bluuebunny/crossref_metadata_2025 huggingface dataset:
When Are Two Heads Better than One and Why?
Authors: Koriat Asher
Published: April 2012

Joint Decisions

In many instances, decisions made by relatively homogeneous groups (two or more people) coalesce around the choice that people are most confident in, and this in turn stems from the sampling of representations that individuals perform when making their choices.
Koriat
(p.
360
; see the Perspective by

Hertwig

) found that if most of the group members are able to form accurate judgments, then confidence and accuracy coincide and the consensus choice is the correct one. By contrast, if few people know the right answer, then heterogeneity in people's representations appeared to offer a surer path to accuracy.
Synthetic Genetic Polymers Capable of Heredity and Evolution
Authors: Pinheiro Vitor B. , Taylor Alexander I. , Cozens Christopher , Abramov Mikhail , Renders Marleen , Zhang Su , Chaput John C. , Wengel Jesper , Peak-Chew Sew-Yeu , McLaughlin Stephen H. , Herdewijn Piet , Holliger Philipp
Published: April 2012

Unnatural Bases

The genetic basis of all life on the planet is comprised of deoxyribonucleic acid (DNA) with four nitrogenous nucleotide bases, abbreviated to A, G, C, and T. But there are variations on this theme, and

Pinheiro
et al.

(p.
341
; see the Perspective by

Joyce

) describe the directed evolution of unnatural nucleic acid–like genetic polymers. Variant enzymes were developed that efficiently transcribed DNA to anhydrohexitol (HNA), cyclohexenyl (CeNA), locked (LNA), and threofuranosyl (TNA) nuceic acid analogs. Further variant enzymes were developed to reverse-transcribe these analogs back to DNA. Thus, man-made nucleic acid analogs can be designed and selected that have the potential to operate in a way analogous to the natural process of heredity and evolution.
A Universal Method to Produce Low–Work Function Electrodes for Organic Electronics
Authors: Zhou Yinhua , Fuentes-Hernandez Canek , Shim Jaewon , Meyer Jens , Giordano Anthony J. , Li Hong , Winget Paul , Papadopoulos Theodoros , Cheun Hyeunseok , Kim Jungbae , Fenoll Mathieu , Dindar Amir , Haske Wojciech , Najafabadi Ehsan , Khan Talha M. , Sojoudi Hossein , Barlow Stephen , Graham Samuel , Brédas Jean-Luc , Marder Seth R. , Kahn Antoine , Kippelen Bernard
Published: April 2012

A Sturdy Electrode Coating

To operate efficiently, organic devices—such as light-emitting diodes—require electrodes that emit or take up electrons at low applied voltages (that is, have low work functions). Often these electrodes are metals, such as calcium, that are not stable in air or water vapor and have to be protected from environmental damage.

Zhou
et al.

(p.
327
; see the Perspective by

Helander

) report that a coating polymer containing aliphatic amine groups can lower the work functions of various types of electrodes by up to 1.7 electron volts and can be used in a variety of devices.
Oxidation of the Guanine Nucleotide Pool Underlies Cell Death by Bactericidal Antibiotics
Authors: Foti James J. , Devadoss Babho , Winkler Jonathan A. , Collins James J. , Walker Graham C.
Published: April 2012

A Specific Oxidative Catastrophe

Three different classes of antibiotics induce bacterial cell death by the production of hydroxyl radicals. Hydroxyl radicals are powerful oxidizing agents in living cells and will oxidize the nucleic acid base, guanine, to form 8-oxoguanine, which is potentially mutagenic because it can pair with both cytosine and adenine and form lethal double-strand DNA breaks.

Foti
et al.

(p.
315
) discovered that overproduction of the nucleotide sanitizer MutT, which hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, gives striking protection against cell death.
Heterogeneity and Tumor History
Authors: Shibata Darryl
Published: April 2012

What can genomic heterogeneity within a single tumor reveal about the tumor's evolution and its diagnosis?
Trouble on the Yangtze
Authors: Qiu Jane
Published: April 2012

Upriver habitats—including a critical refuge created when construction began on the Three Gorges Dam—are now at risk from a series of new projects.
Mother-Infant Transfer of Anti-Human Papillomavirus (HPV) Antibodies following Vaccination with the Quadrivalent HPV (Type 6/11/16/18) Virus-Like Particle Vaccine
Authors: Matys Katie , Mallary Sara , Bautista Oliver , Vuocolo Scott , Manalastas Ricardo , Pitisuttithum Punee , Saah Alfred
Published: April 2012

The exploratory immunogenicity objective of this analysis was to characterize the titer of vaccine human papillomavirus (HPV)-type immunoglobulins in both peripartum maternal blood and the cord blood of infants born to women who received blinded therapy. Data were derived from a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study (protocol 019; NCT00090220). This study enrolled 3,819 women between the ages of 24 and 45 years from 38 international study sites between 18 June 2004 and 30 April 2005. Data in the current analysis are from subjects enrolled in Philippines and Thailand. For each of HPV types 6, 11, 16, and 18, maternal anti-HPV was found in cord blood samples. Furthermore, HPV titers in cord blood samples were highly positively correlated with maternal HPV titers. Additionally, there were instances when anti-HPV antibodies were no longer detectable in maternal serum samples and yet were detected in matched cord blood samples. These results demonstrate that quadrivalent HPV (qHPV) vaccine-induced antibodies cross the placenta and could potentially provide some benefit against vaccine-type HPV infection and related diseases such as recurrent respiratory papillomatosis.
Comparative Evaluation of Two Hemagglutinating Encephalomyelitis Coronavirus Vaccine Candidates in Mice
Authors: Chen Keyan , Zhao Kui , He Wenqi , Gao Wei , Zhao Chuanbo , Wang Li , Pan Wei , Song Deguang , Wang Chengli , Gao Feng
Published: April 2012

