bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Monocytes Downregulates Expression of Adaptive Immune Response Costimulatory Receptors and Proinflammatory Cytokines
Authors: Gregory Sean M. , Wang Ling , West John A. , Dittmer Dirk P. , Damania Blossom
Published: January 2012

Kaposi's sarcoma-associated herpesvirus (KSHV) infection is associated with the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. We report the establishment of a monocytic cell line latently infected with KSHV (KSHV-THP-1). We profiled viral and cytokine gene expression in the KSHV-THP-1 cells compared to that in uninfected THP-1 cells and found that several genes involved in the host immune response were downregulated during latent infection, including genes for CD80, CD86, and the cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Thus, KSHV minimizes its immunological signature by suppressing key immune response factors, enabling persistent infection and evasion from host detection.
Analysis of Hepatitis C Virus Intrahost Diversity across the Coding Region by Ultradeep Pyrosequencing
Authors: Lauck Michael , Alvarado-Mora Mónica V. , Becker Ericka A. , Bhattacharya Dipankar , Striker Rob , Hughes Austin L. , Carrilho Flair J. , O'Connor David H. , Pinho João R. Rebello
Published: January 2012

Hepatitis C virus (HCV) is the leading cause of liver disease worldwide. In this study, we analyzed four treatment-naïve patients infected with subtype 1a and performed Roche/454 pyrosequencing across the coding region. We report the presence of low-level drug resistance mutations that would most likely have been missed using conventional sequencing methods. The approach described here is broadly applicable to studies of viral diversity and could help to improve the efficacy of direct-acting antiviral agents (DAA) in the treatment of HCV-infected patients.
Activation of the Nipah Virus Fusion Protein in MDCK Cells Is Mediated by Cathepsin B within the Endosome-Recycling Compartment
Authors: Diederich Sandra , Sauerhering Lucie , Weis Michael , Altmeppen Hermann , Schaschke Norbert , Reinheckel Thomas , Erbar Stephanie , Maisner Andrea
Published: January 2012

Proteolytic activation of the fusion protein of the highly pathogenic Nipah virus (NiV F) is a prerequisite for the production of infectious particles and for virus spread via cell-to-cell fusion. Unlike other paramyxoviral fusion proteins, functional NiV F activation requires endocytosis and pH-dependent cleavage at a monobasic cleavage site by endosomal proteases. Using prototype Vero cells, cathepsin L was previously identified to be a cleavage enzyme. Compared to Vero cells, MDCK cells showed substantially higher F cleavage rates in both NiV-infected and NiV F-transfected cells. Surprisingly, this could not be explained either by an increased F endocytosis rate or by elevated cathepsin L activities. On the contrary, MDCK cells did not display any detectable cathepsin L activity. Though we could confirm cathepsin L to be responsible for F activation in Vero cells, inhibitor studies revealed that in MDCK cells, cathepsin B was required for F-protein cleavage and productive replication of pathogenic NiV. Supporting the idea of an efficient F cleavage in early and recycling endosomes of MDCK cells, endocytosed F proteins and cathepsin B colocalized markedly with the endosomal marker proteins early endosomal antigen 1 (EEA-1), Rab4, and Rab11, while NiV F trafficking through late endosomal compartments was not needed for F activation. In summary, this study shows for the first time that endosomal cathepsin B can play a functional role in the activation of highly pathogenic NiV.
Rhesus Rotavirus Trafficking during Entry into MA104 Cells Is Restricted to the Early Endosome Compartment
Authors: Wolf Marie , Deal Emily M. , Greenberg Harry B.
Published: January 2012

Endocytosis has recently been implicated in rotavirus (RV) entry. We examined the role of Rabs, which regulate endosomal trafficking, during RV entry. Several structural proteins of neuraminidase-sensitive and -insensitive RVs colocalized with Rab5, an early endosome marker, but not Rab7, a late endosome marker. Dominant-negative and constitutively active mutants demonstrated that Rab5 but not Rab4 or Rab7 affects rhesus RV (RRV) infectivity. These data suggest that early RRV trafficking is confined to the early endosome compartment and requires Rab5.
Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis
Authors: Laska Magdalena Janina , Brudek Tomasz , Nissen Kari Konstantin , Christensen Tove , Møller-Larsen Anné , Petersen Thor , Nexø Bjørn Andersen
Published: January 2012

Multiple sclerosis (MS) is considered to be an autoimmune disease with an unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS. Human endogenous retroviruses (HERVs) constitute 5 to 8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS. We studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in peripheral blood mononuclear cells (PBMCs) from healthy controls and from MS patients with nonactive or active disease. There was a significant increase in HERV-H/F Gag expression in CD4+(P< 0.001) and CD8+(P< 0.001) T lymphocytes and in monocytes (P= 0.0356) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute quantitative PCR (Q-PCR) evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We found a 4-fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS compared with healthy controls (P< 0.001). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expression levels will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.
Analysis of the Autographa californica Multiple Nucleopolyhedrovirus Overlapping Gene Pair
lef3
and
ac68
Reveals that AC68 Is a
Per Os
Infectivity Factor and that LEF3 Is Critical, but Not Essential, for Virus Replication
Authors: Nie Yingchao , Fang Minggang , Erlandson Martin A. , Theilmann David A.
Published: January 2012

