bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing the hypothesis that diphtheria–tetanus–pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries
Authors: Aaby Peter , Benn Christine , Nielsen Jens , Lisse Ida Maria , Rodrigues Amabelia , Ravn Henrik
Published: May 2012

Background

Measles vaccines (MV) have sex-differential effects on mortality not explained by protection against measles infection.

Objective

The authors examined whether whole-cell diphtheria–tetanus–pertussis (DTP) vaccine has sex-differential and non-specific effects.

Data sources and eligibility

Following previous reviews and a new search, the effect of DTP on mortality up to the next vaccination was assessed in all studies where DTP was given after BCG or DTP was given after MV and there was prospective follow-up after ascertainment of vaccination status.

Setting

High-mortality countries in Africa and Asia.

Methods

The initial observation of negative effect of DTP generated six hypotheses, which were examined in all available studies and two randomised trials reducing the time of exposure to DTP.

Main outcome

Consistency between studies.

Results

In the first study, DTP had negative effects on survival in contrast to the beneficial effects of BCG and MV. This pattern was repeated in the six other studies available. Second, the two ‘natural experiments’ found significantly higher mortality for DTP-vaccinated compared with DTP-unvaccinated children. Third, the female–male mortality ratio was increased after DTP in all nine studies; in contrast, the ratio was decreased after BCG and MV in all studies. Fourth, the increased female mortality associated with high-titre measles vaccine was found only among children who had received DTP after high-titre measles vaccine. Fifth, in six randomised trials of early MV, female but not male mortality was increased if DTP was likely to be given after MV. Sixth, the mortality rate declined markedly for girls but not for boys when DTP-vaccinated children received MV. The authors reduced exposure to DTP as most recent vaccination by administering a live vaccine (MV and BCG) shortly after DTP. Both trials reduced child mortality.

Conclusions

These observations are incompatible with DTP merely protecting against the targeted diseases. With herd immunity to whooping cough, DTP is associated with higher mortality for girls. Randomised studies of DTP are warranted to measure the true impact on survival.
Relationship between years in the trade and the development of radiographic knee osteoarthritis and MRI-detected meniscal tears and bursitis in floor layers. A cross-sectional study of a historical cohort
Authors: Jensen Lilli Kirkeskov , Rytter Søren , Marott Jacob Louis , Bonde Jens Peter
Published: May 2012

Objectives

An increased risk of developing knee disorders including radiographic knee osteoarthritis (OA) have been shown among workers with kneeling working demands. There may also be a dose-related association between duration of employment in occupations with kneeling work and development of radiographic knee OA and magnetic resonance imaging (MRI)-detected meniscal tears and bursitis.

Design

A cross-sectional study of a historical cohort.

Setting

Members of the trade unions for floor layers and graphic designers in Denmark.

Participants

92 male floor layers and 49 graphic designers aged 36–70 years were randomly selected among participants from a clinical and radiographic study of 156 floor layers and 152 graphic designers.

Outcome measures

Radiographic tibiofemoral (TF) and patellofemoral (PF) knee-OA and MRI-detected meniscal tears and bursitis. Results were adjusted for age, earlier knee traumas, sports activities and body mass index in logistic regression models. Association between TF OA and years in the floor-laying trade was graphically examined by a restricted cubic spline with four knots.

Results

Increase in number of years with exposure to kneeling work is associated with radiographic TF knee OA with ORs 0.7, 95% CI 0.07 to 4.42; OR 1.89, 95% CI 0.29 to 12.3; OR 4.82, 95% CI 1.38 to 17 for <20 years, 20–30 years and >30 years of kneeling work, respectively. MRI-verified medial meniscal tears was increased among subjects with kneeling work with OR 1.96, 95% CI 0.79 to 4.88 to OR 4.73, 95% CI 1.16 to 19.4 but was not associated with duration of employment. Periarticular bursitis was increased in subjects with <20 years of kneeling working activity. Lateral meniscal tears and PF knee OA were not associated with duration of kneeling working activity or with kneeling work in general.

Conclusions

The findings suggest a dose–response relationship for radiographic TF knee OA in floor layers with a significant amount of kneeling work and an increase of MRI-verified medial meniscal tears among workers with kneeling work.
Do statins improve outcomes in patients with asthma on inhaled corticosteroid therapy? A retrospective cohort analysis
Authors: Lokhandwala Tasneem , West-Strum Donna , Banahan Benjamin F , Bentley John P , Yang Yi
Published: May 2012

Objectives

Animal studies and clinical trials have examined the potential benefits of statins in asthma management with contradictory results. The objective of this study was to determine if asthma patients on concurrent statins are less likely to have asthma-related hospitalisations.

Design

A retrospective cohort study using Mississippi Medicaid data for 2002–2004.

Participants

Asthma patients ≥18 years were identified using the ICD9 code 493.xx from 1 July 2002 through 31 December 2003. The index date for an exposed subject was any date within the identification period, 180 days prior to which the subject had at least one inhaled corticosteroid prescription and at least an 80% adherence rate to statins. Asthma patients on inhaled corticosteroids, but not on statins, were selected as the unexposed population. The two groups were matched and followed for 1 year beginning the index date.

