bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigenic and Receptor Binding Properties of Enterovirus 68
Authors: Imamura Tadatsugu , Okamoto Michiko , Nakakita Shin-ichi , Suzuki Akira , Saito Mariko , Tamaki Raita , Lupisan Socorro , Roy Chandra Nath , Hiramatsu Hiroaki , Sugawara Kan-etsu , Mizuta Katsumi , Matsuzaki Yoko , Suzuki Yasuo , Oshitani Hitoshi
Published: December 2013

Increased detection of enterovirus 68 (EV68) among patients with acute respiratory infections has been reported from different parts of the world in the late 2000s since its first detection in pediatric patients with lower-respiratory-tract infections in 1962. However, the underlying molecular mechanisms for this trend are still unknown. We therefore aimed to study the antigenicity and receptor binding properties of EV68 detected in recent years in comparison to the prototype strain of EV68, the Fermon strain. We first performed neutralization (NT) and hemagglutination inhibition (HI) tests using antisera generated for EV68 strains detected in recent years. We found that the Fermon strain had lower HI and NT titers than recently detected EV68 strains. The HI and NT titers were also significantly different between strains of different genetic lineages among recently detected EV68 strains. We further studied receptor binding specificities of EV68 strains for sialyloligosaccharides using glycan array analysis. In glycan array analysis, all tested EV68 strains showed affinity for α2-6-linked sialic acids (α2-6 SAs) compared to α2-3 SAs. Our study demonstrates that emergence of strains with different antigenicity is the possible reason for the increased detection of EV68 in recent years. Additionally, we found that EV68 preferably binds to α2-6 SAs, which suggests that EV68 might have affinity for the upper respiratory tract.

IMPORTANCE
Numbers of cases of enterovirus 68 (EV68) infection in different parts of the world increased significantly in the late 2000s. We studied the antigenicity and receptor binding properties of recently detected EV68 strains in comparison to the prototype strain of EV68, Fermon. The hemagglutination inhibition (HI) and neutralization (NT) titers were significantly different between strains of different genetic lineages among recently detected EV68 strains. We further studied receptor binding specificities of EV68 strains for sialyloligosaccharides using glycan array analysis, which showed affinity for α2-6-linked sialic acids (α2-6 SAs) compared to α2-3 SAs. Our study suggested that the emergence of strains with different antigenicities was the possible reason for the increased detections of EV68 in recent years. Additionally, we revealed that EV68 preferably binds to α2-6 SAs. This is the first report describing the properties of EV68 receptor binding to the specific types of sialic acids.
Morbillivirus Control of the Interferon Response: Relevance of STAT2 and mda5 but Not STAT1 for Canine Distemper Virus Virulence in Ferrets
Authors: Svitek Nicholas , Gerhauser Ingo , Goncalves Christophe , Grabski Elena , Döring Marius , Kalinke Ulrich , Anderson Danielle E. , Cattaneo Roberto , von Messling Veronika
Published: December 2013

The V proteins of paramyxoviruses control the innate immune response. In particular, the V protein of the genus
Morbillivirus
interferes with the signal transducer and activator of transcription 1 (STAT1), STAT2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. To characterize the contributions of these pathways to canine distemper virus (CDV) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus V protein with these key regulators of innate immunity. We generated recombinant CDVs with V proteins unable to properly interact with STAT1, STAT2, or mda5. A virus with combined STAT2 and mda5 deficiencies was also generated, and available wild-type and V-protein-knockout viruses were used as controls. Ferrets infected with wild-type and STAT1-blind viruses developed severe leukopenia and loss of lymphocyte proliferation activity and succumbed to the disease within 14 days. In contrast, animals infected with viruses with STAT2 or mda5 defect or both STAT2 and mda5 defects developed a mild self-limiting disease similar to that associated with the V-knockout virus. This study demonstrates the importance of interference with STAT2 and mda5 signaling for CDV immune evasion and provides a starting point for the development of morbillivirus vectors with reduced immunosuppressive properties.

IMPORTANCE
The V proteins of paramyxoviruses interfere with the recognition of the virus by the immune system of the host. For morbilliviruses, the V protein is known to interact with the signal transducer and activator of transcription 1 (STAT1) and STAT2 and the melanoma differentiation-associated protein 5 (mda5), which are involved in interferon signaling. Here, we examined the contribution of each of these signaling pathways to the pathogenesis of the carnivore morbillivirus canine distemper virus. Using viruses selectively unable to interfere with the respective signaling pathway to infect ferrets, we found that inhibition of STAT2 and mda5 signaling was critical for lethal disease. Our findings provide new insights in the mechanisms of morbillivirus immune evasion and may lead to the development of new vaccines and oncolytic vectors.
A proposed model for prediction of survival based on a follow-up study in unresectable pancreatic cancer
Authors: Forssell Henrik , Wester Michael , Åkesson Katrin , Johansson Sigrid
Published: December 2013

Objectives

To define an easy-to-use model for prediction of survival time in patients with unresectable pancreatic cancer in order to optimise patient' care.

