bluuebunny/crossref_metadata_2025 huggingface dataset:
Two novel missense mutations associated with hemophilia A in a family of Boxers, and a German Shepherd dog
Authors: Christopherson Pete W. , Bacek Lenore M. , King Kevin B. , Boudreaux Mary K.
Published: July 2014

Background

Hemophilia A is an X‐linked disorder caused by a deficiency in coagulation factor VIII. Over 2300 unique mutations in the gene‐encoding factor VIII have been documented in people, but limited information is known in dogs. An 11‐week‐old male Boxer and a 5‐year‐old male German Shepherd were diagnosed with hemophilia A based on diminished factor VIII activity.

Objective

The purpose of the study was to identify genetic mutations associated with hemophilia A in both dogs.

Methods

Genomic DNA was isolated from EDTA blood samples from the affected German Shepherd and Boxer, the Boxer's dam, 3 female siblings, and one asymptomatic male sibling. Primers were designed in noncoding regions to amplify the 26 exons of the factor VIII gene via PCR.

Results

The affected Boxer sequence revealed a single nucleotide change, cytosine to guanine, at nucleotide position 1412 (1412C>G) in exon 10. The change is predicted to result in the substitution of arginine for proline at amino acid 471 (P471R) in the A2 domain of factor VIII. The dam and female siblings were carriers, the male sibling did not have the mutation. The German Shepherd dog had a single nucleotide change of a guanine to adenine at position 1643 (1643G>A) in exon 11, predicting the substitution of tyrosine for cysteine at amino acid 548 (C548Y) in the A2 domain.

Conclusions

Here we document 2 mutations associated with canine hemophilia A associated with < 1% factor VIII activity, similar to that in people. Another related Boxer with the P471R mutation was later identified.
Resource Allocation for Lean Product Development Using a Value Creation Cell Model
Authors: Cai Tianyi , Freiheit Theodor
Published: July 2014

Lean can be applied to product development processes to improve value creation management. However, allocating resources to a project or a development program in order to maximize the value generated by project activities can be difficult in complex product development processes. This paper discusses how value creation activities can be better managed by regulating the resource allocation process. A mathematical model is proposed to describe value growth and its application to resource allocation is demonstrated that gives insight into value creation trajectories. The application is demonstrated with scenarios developed from the computer industry and a design project.
Nine Principles for Design for the Developing World as Derived From the Engineering Literature
Authors: Mattson Christopher A. , Wood Amy E.
Published: July 2014

This paper reviews the findings of several engineering researchers and practitioners on the topic of design for the developing world. We arrange these findings into nine guiding principles aimed at helping those who are searching for effective approaches for design for the developing world. The findings reviewed come from the mechanical engineering discipline, as well as from other engineering and nonengineering disciplines. For each principle, we provide references to various studies as a means of supporting the principle. We also provide a detailed example of each principle. Based on our own experience and based on the many papers reviewed, we provide a succinct list of suggestions for using each principle. Finally, we relate these nine principles to traditional design principles. Ultimately, we believe that the principles introduced here help overcome the challenges of design for the developing world, which are often dominated by designer unfamiliarity with poverty and foreign culture and the constraint of extreme affordability.
Editorial
Authors: Schirato Tony
Published: July 2014

Editorial
The Role of Indigenous Media in Establishing National Identity
Authors: McCulloch Craig
Published: July 2014

The Role of Indigenous Media in Establishing National Identity
Acute Effects of a Loaded Warm-Up Protocol on Change of Direction Speed in Professional Badminton Players
Authors: Maloney Sean J. , Turner Anthony N. , Miller Stuart
Published: July 2014

It has previously been shown that a loaded warm-up may improve power performances. We examined the acute effects of loaded dynamic warm-up on change of direction speed (CODS), which had not been previously investigated. Eight elite badminton players participated in three sessions during which they performed vertical countermovement jump and CODS tests before and after undertaking the dynamic warm-up. The three warm-up conditions involved wearing a weighted vest (a) equivalent to 5% body mass, (b) equivalent to 10% body mass, and (c) a control where a weighted vest was not worn. Vertical jump and CODS performances were then tested at 15 seconds and 2, 4, and 6 minutes post warm-up. Vertical jump and CODS significantly improved following all warm-up conditions (P < .05). Post warm-up vertical jump performance was not different between conditions (P = .430). Post warm-up CODS was significantly faster following the 5% (P = .02) and 10% (P < .001) loaded conditions compared with the control condition. In addition, peak CODS test performances, independent of recovery time, were faster than the control condition following the 10% loaded condition (P = .012). In conclusion, the current study demonstrates that a loaded warm-up augmented CODS, but not vertical jump performance, in elite badminton players.
Climbing Skill and Complexity of Climbing Wall Design: Assessment of Jerk as a Novel Indicator of Performance Fluency
Authors: Seifert Ludovic , Orth Dominic , Boulanger Jérémie , Dovgalecs Vladislavs , Hérault Romain , Davids Keith
Published: July 2014