Main outcomes measures

Patient outcomes in terms of hospitalisations and ER visits were compared using conditional logistic regression.

Results

After matching, there were 479 exposed subjects and 958 corresponding unexposed subjects. The odds of asthma-related hospitalisation and/or emergency room (ER) visits for asthma patients on concurrent statins were almost half the odds for patients not on statins (OR=0.55; 95% CI (0.37 to 0.84); p=0.0059). Similarly, the odds of asthma-related ER visits were significantly lower for patients on statins (OR=0.48; 95% CI (0.28 to 0.82); p=0.0069).

Conclusion

The findings suggest beneficial effects of statins in asthma management. Further prospective investigations are required to provide more conclusive evidence.
Image label completion by pursuing contextual decomposability
Authors: Liu Xiaobai , Yan Shuicheng , Chua Tat-Seng , Jin Hai
Published: May 2012

This article investigates how to automatically complete the missing labels for the partially annotated images, without image segmentation. The label completion procedure is formulated as a nonnegative data factorization problem, to decompose the global image representations that are used for describing the entire images, for instance, various image feature descriptors, into their corresponding label representations, that are used for describing the local semantic regions within images. The solution provided in this work is motivated by following observations. First, label representations of the regions with the same label often share certain commonness, yet may be essentially different due to the large intraclass variations. Thus, each label or concept should be represented by using a subspace spanned by an ensemble of basis, instead of a single one, to characterize the intralabel diversities. Second, the subspaces for different labels are different from each other. Third, while two images are similar with each other, the corresponding label representations should be similar. We formulate this cross-image context as well as the given partial label annotations in the framework of nonnegative data factorization and then propose an efficient multiplicative nonnegative update rules to alternately optimize the subspaces and the reconstruction coefficients. We also provide the theoretic proof of algorithmic convergence and correctness. Extensive experiments over several challenging image datasets clearly demonstrate the effectiveness of our proposed solution in boosting the quality of image label completion and image annotation accuracy. Based on the same formulation, we further develop a label ranking algorithms, to refine the noised image labels without any manual supervision. We compare the proposed label ranking algorithm with the state-of-the-arts over the popular evaluation databases and achieve encouragingly improvements.
Peer-to-Peer Information Retrieval
Authors: Tigelaar Almer S. , Hiemstra Djoerd , Trieschnigg Dolf
Published: May 2012

Peer-to-peer technology is widely used for file sharing. In the past decade a number of prototype peer-to-peer information retrieval systems have been developed. Unfortunately, none of these has seen widespread real-world adoption and thus, in contrast with file sharing, information retrieval is still dominated by centralized solutions. In this article we provide an overview of the key challenges for peer-to-peer information retrieval and the work done so far. We want to stimulate and inspire further research to overcome these challenges. This will open the door to the development and large-scale deployment of real-world peer-to-peer information retrieval systems that rival existing centralized client-server solutions in terms of scalability, performance, user satisfaction, and freedom.
Oracle in Image Search
Authors: Nie Liqiang , Wang Meng , Zha Zheng-Jun , Chua Tat-Seng
Published: May 2012

This article studies a novel problem in image search. Given a text query and the image ranking list returned by an image search system, we propose an approach to automatically predict the search performance. We demonstrate that, in order to estimate the mathematical expectations of Average Precision (AP) and Normalized Discounted Cumulative Gain (NDCG), we only need to predict the relevance probability of each image. We accomplish the task with a query-adaptive graph-based learning based on the images’ ranking order and visual content. We validate our approach with a large-scale dataset that contains the image search results of 1,165 queries from 4 popular image search engines. Empirical studies demonstrate that our approach is able to generate predictions that are highly correlated with the real search performance. Based on the proposed image search performance prediction scheme, we introduce three applications: image metasearch, multilingual image search, and Boolean image search. Comprehensive experiments are conducted to validate our approach.
A Measurement Framework for Evaluating Emulators for Digital Preservation
Authors: Guttenbrunner Mark , Rauber Andreas
Published: May 2012

Accessible emulation is often the method of choice for maintaining digital objects, specifically complex ones such as applications, business processes, or electronic art. However, validating the emulator’s ability to faithfully reproduce the original behavior of digital objects is complicated.

This article presents an evaluation framework and a set of tests that allow assessment of the degree to which system emulation preserves original characteristics and thus significant properties of digital artifacts. The original system, hardware, and software properties are described. Identical environment is then recreated via emulation. Automated user input is used to eliminate potential confounders. The properties of a rendered form of the object are then extracted automatically or manually either in a target state, a series of states, or as a continuous stream. The concepts described in this article enable preservation planners to evaluate how emulation affects the behavior of digital objects compared to their behavior in the original environment. We also review how these principles can and should be applied to the evaluation of migration and other preservation strategies as a general principle of evaluating the invocation and faithful rendering of digital objects and systems. The article concludes with design requirements for emulators developed for digital preservation tasks.
Multijoint error compensation mediates unstable object control
Authors: Cluff Tyler , Manos Aspasia , Lee Timothy D. , Balasubramaniam Ramesh
Published: May 2012