Design

An observational retrospective study on patients with unresectable pancreatic cancer. The initial radiographs at presentation of symptoms were reviewed and the maximum diameter of the primary tumour was determined. The occurrence of liver metastases and performance status that determines initiation of chemotherapy was also used in the regression analysis to identify prognostic subgroups.

Setting

County hospital in south-east of Sweden.

Population

Consecutive patients with unresectable pancreatic cancer who were diagnosed between January 2003 and May 2010 (n=132).

Main outcome measures

Statistical analyses were performed using Stata V.13. Survival time was assessed with Kaplan-Meier analysis, log-rank test for equality of survivor functions and Cox regression for calculation of individual hazard based on tumour diameter, presence of liver metastases and initiation of chemotherapy treatment according to patient performance status.

Results

The individual hazard was log h=0.357 tumour size+1.181 liver metastases−0.989 performance status/chemotherapy. Three prognostic groups could be defined: a low-risk group with a median survival time of 6.7 (IQR 9.7) months, a medium-risk group with a median survival time of 4.5 (IQR 4.5) months and a high-risk group with a median survival time of 1.2 (IQR 1.7) months.

Conclusions

The maximum diameter of the primary tumour and the presence of liver metastases found at the X-ray examination of patients with pancreatic cancer, in conjunction with whether or not chemotherapy is initiated according to performance status, predict the survival time for patients who do not undergo surgical resection. The findings result in an easy-to-use model for predicting the survival time.
IN SEARCH OF MOST COMPLEX REGULAR LANGUAGES
Authors: BRZOZOWSKI JANUSZ
Published: December 2013

Sequences (Ln| n ≥ k), called streams, of regular languages Lnare considered, where k is some small positive integer, n is the state complexity of Ln, and the languages in a stream differ only in the parameter n, but otherwise, have the same properties. The following measures of complexity are proposed for any stream: (1) the state complexity n of Ln, that is, the number of left quotients of Ln(used as a reference); (2) the state complexities of the left quotients of Ln; (3) the number of atoms of Ln; (4) the state complexities of the atoms of Ln; (5) the size of the syntactic semigroup of Ln; and the state complexities of the following operations: (6) the reverse of Ln; (7) the star of Ln; (8) union, intersection, difference and symmetric difference of Lmand Ln; and (9) the concatenation of Lmand Ln. A stream that has the highest possible complexity with respect to these measures is then viewed as a most complex stream. The language stream (Un(a, b, c) | n ≥ 3) is defined by the deterministic finite automaton with state set {0, 1, … , n−1}, initial state 0, set {n−1} of final states, and input alphabet {a, b, c}, where a performs a cyclic permutation of the n states, b transposes states 0 and 1, and c maps state n − 1 to state 0. This stream achieves the highest possible complexities with the exception of boolean operations where m = n. In the latter case, one can use Un(a, b, c) and Un(b, a, c), where the roles of a and b are interchanged in the second language. In this sense, Un(a, b, c) is a universal witness. This witness and its extensions also apply to a large number of combined regular operations.
WEIGHTED AUTOMATA AS COALGEBRAS IN CATEGORIES OF MATRICES
Authors: OLIVEIRA JOSÉ N.
Published: December 2013

The evolution from non-deterministic to weighted automata represents a shift from qualitative to quantitative methods in computer science. The trend calls for a language able to reconcile quantitative reasoning with formal logic and set theory, which have for so many years supported qualitative reasoning. Such a lingua franca should be typed, polymorphic, diagrammatic, calculational and easy to blend with conventional notation.

This paper puts forward typed linear algebra as a candidate notation for such a unifying role. This notation, which emerges from regarding matrices as morphisms of suitable categories, is put at work in describing weighted automata as coalgebras in such categories.

Some attention is paid to the interface between the index-free (categorial) language of matrix algebra and the corresponding index-wise, set-theoretic notation.
HYPER-MINIMIZATION FOR DETERMINISTIC TREE AUTOMATA
Authors: JEŻ ARTUR , MALETTI ANDREAS
Published: December 2013

Hyper-minimization is a recent automaton compression technique that can reduce the size of an automaton beyond the limits imposed by classical minimization. The additional compression power is enabled by allowing a finite difference in the represented language. The necessary theory for hyper-minimization is developed for (bottom-up) deterministic tree automata. The hyper-minimization problem for deterministic tree automata is reduced to the hyper-minimization problem for deterministic finite-state string automata, for which fast algorithms exist. The fastest algorithm obtained in this way runs in time [Formula: see text], where m is the size of the transition table and n is the number of states of the input tree automaton.
SELF STABILIZATION IN DISTRIBUTED KNOT DETECTION
Authors: SANTHOSH PRABHU M.
Published: December 2013

