bluuebunny/crossref_metadata_2025 huggingface dataset:
Lentivector Knockdown of CCR5 in Hematopoietic Stem and Progenitor Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice
Authors: Myburgh Renier , Ivic Sandra , Pepper Michael S. , Gers-Huber Gustavo , Li Duo , Audigé Annette , Rochat Mary-Aude , Jaquet Vincent , Regenass Stephan , Manz Markus G. , Salmon Patrick , Krause Karl-Heinz , Speck Roberto F.
Published: April 2015

Gene-engineered CD34
+
hematopoietic stem and progenitor cells (HSPCs) can be used to generate an HIV-1-resistant immune system. However, a certain threshold of transduced HSPCs might be required for transplantation into mice for creating an HIV-resistant immune system. In this study, we combined CCR5 knockdown by a highly efficient microRNA (miRNA) lentivector with pretransplantation selection of transduced HSPCs to obtain a rather pure population of gene engineered CD34
+
cells. Low-level transduction of HSPCs and subsequent sorting by flow cytometry yielded >70% transduced cells. Mice transplanted with these cells showed functional and persistent resistance to a CCR5-tropic HIV strain: viral load was significantly decreased over months, and human CD4
+
T cells were preserved. In one mouse, viral mutations, resulting presumably in a CXCR4-tropic strain, overcame HIV resistance. Our results suggest that HSPC-based CCR5 knockdown may lead to efficient control of HIV
in vivo
. We overcame a major limitation of previous HIV gene therapy in humanized mice in which only a proportion of the cells in chimeric mice
in vivo
are anti-HIV engineered. Our strategy underlines the promising future of gene engineering HIV-resistant CD34
+
cells that produce a constant supply of HIV-resistant progeny.

IMPORTANCE
Major issues in experimental long-term
in vivo
HIV gene therapy have been (i) low efficacy of cell transduction at the time of transplantation and (ii) transduction resulting in multiple copies of heterologous DNA in target cells. In this study, we demonstrated the efficacy of a transplantation approach with a selection step for transduced cells that allows transplantation of an enriched population of HSPCs expressing a single (low) copy of a CCR5 miRNA. Efficient maintenance of CD4
+
T cells and a low viral titer resulted only when at least 70% of the HIV target cells were genetically modified. These findings imply that clinical protocols of HIV gene therapy require a selective enrichment of genetically targeted cells because positive selection of modified cells is likely to be insufficient below this threshold. This selection approach may be beneficial not only for HIV patients but also for other patients requiring transplantation of genetically modified cells.
Deciphering Poxvirus Gene Expression by RNA Sequencing and Ribosome Profiling
Authors: Yang Zhilong , Cao Shuai , Martens Craig A. , Porcella Stephen F. , Xie Zhi , Ma Ming , Shen Ben , Moss Bernard
Published: April 2015

The more than 200 closely spaced annotated open reading frames, extensive transcriptional read-through, and numerous unpredicted RNA start sites have made the analysis of vaccinia virus gene expression challenging. Genome-wide ribosome profiling provided an unprecedented assessment of poxvirus gene expression. By 4 h after infection, approximately 80% of the ribosome-associated mRNA was viral. Ribosome-associated mRNAs were detected for most annotated early genes at 2 h and for most intermediate and late genes at 4 and 8 h. Cluster analysis identified a subset of early mRNAs that continued to be translated at the later times. At 2 h, there was excellent correlation between the abundance of individual mRNAs and the numbers of associated ribosomes, indicating that expression was primarily transcriptionally regulated. However, extensive transcriptional read-through invalidated similar correlations at later times. The mRNAs with the highest density of ribosomes had host response, DNA replication, and transcription roles at early times and were virion components at late times. Translation inhibitors were used to map initiation sites at single-nucleotide resolution at the start of most annotated open reading frames although in some cases a downstream methionine was used instead. Additional putative translational initiation sites with AUG or alternative codons occurred mostly within open reading frames, and fewer occurred in untranslated leader sequences, antisense strands, and intergenic regions. However, most open reading frames associated with these additional translation initiation sites were short, raising questions regarding their biological roles. The data were used to construct a high-resolution genome-wide map of the vaccinia virus translatome.

IMPORTANCE
This report contains the first genome-wide, high-resolution analysis of poxvirus gene expression at both transcriptional and translational levels. The study was made possible by recent methodological advances allowing examination of the translated regions of mRNAs including start sites at single-nucleotide resolution. Vaccinia virus ribosome-associated mRNA sequences were detected for most annotated early genes at 2 h and for most intermediate and late genes at 4 and 8 h after infection. The ribosome profiling approach was particularly valuable for poxviruses because of the close spacing of approximately 200 open reading frames and extensive transcriptional read-through resulting in overlapping mRNAs. The expression of intermediate and late genes, in particular, was visualized with unprecedented clarity and quantitation. We also identified novel putative translation initiation sites that were mostly associated with short protein coding sequences. The results provide a framework for further studies of poxvirus gene expression.
Multifunctionality of a Picornavirus Polymerase Domain: Nuclear Localization Signal and Nucleotide Recognition
Authors: Ferrer-Orta Cristina , de la Higuera Ignacio , Caridi Flavia , Sánchez-Aparicio María Teresa , Moreno Elena , Perales Celia , Singh Kamalendra , Sarafianos Stefan G. , Sobrino Francisco , Domingo Esteban , Verdaguer Nuria
Published: April 2015