This study investigated a new performance indicator to assess climbing fluency (smoothness of the hip trajectory and orientation of a climber using normalized jerk coefficients) to explore effects of practice and hold design on performance. Eight experienced climbers completed four repetitions of two, 10-m high routes with similar difficulty levels, but varying in hold graspability (holds with one edge vs holds with two edges). An inertial measurement unit was attached to the hips of each climber to collect 3D acceleration and 3D orientation data to compute jerk coefficients. Results showed high correlations (r = .99, P < .05) between the normalized jerk coefficient of hip trajectory and orientation. Results showed higher normalized jerk coefficients for the route with two graspable edges, perhaps due to more complex route finding and action regulation behaviors. This effect decreased with practice. Jerk coefficient of hip trajectory and orientation could be a useful indicator of climbing fluency for coaches as its computation takes into account both spatial and temporal parameters (ie, changes in both climbing trajectory and time to travel this trajectory).
Harnessing naturally occurring data to measure the response of spending to income
Authors: Gelman Michael , Kariv Shachar , Shapiro Matthew D. , Silverman Dan , Tadelis Steven
Published: July 2014

Balancing your incomings and outgoings

Economic theory predicts that when someone receives money should have little effect on their spending patterns. Gelman
et al.
constructed a data set of 60 million transactions made by 75,000 people to test this theory. People do seem to go on a mini–spending spree after they get their paychecks or pensions. However, closer inspection reveals that that's mostly explained by the convenience of linking regular payments, such as rent and utilities, to regular income. Unsurprisingly, cash-strapped people are more likely to increase their spending in response to receiving income.

Science
, this issue p.
212
Microplastics in the seas
Authors: Law Kara Lavender , Thompson Richard C.
Published: July 2014

Concern is rising about widespread contamination of the marine environment by microplastics.
A flipping cell wall ferry
Authors: Young Kevin D.
Published: July 2014

How bacteria “flip” carbohydrate precursors across the cytoplasmic membrane.

[Also see Report by

Sham
et al.

]
A fitness bottleneck in HIV-1 transmission
Authors: Joseph Sarah B. , Swanstrom Ronald
Published: July 2014

A successful infection is determined in part by how close a viral genome is to an ideal sequence.

[Also see Research Article by

Carlson
et al.

]
India plans the grandest of canal networks
Authors: Bagla Pallava
Published: July 2014

Nationwide water transfer scheme could aid farming, but critics fear ecological havoc.
Diagnosis of Pneumocystis jirovecii Pneumonia in Immunocompromised Patients by Real-Time PCR: a 4-Year Prospective Study
Authors: Robert-Gangneux Florence , Belaz Sorya , Revest Matthieu , Tattevin Pierre , Jouneau Stéphane , Decaux Olivier , Chevrier Sylviane , Le Tulzo Yves , Gangneux Jean-Pierre
Published: July 2014

Pneumocystis jirovecii
pneumonia (PCP) is a life-threatening infection in immunocompromised patients. Quantitative real-time PCR (qPCR) is more sensitive than microscopic examination for the detection of
P. jirovecii
but also detects colonized patients. Hence, its positive predictive value (PPV) needs evaluation. In this 4-year prospective observational study, all immunocompromised patients with acute respiratory symptoms who were investigated for PCP were included, totaling 659 patients (814 bronchoalveolar lavage fluid samples). Patients with negative microscopy but positive qPCR were classified through medical chart review as having retained PCP, possible PCP, or colonization, and their clinical outcomes were compared to those of patients with microscopically proven PCP. Overall, 119 patients were included for analysis, of whom 35, 41, and 43 were classified as having retained PCP, possible PCP, and colonization, respectively. The 35 patients with retained PCP had clinical findings similar to those with microscopically proven PCP but lower fungal loads (
P
< 0.001) and were mainly non-HIV-infected patients (
P
< 0.05). Although the mean amplification threshold was higher in colonized patients, it was not possible to determine a discriminant qPCR cutoff. The PPV of qPCR in patients with negative microscopy were 29.4% and 63.8% when considering retained PCP and retained plus possible PCP, respectively. Patients with possible PCP had a higher mortality rate than patients with retained PCP or colonization (63% versus 3% and 16%, respectively); patients who died had not received co-trimoxazole. In conclusion, qPCR is a useful tool to diagnose PCP in non-HIV patients, and treatment might be better targeted through a multicomponent algorithm including both clinical/radiological parameters and qPCR results.
Rapid Expansion of CD8
+
T Cells in Wild-Type and Type I Interferon Receptor-Deficient Mice Correlates with Protection after Low-Dose Emergency Immunization with Modified Vaccinia Virus Ankara
Authors: Volz Asisa , Langenmayer Martin , Jany Sylvia , Kalinke Ulrich , Sutter Gerd
Published: July 2014