This paper describes a failure scenario in the known self-stabilizing algorithm for knot detection in directed graphs, occurring due to incorrect computation of certain variables. A modified algorithm is proposed, which overcomes the shortcomings of the known algorithm.
A POSSIBLE REASON FOR MH ≃126 GeV
Authors: FRAMPTON PAUL H. , HUNG PHAM Q.
Published: December 2013

It is speculated that a possible reason for the scalar mass MH ≃126 GeV is equality of the lifetimes for vacuum decay and instanton-induced proton decay.
DESIGN AND IMPLEMENTATION OF CONFIGURABLE LFSR INSTRUCTIONS TARGETED AT STREAM CIPHER PROCESSING
Authors: DAI ZIBIN , NAN LONGMEI , YANG XUAN , LI XIAONAN
Published: December 2013

By analyzing the operation characteristic of linear feedback shifter registers (LFSRs) in many public stream cipher algorithms and its bottleneck realized by general processor, each specific instruction and reconfigurable hardware cell are proposed in this paper, which can neatly execute LFSR computing operation in parallel with high performance. The LFSR instructions can sustain different operation data widths, different operating models. Instruction-level parallelism based on VLIW system structure and instruction inner parallelism by operating several steps at one time are exploited too. Corresponding reconfigurable hardware units to sustain the implementation of each instruction forcefully by configurating is also developed. The circuit can be used as an important accelerated unit in special processing for stream cipher.
AN UNIVERSAL PHENOMENON IN MUTUALLY COUPLED CHUA'S CIRCUIT FAMILY
Authors: VOLOS CHRISTOS K. , KYPRIANIDIS IOANNIS M. , STOUBOULOS IOANNIS N.
Published: December 2013

This paper presents the universality of the coexistence of complete synchronization with the recently new proposed inverse π-lag synchronization, in the case of mutually coupled systems of Chua's circuit family. The phenomenon of multistability and the nature of this circuit family systems are the key-points which lead to the explanation of this coexistence. For the need of this work, the most representative circuit of this circuits' family, the Chua oscillator, is used. Simulation results confirm this universality in the class of Chua's circuit family.
Adapted random perturbations for non-uniformly expanding maps
Authors: Araujo Vitor , Pacifico Maria Jose , Pinheiro Mariana
Published: December 2013

We obtain stochastic stability of C2 non-uniformly expanding one-dimensional endomorphisms, requiring only that the first hyperbolic time map be Lp-integrable for p > 3. We show that, under this condition (which depends only on the unperturbed dynamics), we can construct a random perturbation that preserves the original hyperbolic times of the unperturbed map and, therefore, to obtain non-uniform expansion for random orbits. This ensures that the first hyperbolic time map is uniformly integrable for all small enough noise levels, which is known to imply stochastic stability. The method enables us to obtain stochastic stability for a class of maps with infinitely many critical points. For higher dimensional endomorphisms, a similar result is obtained, but under stronger assumptions.
RESEARCHING BLACK ENTREPRENEURSHIP: EXPLORING THE CHALLENGE OF RESPONSE BIAS
Authors: OGBOLU MICHAEL N. , SINGH ROBERT P.
Published: December 2013

The reasons for the long term lagging rate of black entrepreneurship are not well understood. Although there has been growing research on black entrepreneurship, race related research can be challenging and may be susceptible to bias resulting from socially desirable responses. Using survey data collected on consumer perceptions of white and black entrepreneurs from 843 white and black respondents by white and black data collectors, we found evidence of response bias. The paper illuminates research methodology issues that should be factored into race-based entrepreneurship research. The important practical and academic implications are discussed and suggestions for future research are offered.
HEALTH INSURANCE AVAILABILITY AND ENTREPRENEURSHIP
Authors: AGGARWAL RAJ , HOLLY KRISZTINA 'Z' , WADHWA VIVEK
Published: December 2013

Unlike prior studies of the impact of health insurance on entrepreneurship, this paper uses primary data from a representative recent survey of entrepreneurs. First, we report the characteristics and socio-economic backgrounds of entrepreneurs. Second, we document that the lack of health insurance has a significant inhibiting impact on entrepreneurs. This paper also documents that the importance of health insurance availability increases for entrepreneurs who are self-funded, married, have children, are from less privileged backgrounds and are in advanced stages of their lives as indicated by having advanced degrees or long work experience when they become entrepreneurs. These results should be of much interest to scholars, managers and policymakers.
The Rise and Fall of Global Climate Policy: Stockholm to Rio 1992, Rio + 20 and Beyond
Authors: SANWAL Mukul
Published: December 2013