A key feature of skilled object control is the ability to correct performance errors. This process is not straightforward for unstable objects (e.g., inverted pendulum or “stick” balancing) because the mechanics of the object are sensitive to small control errors, which can lead to rapid performance changes. In this study, we have characterized joint recruitment and coordination processes in an unstable object control task. Our objective was to determine whether skill acquisition involves changes in the recruitment of individual joints or distributed error compensation. To address this problem, we monitored stick-balancing performance across four experimental sessions. We confirmed that subjects learned the task by showing an increase in the stability and length of balancing trials across training sessions. We demonstrated that motor learning led to the development of a multijoint error compensation strategy such that after training, subjects preferentially constrained joint angle variance that jeopardized task performance. The selective constraint of destabilizing joint angle variance was an important metric of motor learning. Finally, we performed a combined uncontrolled manifold-permutation analysis to ensure the variance structure was not confounded by differences in the variance of individual joint angles. We showed that reliance on multijoint error compensation increased, whereas individual joint variation (primarily at the wrist joint) decreased systematically with training. We propose a learning mechanism that is based on the accurate estimation of sensory states.
MARCKS Regulates Growth and Radiation Sensitivity and Is a Novel Prognostic Factor for Glioma
Authors: Jarboe John S. , Anderson Joshua C. , Duarte Christine W. , Mehta Tapan , Nowsheen Somaira , Hicks Patricia H. , Whitley Alexander C. , Rohrbach Timothy D. , McCubrey Raymond O. , Chiu Sherard , Burleson Tamara M. , Bonner James A. , Gillespie G. Yancey , Yang Eddy S. , Willey Christopher D.
Published: May 2012

Purpose: This study assessed whether myristoylated alanine-rich C-kinase substrate (MARCKS) can regulate glioblastoma multiforme (GBM) growth, radiation sensitivity, and clinical outcome.

Experimental Design: MARCKS protein levels were analyzed in five GBM explant cell lines and eight patient-derived xenograft tumors by immunoblot, and these levels were correlated to proliferation rates and intracranial growth rates, respectively. Manipulation of MARCKS protein levels was assessed by lentiviral-mediated short hairpin RNA knockdown in the U251 cell line and MARCKS overexpression in the U87 cell line. The effect of manipulation of MARCKS on proliferation, radiation sensitivity, and senescence was assessed. MARCKS gene expression was correlated with survival outcomes in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) Database and The Cancer Genome Atlas (TCGA).

Results: MARCKS protein expression was inversely correlated with GBM proliferation and intracranial xenograft growth rates. Genetic silencing of MARCKS promoted GBM proliferation and radiation resistance, whereas MARCKS overexpression greatly reduced GBM growth potential and induced senescence. We found MARCKS gene expression to be directly correlated with survival in both the REMBRANDT and TCGA databases. Specifically, patients with high MARCKS expressing tumors of the proneural molecular subtype had significantly increased survival rates. This effect was most pronounced in tumors with unmethylated O6-methylguanine DNA methyltransferase (MGMT) promoters, a traditionally poor prognostic factor.

Conclusions: MARCKS levels impact GBM growth and radiation sensitivity. High MARCKS expressing GBM tumors are associated with improved survival, particularly with unmethylated MGMT promoters. These findings suggest the use of MARCKS as a novel target and biomarker for prognosis in the proneural subtype of GBM. Clin Cancer Res; 18(11); 3030–41. ©2012 AACR.
Yes-Associated Protein 1 Is Activated and Functions as an Oncogene in Meningiomas
Authors: Baia Gilson S. , Caballero Otavia L. , Orr Brent A. , Lal Anita , Ho Janelle S. Y. , Cowdrey Cynthia , Tihan Tarik , Mawrin Christian , Riggins Gregory J.
Published: May 2012

The Hippo signaling pathway is functionally conserved in Drosophila melanogaster and mammals, and its proposed function is to control tissue homeostasis by regulating cell proliferation and apoptosis. The core components are composed of a kinase cascade that culminates with the phosphorylation and inhibition of Yes-associated protein 1 (YAP1). Phospho-YAP1 is retained in the cytoplasm. In the absence of Hippo signaling, YAP1 translocates to the nucleus, associates with co-activators TEAD1-4, and functions as a transcriptional factor promoting the expression of key target genes. Components of the Hippo pathway are mutated in human cancers, and deregulation of this pathway plays a role in tumorigenesis. Loss of the NF2 tumor suppressor gene is the most common genetic alteration in meningiomas, and the NF2 gene product, Merlin, acts upstream of the Hippo pathway. Here, we show that primary meningioma tumors have high nuclear expression of YAP1. In meningioma cells, Merlin expression is associated with phosphorylation of YAP1. Using an siRNA transient knockdown of YAP1 in NF2-mutant meningioma cells, we show that suppression of YAP1 impaired cell proliferation and migration. Conversely, YAP1 overexpression led to a strong augment of cell proliferation and anchorage-independent growth and restriction of cisplatin-induced apoptosis. In addition, expression of YAP1 in nontransformed arachnoidal cells led to the development of tumors in nude mice. Together, these findings suggest that in meningiomas, deregulation of the Hippo pathway is largely observed in primary tumors and that YAP1 functions as an oncogene promoting meningioma tumorigenesis. Mol Cancer Res; 10(7); 904–13. ©2012 AACR.
Key Principles and Clinical Applications of “Next-Generation” DNA Sequencing
Authors: Rizzo Jason M. , Buck Michael J.
Published: May 2012

