bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal polynomials for singular curves on surfaces
Authors: Li Jun , Tzeng Yu-jong
Published: June 2014

Let$\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}S$be a complex smooth projective surface and$L$be a line bundle on$S$. For any given collection of isolated topological or analytic singularity types, we show the number of curves in the linear system$|L|$with prescribed singularities is a universal polynomial of Chern numbers of$L$and$S$, assuming$L$is sufficiently ample. More generally, we show for vector bundles of any rank and smooth varieties of any dimension, similar universal polynomials also exist and equal the number of singular subvarieties cutting out by sections of the vector bundle. This work is a generalization of Göttsche’s conjecture.
Allocation and Sizing of Dispersed Photovoltaic Generation in Diesel Isolated Electrical Systems Using an Analytical Approach
Authors: Goncalves Claudio , A. Vieira J. Paulo , Vieira Dione J. A. , L. Tostes M. Emilia , Bernardes Bernard C. , Bezerra Ubiratan H.
Published: June 2014

This paper proposes an analytical methodology to allocate and size active power photovoltaic generation (PVG) units with embedded DC/AC inverter (PVGI) to be integrated as concentrated or dispersed generation in isolated medium voltage electrical grids. The methodology considers multiple objectives: improving the electrical grid voltage profile; reducing active power losses and the diesel generation participation. To validate the proposed methodology, the IEEE 33 and 69 buses networks and an isolated real electrical system were simulated. The results obtained demonstrated that the proposed methodology is effective in providing a solution with improvement in voltage profile, active power losses reduction, diesel generation participation reduction.
The Decline in Gross Efficiency in Relation to Cycling Time-Trial Length
Authors: Noordhof Dionne A. , Mulder Roy C.M. , Malterer Katherine R. , Foster Carl , de Koning Jos J.
Published: June 2014

Purpose:

To evaluate whether gross efficiency (GE), determined during submaximal cycling, is lower after time trials and if the magnitude of the decrease differs in relation to race distance. Secondary purposes were to study the rate of the decline in GE and whether changes in muscle-fiber recruitment could explain the decline.

Methods:

Cyclists completed 9 GE tests consisting of submaximal exercise performed before and after time trials of different length (500 m, 1000 m, 2000 m, 4000 m, 15,000 m, and 40,000 m). In addition, subjects performed time trials as if they were a 1000-m, 4000-m, or 40,000-m time trial during which they were stopped at 50% of the final time of the preceding “full” time trial. Power output, gas exchange, and EMG were measured continuously throughout the GE tests.

Results:

A significant interaction effect between distance and time was found for GE (P = .001). GE was significantly lower immediately after the time trials than before (P < .05), and the decline in GE differed between distances (P < .001). GE seemed to decline linearly during the relatively short trials, while it declined more hyperbolically during the 40,000-m. A significant effect of time (P = .04) on mean EMG amplitude was found. However, post hoc comparisons showed no significant differences in mean EMG amplitude between the different time points (before and after the time trials).

Conclusion:

GE decreases during time-trial exercise. Unfortunately, the cause of the decrease remains uncertain. Future modeling studies should consider using a declining instead of a constant GE. In sport situations, the declining GE has to be taken into account when selecting a pacing strategy.
The Validity of Microsensors to Automatically Detect Bowling Events and Counts in Cricket Fast Bowlers
Authors: McNamara Dean J. , Gabbett Tim J. , Chapman Paul , Naughton Geraldine , Farhart Patrick
Published: June 2014

Purpose:

Bowling workload is linked to injury risk in cricket fast bowlers. This study investigated the validity of microtechnology in the automated detection of bowling counts and events, including run-up distance and velocity, in cricket fast bowlers.

Method:

Twelve highly skilled fast bowlers (mean ± SD age 23.5 ± 3.7 y) performed a series of bowling, throwing, and fielding activities in an outdoor environment during training and competition while wearing a microtechnology unit (MinimaxX). Sensitivity and specificity of a bowling-detection algorithm were determined by comparing the outputs from the device with manually recorded bowling counts. Run-up distance and run-up velocity were measured and compared with microtechnology outputs.

Results:

No significant differences were observed between direct measures of bowling and nonbowling events and true positive and true negative events recorded by the MinimaxX unit (P = .34, r = .99). The bowling-detection algorithm was shown to be sensitive in both training (99.0%) and competition (99.5%). Specificity was 98.1% during training and 74.0% during competition. Run-up distance was accurately recorded by the unit, with a percentage bias of 0.8% (r = .90). The final 10-m (–8.9%, r = .88) and 5-m (–7.3%, r = .90) run-up velocities were less accurate.