Reconciling competing resource needs with respect to maintaining lifestyles and eradication of poverty is at the core of the climate negotiations, and the global biophysical limits to growth should mean lifestyle changes not depriving the poor. With prospects for legally binding commitments fading, new rules to establish national carbon budgets, shifting the focus from flows to stocks of carbon in the atmosphere, will be more scientific and lead to sustainability of our common wellbeing. The way the issue of global environmentalism is now being framed around modifying longer term trends in consumption and production patterns may succeed in securing international cooperation in a manner that the focus on percentage reductions in greenhouse gases, that considered symptoms rather than the causes of climate change, was not able to achieve. The unresolved issue is whether in writing its own urban future China will shape an alternative global vision. Redistribution has so far been kept out of the agenda of the United Nations, and new global goals and rules to share both responsibility and prosperity can lead to a new world order.
Geoengineering: Ethical Considerations and Global Governance
Authors: CHEN Ying , LIU Zhe
Published: December 2013

Human society is facing great challenges to address global climate change. How to move the international climate process forward is still a serious problem for politicians. Geoengineering's, so called Plan B to cope with climate change has attracted attentions of the international community with a lot of debate on its impact, risks from an ethical view as well as global governance at the level. In this paper, we focus on some important issues of geoengineering including the definition, characteristics, ethics and global governance, etc. and then put forward some suggestions for China's considerations.
Vitamin E protection of obesity-enhanced vascular calcification in uremic rats
Authors: Peralta-Ramírez A. , Montes de Oca A. , Raya A. I. , Pineda C. , López I. , Guerrero F. , Diez E. , Muñoz-Castañeda J. R. , Martinez J. , Almaden Y. , Rodríguez M. , Aguilera-Tejero E.
Published: December 2013

This study aimed to determine the extent of extraskeletal calcification in uremic Zucker rats, by comparing obese and lean phenotypes, and to evaluate the influence of vitamin E (VitE) on the development of calcifications in both uremic rats and human vascular smooth muscle cells (HVSMCs) cultured in vitro. Zucker rats of lean and obese phenotypes with normal renal function [control (C); C-lean and C-obese groups] and with uremia [5/6 nephrectomy (Nx); Nx-lean and Nx-obese groups] and uremic rats treated with VitE (Nx-lean + VitE and Nx-obese + VitE groups) were studied. Uremic groups were subjected to Nx, fed a 0.9% phosphorus diet, and treated with calcitriol (80 ng/kg ip). The aortic calcium concentration was significantly higher ( P < 0.05) in Nx-obese rats (10.0 ± 2.1 mg/g tissue) than in Nx-lean rats (3.6 ± 1.3 mg/g tissue). A decrease in plasma glutathione peroxidase activity was observed in Nx-obese rats compared with Nx-lean rats (217.2 ± 18.2 vs. 382.3 ± 15.5 nmol·min−1·ml−1, P < 0.05). Treatment with VitE restored glutathione peroxidase activity and reduced the aortic calcium concentration to 4.6 ± 1.3 mg/g tissue. The differences in mineral deposition between Nx-lean, Nx-obese, Nx-lean + VitE, and Nx-obese + VitE rats were also evidenced in other soft tissues. In HVSMCs incubated with high phosphate, VitE also prevented oxidative stress and reduced calcium content, bone alkaline phosphatase, and gene expression of core-binding factor-α1. In conclusion, uremic obese rats develop more severe calcifications than uremic lean rats and VitE reduces oxidative stress and vascular calcifications in both rats and cultures of HVSMCs.
Angiotensin II stimulates basolateral 50-pS K channels in the thick ascending limb
Authors: Wang Mingxiao , Luan Haiyan , Wu Peng , Fan Lili , Wang Lijun , Duan Xinpeng , Zhang Dandan , Wang Wen-Hui , Gu Ruimin
Published: December 2013

We used the patch-clamp technique to examine the effect of angiotensin II (ANG II) on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. Application of ANG II increased the channel activity and the current amplitude of the basolateral 50-pS K channel. The stimulatory effect of ANG II on the K channels was completely abolished by losartan, an inhibitor of type 1 angiotensin receptor (AT1R), but not by PD123319, an AT2R antagonist. Moreover, inhibition of phospholipase C (PLC) and protein kinase C (PKC) also abrogated the stimulatory effect of ANG II on the basolateral K channels in the TAL. This suggests that the stimulatory effect of ANG II on the K channels was induced by activating PLC and PKC pathways. Western blotting demonstrated that ANG II increased the phosphorylation of c-Src at tyrosine residue 416, an indication of c-Src activation. This effect was mimicked by PKC stimulator but abolished by calphostin C. Moreover, inhibition of NADPH oxidase (NOX) also blocked the effect of ANG II on c-Src tyrosine phosphorylation. The role of Src-family protein tyrosine kinase (SFK) in mediating the effect of ANG II on the basolateral K channel was further suggested by the experiments in which inhibition of SFK abrogated the stimulatory effect of ANG II on the basolateral 50-pS K channel. We conclude that ANG II increases basolateral 50-pS K channel activity via AT1R and that activation of AT1R stimulates SFK by a PLC-PKC-NOX-dependent mechanism.
A PTBA small molecule enhances recovery and reduces postinjury fibrosis after aristolochic acid-induced kidney injury
Authors: Novitskaya Tatiana , McDermott Lee , Zhang Ke Xin , Chiba Takuto , Paueksakon Paisit , Hukriede Neil A. , de Caestecker Mark P.
Published: December 2013