Porcine hemagglutinating encephalomyelitis (PHE) is caused by the coronavirus hemagglutinating encephalomyelitis virus (PHE-CoV), and the recent, rapid spread of PHE-CoV in piglets from many countries emphasizes the urgent need for a PHE-CoV vaccine. Here we use a murine model for evaluation of the induction of humoral and cellular immune responses by inactivated and PHE-CoV DNA vaccines in order to define the immune correlates for protection against PHE-CoV. The inactivated vaccine was composed of purified PHE-CoV and aluminum hydroxide gel (alum), which was chosen as an adjuvant because of its long history of safety for human use. The PHE-CoV DNA vaccine was constructed by subcloning the S1 gene of PHE-CoV into the pVAX1 vector to create the recombinant plasmid pV-S1. Our results showed that the inactivated PHE-CoV vaccine (IPV) elicited a high level of humoral immunity, resulting in good protection efficacy against PHE-CoV challenge. The IPV induced the IgG1 subclass of serum antibodies and expression of the cytokine interleukin-4 (IL-4), suggesting that the IPV generated a predominantly Th2-type immune response. The DNA vaccine was found to mediate primarily a cellular immune response with high levels of IgG2a and the cytokines IL-2 and gamma interferon (IFN-γ). However, mice that were vaccinated twice with the DNA vaccine and boosted with the IPV could mount a sufficient neutralizing antibody response against live PHE-CoV, with little variation in IgG1 and IgG2a levels, and showed high levels of IL-2 and IL-4. This response may activate both B and T cells to mount a specific humoral and cellular immune response that could, in turn, elicit a phagocyte-mediated defense against PHE-CoV infections to achieve viral clearance.
Outbreak of Transient Conversions of the QuantiFERON-TB Gold In-Tube Test in Laboratory Health Care Worker Screenings
Authors: Zanetti Caterina , Peracchi Marta , Zorzi Diego , Fiorio Silvia , Fallico Loredana , Palù Giorgio
Published: April 2012

Gamma interferon release assays were recently introduced in health care worker (HCWs) screenings for tuberculosis surveillance. In longitudinal surveys, conversions and reversions are seen, and yet whether these changes are unspecific or are an expression of new infections and microbial clearance remains unclear. In order to further elucidate these changes, we analyzed an outbreak of 15 transient conversions in 53 HCWs who operate in the same laboratory and handle specimens potentially containing
Mycobacterium tuberculosis
who underwent screening by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test between 11 May and 30 June 2010: 15/46 (33%) negative HCWs showed a conversion and then reverted after 7 to 107 days. To validate these results, an evaluation of methodological procedures and test reliability, as well as an analysis of results obtained during the same period and processed by the same laboratory, was carried out. For the latter purpose, QFT-GIT results determined for 78 ward HCWs who underwent screening during the same period and were employed in departments with at least 3 infectious tuberculosis patients per year or had cared for an infectious patient without airborne precautions were analyzed with the following results: 6/63 (9%) HCWs with negative results in 3 different departments showed transient conversion (
P
= 0.002; odds ratio, 4.60; 95% confidence interval, 1.62 to 13.04). A retrospective survey of in-house biosafety practices led to determination of a single exposure factor within the laboratory. These data emphasize the validity of the hypothesis that a transient conversion demonstrates the presence of a real tubercular infection and could be an important indicator for occupational biosafety concerns. They also confirm that subjects with recent conversion should be retested before chest radiography and chemotherapy is offered.
Epstein-Barr Virus Latent Membrane Protein 2A Promotes Invasion of Nasopharyngeal Carcinoma Cells through ERK/Fra-1-Mediated Induction of Matrix Metalloproteinase 9
Authors: Lan Yu-Yan , Hsiao Jenn-Ren , Chang Kung-Chao , Chang Jeffrey Shu-Ming , Chen Chaio-Wei , Lai Hsiao-Ching , Wu Shih-Yi , Yeh Tzu-Hao , Chang Fang-Hsin , Lin Wei-Hung , Su Ih-Jen , Chang Yao
Published: April 2012