The N-terminal region of the foot-and-mouth disease virus (FMDV) 3D polymerase contains the sequence MRKTKLAPT (residues 16 to 24) that acts as a nuclear localization signal. A previous study showed that substitutions K18E and K20E diminished the transport to the nucleus of 3D and 3CD and severely impaired virus infectivity. These residues have also been implicated in template binding, as seen in the crystal structures of different 3D-RNA elongation complexes. Here, we report the biochemical and structural characterization of different mutant polymerases harboring substitutions at residues 18 and 20, in particular, K18E, K18A, K20E, K20A, and the double mutant K18A K20A (KAKA). All mutant enzymes exhibit low RNA binding activity, low processivity, and alterations in nucleotide recognition, including increased incorporation of ribavirin monophosphate (RMP) relative to the incorporation of cognate nucleotides compared with the wild-type enzyme. The structural analysis shows an unprecedented flexibility of the 3D mutant polymerases, including both global rearrangements of the closed-hand architecture and local conformational changes at loop β9-α11 (within the polymerase motif B) and at the template-binding channel. Specifically, in 3D bound to RNA, both K18E and K20E induced the opening of new pockets in the template channel where the downstream templating nucleotide at position +2 binds. The comparisons of free and RNA-bound enzymes suggest that the structural rearrangements may occur in a concerted mode to regulate RNA replication, processivity, and fidelity. Thus, the N-terminal region of FMDV 3D that acts as a nuclear localization signal (NLS) and in template binding is also involved in nucleotide recognition and can affect the incorporation of nucleotide analogues.

IMPORTANCE
The study documents multifunctionality of a nuclear localization signal (NLS) located at the N-terminal region of the foot-and-mouth disease viral polymerase (3D). Amino acid substitutions at this polymerase region can impair the transport of 3D to the nucleus, reduce 3D binding to RNA, and alter the relative incorporation of standard nucleoside monophosphate versus ribavirin monophosphate. Structural data reveal that the conformational changes in this region, forming part of the template channel entry, would be involved in nucleotide discrimination. The results have implications for the understanding of viral polymerase function and for lethal mutagenesis mechanisms.
Intrinsic motivation of preclinical medical students participating in high-fidelity mannequin simulation
Authors: Thoma Brent , Hayden Emily M , Wong Nelson , Sanders Jason L , Malin Greg , Gordon James A
Published: April 2015

Introduction

While medical schools strive to foster students’ lifelong learning, motivational theories have not played an explicit role in curricular design. Self-determination Theory is a prominent motivational theory. It posits that perceived autonomy, competence and relatedness foster intrinsic motivation. This study explores the effects of autonomy on intrinsic motivation in medical students participating in high-fidelity mannequin simulation.

Methods

A non-randomised crossover trial compared first-year medical students participating in (1) required simulation sessions with predetermined learning objectives and (2) extracurricular simulation sessions with student-directed learning objectives. An adapted Intrinsic Motivation Inventory (IMI) was used to assess intrinsic motivation, perceived autonomy, competence and relatedness. Each participant completed the IMI survey after each type of session. Variables were compared with signed-rank tests.

Results

All 22 participants completed the IMI after both types of session. Perceived autonomy was significantly higher during extracurricular simulation (p<0.001), but intrinsic motivation, competence and relatedness were not. Intrinsic motivation correlated with autonomy (RS=0.57 and extracurricular simulation, ES=0.52), competence (RS=0.46 and ES=0.15) and relatedness (RS=0.51 and ES=0.64). The IMI subscales had good internal consistency (Cronbach's α=0.84, 0.90, 0.90 and 0.76 for intrinsic motivation, autonomy, competence and relatedness, respectively).

Conclusions

Extracurricular sessions increased students’ perceived autonomy, but they were highly intrinsically motivated in both settings. Further study is needed to understand the relationship between perceived autonomy and intrinsic motivation in medical education learning activities. The IMI shows promise as a measurement tool for this work.
Travel health and pretravel preparation in the patient with inflammatory bowel disease
Authors: Greveson Kay , Shepherd Thomas , Mulligan John P , Hamilton Mark , Woodward Sue , Norton Christine , Murray Charles
Published: April 2015

Background and aims

Foreign travel for people with inflammatory bowel disease (IBD) carries an increased risk of travel-related morbidity. There is limited research looking specifically at travel-associated health risks and travel preparation in patients with IBD. The aims of this study are to explore the experience of travel, pretravel preparation undertaken by the patient with IBD and examine IBD healthcare professionals’ (HCP) confidence at providing travel advice and the content of that advice.

Methods

A survey of patients with IBD attending an outpatient clinic with a separate online survey sent to IBD HCPs recruited using regional and international network databases.