Autographa californica
multiple nucleopolyhedrovirus
ac68
is a core gene that overlaps
lef3
which encodes the single-stranded DNA binding protein. A knockout (KO) virus lacking both
lef3
and
ac68
was generated (
lef3-ac68
2×KO) to enable the functional study of
ac68
. To produce an
ac68
KO virus that did not impact
lef3
expression, the
lef3-ac68
2×KO virus was repaired with a DNA fragment containing
lef3
and
ac68
, in which
ac68
contained point mutations so that only LEF3 was expressed. Repair of
lef3-ac68
2×KO with just
ac68
generated an
lef3
KO virus. Analysis of the a
c68
KO virus showed that viral DNA replication and budded virus (BV) levels were unaffected compared to levels in the double-repair or wild-type (WT) control virus. Bioassay analyses of
Trichoplusia ni
larvae injected with BV directly into the hemolymph, bypassing the gut, showed no difference in mortality rates between the
ac68
KO and the WT viruses. However, in oral bioassays the
ac68
KO occlusion bodies failed to kill larvae. These results show that the core gene
ac68
encodes a
per os
infectivity factor (
pif6
). The
lef3
KO virus was also analyzed, and virus replication was drastically reduced compared to WT virus, but very low levels of
lef3
KO virus DNA replication and BV production could be detected. In addition, in transfected cells P143 was transported to the nucleus in the absence of LEF3. This study therefore shows for the first time that even though the loss of LEF3 severely impairs virus replication, it is not absolutely essential for P143 nuclear import or viral replication.
Genome Sequence of Chinese Porcine Parvovirus Strain PPV2010
Authors: Cui Jin , Wang Xin , Ren Yudong , Cui Shangjin , Li Guangxing , Ren Xiaofeng
Published: January 2012

Porcine parvovirus (PPV) isolate PPV2010 has recently emerged in China. Herein, we analyze the complete genome sequence of PPV2010. Our results indicate that the genome of PPV2010 bears mixed characteristics of virulent PPV and vaccine strains. Importantly, PPV2010 has the potential to be a naturally attenuated candidate vaccine strain.
Complete Genome Sequences of 138 Mycobacteriophages
Authors: Hatfull Graham F. ,   the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science Program,   the KwaZulu-Natal Research Institute for Tuberculosis and HIV Mycobacterial Genetics Course Students,   the Phage Hunters Integrating Research and Education Program
Published: January 2012

Bacteriophages are the most numerous biological entities in the biosphere, and although their genetic diversity is high, it remains ill defined. Mycobacteriophages—the viruses of mycobacterial hosts—provide insights into this diversity as well as tools for manipulating
Mycobacterium tuberculosis
. We report here the complete genome sequences of 138 new mycobacteriophages, which—together with the 83 mycobacteriophages previously reported—represent the largest collection of phages known to infect a single common host,
Mycobacterium smegmatis
mc
2
155.
HLA B*5701-Positive Long-Term Nonprogressors/Elite Controllers Are Not Distinguished from Progressors by the Clonal Composition of HIV-Specific CD8
+
T Cells
Authors: Mendoza Daniel , Royce Cassandra , Ruff Laura E. , Ambrozak David R. , Quigley Máire F. , Dang Thurston , Venturi Vanessa , Price David A. , Douek Daniel C. , Migueles Stephen A. , Connors Mark
Published: January 2012

To better understand the qualitative features of effective human immunodeficiency virus (HIV)-specific immunity, we examined the TCR clonal composition of CD8
+
T cells recognizing conserved HIV p24-derived epitopes in HLA-B*5701-positive long-term nonprogressors/elite controllers (LTNP/EC) and HLA-matched progressors. Both groups displayed oligoclonal HLA-B5701-restricted p24-specific CD8
+
T-cell responses with similar levels of diversity and few public clonotypes. Thus, HIV-specific CD8
+
T-cell responses in LTNP/EC are not differentiated from those of progressors on the basis of clonal diversity or TCR sharing.
Herpesvirus Saimiri Antagonizes Nuclear Domain 10-Instituted Intrinsic Immunity via an ORF3-Mediated Selective Degradation of Cellular Protein Sp100
Authors: Full Florian , Reuter Nina , Zielke Katrin , Stamminger Thomas , Ensser Armin
Published: January 2012