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is highly metastatic, and this malignant feature may be promoted by an EBV oncoprotein, latent membrane protein 2A (LMP2A). Acting as a signal regulator, LMP2A can enhance invasiveness and motility of epithelial cells. Downstream from the LMP2A-triggered signaling events, it is largely unknown what key effector proteins are induced and essentially promote cell invasion. In the present study, we found that in NPC cells, LMP2A upregulated matrix metalloproteinase 9 (MMP9), a metastasis-associated protease. LMP2A increased MMP9 expression at both the mRNA and protein levels. It also activated the MMP9 promoter, in which two AP-1 elements were required for the promoter activation. Among AP-1 transcription factors, Fra-1 was induced by LMP2A and is essential for LMP2A-triggered MMP9 expression. Induction of Fra-1 was dependent on the LMP2A-activated ERK1/2 pathway, and induction of the ERK1/2–Fra-1–MMP9 axis required PY motifs in the amino-terminal domain of LMP2A. Notably, LMP2A-promoted invasion of NPC cells was blocked when MMP9 expression, Fra-1 induction, or ERK1/2 activation was inhibited. In addition, we found an association of LMP2A with MMP9 expression in NPC tumor biopsy specimens, where Fra-1 was a major mediation factor. This study reveals an underlying mechanism of LMP2A-induced cell invasion, from signal transduction to upregulation of a critical protease. Considering that MMP9 can also be upregulated by another EBV oncoprotein, LMP1, this protease may be a pivotal effector at which the EBV-induced, invasion-promoting mechanisms converge, serving as an attractive therapeutic target for NPC treatment.
Genomic Sequences of Australian Bluetongue Virus Prototype Serotypes Reveal Global Relationships and Possible Routes of Entry into Australia
Authors: Boyle David B. , Bulach Dieter M. , Amos-Ritchie Rachel , Adams Mathew M. , Walker Peter J. , Weir Richard
Published: April 2012

Bluetongue virus (BTV) is transmitted by biting midges (
Culicoides
spp.). It causes disease mainly in sheep and occasionally in cattle and other species. BTV has spread into northern Europe, causing disease in sheep and cattle. The introduction of new serotypes, changes in vector species, and climate change have contributed to these changes. Ten BTV serotypes have been isolated in Australia without apparent associated disease. Simplified methods for preferential isolation of double-stranded RNA (dsRNA) and template preparation enabled high-throughput sequencing of the 10 genome segments of all Australian BTV prototype serotypes. Phylogenetic analysis reinforced the Western and Eastern topotypes previously characterized but revealed unique features of several Australian BTVs. Many of the Australian BTV genome segments (Seg-) were closely related, clustering together within the Eastern topotypes. A novel Australian topotype for Seg-5 (NS1) was identified, with taxa spread across several serotypes and over time. Seg-1, -2, -3, -4, -6, -7, -9, and -10 of BTV_2_AUS_2008 were most closely related to the cognate segments of viruses from Taiwan and Asia and not other Australian viruses, supporting the conclusion that BTV_2 entered Australia recently. The Australian BTV_15_AUS_1982 prototype was revealed to be unusual among the Australian BTV isolates, with Seg-3 and -8 distantly related to other BTV sequences from all serotypes.
Structural Analysis of Coxsackievirus A7 Reveals Conformational Changes Associated with Uncoating
Authors: Seitsonen Jani J. T. , Shakeel Shabih , Susi Petri , Pandurangan Arun P. , Sinkovits Robert S. , Hyvönen Heini , Laurinmäki Pasi , Ylä-Pelto Jani , Topf Maya , Hyypiä Timo , Butcher Sarah J.
Published: April 2012

Coxsackievirus A7 (CAV7) is a rarely detected and poorly characterized serotype of theEnterovirusspeciesHuman enterovirus A(HEV-A) within thePicornaviridaefamily. The CAV7-USSR strain has caused polio-like epidemics and was originally thought to represent the fourth poliovirus type, but later evidence linked this strain to the CAV7-Parker prototype. Another isolate, CAV7-275/58, was also serologically similar to Parker but was noninfectious in a mouse model. Sequencing of the genomic region encoding the capsid proteins of the USSR and 275/58 strains and subsequent comparison with the corresponding amino acid sequences of the Parker strain revealed that the Parker and USSR strains are nearly identical, while the 275/58 strain is more distant. Using electron cryomicroscopy and three-dimensional image reconstruction, the structures of the CAV7-USSR virion and empty capsid were resolved to 8.2-Å and 6.1-Å resolutions, respectively. This is one of the first detailed structural analyses of theHEV-Aspecies. Using homology modeling, reconstruction segmentation, and flexible fitting, we constructed a pseudoatomic T = 1 (pseudo T = 3) model incorporating the three major capsid proteins (VP1 to VP3), addressed the conformational changes of the capsid and its constituent viral proteins occurring during RNA release, and mapped the capsid proteins' variable regions to the structure. During uncoating, VP4 and RNA are released analogously to poliovirus 1, the interfaces of VP2 and VP3 are rearranged, and VP1 rotates. Variable regions in the capsid proteins were predicted to map mainly to the surface of VP1 and are thus likely to affect the tropism and pathogenicity of CAV7.
Pellino-1 Selectively Regulates Epithelial Cell Responses to Rhinovirus
Authors: Bennett Julie A. , Prince Lynne R. , Parker Lisa C. , Stokes Clare A. , de Bruin Harold G. , van den Berge Maarten , Heijink Irene H. , Whyte Moira K. , Sabroe Ian
Published: April 2012