Results

A total of 132 patients with IBD, Crohn's disease (67/132, 51%), male (60/132, 45%) and 128 HCPs (IBD nurse specialist 113, 88%; IBD physician 15, 12%) completed the questionnaires. IBD affected travel to some extent in 62% (82/132) of patients, and 64% (84/132) had experienced an IBD flare, of whom 64% still travelled overseas during this time. Only 23% (31/132) travellers sought pretravel medical advice and 40% (53/132) obtained travel insurance. Forty-eight per cent of respondents on immunomodulator therapy were unaware of the need to avoid live vaccines. Twenty-seven per cent (34/128) of IBD HCPs are not confident at providing pretravel advice; vaccination advice (54%), obtaining travel insurance (61%) and healthcare abroad (78%) are the areas of most uncertainty.

Conclusions

Patients do not seek adequate pretravel advice and consultations for those who do are often deficient. The majority of IBD professionals are not confident to provide comprehensive travel advice. Greater IBD-specific travel education and awareness is needed for both patients with IBD and professionals.
Disease-related pregnancy concerns and reproductive planning in women with inflammatory bowel diseases
Authors: Gawron Lori M , Goldberger Adina R , Gawron Andrew J , Hammond Cassing , Keefer Laurie
Published: April 2015

Background

Women with inflammatory bowel diseases (IBD) endorse disease-related pregnancy concerns that influence parity. Improvements in IBD management have potentially altered reproductive planning. Additionally, the proportion of American women who choose not to have children is increasing.

Aim

To explore the effect of disease-related pregnancy concerns on parity and reproductive planning in a subset of women with IBD.

Design and setting

Cross-sectional qualitative phone survey in an academic gastroenterology practice.

Methods

Questions included demographics, medical and reproductive history, future pregnancy plans, and if IBD affected pregnancy decision-making. Qualitative data were coded and frequencies and proportions calculated.

Results

The 129 female participants (31% response rate) were predominately white (85%), had at least some college education (97%) and a mean age of 34.3 years [standard deviation 6.2]. Some 60% had Crohn's disease and 30% had undergone IBD-related surgery. Half were nulliparae, 53% reported IBD-related pregnancy concerns and 57% desired future pregnancy. Women who desired a future pregnancy and had IBD-related concerns had higher parity than those without concerns (p=0.02). Women desiring a future pregnancy and those with Crohn's disease had increased IBD-related concerns. Only four (3.1%) women identified IBD-related concerns that led to a smaller family size than desired.

Conclusions

IBD-related concerns appear to be less likely to affect a woman's planned family size than previously reported. Concern about adverse pregnancy outcomes is more common in women with Crohn's disease and those desiring future pregnancy, suggesting a need for targeted counselling to moderate risk perception.
Welfare in horse breeding
Authors: Campbell M. L. H. , Sandøe P.
Published: April 2015

Welfare problems related to the way horses are bred, whether by coitus or by the application of artificial reproduction techniques (ARTs), have been given no discrete consideration within the academic literature. This paper reviews the existing knowledge base about welfare issues in horse breeding and identifies areas in which data is lacking. We suggest that all methods of horse breeding are associated with potential welfare problems, but also that the judicious use of ARTs can sometimes help to address those problems. We discuss how negative welfare effects could be identified and limited and how positive welfare effects associated with breeding might be maximised. Further studies are needed to establish an evidence base about how stressful or painful various breeding procedures are for the animals involved, and what the lifetime welfare implications of ARTs are for future animal generations.
Shoot apical meristem ontogeny inArabidopsisembryo explants treated with abscisic acid
Authors: Paulraj Subramanian , Lopez-Villalobos Arturo , Yeung Edward C.
Published: April 2015

The formation of meristemoids and the ontogeny of the shoot apical meristem (SAM) were studied using cultured zygotic embryos of Arabidopsis thaliana (L.) Heynh. LER ecotype. In the callus induction treatment, the procambial cells within the cotyledons of the embryo explants proliferated and gave rise to callus tissues. At the end of the treatment, a band of small cytoplasmic-rich cells derived from the procambium was produced and located at the outer surface of the callus. Upon transfer to the shoot induction medium (SIM) in the absence of abscisic acid (ABA), the cytoplasmic cells differentiated mainly into vascular elements and vacuolated parenchyma cells. This pattern of development negatively affected the explants’ ability to produce meristemoids and SAMs. Contrary to the control, the inclusion of ABA in the SIM resulted first in starch synthesis and accumulation in the surface cytoplasmic cells. This was followed by the formation of cytoplasmic cells among the starch-rich cells; further proliferation of the cytoplasmic cells resulted in the formation of meristemoids. The formation of tracheary elements was suppressed in the ABA-containing SIM. Upon transferring to the shoot development medium, which lacked plant growth regulators, some meristemoids differentiated into apical meristem cells. These cells had distinct nuclei and nucleoli, with little starch present. Additional cell divisions increased the size of the future SAM. Shoot buds with distinct SAMs were clearly delineated with the appearance of leaf primordia.
Inhibition and compressive-strength performance of Na2Cr2O7and C10H14N2Na2O8·2H2O in steel-reinforced concrete in corrosive environments
Authors: Okeniyi Joshua Olusegun , Oladele Isaac Oluwaseun , Omoniyi Oluwafemi Michael , Loto Cleophas Akintoye , Popoola Abimbola Patricia Idowu
Published: April 2015

