bluuebunny/crossref_metadata_2025 huggingface dataset:
The Baculovirus Core Gene
ac83
Is Required for Nucleocapsid Assembly and
Per Os
Infectivity of Autographa californica Nucleopolyhedrovirus
Authors: Zhu Shimao , Wang Wei , Wang Yan , Yuan Meijin , Yang Kai
Published: July 2013

Autographa californica multiple nucleopolyhedrovirus
(AcMNPV)
ac83
is a baculovirus core gene whose function in the AcMNPV life cycle is unknown. In the present study, an
ac83
-knockout AcMNPV (vAc83KO) was constructed to investigate the function of
ac83
through homologous recombination in
Escherichia coli
. No budded virions were produced in vAc83KO-transfected Sf9 cells, although viral DNA replication was unaffected. Electron microscopy revealed that nucleocapsid assembly was aborted due to the
ac83
deletion. Domain-mapping studies revealed that the expression of Ac83 amino acid residues 451 to 600 partially rescued the ability of AcMNPV to produce infectious budded virions. Bioassays indicated that deletion of the chitin-binding domain of Ac83 resulted in the failure of oral infection of
Trichoplusia ni
larvae by AcMNPV, but AcMNPV remained infectious following intrahemocoelic injection, suggesting that the domain is involved in the binding of occlusion-derived virions to the peritrophic membrane and/or to other chitin-containing insect tissues. It has been demonstrated that Ac83 is the only component with a chitin-binding domain in the
per os
infectivity factor complex on the occlusion-derived virion envelope. Interestingly, a functional inner nuclear membrane sorting motif, which may facilitate the localization of Ac83 to the envelopes of occlusion-derived virions, was identified by immunofluorescence analysis. Taken together, these results demonstrate that Ac83 plays an important role in nucleocapsid assembly and the establishment of oral infection.
Targeting of Human Antigen-Presenting Cell Subsets
Authors: Goyvaerts Cleo , Dingemans Jozef , De Groeve Kurt , Heirman Carlo , Van Gulck Ellen , Vanham Guido , De Baetselier Patrick , Thielemans Kris , Raes Geert , Breckpot Karine
Published: July 2013

Antigen-presenting cells are a heterogeneous group of cells that are characterized by their functional specialization. Consequently, targeting specific antigen-presenting cell subsets offers opportunities to induce distinct T cell responses. Here we report on the generation and use of nanobodies (Nbs) to target lentivectors specifically to human lymph node-resident myeloid dendritic cells, demonstrating that Nbs represent a powerful tool to redirect lentivectors to human antigen-presenting cell subsets.
Renal arteriovenous malformation: an unusual cause of recurrent haematuria
Authors: Ali Mazhar , Aziz Wajahat , Abbas Farhat
Published: July 2013

A 54-year-old woman presented with gross painless haematuria. Initial workup showed no abnormality except mild hydronephrosis on CT scan. Cystoscopy and retrograde pyelography did not find any gross lesion and her urine cytology was also negative. She had recurrent haematuria so her CT was reviewed with the radiologist with clinical suspicion of arteriovenous malformation (AVM) which was suggested by relatively increased contrast density in the hemiazygous vein and renal vein in the arterial phase. She underwent angioembiolisation of left renal AVM after which her haematuria settled.
Cardiac tamponade: an initial presentation of SLE
Authors: Cheng Wilson , Balachandar Ramya , Mistry Paresh
Published: July 2013

A 45-year-old woman presented with dyspnoea, chest pain, orthopnoea and bilateral leg oedema. On admission, she was found to have nephrotic syndrome and global pericardial effusion with impending tamponade for which pericardiocentesis was performed. The diagnosis of systemic lupus erythematosus was made based on the clinical and biochemical findings. She was also started on dialysis and immunosuppressants for lupus nephritis.
Impact of clinical trial findings on Bell's palsy management in general practice in the UK 2001–2012: interrupted time series regression analysis
Authors: Morales Daniel R , Donnan Peter T , Daly Fergus , Staa Tjeerd Van , Sullivan Frank M
Published: July 2013

Objectives

To measure the incidence of Bell's palsy and determine the impact of clinical trial findings on Bell's palsy management in the UK.

Design

Interrupted time series regression analysis and incidence measures.

Setting

General practices in the UK contributing to the Clinical Practice Research Datalink (CPRD).

Participants

Patients ≥16 years with a diagnosis of Bell's palsy between 2001 and 2012.

Interventions

(1) Publication of the 2004 Cochrane reviews of clinical trials on corticosteroids and antivirals for Bell's palsy, which made no clear recommendation on their use and (2) publication of the 2007 Scottish Bell's Palsy Study (SBPS), which made a clear recommendation that treatment with prednisolone alone improves chances for complete recovery.

Main outcome measures

Incidence of Bell's palsy per 100 000 person-years. Changes in the management of Bell's palsy with either prednisolone therapy, antiviral therapy, combination therapy (prednisolone with antiviral therapy) or untreated cases.