In recent studies, the nuclear domain 10 (ND10) components PML, Sp100, human Daxx (hDaxx), and ATRX were identified to be cellular restriction factors that are able to inhibit the replication of several herpesviruses. The antiviral function of ND10, however, is antagonized by viral effector proteins by a variety of strategies, including degradation of PML or relocalization of ND10 proteins. In this study, we analyzed the interplay between infection with herpesvirus saimiri (HVS), the prototypic rhadinovirus, and cellular defense by ND10. In contrast to other herpesviruses, we found that HVS specifically degraded the cellular ND10 component Sp100, whereas other factors like PML or hDaxx remained intact. We could further identify the ORF3 tegument protein of HVS, which shares homology with the cellular formylglycinamide ribotide amidotransferase (FGARAT) enzyme, to be the viral factor that induces the proteasomal degradation of Sp100. Interestingly, recent studies showed that the ORF3-homologous proteins ORF75c of murine gammaherpesvirus 68 and BNRF-1 of Epstein-Barr virus modulate the ND10 proteins PML and ATRX, respectively, suggesting that the ND10 targets of viral FGARAT-homologous proteins diversified during evolution. Furthermore, a virus with the ORF3 deletion was efficiently complemented in Sp100-depleted cells, indicating that Sp100 is able to inhibit HVS in the absence of antagonistic mechanisms. In contrast, we observed that PML, which was neither degraded nor redistributed after HVS infection, strongly restricted both wild-type HVS and virus with the ORF3 deletion. Thus, HVS may lack a factor that efficiently counteracts the repressive function of PML, which may foster latency as the outcome of infection.
tirant
, a Newly Discovered Active Endogenous Retrovirus in Drosophila simulans
Authors: Akkouche Abdou , Rebollo Rita , Burlet Nelly , Esnault Caroline , Martinez Sonia , Viginier Barbara , Terzian Christophe , Vieira Cristina , Fablet Marie
Published: January 2012

Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of
gypsy
, few endogenous retroviruses have been identified in insects. In this study, we describe the
tirant
endogenous retrovirus in a subset of
Drosophila simulans
natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for
tirant
within one population of this species.
Electrochemical reduction of dodecylpyridinium bromide in aprotic solvents: Mechanistic studies
Authors: Hromadová Magdaléna , Pospíšil Lubomír , Sokolová Romana , Kolivoška Viliam
Published: January 2012

Reduction mechanism of 1-dodecylpyridin-1-ium bromide (DPBr) in dimethylsulfoxide has been studied on mercury electrode. Based on the classical polarographic methods as well as on the use of AC techniques it was shown that DPBr is reduced in a reversible one electron transfer step followed by dimerization of the corresponding radical species. Reduction process is accompanied by the adsorption phenomena even in the non-aqueous solvents. Possible modes of DPBr adsorption have been studied by the ex situ scanning tunnelling microscopy (STM) imaging of these molecules on highly oriented pyrolytic graphite.
Moderators of the intention-behaviour relationship in the physical activity domain: a systematic review
Authors: Rhodes Ryan E , Dickau Leanne
Published: January 2012

Intention is theorised as the proximal determinant of behaviour in many leading theories and yet intention-behaviour discord is prevalent. The purpose of this review was to retrieve, theme and appraise the variables that have been evaluated as the potential moderators of the intention-behaviour relationship in the physical activity (PA) domain. Eligible studies were selected from English peer-reviewed journals and had to report an empirical test of moderation of intention-PA (I-PA) with a third variable. Fifty-seven studies passed the inclusion criteria and these represented 38 different potential moderators of I-PA. Intention stability proved to be the most consistent moderator of I-PA, suggesting that much of the discordance may be from motivational flux between initial intention and eventual behaviour. Anticipated regret and conscientiousness also had evidence as the moderators of I-PA. Perceived control/self-efficacy, planning, extraversion, habit and environmental proximity to recreation showed some evidence for moderation, while gender, agreeableness, openness, body mass index and ethnicity did not appear to moderate I-PA. The findings demonstrate that traditional intention theories may need augmentation to better account for the evidence present in I-PA discordance.
The tip of an iceberg? A cross-sectional study of the general public's experiences of reporting healthcare complaints in Stockholm, Sweden
Authors: Wessel Maja , Lynøe Niels , Juth Niklas , Helgesson Gert
Published: January 2012

Objectives

To investigate the hypothesis that complaints of adverse events related to encounters with healthcare personnel are underreported and to identify barriers to filing such complaints.

Design

A cross-sectional study, where a questionnaire was sent to the respondents asking whether or not they have filed complaints of adverse events. Respondents were also asked whether they have had reasons for doing so but abstained, and if so their reasons for not complaining. The authors also asked about participants' general experience of and trust in healthcare.

Setting

The County of Stockholm, Sweden.

Participants

A random sample of 1500 individuals of the general population registered by the Swedish National Tax Board as living in the County of Stockholm in April 2008. Of the selected group, aged 18–99 years, 50% were women and 50% men. Response rate was 62.1%, of which 58% were women and 42% were men; the median age was 49 years.

Primary and secondary outcome measures

Primary outcome measures were whether the participants have filed a formal complaint with the Patients' Advisory Committee and whether they have had reason to file a complaint but have refrained from doing so. Secondary outcome measures were the participants' general experience of and trust in healthcare.

Results

Official complaints have been filed by 23 respondents (2.7%, 95% CI 1.7% to 3.7%), while 159 (18.5%, 95% CI 15.9% to 21.1%) stated that they have had legitimate reasons to file a complaint but have abstained (p<0.001). The degree of under-reporting was greater among patients with a general negative experience of healthcare (37.3%, 95% CI 31.9% to 42.7%) compared with those with a general positive experience (4.8%, 95% CI 2.4% to 7.2%). The reasons given for abstaining were, among others, ‘I did not have the strength’, ‘I did not know where to turn’ and ‘It makes no difference anyway’. Respondents with a general negative experience also had lower trust in healthcare.