This paper studied corrosion-inhibition and compressive-strength performances of Na2Cr2O7(sodium dichromate) and C10H14N2Na2O8·2H2O (ethylenediaminetetraacetic disodium salt: EDTA-Na2) admixtures in steel-reinforced concrete immersed in NaCl and in H2SO4corrosive environments. Electrochemical methods were used for studying corrosion responses of different concentrations of the individual admixtures and their synergies, in the model that partially replace the toxic Na2Cr2O7by the environmentally-friendly C10H14N2Na2O8·2H2O, in steel-reinforced concretes. After the electrochemical experiment, the steel-reinforced concrete samples were subjected to the compressive-strength testing and analyses of ASTM C39/C39M-03 and ASTM C267-01(2012). Results showed that the use of environmentally-friendly EDTA-Na2for partially replacing toxic Na2Cr2O7chemical exhibited better corrosion-inhibition and compressive-strength improvement in the NaCl-immersed concretes, than in the H2SO4-immersed concretes. The 2 g Na2Cr2O7+ 6 g EDTA-Na2admixture (representing partial replacement model of 6 g Na2Cr2O7by 6 g EDTA-Na2) exhibited optimal corrosion inhibition efficiency (η = 99.0%) and very good compressive-strength improvement advantage in the NaCl-immersed concretes. In contrast, comparatively low compressive-strength reduction trade-off with the good inhibition effectiveness of η = 79.9% support use of 6 g EDTA-Na2admixture only (i.e., without Na2Cr2O7addition) for inhibiting reinforcing-steel corrosion in the H2SO4-immersed concretes.
High-order corrections of neutron–neutron scattering cross-section by renormalized hybrid loop-chain propagator in isospin space
Authors: Wen Hao , Li Fangyu , Fang Zhenyun
Published: April 2015

Bottomed on isospin-SU(2) invariant coupling model which describes the strong interaction between pion and nucleon–antinucleon, for the first time the differential cross-section (DCS) of neutron–neutron scattering with renormalized infinite high-order hybrid loop-chain propagators is "strictly" calculated. DCSs between cases of the hybrid loop-chain propagator (HLCP) and the tree propagator are compared, and it shows that the radiative corrections we obtained are mainly less than 0.9 in typical range of parameters. These results may indicate that the utilization of HLCP underlying the effective way towards the enhanced precision would be considerable. The outcomes might contribute to studies on the nucleon collisions and also possible issues of some phenomena in particle astrophysics.
Viscosities of gluon dominated QGP model within relativistic non-Abelian hydrodynamics
Authors: Djun T. P. , Handoko L. T. , Soegijono B. , Mart T.
Published: April 2015

Based on the first principle calculation, a Lagrangian for the system describing quarks, gluons, and their interactions, is constructed. Ascribed to the existence of dissipative behavior as a consequence of strong interaction within quark–gluon plasma (QGP) matter, auxiliary terms describing viscosities are constituted into the Lagrangian. Through a "kind" of phase transition, gluon field is redefined as a scalar field with four-vector velocity inherently attached. Then, the Lagrangian is elaborated further to produce the energy–momentum tensor of dissipative fluid-like system and the equation of motion (EOM). By imposing the law of energy and momentum conservation, the values of shear and bulk viscosities are analytically calculated. Our result shows that, at the energy level close to hadronization, the bulk viscosity is bigger than shear viscosity. By making use of the conjectured values η/s~1/4π and ζ/s~1, the ratio of bulk to shear viscosity is found to be ζ/η>4π.
Four-dimensional gravity as an almost-Poisson system
Authors: Ita Eyo Eyo
Published: April 2015

In this paper, we examine the phase space structure of a noncanonical formulation of four-dimensional gravity referred to as the Instanton representation of Plebanski gravity (IRPG). The typical Hamiltonian (symplectic) approach leads to an obstruction to the definition of a symplectic structure on the full phase space of the IRPG. We circumvent this obstruction, using the Lagrange equations of motion, to find the appropriate generalization of the Poisson bracket. It is shown that the IRPG does not support a Poisson bracket except on the vector constraint surface. Yet there exists a fundamental bilinear operation on its phase space which produces the correct equations of motion and induces the correct transformation properties of the basic fields. This bilinear operation is known as the almost-Poisson bracket, which fails to satisfy the Jacobi identity and in this case also the condition of antisymmetry. We place these results into the overall context of nonsymplectic systems.
Kinodynamically Consistent Motion Retargeting for Humanoids
Authors: Bin Hammam Ghassan , Wensing Patrick M. , Dariush Behzad , Orin David E.
Published: April 2015