Results

During the 12-year period, 14 460 cases of Bell's palsy were identified with an overall incidence of 37.7/100 000 person-years. The 2004 Cochrane reviews were associated with immediate falls in prednisolone therapy (−6.3% (−11.0 to −1.6)), rising trends in combination therapy (1.1% per quarter (0.5 to 1.7)) and falling trends for untreated cases (−0.8% per quarter (−1.4 to −0.3)). SBPS was associated with immediate increases in prednisolone therapy (5.1% (0.9 to 9.3)) and rising trends in prednisolone therapy (0.7% per quarter (0.4 to 1.2)); falling trends in combination therapy (−1.7% per quarter (−2.2 to −1.3)); and rising trends for untreated cases (1.2% per quarter (0.8 to 1.6)). Despite improvements, 44% still remain untreated.

Conclusions

SBPS was clearly associated with change in management, but a significant proportion of patients failed to receive effective treatment, which cannot be fully explained. Clarity and uncertainty in clinical trial recommendations may change clinical practice. However, better ways are needed to understand and circumvent barriers in implementing clinical trial findings.
Characteristics of 5-year-olds who catch-up with MMR: findings from the UK Millennium Cohort Study
Authors: Pearce Anna , Mindlin Miranda , Cortina-Borja Mario , Bedford Helen
Published: July 2013

Objectives

To examine predictors of partial and full measles, mumps and rubella (MMR) vaccination catch-up between 3 and 5 years.

Design

Secondary data analysis of the nationally representative Millennium Cohort Study (MCS).

Setting

Children born in the UK, 2000–2002.

Participants

751 MCS children who were unimmunised against MMR at age 3, with immunisation information at age 5.

Main outcome measures

Catch-up status: unimmunised (received no MMR), partial catch-up (received one MMR) or full catch-up (received two MMRs).

Results

At age 5, 60.3% (n=440) children remained unvaccinated, 16.1% (n=127) had partially and 23.6% (n=184) had fully caught-up. Children from families who did not speak English at home were five times as likely to partially catch-up than children living in homes where only English was spoken (risk ratio 4.68 (95% CI 3.63 to 6.03)). Full catch-up was also significantly more likely in those did not speak English at home (adjusted risk ratio 1.90 (1.08 to 3.32)). In addition, those from Pakistan/Bangladesh (2.40 (1.38 to 4.18)) or ‘other’ ethnicities (such as Chinese) (1.88 (1.08 to 3.29)) were more likely to fully catch-up than White British. Those living in socially rented (1.86 (1.34 to 2.56)) or ‘Other’ (2.52 (1.23 to 5.18)) accommodations were more likely to fully catch-up than home owners, and families were more likely to catch-up if they lived outside London (1.95 (1.32 to 2.89)). Full catch-up was less likely if parents reported medical reasons (0.43 (0.25 to 0.74)), a conscious decision (0.33 (0.23 to 0.48)), or ‘other’ reasons (0.46 (0.29 to 0.73)) for not immunising at age 3 (compared with ‘practical’ reasons).

Conclusions

Parents who partially or fully catch-up with MMR experience practical barriers and tend to come from disadvantaged or ethnic minority groups. Families who continue to reject MMR tend to have more advantaged backgrounds and make a conscious decision to not immunise early on. Health professionals should consider these findings in light of the characteristics of their local populations.
Prevalence ofChlamydia trachomatisinfection in the general population of women in Qatar
Authors: Al-Thani Asma , Abdul-Rahim Hanan , Alabsi Enas , Bsaisu Haneen N , Haddad Pascale , Mumtaz Ghina R , Abu-Raddad Laith J
Published: July 2013

Objectives

The Arabian Gulf region has limited epidemiological data related to sexually transmitted infections. The objective of this study was to estimate the prevalence ofChlamydia trachomatisinfection among general population women in Doha, Qatar.

Methods

Endocervical swabs were collected from healthy women attending primary healthcare centres in Doha, June–December 2008. The specimens were tested forC trachomatisby a commercially available PCR-based assay. Data on basic socio-demographic characteristics, medical history and sexual behaviour were obtained using self-administered questionnaires. The prevalence ofC trachomatisand of background variables were stratified by nationality, Qatari nationals versus non-Qatari residents.

Results

A total of 377 women were enrolled in the study, out of whom 351 (37.9% Qataris, 62.1% non-Qataris) were tested for the presence ofC trachomatisin their specimens. The mean age of participants was 41.2 years, and the vast majority (93%, 95% CI 90.3 to 95.7) were married. The mean age at sexual debut was significantly lower among Qatari women compared with non-Qatari women (19.2 vs 22.2 years, respectively p<0.001), but the mean number of reported lifetime sexual partners (1.1 partner) was nearly the same in both groups (p=0.110). The prevalence ofC trachomatisinfection was 5.3% among Qatari women and 5.5% among non-Qatari women, with no statistically significant difference between both groups (p=0.923).

Conclusions

The prevalence ofC trachomatisamong women was higher than expected, with no significant difference between Qatari nationals and expatriate residents. The higher prevalence may reflect, in part, the limited access to and use of chlamydia screening and management.
Seasonal and sexual differences in the thermal preferences and movements of American lobsters
Authors: Jury Steven H. , Watson Winsor H.
Published: July 2013

