bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptide Y Has a Protective Role during Murine Retrovirus-Induced Neurological Disease
Authors: Du Min , Butchi Niranjan B. , Woods Tyson , Morgan Timothy W. , Peterson Karin E.
Published: August 2010

Viral infections in the central nervous system (CNS) can lead to neurological disease either directly by infection of neurons or indirectly through activation of glial cells and production of neurotoxic molecules. Understanding the effects of virus-mediated insults on neuronal responses and neurotrophic support is important in elucidating the underlying mechanisms of viral diseases of the CNS. In the current study, we examined the expression of neurotrophin- and neurotransmitter-related genes during infection of mice with neurovirulent polytropic retrovirus. In this model, virus-induced neuropathogenesis is indirect, as the virus predominantly infects macrophages and microglia and does not productively infect neurons or astrocytes. Virus infection is associated with glial cell activation and the production of proinflammatory cytokines in the CNS. In the current study, we identified increased expression of neuropeptide Y (NPY), a pleiotropic growth factor which can regulate both immune cells and neuronal cells, as a correlate with neurovirulent virus infection. Increased levels ofNpymRNA were consistently associated with neurological disease in multiple strains of mice and were induced only by neurovirulent, not avirulent, virus infection. NPY protein expression was primarily detected in neurons near areas of virus-infected cells. Interestingly, mice deficient in NPY developed neurological disease at a faster rate than wild-type mice, indicating a protective role for NPY. Analysis of NPY-deficient mice indicated that NPY may have multiple mechanisms by which it influences virus-induced neurological disease, including regulating the entry of virus-infected cells into the CNS.
The Glycosylated Gag Protein of a Murine Leukemia Virus Inhibits the Antiretroviral Function of APOBEC3
Authors: Kolokithas Angelo , Rosenke Kyle , Malik Frank , Hendrick Duncan , Swanson Lukas , Santiago Mario L. , Portis John L. , Hasenkrug Kim J. , Evans Leonard H.
Published: August 2010

APOBEC proteins have evolved as innate defenses against retroviral infections. Human immunodeficiency virus (HIV) encodes the Vif protein to evade human APOBEC3G; however, mouse retroviruses do not encode a Vif homologue, and it has not been understood how they evade mouse APOBEC3. We report here a murine leukemia virus (MuLV) that utilizes its glycosylated Gag protein (gGag) to evade APOBEC3. gGag is critical for infection of
in vitro
cell lines in the presence of APOBEC3. Furthermore, a gGag-deficient virus restricted for replication in wild-type mice replicates efficiently in APOBEC3 knockout mice, implying a novel role of gGag in circumventing the action of APOBEC3
in vivo
.
Endogenous CD317/Tetherin Limits Replication of HIV-1 and Murine Leukemia Virus in Rodent Cells and Is Resistant to Antagonists from Primate Viruses
Authors: Goffinet Christine , Schmidt Sarah , Kern Christian , Oberbremer Lena , Keppler Oliver T.
Published: August 2010

Human CD317 (BST-2/tetherin) is an intrinsic immunity factor that blocks the release of retroviruses, filoviruses, herpesviruses, and arenaviruses. It is unclear whether CD317 expressed endogenously in rodent cells has the capacity to interfere with the replication of the retroviral rodent pathogen murine leukemia virus (MLV) or, in the context of small-animal model development, contributes to the well-established late-phase restriction of human immunodeficiency virus type 1 (HIV-1). Here, we show that small interfering RNA (siRNA)-mediated knockdown of CD317 relieved a virion release restriction and markedly enhanced the egress of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) in rat cells, including primary macrophages. Moreover, rodent CD317 potently inhibited MLV release, and siRNA-mediated depletion of CD317 in a mouse T-cell line resulted in the accelerated spread of MLV. Several virus-encoded antagonists have recently been reported to overcome the restriction imposed by human or monkey CD317, including HIV-1 Vpu, envelope glycoproteins of HIV-2 and Ebola virus, Kaposi's sarcoma-associated herpesvirus K5, and SIV Nef. In contrast, both rat and mouse CD317 showed a high degree of resistance to these viral antagonists. These data suggest that CD317 is a broadly acting and conserved mediator of innate control of retroviral infection and pathogenesis that restricts the release of retroviruses and lentiviruses in rodents. The high degree of resistance of the rodent CD317 restriction factors to antagonists from primate viruses has implications for HIV-1 small-animal model development and may guide the design of novel antiviral interventions.
Gag-Protease-Mediated Replication Capacity in HIV-1 Subtype C Chronic Infection: Associations with HLA Type and Clinical Parameters
Authors: Wright Jaclyn K. , Brumme Zabrina L. , Carlson Jonathan M. , Heckerman David , Kadie Carl M. , Brumme Chanson J. , Wang Bingxia , Losina Elena , Miura Toshiyuki , Chonco Fundisiwe , van der Stok Mary , Mncube Zenele , Bishop Karen , Goulder Philip J. R. , Walker Bruce D. , Brockman Mark A. , Ndung'u Thumbi
Published: August 2010