Human-to-humanoid motion retargeting is an important tool to generate human-like humanoid motions. This retargeting problem is often formulated as a Cartesian control problem for the humanoid from a set of task points in the captured human data. Classically, Cartesian control has been developed for redundant systems. While redundancy fundamentally adds new sub-task capabilities, the degree to which secondary objectives can be faithfully executed cannot be determined in advance. In fact, a robot that exhibits redundancy with respect to an operational task may have insufficient degrees of freedom (DOFs) to satisfy more critical constraints. In this paper, we present a Cartesian space resolved acceleration control framework to handle execution of operational tasks and constraints for redundant and nonredundant task specifications. The approach is well suited for online control of humanoid robots from captured human motion data expressed by Cartesian variables. The current formulation enforces kinematic constraints such as joint limits, self-collisions, and foot constraints and incorporates a dynamically-consistent redundancy resolution approach to minimize costly joint motions. The efficacy of the proposed algorithm is demonstrated by simulated and real-time experiments of human motion replication on a Honda humanoid robot model. The algorithm closely tracks all input motions while smoothly and automatically transitioning between regimes where different constraints are binding.
Walking Gait of a Biped with a Wearable Walking Assist Device
Authors: Aoustin Yannick
Published: April 2015

A ballistic walking gait is designed for a planar biped equipped with a wearable walking assist device. The biped is a seven-link planar biped with two legs, two feet, and a trunk. The wearable walking assist device is composed of a bodyweight support, two upper legs, two lower legs, and two shoes. The dynamic model of the biped with its walking assist device, containing two closed kinematic chains, is calculated by virtually cutting each of both loops at one of their point. In the single support phase, the biped with its assist device moves due to the existence of a momentum, produced mechanically, without applying active torques in the inter-link joints. The biped and this assist device are controlled with impulsive torques at the instantaneous double support to obtain a cyclic gait. The impulsive torques are applied in the six inter-link joints of the biped and in several inter-link joints of the wearable walking assist device. The following distributions of impulsive torques, in the knees or the ankles, hips and knees, hips and ankles, or knees and ankles and the fully assist device, are compared with the case of no assistance for the biped. Each time, an infinity of solutions exists to find the impulsive torques. An energy cost functional defined from these impulsive torques is minimized to determine a unique solution. Numerical results show that for a given time period and a given length of the walking gait step, the assistance of the hips is a good compromise to help the biped.
A note on the origins of engineering geomorphology in the UK
Authors: Lee E. M. , Fookes P. G.
Published: April 2015

Engineering geomorphology is one of the key services that most major UK consulting engineers provide for their clients. But it was not always the case. In the late 1960s and early 1970s very few engineers were aware of the discipline, and there were no career opportunities for geomorphologists in ground engineering. In the UK, the transformation can be traced directly back to events in south Wales and the Himalayas in the early to mid-1970s, and the pioneering landslide mapping work of a handful of academic physical geographers (Denys Brunsden, David Jones and John Doornkamp). This technical note describes these events.
The late field life of the East Midlands Petroleum Province; a new geothermal prospect?
Authors: Hirst Catherine M. , Gluyas Jon G. , Mathias Simon A.
Published: April 2015

Modification of existing oilfield infrastructure could deliver a cost-effective way to extend the economic life of depleted onshore oilfields. Naturally warm connate and injection water contained within these fields could be initially co-produced with remaining oil reserves and used to deliver clean, cheap, non-intermittent heating. The East Midlands Petroleum Province contains over 30 fields with a production history spanning 95 years, and we have chosen to examine the Welton field in detail. Well data for the Welton field have been analysed to ascertain extractable heat within both oil- and non-oil-bearing (water-bearing) strata within the field. Production rates were calculated to be 728 m
3
 d
−1
oil and 854 m
3
 d
−1
water. These values also include productivity of intervening largely water-bearing intervals. Target formation temperature at 1500 m was determined to be 52.5°C, allowing an extractable heat energy calculation to be undertaken for a range of temperature differentials. For a 30°C depletion in temperature, 1.6 MW
t
extractable heat is available within the Welton field alone. This equates to 14040 MWh of heat energy available for consumption by the domestic market or within commercial greenhouses.
Cavin 1 function does not follow caveolar morphology
Authors: Timmel Tobias , Kunz Séverine , Seifert Franziska , Schuelke Markus , Spuler Simone
Published: April 2015

The function of caveolae, small invaginations of the plasma membrane, remains a matter of debate. We discuss endocytosis and compartmentalization of metabolic and signaling pathways. Caveolin 3 (CAV3) and polymerase I and transcript release factor (PTRF) are important proteins that ensure shaping of caveolae in muscle cells. We investigated caveolae morphologically by electron microscopy in myotubes obtained from patients with CAV3 mutations and performed functional analyses in fibroblasts from a patient with a mutation in PTRF. Despite the complete clinical picture of a caveolinopathy, we found that caveolae in the CAV3-deficient myotubes were normal in shape and number. Furthermore, we found a difference in uptake of cholera toxin B between PTRF-deficient fibroblasts devoid of caveolae and normal fibroblasts. However, after caveolae were rescued by transfection of PTRF, cholera toxin B uptake did not normalize. We conclude that the presence of caveolae as an anatomic structure is not sufficient to ensure their proper function. Alternatively, the functional properties assigned to caveolae might be mediated by different mechanisms that have yet to be resolved.
Melatonin pretreatment of human adipose tissue-derived mesenchymal stromal cells enhances their prosurvival and protective effects on human kidney cells
Authors: Zhao Jing , Young Yoon Kow , Fradette Julie , Eliopoulos Nicoletta
Published: April 2015

The efficacy of cell therapy for many diseases can be limited by the poor survival of implanted cells in an environment of tissue injury. Melatonin has been reported to have antioxidative and antiapoptotic effects. Adipose tissue-derived mesenchymal stromal cells (ASCs), cells easily obtained in high amounts and with minimal discomfort, have shown great promise in cell therapy applications, such as in acute kidney injury. We hypothesized that melatonin pretreatment of human ASCs (hASCs) would improve their renoprotective and prosurvival effects. We therefore investigated the action of melatonin on hASCs, as well as the effect of the resulting hASCs-conditioned media (CM) on human kidney cells exposed to oxidative and apoptotic injury-provoking doses of cisplatin. Our results demonstrated that pretreatment of hASCs with melatonin, 100 μM for 3 h, significantly increased their proliferation and their expression of prosurvival P-Erk1/2 and P-Akt, and of antioxidative enzymes catalase and heme oxygenase (HO)-1. In addition, the CM from hASCs pretreated with melatonin provoked a significantly higher proliferation and migration of HK-2 human kidney epithelial cells. Furthermore, this CM exerted significantly higher prosurvival and antiapoptotic actions on HK-2 cells exposed to cisplatin in vitro. Western blot analysis showed higher expression of P-Erk1/2, Bcl-2, SOD-1, and HO-1 in the HK-2 cells exposed to cisplatin in the presence of CM from melatonin-pretreated hASCs. In sum, our study revealed that in vitro pretreatment of hASCs with melatonin may significantly enhance their survival and their therapeutic effectiveness on injured tissue.
Characteristics of preceding Ia activity on postactivation depression in health and disease
Authors: Tahayori Behdad , Tahayori Bahman , Koceja David
Published: April 2015

Previous activation of the soleus Ia afferents causes a depression in the amplitude of the H-reflex. This mechanism is referred to as postactivation depression (PAD) and is suggested to be presynaptically mediated. With the use of a paired reflex depression paradigm (eliciting two H-reflexes with conditioning-test intervals from 80 ms to 300 ms), PAD was examined in a group of healthy individuals and a group of hemiplegic patients. Healthy individuals showed substantial depression of the test H-reflex at all intervals. Although the patient group showed substantially less depression at all intervals, increasing the interval between the two reflexes sharply reduced the depression. In a separate experiment, we varied the size of the conditioning H-reflex against a constant test H-reflex. In healthy individuals, by increasing the size of the conditioning H-reflex, the amplitude of the test H-reflex exponentially decreased. In the patient group, however, this pattern was dependent on the conditioning-test interval; increasing the size of the conditioning H-reflex caused an exponential decrease in the size of the test reflex at intervals shorter than 150 ms. This pattern was similar to that of healthy individuals. However, conducting the same protocol at a longer interval (300 ms) in these patients resulted in an abnormal pattern (instead of an exponential decrease in the size of the test reflex, exaggerated responses were observed). Fisher discriminant analysis suggested that these two patterns (which differed only in the timing between the two stimuli) were substantially different from each other. Therefore, it is suggested that the abnormal pattern of PAD in hemiplegic stroke patients could be a contributing factor for the pathophysiology of spasticity.
Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord
Authors: Hofstoetter Ursula S. , Danner Simon M. , Freundl Brigitta , Binder Heinrich , Mayr Winfried , Rattay Frank , Minassian Karen
Published: April 2015

In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22–60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5–26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits.
Explicit knowledge enhances motor vigor and performance: motivation versus practice in sequence tasks
Authors: Wong Aaron L. , Lindquist Martin A. , Haith Adrian M. , Krakauer John W.
Published: April 2015

Motor skill learning involves a practice-induced improvement in the speed and/or accuracy of a discrete movement. It is often thought that paradigms involving repetitive practice of discrete movements performed in a fixed sequence result in a further enhancement of skill beyond practice of the individual movements in a random order. Sequence-specific performance improvements could, however, arise without practice as a result of knowledge of the sequence order; knowledge could operate by either enabling advanced motor planning of the known sequence elements or by increasing overall motivation. Here, we examined how knowledge and practice contribute to performance of a sequence of movements. We found that explicit knowledge provided through instruction produced practice-independent improvements in reaction time and execution quality. These performance improvements occurred even for random elements within a partially known sequence, indicative of a general motivational effect rather than a sequence-specific effect of advanced planning. This motivational effect suggests that knowledge influences performance in a manner analogous to reward. Additionally, practice led to similar improvements in execution quality for both known and random sequences. The lack of interaction between knowledge and practice suggests that any skill acquisition occurring during discrete sequence tasks arises solely from practice of the individual movement elements, independent of their order. We conclude that performance improvements in discrete sequence tasks arise from the combination of knowledge-based motivation and sequence-independent practice; investigating this interplay between cognition and movement may facilitate a greater understanding of the acquisition of skilled behavior.
Zinc Transporters and Zinc Signaling: New Insights into Their Role in Type 2 Diabetes
Authors: Myers Stephen A.
Published: April 2015