Conclusions

The authors found a considerable discrepancy between the actual complaint rate and the number of respondents stating that they have had reasons to complain but have abstained. This indicates that in official reports of complaints, the authors only see ‘the tip of an iceberg’.
Cyberknife radiosurgery in treating trigeminal neuralgia
Authors: Lazzara Bryan M , Ortiz Orlando , Bordia Ritu , Witten Matthew R , Haas Jonathan A , Katz Alan J , Brown Jeffrey A
Published: January 2012

Purpose

To assess the short term efficacy of Cyberknife stereotactic radiosurgical treatment of trigeminal neuralgia (TN).

Methods

17 consecutive patients with medically or surgically refractory unilateral TN were treated with Cyberknife radiosurgery. Using superimposed CT cisternogram and MR images, the target segment of the trigeminal nerve was consistently defined as a 6 mm length of nerve approximately 2–3 mm distal to the dorsal root entry zone of the brainstem. A radiosurgical rhizotomy was performed with the Cyberknife utilizing a single collimator to deliver an average maximum dose of 73.06 Gy (range 72.91–73.73) to the target.

Results

Follow-up data were available for 16 of the 17 patients post-treatment (range 1–27 months, average 11.8 months). Overall, 14 of 16 (88%) patients responded favorably with either partial or complete relief of symptomatology. 11 of these patients were successfully free of all pain at some point in their post-treatment course, with seven patients pain free to the last follow-up visit (average 5.0 months, range 1–13 months). Symptoms recurred in four patients, taking place at 3, 7.75, 9 and 18 months after Cyberknife therapy. Only two patients reported side effects. One patient developed a bothersome feathery dysesthesia while the second patient reported a non-bothersome mild jaw hypoesthesia. There were no substantial complications related to stereotactic radiosurgery.

Conclusion

Cyberknife radiosurgery is a viable treatment alternative in patients with TN with competitive efficacy demonstrated in our group of patients while minimizing adverse effects.
Genetic and environmental influences on faecal nematode egg counts of Jamunapari goats in India
Authors: Mandal A. , Sharma D. K. , Roy R.
Published: January 2012

The present study was carried out from 1999 to 2003 to determine the genetic and environmental influences of faecal egg count (FEC), an indicator of host resistance, in adult Jamunapari goats with naturally acquired gastrointestinal nematode parasite infections (predominantly Haemonchus contortus). FEC data on 670 records of Jamunapari goats descended from 54 bucks and 208 does were used in this study. Analyses were carried out by restricted maximum likelihood estimation, fitting an animal model. Four different animal models ignoring or including maternal genetic or permanent environmental effects were fitted. Different environmental effects, that is, sampling year, month and the sex of the animals, significantly (P<0.01) influenced FECs in the goats. Direct heritability estimates were inflated substantially for this trait when maternal effects were ignored. The direct heritability estimates for the trait ranged from 0.11 to 0.16 depending on the model used. Low estimates of maternal heritability (m2 =0.06) and the fraction of variance due to maternal permanent environmental effects (c2 =0.09) for FECs were observed in the present study. The results suggest that direct and permanent environmental maternal effects were important for this trait; however, maternal additive effects had less impact on this trait. These results also indicate that modest rates of genetic progress appear possible for FECs.
Modelling of viscous effects in natural clays
Authors: Clarke S.D. , Hird C.C.
Published: January 2012

A new approach to allow the modelling of the viscous behaviour of natural clay soils, including creep, stress relaxation and the effects of applied strain rate on soil stiffness, has been developed based on the BRICK constitutive model (published by Simpson in 1992). The new model, “strain rate–dependent” (SRD) BRICK, was used in a series of simulations to demonstrate its capabilities in predicting realistic behaviour during one-dimensional compression and undrained triaxial tests in which applied strain rates were varied. Triaxial stress path tests conducted by Gasparre et al. in 2007 to assess the influence of creep, resulting from recent stress history, on soil stiffness were also simulated. The observed trends concerning the stiffness at small strains were successfully modelled.
Design of shallow footings on heavily overconsolidated clays
Authors: Budhu Muniram
Published: January 2012

This paper presents an integrated bearing capacity–settlement approach to the design of shallow foundations on heavily overconsolidated clays by alterations of the “modified Cam clay” (MCC) model. The bearing capacity of soils and their settlements from loads imposed on shallow footings have been studied extensively. Yet, there is no consensus on a method that provides both reliable load-bearing capacity and settlement predictions. Current methods treat the soil under shallow footings as different ideal materials for the purpose of calculating the bearing capacity and settlement. The method proposed in this paper treats the soil as a single ideal material for both bearing capacity and settlement. The MCC model is tailored by adding Hvorslev’s findings on overconsolidated clays and delineating stress states that bring the soil to tensile failure from those that cause it to yield or behave elastically or to show discontinuous response. A limiting stress surface is established as defining a limiting bearing capacity. A heavily overconsolidated clay is assumed to behave elastically if its stress state is below the limiting stress surface. Predictions from the method proposed in this paper compare favorably with model tests and field test results. Examples are provided illustrating how to use the proposed method.
Influence of thermomechanics in the catastrophic collapse of planar landslides
Authors: Cecinato Francesco , Zervos Antonis
Published: January 2012