Thermal preferences of lobsters (Homarus americanus) were determined in the laboratory and compared with seasonal movements and distribution of lobsters in the Great Bay Estuary, New Hampshire. Lobsters preferred 11.0 ± 0.6 °C, or 2.8 ± 0.7 °C warmer than ambient temperature, during the colder months of the year. However, during the warmer months they selected 15.7 ± 0.4 °C, which was 0.2 ± 0.4 °C warmer than the ambient temperature. Overall, the lobsters tested had a final preferred temperature of 15.9 °C, and males selected warmer temperatures than females. Catch per unit effort was highest at sites where temperatures were similar to the temperatures lobsters preferred in the laboratory studies and lowest at sites ≥18 °C or <12 °C. Significantly more males than females were captured in areas with temperatures >16 °C. Lobsters tagged, and subsequently recaptured within 7–35 days, moved relatively little when released into areas where temperatures were similar to their preferred temperatures. Thermal preferences may influence the movement of lobsters in thermally heterogeneous habitats, and climate change is expected to have a major impact on lobster distribution, especially in estuarine and coastal habitats.
Room temperature frequency-dependent complex impedance and conductivity behavior of BaTiO3–La0.7Ca0.3MnO3 composites
Authors: Khan Momin Hossain , Pal Sudipta , Bose Esa
Published: July 2013

A series of composite materials (100 − x)BaTiO3 (BTO) − (x)La0.7Ca0.3MnO3 (LCMO) has been prepared using the solid state reaction route varying x in wt%. The influence of LCMO on the frequency-dependent complex impedance and conductivity of BTO has been investigated. The Cole–Cole plots of real and imaginary parts of the complex impedance indicates separate contributions of various factors, such as bulk effect, grain boundary, and interface effects in frequency-dependent conductivity in the composites. Non-Debye-like relaxation has been observed in the BTO–LCMO composites. Interestingly a typical universal dielectric response in the frequency-dependent conductivity at room temperature (300 K) has been found for all the compounds.
SYMMETRIES FOR BORCHERDS LIFTS ON HILBERT MODULAR GROUPS AND HIRZEBRUCH–ZAGIER DIVISORS
Authors: HEIM BERNHARD , MURASE ATSUSHI
Published: July 2013

We show certain symmetries for Borcherds lifts on the Hilbert modular group over a real quadratic field. We give two different proofs, the one analytic and the other arithmetic. The latter proof yields an explicit description of the action of Hecke operators on Borcherds lifts.
TOP QUARK PHYSICS, AN EXPERIMENTAL PERSPECTIVE
Authors: BARBERIS EMANUELA
Published: July 2013

An experimental review of the current status of the top quark physics program at hadron colliders is presented. Since the discovery of the top quark at the Fermilab Tevatron collider in 1995, its production and the decay have been studied with an extraordinary level of sophistication both at the Tevatron and at the Large Hadron Collider. The top quark is the heaviest known elementary particle, with possible unique connections to the mechanism of electroweak symmetry breaking.
PARTON DENSITIES WITH THE QUARK LINEAR POTENTIAL IN THE STATISTICAL APPROACH
Authors: MIRJALILI ABOLFAZL , DEHGHANI MAJID , YAZDANPANAH MOHAMMAD MEHDI
Published: July 2013

The statistical approach is used to calculate the parton distribution functions (PDFs) of the nucleon. At first it is assumed that the partons are free particles and the light-front kinematic variables are employed to extract the Bjorken x-dependence of the PDFs. These PDFs are used to evaluate the combinations of the sea quarks such as [Formula: see text]. As our first attempt to improve the result, we make the statistical parameters to depend on Q2, using different values of Gottfried sum rule. The related results are indicating better behavior by accessing to the PDFs while they contain the Q2 dependence parameters. As a further task and in order to have more improvement in the calculations, a linear potential is considered to describe the quark interactions. The solution of the related Dirac equation yields the Airy function and is considered as a wave function in spatial space. Using the Fourier transformation the wave functions are obtained in momentum space. Based on the light-front kinematic variables and using a special method which we call it "k-method," these functions can be written in terms of the Bjorken x-variable. Following that the statistical features are accompanied with these functions. Considering an effective approach which is used in this paper, we do not need to resort to any extra effects as were assumed in some papers to get proper results for PDFs. The obtained results for [Formula: see text] and the [Formula: see text] ratio, using our effective approach, are in good agreement with the available experimental data and some theoretical results.
CROSS-VIEW GAIT RECOGNITION WITH SHORT PROBE SEQUENCES: FROM VIEW TRANSFORMATION MODEL TO VIEW-INDEPENDENT STANCE-INDEPENDENT IDENTITY VECTOR
Authors: HU MAODI , WANG YUNHONG , ZHANG ZHAOXIANG
Published: July 2013

Considering it is difficult to guarantee that at least one continuous complete gait cycle is captured in real applications, we address the multi-view gait recognition problem with short probe sequences. With unified multi-view population hidden markov models (umvpHMMs), the gait pattern is represented as fixed-length multi-view stances. By incorporating the multi-stance dynamics, the well-known view transformation model (VTM) is extended into a multi-linear projection model in a four-order tensor space, so that a view-independent stance-independent identity vector (VSIV) can be extracted. The main advantage is that the proposed VSIV is stable for each subject regardless of the camera location or the sequence length. Experiments show that our algorithm achieves encouraging performance for cross-view gait recognition even with short probe sequences.
NATURAL ORBITALS REPRESENTATION AND FERMI SEA DEPLETION IN FINITE NUCLEI AND NUCLEAR MATTER
Authors: PSONIS V. P. , MOUSTAKIDIS Ch. C. , MASSEN S. E.
Published: July 2013

The natural orbitals (NOs) and natural occupation numbers (NON) of various N = Z, sp and sd shell nuclei are calculated by applying a correlated one-body density matrix (OBDM). The correlated density matrix has been evaluated by considering central correlations of Jastrow type and an approximation named factor cluster expansion. The correlation effects on NOs, NON and the Fermi sea depletion (FSD) are discussed and analyzed. In addition, an approximate expression for the correlated OBDM of the nuclear matter has been used for the evaluation of the relative momentum distribution and FSD. We found that the value of FSD is higher in closed shell nuclei compared to open shell ones and it is lower compared to the case of nuclear matter. This statement could be confirmed by relevant experimental studies.
FIRST-PRINCIPLES STUDY OF Ti-CATALYZED HYDROGEN ADSORPTION ON LiB (001) SURFACE
Authors: ZHANG WEIBIN , WU AILING , LIU YIDING , ZHANG SHAOLIN , GONG JIANHONG , CHANG LAN , LI JIAN , ZHANG HUI , LIU HAIFENG , LI KEHUA , HUANG KAI , YANG WOOCHUL
Published: July 2013

Ti -doped LiB (001) is a promising material for hydrogen storage. The adsorption of H 2 is greatly enhanced by doping Ti into LiB (001), change the electronic structures of the surface Li , B atoms. After H 2 is adsorbed on the surface, the E ad of the ( H 2)n@ Ti / LiB (001) system is considered. It is around -0.22 eV/ H 2 to -0.31 eV/ H 2, which is close to the target specified by U.S. Department of Energy. The nature of the bonding between Ti and H 2 is due to the H 1s, Ti 4s and B 2s orbital hybridization. In addition, Ti 3d orbital is hybridized strongly with B -2p orbital, resulting in more stable Ti / LiB (001) system. These results are verified by the electron density distribution intuitively. It is found that the system can adsorb up to four H 2 at ambient temperature and pressure. Therefore, the Ti -doped LiB (001) would be a promising hydrogen storage material. Such optimal molecular hydrogen adsorption system makes H 2 adsorption feasible at ambient conditions, which is critical for practical applications.
Integration of spectral gamma-ray and geochemical analyses for the characterization of the upper Jurassic Arab-D carbonate reservoir: outcrop analogue approach, central Saudi Arabia
Authors: Eltom H. , Abdullatif O. , Makkawi M. , Yasin M.
Published: July 2013

Investigation by spectral gamma-ray (SGR) and inductively coupled plasma-mass spectrometry (ICP-MS) geochemical analyses of the Upper Jurassic Arab-D reservoir analogue (central Saudi Arabia) revealed a strong correlation between the SGR response of the outcrop lithofacies and their elemental content. The two units of the reservoir (the Upper Jubaila Member of the Jubaila Formation and the Arab-D Member of the Arab Formation) showed distinctive SGR log profiles controlled mainly by their lithofacies associations. The geochemical analysis revealed four groups of chemical associations. Group 1 includes SiO
2
, Al
3
O
2
, Fe
2
O
3
, K
2
O, TiO
2
, Zr and Zn. This group has a strong relationship with the radioactive elements U, K and Th (Group 4). The reservoir facies exhibit high concentrations of chemicals from these two clusters. Group 2 includes CaO and Sr. A high concentration of chemicals from this group indicates a tendency towards pure carbonate facies and fewer siliciclastic impurities. A high concentration of MgO, the only chemical included in Group 3, marks dolomitic zones. Group 4 contains the radioactive elements. The boundary between the Upper Jubaila Member and the Arab-D Member is clearly defined from vertical SGR log profiles, vertical geochemical data logging and cross-plots of Group 1 chemicals with the radioactive elements in Group 4. The geochemical data for the Upper Jubaila Member show a very low concentration of U, K and Th. Consequently, the SGR response of the lithofacies was very low. All of the reservoir lithofacies showed high concentration of Group 1 and Group 4 components compared with the non-reservoir lithofacies. The Th/U ratio indicates a general shoaling upwards following the same trend of the outcrop lithofacies. A high Th/U ratio characterizes reservoir lithofacies, whereas a low ratio characterizes non-reservoir lithofacies. The lithofacies and the SGR log motifs were related in the measured sections. This study provides a method for predicting lithofacies from SGR log motifs within a high-resolution stratigraphic framework integrated with the geochemical data analysis. Here, we introduce an exploration guide for subsurface reservoir zonation and the identification of formation tops.
Evolution in the use of natural building stone in Madrid, Spain
Authors: Fort Rafael , Alvarez de Buergo Monica , Perez-Monserrat Elena M. , Gomez-Heras Miguel , Jose Varas-Muriel M. , Freire David M.
Published: July 2013

Many types of stone have been used for construction in Madrid. In historical times, their use was determined by the proximity of the geological resources, the ease of quarrying and transportation links to the city. More recently, as transport connections and quarrying techniques have improved, quality and durability have become key determinants of building stone selection. Local flint was used intensively from the ninth to the eleventh century, when it was replaced by
Redueña
dolostone, used in turn until the seventeenth century. Granitic rocks from the Guadarrama Mountain Range that crop out in the northern and western area of the province increasingly began to be used in the city from the sixteenth century. Traditionally known as
Berroqueña
stone, this building stone was quarried in a number of areas; the primary point of supply was Zarzalejo, and from the eighteenth century the granite used was mainly quarried in the Alpedrete area. Eighteenth century advances in underground quarrying made it possible to extract a limestone (
Colmenar
stone) located in the southeastern part of the region. Together with
Berroqueña
stone, this limestone became one of Madrid’s traditional building stones, and both, highly esteemed for their excellent petrophysical properties and durability, are still used today.
Visual assessment of sandstone building façades: condition factors related to cleaning
Authors: Zurakowska Marta , Hughes John J.
Published: July 2013

Cleaning of traditional stone building facades became widespread from the 1960s in many cities across the UK, where it became a totemic factor in economic and social regeneration. Debate continues on the effects of cleaning on the health of stone buildings, often without a sound evidence base for decision making. In this study we attempt to determine whether stone cleaning is a stone decay factor. A survey technique based on assessing selected blocks in buildings, excluding areas where multiple factors contribute to high risk of decay, was applied in a semi-quantitative analysis of buildings in Paisley constructed from blonde-coloured carbonate-cemented quartz arenite, to recognize decay problems related to cleaning. Amounts of decay were evaluated on blocks from cleaned and non-cleaned buildings. The results show that there is no significant difference in amount of decay between these groups of buildings when areas subject to high decay stress are disregarded, and therefore that cleaning is not a risk factor in the stone surveyed. Decay is strongly centred on building elements that have a high risk of decay, with a strong predeposition towards moisture retention and associated soiling (i.e. projecting and recessed ornament and architectural detail).
Conservation issues with calcarenites used as historical building materials in Syracuse (Southern Italy)
Authors: Calia A. , Mecchi A. M. , Colangiuli D. , Scudeler Baccelle L.
Published: July 2013

The Mediterranean basin typically shows the ubiquitous presence of historical towns constituting a rich architectural heritage that has only recently become the object of conservation policy. Diagnostic knowledge can effectively contribute to the adoption of suitable conservation strategies. This work focuses on the historical building materials employed in the Sicilian town of Syracuse (Southern Italy), with the aim of identifying the causes and mechanisms of deterioration of the materials employed, as well as possible remedies. An extensive survey of the stones and their main decay morphologies within buildings was carried out. Laboratory analyses by optical microscopy, mercury intrusion porosimetry and ion chromatography were also performed. Several soft and porous calcarenites, having different mineralogical–petrographical and porosity features, were recognized. The study identified a decay scenario typical of a Mediterranean context, with sea spray as the main cause of decay, together with water and wind. Different decay levels observed in the stones were related to their fabric and porosimetric structure, but specific use and position within buildings also proved important. The findings of this study are of interest for similar urban and geographical contexts where soft and porous calcarenites are employed, and provide information for conservation works.
An overview of the results of 61
in situ
thermal response tests in the UK
Authors: Banks D. , Withers J. G. , Cashmore G. , Dimelow C.
Published: July 2013

The results of 61
in situ
UK thermal response tests, derived from three commercial test-rigs, have been analysed. Derived values of thermal conductivity yield a median of 2.25 W m K
−1
, with 25th and 75th percentiles of 1.86 and 3.0 W m K
−1
. The lowest single values are derived from Northern Irish basalt (1.1 W m K
-1
) and from Mesozoic and Tertiary argillites (often in the range 1.43–2 W m K
−1
), whereas the highest (>5 W m K
−1
) are from Sherwood Sandstone and Coal Measures strata where advective heat transport with groundwater flow may have led to an elevated apparent conductivity. Borehole thermal resistance exhibits 25th percentile, median and 75th percentile values of 0.09, 0.11 and 0.14 K m W
−1
and correlates with borehole heat exchanger diameter and configuration. Undisturbed ground temperature exhibits 25th percentile, median and 75th percentile values of 11.7, 12.3 and 13.2 °C and exhibits a latitude dependence.
Micro- and Nanoscale Engineering of Cell Signaling
Authors: Kam L.C. , Shen K. , Dustin M.L.
Published: July 2013

It is increasingly recognized that cell signaling, as a chemical process, must be considered at the local, micrometer scale. Micro- and nanofabrication techniques provide access to these dimensions, with the potential to capture and manipulate the spatial complexity of intracellular signaling in experimental models. This review focuses on recent advances in adapting surface engineering for use with biomolecular systems that interface with cell signaling, particularly with respect to surfaces that interact with multiple receptor systems on individual cells. The utility of this conceptual and experimental approach is demonstrated in the context of epithelial cells and T lymphocytes, two systems whose ability to perform their physiological function is dramatically impacted by the convergence and balance of multiple signaling pathways.
Topology and Dynamics of Signaling Networks: In Search of Transcriptional Control of the Inflammatory Response
Authors: Androulakis Ioannis P. , Kamisoglu Kubra , Mattick John S.
Published: July 2013

Over the past several decades, to develop a fundamental understanding of inflammation's progression, research has focused on extracellular mediators, such as cytokines, as characteristic components of inflammatory response. These efforts have recently been complemented by advances in proteomics that allow analysis of multiple signaling proteins in parallel, to provide more complete mechanistic models of inflammation. In this review, we discuss various techniques for assessing protein activity, as well as computational techniques that are well suited for interpreting large amounts of proteomic data to generate signaling networks or for modeling the dynamics of known network interactions. We also discuss examples that explore these experimental and computational techniques in tandem to generate signaling networks under various conditions and that link those networks to transcriptional activity. Further advancements in this field will likely provide an explicit description of inflammatory response, paving the way for better diagnostics and therapies in clinic.
Sensors and Decoding for Intracortical Brain Computer Interfaces
Authors: Homer Mark L. , Nurmikko Arto V. , Donoghue John P. , Hochberg Leigh R.
Published: July 2013