Immunization with modified vaccinia virus Ankara (MVA) can rapidly protect mice against lethal ectromelia virus (ECTV) infection, serving as an experimental model for severe systemic infections. Importantly, this early protective capacity of MVA vaccination completely depends on virus-specific cytotoxic CD8
+
T cell responses. We used MVA vaccination in the mousepox challenge model using ECTV infection to investigate the previously unknown factors required to elicit rapid protective T cell immunity in normal C57BL/6 mice and in mice lacking the interferon alpha/beta receptor (IFNAR
−/−
). We found a minimal dose of 10
5
PFU of MVA vaccine fully sufficient to allow robust protection against lethal mousepox, as assessed by the absence of disease symptoms and failure to detect ECTV in organs from vaccinated animals. Moreover, MVA immunization at low dosage also protected IFNAR
−/−
mice, indicating efficient activation of cellular immunity even in the absence of type I interferon signaling. When monitoring for virus-specific CD8
+
T cell responses in mice vaccinated with the minimal protective dose of MVA, we found significantly enhanced levels of antigen-specific T cells in animals that were MVA vaccinated and ECTV challenged compared to mice that were only vaccinated. The initial priming of naive CD8
+
T cells by MVA immunization appears to be highly efficient and, even at low doses, mediates a rapid
in vivo
burst of pathogen-specific T cells upon challenge. Our findings define striking requirements for protective emergency immunization against severe systemic infections with orthopoxviruses.

IMPORTANCE
We demonstrate that single-shot low-dose immunizations with vaccinia virus MVA can rapidly induce T cell-mediated protective immunity against lethal orthopoxvirus infections. Our data provide new evidence for an efficient protective capacity of vaccination with replication-deficient MVA. These data are of important practical relevance for public health, as the effectiveness of a safety-tested, next-generation smallpox vaccine based on MVA is still debated. Furthermore, producing sufficient amounts of vaccine is expected to be a major challenge should an outbreak occur. Moreover, prevention of other infections may require rapidly protective immunization; hence, MVA could be an extremely useful vaccine for delivering heterologous T cell antigens, particularly for infectious diseases that fit a scenario of emergency vaccination.
Detailed Study of the Interaction between Human Herpesvirus 6B Glycoprotein Complex and Its Cellular Receptor, Human CD134
Authors: Tang Huamin , Wang Junjie , Mahmoud Nora F. , Mori Yasuko
Published: July 2014

Recently, we identified a novel receptor, CD134, which interacts with the human herpesvirus 6B (HHV-6B) glycoprotein (g)H/gL/gQ1/gQ2 complex and plays a key role in the entry of HHV-6B into target cells. However, details of the interaction between the HHV-6B gH/gL/gQ1/gQ2 complex and CD134 were unknown. In this study, we identified a cysteine-rich domain (CRD), CDR2, of CD134 that is critical for binding to the HHV-6B glycoprotein complex and HHV-6B infection. Furthermore, we found that the expression of HHV-6B gQ1 and gQ2 subunits was sufficient for CD134 binding, which is different from the binding of human herpesvirus 6A (HHV-6A) to its receptor, CD46. Finally, we identified a region in gQ1 critical for HHV-6B gQ1 function. These results contribute much to our understanding of the interaction between this ligand and receptor.

IMPORTANCE
We identified the domain in HHV-6B entry receptor CD134 and the components in the HHV-6B gH/gL/gQ1/gQ2 complex required for ligand-receptor binding during HHV-6B infection. Furthermore, we identified domains in gQ1 proteins of HHV-6A and -6B and a key amino acid residue in HHV-6B gQ1 required for its function. These data should be the basis for further investigation of ligand-receptor interaction in the study of HHV-6A and -6B.
Type III Interferon Attenuates a Vesicular Stomatitis Virus-Based Vaccine Vector
Authors: Guayasamin Ryann C. , Reynolds Tracy D. , Wei Xin , Fujiwara Mai , Robek Michael D.
Published: July 2014

Vesicular stomatitis virus (VSV) has been extensively studied as a vaccine vector and oncolytic agent. Nevertheless, safety concerns have limited its widespread use in humans. The type III lambda interferon (IFN-λ) family of cytokines shares common signaling pathways with the IFN-α/β family and thus evokes similar antiviral activities. However, IFN-λ signals through a distinct receptor complex that is expressed in a cell type-specific manner, which restricts its activity to epithelial barriers, particularly those corresponding to the respiratory and gastrointestinal tracts. In this study, we determined how IFN-λ expression from recombinant VSV would influence vector replication, spread, and immunogenicity. We demonstrate that IFN-λ expression severely attenuates VSV in cell culture.
In vivo
, IFN-λ limits VSV replication in the mouse lung after intranasal administration and reduces virus spread to other organs. Despite this attenuation, however, the vector retains its capacity to induce protective CD8 T cell and antibody responses after a single immunization. These findings demonstrate a novel method of viral vector attenuation that could be used in both vaccine and oncolytic virus applications.

IMPORTANCE
Viruses such as VSV that are used as vaccine vectors can induce protective T cell and antibody responses after a single dose. Additionally, IFN-λ is a potent antiviral agent that has certain advantages for clinical use compared to IFN-α/β, such as fewer patient side effects. Here, we demonstrate that IFN-λ attenuates VSV replication and spread following intranasal virus delivery but does not reduce the ability of VSV to induce potent protective immune responses. These findings demonstrate that the type III IFN family may have widespread applicability for improving the safety and efficacy of viral vaccine and oncolytic vectors.
Paradoxical air embolism and neurological insult during removal of a pulmonary artery catheter introducer
Authors: Bowles Philippe Frederick , Lear Christopher , Maccario Marco , Kong Robert
Published: July 2014