The mechanisms underlying HIV-1 control by protective HLA class I alleles are not fully understood and could involve selection of escape mutations in functionally important Gag epitopes resulting in fitness costs. This study was undertaken to investigate, at the population level, the impact of HLA-mediated immune pressure in Gag on viral fitness and its influence on HIV-1 pathogenesis. Replication capacities of 406 recombinant viruses encoding plasma-derived Gag-protease from patients chronically infected with HIV-1 subtype C were assayed in an HIV-1-inducible green fluorescent protein reporter cell line. Viral replication capacities varied significantly with respect to the specific HLA-B alleles expressed by the patient, and protective HLA-B alleles, most notably HLA-B*81, were associated with lower replication capacities. HLA-associated mutations at low-entropy sites, especially the HLA-B*81-associated 186S mutation in the TL9 epitope, were associated with lower replication capacities. Most mutations linked to alterations in replication capacity in the conserved p24 region decreased replication capacity, while most in the highly variable p17 region increased replication capacity. Replication capacity also correlated positively with baseline viral load and negatively with baseline CD4 count but did not correlate with the subsequent rate of CD4 decline. In conclusion, there is evidence that protective HLA alleles, in particular HLA-B*81, significantly influence Gag-protease function by driving sequence changes in Gag and that conserved regions of Gag should be included in a vaccine aiming to drive HIV-1 toward a less fit state. However, the long-term clinical benefit of immune-driven fitness costs is uncertain given the lack of correlation with longitudinal markers of disease progression.
Side Chain Packing below the Fusion Peptide Strongly Modulates Triggering of the Hendra Virus F Protein
Authors: Smith Everett Clinton , Dutch Rebecca Ellis
Published: August 2010

Triggering of the Hendra virus fusion (F) protein is required to initiate the conformational changes which drive membrane fusion, but the factors which control triggering remain poorly understood. Mutation of a histidine predicted to lie near the fusion peptide to alanine greatly reduced fusion despite wild-type cell surface expression levels, while asparagine substitution resulted in a moderate restoration in fusion levels. Slowed kinetics of six-helix bundle formation, as judged by sensitivity to heptad repeat B-derived peptides, was observed for all H372 mutants. These data suggest that side chain packing beneath the fusion peptide is an important regulator of Hendra virus F triggering.
Very Few Substitutions in a Germ Line Antibody Are Required To Initiate Significant Domain Exchange
Authors: Huber Michael , Le Khoa M. , Doores Katie J. , Fulton Zara , Stanfield Robyn L. , Wilson Ian A. , Burton Dennis R.
Published: August 2010

2G12 is a broadly neutralizing anti-HIV-1 monoclonal human IgG1 antibody reactive with a high-mannose glycan cluster on the surface of glycoprotein gp120. A key feature of this very highly mutated antibody is domain exchange of the heavy-chain variable region (VH) with the VHof the adjacent Fab of the same immunoglobulin, which assembles a multivalent binding interface composed of two primary binding sites in close proximity. A non-germ line-encoded proline in the elbow between VHand CH1 and an extensive network of hydrophobic interactions in the VH/VH′ interface have been proposed to be crucial for domain exchange. To investigate the origins of domain exchange, a germ line version of 2G12 that behaves as a conventional antibody was engineered. Substitution of 5 to 7 residues for those of the wild type produced a significant fraction of domain-exchanged molecules, with no evidence of equilibrium between domain-exchanged and conventional forms. Two substitutions not previously implicated, AH14and EH75, are the most crucial for domain exchange, together with IH19at the VH/VH′ interface and PH113in the elbow region. Structural modeling gave clues as to why these residues are essential for domain exchange. The demonstration that domain exchange can be initiated by a small number of substitutions in a germ line antibody suggests that the evolution of a domain-exchanged antibody responsein vivomay be more readily achieved than considered to date.
Stably Expressed APOBEC3F Has Negligible Antiviral Activity
Authors: Miyagi Eri , Brown Charles R. , Opi Sandrine , Khan Mohammad , Goila-Gaur Ritu , Kao Sandra , Walker Robert C. , Hirsch Vanessa , Strebel Klaus
Published: August 2010