Conclusions:

The bowling-detection algorithm from the MinimaxX device is sensitive to detect bowling counts in both cricket training and competition. Although specificity is high during training, the number of false positive events increased during competition. Additional bowling workload measures require further development.
Correlates of Low Physical Activity Levels in Aging Men and Women: The DR’s EXTRA Study (ISRCTN45977199)
Authors: Hakola L. , Hassinen M. , Komulainen P. , Lakka T.A. , Savonen K. , Rauramaa R.
Published: June 2014

Recognizing correlates of low physical activity (PA) can help in targeting PA interventions for individuals who would benefit most from increasing their PA. We studied the associations of demographic, social, health, and lifestyle factors with low PA by sex in a population sample of 1,303 Finnish individuals aged 57–78 years. We defined low PA as no moderate or vigorous leisure-time PA reported in an interview. Altogether, 39% of men and 48% of women reported low PA. Satisfactory or poor perceived health and high BMI were independently associated with low PA in both sexes. In men, factors such as age, being divorced or separated, still working, having a weak social network, poor diet, and a health professional’s suggestion to increase PA were associated with low PA. In women, cardiovascular disease and depressive symptoms were associated with low PA. These results can be applied in targeting PA interventions.
Whole-Genome Sequences of Low-Virulence Strain CB3 and Mild Strain CB7 of Chlamydia psittaci
Authors: Chu Jun , Sun Ruixue , Wu Zongxue , Liu Shanshan , Li Dongfang , Zhang Qiang , Ling Yong , Gong Yanping , Wu Renhua , Wu Honglong , Zhou Jizhang , He Cheng , Ni Peixiang
Published: June 2014

Avian
Chlamydia psittaci
is an obligate intracellular zoonotic pathogen especially dispersed from birds, and it is known to cause pericarditis, pneumonia, lateral nasal adenitis, peritonitis, hepatitis, splenitis, and other diseases. Generalized infections result in fever, anorexia, lethargy, and diarrhea, depending on the chlamydial genotype and the affected bird species. Although many complete genomes of
C. psittaci
have been sequenced, we report here the genomes of two strains isolated from the free-living sparrows (strain CB3) and vinous-throated parrotbill (strain CB7) in China, which were first isolated from the spleens of healthy birds in a routine investigation.
Genome Sequences of Two Leuconostoc pseudomesenteroides Strains Isolated from Danish Dairy Starter Cultures
Authors: Pedersen T. B. , Kot W. P. , Hansen L. H. , Sørensen S. J. , Broadbent J. R. , Vogensen F. K. , Ardö Y.
Published: June 2014

The lactic acid bacterium
Leuconostoc pseudomesenteroides
can be found in mesophilic cheese starters, where it produces aromatic compounds from, e.g., citrate. Here, we present the draft genome sequences of two
L. pseudomesenteroides
strains isolated from traditional Danish cheese starters.
Genome Sequence of a Promising Hydrogen-Producing Facultative Anaerobic Bacterium, Brevundimonas naejangsanensis Strain B1
Authors: Su Haijia , Zhang Ting , Bao Meidan , Jiang Yixin , Wang Yu , Tan Tianwei
Published: June 2014

Brevundimonas naejangsanensis
strain B1 is a newly isolated, facultative anaerobic bacterium capable of producing hydrogen with high efficiency. Here, we present a 2.94-Mb assembly of the genome sequence of strain B1, which may provide further insights into the molecular mechanism of hydrogen production from bioresource.
Draft Genome Sequences of
Geobacillus
sp. Strains CAMR5420 and CAMR12739
Authors: De Maayer Pieter , Williamson Carolyn E. , Vennard Christopher T. , Danson Michael J. , Cowan Don A.
Published: June 2014

Thermophilic
Geobacillus
spp. can efficiently hydrolyze hemicellulose polymers and are therefore of interest in biotechnological applications. Here we report the genome sequences of two hemicellulolytic strains,
Geobacillus
sp. CAMR12739 and CAMR5420.
Obstructive sleep apnoea and arthrogryposis
Authors: Jon Cindy , Mosquera Ricardo Alberto , Mitchell Sarah , Mazur Lynnette J
Published: June 2014

Arthrogryposis is a rare condition characterised by multiple congenital joint contractures. We present a case of a 10-year-old child with arthrogryposis and snoring. Polysomnography revealed significant obstructive sleep apnoea and hypoventilation that improved but did not completely resolve with adenotonsillectomy. With continuous positive airway pressure (CPAP) therapy, there was full resolution of all sleep disordered breathing. Initially, the patient admitted to difficulty tolerating nasal CPAP at home. However, she steadily improved adherence to therapy and admitted that with nasal CPAP use for the whole night, she felt more energised during the daytime.
Progressive intracranial hypertension and cerebral hypoperfusion in a fatal case of cerebral aspergilloma
Authors: Toksvang Linea Natalie , Plovsing Ronni R , Berg Ronan M G
Published: June 2014