A 54-year-old man was admitted to the intensive care unit following cardiac surgery. On day 6 postoperatively, approximately 2–3 min following the removal of the pulmonary artery (PA) catheter introducer sited in the right internal jugular vein, the patient became agitated, confused and then unresponsive. He was urgently moved onto the bed, laid supine, sedated with a propofol infusion, intubated and mechanically ventilated. A bedside transthoracic echocardiogram revealed extensive multiple air emboli in all cardiac chambers and review of the patient's intraoperative imaging confirmed the presence of patent foramen ovale (PFO). The following morning, sedation was discontinued and the trachea extubated. The patient was later transferred to the ward and then discharged home with no evidence of neurological deficit. This case reminds us of the importance of strict adherence to safety protocols when manipulating centrally positioned catheters and the high prevalence of undiagnosed PFO.
Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study
Authors: Hughes Shannon , Cohen David , Jaggi Rachel
Published: July 2014

Objective

To examine the degree of concordance in reporting serious adverse events (SAEs) from antidepressant and antipsychotic drug trials among journal articles and clinical trial summaries, and to categorise types of discrepancies.

Design

Cross-sectional study of summaries of all antidepressant and antipsychotic trials included in an online trial registry and their first associated stand-alone journal articles.

Setting

Clinicalstudyresults.org, sponsored by Pharmaceutical Research and Manufacturers of America; clinicaltrials.gov, administered by the US National Institutes of Health.

Main outcome measure

3 coders extracted data on the numbers and types of SAEs.

Results

244 trial summaries for six antidepressant and antipsychotic drugs were retrieved, 142 (58.2%) listing an associated article. Of 1608 SAEs in drug-treated participants according to trial summaries, 694 (43.2%) did not appear in associated articles. Nearly 60% of SAEs counted in articles and 41% in trial summaries had no description. Most cases of death (62.3%) and suicide (53.3%) were not reported in articles. Half or more of the 142 pairs were discordant in reporting the number (49.3%) or description (67.6%) of SAEs. These discrepancies resulted from journal articles’ (1) omission of complete SAE data, (2) reporting acute phase study results only and (3) more restrictive reporting criteria. Trial summaries with zero SAE were 2.35 (95% CI, 1.58 to 3.49; p<0.001) times more likely to be published with no discrepancy in their associated journal article. Since clinicalstudyresults.org was removed from the Internet in 2011, only 7.8% of retrieved trial summaries appear with results on clinicaltrials.gov.

Conclusions

Substantial discrepancies exist in SAE data found in journal articles and registered summaries of antidepressant and antipsychotic drug trials. Two main scientific sources accessible to clinicians and researchers are limited by incomplete, ambiguous and inconsistent reporting. Access to complete and accurate data from clinical trials of drugs currently in use remains a pressing concern.
Pharmacists’ response to anaphylaxis in the community (PRAC): a randomised, simulated patient study of pharmacist practice
Authors: Salter Sandra M , Delfante Brock , de Klerk Sarah , Sanfilippo Frank M , Clifford Rhonda M
Published: July 2014

Objective

To evaluate how community pharmacists manage patients with anaphylaxis.

Design

A randomised, cross-sectional, simulated patient study of community pharmacist practice.

Setting

300 metropolitan pharmacies located in Perth Australia, randomised to three groups of 100 pharmacies. Each group corresponded to a different epinephrine autoinjector: original EpiPen, new-look EpiPen or Anapen.

Participants

300 pharmacies were visited with 271 simulated patient visits included in the final analysis (88=original EpiPen, 92=new-look EpiPen, 91=Anapen).

Outcome measures

Primaryanaphylaxis preparedness (readiness to treat acute anaphylaxis).Secondaryanaphylaxis engagement (willingness to engage the patient in a discussion about their anaphylaxis).

Methods

Simulated patients approached pharmacists, using a standardised scenario, for assistance with epinephrine autoinjector use and advice about the use of antihistamines in anaphylaxis. Scores for each outcome were obtained based on the number of predefined statements addressed by the pharmacist during the consultation (maximum score=5 for preparedness and 8 for engagement).

Results

The mean anaphylaxis preparedness score was 2.39 points (SD 1.17). Scores for new-look EpiPen were significantly higher than for original EpiPen and Anapen (2.75 vs 2.38 points, p=0.027; 2.75 vs 2.03 points, p<0.001, respectively). Overall, 17.3% of pharmacists correctly demonstrated the epinephrine autoinjector. The mean anaphylaxis engagement score was 3.11 points (SD 1.73). Scores for new-look EpiPen were similar to original EpiPen and Anapen (3.11 vs 3.32 points; 3.11 vs 2.90 points, both p=0.42). Engagement was associated with preparedness. For each additional engagement point, preparedness increased by 7% (0.357 points; 95% CI 0.291 to 0.424; p<0.001).