Pellino-1 has recently been identified as a regulator of interleukin-1 (IL-1) signaling, but its roles in regulation of responses of human cells to human pathogens are unknown. We investigated the potential roles of Pellino-1 in the airways. We show for the first time that Pellino-1 regulates responses to a human pathogen, rhinovirus minor group serotype 1B (RV-1B). Knockdown of Pellino-1 by small interfering RNA (siRNA) was associated with impaired production of innate immune cytokines such as CXCL8 from human primary bronchial epithelial cells in response to RV-1B, without impairment in production of antiviral interferons (IFN), and without loss of control of viral replication. Pellino-1 actions were likely to be independent of interleukin-1 receptor-associated kinase-1 (IRAK-1) regulation, since Pellino-1 knockdown in primary epithelial cells did not alter responses to IL-1 but did inhibit responses to poly(I·C), a Toll-like receptor 3 (TLR3) activator that does not signal via IRAK-1 to engender a response. These data indicate that Pellino-1 represents a novel target that regulates responses of human airways to human viral pathogens, independently of IRAK signaling. Neutralization of Pellino-1 may therefore provide opportunities to inhibit potentially harmful neutrophilic inflammation of the airways induced by respiratory viruses, without loss of control of the underlying viral infection.
The Ubiquitin-Specific Protease USP7 Modulates the Replication of Kaposi's Sarcoma-Associated Herpesvirus Latent Episomal DNA
Authors: Jäger Wiebke , Santag Susann , Weidner-Glunde Magdalena , Gellermann Eva , Kati Semra , Pietrek Marcel , Viejo-Borbolla Abel , Schulz Thomas F.
Published: April 2012

Kaposi's sarcoma herpesvirus (KSHV) belongs to the gamma-2
Herpesviridae
and is associated with three neoplastic disorders: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). The viral latency-associated nuclear antigen 1 (LANA) is expressed in all latently KSHV-infected cells and is involved in viral latent replication and maintenance of the viral genome. We show that LANA interacts with the ubiquitin-specific protease USP7 through its N-terminal TRAF (tumor necrosis factor [TNF] receptor-associated factor) domain. This interaction involves a short sequence (amino acids [aa] 971 to 986) within the C-terminal domain of LANA with strong similarities to the USP7 binding site of the Epstein-Barr virus (EBV) EBNA-1 protein. A LANA mutant with a deletion of the identified USP7 binding site showed an enhanced ability to replicate a plasmid containing the KSHV latent origin of replication but was comparable to the wild-type LANA (LANA WT) with regard to the regulation of viral and cellular promoters. Furthermore, the LANA homologues of two other gamma-2 herpesviruses, MHV68 and RRV, also recruit USP7. Our findings suggest that recruitment of USP7 to LANA could play a role in the regulation of viral latent replication. The recruitment of USP7, and its role in herpesvirus latent replication, previously described for the latent EBNA-1 protein of the gamma-1 herpesvirus (lymphocryptovirus) EBV (M. N. Holowaty et al., J. Biol. Chem. 278:29987–29994, 2003), may thereby be a conserved feature among gammaherpesvirus latent origin binding proteins.
The trajectory to diagnosis with pulmonary arterial hypertension: a qualitative study
Authors: Armstrong Ian , Rochnia Nikki , Harries Carl , Bundock Sarah , Yorke Janelle
Published: April 2012

Objectives

To investigate the patient's experience of the trajectory to receiving a diagnosis of pulmonary arterial hypertension (PAH) and inform the provision of care for this patient group.

Design

Qualitative study using in-depth one-to-one interviews and pictorial representations. Data were analysed using thematic analysis.

Setting

Participants were interviewed in their own homes across England.

Participants

30 patients with a diagnosis of pulmonary hypertension (18 participants were women, mean age 56 and range 26-80 years and time since diagnosis ranged from a few months to more than 12 years) participated.

Results

All participants, regardless of the time since diagnosis, vividly described the process from manifestation of symptoms to receiving a confirmed diagnosis. The authors present data using three major themes: (i) making sense of symptoms, (ii) process of elimination and (iii) being diagnosed with PAH. Making sense of symptoms represented an early period of perseverance—people tried to carry-on as usual despite ‘unexplained breathlessness’. As time progressed, this period was punctuated by critical events that triggered seeking medical advice. Once medical contact had been made, patients described a period of ‘elimination’ and convoluted contact with the medical profession. Dyspnoea misdiagnosis was a key factor that delayed the PAH diagnosis. Diagnosis disclosure by some medical professionals was also viewed as lacking empathy. More positive experiences were relayed when the medical team disclosing the diagnosis acknowledged previous limitations.