Intracortical brain computer interfaces (iBCIs) are being developed to enable people to drive an output device, such as a computer cursor, directly from their neural activity. One goal of the technology is to help people with severe paralysis or limb loss. Key elements of an iBCI are the implanted sensor that records the neural signals and the software that decodes the user's intended movement from those signals. Here, we focus on recent advances in these two areas, placing special attention on contributions that are or may soon be adopted by the iBCI research community. We discuss how these innovations increase the technology's capability, accuracy, and longevity, all important steps that are expanding the range of possible future clinical applications.
Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases the trafficking of Kv11.1 channels stored in the transitional endoplasmic reticulum
Authors: Smith Jennifer L. , Reloj Allison R. , Nataraj Parvathi S. , Bartos Daniel C. , Schroder Elizabeth A. , Moss Arthur J. , Ohno Seiko , Horie Minoru , Anderson Corey L. , January Craig T. , Delisle Brian P.
Published: July 2013

KCNH2 encodes Kv11.1 and underlies the rapidly activating delayed rectifier K+ current ( IKr) in the heart. Loss-of-function KCNH2 mutations cause the type 2 long QT syndrome (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channels. Drugs that bind to Kv11.1 and block IKr (e.g., E-4031) can act as pharmacological chaperones to increase the trafficking and functional expression for most LQT2 channels (pharmacological correction). We previously showed that LQT2 channels are selectively stored in a microtubule-dependent compartment within the endoplasmic reticulum (ER). We tested the hypothesis that pharmacological correction promotes the trafficking of LQT2 channels stored in this compartment. Confocal analyses of cells expressing the trafficking-deficient LQT2 channel G601S showed that the microtubule-dependent ER compartment is the transitional ER. Experiments with E-4031 and the protein synthesis inhibitor cycloheximide suggested that pharmacological correction promotes the trafficking of G601S stored in this compartment. Treating cells in E-4031 or ranolazine (a drug that blocks IKr and has a short half-life) for 30 min was sufficient to cause pharmacological correction. Moreover, the increased functional expression of G601S persisted 4–5 h after drug washout. Coexpression studies with a dominant-negative form of Rab11B, a small GTPase that regulates Kv11.1 trafficking, prevented the pharmacological correction of G601S trafficking from the transitional ER. These data suggest that pharmacological correction quickly increases the trafficking of LQT2 channels stored in the transitional ER via a Rab11B-dependent pathway, and we conclude that the pharmacological chaperone activity of drugs like ranolazine might have therapeutic potential.
Fulvene-5 inhibition of Nadph oxidases attenuates activation of epithelial sodium channels in A6 distal nephron cells
Authors: Trac David , Liu Bingchen , Pao Alan C. , Thomas Sheela V. , Park Michael , Downs Charles A. , Ma He-Ping , Helms My N.
Published: July 2013

Nadph oxidase 4 is an important cellular source of reactive oxygen species (ROS) generation in the kidney. Novel antioxidant drugs, such as Nox4 inhibitor compounds, are being developed. There is, however, very little experimental evidence for the biological role and regulation of Nadph oxidase isoforms in the kidney. Herein, we show that Fulvene-5 is an effective inhibitor of Nox-generated ROS and report the role of Nox isoforms in activating epithelial sodium channels (ENaC) in A6 distal nephron cells via oxidant signaling and cell stretch activation. Using single-channel patch-clamp analysis, we report that Fulvene-5 blocked the increase in ENaC activity that is typically observed with H2O2treatment of A6 cells: average ENaC NPovalues decreased from a baseline level of 1.04 ± 0.18 (means ± SE) to 0.25 ± 0.08 following Fulvene-5 treatment. H2O2treatment failed to increase ENaC activity in the presence of Fulvene-5. Moreover, Fulvene-5 treatment of A6 cells blocked the osmotic cell stretch response of A6 cells, indicating that stretch activation of Nox-derived ROS plays an important role in ENaC regulation. Together, these findings indicate that Fulvene-5, and perhaps other classes of antioxidant inhibitors, may represent a novel class of compounds useful for the treatment of pathological disorders stemming from inappropriate ion channel activity, such as hypertension.
An anatomically unbiased approach for analysis of renal BOLD magnetic resonance images
Authors: Menzies Robert I. , Zammit-Mangion Andrew , Hollis Lyam M. , Lennen Ross J. , Jansen Maurits A. , Webb David J. , Mullins John J. , Dear James W. , Sanguinetti Guido , Bailey Matthew A.
Published: July 2013