Zinc is an essential trace element that plays a vital role in many biological processes including growth and development, immunity, and metabolism. Recent studies have highlighted zinc’s dynamic role as a “cellular second messenger” in the control of insulin signaling and glucose homeostasis. Accordingly, mechanisms that contribute to dysfunctional zinc signaling are suggested to be associated with metabolic disease states including cancer, cardiovascular disease, Alzheimer’s disease, and diabetes. The actions of the proteins that control the uptake, storage, and distribution of zinc, the zinc transporters, are under intense investigation due to their emerging role in type 2 diabetes. The synthesis, secretion, and action of insulin are dependent on zinc and the transporters that make this ion available to cellular processes. This suggests that zinc plays a previously unidentified role where changes in zinc status over time may affect insulin activity. This previously unexplored concept would raise a whole new area of research into the pathophysiology of insulin resistance and introduce a new class of drug target with utility for diabetes pharmacotherapy.
Antimycobacterial and HIV-1 Reverse Transcriptase Activity of Julianaceae and Clusiaceae Plant Species from Mexico
Authors: Gómez-Cansino Rocio , Espitia-Pinzón Clara Inés , Campos-Lara María Guadalupe , Guzmán-Gutiérrez Silvia Laura , Segura-Salinas Erika , Echeverría-Valencia Gabriela , Torras-Claveria Laura , Cuevas-Figueroa Xochitl Marisol , Reyes-Chilpa Ricardo
Published: April 2015

The extracts of 14 Julianaceae and 5 Clusiaceae species growing in Mexico were testedin vitro(50 µg/mL) againstMycobacterium tuberculosisH37Rv and HIV reverse transcriptase (HIV-RT). The Julianaceae bark and leaf extracts inhibitedM. tuberculosis(>84.67%) and HIV-RT (<49.89%). The Clusiaceae leaves extracts also inhibited both targets (>58.3% and >67.6%), respectively. The IC50values for six selected extracts and their cytotoxicity (50 µg/mL) to human macrophages were then determined.Amphipterygium glaucum,A. molle, andA. simplicifoliumfairly inhibitedM. tuberculosiswith IC50of 1.87–2.35 µg/mL; but their IC50against HIV-RT was 59.25–97.83 µg/mL.Calophyllum brasiliense,Vismia baccifera, andVismia mexicanaeffect onM. tuberculosiswas noteworthy (IC503.02–3.64 µg/mL) and also inhibited RT-HIV (IC5026.24–35.17 µg/mL). These 6 extracts (50 µg/mL) presented low toxicity to macrophages (<23.8%). The HPLC profiles ofA. glaucum,A. molle, andA. simplicifoliumindicated that their antimycobacterial activity cannot be related to masticadienonic, 3α, or 3β-hydromasticadienonic acids, suggesting that other compounds may be responsible for the observed activity or this might be a synergy result. The anti-HIV-RT and antimycobacterial activities induced byC. brasiliensecan be attributed to the content of calanolides A, B, as well as soulatrolide.
Optimization of Solar Module Encapsulant Lamination by Optical Constant Determination of Ethylene-Vinyl Acetate
Authors: Chen Bing-Mau , Peng Cheng-Yu , Cho Ju-Lu , Porter Glen Andrew
Published: April 2015

This investigation elucidates the physical properties of ethylene-vinyl acetate (EVA) used in the lamination process of module encapsulation and the module performance from the optical transmission to the photoelectric power. In module encapsulation, the effects of the lamination parameters on the module performance, transmittance, and stack adhesion have been considered as they were found to influence the reliability of the module. The determination of the optical constants of EVA may serve as a nondestructive analytical method for optimizing the module encapsulation, on the basis of its effects on the optical transmittance, gel content, peel strength, and performance power.
Obtaining Cross Modal Similarity Metric with Deep Neural Architecture
Authors: Li Ruifan , Feng Fangxiang , Wang Xiaojie , Lu Peng , Li Bohan
Published: April 2015

Analyzing complex system with multimodal data, such as image and text, has recently received tremendous attention. Modeling the relationship between different modalities is the key to address this problem. Motivated by recent successful applications of deep neural learning in unimodal data, in this paper, we propose a computational deep neural architecture, bimodal deep architecture (BDA) for measuring the similarity between different modalities. Our proposed BDA architecture has three closely related consecutive components. For image and text modalities, the first component can be constructed using some popular feature extraction methods in their individual modalities. The second component has two types of stacked restricted Boltzmann machines (RBMs). Specifically, for image modality a binary-binary RBM is stacked over a Gaussian-binary RBM; for text modality a binary-binary RBM is stacked over a replicated softmax RBM. In the third component, we come up with a variant autoencoder with a predefined loss function for discriminatively learning the regularity between different modalities. We show experimentally the effectiveness of our approach to the task of classifying image tags on public available datasets.
A Comprehensive Systems Biological Study of Autophagy-Apoptosis Crosstalk during Endoplasmic Reticulum Stress
Authors: Holczer Marianna , Márton Margita , Kurucz Anita , Bánhegyi Gábor , Kapuy Orsolya
Published: April 2015

One of the most important tasks of a living organism is to maintain its genetic integrity with respect to stress. Endoplasmic reticulum (ER) has a crucial role in sensing cellular homeostasis by controlling metabolism, proteostasis, and several signaling processes. ER stressors can induce autophagy-dependent survival; however excessive level of stress results in apoptotic cell death. Although many molecular components of these networks have already been discovered, the analysis of the dynamical features of the regulatory network of life-or-death decision is still lacking. Our goal was to incorporate both theoretical and molecular biological techniques to explore the autophagy-apoptosis crosstalk under ER stress. Using various levels of different ER stressors we confirmed that the control network always generated an evidently detectable autophagy-dependent threshold for apoptosis activation. We explored the features of this threshold by introducing both autophagy activators and inhibitors, and transient treatment with excessive level of ER stressor was also performed. Our experimental data were also supported by a stochastic approach. Our analysis suggests that even if the switch-like characteristic of apoptosis activation is hardly seen on population level the double negative feedback loop between autophagy and apoptosis inducers introduces bistability in the control network.
DC Characteristics Optimization of a Double G-Shield 50 V RF LDMOS
Authors: Xu Xiangming , Ci Pengliang , Tang Xiaoyu , Shi Jing , Zhou Zhengliang , Huang Jingfeng , Wang Peng-Fei , Zhang David Wei
Published: April 2015

An N-type 50 V RF LDMOS with a RESURF (reduced surface field) structure of dual field plates (grounded shield, or G-shield) was investigated. The effect of the two field plates and N-drift region, including the junction depth and dopant concentration, on the DC characteristics was analyzed by employing the Taurus TCAD device simulator. A high BV (breakdown voltage) can be achieved while keeping a lowRDSON(on-resistance). The simulation results show that the N-drift region dopant concentration has an obvious effect on the BV andRDSONand the junction depth affected these values less. There is an optimized length for the second field plate for a given dopant concentration of the N-drift region. Both factors should be optimized together to determine the best DC characteristics. Meanwhile, the effect of the first field plate on the BV andRDSONcan be ignored. According to the simulation results, 50 V RF LDMOS with an optimized RESURF structure of a double G-shield was fabricated using 0.35 µm technologies. The measurement data show the same trend as the TCAD simulation, where a BV of 118 V andRDSONof 26 ohm·mm were achieved.
Stochastic Fractional Heat Equations Driven by Fractional Noises
Authors: Sun Xichao , Li Ming
Published: April 2015

This paper is concerned with the following stochastically fractional heat equation on(t,x)∈[0,T]×Rddriven by fractional noise:∂u(t,x)/∂t=Dδαu(t,x)+WH(t,x)⋄u(t,x), where the Hurst parameterH=(h0,h1,…,hd)and⋄denotes the Skorokhod integral. A unique solution of that equation in an appropriate Hilbert space is constructed. Moreover, the Lyapunov exponent of the solution is estimated, and the Hölder continuity of the solution on both space and time parameters is discussed. On the other hand, the absolute continuity of the solution is also obtained.
Evaluating a Pivot-Based Approach for Bilingual Lexicon Extraction
Authors: Kim Jae-Hoon , Kwon Hong-Seok , Seo Hyeong-Won
Published: April 2015

A pivot-based approach for bilingual lexicon extraction is based on the similarity of context vectors represented by words in a pivot language like English. In this paper, in order to show validity and usability of the pivot-based approach, we evaluate the approach in company with two different methods for estimating context vectors: one estimates them from two parallel corpora based on word association between source words (resp., target words) and pivot words and the other estimates them from two parallel corpora based on word alignment tools for statistical machine translation. Empirical results on two language pairs (e.g., Korean-Spanish and Korean-French) have shown that the pivot-based approach is very promising for resource-poor languages and this approach observes its validity and usability. Furthermore, for words with low frequency, our method is also well performed.
The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with Classic Type in the Patients with Coexisting Hashimoto’s Thyroiditis
Authors: Yeo Min-kyung , Bae Ja Seong , Lee Sohee , Kim Min-Hee , Lim Dong-Jun , Lee Youn Soo , Jung Chan Kwon
Published: April 2015

Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear.Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC.BRAFmutation was tested with pyrosequencing.Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto’s thyroiditis than classic PTCs (93% versus 36%, resp.,P< 0.001) and showed significantly lower rate ofBRAFmutation when compared to classic PTCs (65% versus 84%, resp.,P= 0.007). In classic PTC, the frequency ofBRAFmutations was negatively correlated with coexisting Hashimoto’s thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto’s thyroiditis, there were no significant differences in clinicopathologic characteristics or theBRAFmutational rate between the two groups.Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto’s thyroiditis.