Demand for fast, inexpensive, and accurate DNA sequencing data has led to the birth and dominance of a new generation of sequencing technologies. So-called “next-generation” sequencing technologies enable rapid generation of data by sequencing massive amounts of DNA in parallel using diverse methodologies which overcome the limitations of Sanger sequencing methods used to sequence the first human genome. Despite opening new frontiers of genomics research, the fundamental shift away from the Sanger sequencing that next-generation technologies has created has also left many unaware of the capabilities and applications of these new technologies, especially those in the clinical realm. Moreover, the brisk evolution of sequencing technologies has flooded the market with commercially available sequencing platforms, whose unique chemistries and diverse applications stand as another obstacle restricting the potential of next-generation sequencing. This review serves to provide a primer on next-generation sequencing technologies for clinical researchers and physician scientists. We provide an overview of the capabilities and clinical applications of DNA sequencing technologies to raise awareness among researchers about the power of these novel genomic tools. In addition, we discuss that key sequencing principles provide a comparison between existing and near-term technologies and outline key advantages and disadvantages between different sequencing platforms to help researchers choose an appropriate platform for their research interests. Cancer Prev Res; 5(7); 887–900. ©2012 AACR.
Hippocampal–Prefrontal Engagement and Dynamic Causal Interactions in the Maturation of Children's Fact Retrieval
Authors: Cho Soohyun , Metcalfe Arron W. S. , Young Christina B. , Ryali Srikanth , Geary David C. , Menon Vinod
Published: May 2012

Children's gains in problem-solving skills during the elementary school years are characterized by shifts in the mix of problem-solving approaches, with inefficient procedural strategies being gradually replaced with direct retrieval of domain-relevant facts. We used a well-established procedure for strategy assessment during arithmetic problem solving to investigate the neural basis of this critical transition. We indexed behavioral strategy use by focusing on the retrieval frequency and examined changes in brain activity and connectivity associated with retrieval fluency during arithmetic problem solving in second- and third-grade (7- to 9-year-old) children. Children with higher retrieval fluency showed elevated signal in the right hippocampus, parahippocampal gyrus (PHG), lingual gyrus (LG), fusiform gyrus (FG), left ventrolateral PFC (VLPFC), bilateral dorsolateral PFC (DLPFC), and posterior angular gyrus. Critically, these effects were not confounded by individual differences in problem-solving speed or accuracy. Psychophysiological interaction analysis revealed significant effective connectivity of the right hippocampus with bilateral VLPFC and DLPFC during arithmetic problem solving. Dynamic causal modeling analysis revealed strong bidirectional interactions between the hippocampus and the left VLPFC and DLPFC. Furthermore, causal influences from the left VLPFC to the hippocampus served as the main top–down component, whereas causal influences from the hippocampus to the left DLPFC served as the main bottom–up component of this retrieval network. Our study highlights the contribution of hippocampal–prefrontal circuits to the early development of retrieval fluency in arithmetic problem solving and provides a novel framework for studying dynamic developmental processes that accompany children's development of problem-solving skills.
Uncatalogued Turkish manuscripts in the collection of the Cambridge University Library
Authors: Polat Süleyman
Published: May 2012

Many Ottoman manuscripts can be found in national libraries, university libraries and private collections in Europe. One such library is that of the University of Cambridge in Britain. Turkish manuscripts in this library have been catalogued by E.G. Browne. After his death in 1926, Turkish manuscripts continued to be added to the collection of the Cambridge University Library but these were not catalogued. This article is an initial survey of the as yet un-catalogued Turkish manuscripts in the Cambridge University Library collection which it is hoped will be of use to researchers.
The Influence of Topography and Ambient Stability on the Characteristics of Cold-Air Pools: A Numerical Investigation
Authors: Katurji Marwan , Zhong Shiyuan
Published: May 2012

A high-resolution numerical investigation of a cold-air pooling process (under quiescent conditions) is carried out that systematically highlights the relations between the characteristics of the cold-air pools (e.g., slope winds, vertical temperature and wind structure, and cooling rate) and the characteristics of the topography (e.g., basin size and slope angle) under different ambient stabilities. The Advanced Regional Prediction System model is used to simulate 40 different scenarios at 100-m (10 m) horizontal (vertical) resolution. Results are within the range of similar observed phenomena. The main physical process governing the cooling process near the basin floor (<200 m in height) was found to be longwave radiative flux divergence, whereas vertical advection of temperature dominated the cooling process for the upper-basin areas. The maximum downslope wind speed is linearly correlated with both basin size and slope angle, with stronger wind corresponding to larger basin and lower slope angle. As the basin size increases, the influence of slope angle on maximum downslope wind decreases and the maximum is located farther down the slope. These relationships do not appear to be sensitive to stability, but weaker stability produces more cooling in the basin atmosphere by allowing stronger rising motion and adiabatic cooling. Insight gained from this study helps to improve the understanding of the cold-air pooling process within the investigated settings.
Consensus on Climate Trends in Western North Pacific Tropical Cyclones
Authors: Kang Nam-Young , Elsner James B.
Published: May 2012