Oxygenation defects may contribute to renal disease progression, but the chronology of events is difficult to define in vivo without recourse to invasive methodologies. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) provides an attractive alternative, but the R2* signal is physiologically complex. Postacquisition data analysis often relies on manual selection of region(s) of interest. This approach excludes from analysis significant quantities of biological information and is subject to selection bias. We present a semiautomated, anatomically unbiased approach to compartmentalize voxels into two quantitatively related clusters. In control F344 rats, low R2* clustering was located predominantly within the cortex and higher R2* clustering within the medulla (70.96 ± 1.48 vs. 79.00 ± 1.50; 3 scans per rat; n = 6; P < 0.01) consistent anatomically with a cortico-medullary oxygen gradient. An intravenous bolus of acetylcholine caused a transient reduction of the R2* signal in both clustered segments ( P < 0.01). This was nitric oxide dependent and temporally distinct from the hemodynamic effects of acetylcholine. Rats were then chronically infused with angiotensin II (60 ng/min) and rescanned 3 days later. Clustering demonstrated a disruption of the cortico-medullary gradient, producing less distinctly segmented mean R2* clusters (71.30 ± 2.00 vs. 72.48 ± 1.27; n = 6; NS). The acetylcholine-induced attenuation of the R2* signal was abolished by chronic angiotensin II infusion, consistent with reduced nitric oxide bioavailability. This global map of oxygenation, defined by clustering individual voxels on the basis of quantitative nearness, might be more robust in defining deficits in renal oxygenation than the absolute magnitude of R2* in small, manually selected regions of interest defined exclusively by anatomical nearness.
Novel diuretic targets
Authors: Denton Jerod S. , Pao Alan C. , Maduke Merritt
Published: July 2013

As the molecular revolution continues to inform a deeper understanding of disease mechanisms and pathways, there exist unprecedented opportunities for translating discoveries at the bench into novel therapies for improving human health. Despite the availability of several different classes of antihypertensive medications, only about half of the 67 million Americans with hypertension manage their blood pressure appropriately. A broader selection of structurally diverse antihypertensive drugs acting through different mechanisms would provide clinicians with greater flexibility in developing effective treatment regimens for an increasingly diverse and aging patient population. An emerging body of physiological, genetic, and pharmacological evidence has implicated several renal ion-transport proteins, or regulators thereof, as novel, yet clinically unexploited, diuretic targets. These include the renal outer medullary potassium channel, ROMK (Kir1.1), Kir4.1/5.1 potassium channels, ClC-Ka/b chloride channels, UTA/B urea transporters, the chloride/bicarbonate exchanger pendrin, and the STE20/SPS1-related proline/alanine-rich kinase (SPAK). The molecular pharmacology of these putative targets is poorly developed or lacking altogether; however, recent efforts by a few academic and pharmaceutical laboratories have begun to lessen this critical barrier. Here, we review the evidence in support of the aforementioned proteins as novel diuretic targets and highlight examples where progress toward developing small-molecule pharmacology has been made.
Predicting spike timing in highly synchronous auditory neurons at different sound levels
Authors: Fontaine Bertrand , Benichoux Victor , Joris Philip X. , Brette Romain
Published: July 2013

A challenge for sensory systems is to encode natural signals that vary in amplitude by orders of magnitude. The spike trains of neurons in the auditory system must represent the fine temporal structure of sounds despite a tremendous variation in sound level in natural environments. It has been shown in vitro that the transformation from dynamic signals into precise spike trains can be accurately captured by simple integrate-and-fire models. In this work, we show that the in vivo responses of cochlear nucleus bushy cells to sounds across a wide range of levels can be precisely predicted by deterministic integrate-and-fire models with adaptive spike threshold. Our model can predict both the spike timings and the firing rate in response to novel sounds, across a large input level range. A noisy version of the model accounts for the statistical structure of spike trains, including the reliability and temporal precision of responses. Spike threshold adaptation was critical to ensure that predictions remain accurate at different levels. These results confirm that simple integrate-and-fire models provide an accurate phenomenological account of spike train statistics and emphasize the functional relevance of spike threshold adaptation.
Regulation of epileptiform discharges in rat neocortex by HCN channels
Authors: Albertson Asher J. , Williams Sidney B. , Hablitz John J.
Published: July 2013

Hyperpolarization-activated, cyclic nucleotide-gated, nonspecific cation (HCN) channels have a well-characterized role in regulation of cellular excitability and network activity. The role of these channels in control of epileptiform discharges is less thoroughly understood. This is especially pertinent given the altered HCN channel expression in epilepsy. We hypothesized that inhibition of HCN channels would enhance bicuculline-induced epileptiform discharges. Whole cell recordings were obtained from layer (L)2/3 and L5 pyramidal neurons and L1 and L5 GABAergic interneurons. In the presence of bicuculline (10 μM), HCN channel inhibition with ZD 7288 (20 μM) significantly increased the magnitude (defined as area) of evoked epileptiform events in both L2/3 and L5 neurons. We recorded activity associated with epileptiform discharges in L1 and L5 interneurons to test the hypothesis that HCN channels regulate excitatory synaptic inputs differently in interneurons versus pyramidal neurons. HCN channel inhibition increased the magnitude of epileptiform events in both L1 and L5 interneurons. The increased magnitude of epileptiform events in both pyramidal cells and interneurons was due to an increase in network activity, since holding cells at depolarized potentials under voltage-clamp conditions to minimize HCN channel opening did not prevent enhancement in the presence of ZD 7288. In neurons recorded with ZD 7288-containing pipettes, bath application of the noninactivating inward cationic current ( Ih) antagonist still produced increases in epileptiform responses. These results show that epileptiform discharges in disinhibited rat neocortex are modulated by HCN channels.
Observing motor learning produces somatosensory change
Authors: Bernardi Nicolò F. , Darainy Mohammad , Bricolo Emanuela , Ostry David J.
Published: July 2013