Conclusions

A lack of awareness of this illness from both the sufferer themselves and the medical profession emerged as a central theme and led to prolonged periods of being misdiagnosed. The application of a diagnostic pathway for unexplained dyspnoea that alerts practitioners to rare conditions could expedite the process of correct diagnosis.
BOSE–EINSTEIN CONDENSATION OF A RELATIVISTIC IDEAL BOSE GAS IN RANDOM BOX
Authors: LI HONG , WANG YING , KONG XIANG-MU , LIN ZHEN-QUAN
Published: April 2012

Using semi-classical approximation method, the Bose–Einstein condensation (BEC) of a relativistic ideal boson gas (RIBG) in random box is studied. The exact BEC transition temperature Tc and Helmholtz free energy at Tc are derived. The phase diagrams in the (Δ, T) plane are obtained, where Δ is the fluctuation of the box length and T is the temperature of the system. We find that Tc is lowered by the presence of the quenched disorder caused by the random boundary conditions. The effects of antibosons on the RIBG are also studied and it is found that the Helmholtz free energy of the system with antibosons at Tc is lower than that of the system without antibosons. This implies that the omission of antibosons always leads to a metastable state.
PRACTICE SELECTION FRAMEWORK
Authors: IVARSSON MARTIN , GORSCHEK TONY
Published: April 2012

Knowledge management (KM) in software engineering and software process improvement (SPI) are challenging. Most existing KM and SPI frameworks are too expensive to deploy or do not take an organization's specific needs or knowledge into consideration. There is thus a need for scalable improvement approaches that leverage knowledge already residing in the organizations.

This paper presents the Practice Selection Framework (PSF), an Experience Factory approach, enabling lightweight experience capture and use by utilizing postmortem reviews. Experiences gathered concern performance and applicability of practices used in the organization, gained from concluded projects. Project managers use these as decision support for selecting practices to use in future projects, enabling explicit knowledge transfer across projects and the development organization as a whole. Process managers use the experiences to determine if there is potential for improvement of practices used in the organization. This framework was developed and subsequently validated in industry to get feedback on usability and usefulness from practitioners. The validation consisted of tailoring and testing the framework using real data from the organization and comparing it to current practices used in the organization to ensure that the approach meets industry needs. The results from the validation are encouraging and the participants' assessment of PSF and particularly the tailoring developed was positive.
MODELING, DEPLOYING, AND CONTROLLING VOLATILE FUNCTIONALITIES IN WEB APPLICATIONS
Authors: URBIETA MATIAS , ROSSI GUSTAVO , DISTANTE DAMIANO , GINZBURG JERONIMO
Published: April 2012

One of the main characteristics of most Web applications is their high dynamism. Once implemented and deployed for the first time, new functionalities are added to meet new or changed requirements. Some of these functionalities may appear on the Web in response to an unexpected event, or phenomena (such as a natural calamity) after which they are removed. Some others are activated periodically, to coincide with a particular date, or period of the year (such as, return to school, Christmas holidays, etc.). Implementing such volatile functionalities usually impacts on a number of aspects of a Web application, including content, navigation, presentation, business processes, and user operations. Their cyclic activation/deactivation, which requires repetitive changes in the application code, may be the cause of waste of effort and application quality deterioration, up to incorrect functioning.

In this paper, we present an approach to decouple the design and implementation of volatile functionalities from that of stable ones, i.e. the core functionalities of the application. The approach is instantiated in the context of the Object-Oriented Hypermedia Design Method (OOHDM), but its principles and related techniques are generally applicable to any other Web engineering method. We show how our approach enables the deployment and removal of these functionalities in a cost-effective and safe way and at runtime, thus providing business agility. A framework to classify volatile functionalities and a number of examples are also reported.
Neural targets for relieving parkinsonian rigidity and bradykinesia with pallidal deep brain stimulation
Authors: Johnson Matthew D. , Zhang Jianyu , Ghosh Debabrata , McIntyre Cameron C. , Vitek Jerrold L.
Published: April 2012

Clinical evidence has suggested that subtle changes in deep brain stimulation (DBS) settings can have differential effects on bradykinesia and rigidity in patients with Parkinson's disease. In this study, we first investigated the degree of improvement in bradykinesia and rigidity during targeted globus pallidus DBS in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus macaques. Behavioral outcomes of DBS were then coupled with detailed, subject-specific computational models of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and internal capsule (IC) to determine which neuronal pathways when modulated with high-frequency electrical stimulation best correlate with improvement in motor symptoms. The modeling results support the hypothesis that multiple neuronal pathways can underlie the therapeutic effect of DBS on parkinsonian bradykinesia and rigidity. Across all three subjects, improvements in rigidity correlated most strongly with spread of neuronal activation into IC, driving a small percentage of fibers within this tract (<10% on average). The most robust effect on bradykinesia resulted from stimulating a combination of sensorimotor axonal projections within the GP, specifically at the site of the medial medullary lamina. Thus the beneficial effects of pallidal DBS for parkinsonian symptoms may occur from multiple targets within and near the target nucleus.
Effects of galvanic vestibular stimulation on postural limb reflexes and neurons of spinal postural network
Authors: Hsu L.-J. , Zelenin P. V. , Orlovsky G. N. , Deliagina T. G.
Published: April 2012