Research on trends in western North Pacific tropical cyclone (TC) activity is limited by problems associated with different wind speed conversions used by the various meteorological agencies. This paper uses a quantile method to effectively overcome this conversion problem. Following the assumption that the intensity ranks of TCs are the same among agencies, quantiles at the same probability level in different data sources are regarded as having the same wind speed level. Tropical cyclone data from the Joint Typhoon Warning Center (JTWC) and Japan Meteorological Agency (JMA) are chosen for research and comparison. Trends are diagnosed for the upper 45% of the strongest TCs annually. The 27-yr period beginning with 1984, when the JMA began using the Dvorak (1982) technique, is determined to be the most reliable for achieving consensus among the two agencies regarding these trends. The start year is a compromise between including as many years in the data as possible, but not so many that the period includes observations that result in inconsistent trend estimates. The consensus of TC trends between the two agencies over the period is interpreted as fewer but stronger events since 1984, even with the lower power dissipation index (PDI) in the western North Pacific in recent years.
Soil Moisture–Precipitation Feedback Processes in the Indian Summer Monsoon Season
Authors: Asharaf Shakeel , Dobler Andreas , Ahrens Bodo
Published: May 2012

Soil moisture can influence precipitation through a feedback loop with land surface evapotranspiration. A series of numerical simulations, including soil moisture sensitivity experiments, have been performed for the Indian summer monsoon season (ISM). The simulations were carried out with the nonhydrostatic regional climate model Consortium for Small-Scale Modeling (COSMO) in climate mode (COSMO-CLM), driven by lateral boundary conditions derived from the ECMWF Interim reanalysis (ERA-Interim). Positive as well as negative feedback processes through local and remote effects are shown to be important. The regional moisture budget studies have exposed that changes in precipitable water and changes in precipitation efficiency vary in importance, in time, and in space in the simulations for India. Overall, the results show that the premonsoonal soil moisture has a significant influence on the monsoonal precipitation, and thus confirmed that modeling of soil moisture is essential for reliable simulation and forecasting of the ISM.
Ensemble-Based Data Assimilation for Estimation of River Depths
Authors: Wilson Greg , Özkan-Haller H. Tuba
Published: May 2012

A method is presented for estimating bathymetry in a river, based on observations of depth-averaged velocity during steady flow. The estimator minimizes a cost function that combines known information in the form of a prior estimate and measured data (including measurement noise). State augmentation is used to relate the measured variable (velocity) to the unknown parameter (bathymetry). Specifically, the unknown consists of deviations in depth about a known along-channel mean. Verification of the method is performed using a simple 1D channel geometry as well as for two real-world reaches. In all cases, the verification is based on nominal river depths of 3–10 m, channel widths of 50–100 m, and Froude numbers much less than one. Further tests are performed to assess the usefulness of various observation types and sampling schemes for this type of estimation.
Assimilation of Radar Radial Velocity Data with the WRF Hybrid Ensemble–3DVAR System for the Prediction of Hurricane Ike (2008)
Authors: Li Yongzuo , Wang Xuguang , Xue Ming
Published: May 2012

An enhanced version of the hybrid ensemble–three-dimensional variational data assimilation (3DVAR) system for the Weather Research and Forecasting Model (WRF) is applied to the assimilation of radial velocity (Vr) data from two coastal Weather Surveillance Radar-1988 Doppler (WSR-88D) radars for the prediction of Hurricane Ike (2008) before and during its landfall. In this hybrid system, flow-dependent ensemble covariance is incorporated into the variational cost function using the extended control variable method. The analysis ensemble is generated by updating each forecast ensemble member with perturbed radar observations using the hybrid scheme itself. The Vr data are assimilated every 30 min for 3 h immediately after Ike entered the coverage of the two coastal radars.

The hybrid method produces positive temperature increments indicating a warming of the inner core throughout the depth of the hurricane. In contrast, the 3DVAR produces much weaker and smoother increments with negative values at the vortex center at lower levels. Wind forecasts from the hybrid analyses fit the observed radial velocity better than that from 3DVAR, and the 3-h accumulated precipitation forecasts from the hybrid are also more skillful. The track forecast is slightly improved by the hybrid method and slightly degraded by the 3DVAR compared to the forecast from the Global Forecast System (GFS) analysis. All experiments assimilating the radar data show much improved intensity analyses and forecasts compared to the experiment without assimilating radar data. The better forecast of the hybrid indicates that the hybrid method produces dynamically more consistent state estimations. Little benefit of including the tuned static component of background error covariance in the hybrid is found.
An Analysis of Vortices Embedded within a Quasi-Linear Convective System Using X-Band Polarimetric Radar
Authors: Mahale Vivek N. , Brotzge Jerald A. , Bluestein Howard B.
Published: May 2012