Conclusions

Pharmacists demonstrated reasonable knowledge of anaphylaxis symptoms and emergency care, but had poor epinephrine autoinjector technique and rarely discussed anaphylaxis action plans. Pharmacists who had a more comprehensive discussion about anaphylaxis with patients, were more prepared for anaphylaxis emergencies. Future research should evaluate the nature and significance of errors in pharmacists’ autoinjector technique.
What is time in quantum mechanics?
Authors: Jadczyk Arkadiusz
Published: July 2014

Time of arrival in quantum mechanics is discussed in two versions: the classical axiomatic "time of arrival operator" introduced by Kijowski and the event enhanced quantum theory (EEQT) method. It is suggested that for free particles the two methods may lead to the same result. On the other hand, the EEQT method can be easily geometrized within the framework of Galilei–Newton general relativistic quantum mechanics developed by M. Modugno and collaborators, and it can be applied to non-free evolutions. The way of geometrization of irreversible quantum dynamics based on dissipative Liouville equation is suggested.
CURRENT STATE OF THE SEA SYSTEM IN BRAZIL: A COMPARATIVE STUDY
Authors: MONTAÑO MARCELO , OPPERMANN PRISCILA , MALVESTIO ANNE CAROLINE , SOUZA MARCELO PEREIRA
Published: July 2014

After the first applications in the early 1990's, the practice of SEA in Brazil has been going through a slow, but important evolution. In this paper we elaborate on the main aspects of this evolution, based on the findings of a comparative study that put the practice of SEA in different contexts into perspective. SEA systems considered included consolidated (UK, Spain and Portugal) and unconsolidated (South Africa, Mexico, Angola and Mozambique) systems. The Brazilian system is characterised by a disperse structure and a low level of self-organisation, which makes integration with plan making difficult while, at the same time, stimulating "flexible" and "adaptive" SEA processes. We suggest that the lack of both, institutional drivers and a clear procedural framework are hindering further development of the Brazilian system.
Counting points of given height that generate a quadratic extension of a function field
Authors: Kettlestrings David , Thunder Jeffrey Lin
Published: July 2014

Let K be a finite algebraic extension of the field of rational functions in one indeterminate over a finite field and let [Formula: see text] denote an algebraic closure of K. We count points in projective space [Formula: see text] with given height and generating a quadratic extension of K. If n > 2, we derive an asymptotic estimate for the number of such points as the height tends to infinity. Such estimates are analogous to previous results of Schmidt where the field K is replaced by the field of rational numbers ℚ.
Collective Circumnavigation
Authors: Swartling Johanna O. , Shames Iman , Johansson Karl H. , Dimarogonas Dimos V.
Published: July 2014

This paper considers the problem of localization and circumnavigation of a slowly drifting target with an unknown speed by a group of autonomous agents while they form a regular polygon at a known distance from the target. The goal is achieved in a distributed way where each of the agents coordinates its motion knowing its own position and either the bearing angle of the target or the distance to the target, and the position of one of its neighbors. First, we solve the problem for the case where the target is stationary and propose a two-stage control law that forces the agents to move on a circular trajectory around the target and form a regular polygon formation. Then, we consider the case where the target is undergoing a slow but possibly persistent movement. Later, we consider the case where only one of the agents know the desired distance from the target. In the end, the case in which only a subset of agents can measure either the bearing or the distance to the target is considered. The performance of the controllers proposed is verified analytically, through simulations, and in an experimental setup.
Alterations in the cholinergic system of brain stem neurons in a mouse model of Rett syndrome
Authors: Oginsky Max F. , Cui Ningren , Zhong Weiwei , Johnson Christopher M. , Jiang Chun
Published: July 2014

Rett syndrome is an autism-spectrum disorder resulting from mutations to the X-linked gene, methyl-CpG binding protein 2 (MeCP2), which causes abnormalities in many systems. It is possible that the body may develop certain compensatory mechanisms to alleviate the abnormalities. The norepinephrine system originating mainly in the locus coeruleus (LC) is defective in Rett syndrome and Mecp2-null mice. LC neurons are subject to modulation by GABA, glutamate, and acetylcholine (ACh), providing an ideal system to test the compensatory hypothesis. Here we show evidence for potential compensatory modulation of LC neurons by post- and presynaptic ACh inputs. We found that the postsynaptic currents of nicotinic ACh receptors (nAChR) were smaller in amplitude and longer in decay time in the Mecp2-null mice than in the wild type. Single-cell PCR analysis showed a decrease in the expression of α3-, α4-, α7-, and β3-subunits and an increase in the α5- and α6-subunits in the mutant mice. The α5-subunit was present in many of the LC neurons with slow-decay nAChR currents. The nicotinic modulation of spontaneous GABAA-ergic inhibitory postsynaptic currents in LC neurons was enhanced in Mecp2-null mice. In contrast, the nAChR manipulation of glutamatergic input to LC neurons was unaffected in both groups of mice. Our current-clamp studies showed that the modulation of LC neurons by ACh input was reduced moderately in Mecp2-null mice, despite the major decrease in nAChR currents, suggesting possible compensatory processes may take place, thus reducing the defects to a lesser extent in LC neurons.
ANG II receptor subtype 1a gene knockdown in the subfornical organ prevents increased drinking behavior in bile duct-ligated rats
Authors: Walch Joseph D. , Nedungadi T. Prashant , Cunningham J. Thomas
Published: July 2014