Quadrupeds maintain the dorsal side up body orientation due to the activity of the postural control system driven by limb mechanoreceptors. Binaural galvanic vestibular stimulation (GVS) causes a lateral body sway toward the anode. Previously, we have shown that this new position is actively stabilized, suggesting that GVS changes a set point in the reflex mechanisms controlling body posture. The aim of the present study was to reveal the underlying neuronal mechanisms. Experiments were performed on decerebrate rabbits. The vertebral column was rigidly fixed, whereas hindlimbs were positioned on a platform. Periodic lateral tilts of the platform caused postural limb reflexes (PLRs): activation of extensors in the loaded and flexing limb and a decrease in extensor activity in the opposite (unloaded and extending) limb. Putative spinal interneurons were recorded in segments L4–L5 during PLRs, with and without GVS. We have found that GVS enhanced PLRs on the cathode side and reduced them on the anode side. This asymmetry in PLRs can account for changes in the stabilized body orientation observed in normal rabbits subjected to continuous GVS. Responses to platform tilts (frequency modulation) were observed in 106 spinal neurons, suggesting that they can contribute to PLR generation. Two neuron groups were active in opposite phases of the tilt cycle of the ipsi-limb: F-neurons in the flexion phase, and E-neurons in the extension phase. Neurons were driven mainly by afferent input from the ipsi-limb. If one supposes that F- and E-neurons contribute, respectively, to excitation and inhibition of extensor motoneurons, one can expect that the pattern of response to GVS in F-neurons will be similar to that in extensor muscles, whereas E-neurons will have an opposite pattern. We have found that ∼40% of all modulated neurons meet this condition, suggesting that they contribute to the generation of PLRs and to the GVS-caused changes in PLRs.
The role of the right presupplementary motor area in stopping action: two studies with event-related transcranial magnetic stimulation
Authors: Cai Weidong , George Jobi S. , Verbruggen Frederick , Chambers Christopher D. , Aron Adam R.
Published: April 2012

Rapidly stopping action engages a network in the brain including the right presupplementary motor area (preSMA), the right inferior frontal gyrus, and the basal ganglia. Yet the functional role of these different regions within the overall network still remains unclear. Here we focused on the role of the right preSMA in behavioral stopping. We hypothesized that the underlying neurocognitive function of this region is one or more of setting up a stopping rule in advance, modulating response tendencies (e.g., slowing down in anticipation of stopping), and implementing stopping when the stop signal occurs. We performed two experiments with magnetic resonance imaging (MRI)–guided, event-related, transcranial magnetic stimulation(TMS), during the performance of variants of the stop signal task. In experiment 1 we show that stimulation of the right preSMA versus vertex (control site) slowed the implementation of stopping (measured via stop signal reaction time) but had no influence on modulation of response tendencies. In experiment 2, we showed that stimulation of the right preSMA slowed implementation of stopping in a mechanistically selective form of stopping but had no influence on setting up stopping rules. The results go beyond the replication of prior findings by showing that TMS of the right preSMA impairs stopping behavior (including a behaviorally selective form of stopping) through a specific disruption of the implementation of stopping. Future studies are required to establish whether this was due to stimulation of the right preSMA itself or because of remote effects on the wider stopping network.
Sensory regulation of quadrupedal locomotion: a top-down or bottom-up control system?
Authors: Thibaudier Yann , Hurteau Marie-France
Published: April 2012

Propriospinal pathways are thought to be critical for quadrupedal coordination by coupling cervical and lumbar central pattern generators (CPGs). However, the mechanisms involved in relaying information between girdles remain largely unexplored. Using an in vitro spinal cord preparation in neonatal rats, Juvin and colleagues ( Juvin et al. 2012 ) have recently shown sensory inputs from the hindlimbs have greater influence on forelimb CPGs than forelimb sensory inputs on hindlimb CPGs, in other words, a bottom-up control system. However, results from decerebrate cats suggest a top-down control system. It may be that both bottom-up and top-down control systems exist and that the dominance of one over the other is task or context dependent. As such, the role of sensory inputs in controlling quadrupedal coordination before and after injury requires further investigation.
How does the motor system correct for errors in time and space during locomotor adaptation?
Authors: Malone Laura A. , Bastian Amy J. , Torres-Oviedo Gelsy
Published: April 2012

Walking is a complex behavior for which the healthy nervous system favors a smooth, symmetric pattern. However, people often adopt an asymmetric walking pattern after neural or biomechanical damage (i.e., they limp). To better understand this aberrant motor pattern and how to change it, we studied walking adaptation to a split-belt perturbation where one leg is driven to move faster than the other. Initially, healthy adult subjects take asymmetric steps on the split-belt treadmill, but within 10–15 min people adapt to reestablish walking symmetry. Which of the many walking parameters does the nervous system change to restore symmetry during this complex act (i.e., what motor mappings are adapted to restore symmetric walking in this asymmetric environment)? Here we found two parameters that met our criteria for adaptive learning: a temporal motor output consisting of the duration between heel-strikes of the two legs (i.e., “when” the feet land) and a spatial motor output related to the landing position of each foot relative to one another (i.e., “where” the feet land). We found that when subjects walk in an asymmetric environment they smoothly change their temporal and spatial motor outputs to restore temporal and spatial symmetry in the interlimb coordination of their gait. These changes in motor outputs are stored and have to be actively deadapted. Importantly, the adaptation of temporal and spatial motor outputs is dissociable since subjects were able to adapt their temporal motor output without adapting the spatial output. Taken together, our results suggest that temporal and spatial control for symmetric gait can be adapted separately, and therefore we could potentially develop interventions targeting either temporal or spatial walking deficits.
Auditory signals evolve from hybrid- to eye-centered coordinates in the primate superior colliculus
Authors: Lee Jungah , Groh Jennifer M.
Published: April 2012