APOBEC3F (A3F) is a member of the family of cytidine deaminases that is often coexpressed with APOBEC3G (A3G) in cells susceptible to HIV infection. A3F has been shown to have strong antiviral activity in transient-expression studies, and together with A3G, it is considered the most potent cytidine deaminase targeting HIV. Previous analyses suggested that the antiviral properties of A3F can be dissociated from its catalytic deaminase activity. We were able to confirm the deaminase-independent antiviral activity of exogenously expressed A3F; however, we also noted that exogenous expression was associated with very high A3F mRNA and protein levels. In analogy to our previous study of A3G, we produced stable HeLa cell lines constitutively expressing wild-type or deaminase-defective A3F at levels that were more in line with the levels of endogenous A3F in H9 cells. A3F expressed in stable HeLa cells was packaged into Vif-deficient viral particles with an efficiency similar to that of A3G and was properly targeted to the viral nucleoprotein complex. Surprisingly, however, neither wild-type nor deaminase-defective A3F inhibited HIV-1 infectivity. These results imply that the antiviral activity of endogenous A3F is negligible compared to that of A3G.
Onchocerciasis in Anambra State, Southeast Nigeria: endemicity and clinical manifestations
Authors: Mbanefo Evaristus Chibunna , Eneanya Christine Ifeoma , Nwaorgu Obioma C , Otiji Moses Obiefuna , Oguoma Victor Mmaduabuchi , Ogolo Bernice Amala
Published: August 2010

Background

A cross-sectional study was performed to determine the current endemicity of onchocerciasis in Ayamelum Local Council, Anambra State, Southeast Nigeria, where community-directed treatment with ivermectin has been implemented for over a decade.

Methods

An estimate of the endemicity of onchocerciasis was obtained using the rapid assessment method in 894 subjects from 13 communities selected by multistage sampling. Dermatological and ocular manifestations were analysed and classified using standard criteria.

Results

Onchocerca volvulus nodules were recorded in 86 (9.6±1.9%) of the subjects, and 186 (20.8±3.7%) had one or more of the various classes of onchocercal skin diseases (OSD). Prevalence was dependent on age (p=0.001), but not on sex (p=0.31). There was a total absence of symptoms in the youngest age group and a low prevalence among subjects in their second decade of life. Pearson’s correlation showed a strong positive correlation between nodular rate and prevalence of chronic papular onchodermatitis (r=0.943) and a poor correlation with acute papular onchodermatitis (r=0.259). Age-dependent analysis of various classes of OSDs showed that the rate of acute papular onchodermatitis increased with age up to the third decade of life and decreased steadily thereafter, while the chronic forms of OSD increased with age for both sexes. Infection was dependent on occupation and proximity of the village to the vector breeding sites.

Conclusions

Generally low prevalence in the population and absence of symptoms among the youngest age group emphasise the success of the intervention, but the persistent occurrence of acute disease may suggest a shortfall due to low coverage or non-compliance with the mass chemotherapeutic regimen.
Considerations and proposals for the management of patients after prolonged intensive care unit admission
Authors: Johns Robin H , Dawson Deborah , Ball Jonathan
Published: August 2010

The majority of patients admitted to the intensive care unit (ICU) have a short stay of only a few days. However a small but significant number require prolonged intensive care. This is typically due to persisting, and sometimes complex, medical/surgical problems. Discharge of such ICU patients requires a comprehensive, multidisciplinary, verbal and written handover to the receiving ward team. As with any acutely ill adult in hospital, post-ICU patients should be carefully monitored with ‘track and trigger’ systems such as the Early Warning Score. Those with unexpected physiological deterioration should be promptly reviewed by senior clinicians and/or medical emergency/critical care outreach teams and considered for ICU re-admission where appropriate. Patients who have received prolonged organ support in the ICU are often affected by a number of specific medical problems such as ventilatory insufficiency, cardiac dysfunction, kidney injury, nutritional deficiency, ICU acquired weakness, and brain injury. They also frequently experience physical disability and psychosocial problems including delirium, anxiety, depression, post-traumatic stress disorder, cognitive dysfunction, and disturbed sleep. Structured rehabilitation programmes for post-ICU patients, tailored to individual needs, should be commenced on the ICU and continued through to and beyond hospital discharge. Care bundles, which are widely used on the ICU, are groups of interventions employed to optimise treatments or minimise complication rates. They may be additionally useful in the post-ICU ward setting by prompting clinicians to focus on, and address, commonly occurring medical and psychosocial problems in these patients.
ON AN INEQUALITY BETWEEN UNKNOTTING NUMBER AND CROSSING NUMBER OF LINKS
Authors: HANAKI RYO , KANADOME JUNSUKE
Published: August 2010