Bile duct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes, resulting in dilutional hyponatremia due to increased water intake and vasopressin release. This project tested the hypothesis that angiotensin signaling at the subfornical organ (SFO) augments drinking behavior in BDL rats. A genetically modified adeno-associated virus containing short hairpin RNA (shRNA) for ANG II receptor subtype 1a (AT1aR) gene was microinjected into the SFO of rats to knock down expression. Two weeks later, BDL or sham surgery was performed. Rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. The rats were euthanized 28 days after BDL surgery for analysis. A group of rats was perfused for immunohistochemistry, and a second group was used for laser-capture microdissection for analysis of SFO AT1aR gene expression. BDL rats showed increased water intake that was attenuated in rats that received SFO microinjection of AT1aR shRNA. Among BDL rats treated with scrambled (control) and AT1aR shRNA, we observed an increased number of vasopressin-positive cells in the supraoptic nucleus that colocalized with ΔFosB staining, suggesting increased vasopressin release in both groups. These results indicate that angiotensin signaling through the SFO contributes to increased water intake, but not dilutional hyponatremia, during congestive liver failure.
Rho-kinase regulation of TNF-α-induced nuclear translocation of NF-κB RelA/p65 and M-CSF expression via p38 MAPK in mesangial cells
Authors: Matoba Keiichiro , Kawanami Daiji , Tsukamoto Masami , Kinoshita Jun , Ito Tomoko , Ishizawa Sho , Kanazawa Yasushi , Yokota Tamotsu , Murai Noriyuki , Matsufuji Senya , Utsunomiya Kazunori
Published: July 2014

The small GTPase Rho and its downstream effector, Rho-associated coiled-coil containing protein kinase (Rho-kinase), regulate a number of cellular processes, including organization of the actin cytoskeleton, cell adhesion, and migration. While pharmacological inhibitors of Rho-kinase signaling are known to block renal inflammation, the molecular basis for this effect is unclear. Here, we provide evidence that proinflammatory TNF-α promotes mesangial expression of macrophage colony-stimulating factor (M-CSF), a key regulator for the growth and differentiation of mononuclear phagocytes, in a Rho-kinase-dependent manner. Consistent with this observation, TNF-α-mediated renal expression of M-CSF in insulin-resistant db/db mice was downregulated by Rho-kinase inhibition. Small interfering RNA-facilitated knockdown of Rho-kinase isoforms ROCK1 and ROCK2 indicated that both isoforms make comparable contributions to regulation of M-CSF expression in mesangial cells. From a mechanistic standpoint, Western blotting and EMSA showed that Rho-kinase and its downstream target p38 MAPK regulate nuclear translocation of NF-κB RelA/p65 and subsequent DNA binding activity, with no significant effects on IκBα degradation and RelA/p65 phosphorylation. Moreover, we showed that Rho-kinase-mediated cytoskeletal organization is required for the nuclear uptake of RelA/p65. Collectively, these findings identify Rho-kinase as a critical regulator of chemokine expression and macrophage proliferation.
Initiation of sleep-dependent cortical-hippocampal correlations at wakefulness-sleep transition
Authors: Haggerty Daniel C. , Ji Daoyun
Published: July 2014

Sleep is involved in memory consolidation. Current theories propose that sleep-dependent memory consolidation requires active communication between the hippocampus and neocortex. Indeed, it is known that neuronal activities in the hippocampus and various neocortical areas are correlated during slow-wave sleep. However, transitioning from wakefulness to slow-wave sleep is a gradual process. How the hippocampal-cortical correlation is established during the wakefulness-sleep transition is unknown. By examining local field potentials and multiunit activities in the rat hippocampus and visual cortex, we show that the wakefulness-sleep transition is characterized by sharp-wave ripple events in the hippocampus and high-voltage spike-wave events in the cortex, both of which are accompanied by highly synchronized multiunit activities in the corresponding area. Hippocampal ripple events occur earlier than the cortical high-voltage spike-wave events, and hippocampal ripple incidence is attenuated by the onset of cortical high-voltage spike waves. This attenuation leads to a temporary weak correlation in the hippocampal-cortical multiunit activities, which eventually evolves to a strong correlation as the brain enters slow-wave sleep. The results suggest that the hippocampal-cortical correlation is established through a concerted, two-step state change that first synchronizes the neuronal firing within each brain area and then couples the synchronized activities between the two regions.
Predicting Tooth Surface Loss Using Genetic Algorithms-Optimized Artificial Neural Networks
Authors: Al Haidan Ali , Abu-Hammad Osama , Dar-Odeh Najla
Published: July 2014

Our aim was to predict tooth surface loss in individuals without the need to conduct clinical examinations. Artificial neural networks (ANNs) were used to construct a mathematical model. Input data consisted of age, smoker status, type of tooth brush, brushing, and consumption of pickled food, fizzy drinks, orange, apple, lemon, and dried seeds. Output data were the sum of tooth surface loss scores for selected teeth. The optimized constructed ANN consisted of 2-layer network with 15 neurons in the first layer and one neuron in the second layer. The data of 46 subjects were used to build the model, while the data of 15 subjects were used to test the model. Accepting an error of ±5 scores for all chosen teeth, the accuracy of the network becomes more than 80%. In conclusion, this study shows that modeling tooth surface loss using ANNs is possible and can be achieved with a high degree of accuracy.
A Comparative Holistic Fuzzy Approach for Evaluation of the Chain Performance of Suppliers
Authors: Eraslan Ergün , Atalay Kumru Didem
Published: July 2014