Phenylthiobutanoic acids (PTBAs) are a new class of histone deacetylase (HDAC) inhibitors that accelerate recovery and reduce postinjury fibrosis after ischemia-reperfusion-induced acute kidney injury. However, unlike the more common scenario in which patients present with protracted and less clearly defined onset of renal injury, this model of acute kidney injury gives rise to a clearly defined injury that begins to resolve over a short period of time. In these studies, we show for the first time that treatment with the PTBA analog methyl-4-(phenylthio)butanoate (M4PTB) accelerates recovery and reduces postinjury fibrosis in a progressive model of acute kidney injury and renal fibrosis that occurs after aristolochic acid injection in mice. These effects are apparent when M4PTB treatment is delayed 4 days after the initiating injury and are associated with increased proliferation and decreased G2/M arrest of regenerating renal tubular epithelial cells. In addition, there is reduced peritubular macrophage infiltration and decreased expression of the macrophage chemokines CX3Cl1 and CCL2. Since macrophage infiltration plays a role in promoting kidney injury, and since renal tubular epithelial cells show defective repair and a marked increase in maladaptive G2/M arrest after aristolochic acid injury, these findings suggest M4PTB may be particularly beneficial in reducing injury and enhancing intrinsic cellular repair even when administered days after aristolochic acid ingestion.
Mature IGF-I excels in promoting functional muscle recovery from disuse atrophy compared with pro-IGF-IA
Authors: Park SooHyun , Brisson Becky K. , Liu Min , Spinazzola Janelle M. , Barton Elisabeth R.
Published: December 2013

Prolonged disuse of skeletal muscle results in atrophy, and once physical activity is resumed, there is increased susceptibility to injury. Insulin-like growth factor-I (IGF-I) is considered a potential therapeutic target to attenuate atrophy during unloading and to enhance rehabilitation upon reloading of skeletal muscles, due to its multipronged actions on satellite cell proliferation, differentiation, and survival, as well as its actions on muscle fibers to boost protein synthesis and inhibit protein degradation. However, the form of IGF-I delivered may alter the success of treatment. Using the hindlimb suspension model of disuse atrophy, we compared the efficacy of two IGF-I forms in protection against atrophy and enhancement of recovery: mature IGF-I (IGF-IS) lacking the COOH-terminal extension, called the E-peptide, and IGF-IA, which is the predominant form retaining the E-peptide. Self-complementary adeno-associated virus harboring the murine Igf1 cDNA constructs were delivered to hindlimbs of adult female C57BL6 mice 3 days prior to hindlimb suspension. Hindlimb muscles were unloaded for 7 days and then reloaded for 3, 7, and 14 days. Loss of muscle mass following suspension was not prevented by either IGF-I construct. However, IGF-IS expression maintained soleus muscle force production. Further, IGF-IS treatment caused rapid recovery of muscle fiber morphology during reloading and maintained muscle strength. Analysis of gene expression revealed that IGF-IS expression accelerated the downregulation of atrophy-related genes compared with untreated or IGF-IA-treated samples. We conclude that mature-IGF-I may be a better option than pro-IGF-IA to promote skeletal muscle recovery following disuse atrophy.
Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia
Authors: Dempsey Jerome A. , Powell Frank L. , Bisgard Gerald E. , Blain Gregory M. , Poulin Marc J. , Smith Curtis A.
Published: December 2013

During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of “sleep high-train low”!
Three-dimensional deformation and transverse rotation of the human free Achilles tendon in vivo during isometric plantarflexion contraction
Authors: Obst Steven J. , Renault Jean-Baptiste , Newsham-West Richard , Barrett Rod S.
Published: December 2013