It is well-known that for any link L, twice the unknotting number of L is less than or equal to the crossing number of L. Taniyama characterized the links which satisfy the equality. We characterize the links where twice the unknotting number is equal to the crossing number minus one. As a corollary, we show that for any link L with twice the unknotting number of L is greater than or equal to the crossing number of L minus two, every minimal diagram of L realizes the unknotting number.
THE JONES AND ALEXANDER POLYNOMIALS FOR SINGULAR LINKS
Authors: FIEDLER THOMAS
Published: August 2010

We extend the Kauffman state models of the Jones and Alexander polynomials of classical links to state models of their two-variable extensions in the case of singular links. Moreover, we extend both of them to polynomials with d + 1 variables for long singular knots with exactly d double points. These extensions can detect non-invertibility of long singular knots.
CONJUGATE GENERATORS OF KNOT AND LINK GROUPS
Authors: CALLAHAN JASON
Published: August 2010

This note establishes a stronger version of a conjecture of Reid and others in the arithmetic case: if two elements of equal trace (e.g. conjugate elements) generate an arithmetic two-bridge knot or link group, then the elements are parabolic (and hence peripheral). This includes the figure-eight knot and Whitehead link groups. Similarly, if two conjugate elements generate the trefoil knot group, then the elements are peripheral.
ENCRYPTION-BASED NETWORKING QUANTUM TELEPORTATION WITH TRIPLET GREENBERGER–HORNE–ZEILINGER STATES
Authors: GUO YING , Zeng Guihua
Published: August 2010

An encryption-based networking quantum teleportation scheme is proposed for the secure quantum communication network based on the novel networking quantum key distribution (NQKD) with the Greenberger–Horne–Zeilinger (GHZ) state. The security is exactly guaranteed via the entanglement of the GHZ quantum system. In the process of quantum teleportation, the server Charlie prepares the GHZ states and the users exploit the four local unitary operations corresponding to the keys shared aforehand to encrypt/decrpt for the initial messages. One legal user can communicate with another on the network securely as they may perform a quantum privacy application on the encrypted quantum states transmitted in quantum channel. Its intrinsic efficiency is high as almost all the instances are useful and each GHZ state can carry two different encrypted single-qubit states. To reconstruct these transmitted messages, the users exploit Bell measurement and perform local operations with respect to the shared keys in NQKD, which will improve its security in a noise quantum channel.
QUANTUM TELEPORTATION VIA PHOTONIC FARADAY ROTATION
Authors: CHEN JUAN-JUAN , AN JUN-HONG
Published: August 2010

We propose a scheme for deterministically teleporting a pure quantum state, making use of the Faraday rotation of photonic polarization in cavity QED system. Based on the single-photon input-output process regarding cavities, the scheme works well even in low-Q cavities. Since only virtual excitation of the atoms is involved, it is also insensitive to atomic spontaneous emission. Besides, the CNOT operation replaced by the Faraday rotation is not needed in the scheme, which could greatly relax the experimental difficulty.
DECAY OF COHERENCE AND ENTANGLEMENT OF A SUPERPOSITION STATE FOR A CONTINUOUS VARIABLE SYSTEM IN AN ARBITRARY HEAT BATH
Authors: FORD G. W. , O'CONNELL R. F.
Published: August 2010

We consider the case of a pair of particles initially in a superposition state corresponding to a separated pair of wave packets. In contrast to a previous related work, we avoid a master equation approach and we calculate exactly the time development of this non-Gaussian state due to interaction with an arbitrary heat bath. We find that coherence decays continuously, as expected. We then investigate entanglement and find that at a finite time the system becomes separable (not entangled). Thus, we see that entanglement sudden death is also prevalent in continuous variable systems which should raise concern for the designers of entangled systems.
EXACT NON-IDENTITY CHECK IS NQP-COMPLETE
Authors: TANAKA YU
Published: August 2010

To understand quantum gate array complexity, we define a problem named exact non-identity check, which is a decision problem to determine whether a given classical description of a quantum circuit is strictly equivalent to the identity or not. We show that the computational complexity of this problem is non-deterministic quantum polynomial-time (NQP)-complete. As corollaries, it is derived that exact non-equivalence check of two given classical descriptions of quantum circuits is also NQP-complete and that minimizing the number of quantum gates for a given quantum circuit without changing the implemented unitary operation is NQP-hard.
β-octabromo-meso-tris(pentafluorophenyl)corrole: reductive demetalation-based synthesis of a heretofore inaccessible, perhalogenated free-base corrole
Authors: Capar Can , Hansen Lars-Kristian , Conradie Jeanet , Ghosh Abhik
Published: August 2010