On 2 April 2010, a developing quasi-linear convective system (QLCS) moved rapidly northeastward through central Oklahoma spawning at least three intense, mesoscale vortices. At least two of these vortices caused damage rated as category 0 to 1 on the enhanced Fujita scale (EF0–EF1) in and near the town of Rush Springs. Two radar networks—the National Weather Service Weather Surveillance Radar-1988 Doppler network (WSR-88D) and the Engineering Research Center for Collaborative Adaptive Sensing of the Atmosphere (CASA) radar network—collected high spatial and temporal resolution data of the event. This study is an in-depth polarimetric analysis of mesovortices within a QLCS. In this case study, the storm development and evolution of the QLCS mesovortices are examined. Significant findings include the following: 1) The damage in Rush Springs was caused by a combination of the fast translation speed and the embedded circulations associated with QLCS vortices. The vortices’ relative winds nearly negated the storm motion to the left of the vortex, but doubled the ground-relative wind to the right of the vortex. 2) A significant differential reflectivity (ZDR) arc developed along the forward flank of the first vortex. The ZDR arc propagated northeastward along the QLCS with the development of each new vortex. 3) A minimum in the copolar correlation coefficient (ρhv) in the center of the strongest vortex was observed, indicating the likely existence of a polarimetric tornado debris signature (TDS). A secondary ρhv minimum also was found just to the right of the vortex center, possibly associated with lofted debris from straight-line winds.
CCR1 blockade reduces tumor burden and osteolysis in vivo in a mouse model of myeloma bone disease
Authors: Dairaghi Daniel J. , Oyajobi Babatunde O. , Gupta Anjana , McCluskey Brandon , Miao Shichang , Powers Jay P. , Seitz Lisa C. , Wang Yu , Zeng Yibin , Zhang Penglie , Schall Thomas J. , Jaen Juan C.
Published: May 2012

The chemokine CCL3/MIP-1α is a risk factor in the outcome of multiple myeloma (MM), particularly in the development of osteolytic bone disease. This chemokine, highly overexpressed by MM cells, can signal mainly through 2 receptors, CCR1 and CCR5, only 1 of which (CCR1) is responsive to CCL3 in human and mouse osteoclast precursors. CCR1 activation leads to the formation of osteolytic lesions and facilitates tumor growth. Here we show that formation of mature osteoclasts is blocked by the highly potent and selective CCR1 antagonist CCX721, an analog of the clinical compound CCX354. We also show that doses of CCX721 selected to completely inhibit CCR1 produce a profound decrease in tumor burden and osteolytic damage in the murine 5TGM1 model of MM bone disease. Similar effects were observed when the antagonist was used prophylactically or therapeutically, with comparable efficacy to that of zoledronic acid. 5TGM1 cells were shown to express minimal levels of CCR1 while secreting high levels of CCL3, suggesting that the therapeutic effects of CCX721 result from CCR1 inhibition on non-MM cells, most likely osteoclasts and osteoclast precursors. These results provide a strong rationale for further development of CCR1 antagonists for the treatment of MM and associated osteolytic bone disease.
Endoplasmic Reticulum Stress Induces the Expression of Fetuin-A to Develop Insulin Resistance
Authors: Ou Horng-Yih , Wu Hung-Tsung , Hung Hao-Chang , Yang Yi-Ching , Wu Jin-Shang , Chang Chih-Jen
Published: May 2012

Fetuin-A is a biomarker reported to be important in many metabolic disorders, including obesity, diabetes, and hepatic steatosis. Although it is well known that fetuin-A is increased in diabetes and nonalcoholic fatty liver disease (NAFLD), the levels of fetuin-A in diabetic patients with NAFLD are unknown. Furthermore, the regulation of fetuin-A expression is still obscure. In this study, a total of 180 age- and sex-matched subjects with normal glucose tolerance, NAFLD, newly diagnosed diabetes (NDD), and NDD with NAFLD were recruited. We found that the levels of fetuin-A were significantly increased in NDD with NAFLD as compared with NDD or NAFLD subjects. We further used HepG2 cells to investigate the regulation of fetuin-A. Treatment with endoplasmic reticulum (ER) stress activator, thapsigargin, increased the expression of fetuin-A mRNA and protein in a time- and dose-dependent manner. Pretreatment with ER stress inhibitor, 4-phenylbutyrate, reversed high glucose or palmitate-induced fetuin-A expression. Moreover, treatment with 4-phenylbutyrate in both streptozotocin-induced and high-fat diet-induced diabetic mice not only decreased hepatic fetuin-A levels but also improved hyperglycemia. Taken together, we found that fetuin-A levels were increased in diabetes patients with NAFLD. Moreover, ER stress induced by high glucose and palmitate increased the expression of fetuin-A and further contributed to the development of insulin resistance.
The axonal transport of mitochondria
Authors: Saxton William M. , Hollenbeck Peter J.
Published: May 2012