Visual and auditory spatial signals initially arise in different reference frames. It has been postulated that auditory signals are translated from a head-centered to an eye-centered frame of reference compatible with the visual spatial maps, but, to date, only various forms of hybrid reference frames for sound have been identified. Here, we show that the auditory representation of space in the superior colliculus involves a hybrid reference frame immediately after the sound onset but evolves to become predominantly eye centered, and more similar to the visual representation, by the time of a saccade to that sound. Specifically, during the first 500 ms after the sound onset, auditory response patterns ( N = 103) were usually neither head nor eye centered: 64% of neurons showed such a hybrid pattern, whereas 29% were more eye centered and 8% were more head centered. This differed from the pattern observed for visual targets ( N = 156): 86% were eye centered, <1% were head centered, and only 13% exhibited a hybrid of both reference frames. For auditory-evoked activity observed within 20 ms of the saccade ( N = 154), the proportion of eye-centered response patterns increased to 69%, whereas the hybrid and head-centered response patterns dropped to 30% and <1%, respectively. This pattern approached, although did not quite reach, that observed for saccade-related activity for visual targets: 89% were eye centered, 11% were hybrid, and <1% were head centered ( N = 162). The plainly eye-centered visual response patterns and predominantly eye-centered auditory motor response patterns lie in marked contrast to our previous study of the intraparietal cortex, where both visual and auditory sensory and motor-related activity used a predominantly hybrid reference frame ( Mullette-Gillman et al. 2005 , 2009 ). Our present findings indicate that auditory signals are ultimately translated into a reference frame roughly similar to that used for vision, but suggest that such signals might emerge only in motor areas responsible for directing gaze to visual and auditory stimuli.
Forebrain organization representing baroreceptor gating of somatosensory afferents within the cortical autonomic network
Authors: Goswami Ruma , Frances Maria Fernanda , Steinback Craig Douglas , Shoemaker J. Kevin
Published: April 2012

Somatosensory afferents are represented within the cortical autonomic network (CAN). However, the representation of somatosensory afferents, and the consequent cardiovascular effects, may be modified by levels of baroreceptor input. Thus, we examined the cortical regions involved with processing somatosensory inputs during baroreceptor unloading. Neuroimaging sessions (functional magnetic resonance imaging [fMRI]) recorded brain activity during 30 mmHg lower-body negative pressure (LBNP) alone and combined with somatosensory stimulation (LBNP+SS) of the forearm ( n = 14). Somatosensory processing was also assessed during increased sympathetic outflow via end-expiratory apnea. Heart rate (HR), blood pressure (BP), cardiac output (Q), and muscle sympathetic nerve activity (MSNA) were recorded during the same protocols in a separate laboratory session. SS alone had no effect on any cardiovascular or MSNA variable at rest. Measures of HR, BP, and Q during LBNP were not different compared with LBNP+SS. The rise in MSNA burst frequency was attenuated during LBNP+SS versus LBNP alone (8 vs. 12 bursts/min, respectively, P < 0.05). SS did not affect the change in MSNA during apnea. Activations within the insula and dorsal anterior cingulate cortex (ACC) observed during LBNP were not seen during LBNP+SS. Anterior insula and ACC activations occurring during apnea were not modified by SS. Thus, the absence of insular and dorsal ACC activity during LBNP+SS along with an attenuation of MSNA burst frequency suggest sympathoinhibitory effects of sensory stimulation during decreased baroreceptor input by a mechanism that includes conjoint insula-dorsal ACC regulation. These findings reveal that the level of baroreceptor input influences the forebrain organization of somatosensory afferents.
Spatial pattern of BOLD fMRI activation reveals cross-modal information in auditory cortex
Authors: Hsieh P.-J. , Colas J. T. , Kanwisher N.
Published: April 2012

Recent findings suggest that neural representations in early auditory cortex reflect not only the physical properties of a stimulus, but also high-level, top-down, and even cross-modal information. However, the nature of cross-modal information in auditory cortex remains poorly understood. Here, we used pattern analyses of fMRI data to ask whether early auditory cortex contains information about the visual environment. Our data show that 1) early auditory cortex contained information about a visual stimulus when there was no bottom-up auditory signal, and that 2) no influence of visual stimulation was observed in auditory cortex when visual stimuli did not provide a context relevant to audition. Our findings attest to the capacity of auditory cortex to reflect high-level, top-down, and cross-modal information and indicate that the spatial patterns of activation in auditory cortex reflect contextual/implied auditory information but not visual information per se.
Design and Evaluation of a New Type of Knee Orthosis to Align the Mediolateral Angle of the Knee Joint with Osteoarthritis
Authors: Esrafilian Amir , Karimi Mohammad Taghi , Eshraghi Arezoo
Published: April 2012

Background. Osteoarthritis (OA) is a disease which influences the performance of the knee joint. Moreover, the force and moments applied on the joint increase in contrast to normal subjects. Various types of knee orthoses have been designed to solve the mentioned problems. However, there are other problems in terms of distal migration during walking and the alignment of the orthosis which cannot be changed following the use of brace. Therefore, the main aim of the research was to design an orthosis to solve the aforementioned problems.Method. A new type of knee orthosis was designed with a modular structure. Two patients with knee OA participated in this research project. The force applied on the foot, moment transmitted through the knee joint, and spatiotemporal gait parameters were measured by use of a motion analysis system.Results. The results of the research showed that the adduction moment applied on the knee joint decreased while subjects walked with the new knee orthosis (P-value < 0.05).Conclusion. The new design of the knee brace can be used as an effective treatment to decrease the loads applied on the knee joint and to improve the alignment whilst walking.
Spiritually Integrated Treatment of Depression: A Conceptual Framework
Authors: Peteet John R.
Published: April 2012