Freehand three-dimensional ultrasound (3DUS) was used to investigate longitudinal and biaxial transverse deformation and rotation of the free Achilles tendon in vivo during a voluntary submaximal isometric muscle contraction. Participants ( n = 8) were scanned at rest and during a 70% maximal voluntary isometric contraction (MVIC) of the plantarflexors. Ultrasound images were manually digitized to render a 3D reconstruction of the free Achilles tendon for the computation of tendon length, volume, cross-sectional area (CSA), mediolateral diameter (MLD), anteroposterior diameter (APD), and transverse rotation. Tendon longitudinal and transverse (CSA, APD, and MLD) deformation and strain at 70% MVIC were calculated relative to the resting condition. There was a significant main effect of contraction on tendon length and mean CSA, MLD, and APD ( P < 0.05), but no effect on tendon volume ( P = 0.70). Group mean transverse strains for CSA, MLD, and APD averaged over the length of the tendon were −5.5%, −8.7% and 8.7%, respectively. Peak CSA, MLD, and APD transverse strains all occurred between 40% and 60% of tendon length. Transverse rotation of the free tendon was negligible at rest but increased under load, becoming externally rotated relative to the calcaneal insertion. The relationship between longitudinal and transverse strains of the free Achilles tendon during muscle-induced elongation may be indicative of interfascicle reorganization. The finding that transverse rotation and strain peaked in midportion of the free Achilles tendon may have important implications for tendon injury mechanisms and estimation of tendon stress in vivo.
Haptic feedback enhances rhythmic motor control by reducing variability, not improving convergence rate
Authors: Ankarali M. Mert , Tutkun Şen H. , De Avik , Okamura Allison M. , Cowan Noah J.
Published: December 2013

Stability and performance during rhythmic motor behaviors such as locomotion are critical for survival across taxa: falling down would bode well for neither cheetah nor gazelle. Little is known about how haptic feedback, particularly during discrete events such as the heel-strike event during walking, enhances rhythmic behavior. To determine the effect of haptic cues on rhythmic motor performance, we investigated a virtual paddle juggling behavior, analogous to bouncing a table tennis ball on a paddle. Here, we show that a force impulse to the hand at the moment of ball-paddle collision categorically improves performance over visual feedback alone, not by regulating the rate of convergence to steady state (e.g., via higher gain feedback or modifying the steady-state hand motion), but rather by reducing cycle-to-cycle variability. This suggests that the timing and state cues afforded by haptic feedback decrease the nervous system's uncertainty of the state of the ball to enable more accurate control but that the feedback gain itself is unaltered. This decrease in variability leads to a substantial increase in the mean first passage time, a measure of the long-term metastability of a stochastic dynamical system. Rhythmic tasks such as locomotion and juggling involve intermittent contact with the environment (i.e., hybrid transitions), and the timing of such transitions is generally easy to sense via haptic feedback. This timing information may improve metastability, equating to less frequent falls or other failures depending on the task.
Transfer of postural adaptation depends on context of prior exposure
Authors: Pienciak-Siewert Alison , Barletta Anthony J. , Ahmed Alaa A.
Published: December 2013

Postural control is significantly affected by the postural base of support; however, the effects on postural adaptation are not well understood. Here we investigated how adaptation and transfer of anticipatory postural control are affected by stance width. Subjects made reaching movements in a novel dynamic environment while holding the handle of a force-generating robotic arm. Each subject initially adapted to the dynamics while standing in a wide stance and then switched to a narrow stance, or vice versa. Our hypothesis is that anticipatory postural control, reflected in center of pressure (COP) movement, is not affected by stance width, as long as the control remains within functional limits; therefore we predicted that subjects in either stance would show similar COP movement by the end of adaptation and immediately upon transfer to the other stance. We found that both groups showed similar adaptation of postural control, by using different muscle activation strategies to account for the differing stance widths. One group, after adapting in wide stance, transferred similar postural control to narrow stance, by modifying their muscle activity to account for the new stance. Interestingly, the other group showed an increase in postural control when transferring from narrow to wide stance, associated with no change in muscle activity. These results confirm that adaptation of anticipatory postural control is not affected by stance width, as long as the control remains within biomechanical limits. However, transfer of control between stance widths is affected by the initial context in which the task is learned.
Visual and vestibular perceptual thresholds each demonstrate better precision at specific frequencies and also exhibit optimal integration
Authors: Karmali Faisal , Lim Koeun , Merfeld Daniel M.
Published: December 2013

Prior studies show that visual motion perception is more precise than vestibular motion perception, but it is unclear whether this is universal or the result of specific experimental conditions. We compared visual and vestibular motion precision over a broad range of temporal frequencies by measuring thresholds for vestibular (subject motion in the dark), visual (visual scene motion) or visual-vestibular (subject motion in the light) stimuli. Specifically, thresholds were measured for motion frequencies spanning a two-decade physiological range (0.05-5 Hz) using single-cycle sinusoidal acceleration roll tilt trajectories (i.e., distinguishing left-side down from right-side down). We found that, while visual and vestibular thresholds were broadly similar between 0.05 and 5.0 Hz, each cue is significantly more precise than the other at certain frequencies. Specifically, we found that 1) visual and vestibular thresholds were indistinguishable at 0.05 Hz and 2 Hz (i.e., similarly precise); 2) visual thresholds were lower (i.e., vision more precise) than vestibular thresholds between 0.1 Hz and 1 Hz; and 3) visual thresholds were higher (i.e., vision less precise) than vestibular thresholds above 2 Hz. This shows that vestibular perception can be more precise than visual perception at physiologically relevant frequencies. We also found that sensory integration of visual and vestibular information is consistent with static Bayesian optimal integration of visual-vestibular cues. In contrast with most prior work that degraded or altered sensory cues, we demonstrated static optimal integration using natural cues.
Retinoic acid induces changes in electrical properties of adult neurons in a dose- and isomer-dependent manner
Authors: Vesprini Nicholas D. , Spencer Gaynor E.
Published: December 2013