Observing the actions of others has been shown to affect motor learning, but does it have effects on sensory systems as well? It has been recently shown that motor learning that involves actual physical practice is also associated with plasticity in the somatosensory system. Here, we assessed the idea that observational learning likewise changes somatosensory function. We evaluated changes in somatosensory function after human subjects watched videos depicting motor learning. Subjects first observed video recordings of reaching movements either in a clockwise or counterclockwise force field. They were then trained in an actual force-field task that involved a counterclockwise load. Measures of somatosensory function were obtained before and after visual observation and also following force-field learning. Consistent with previous reports, video observation promoted motor learning. We also found that somatosensory function was altered following observational learning, both in direction and in magnitude, in a manner similar to that which occurs when motor learning is achieved through actual physical practice. Observation of the same sequence of movements in a randomized order did not result in somatosensory perceptual change. Observational learning and real physical practice appear to tap into the same capacity for sensory change in that subjects that showed a greater change following observational learning showed a reliably smaller change following physical motor learning. We conclude that effects of observing motor learning extend beyond the boundaries of traditional motor circuits, to include somatosensory representations.
Dynamic effects of TNF-α on synaptic transmission in mice over time following sciatic nerve chronic constriction injury
Authors: Zhang Hongmei , Zhang Haijun , Dougherty Patrick M.
Published: July 2013

Nerve injury-induced central sensitization can manifest as an increase in excitatory synaptic transmission and/or as a decrease in inhibitory synaptic transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis factor-α (TNF-α) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-α in modulating excitatory and inhibitory synaptic input to spinal substantia gelatinosa (SG) neurons over time in mice following chronic constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp studies from SG neurons showed that TNF-α enhanced overall excitability of the spinal cord early in time following nerve injury 3 days after CCI compared with that in sham control mice. In contrast, the effects of TNF were blunted 14 days after CCI in nerve-injured mice compared with sham surgery mice. Immunohistochemical staining showed that the expression of TNF-α receptor 1 (TNFR1) was increased at 3 days but decreased at 14 days following CCI in the ipsilateral vs. the contralateral spinal cord dorsal horn. These results suggest that TNF-α acting at TNFR1 is important in the development of neuropathic pain by facilitating excitatory synaptic signaling in the acute phases after nerve injury but has a reduced effect on spinal neuron signaling in the later phases of nerve injury-induced pain. Failure of the facilatory effects of TNF-α on excitatory synaptic signaling in the dorsal horn to resolve following nerve injury may be an important component in the transition between acute and chronic pain conditions.
Curcumin-Loaded Chitosan/Gelatin Composite Sponge for Wound Healing Application
Authors: Nguyen Van Cuong , Nguyen Van Boi , Hsieh Ming-Fa
Published: July 2013

Three composite sponges were made with 10% of curcumin and by using polymers, namely, chitosan and gelatin with various ratios. The chemical structure and morphology were evaluated by FTIR and SEM. These sponges were evaluated for water absorption capacity, antibacterial activity,in vitrodrug release, andin vivowound healing studies by excision wound model using rabbits. Thein vivostudy presented a greater wound closure in wounds treated with curcumin-composite sponge than those with composite sponge without curcumin and untreated group. These obtained results showed that combination of curcumin, chitosan and gelatin could improve the wound healing activity in comparison to chitosan, and gelatin without curcumin.
A Fuzzy Inference System for the Conjunctive Use of Surface and Subsurface Water
Authors: Chang Liang-Cheng , Chu Hone-Jay , Chen Yi-Wen
Published: July 2013

This study develops the water resources management model for conjunctive use of surface and subsurface water using a fuzzy inference system (FIS). The study applies the FIS to allocate the demands of surface and subsurface water. Subsequently, water allocations in the surface water system are simulated by using linear programming techniques, and the responses of subsurface water system with respect to pumping are forecasted by using artificial neural networks. The operating rule for the water systems is that the more abundant water system supplies more water. By using the fuzzy rule, the FIS conjunctive use model easily incorporates expert knowledge and operational polices into water resources management. The result indicates that the FIS model is more effective and efficient when compared with the decoupled conjunctive use and simulation-optimization models. Furthermore, the FIS model is an alternative way to obtain the conjunctive use policies between surface and subsurface water.
SIVIC: Open-Source, Standards-Based Software for DICOM MR Spectroscopy Workflows
Authors: Crane Jason C. , Olson Marram P. , Nelson Sarah J.
Published: July 2013

Quantitative analysis of magnetic resonance spectroscopic imaging (MRSI) data provides maps of metabolic parameters that show promise for improving medical diagnosis and therapeutic monitoring. While anatomical images are routinely reconstructed on the scanner, formatted using the DICOM standard, and interpreted using PACS workstations, this is not the case for MRSI data. The evaluation of MRSI data is made more complex because files are typically encoded with vendor-specific file formats and there is a lack of standardized tools for reconstruction, processing, and visualization. SIVIC is a flexible open-source software framework and application suite that enables a complete scanner-to-PACS workflow for evaluation and interpretation of MRSI data. It supports conversion of vendor-specific formats into the DICOM MR spectroscopy (MRS) standard, provides modular and extensible reconstruction and analysis pipelines, and provides tools to support the unique visualization requirements associated with such data. Workflows are presented which demonstrate the routine use of SIVIC to support the acquisition, analysis, and delivery to PACS of clinical1H MRSI datasets at UCSF.