Long known in various metal-complexed forms, β-octabromo-meso-tris(pentafluorophenyl)corrole, H3[Br8TPFPC ], has not been available as a free ligand until now. It can be prepared in high yield (86%) via reductive demetalation (conc. H2SO4 , FeCl2 ) of Mn[Br8TPFPC ]. Interestingly, the same conditions did not result in demetalation of the analogous copper complex, which may be contrasted to the behavior of many other copper corroles, which demetalate cleanly. X-ray crystallographic analysis revealed a unique "half-saddled" conformation, wherein two of the pyrrole rings on one side of the direct pyrrole-pyrrole linkage are strongly tilted up and down relative to each other, whereas the other two pyrrole rings are roughly in the mean plane of the macrocycle.
Synthesis and optical properties of tetrapyrazinoporphyrazines containing asymmetrical alkyl chains and t-butylphenyl groups
Authors: Jang Chun Keun , Kim Song Hak , Jaung Jae-Yun
Published: August 2010

Tetrapyrazinoporphyrazine magnesium complexes with four long alkyl groups and four 4-tert-butyl phenyl groups at the peripheral positions were synthesized from 2,3-dicyano-5-(4-tert-butylphenyl)-6-alkyl pyrazine derivatives using freshly prepared solutions of magnesium butoxide in n-butanol. The corresponding metal-free derivatives were obtained through treatment with p-toluenesulfonic acid. The resulting chromophores contained alkyl chains substituted at their peripheries and showed good solubility in organic solvents. The fluorescence of the tetrapyrazinoporphyrazine magnesium complexes was greatly influenced by the intermolecular aggregation. Q band spectra of the porphyrazine magnesium complexes in DMF exhibited the characteristic patterns of the monomeric species, with fluorescence maxima at 653–658 nm. These new compounds were characterized using UV-visible spectroscopy, MALDI-TOF-MS and 1H NMR spectroscopy.
SV2 regulates neurotransmitter release via multiple mechanisms
Authors: Nowack Amy , Yao Jia , Custer Kenneth L. , Bajjalieh Sandra M.
Published: August 2010

Among the proteins that mediate calcium-stimulated transmitter release, the synaptic vesicle protein 2 (SV2) stands out as a unique modulator specific to the neurons and endocrine cells of vertebrates. In synapses, SV2 regulates the expression and trafficking of the calcium sensor protein synaptotagmin, an action consistent with the reduced calcium-mediated exocytosis observed in neurons lacking SV2. Yet SV2 contains amino acid motifs consistent with it performing other actions that could regulate presynaptic functioning and that might underlie the mechanism of drug action. To test the role of these functional motifs, we performed a mutagenic analysis of SV2A and assessed the ability of mutant SV2A proteins to restore normal synaptic transmission in neurons from SV2A/B knockout mice. We report that SV2A-R231Q, harboring a mutation in a canonical transporter motif, restored normal synaptic depression (a measure of release probability and signature deficit of neurons lacking SV2). In contrast, normal synaptic depression was not restored by SV2A-W300A and SV2A-W666A, harboring mutations of conserved tryptophans in the 5th and 10th transmembrane domains. Although they did not rescue normal neurotransmission, SV2A-W300A and SV2A-W666A did restore normal levels of synaptotagmin expression and internalization. This indicates that tryptophans 300 and 666 support an essential action of SV2 that is unrelated to its role in synaptotagmin expression or trafficking. These results indicate that SV2 performs at least two actions at the synapse that contribute to neurotransmitter release.
Effect of Ca2+ binding properties of troponin C on rate of skeletal muscle force redevelopment
Authors: Lee Ryan S. , Tikunova Svetlana B. , Kline Kristopher P. , Zot Henry G. , Hasbun Javier E. , Minh Nguyen Van , Swartz Darl R. , Rall Jack A. , Davis Jonathan P.
Published: August 2010

To investigate effects of altering troponin (Tn)C Ca2+ binding properties on rate of skeletal muscle contraction, we generated three mutant TnCs with increased or decreased Ca2+ sensitivities. Ca2+ binding properties of the regulatory domain of TnC within the Tn complex were characterized by following the fluorescence of an IAANS probe attached onto the endogenous Cys99 residue of TnC. Compared with IAANS-labeled wild-type Tn complex, V43QTnC, T70DTnC, and I60QTnC exhibited ∼1.9-fold higher, ∼5.0-fold lower, and ∼52-fold lower Ca2+ sensitivity, respectively, and ∼3.6-fold slower, ