaining 8 patients (30.7%) advanced F3 or F4 fibrosis could be established with an LS > 8 kPa. Overall, CYP3A4, CYP2E1, and solute carrier organic anion transporter 1B1 (SLCO1B1) were negatively correlated with increasing LS. CYPs and drug transporters tended to be up‐regulated in alcoholics without advanced fibrosis (LS < 8.0 kPa) compared to healthy controls supporting data of boosted drug elimination in alcoholics without advanced ALD. However, in alcoholics with severely increased LS (>8 kPa), expression levels of CYP2E1, SLC22A2, and SLCO1B1 were significantly lower.

Conclusions

In conclusion, CYPs and drug transporters seem to be induced in chronic alcoholics without irreversible liver damage but decline in case of manifest cirrhosis. Our study also suggests that noninvasive measurements of LS could be useful for pharmacokinetic predictions and individualized pharmacotherapy.
Understanding Men's Aggression in Bars: Development of the Beliefs and Attitudes toward Male Alcohol‐Related Aggression (BAMARA) Inventory
Authors: Wells Samantha , Tremblay Paul F. , Graham Kathryn
Published: July 2012

Background

While several qualitative studies suggest that beliefs and attitudes are important in explaining men's alcohol‐related aggression, no quantitative instrument measuring men's beliefs and attitudes about male alcohol‐related aggression has been developed. The purpose of this study was to develop and test a theoretically based multidimensional inventory measuring Beliefs and Attitudes toward Male Alcohol‐Related Aggression (BAMARA) consisting of 9 dimensions: (i) expected negative consequences; (ii) expected positive consequences; (iii) personal approval; (iv) perceived male peer approval; (v) perceived female peer approval; (vi) perceived normality; (vii) relaxed norms when drinking; (viii) alcohol as an excuse; and (ix) male honor/protection of masculinity.

Methods

A random sample of 1,343 young adult male college and university students participated in an online survey. Item analyses using confirmatory factor analytic (CFA) and item‐response theory (IRT) procedures were conducted to select a refined pool of items promoting high internal consistency and discriminant validity of the 9 scales. We evaluated the criterion validity of the 9 scales, the BAMARA total score (BAMARA‐Total), and a short form of the inventory (BAMARA‐SF) in terms of their association with experiences of barroom aggression and other theoretically linked constructs.

Results

CFA and IRT analyses resulted in a 53‐item inventory consisting of the 9 scales with adequate model fit and good internal consistency indices. Criterion validity was demonstrated, with the BAMARA scales correlating well with reports of actual experiences of aggression in bars. BAMARA‐Total and BAMARA‐SF were found to be significantly associated with barroom aggression controlling for a number of important control variables.

Conclusions

This new instrument is expected to have many important applications in the male aggression literature, with the full BAMARA being employed for the assessment of specific beliefs and attitudes and the BAMARA‐SF used as a general attitudinal measure.
Pedometer‐Determined Physical Activity and Body Composition in Chinese Working Adults
Authors: Lam Simon C. , Lee Linda Y. K. , Wong S. L. , Wong Alisa K. P.
Published: July 2012

Purpose: Overweight and obesity are prevalent public health problems in many developed and developing regions. Despite extensive documentation on the health benefits of physical activities, little is known about the level of physical activity in the Hong Kong Chinese population. Working adults, in particular, deserve primary attention because they account for the largest proportion of Hong Kong society. The purposes of this study were to investigate pedometer‐determined physical activity and examine the associations between physical activity and body composition variables among Chinese working adults in Hong Kong.

Design: This study adopted a descriptive cross‐sectional design.

Methods: A quota sample of 913 working adults from nine major occupational categories was recruited. Demographic characteristics and body composition parameters (weight, height, and waist and hip circumferences) were assessed. Body mass index and waist‐to‐hip ratio were then calculated. Physical activity was measured in terms of daily walking steps using a pedometer over 1 week. Participants were then categorized as “inactive,”“somewhat active,” or “regularly active.” Descriptive and inferential statistics (analysis of variance, t test, and χ2 test) were used appropriately.

Findings: Of the 913 participants, 893 returned complete step count records. The completion rate was 97.8%. Participants on average walked 8,661 steps per day, suggesting a “somewhat active” populace. Significant differences were found between the group “regularly active” and “inactive” in most of the body composition parameters. However, a significant weak correlation was found between physical activity and body mass index (r= 0.12, p= .001). Such findings deserve further investigation.

Conclusions: The Chinese working adults in Hong Kong were found to be somewhat active in physical activity.

Clinical Relevance: Findings pose implications for healthcare professionals who are responsible for health promotion in the Asian community setting. Leisure‐type physical activity, such as walking, can be incorporated into daily routines.
Exchange Rising? Karl Polanyi and Contentious Politics in Contemporary Latin America
Authors: Silva Eduardo
Published: July 2012

Free-market reforms in the last quarter of the twentieth century weakened the point of production—labor unions—asthesource of effective nonparty political countermovement to liberal capitalism. Has another significant source of societal resistance arisen in association with the resurgence of market economics? Building on the work of Karl Polanyi, this article argues that circuits of exchange—the commodification of labor, land, and money—can be powerful sources of movement against contemporary forms of free-market capitalism. It draws on the cases of Argentina, Bolivia, and Ecuador to explore how Polanyi's exchange-based approach helps to elucidate three phenomena: the great variety of identities behind the myriad movements against free-market capitalism, the emergence of community as a powerful locus for organizing, and the proliferation of new forms of transgressive and highly disruptive direct action to reinforce the debilitated effectiveness of the strike.
Death Following Injection Sclerotherapy Due to Phenol Toxicity
Authors: Philip Abraham T. , Marraffa Jeanna M.
Published: July 2012

Prolapse rectum (PR) or protrusion of the rectum beyond the anus occurs frequently in populations at both extremes of age. In the pediatric population, in developed countries, the commonest cause for PR is thought to be cystic fibrosis (CF). Treatment options for CF include conservative management, surgical resection and fixation, suturing, and injection sclerotherapy (IS). The last is considered an attractive treatment option because it is minimally invasive. In this case report, the authors present the details about a 2‐year‐old female child, with PR and CF, who died after IS, using phenol as the sclerotherapeutic agent. Autopsy findings and toxicology tests performed to establish phenol toxicity are documented. The available literature is reviewed. This case report underscores the risks of using phenol for IS and emphasizes the point that the procedure is not innocuous and an adverse outcome including fatality is a possibility.
Endophytic fungus fine‐tunes the persistence strategy of its alpine host grass in response to soil resource levels
Authors: Gibert Anaïs , Magda Danièle , Hazard Laurent
Published: July 2012

An understanding of hereditary endophytic fungi, and the effects on grass persistence strategies (i.e. relative investment in sexual reproduction and vegetative growth) under natural conditions may help to predict how some alpine ecosystems will respond to environmental change. Grass persistence and endophyte maintenance in host populations are closely related, but could become independent due to endophyte loss mechanisms. We used native grass and endophyte populations to test the hypothesis that fungal endophytes manipulate grass persistence strategies to secure endophyte maintenance in plant populations. Two conditions were required to verify this hypothesis: 1) the fungus caused alterations in host plant strategies; and 2) plant phenotypic changes induced by the fungal endophyte increased endophyte transmission. We compared symbiotic (S) and non‐symbiotic (NS) persistence strategies of Festuca eskia (Poaceae), an alpine grass infected by the asexual form of the fungal endophyte Epichloë festucae. We characterised endophyte transmission efficiency, and described vegetative growth and sexual reproduction in a field population that naturally supports approximately 50% S plants. We built a demographic model to estimate plant vegetative growth rates. A correlation between plant persistence strategy, and fungal maintenance was evaluated by increasing soil resource levels. Under natural conditions, S and NS plants exploited different persistence strategies in the same population; S plants exhibited greater vegetative growth than their NS counterparts, while maintaining the same reproductive output. In response to higher soil resource levels, S plants shifted in persistence strategies and phenology, whereas NS plants maintained the same strategies. Therefore, results suggested the fungal endophyte fine‐tuned host persistence strategies according to soil resource level. Finally, we found no direct relationship between the changes induced by fungal endophyte and endophyte transmission. Consequently, fungal endophytes affected host persistence strategies, but did not directly increase endophyte transmission.
Nutrient‐specific foraging leads to Allee effects and dynamic functional responses
Authors: Neeson Thomas M. , Salomon Mor , Coll Moshe
Published: July 2012

Most animals forage in nutritionally complicated environments in which the densities of complementary foods vary in space and time. Locally rare foods can lead to nutritional deficiencies in consumers, yet there has been little consideration of the influence of nutritional deficits, and consumers’ efforts to redress these deficits, on population and community dynamics. A taxonomically and trophically diverse group of animals can redress accumulated deficits using nutrient‐specific foraging, defined here as the ability of an animal to bias its foraging effort towards certain foods on the basis of its own nutritional state. We focus on the true omnivores, because they feed on vastly different nutrient sources, animals and plants. We use an ordinary differential equation model to show that nutrient‐specific foraging may destabilize omnivore–prey population dynamics, depending on the degree to which the omnivore alters its foraging in an attempt to balance its nutritional state. In particular, a high behavioral sensitivity to nutritional imbalances led to a novel type of Allee effect driven by the interaction between prey density and nutritional deficiencies in the omnivore. Our model overall is characterized by a causal loop between the omnivore's nutritional state, food preferences and population dynamics. Consequently, the omnivore exhibited a dynamic functional response, in which the relationship between prey density and omnivore per capita consumption of prey was influenced by the current nutritional state of the omnivore. With regards to omnivory in general, our results reinforce the idea that statements about the effects of omnivory on population or community stability are not possible without a consideration of the behavioral mechanisms of diet mixing.
The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study
Authors: Shopsin Baron
Published: July 2012

Objectives

To examine and record the clinical antidepressant effect of exogenous agmatine, an amino acid derived central glutamaergic modulator in endogenously depressed subjects. It was also the author's intention to examine the effects of parachlorophenylalanine (PCPA) in therapeutic responders to determine if serotonergic mechanisms mediate agmatine's antidepressant effect.

Methodology

Exogenous agmatine was ingested in doses of 2‐3mg/day by depressed subjects with Major Depresssive Disorder (MDD), clinically assessed using the 21 item Hamilton Rating Scale for Depression (HAM‐D), the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS). Antidepressant responders volunteered to concommittantly ingest parachlorophenylalanine (PCPA) at starting doses of 250mg/day, and increased until depressive relapse, mitigating side effects, or a maximum dosage of 1250mg/day.

Results

Three depressed subjects showing total illness remission with exogenous agmatine did not relapse after concomitantly adding PCPA. Effective in relieving both psychomotor agitation and retardation, the antidepressant effect was free of physical or behavioural side effects: gastrointestinal discomfort and loose stools in one subject resolved spontaneously within days. All three subjects refused to risk depressive relapse by temporarily stopping agmatine after PCPA was stopped.

Conclusion

The antidepressant effect of exogenous agmatine was documented in a small number of MDD subjects, and was not reversed/modified by PCPA confirming findings in animals that therapeutic response is not mediated by serotonergic mechanisms. A NAMDA (N‐methyl‐D‐aspartate) receptor antagonist, agmatine's recognized function in brain as inhibitory modulator of excitatory glutamatergic transmission suggests a pivotal role for brain glutamate, contributing to the ripening glutamatergic basis of depression, and a rational basis for future antidepressant pharmacotherapy.
Race, Attorney Influence, and Bankruptcy Chapter Choice
Authors: Braucher Jean , Cohen Dov , Lawless Robert M.
Published: July 2012

We report on racially disparate uses of Chapter 13 bankruptcy. Currently, approximately 1,500,000 bankruptcy petitions are filed each year, with about 30 percent of those petitions being Chapter 13 cases. Although Chapter 13 can offer some legal advantages for persons seeking to protect valuable assets such as a house or automobile, it generally offers less relief and costs more than the primary alternative available to consumers, Chapter 7. The chief feature of a Chapter 13 bankruptcy case is a plan under which the debtor must devote all his or her disposable income to creditor repayment over a three‐ to five‐year period. Chapter 7, in contrast, requires only that the debtor turn over all nonexempt assets, with over 90 percent of Chapter 7 debtors having no assets to turn over. This article reports on two studies, one using data from actual bankruptcy cases and the other involving an experiment with a national random sample of bankruptcy attorneys. Because the court system does not collect racial data on bankruptcy filers, the first study uses data from the Consumer Bankruptcy Project. Even after controlling for financial, demographic, and legal factors that might favor a Chapter 13 filing, African Americans are much more likely to file Chapter 13, as compared to debtors of other races. The second study reports on an experimental vignette sent to a random sample of consumer bankruptcy attorneys who represented debtors. The attorneys were more likely to recommend Chapter 13 when the hypothetical debtors were a couple named “Reggie & Latisha,” who attended an African Methodist Episcopal Church, as compared to a couple named “Todd & Allison,” who attended a United Methodist Church. Also, attorneys viewed “Reggie & Latisha” as having better values and being more competent when they expressed a preference for Chapter 13 as compared to “Todd & Allison,” who were seen as having better values and being more competent when they wanted to file Chapter 7, giving them a “fresh start.” Previous research and the results from the present experimental vignette study suggest that consumer bankruptcy attorneys may be playing a very important, although likely unintentional, role in creating the racial disparity in chapter choice. Together, the two studies raise questions about the fairness of the bankruptcy system.
Quantifying Tropical Dry Forest Type and Succession: Substantial Improvement with LiDAR
Authors: Martinuzzi Sebastián , Gould William A. , Vierling Lee A. , Hudak Andrew T. , Nelson Ross F. , Evans Jeffrey S.
Published: July 2012

Improved technologies are needed to advance our knowledge of the biophysical and human factors influencing tropical dry forests, one of the world's most threatened ecosystems. We evaluated the use of light detection and ranging (LiDAR) data to address two major needs in remote sensing of tropical dry forests, i.e., classification of forest types and delineation of forest successional status. We evaluated LiDAR‐derived measures of three‐dimensional canopy structure and subcanopy topography using classification‐tree techniques to separate different dry forest types and successional stages in the Guánica Biosphere Reserve in Puerto Rico. We compared the LiDAR‐based results with classifications made from commonly used remote sensing data, including Landsat satellite imagery and radar‐based topographic data. The accuracy of the LiDAR‐based forest type classification (including native‐ and exotic‐dominated forest classes) was substantially higher than those from previously available data (kappa = 0.90 and 0.63, respectively). The best result was obtained when combining LiDAR‐derived metrics of canopy structure and topography, and adding Landsat spectral data did not improve the classification. For the second objective, we observed that LiDAR‐derived variables of vegetation structure were better predictors of forest successional status (i.e., mid‐secondary, late‐secondary, and primary forests) than was spectral information from Landsat. Importantly, the key LiDAR predictors identified within each classification‐tree model agreed with previous ecological knowledge of these forests. Our study highlights the value of LiDAR remote sensing for assessing tropical dry forests, reinforcing the potential for this novel technology to advance research and management of tropical forests in general.
Accounting for Algae
Authors: Pena Naomi , Frieden Dorian , Bird David Neil
Published: July 2012

Interest and research in the use of algae for energy is growing but an analysis of the different methods for the accounting for the carbon dioxide (CO
2) emissions that result, is lacking. In this article, four accounting systems are evaluated for their completeness, simplicity, sectoral accuracy, and scale‐independence. Two options under the Kyoto Protocol (KP), a value‐chain (end‐user responsibility) approach, and Point of Uptake and Release (POUR) are evaluated.

Algal material is used in biofuels, animal feeds, human foods, and food supplements, and a range of products such as paints, cosmetics, and plastics. There are also proposals for using algae as a soil amendment. This variety of uses for algal material together with the fact that it will probably contain carbon of fossil origin presents accounting challenges and reveals inconsistencies that have lain in the KPs treatment of biomass emissions. Furthermore, a key conclusion of the article is that neither proposed KP accounting approach for algae leads to correct accounting of emissions for all uses. Both value chain and POUR approaches more correctly and consistently account for algal emissions across uses. POUR offers the potential to provide comprehensive, consistent emission accounting across all uses of biomass, which represents a major step forward in accounting for CO
2 emissions due to use of biomass.
Reverse the Trend for Proximal Humeral Fractures: A Review of the Evidence for the Use of Reverse Shoulder Replacement in Acute Trauma
Authors: Taylor Clare , Cosker Thomas , Smith Christopher
Published: July 2012

Background

Proximal humeral fractures in the elderly population represent a particularly demanding subset of fractures. These have been traditionally treated with Hemi-arthroplasty (HA). Recently there has been a trend towards using a Reverse shoulder replacement (RSR) in some of these patients. The primary aim of the study was to systematically review the literature on the functional outcome scores for RSR in proximal humeral fractures and compare it with the best quality literature available for HA. Secondarily to compare range of movement, complication rates, re-operation rates and x-ray changes.

Methods

A systematic review of the literature was performed using the keywords: Delta, inverse, shoulder, trauma, and fracture. Only studies with 10 patients or more, presenting new data on the functional outcome scores of RSR for acute trauma were included. Studies reporting the use of RSR for fracture sequalae were excluded. These results were compared to the most comprehensive and up to date literature available for HA for proximal humeral fractures.

Results

Eight papers met the full inclusion and exclusion criteria. Data was available for 178 patients with a minimum follow-up of only 3 months. The mean absolute constant score for RSR patients was 54% and 57% for HA patients. RSR had an infection rate of 3%, a dislocation rate of 4% and an overall re-operation rate of 5.6%.

Conclusion

Functional outcomes and range of movements achieved by RSR seem to be similar to those achieved by HA and may eventually be proven to have better outcomes in a certain sub-group of patients. However, there is currently less than 200 patients reported in the literature with a very short term follow-up. RSR is more expensive than HA, and there is a definite learning curve associated with this prosthesis. Although RSR may be valuable in patients where a traditional HA is deemed not suitable, caution must be used until better quality research is available. Level of evidence: Level III systematic review of Level III studies
Diaphragmatic repair of hepatic hydrothorax with VATS after abdominal insufflation with CO2
Authors: Nakamura Y , Iwazaki M , Yasui N , Seki H , Matsumoto H , Masuda R , Nishiumi N , Shimada A
Published: July 2012

Hepatic hydrothorax is defined as the presence of a significant pleural effusion that develops in a patient with cirrhosis of the liver who does not have an underlying cardiac or pulmonary disease. There have been few published case reports dealing with hepatic hydrothorax treated surgically. Recently, we treated a patient with refractory hepatic hydrothorax by directly suturing the diaphragmatic defect during VATS. During surgery, the diaphragmatic defect was identified by using abdominal insufflation with CO
2. The defect was sutured and the diaphragm was covered by polyglycolic acid felt and fibrin glue. After surgery, the patient's pleural effusion improved, his postoperative course was uneventful and he did not require a drainage tube at discharge.
Control of neuronal excitability by NMDA‐type glutamate receptors in early developing binaural auditory neurons
Authors: Sanchez Jason Tait , Seidl Armin H. , Rubel Edwin W. , Barria Andres
Published: July 2012

Key points

Mature nucleus laminaris (NL) neurons in the avian auditory brainstem respond with one or two action potentials to repetitive synaptic stimulation due to strong expression of low‐voltage‐activated K+ channels (KLVA) and other intrinsic factors.

We observe early in development, before the onset of hearing, NL neurons respond in similar fashion despite low expression of KLVA channels. At this age, synaptic NMDA‐type glutamate receptors (NMDA‐Rs) contain primarily the GluN2B subunit, which allow the summation of synaptic responses and keep voltage‐dependent Na+ channels inactivated.

Weaker Mg2+ blockade of NMDA‐Rs and an immature reuptake system cause a tonic NMDA‐R‐mediated current that sets the membrane potential at more depolarized values. Small KLVA conductances localized in dendrites prevent ramping depolarization and excessive excitability.

Our data show that before intrinsic properties are fully developed, NMDA‐Rs limit the output of NL neurons.

Abstract  Precise control of neuronal excitability in the auditory brainstem is fundamental for processing timing cues used for sound localization and signal discrimination in complex acoustic environments. In mature nucleus laminaris (NL), the first nucleus responsible for binaural processing in chickens, neuronal excitability is governed primarily by voltage‐activated potassium conductances (KVA). High levels of KVA expression in NL neurons result in one or two initial action potentials (APs) in response to high‐frequency synaptic activity or sustained depolarization. Here we show that during a period of synaptogenesis and circuit refinement, before hearing onset, KVA conductances are relatively small, in particular low‐voltage‐activated K+ conductances (KLVA). In spite of this, neuronal output is filtered and repetitive synaptic activity generates only one or two initial APs during a train of stimuli. During this early developmental time period, synaptic NMDA‐type glutamate receptors (NMDA‐Rs) contain primarily the GluN2B subunit. We show that the slow decay kinetics of GluN2B‐containing NMDA‐Rs allows synaptic responses to summate, filtering the output of NL neurons before intrinsic properties are fully developed. Weaker Mg2+ blockade of NMDA‐Rs and ambient glutamate early in development generate a tonic NMDA‐R‐mediated current that sets the membrane potential at more depolarized values. Small KLVA conductances, localized in dendrites, prevent excessive depolarization caused by tonic activation of NMDA‐Rs. Thus, before intrinsic properties are fully developed, NMDA‐Rs control the output of NL neurons during evoked synaptic transmission.
Megalin mediates transepithelial albumin clearance from the alveolar space of intact rabbit lungs
Authors: Buchäckert Yasmin , Rummel Sebastian , Vohwinkel Christine U. , Gabrielli Nieves M. , Grzesik Benno A. , Mayer Konstantin , Herold Susanne , Morty Rory E. , Seeger Werner , Vadász István
Published: July 2012

Key points

Under physiological conditions the lung alveoli are impermeable to protein.

In patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) protein‐rich oedema fluid accumulates in the distal airspaces and leads to a life‐threatening impairment of alveolar gas exchange.

Albumin is a ligand of megalin, a member of the low‐density lipoprotein (LDL)‐receptor family.

We show that clearance of albumin from the distal air spaces is facilitated by active megalin‐mediated transport across the alveolar epithelium.

Understanding of protein clearance mechanisms in the lung may ultimately lead to novel therapeutic approaches for the treatment of ALI/ARDS.

Abstract  The alveolo‐capillary barrier is effectively impermeable to large solutes such as proteins. A hallmark of acute lung injury/acute respiratory distress syndrome is the accumulation of protein‐rich oedema fluid in the distal airspaces. Excess protein must be cleared from the alveolar space for recovery; however, the mechanisms of protein clearance remain incompletely understood. In intact rabbit lungs 29.8 ± 2.2% of the radio‐labelled alveolar albumin was transported to the vascular compartment at 37°C within 120 min, as assessed by real‐time measurement of 125I‐albumin clearance from the alveolar space. At 4°C or 22°C significantly lower albumin clearance (3.7 ± 0.4 or 16.2 ± 1.1%, respectively) was observed. Deposition of a 1000‐fold molar excess of unlabelled albumin into the alveolar space or inhibition of cytoskeletal rearrangement or clathrin‐dependent endocytosis largely inhibited the transport of 125I‐albumin to the vasculature, while administration of unlabelled albumin to the vascular space had no effect on albumin clearance. Furthermore, albumin uptake capacity was measured as about 0.37 mg ml−1 in cultured rat lung epithelial monolayers, further highlighting the (patho)physiological relevance of active alveolar epithelial protein transport. Moreover, gene silencing and pharmacological inhibition of the multi‐ligand receptor megalin resulted in significantly decreased albumin binding and uptake in monolayers of primary alveolar type II and type I‐like and cultured lung epithelial cells. Our data indicate that clearance of albumin from the distal air spaces is facilitated by an active, high‐capacity, megalin‐mediated transport process across the alveolar epithelium. Further understanding of this mechanism is of clinical importance, since an inability to clear excess protein from the alveolar space is associated with poor outcome in patients with acute lung injury/acute respiratory distress syndrome.
New perspectives concerning feedback influences on cardiorespiratory control during rhythmic exercise and on exercise performance
Authors: Dempsey Jerome A.
Published: July 2012

Abstract  The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward ‘central command’ mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types of feedback afferents on the cardiorespiratory response to voluntary, rhythmic exercise by inhibiting their normal ‘tonic’ activity in healthy animals and humans and in chronic heart failure. Transient inhibition of the carotid chemoreceptors during moderate intensity exercise reduced muscle sympathetic nerve activity (MSNA) and increased limb vascular conductance and blood flow; and reducing the normal level of respiratory muscle work during heavier intensity exercise increased limb vascular conductance and blood flow. These cardiorespiratory effects were prevented via ganglionic blockade and were enhanced in chronic heart failure and in hypoxia. Blockade of μ opioid sensitive locomotor muscle afferents, with preservation of central motor output via intrathecal fentanyl: (a) reduced the mean arterial blood pressure (MAP), heart rate and ventilatory responses to all steady state exercise intensities; and (b) during sustained high intensity exercise, reduced O2 transport, increased central motor output and end‐exercise muscle fatigue and reduced endurance performance. We propose that these three afferent reflexes – probably acting in concert with feedforward central command – contribute significantly to preserving O2 transport to locomotor and to respiratory muscles during exercise. Locomotor muscle afferents also appear to provide feedback concerning the metabolic state of the muscle to influence central motor output, thereby limiting peripheral fatigue development.
Investigation of Strain Gradients and Magnitudes During Microbending
Authors: Wang Lijie , Korkolis Yannis , Kinsey Brad L.
Published: July 2012

Sheet metal forming of parts with microscale dimensions is gaining importance due to the current trend toward miniaturization, especially in the electronics industry. In microforming, although the process dimensions are scaled down, the polycrystalline material stays the same (e.g., the grain size remains constant). When the specimen feature size approaches the grain size, the properties of individual grains begin to affect the overall deformation behavior. This results in inhomogeneous deformation and increased data scatter of the process parameters. In this research, the influence of the specimen size and the grain size on the distribution of plastic deformation through the thickness during a three-point microbending process is investigated via digital image correlation (DIC). Results showed that with miniaturization, a decrease in the strain gradient existed which matched previous research with respect to microhardness measurement.
Numerical Modeling of Transport Phenomena and Dendritic Growth in Laser Spot Conduction Welding of 304 Stainless Steel
Authors: Tan Wenda , Bailey Neil S. , Shin Yung C.
Published: July 2012

A multiscale model is developed to investigate the heat/mass transport and dendrite growth in laser spot conduction welding. A macroscale transient model of heat transport and fluid flow is built to study the evolution of temperature and velocity field of the molten pool. The molten pool shape is calculated and matches well with the experimental result. On the microscale level, the dendritic growth of 304 stainless steel is simulated by a novel model that has coupled the cellular automata (CA) and phase field (PF) methods. The epitaxial growth is accurately identified by defining both the grain density and dendrite arm density at the fusion line. By applying the macroscale thermal history onto the microscale calculation domain, the microstructure evolution of the entire molten pool is simulated. The predicted microstructure achieves a good quantitative agreement with the experimental results.
Distinct Spatial and Molecular Features of Notch Pathway Assembly in Regulatory T Cells
Authors: Perumalsamy Lakshmi R. , Marcel Nimi , Kulkarni Sneha , Radtke Freddy , Sarin Apurva
Published: July 2012

A cytosolic function of Notch helps regulatory T cells survive.
p53 Functions in Endothelial Cells to Prevent Radiation-Induced Myocardial Injury in Mice
Authors: Lee Chang-Lung , Moding Everett J. , Cuneo Kyle C. , Li Yifan , Sullivan Julie M. , Mao Lan , Washington Iman , Jeffords Laura B. , Rodrigues Rafaela C. , Ma Yan , Das Shiva , Kontos Christopher D. , Kim Yongbaek , Rockman Howard A. , Kirsch David G.
Published: July 2012

Without the transcription factor p53 in cardiac endothelial cells, the heart is more susceptible to radiation-induced damage.
Redox Status Incites Gametogenesis
Authors: Hines Pamela J.
Published: July 2012

Maize anthers use cellular redox status rather than a specific germ cell lineage to signal production of new germ cells.
Finding Another Role for NEMO
Authors: Foley John F.
Published: July 2012

The adaptor protein NEMO, which is required for activation of the kinase IKKβ, also controls its specificity to ensure NF-κB activation.
Systematic Analysis of Pyrazinamide-Resistant Spontaneous Mutants and Clinical Isolates of Mycobacterium tuberculosis
Authors: Stoffels Karolien , Mathys Vanessa , Fauville-Dufaux Maryse , Wintjens René , Bifani Pablo
Published: July 2012

Pyrazinamide (PZA) is a first-line antitubercular drug known for its activity against persistent
Mycobacterium tuberculosis
bacilli. We set out to systematically determine the PZA susceptibility profiles and mutations in the pyrazinamidase (
pncA
) gene of a collection of multidrug-resistant tuberculosis (MDR-TB) clinical isolates and PZA-resistant (PZA
r
) spontaneous mutants. The frequency of acquired resistance to PZA was determined to be 10
−5
bacilli
in vitro
. Selection at a lower concentration of PZA yielded a significantly larger number of spontaneous mutants. The methodical approach employed allowed for determination of the frequency of the PZA
r
phenotype correlated with mutations in the
pncA
gene, which was 87.5% for the laboratory-selected spontaneous mutants examined in this study. As elucidated by structural analysis, most of the identified mutations were foreseen to affect protein activity through either alteration of an active site residue or destabilization of protein structure, indicating some preferential mutation site rather than random scattering. Twelve percent of the PZA
r
mutants did not have a
pncA
mutation, strongly indicating the presence of at least one other mechanism(s) of PZA
r
.
A Potential Substrate Binding Conformation of β-Lactams and Insight into the Broad Spectrum of NDM-1 Activity
Authors: Yuan Qinghui , He Lin , Ke Hengming
Published: July 2012

New Delhi metallo-β-lactamase 1 (NDM-1) is a key enzyme that the pathogen
Klebsiella pneumonia
uses to hydrolyze almost all β-lactam antibiotics. It is currently unclear why NDM-1 has a broad spectrum of activity. Docking of the representatives of the β-lactam families into the active site of NDM-1 is reported here. All the β-lactams naturally fit the NDM-1 pocket, implying that NDM-1 can accommodate the substrates without dramatic conformation changes. The docking reveals two major binding modes of the β-lactams, which we tentatively name the S (substrate) and I (inhibitor) conformers. In the S conformers of all the β-lactams, the amide oxygen and the carboxylic group conservatively interact with two zinc ions, while the substitutions on the fused rings show dramatic differences in their conformations and positions. Since the bridging hydroxide ion/water in the S conformer is at the position for the nucleophilic attack, the S conformation may simulate the true binding of a substrate to NDM-1. The I conformer either blocks or displaces the bridging hydroxide ion/water, such as in the case of aztreonam, and is thus inhibitory. The docking also suggests that substitutions on the β-lactam ring are required for β-lactams to bind in the S conformation, and therefore, small β-lactams such as clavulanic acid would be inhibitors of NDM-1. Finally, our docking shows that moxalactam uses its tyrosyl-carboxylic group to compete with the S conformer and would thus be a poor substrate of NDM-1.
Prc Contributes to Escherichia coli Evasion of Classical Complement-Mediated Serum Killing
Authors: Wang Chin-Ya , Wang Shainn-Wei , Huang Wen-Chun , Kim Kwang Sik , Chang Nan-Shan , Wang Ying-Hsiang , Wu Meng-Hsing , Teng Ching-Hao
Published: July 2012

Escherichia coliis a common Gram-negative organism that causes bacteremia. Prc, a bacterial periplasmic protease, and its homologues are known to be involved in the pathogenesis of Gram-negative bacterial infections. The present study examined the role of Prc inE. colibacteremia and characterized the ability of theprcmutant of the pathogenicE. colistrain RS218 to cause bacteremia and survive in human serum. Theprcmutant of RS218 exhibited a decreased ability to cause a high level of bacteremia and was more sensitive to serum killing than strain RS218. This sensitivity was due to the mutant's decreased ability to avoid the activation of the antibody-dependent and -independent classical complement cascades as well as its decreased resistance to killing mediated by the membrane attack complex, the end product of complement system activation. The demonstration of Prc in the evasion of classical complement-mediated serum killing of pathogenicE. colimakes this factor a potential target for the development of therapeutic and preventive measures againstE. colibacteremia.
OxyR Activation in Porphyromonas gingivalis in Response to a Hemin-Limited Environment
Authors: Xie Hua , Zheng Cunge
Published: July 2012

Porphyromonas gingivalis
is a Gram-negative obligately anaerobic bacterium associated with several forms of periodontal disease, most closely with chronic periodontitis. Previous studies demonstrated that OxyR plays an important role in the aerotolerance of
P. gingivalis
by upregulating the expression of oxidative-stress genes. Increases in oxygen tension and in H
2
O
2
both induce activation of OxyR. It is also known that
P. gingivalis
requires hemin as an iron source for its growth. In this study, we found that a hemin-limited growth environment significantly enhanced OxyR activity in
P. gingivalis
. As a result, expression of
sod
,
dps
, and
ahpC
was also upregulated. Using a chromatin immunoprecipitation quantitative PCR (qPCR) analysis, DNA binding of activated OxyR to the promoter of the
sod
gene was enhanced in
P. gingivalis
grown under hemin-limited conditions compared to excess-hemin conditions. Cellular tolerance of H
2
O
2
was also enhanced when hemin was limited in the growth medium of
P. gingivalis
. Our work supports a model in which hemin serves as a signal for the regulation of OxyR activity and indicates that
P. gingivalis
coordinately regulates expression of oxidative-stress-related genes by this hemin concentration-dependent pathway.
QUESTIONS AND PROSPECTS IN QUARKONIUM POLARIZATION MEASUREMENTS FROM PROTON–PROTON TO NUCLEUS–NUCLEUS COLLISIONS
Authors: FACCIOLI PIETRO
Published: July 2012

Polarization measurements are the best instrument to understand how quark and antiquark combine into the different quarkonium states, but no model has so far succeeded in explaining the measured J/ψ and ϒ polarizations. On the other hand, the experimental data in proton–antiproton and proton–nucleus collisions are inconsistent, incomplete and ambiguous. New analyses will have to properly address often underestimated issues: the existence of azimuthal anisotropies, the dependence on the reference frame, the influence of the experimental acceptance on the comparison with other measurements and with theory. Additionally, a recently developed frame-invariant formalism will provide an alternative and often more immediate physical viewpoint and, at the same time, will help probing systematic effects due to experimental biases. The role of feed-down decays from heavier states, a crucial missing piece in the current experimental knowledge, will have to be investigated. Ultimately, quarkonium polarization measurements will also offer new possibilities in the study of the properties of the quark–gluon plasma.
PARAMETRIC INSTABILITY IN SCALAR GRAVITATIONAL FIELDS
Authors: DAVIES TREVOR B. , WANG CHARLES H.-T. , BINGHAM ROBERT , TITO MENDONÇA J.
Published: July 2012