Frictional heating has long been considered a mechanism responsible for the high velocities and long run-out of some large-scale landslides. In this work a landslide model is presented, applicable to large-scale planar landslides occurring in a coherent fashion. The model accounts for temperature rise in the slip zone due to the heat produced by friction, leading to water expansion, thermoplastic collapse of the soil skeleton, and subsequently to an increase of pore-water pressure. The landslide model, comprising equations that describe heat and pore pressure diffusion and the dynamics of the moving mass, is used to analyse the evolution of the Jiufengershan planar landslide as an example. Further, its parameter space is systematically and efficiently explored using a Taguchi parametric analysis in an attempt to quantify dominant parameters. It is shown that the process of sliding is dominated by the softening properties of the material, as expected, but also by the permeability of the slip zone and the thickness of the sliding mass. It is worth noting that the latter two parameters do not enter traditional stability analyses of uniform slopes.
Effects of current suction ratio and recent suction history on small-strain behaviour of an unsaturated soil
Authors: Ng C.W.W. , Xu J.
Published: January 2012

Although the small-strain shear modulus of saturated soils is known to be significantly affected by stress history, consisting of the overconsolidation ratio (OCR) and recent stress history, the effects of suction history on the small-strain shear modulus of unsaturated soils have rarely been reported. In this study, the effects of suction history, which refers to current suction ratio (CSR) and recent suction history, on both the very-small-strain shear modulus (G0) and shear modulus reduction curve of an unsaturated soil, are investigated by carrying out constant net mean stress compression triaxial tests with bender elements and local strain measurements. In addition, the effect of suction magnitude on G0and the shear modulus reduction curve is also investigated. At a given suction, G0, elastic threshold strain (εe), and the rate of shear modulus reduction all increase with CSR. On the other hand, the effect of recent suction history on G0is not significant. The effect of direction of recent suction path (θ) on the shear modulus reduction curve is not distinct. However, the magnitude of recent suction path (l) affects the shear modulus reduction curve significantly when θ = –90°.
EXPERIMENTAL EVALUATION OF CARTESIAN AND JOINT IMPEDANCE CONTROL WITH ADAPTIVE FRICTION COMPENSATION FOR THE DEXTEROUS ROBOT HAND DLR-HIT II
Authors: CHEN ZHAOPENG , LII NEAL Y. , WIMBÖCK THOMAS , FAN SHAOWEI , LIU HONG
Published: January 2012

This paper presents impedance controllers with adaptive friction compensation for the five-finger dexterous robot hand DLR-HIT II in both joint and Cartesian space. An FPGA-based control hardware and software architecture with real-time communication is designed to fulfill the requirements of the impedance controller. Modeling of the robot finger with flexible joints and mechanical couplings in the differential gear-box are described in this paper. In order to address the friction due to the complex transmission system and joint coupling, an adaptive model-based friction estimation method is carried out with an extended Kalman filter. The performance of the impedance controller with both adaptive and parameter-fixed friction compensations for the robot hand DLR-HIT II are analyzed and compared in this paper. Furthermore, gravity estimation is implemented with Least Squares technique to address uncertainties in gravity compensation due to the close proximity and complexity of robot hand components. Experimental results prove that accurate position tracking and stable torque/force response can be achieved with the proposed impedance controller with friction compensation on five-finger dexterous robot hand DLR-HIT II.
CHARACTERISTICS OF THE ROBOTIC JOINT OF A 9-DOF UPPER LIMB REHABILITATION ROBOT DRIVEN BY PNEUMATIC MUSCLES
Authors: JIANG XIAN-ZHI , XIONG CAI-HUA , SUN RONG-LEI , XIONG YOU-LUN
Published: January 2012

This paper presents a wearable exoskeleton upper limb rehabilitation robot that consists of eight active joints and one passive joint. Each active joint is driven by two pneumatic muscles (PMs) in opposing pair configuration and each PM drives the joint through a steel wire with a flexible sleeve and a tension device. These factors incorporate with characteristics of PM make the rehabilitation robot system very complex (nonlinear, time-varying, and time-delay). In this paper, the friction force and characteristics of open-loop control of one of the robotic joints has been studied. The quasi-static model of the robotic joint have been established based on experimental methods. In addition, the performances of three control modes have also been researched. These works would be helpful to the future work such as the control of the rehabilitation robot.
EFFICIENT GRASP PLANNING WITH REACHABILITY ANALYSIS
Authors: XUE ZHIXING , DILLMANN RUEDIGER
Published: January 2012

Grasping can be seen as two steps: placing the hand at a grasping pose and closing the fingers. In this paper, we introduce an efficient algorithm for grasping pose generation. By the use of preshaping and eigen-grasping actions, the dimension of the space of possible hand configurations is reduced. The object to be grasped is decomposed into boxes of a discrete set of different sizes. By performing finger reachability analysis on the boxes, the kinematic feasibility of a grasp can be determined. If a reachable grasp is force-closure and can be performed by the robotic arm, its grasping forces are optimized and can be executed. The novelty of our algorithm is that it takes into account both the object geometrical information and the kinematic information of the hand to determine the grasping pose, so that a reachable grasping pose can be found very quickly. Real experiments with two different robotic hands show the efficiency and feasibility of our method.
LENGTHS OF SIMPLE PERIODIC GEODESICS ON TWO-DIMENSIONAL RIEMANNIAN SPHERES
Authors: NABUTOVSKY ALEXANDER , ROTMAN REGINA
Published: January 2012