The competition between the companies in the dynamic market conditions has made the Supply Chain Management (SCM) a more important issue. The companies which have organized their supply chain effectively have obtained more flexibility in their manufacturing processes in addition to delivery of the customer demands. In this study, two different multicriteria decision making algorithms composed of the FAHP and a holistic hybrid method using FTOPSIS were utilized for an electronic company in wholly fuzzy processes. The FAHP is used for determination of the global weights of the factors and the performances of alternative suppliers are evaluated by using both FAHP-based and FAHP-FTOPSIS hybrid methods for synthetic extent values of pairwise comparisons. The sequences of the suppliers differed for the algorithms. The performances of the proposed approaches are quite successful and flexible in a narrow interval. The managerial advantages obtained from the proposed fuzzy algorithms are also analyzed and interpreted.
A Synchronous-Asynchronous Particle Swarm Optimisation Algorithm
Authors: Ab Aziz Nor Azlina , Mubin Marizan , Mohamad Mohd Saberi , Ab Aziz Kamarulzaman
Published: July 2014

In the original particle swarm optimisation (PSO) algorithm, the particles’ velocities and positions are updated after the whole swarm performance is evaluated. This algorithm is also known as synchronous PSO (S-PSO). The strength of this update method is in the exploitation of the information. Asynchronous update PSO (A-PSO) has been proposed as an alternative to S-PSO. A particle in A-PSO updates its velocity and position as soon as its own performance has been evaluated. Hence, particles are updated using partial information, leading to stronger exploration. In this paper, we attempt to improve PSO by merging both update methods to utilise the strengths of both methods. The proposed synchronous-asynchronous PSO (SA-PSO) algorithm divides the particles into smaller groups. The best member of a group and the swarm’s best are chosen to lead the search. Members within a group are updated synchronously, while the groups themselves are asynchronously updated. Five well-known unimodal functions, four multimodal functions, and a real world optimisation problem are used to study the performance of SA-PSO, which is compared with the performances of S-PSO and A-PSO. The results are statistically analysed and show that the proposed SA-PSO has performed consistently well.
Andrographolide Inhibits Nuclear Factor-κB Activation through JNK-Akt-p65 Signaling Cascade in Tumor Necrosis Factor-α-Stimulated Vascular Smooth Muscle Cells
Authors: Chen Yu-Ying , Hsu Ming-Jen , Hsieh Cheng-Ying , Lee Lin-Wen , Chen Zhih-Cherng , Sheu Joen-Rong
Published: July 2014

Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves ofAndrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α(TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBαdegradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.
Ginsenoside Rb1 Protects Neonatal Rat Cardiomyocytes from Hypoxia/Ischemia Induced Apoptosis and Inhibits Activation of the Mitochondrial Apoptotic Pathway
Authors: Yan Xu , Tian Jinwen , Wu Hongjin , Liu Yuna , Ren Jianxun , Zheng Sidao , Zhang Chengying , Yang Cui , Li Yang , Wang Shengqi
Published: July 2014

Aim. To investigate the effect of Ginsenoside Rb1 (GS‐Rb1) on hypoxia/ischemia (H/I) injury in cardiomyocytes in vitro and the mitochondrial apoptotic pathway mediated mechanism. Methods. Neonatal rat cardiomyocytes (NRCMs) for the H/I groups were kept in DMEM without glucose and serum, and were placed into a hypoxic jar for 24 h. GS‐Rb1 at concentrations from 2.5 to 40 µM was given during hypoxic period for 24 h. NRCMs injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. Cell apoptosis, ROS accumulation, and mitochondrial membrane potential (MMP) were assessed by flow cytometry. Cytosolic translocation of mitochondrial cytochrome c and Bcl‐2 family proteins were determined by Western blot. Caspase‐3 and caspase‐9 activities were determined by the assay kit. Results. GS‐Rb1 significantly reduced cell death and LDH leakage induced by H/I. It also reduced H/I induced NRCMs apoptosis induced by H/I, in accordance with a minimal reactive oxygen species (ROS) burst. Moreover, GS‐Rb1 markedly decreased the translocation of cytochrome c from the mitochondria to the cytosol, increased the Bcl‐2/ Bax ratio, and preserved mitochondrial transmembrane potential (ΔΨm). Its administration also inhibited activities of caspase‐9 and caspase‐3. Conclusion. Administration of GS‐Rb1 during H/I in vitro is involved in cardioprotection by inhibiting apoptosis, which may be due to inhibition of the mitochondrial apoptotic pathway.
Data-Weighting Periodic RLS Based Adaptive Control Design and Analysis without Linear Growth Condition
Authors: Chi Ronghu , Hou Zhongsheng , Jin Shangtai
Published: July 2014