We present a brief review on a new dynamical mechanism for a strong field effect in scalar–tensor theory. Starting with a summary of the essential features of the theory and subsequent work by several authors, we analytically investigate the parametric excitation of a scalar gravitational field in a spherically symmetric radially pulsating neutron star.
NEW SPHERICAL SCALAR MODES ON THE DE SITTER EXPANDING UNIVERSE
Authors: PASCU GABRIEL
Published: July 2012

New spherical scalar modes on the expanding part of Sitter spacetime, eigenfunctions of a conserved Hamiltonian-like operator are found by solving the Klein–Gordon equation in the appropriate coordinate chart, with the help of a time evolution picture technique specially developed for spatially flat Friedmann–Lemaître–Robertson–Walker (FLRW) charts. Transition coefficients are computed between these modes and the rest of the scalar spherical and plane wave modes, either momentum or energy eigenfunctions on the spatially flat FLRW chart.
ON RENORMALIZABILITY OF THE EFFECTIVE FIELD THEORY OF MASSIVE YANG–MILLS FIELDS
Authors: GEGELIA J. , JAPARIDZE G.
Published: July 2012

Effective field theory (EFT) of massive Yang–Mills fields interacting with fermions is considered. Perturbative renormalizability in the framework of EFT is shown. It is argued that the limit of vanishing vector boson mass leads to massless gauge EFT. Possible relevance for the solution to the strong CP problem is discussed.
GRAVITATIONAL CHERENKOV RADIATION FROM EXTENDED THEORIES OF GRAVITY
Authors: DE LAURENTIS M. , CAPOZZIELLO S. , BASINI G.
Published: July 2012

We linearize the field equations for higher order theories of gravity that contain scalar invariants other than the Ricci scalar. We find that besides a massless spin-2 field (the standard graviton), the theory contains also spin-0 and spin-2 massive modes with the latter being, in general, ghost modes. The rate at which such particles would emit gravitational Cherenkov radiation is calculated for some interesting physical cases.
THE ωρπ COUPLING IN THE VMD MODEL REVISITED
Authors: GUDIÑO D. GARCÍA , SÁNCHEZ G. TOLEDO
Published: July 2012

We determine the value of the ω-ρ-π mesons coupling (gωρπ), in the context of the vector meson dominance model, from radiative decays, the ω→3π decay width and the e+e-→3π cross-section. For the last two observables we consider the effect of either a heavier resonance (ρ′(1450)) or a contact term. A weighted average of the results from the set of observables yields gωρπ = 14.7±0.1 GeV -1 in absence of those contributions, and gωρπ = 11.9 ± 0.2 GeV -1 or gωρπ = 11.7 ± 0.1 GeV -1 when including the ρ′ or contact term, respectively. The inclusion of these additional terms makes the estimates from the different observables to lay in a more reduced range. Improved measurements of these observables and the ρ′(1450) meson parameters are needed to give a definite answer on the pertinence of the inclusion of this last one in the considered processes.
DIRAC THEORY ON A SPACE WITH LINEAR LIE TYPE FUZZINESS
Authors: SHARIATI AHMAD , KHORRAMI MOHAMMAD , FATOLLAHI AMIR H.
Published: July 2012

A spinor theory on a space with linear Lie type noncommutativity among spatial coordinates is presented. The model is based on the Fourier space corresponding to spatial coordinates, as this Fourier space is commutative. When the group is compact, the real space exhibits lattice characteristics (as the eigenvalues of space operators are discrete), and the similarity of such a lattice with ordinary lattices is manifested, among other things, in a phenomenon resembling the famous fermion doubling problem. A projection is introduced to make the dynamical number of spinors equal to that corresponding to the ordinary space. The actions for free and interacting spinors (with Fermi-like interactions) are presented. The Feynman rules are extracted and 1-loop corrections are investigated.
DIRAC EQUATION FOR QUASI-PARTICLES IN GRAPHENE AND QUANTUM FIELD THEORY OF THEIR COULOMB INTERACTION
Authors: RIAZUDDIN
Published: July 2012

There is evidence for existence of massless Dirac quasiparticles in graphene, which satisfy Dirac equation in (1+2) dimensions near the so called Dirac points which lie at the corners at the graphene's brilluoin zone. We revisit the derivation of Dirac equation in (1+2) dimensions obeyed by quasiparticles in graphene near the Dirac points. It is shown that parity operator in (1+2) dimensions play an interesting role and can be used for defining "conserved" currents resulting from the underlying Lagrangian for Dirac quasiparticles in graphene which is shown to have UA(1) × UB(1) symmetry. Further the quantum field theory (QFT) of Coulomb interaction of 2D graphene is developed and applied to vacuum polarization and electron self-energy and the renormalization of the effective coupling g of this interaction and Fermi velocity vf which has important implications in the renormalization group analysis of g and vf.