Let M be a Riemannian two-sphere. A classical result of Lyusternik–Shnirelman asserts the existence of three distinct simple nontrivial periodic geodesics on M. In this paper, we will prove that the lengths of two of them do not exceed 5d and 10d respectively, where d is the diameter of M.
EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic carcinogen dimethylhydrazine
Authors: Nautiyal Jyoti , Du Jianhua , Yu Yingjie , Kanwar Shailender S. , Levi Edi , Majumdar Adhip P. N.
Published: January 2012

One of the most consistent pathological conditions in the gastrointestinal tract with advancing age is malignancy, particularly gastrointestinal cancers, the incidence of which increases sharply with aging. Although the reasons for the age-related rise in colorectal cancer are not fully understood, we hypothesize that aging increases susceptibility of the colon to carcinogen(s)/toxicant(s), leading to an increase in cancer stem-like cells (CSLCs) that express cancer stem cell markers, in the colonic mucosa. The current study demonstrates that aging is associated with increased expression of several colon CSLC markers [CD44, CD166, and aldehyde dehydrogenase 1 (ALDH-1)] and a higher proportion of cells expressing these markers. Aging is also accompanied by increased expression of miR-21 in colon. These increases are further increased in response to the colonic carcinogen dimethylhydrazine (DMH). Aging is also associated with increased tyrosine-phosphorylated epidermal growth factor receptor (EGFR). Inhibition of EGFR using the EGFR inhibitor cetuximab abrogated the age-related increase in CD166 and ALDH-1 as well as miRNA (miR)-21. Our results provide new evidence that aging and DMH are associated with increases in CSLC biomarkers and miR21, each of which have been linked to colorectal cancer. EGFR inhibition attenuates these changes, indicating a role for EGFR in age- and mutagen-associated changes in CSLCs.
Development aggravates the severity of skeletal muscle catabolism induced by endotoxemia in neonatal pigs
Authors: Orellana Renán A. , Suryawan Agus , Wilson Fiona A. , Gazzaneo María C. , Fiorotto Marta L. , Nguyen Hanh V. , Davis Teresa A.
Published: January 2012

Accretion rates of muscle protein are elevated in normal neonates, but this anabolic drive decreases with maturation. As this change occurs, it is not known whether development also influences muscle protein catabolism induced by sepsis. We hypothesize that protein degradation in skeletal muscle induced by endotoxemia becomes more severe as the neonate develops. Fasted 7- and 26-day-old pigs were infused for 8 h with LPS (0 and 10 μg·kg−1·h−1), while plasma amino acids (AA), 3-methylhistidine (3-MH), and α-actin concentrations and muscle protein degradation signal activation were determined ( n = 5–7/group/age). Plasma full-length α-actin was greater in 7- than 26-day-old pigs, suggesting a higher baseline protein turnover in neonatal pigs. LPS increased plasma total AA, 3-MH, and full-length and cleaved α-actin in 26- than in 7-day-old pigs. In muscle of both age groups, LPS increased AMPK and NF-κB phosphorylation, the abundances of activated caspase 3 and E-3 ligases MuRF1 and atrogin1, as well as the abundance of cleaved α-actin, suggesting activation of muscle proteolysis by endotoxin in muscle. LPS decreased Forkhead box 01 (Fox01) and Fox04 phosphorylation and increased procaspase 3 abundance in muscle of 26-day-old pigs despite the lack of effect of LPS on PKB phosphorylation. The results suggest that skeletal muscle in healthy neonatal pigs maintains high baseline degradation signal activation that cannot be enhanced by endotoxin, but as maturation advances, the effect of LPS on muscle protein catabolism manifests its severity.
Regulation of renin expression by the orphan nuclear receptors Nr2f2 and Nr2f6
Authors: Weatherford Eric T. , Liu Xuebo , Sigmund Curt D.
Published: January 2012

Understanding the transcriptional mechanisms of renin expression is key to understanding the regulation of the renin-angiotensin system. We previously identified the nuclear receptors RAR/RXR and Nr2f6 (EAR2) as positive and negative transcriptional regulators of renin expression, respectively (Liu X, Huang X, Sigmund CD. Circ Res 92: 1033–1040, 2003). Both mediate their effects through a hormone response element (HRE) within the renin enhancer. Here, we determined whether another nuclear receptor, Nr2f2 (Coup-TFII, Arp-1), identified in a screen of proteins that bind the HRE, also regulates renin expression. Luciferase assays indicate that Nr2f2 negatively regulates the renin promoter more potently than Nr2f6. Gel-shift and chromatin immunoprecipitation (ChIP) indicate that Nr2f2 and Nr2f6 can bind directly to the renin enhancer through the HRE. Surprisingly, baseline expression of endogenous renin was not effected when Nr2f2 was knocked down in As4.1 cells, whereas knockdown of Nr2f6 increased renin expression twofold. Interestingly, however, knockdown of Nr2f2 augmented the induction of renin expression caused by retinoic acid. These data indicate that both Nr2f6 and Nr2f2 can negatively regulate the renin promoter, under baseline conditions and in response to physiological queues, respectively. Therefore, Nr2f2 may require an initiating signal that results in a change at the chromatin level or activation of another transcription factor to exert its effects. We conclude that both Nr2f2 and Nr2f6 negatively regulate renin promoter activity, but may do so by divergent mechanisms.
Robustness of muscle synergies underlying three-dimensional force generation at the hand in healthy humans
Authors: Roh Jinsook , Rymer William Z. , Beer Randall F.
Published: January 2012

Previous studies using advanced matrix factorization techniques have shown that the coordination of human voluntary limb movements may be accomplished using combinations of a small number of intermuscular coordination patterns, or muscle synergies. However, the potential use of muscle synergies for isometric force generation has been evaluated mostly using correlational methods. The results of such studies suggest that fixed relationships between the activations of pairs of muscles are relatively rare. There is also emerging evidence that the nervous system uses independent strategies to control movement and force generation, which suggests that one cannot conclude a priori that isometric force generation is accomplished by combining muscle synergies, as shown in movement control. In this study, we used non-negative matrix factorization to evaluate the ability of a few muscle synergies to reconstruct the activation patterns of human arm muscles underlying the generation of three-dimensional (3-D) isometric forces at the hand. Surface electromyographic (EMG) data were recorded from eight key elbow and shoulder muscles during 3-D force target-matching protocols performed across a range of load levels and hand positions. Four synergies were sufficient to explain, on average, 95% of the variance in EMG datasets. Furthermore, we found that muscle synergy composition was conserved across biomechanical task conditions, experimental protocols, and subjects. Our findings are consistent with the view that the nervous system can generate isometric forces by assembling a combination of a small number of muscle synergies, differentially weighted according to task constraints.
Determinants of synaptic strength vary across an axon arbor
Authors: Peng Xiaoyu , Parsons Thomas D. , Balice-Gordon Rita J.
Published: January 2012

We used synaptophysin-pHluorin expressed in hippocampal neurons to address how functional properties of terminals, namely, evoked release, total vesicle pool size, and release fraction, vary spatially across individual axon arbors. Consistent with previous reports, over short arbor distances (∼100 μm), evoked release was spatially heterogeneous when terminals contacted different postsynaptic dendrites or neurons. Regardless of the postsynaptic configuration, the evoked release and total vesicle pool size spatially covaried, suggesting that the fraction of synaptic vesicles available for release (release fraction) was similar over short distances. Evoked release and total vesicle pool size were highly correlated with the amount of NMDA receptors and PSD-95 in postsynaptic specialization. However, when individual axons were followed over longer distances (several hundred micrometers), a significant increase in evoked release was observed distally that was associated with an increased release fraction in distal terminals. The increase in distal release fraction can be accounted for by changes in individual vesicle release probability as well as readily releasable pool size. Our results suggest that for a single axon arbor, presynaptic strength indicated by evoked release over short distances is correlated with heterogeneity in total vesicle pool size, whereas over longer distances presynaptic strength is correlated with the spatial modulation of release fraction. Thus the mechanisms that determine synaptic strength differ depending on spatial scale.
Examining protection from anoxic depolarization by the drugs dibucaine and carbetapentane using whole cell recording from CA1 neurons
Authors: White Sean H. , Brisson C. Devin , Andrew R. David
Published: January 2012

As an immediate consequence of stroke onset, failure of the Na+-K+-ATPase pump evokes a propagating anoxic depolarization (AD) across gray matter. Acute neuronal swelling and dendritic beading arise within seconds in the future ischemic core, imaged as changes in light transmittance (ΔLT). AD is itself not a target for drug-based reduction of stroke injury because it is generated in the 1st min of stroke onset. Peri-infarct depolarizations (PIDs) are milder AD-like events that recur during the hours following AD and contribute to infarct expansion. Inhibiting PIDs with drugs could limit expansion. Two types of drugs, “caines” and σ1-receptor ligands, have been found to inhibit AD onset (and may also oppose PID initiation), yet their underlying actions have not been examined. Imaging ΔLT in the CA1 region simultaneously with whole cell current-clamp recording from CA1 pyramidal neurons reveal that the elevated LT front and onset of the AD are coincident. Either dibucaine or carbetapentane pretreatment significantly delays AD onset without affecting resting membrane potential or neuronal input resistance. Dibucaine decreases excitability by raising spike threshold and decreasing action potential (AP) frequency, whereas carbetapentane eliminates the fast afterhyperpolarization while accentuating the slow afterhyperpolarization to reduce AP frequency. Orthodromic and antidromic APs are eliminated by dibucaine within 15 min but not by carbetapentane. Thus both drugs reduce cortical excitability at the level of the single pyramidal neuron but through strikingly different mechanisms. In vivo, both drugs would likely inhibit recurring PIDs in the expanding penumbra and so potentially could reduce developing neuronal damage over many hours poststroke when PIDs occur.
Corticomuscular coherence during bilateral isometric arm voluntary activity in healthy humans
Authors: Perez Monica A. , Soteropoulos Demetris S. , Baker Stuart N.
Published: January 2012

Bilateral voluntary contractions involve functional changes in both primary motor cortices. We investigated whether a voluntary contraction controlled by one hemisphere can influence oscillatory processes contralaterally. Corticomuscular coherence was calculated between EEG recorded over the motor cortex hand representation and electromyogram from the first dorsal interosseous muscle when the nondominant hand performed a precision grip task. The dominant arm remained at rest or performed a finger abduction or an elbow flexion task at 10, 40, and 70% of maximal isometric voluntary contraction (MVC). Mean coherence in the 15- to 30-Hz range in the hand performing a precision grip increased during 40% (by 72%) and 70% (by 73%) but not during 10% of MVC in the finger abduction task. Similarly, in the elbow flexion task, mean coherence increased during 40% (by 40%) and 70% (by 48%) but not during 10% of MVC. No differences were observed between the increments in coherence between the finger abduction and elbow flexion tasks at a given force level. We speculate that these results reflect the increased complexity of controlling a fine motor task with one hand while performing a strong contraction with the contralateral hand and suggest that increased oscillatory corticomuscular coupling may contribute to successful task performance.
Mechanisms underlying intensity-dependent changes in cortical selectivity for frequency-modulated sweeps
Authors: Razak K. A.
Published: January 2012

Frequency-modulated (FM) sweeps are common components of species-specific vocalizations. The intensity of FM sweeps can cover a wide range in the natural environment, but whether intensity affects neural selectivity for FM sweeps is unclear. Bats, such as the pallid bat, which use FM sweeps for echolocation, are suited to address this issue, because the intensity of echoes will vary with target distance. In this study, FM sweep rate selectivity of pallid bat auditory cortex neurons was measured using downward sweeps at different intensities. Neurons became more selective for FM sweep rates present in the bat's echolocation calls as intensity increased. Increased selectivity resulted from stronger inhibition of responses to slower sweep rates. The timing and bandwidth of inhibition generated by frequencies on the high side of the excitatory tuning curve [sideband high-frequency inhibition (HFI)] shape rate selectivity in cortical neurons in the pallid bat. To determine whether intensity-dependent changes in FM rate selectivity were due to altered inhibition, the timing and bandwidth of HFI were quantified at multiple intensities using the two-tone inhibition paradigm. HFI arrived faster relative to excitation as sound intensity increased. The bandwidth of HFI also increased with intensity. The changes in HFI predicted intensity-dependent changes in FM rate selectivity. These data suggest that neural selectivity for a sweep parameter is not static but shifts with intensity due to changes in properties of sideband inhibition.
The accuracy of membrane potential reconstruction based on spiking receptive fields
Authors: Mohanty Deepankar , Scholl Benjamin , Priebe Nicholas J.
Published: January 2012

A common technique used to study the response selectivity of neurons is to measure the relationship between sensory stimulation and action potential responses. Action potentials, however, are only indirectly related to the synaptic inputs that determine the underlying, subthreshold, response selectivity. We present a method to predict membrane potential, the measurable result of the convergence of synaptic inputs, based on spike rate alone and then test its utility by comparing predictions to actual membrane potential recordings from simple cells in primary visual cortex. Using a noise stimulus, we found that spike rate receptive fields were in precise correspondence with membrane potential receptive fields ( R2 = 0.74). On average, spike rate alone could predict 44% of membrane potential fluctuations to dynamic noise stimuli, demonstrating the utility of this method to extract estimates of subthreshold responses. We also found that the nonlinear relationship between membrane potential and spike rate could also be extracted from spike rate data alone by comparing predictions from the noise stimulus with the actual spike rate. Our analysis reveals that linear receptive field models extracted from noise stimuli accurately reflect the underlying membrane potential selectivity and thus represent a method to generate estimates of the underlying average membrane potential from spike rate data alone.
Joubert Syndrome Presenting with Motor Delay and Oculomotor Apraxia
Authors: Gill Harjinder , Muthusamy Brinda , Atan Denize , Williams Cathy , Ellis Matthew
Published: January 2012

We describe two sisters who presented in early childhood with motor delay and unusual eye movements. Both demonstrated hypotonia and poor visual attention. The older girl at 14 weeks of age showed fine pendular horizontal nystagmus more pronounced on lateral gaze, but despite investigation with cranial MRI no diagnosis was reached. The birth of her younger sister four years later with a similar presentation triggered review of the sisters’ visual behaviour. Each had developed an unusual but similar form of oculomotor apraxia (OMA) with head thrusts tomaintainfixation rather than tochangefixation. MRI of the older sibling demonstrated the characteristic “molar tooth sign” (MTS) of Joubert syndrome which was subsequently confirmed on MRI in the younger sibling. We discuss the genetically heterogeneous ciliopathies now grouped as Joubert syndrome and Related Disorders. Clinicians need to consider this group of disorders when faced with unusual eye movements in the developmentally delayed child.