A new periodic recursive least-squares (PRLS) estimator is developed with data-weighting factors for a class of linear time-varying parametric systems where the uncertain parameters are periodic with a known periodicity. The periodical time-varying parameter can be regarded as a constant in the time interval of a periodicity. Then the proposed PRLS estimates the unknown time-varying parameter from period to period in batches. By using equivalent feedback principle, the feedback control law is constructed for the adaptive control. Another distinct feature of the proposed PRLS-based adaptive control is that the controller design and analysis are done via Lyapunov technology without any linear growth conditions imposed on the nonlinearities of the control plant. Simulation results further confirm the effectiveness of the presented approach.
The Construct Validity and Reliability of an Assessment Tool for Competency in Cochlear Implant Surgery
Authors: Piromchai Patorn , Kasemsiri Pornthep , Wijewickrema Sudanthi , Ioannou Ioanna , Kennedy Gregor , O'Leary Stephen
Published: July 2014

Introduction. We introduce a rating tool that objectively evaluates the skills of surgical trainees performing cochlear implant surgery.Methods. Seven residents and seven experts performed cochlear implant surgery sessions from mastoidectomy to cochleostomy on a standardized virtual reality temporal bone. A total of twenty-eight assessment videos were recorded and two consultant otolaryngologists evaluated the performance of each participant using these videos.Results. Interrater reliability was calculated using the intraclass correlation coefficient for both the global and checklist components of the assessment instrument. The overall agreement was high. The construct validity of this instrument was strongly supported by the significantly higher scores in the expert group for both components.Conclusion. Our results indicate that the proposed assessment tool for cochlear implant surgery is reliable, accurate, and easy to use. This instrument can thus be used to provide objective feedback on overall and task-specific competency in cochlear implantation.
15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγand Reduction in NF-κB Activity
Authors: Chen Kan , Li Jingjing , Wang Junshan , Xia Yujing , Dai Weiqi , Wang Fan , Shen Miao , Cheng Ping , Zhang Yan , Wang Chengfen , Yang Jing , Zhu Rong , Zhang Huawei , Zheng Yuanyuan , Lu Jie , Fan Zhuoyi , Zhou Yingqun , Guo Chuanyong
Published: July 2014

Objective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice.Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 μg or 25 μg) was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγactivity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 μM) 1 h before the stimulation with ConA (30 μg/mL). The NF-κB and PPARγactivity were determined 30 min after the ConA administration.Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARγ, blocked the degradation of IκBα, and inhibited the translocation of NF-κB into the nucleus.Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARγand the reduction in NF-κB activity.
Study on Macroscopic and Microscopic Mechanical Behavior of Magnetorheological Elastomers by Representative Volume Element Approach
Authors: Sun Shulei , Peng Xiongqi , Guo Zaoyang
Published: July 2014

By using a representative volume element (RVE) approach, this paper investigates the effective mechanical properties of anisotropic magnetorheological elastomers (MREs) in which particles are aligned and form chain-like structure under magnetic field during curing. Firstly, a three-dimensional RVE in zero magnetic field is presented in ABAQUS/Standard to calculate the macroscopic mechanical properties of MREs. It is shown that the initial shear modulus of MREs increases by 56% with a 20% volume fraction of particles compared to that of pure rubber. Then by introducing the Maxwell stress tensor, a two-dimensional plane stress RVE for the MRE is developed in COMSOL Multiphysics to study its response under a magnetic field. The influences of magnetic field intensity, radius of particles, and distance between two adjacent particles on the macroscopic mechanical properties of MRE are also investigated. The results show that the shear modulus increases with the increase of the applied magnetic field intensity and the radius of particles and the decrease of the distance between two adjacent particles in a chain. The predicted numerical results are consistent with theoretical results from Mori-Tanaka model, double inclusion model, and dipole model.
Evaluation of Growth Patterns and Body Composition in C57Bl/6J Mice Using Dual Energy X-Ray Absorptiometry
Authors: Gargiulo Sara , Gramanzini Matteo , Megna Rosario , Greco Adelaide , Albanese Sandra , Manfredi Claudio , Brunetti Arturo
Published: July 2014

The normal growth pattern of female C57BL/6J mice, from 5 to 30 weeks of age, has been investigated in a longitudinal study. Weight, body surface area (BS), and body mass index (BMI) were evaluated in forty mice. Lean mass and fat mass, bone mineral content (BMC), and bone mineral density (BMD) were monitored by dual energy X-ray absorptiometry (DEXA). Weight and BS increased linearly (16.15±0.64–27.64±1.42 g;51.13±0.74–79.57±2.15 cm2,P<0.01), more markedly from 5 to 9 weeks of age(P<0.001). BMD showed a peak at 17 weeks (0.0548±0.0011 g/cm2*m,P<0.01). Lean mass showed an evident gain at 9 (15.8±0.8 g,P<0.001) and 25 weeks (20.5±0.3 g,P<0.01), like fat mass from 13 to 17 weeks (2.0±0.4–3.6±0.7 g,P<0.01). BMI and lean mass index (LMI) reached the highest value at 21 weeks (3.57±0.02–0.284±0.010 g/cm2, resp.), like fat mass index (FMI) at 17 weeks (0.057±0.009 g/cm2) (P<0.01). BMI, weight, and BS showed a moderate positive correlation (0.45–0.85) with lean mass from 5 to 21 weeks. Mixed linear models provided a good prediction for lean mass, fat mass, and BMD. This study may represent a baseline reference for a future comparison of wild-type C57BL/6J mice with models of altered growth.