The electrical activity of neurons is known to play a role in neuronal development, as well as repair of adult nervous tissue. For example, the extension of neurites and motility of growth cones can be modulated by changes in the electrical firing of neurons. The vitamin A metabolite retinoic acid also plays a critical role during nervous system development and is also known to elicit regenerative responses, namely the induction, enhancement, and directionality of neurite outgrowth. However, no studies have previously reported the ability of retinoic acid to modify the electrical activity of neurons. In this study, we determined whether retinoic acid might exert effects on the nervous system by altering the electrical properties of neurons. Using cultured adult neurons from Lymnaea stagnalis, we showed that acute application of retinoic acid can rapidly elicit changes in neuronal firing properties. Retinoic acid caused the presence of atypical firing behavior such as rhythmic bursting and altered the shape of action potentials, causing increases in half-amplitude duration and decay time. Retinoic acid also caused cell silencing, whereby neuronal activity was halted within an hour. These effects of retinoic acid were shown to be both dose and isomer dependent. We then showed that the effects of retinoic acid on cell firing (but not silencing) were significantly reduced in the presence of an retinoid X receptor pan-antagonist HX531. This study suggests that some of the effects of retinoic acid during neuronal development or regeneration might possibly occur as a result of changes in electrical activity of neurons.
Locomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury
Authors: Chen Yi , Chen Lu , Liu Rongliang , Wang Yu , Chen Xiang Yang , Wolpaw Jonathan R.
Published: December 2013

When new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a “negotiated equilibrium” that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery.
Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors
Authors: Tigerholm Jenny , Petersson Marcus E. , Obreja Otilia , Lampert Angelika , Carr Richard , Schmelz Martin , Fransén Erik
Published: December 2013

Action potential initiation and conduction along peripheral axons is a dynamic process that displays pronounced activity dependence. In patients with neuropathic pain, differences in the modulation of axonal conduction velocity by activity suggest that this property may provide insight into some of the pathomechanisms. To date, direct recordings of axonal membrane potential have been hampered by the small diameter of the fibers. We have therefore adopted an alternative approach to examine the basis of activity-dependent changes in axonal conduction by constructing a comprehensive mathematical model of human cutaneous C-fibers. Our model reproduced axonal spike propagation at a velocity of 0.69 m/s commensurate with recordings from human C-nociceptors. Activity-dependent slowing (ADS) of axonal propagation velocity was adequately simulated by the model. Interestingly, the property most readily associated with ADS was an increase in the concentration of intra-axonal sodium. This affected the driving potential of sodium currents, thereby producing latency changes comparable to those observed for experimental ADS. The model also adequately reproduced post-action potential excitability changes (i.e., recovery cycles) observed in vivo. We performed a series of control experiments replicating blockade of particular ion channels as well as changing temperature and extracellular ion concentrations. In the absence of direct experimental approaches, the model allows specific hypotheses to be formulated regarding the mechanisms underlying activity-dependent changes in C-fiber conduction. Because ADS might functionally act as a negative feedback to limit trains of nociceptor activity, we envisage that identifying its mechanisms may also direct efforts aimed at alleviating neuronal hyperexcitability in pain patients.
Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice
Authors: Hattori Yoshiyuki , Date Masataka , Arai Shohei , Kawano Kumi , Yonemochi Etsuo , Maitani Yoshie
Published: December 2013

We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid and sodium cholate (NaChol) or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w) into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15-liposomes), C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80–90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700–1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550–780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.
A Theory of Cartesian Product and Factorization
of Circulant Graphs
Authors: Vilfred V.
Published: December 2013

We determine when the Cartesian product of two circulant graphs is also a circulant graph. This leads to a theory of factorization of circulant graphs.
Two Cases and Review of the Literature: Primary Percutaneous Angiography and Antiplatelet Management in Patients with Immune Thrombocytopenic Purpura
Authors: Torbey Estelle , Yacoub Harout , McCord Donald , Lafferty James
Published: December 2013