We report a case of cerebral aspergilloma in a 25-year-old immunoincompetent man admitted to a general intensive care unit. Monitoring of intracranial pressure was instigated and revealed hour-long epochs of severe intracranial hypertension, despite a normal opening pressure, with decreases in cerebral perfusion pressure. We documented that this was associated with cerebral hypoperfusion by transcranial Doppler ultrasound. The present case illustrates that severe intracranial hypertension may evolve despite a normal opening pressure; it furthermore shows that continuous monitoring of intracranial pressure may be used to predict changes in cerebral haemodynamics in critically ill patients with neuroinfection.
‘Primary extrarenal Wilms’ tumour’: rare presentation of a common paediatric tumour
Authors: Goel Vandana , Verma Amit Kumar , Batra Vineeta , Puri Sunil Kumar
Published: June 2014

Wilms’ tumour (nephroblastoma), the most common abdominal malignancy of childhood, occurs primarily as a malignant renal tumour. Extrarenal Wilms’ tumour is rare with occasional reports from the Indian subcontinent. The various locations of extrarenal Wilms’ tumour include retroperitoneum, uterus, skin and thorax. In this report we will discuss the imaging features highlighting the imaging differential diagnosis in a case of retroperitoneal (extrarenal) primary Wilms’ tumour.
Comparison of the aetiology of stillbirth over five decades in a single centre: a retrospective study
Authors: Wou Karen , Ouellet Marie-Pier , Chen Moy-Fong , Brown Richard N
Published: June 2014

Objective

To compare the rates and aetiologies of stillbirth over the past 50 years.

Study design

We reviewed all autopsy reports for stillbirths occurring between 1989 and 2009 at the McGill University Health Centre to determine the pathological aetiology of stillbirths. We also reviewed maternal characteristics. We compared our results with a previous study published in 1992 on aetiologies of stillbirth from 1961 to 1988 at the same institution.

Results

From among the 79 410 births between 1989 and 2009, 217 stillbirths were included in our study. The mean maternal age was 31.05 (±5.8) years. In 28.1% of cases, there was a history of subfertility. The mean gestational age at diagnosis was 32.69 (±5.58) weeks, with a birthweight of 1888 (±1084) g. The main causes of stillbirth were unknown (26.7%), placental factors (19.8%) and abruptio placentae (12.9%). Other causes included haematogenous or ascending infection (10.6%), fetal malformations (8.3%), maternal hypertension (3.2%), intrauterine growth restriction (2.8%), diabetes (1.8%) and intrapartum asphyxia (1.4%). Other fetal causes were found in 12.4% of cases.

Conclusions

Owing to detailed pathological examination of most stillbirth cases over the past five decades at our tertiary obstetrical centre, we could study the trends in the aetiology of stillbirths in a cohort of more than 150 000 births. In 50 years, the rate of stillbirth has decreased from 115 to 32 cases/10 000 births from the 1960s to 2000s, which represents a reduction of 72%. Stillbirth from unknown cause remains the most common contributor, with 40% of these cases occurring in late pregnancy.
Predictors of injury mortality: findings from a large national cohort in Thailand
Authors: Yiengprugsawan Vasoontara , Berecki-Gisolf Janneke , Bain Christopher , McClure Roderick , Seubsman Sam-ang , Sleigh Adrian C
Published: June 2014

Objective

To present predictors of injury mortality by types of injury and by pre-existing attributes or other individual exposures identified at baseline.

Design

5-year prospective longitudinal study.

Setting

Contemporary Thailand (2005–2010), a country undergoing epidemiological transition.

Participants

Data derived from a research cohort of 87 037 distance-learning students enrolled at Sukhothai Thammathirat Open University residing nationwide.

Measures

Cohort members completed a comprehensive baseline mail-out questionnaire in 2005 reporting geodemographic, behavioural, health and injury data. These responses were matched with national death records using the Thai Citizen ID number. Age–sex adjusted multinomial logistic regression was used to calculate ORs linking exposure variables collected at baseline to injury deaths over the next 5 years.

Results

Statistically significant predictors of injury mortality were being male (adjustedOR 3.87, 95% CI 2.39 to 6.26), residing in the southern areas (AOR 1.71, 95% CI 1.05 to 2.79), being a current smoker (1.56, 95% CI 1.03 to 2.37), history of drunk driving (AOR 1.49, 95% CI 1.01 to 2.20) and ever having been diagnosed for depression (AOR 1.91, 95% CI 1.00 to 3.69). Other covariates such as being young, having low social support and reporting road injury in the past year at baseline had moderately predictive AORs ranging from 1.4 to 1.6 but were not statistically significant.

Conclusions

We complemented national death registration with longitudinal data on individual, social and health attributes. This information is invaluable in yielding insight into certain risk traits such as being a young male, history of drunk driving and history of depression. Such information could be used to inform injury prevention policies and strategies.
Identification of the optimum vagal manoeuvre technique for maximising vagal tone
Authors: Smith Gavin , Broek Alicia , Taylor David McD , Morgans Amee , Cameron Peter
Published: June 2014

Objectives

This study sought to determine the most effective technique for Valsalva Manoeuvre (VM) and Human Dive Reflex Manoeuvre (HDR) generation of vagal tone.

Methods

We conducted a repeated-measures trial of healthy adult volunteers from a university campus, aged 18–56 years, in sinus rhythm. Participants were randomised to VM (in supine or Trendelenberg postures) and HDR (supine or sitting postures) sequentially. Participants performed three trials of each technique, in random order, with a continuous ECG recording. Single-blinded analysis of ECG data was conducted. Mean differences between premanoeuvre and postmanoeuvre R-R intervals and heart rates were calculated for each posture within and between vagal manoeuvres.

Results

Seventy-two participants were enrolled. The difference between VM (supine) and VM (Trendelenberg) was not significant at 0.008 s (−0.023 to 0.038). The difference in mean R-R intervals for HDR (supine) was greater than HDR (sitting) 0.062 (0.031 to 0.093), although this significance was not reflected in a heart-rate change of −0.87 (−3.00 to 1.26). VM supine generated greatest overall mean R-R interval difference, while HDR (sitting) provided the smallest change in R-R interval. The VM (supine) provided a significant maximum effectiveness over the HDR (supine) of 0.102 s (0.071 to 0.132).

Conclusions

This study demonstrates that VM (supine) generates the greatest vagal tone producing the largest transient heart rate decrease in healthy volunteers. No advantage was identified in Trendelenberg posturing for the VM in this study. These results may assist in the standardisation of vagal manoeuvre technique for the range of therapeutic and diagnostic applications.
A THREE-ROUND ADAPTIVE DIAGNOSTIC ALGORITHM IN A DISTRIBUTED SYSTEM MODELED BY DUAL-CUBES
Authors: CHEN JHENG-CHENG , LAI CHIA-JUI , TSAI CHANG-HSIUNG
Published: June 2014

Problem diagnosis in large distributed computer systems and networks is a challenging task that requires fast and accurate inferences from huge volumes of data. In this paper, the PMC diagnostic model is considered, based on the diagnostic approach of end-to-end probing technology. A probe is a test transaction whose outcome depends on some of the system's components; diagnosis is performed by selecting appropriate probes and analyzing the results. In the PMC model, every computer can execute a probe to test a dedicated system's components. Furthermore, any test result reported by a faulty probe station is unreliable and the test result reported by fault-free probe station is always correct. The aim of the diagnosis is to locate all faulty components in the system based on collection of the test results. A dual-cube DC(n) is an (n + 1)-regular spanning subgraph of a (2n + 1)-dimensional hypercube. It uses n-dimensional hypercubes as building blocks and returns the main desirable properties of the hypercube so that it is suitable as a topology for distributed systems. In this paper, we first show that the diagnosability of DC(n) is n + 1 and then show that adaptive diagnosis is possible using at most 22n+1 + n tests for a 22n+1-node distributed system modeled by dual-cubes DC(n) in which at most n + 1 processes are faulty. Furthermore, we propose an adaptive diagnostic algorithm for the DC(n) and show that it diagnoses the DC(n) in three testing rounds and at most 22n+1 + O(n3) tests, where each node is scheduled for at most one test in each round.
Buckling Analysis of Thin-Walled Steel Structural Systems Using Generalized Beam Theory (GBT)
Authors: Basaglia Cilmar , Camotim Dinar
Published: June 2014

This paper deals with the application of beam finite element models based on generalized beam theory (GBT) to analyze the buckling behavior of four thin-walled steel structural systems, namely (i) beams belonging to storage rack systems, (ii) pitched-roof industrial frames, (iii) portal frames built from cold-formed rectangular hollow section (RHS) profiles and (iv) roof-supporting trusses, exhibiting different support conditions and subjected to various loadings. In particular, taking advantage of the GBT unique and structurally clarifying modal features, it is possible to assess how different geometries and/or bracing arrangements affect (improve) the local, distortional and/or global buckling behavior of the above structural systems. The accuracy of the GBT-based buckling results is assessed through the comparison with values yielded by rigorous shell finite element analyzes carried out in the code ANSYS. In spite of the disparity between the numbers of degrees of freedom involved, which are orders of magnitude apart, there is a virtual coincidence between the critical loads and mode shapes provided by the GBT (beam) and ANSYS (shell) finite element analyzes.
A Robust Segmentation Technique for Line, Word and Character Extraction from Kannada Text in Low Resolution Display Board Images
Authors: Angadi S. A. , Kodabagi M. M.
Published: June 2014

Reliable extraction/segmentation of text lines, words and characters is one of the very important steps for development of automated systems for understanding the text in low resolution display board images. In this paper, a new approach for segmentation of text lines, words and characters from Kannada text in low resolution display board images is presented. The proposed method uses projection profile features and on pixel distribution statistics for segmentation of text lines. The method also detects text lines containing consonant modifiers and merges them with corresponding text lines, and efficiently separates overlapped text lines as well. The character extraction process computes character boundaries using vertical profile features for extracting character images from every text line. Further, the word segmentation process uses k-means clustering to group inter character gaps into character and word cluster spaces, which are used to compute thresholds for extracting words. The method also takes care of variations in character and word gaps. The proposed methodology is evaluated on a data set of 1008 low resolution images of display boards containing Kannada text captured from 2 mega pixel cameras on mobile phones at various sizes 240 × 320, 480 × 640 and 960 × 1280. The method achieves text line segmentation accuracy of 97.17%, word segmentation accuracy of 97.54% and character extraction accuracy of 99.09%. The proposed method is tolerant to font variability, spacing variations between characters and words, absence of free segmentation path due to consonant and vowel modifiers, noise and other degradations. The experimentation with images containing overlapped text lines has given promising results.
EFFECT OF STRESS INTENSITY FACTOR IN EVALUATION OF INSTABILITY OF ATHEROSCLEROTIC PLAQUE
Authors: MOHAMMADI HADI , MEQUANINT KIBRET
Published: June 2014

Understanding the relationship between coronary arterial blood pressure, plaque morphology and composition, and sites of fibrous cap (FC) bursting, has been the focus of many recent studies. Instability of atherosclerotic plaques, defined as the propensity for FCs to burst, has been thought to occur at places where FCs are thin and necrotic core (NC) areas are large and highly compliant. However, here we show quantitatively, using a fiber-reinforced, anisotropic and hyperelastic FE model, that FC thickness and NC size and compliance alone are limited in predicting vulnerable and high-risk plaques. We suggest that plaque instabilities primarily occur at sites of high and concentrated mechanical stresses irrespective of fibrous cap thickness or NC area and compliance. Also, limitations of imaging techniques, such as intravascular ultrasound and optical coherence tomography, for providing input into (FE) models of atherosclerosis are discussed. The proposed model can be used to predict vulnerable plaque sites and rupture risks in patients. The current study also provides a framework for future research in which three-dimensional platform and viscoelastic properties of plaque composition can be considered in time-dependent and fatigue studies.
Olver's error bound methods applied to linear ordinary differential equations having a simple turning point
Authors: Dunster T. M.
Published: June 2014

Uniform asymptotic solutions of linear ordinary differential equations having a large parameter and a simple turning point are well known. Classical expansions involve Airy functions and their derivatives, and one of Frank Olver's major achievements was obtaining explicit and realistic error bounds. Here alternative expansions are considered, which involve the Airy function alone (and not its derivative). This is based on the early work of Cherry, and using Olver's techniques explicit error bounds are derived. The derivative of asymptotic solutions of turning point problems is also considered, and again using Olver's techniques, sharper error bounds are derived via the differential equation satisfied by such solutions.
High-DOF Robots in Dynamic Environments Using Incremental Trajectory Optimization
Authors: Park Chonhyon , Pan Jia , Manocha Dinesh
Published: June 2014

We present a novel optimization-based motion planning algorithm for high degree-of-freedom (DOF) robots in dynamic environments. Our approach decomposes the high-dimensional motion planning problem into a sequence of low-dimensional sub-problems. We compute collision-free and smooth paths using optimization-based planning and trajectory perturbation for each sub-problem. The overall algorithm does not require a priori knowledge about global motion or trajectories of dynamic obstacles. Rather, we compute a conservative local bound on the position or trajectory of each obstacle over a short time and use the bound to incrementally compute a collision-free trajectory for the robot. The high-DOF robot is treated as a tightly coupled system, and we incrementally use constrained coordination to plan its motion. We highlight the performance of our planner in simulated environments on robots with tens of DOFs.
Anthropometric Robotic Hand for Pressurized Glove Torque Measurement
Authors: Roberts Dustyn P. , Poon Jack , Patrick Daniella , Kim Joo H.
Published: June 2014

While robotic hands have been developed for tasks such as manipulation and grasping, their potential as tools for evaluation of engineered products — particularly compliant structures that are not easily modeled — has not been broadly studied. In this research, a low-cost anthropometric robotic hand is introduced that is designed to characterize glove stiffness in a pressurized environment. The interaction with the compliant pressurized glove provides unique performance requirements and design constraints. The anthropometric robotic hand was designed to mimic the human hand in a configuration corresponding to the neutral position in zero gravity, including the transverse arch, longitudinal arch, and oblique flexion of the rays. The resulting robotic hand also allows for realistic donning and doffing of the prototype glove, its pressurization, and torque testing of individual joints. Solid modeling and 3D printing enabled the rapid design iterations necessary to work successfully with the compliant pressure garment. An instrumentation and data processing method was used to calculate the required actuator torque at each finger's knuckle joint. The performance of the robotic hand was experimentally demonstrated with a prototype spacesuit glove at different levels of pressure, followed by a statistical repeatability analysis. The reliable measurement method validated the pressure-induced stiffening. The resulting robotic design and testing method provide an objective and systematic way of evaluating the performance of compliant gloves.
Least-order torsion-gravity for fermion fields, and the nonlinear potentials in the standard models
Authors: Fabbri Luca
Published: June 2014

We will consider the least-order torsional completion of gravity for a spacetime filled with fermionic Dirac matter fields, and we study the effects of the background-induced nonlinear potentials for the matter field themselves, in terms of their effects for both standard models of physics: from the one of cosmology to that of particles, we will discuss the mechanisms of generation of the cosmological constant and particles masses as well as the phenomenology of leptonic weak-like forces and neutrino oscillations, the problem of zero-point energy, how there can be neutral massive fields as candidates for dark matter, and the avoidance of gravitationally-induced singularity formation; we will show the way in which all these different effects can nevertheless be altogether described in terms of just a single model, which will be discussed in the beginning.
Activity-Based Profiling of Proteases
Authors: Sanman Laura E. , Bogyo Matthew
Published: June 2014

Proteolytic enzymes are key signaling molecules in both normal physiological processes and various diseases. After synthesis, protease activity is tightly controlled. Consequently, levels of protease messenger RNA and protein often are not good indicators of total protease activity. To more accurately assign function to new proteases, investigators require methods that can be used to detect and quantify proteolysis. In this review, we describe basic principles, recent advances, and applications of biochemical methods to track protease activity, with an emphasis on the use of activity-based probes (ABPs) to detect protease activity. We describe ABP design principles and use case studies to illustrate the application of ABPs to protease enzymology, discovery and development of protease-targeted drugs, and detection and validation of proteases as biomarkers.
Histone Chaperones: Assisting Histone Traffic and Nucleosome Dynamics
Authors: Gurard-Levin Zachary A. , Quivy Jean-Pierre , Almouzni Geneviève
Published: June 2014

The functional organization of eukaryotic DNA into chromatin uses histones as components of its building block, the nucleosome. Histone chaperones, which are proteins that escort histones throughout their cellular life, are key actors in all facets of histone metabolism; they regulate the supply and dynamics of histones at chromatin for its assembly and disassembly. Histone chaperones can also participate in the distribution of histone variants, thereby defining distinct chromatin landscapes of importance for genome function, stability, and cell identity. Here, we discuss our current knowledge of the known histone chaperones and their histone partners, focusing on histone H3 and its variants. We then place them into an escort network that distributes these histones in various deposition pathways. Through their distinct interfaces, we show how they affect dynamics during DNA replication, DNA damage, and transcription, and how they maintain genome integrity. Finally, we discuss the importance of histone chaperones during development and describe how misregulation of the histone flow can link to disease.
Enzyme Inhibitor Discovery by Activity-Based Protein Profiling
Authors: Niphakis Micah J. , Cravatt Benjamin F.
Published: June 2014

Eukaryotic and prokaryotic organisms possess huge numbers of uncharacterized enzymes. Selective inhibitors offer powerful probes for assigning functions to enzymes in native biological systems. Here, we discuss how the chemical proteomic platform activity-based protein profiling (ABPP) can be implemented to discover selective and in vivo–active inhibitors for enzymes. We further describe how these inhibitors have been used to delineate the biochemical and cellular functions of enzymes, leading to the discovery of metabolic and signaling pathways that make important contributions to human physiology and disease. These studies demonstrate the value of selective chemical probes as drivers of biological inquiry.
PTEN
Authors: Worby Carolyn A. , Dixon Jack E.
Published: June 2014

The importance of PTEN in cellular function is underscored by the frequency of its deregulation in cancer. PTEN tumor-suppressor activity depends largely on its lipid phosphatase activity, which opposes PI3K/AKT activation. As such, PTEN regulates many cellular processes, including proliferation, survival, energy metabolism, cellular architecture, and motility. More than a decade of research has expanded our knowledge about how PTEN is controlled at the transcriptional level as well as by numerous posttranscriptional modifications that regulate its enzymatic activity, protein stability, and cellular location. Although the role of PTEN in cancers has long been appreciated, it is also emerging as an important factor in other diseases, such as diabetes and autism spectrum disorders. Our understanding of PTEN function and regulation will hopefully translate into improved prognosis and treatment for patients suffering from these ailments.
Photoacoustic Microscopy and Computed Tomography: From Bench to Bedside
Authors: Wang Lihong V. , Gao Liang
Published: June 2014

Photoacoustic imaging (PAI) of biological tissue has seen immense growth in the past decade, providing unprecedented spatial resolution and functional information at depths in the optical diffusive regime. PAI uniquely combines the advantages of optical excitation and those of acoustic detection. The hybrid imaging modality features high sensitivity to optical absorption and wide scalability of spatial resolution with the desired imaging depth. Here we first summarize the fundamental principles underpinning the technology, then highlight its practical implementation, and finally discuss recent advances toward clinical translation.
Electroporation-Based Technologies for Medicine: Principles, Applications, and Challenges
Authors: Yarmush Martin L. , Golberg Alexander , Serša Gregor , Kotnik Tadej , Miklavčič Damijan
Published: June 2014

When high-amplitude, short-duration pulsed electric fields are applied to cells and tissues, the permeability of the cell membranes and tissue is increased. This increase in permeability is currently explained by the temporary appearance of aqueous pores within the cell membrane, a phenomenon termed electroporation. During the past four decades, advances in fundamental and experimental electroporation research have allowed for the translation of electroporation-based technologies to the clinic. In this review, we describe the theory and current applications of electroporation in medicine and then discuss current challenges in electroporation research and barriers to a more extensive spread of these clinical applications.
Recent Advances in Nanoparticle-Mediated siRNA Delivery
Authors: Williford John-Michael , Wu Juan , Ren Yong , Archang Maani M. , Leong Kam W. , Mao Hai-Quan
Published: June 2014

Inhibiting specific gene expression by short interfering RNA (siRNA) offers a new therapeutic strategy to tackle many diseases, including cancer, metabolic disorders, and viral infections, at the molecular level. The macromolecular and polar nature of siRNA hinders its cellular access to exert its effect. Nanoparticulate delivery systems can promote efficient intracellular delivery. Despite showing promise in many preclinical studies and potential in some clinical trials, siRNA has poor delivery efficiency, which continues to demand innovations, from carrier design to formulation, in order to overcome transport barriers. Previous findings for optimal plasmid DNA delivery cannot be generalized to siRNA delivery owing to significant discrepancy in size and subtle differences in chain flexibility between the two types of nucleic acids. In this review, we highlight the recent advances in improving the stability of siRNA nanoparticles, understanding their intracellular trafficking and release mechanisms, and applying judiciously the promising formulations to disease models.
Inertial Focusing in Microfluidics
Authors: Martel Joseph M. , Toner Mehmet
Published: June 2014

When Segré and Silberberg in 1961 witnessed particles in a laminar pipe flow congregating at an annulus in the pipe, scientists were perplexed and spent decades learning why such behavior occurred, finally understanding that it was caused by previously unknown forces on particles in an inertial flow. The advent of microfluidics opened a new realm of possibilities for inertial focusing in the processing of biological fluids and cellular suspensions and created a field that is now rapidly expanding. Over the past five years, inertial focusing has enabled high-throughput, simple, and precise manipulation of bodily fluids for a myriad of applications in point-of-care and clinical diagnostics. This review describes the theoretical developments that have made the field of inertial focusing what it is today and presents the key applications that will make inertial focusing a mainstream technology in the future.
Emotion and Decision Making: Multiple Modulatory Neural Circuits
Authors: Phelps Elizabeth A. , Lempert Karolina M. , Sokol-Hessner Peter
Published: June 2014

Although the prevalent view of emotion and decision making is derived from the notion that there are dual systems of emotion and reason, a modulatory relationship more accurately reflects the current research in affective neuroscience and neuroeconomics. Studies show two potential mechanisms for affect's modulation of the computation of subjective value and decisions. Incidental affective states may carry over to the assessment of subjective value and the decision, and emotional reactions to the choice may be incorporated into the value calculation. In addition, this modulatory relationship is reciprocal: Changing emotion can change choices. This research suggests that the neural mechanisms mediating the relation between affect and choice vary depending on which affective component is engaged and which decision variables are assessed. We suggest that a detailed and nuanced understanding of emotion and decision making requires characterizing the multiple modulatory neural circuits underlying the different means by which emotion and affect can influence choices.
Functions and Dysfunctions of Adult Hippocampal Neurogenesis
Authors: Christian Kimberly M. , Song Hongjun , Ming Guo-li
Published: June 2014

Adult neurogenesis, a developmental process of generating functionally integrated neurons, occurs throughout life in the hippocampus of the mammalian brain and showcases the highly plastic nature of the mature central nervous system. Significant progress has been made in recent years to decipher how adult neurogenesis contributes to brain functions. Here we review recent findings that inform our understanding of adult hippocampal neurogenesis processes and special properties of adult-born neurons. We further discuss potential roles of adult-born neurons at the circuitry and behavioral levels in cognitive and affective functions and how their dysfunction may contribute to various brain disorders. We end by considering a general model proposing that adult neurogenesis is not a cell-replacement mechanism, but instead maintains a plastic hippocampal neuronal circuit via the continuous addition of immature, new neurons with unique properties and structural plasticity of mature neurons induced by new-neuron integration.
Molecular Mediators Governing Iron-Copper Interactions
Authors: Gulec Sukru , Collins James F.
Published: June 2014

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states.
Fifty Years of Human Space Travel: Implications for Bone and Calcium Research
Authors: Smith S.M. , Abrams S.A. , Davis-Street J.E. , Heer M. , O'Brien K.O. , Wastney M.E. , Zwart S.R.
Published: June 2014

Calcium and bone metabolism remain key concerns for space travelers, and ground-based models of space flight have provided a vast literature to complement the smaller set of reports from flight studies. Increased bone resorption and largely unchanged bone formation result in the loss of calcium and bone mineral during space flight, which alters the endocrine regulation of calcium metabolism. Physical, pharmacologic, and nutritional means have been used to counteract these changes. In 2012, heavy resistance exercise plus good nutritional and vitamin D status were demonstrated to reduce loss of bone mineral density on long-duration International Space Station missions. Uncertainty continues to exist, however, as to whether the bone is as strong after flight as it was before flight and whether nutritional and exercise prescriptions can be optimized during space flight. Findings from these studies not only will help future space explorers but also will broaden our understanding of the regulation of bone and calcium homeostasis on Earth.
The ABCs and 123s of Bacterial Secretion Systems in Plant Pathogenesis
Authors: Chang Jeff H. , Desveaux Darrell , Creason Allison L.
Published: June 2014

Bacteria have many export and secretion systems that translocate cargo into and across biological membranes. Seven secretion systems contribute to pathogenicity by translocating proteinaceous cargos that can be released into the extracellular milieu or directly into recipient cells. In this review, we describe these secretion systems and how their complexities and functions reflect differences in the destinations, states, functions, and sizes of the translocated cargos as well as the architecture of the bacterial cell envelope. We examine the secretion systems from the perspective of pathogenic bacteria that proliferate within plant tissues and highlight examples of translocated proteins that contribute to the infection and disease of plant hosts.
Novel Insights into Rice Innate Immunity Against Bacterial and Fungal Pathogens
Authors: Liu Wende , Liu Jinling , Triplett Lindsay , Leach Jan E. , Wang Guo-Liang
Published: June 2014

Rice feeds more than half of the world's population. Rice blast, caused by the fungal pathogen Magnaporthe oryzae, and bacterial blight, caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae, are major constraints to rice production worldwide. Genome sequencing and extensive molecular analysis has led to the identification of many new pathogen-associated molecular patterns (PAMPs) and avirulence and virulence effectors in both pathogens, as well as effector targets and receptors in the rice host. Characterization of these effectors, host targets, and resistance genes has provided new insight into innate immunity in plants. Some of the new findings, such as the binding activity of X. oryzae transcriptional activator–like (TAL) effectors to specific rice genomic sequences, are being used for the development of effective disease control methods and genome modification tools. This review summarizes the recent progress toward understanding the recognition and signaling events that govern rice innate immunity.
Plant-Parasitic Nematode Infections in Rice: Molecular and Cellular Insights
Authors: Kyndt Tina , Fernandez Diana , Gheysen Godelieve
Published: June 2014

Being one of the major staple foods in the world, and an interesting model monocot plant, rice (Oryza sativa L.) has recently received attention from molecular nematologists studying the cellular and molecular aspects of the interaction between this crop and plant-parasitic nematodes. In this review, we highlight recent advances in this field, with a focus on the best-studied root-knot nematodes. Histological studies have revealed the cellular changes inside root-knot nematode–induced feeding sites, both in the compatible interaction with Oryza sativa and the incompatible interaction with the related species Oryza glaberrima. After comparing the published data from transcriptome analyses, mutant studies, and exogenous hormone applications, we provide a comprehensive model showing the role and interaction of plant hormone pathways in defense of this monocot crop against root nematodes, where jasmonate seems to play a key role. Finally, recent evidence indicates that effectors secreted from rice-infecting nematodes can suppress plant defense.
Virus Infection Cycle Events Coupled to RNA Replication
Authors: Saxena Pooja , Lomonossoff George P.
Published: June 2014

Replication, the process by which the genetic material of a virus is copied to generate multiple progeny genomes, is the central part of the virus infection cycle. For an infection to be productive, it is essential that this process is coordinated with other aspects of the cycle, such as translation of the viral genome, encapsidation, and movement of the genome between cells. In the case of positive-strand RNA viruses, this represents a particular challenge, as the infecting genome must not only be replicated but also serve as an mRNA for the production of the replication-associated proteins. In recent years, it has become apparent that in positive-strand RNA plant viruses all the aspects of the infection cycle are intertwined. This article reviews the current state of knowledge regarding replication-associated events in such viruses.
Consumption- Versus Production-Based Emission Policies
Authors: Jakob Michael , Steckel Jan Christoph , Edenhofer Ottmar
Published: June 2014

Emission leakage could potentially undermine the effectiveness of unilateral climate policies. Significant emission transfers from developing countries to developed countries in the form of emissions embodied in trade have been interpreted as an indication of such leakage. To reduce leakage and provide an appropriate picture of countries’ responsibility for global emissions, an alternative proposal is to attribute emissions on the basis of consumption instead of production. However, as one unit of imported emissions generally cannot be equated with a corresponding increase in emissions released to the atmosphere, putting a price on emissions embodied in imports equal to the social cost of these emissions (e.g., by means of consumption-based emission pricing) is not an optimal policy. Hence, one should consider a broad scope of trade measures to reduce leakage, focusing on a few highly traded, emission-intensive industries. Finally, the optimal policy portfolio to address leakage may also contain free allocation of emission permits and sectoral approaches.