Many studies have found an inverse correlation between religious/spiritual involvement and depression. Yet several obstacles impede spiritually integrated treatment of depressed individuals. These include specialization and fragmentation of care, inexperience of clinicians and spiritual care providers, ideological bias, boundary and ethical concerns, and the lack of an accepted conceptual framework for integrated treatment. Here I suggest a framework for approaching these obstacles, constructed from a unified view of human experience (having emotional, existential, and spiritual dimensions); spirituality seen as a response to existential concerns (in domains such as identity, hope, meaning/purpose, morality, and autonomy in relation to authority, which are frequently distorted and amplified in depression); a rationale for locating spiritually oriented approaches within a clinician's assessment, formulation, and treatment plan; and recognition of the challenges and potential pitfalls of integrated treatment.
Seismic Response of Torsionally Coupled System with Magnetorheological Dampers
Authors: Mevada Snehal V. , Jangid R. S.
Published: April 2012

The seismic response of linearly elastic, idealized single-storey, one-way asymmetric building with semiactive magnetorheological (MR) dampers with clipped-optimal algorithm is investigated. The response is obtained by numerically solving the governing equations of motion. The effects of eccentricity ratio, uncoupled time period, and ratio of uncoupled torsional to lateral frequency are investigated on peak responses which include lateral, torsional and edge displacements and their acceleration counter parts, base shear, and control forces. To study the effectiveness of control system, the controlled response of asymmetric system is compared with the corresponding uncontrolled response. Further, controlled response of asymmetric system is compared with corresponding symmetric system to study the effects of torsional coupling. It is shown that the implementation of semiactive dampers reduces the deformations significantly. Also, the effects of torsional coupling on effectiveness of semiactive system are found to be more sensitive to the variation of eccentricity and torsional to lateral frequency ratio.
Outcome from Complicated versus Uncomplicated Mild Traumatic Brain Injury
Authors: Iverson Grant L. , Lange Rael T. , Wäljas Minna , Liimatainen Suvi , Dastidar Prasun , Hartikainen Kaisa M. , Soimakallio Seppo , Öhman Juha
Published: April 2012

Objective. To compare acute outcome following complicated versus uncomplicated mild traumatic brain injury (MTBI) using neurocognitive and self-report measures.Method. Participants were 47 patients who presented to the emergency department of Tampere University Hospital, Finland. All completed MRI scanning, self-report measures, and neurocognitive testing at 3-4 weeks after injury. Participants were classified into the complicated MTBI or uncomplicated MTBI group based on the presence/absence of intracranial abnormality on day-of-injury CT scan or 3-4 week MRI scan.Results. There was a large statistically significant difference in time to return to work between groups. The patients with uncomplicated MTBIs had a median of 6.0 days (IQR = 0.75–14.75, range = 0–77) off work compared to a median of 36 days (IQR = 13.5–53, range = 3–315) for the complicated group. There were no significant differences between groups for any of the neurocognitive or self-report measures. There were no differences in the proportion of patients who (a) met criteria for ICD-10 postconcussional disorder or (b) had multiple low scores on the neurocognitive measures.Conclusion. Patients with complicated MTBIs took considerably longer to return to work. They did not perform more poorly on neurocognitive measures or report more symptoms, at 3-4 weeks after injury compared to patients with uncomplicated MTBIs.
Emergency Management of Hypertension in Children
Authors: Singh Dinesh , Akingbola Olugbenga , Yosypiv Ihor , El-Dahr Samir
Published: April 2012

Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH), particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information.
OrientalHydrocyphon(Coleoptera: Scirtidae: Scirtinae): Seven New Species from Indonesia, Thailand, Malaysia, and India
Authors: Yoshitomi Hiroyuki
Published: April 2012

Application Specific Instruction-set Processors (ASIPs) expose to the designer a large number of degrees of freedom. Accurate and rapid simulation tools are needed to explore the design space. To this aim, FPGA-based emulators have recently been proposed as an alternative to pure software cycle-accurate simulator. However, the advantages of on-hardware emulation are reduced by the overhead of the RTL synthesis process that needs to be run for each configuration to be emulated. The work presented in this paper aims at mitigating this overhead, exploiting a form of software-driven platform runtime reconfiguration. We present a complete emulation toolchain that, given a set of candidate ASIP configurations, identifies and builds an overdimensioned architecture capable of being reconfigured via software at runtime, emulating all the design space points under evaluation. The approach has been validated against two different case studies, a filtering kernel and an M-JPEG encoding kernel. Moreover, the presented emulation toolchain couples FPGA emulation with activity-based physical modeling to extract area and power/energy consumption figures. We show how the adoption of the presented toolchain reduces significantly the design space exploration time, while introducing an overhead lower than 10% for the FPGA resources and lower than 0.5% in terms of operating frequency.