We report two cases of immune thrombocytopenic purpura (ITP) associated with acute coronary artery syndrome highlighting the interventions done in every case along with the medications used during intervention and as outpatient. The first case is that of a woman with ITP exacerbation while on dual antiplatelet therapy and the second case is that of a male presenting with non-ST elevation myocardial infarction (NSTEMI) while in a thrombocytopenic crisis. In both cases antiplatelet therapy was held and thrombopoietic therapy was initiated before resuming full anticoagulation and coronary intervention. Given the paucity of data on ITP and antiplatelets treatment in the setting of acute coronary syndrome, no strict recommendations can be proposed, but antiplatelets appear to be safe acutely and in the long term in this category of patients as long as few measures are undertaken to minimize the risks of bleeding and thrombosis.
Exophytic Parietal Skin Metastases of Renal Cell Carcinoma
Authors: Kassam Karim , Tiong Elizabeth , Nigar Ezra , Kumar Mahesh
Published: December 2013

The common sites for metastasis of renal cell carcinoma are lung, kidney, adrenal glands, liver, and contralateral kidney. We report an unusual case of cutaneous metastasis of renal cell carcinoma in a 68-year-old woman who was treated for renal cell carcinoma with partial right nephrectomy and multikinase angiogenesis inhibitor (sunitinib) 10 years ago.
Impacts of Pond Change on the Regional Sustainability of Water Resources in Taoyuan, Taiwan
Authors: Liou Yuei-An , Wang Tai-Sheng , Chan Hai-Po
Published: December 2013

Taoyuan tableland faces the increasing water demand associated with the expansion of industrialization and urbanization. The county currently relies on the Shihmen Reservoir as the single water supply system. It will be of great concern in the shortage of water resources. This study aims to explore the impact of changes in farm ponds on the regional agricultural environment in Taoyuan County with multiyear (1993, 2003, and 2010) SPOT satellite imagery. Results show that farm ponds have decreased by 10.55 million m2from 1993 to 2010, and the existing farm ponds were 18.80 million m2in 2010, equivalent to the irrigation water of 21.10~31.65 million m3(tons) and 37.61~56.41 million m3(tons), respectively. The existing farm ponds are able to provide the water supply for 1.88~2.82 thousand hectares of agricultural land, accounting for 6.70%~10.50% of total agricultural area of Taoyuan County. Corresponding to the government’s promotion policy (2012) on activating fallow land, if we redeploy the existing farm ponds for activating fallow fields, it will lessen the water supply burden of Shimen Reservoir. Thus, farm ponds remain the significant water facilities. For the sustainable agriculture, farm ponds shall be classified and cherished as a public asset for the future development.
Herniation of Small Bowel Loop through a Broad Ligament Defect Masquerading as Torsion of Ovarian Cyst
Authors: Bakare Babatola , Akadiri Olumide , Akintayo Akinyemi Akinsoji
Published: December 2013

Torsion of ovarian cyst is a common cause of acute abdomen especially in women of reproductive age-group. It commonly presents with colicky abdominal pain associated with nausea and vomiting. It could however mimic acute intestinal obstruction. The patient was a 32-year-old multipara with no previous history of pelvic or abdominal surgery. She was admitted with colicky lower abdominal pain associated with repeated episodes of vomiting and nausea. Laboratory investigations were essentially normal. Abdominopelvic USS showed a hypoechoic mass lesion in the left adnexium measuring 7.1 × 5.5 cm; surrounding bowel loops were hypoactive, dilated, and fluid filled. Diagnosis of acute abdomen secondary to suspected torsion of ovarian cyst was made. Management began for acute abdomen with intravenous hydration, prophylactic antibiotics, and analgesics. An emergency laparotomy revealed about 6 cm defect in the left broad ligament in which a 20 cm segment of terminal ileum was encased. Liberation of the ileal segment was done and the broad ligament defect closed. Bowel obstruction requires high index of suspicion in a patient with acute abdomen due to suspected torsion ovarian cyst most especially in the absence of previous pelvic or abdominal surgery.
Attitudes of Implanting Physicians about Cardiac Rhythm Management Devices and Their Features
Authors: Elmouchi Darryl A. , Chalfoun Nagib , Gauri Andre
Published: December 2013

Modern cardiac rhythm management systems have become increasingly complex. The decision on which specific system to implant in a given patient often rests with the implanting physician. We conducted a multiple-choice survey to assess the opinions and preferences of cardiologists and electrophysiologists who implant and follow cardiac rhythm management systems. Reliability and battery longevity were viewed as the most important characteristics in device selection. Patient characteristics which most affected device choice were pacing indication and life expectancy. Remote technology was used in 47% of pacemaker patients, 64% of ICD patients, and 65% of CRT-D patients, with wireless (radiofrequency) remote patient monitoring associated with higher patient compliance rates (74% versus 64%, resp.). Wireless remote patient management with alerts for atrial tachyarrhythmias was felt to be important by 76% of respondents. When choosing an MR-conditional device, physicians deemed patients with prior orthopedic problems, a history of cancer, or neurological disorders to be more likely to require a future MRI. Device longevity and reliability remain the most important factors which influence device selection. Wireless remote patient monitoring with alerts is considered increasingly important when choosing a specific cardiac rhythm management system to implant.