Vigorous transport of cytoplasmic components along axons over substantial distances is crucial for the maintenance of neuron structure and function. The transport of mitochondria, which serves to distribute mitochondrial functions in a dynamic and non-uniform fashion, has attracted special interest in recent years following the discovery of functional connections among microtubules, motor proteins and mitochondria, and their influences on neurodegenerative diseases. Although the motor proteins that drive mitochondrial movement are now well characterized, the mechanisms by which anterograde and retrograde movement are coordinated with one another and with stationary axonal mitochondria are not yet understood. In this Commentary, we review why mitochondria move and how they move, focusing particularly on recent studies of transport regulation, which implicate control of motor activity by specific cell-signaling pathways, regulation of motor access to transport tracks and static microtubule–mitochondrion linkers. A detailed mechanism for modulating anterograde mitochondrial transport has been identified that involves Miro, a mitochondrial Ca2+-binding GTPase, which with associated proteins, can bind and control kinesin-1. Elements of the Miro complex also have important roles in mitochondrial fission–fusion dynamics, highlighting questions about the interdependence of biogenesis, transport, dynamics, maintenance and degradation.
New insights into force depression in skeletal muscle
Authors: Joumaa Venus , MacIntosh Brian R. , Herzog Walter
Published: May 2012

Force depression observed following active shortening is not well understood. Previous research suggested that force depression might be associated with a stress-induced inhibition of cross-bridges in the newly formed overlap zone following shortening. Our aim was to investigate this theory in skinned fibres and determine whether there was an inhibition of the attachment of cross-bridges or a decrease in the force produced per cross-bridge. The stress-induced inhibition of cross-bridge theory gives testable predictions, including: (1) skinned fibres should show proportional force and stiffness depression, (2) force after shortening should not be lower than force before shortening, (3) stiffness following shortening should not be lower than stiffness before shortening and (4) force depression should decrease when the stress during shortening is decreased. In agreement with these predictions, force and stiffness depression were approximately proportional, and force depression decreased with decreasing stress during shortening. However, in contrast to the predictions of the stress-induced inhibition of cross-bridge theory, force after shortening from sarcomere lengths of 2.8 and 3.0 μm to a sarcomere length of 2.4 μm was smaller than force before shortening, and this was not accompanied by a corresponding decrease in stiffness. We conclude that the stress-induced inhibition of cross-bridge theory, as proposed previously, cannot be the only mechanism for force depression, but that there is an additional, stress-induced inhibition of cross-bridges in the old overlap zone. Furthermore, both mechanisms, inhibition of cross-bridge attachment and reduction of force produced per cross-bridge, contribute to force depression. Inhibition and/or reduction of force depend(s) on the amount of stress imposed on actin during the shortening phase.
Mitochondrial function in sparrow pectoralis muscle
Authors: Kuzmiak Sarah , Glancy Brian , Sweazea Karen L. , Willis Wayne T.
Published: May 2012

Flying birds couple a high daily energy turnover with double-digit millimolar blood glucose concentrations and insulin resistance. Unlike mammalian muscle, flight muscle predominantly relies on lipid oxidation during locomotion at high fractions of aerobic capacity, and birds outlive mammals of similar body mass by a factor of three or more. Despite these intriguing functional differences, few data are available comparing fuel oxidation and free radical production in avian and mammalian skeletal muscle mitochondria. Thus we isolated mitochondria from English sparrow pectoralis and rat mixed hindlimb muscles. Maximal O2 consumption and net H2O2 release were measured in the presence of several oxidative substrate combinations. Additionally, NAD- and FAD-linked electron transport chain (ETC) capacity was examined in sonicated mitochondria. Sparrow mitochondria oxidized palmitoyl-l-carnitine 1.9-fold faster than rat mitochondria and could not oxidize glycerol-3-phosphate, while both species oxidized pyruvate, glutamate and malate–aspartate shuttle substrates at similar rates. Net H2O2 release was not significantly different between species and was highest when glycolytic substrates were oxidized. Sonicated sparrow mitochondria oxidized NADH and succinate over 1.8 times faster than rat mitochondria. The high ETC catalytic potential relative to matrix substrate dehydrogenases in sparrow mitochondria suggests a lower matrix redox potential is necessary to drive a given O2 consumption rate. This may contribute to preferential reliance on lipid oxidation, which may result in lower in vivo reactive oxygen species production in birds compared with mammals.
Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation
Authors: Lin David C. , Hershey John D. , Mattoon John S. , Robbins Charles T.
Published: May 2012

Hibernating bears retain most of their skeletal muscle strength despite drastically reduced weight-bearing activity. Regular neural activation of muscles is a potential mechanism by which muscle atrophy could be limited. However, both mechanical loading and neural activity are usually necessary to maintain muscle size. An alternative mechanism is that the signaling pathways related to the regulation of muscle size could be altered so that neither mechanical nor neural inputs are needed for retaining strength. More specifically, we hypothesized that muscles in hibernating bears are resistant to a severe reduction in neural activation. To test this hypothesis, we unilaterally transected the common peroneal nerve, which innervates ankle flexor muscles, in hibernating and summer-active brown bears (Ursus arctos). In hibernating bears, the long digital extensor (LDE) and cranial tibial (CT) musculotendon masses on the denervated side decreased after 11 weeks post-surgery by 18±11 and 25±10%, respectively, compared with those in the intact side. In contrast, decreases in musculotendon masses of summer-active bears after denervation were 61±4 and 58±5% in the LDE and CT, respectively, and significantly different from those of hibernating bears. The decrease due to denervation in summer-active bears was comparable to that occurring in other mammals. Whole-muscle cross-sectional areas (CSAs) measured from ultrasound images and myofiber CSAs measured from biopsies decreased similarly to musculotendon mass. Thus, hibernating bears alter skeletal muscle catabolic pathways regulated by neural activity, and exploration of these pathways may offer potential solutions for disuse atrophy of muscles.
Perch diameter and branching patterns have interactive effects on the locomotion and path choice of anole lizards
Authors: Jones Zachary M. , Jayne Bruce C.
Published: May 2012

Natural branches vary conspicuously in their diameter, density and orientation, but how these latter two factors affect animal locomotion is poorly understood. Thus, for three species of arboreal anole lizards found on different size branches and with different limb lengths, we tested sprinting performance on cylinders with five diameters (5–100 mm) and five patterns of pegs, which simulated different branch orientations and spacing. We also tested whether the lizards preferred surfaces that enhanced their performance. The overall responses to different surfaces were similar among the three species, although the magnitude of the effects differed. All species were faster on cylinders with larger diameter and no pegs along the top. The short-limbed species was the slowest on all surfaces. Much of the variation in performance resulted from variable amounts of pausing among different surfaces and species. Lizards preferred to run along the top of cylinders, but pegs along the top of the narrow cylinders interfered with this. Pegs on top of the 100-mm diameter cylinder, however, had little effect on speed as the lizards ran quite a straight path alongside pegs without bumping into them. All three species usually chose surfaces with greater diameters and fewer pegs, but very large diameters with pegs were preferred to much smaller diameter cylinders without pegs. Our results suggest that preferring larger diameters in natural vegetation has a direct benefit for speed and an added benefit of allowing detouring around branches with little adverse effect on speed.
Reporting of post-polyethylene glycol prolactin: precipitation by polyethylene glycol 6000 or polyethylene glycol 8000 will change reference intervals for monomeric prolactin
Authors: Veljkovic Kika , Servedio Dominic , Don-Wauchope Andrew C
Published: May 2012

Background

When screening for macroprolactin, many laboratories use precipitation by polyethylene glycol (PEG) with molecular weight 6000 (PEG6000) or 8000 (PEG8000), and report the percentage prolactin recovery. It has been proposed that reporting of percentage prolactin recovery should be replaced by absolute post-PEG prolactin; however, the post-PEG prolactin reference interval has been established using PEG6000 only. We sought to determine whether the use of PEG8000, instead of PEG6000, changed post-PEG prolactin concentrations.

Methods

We compared the post-PEG6000 and post-PEG8000 prolactin concentrations in hyperprolactinaemic serum samples referred for macroprolactin screening ( n = 40), using Passing–Bablok regression analysis and Bland–Altman difference plot.

Results

The median (25th–75th percentile, range) total prolactin, post-PEG6000 and post-PEG8000 prolactin concentrations were, respectively, 36 (31–46, 23–83) μg/L, 27 (20–38, 18–72) μg/L and 24 (18–35, 16–64) μg/L for male serum samples ( n = 5); and 56 (39–83, 24–596) μg/L, 45 (31–67, 8–503) μg/L and 41 (28–62, 6–457) μg/L for female serum samples ( n = 35) (mIU/L conversion factor: 21.2). The Passing–Bablok analysis demonstrated a significant constant bias of −1.27 and a non-significant proportional bias of 0.96. The Bland–Altman plot showed a bias of −8.2% (95% limits of agreement −19.3–2.9%).

Conclusions

There is a significant constant bias between the two macroprolactin precipitation methods. We changed our PEG precipitation to a PEG6000 method. Laboratories that use PEG8000 should consider the transference of the reference interval established with PEG6000 carefully.
Drivers of Public Trust and Confidence in Police in the UK
Authors: Merry Simon , Power Nicola , McManus Michelle , Alison Laurence
Published: May 2012

The term ‘public confidence’ has become the key indicator of trust, legitimacy and consent in policing and it is this measure of confidence that has become the overarching conceptualisation of successful policing. This paper focuses on providing a greater understanding of drivers of public confidence in the police using three surveys of the same community: Community Safety Survey (N = 4,499), Victim Satisfaction Survey (N = 1,084) and the Anti-Social Behaviour Survey (N = 301). Gender and age differences were found, with females and older participants exhibiting higher confidence in policing. Non-criminal aspects of policing such as improved community cohesion and visibility were found to aid confidence. Further, crime-related policing was found to influence overall satisfaction following an incident with some crimes handled better than others (eg, burglary) and customer care needing improvement in certain areas (eg, updated information). Although this research found confidence levels to be positive overall, there was also evidence of the positive–negative asymmetry effect, where participants' confidence levels shifted following experience with the police. This paper provides further support for citizen-focused initiatives in which community focus and communication should be at the centre of strategies for improving confidence in policing.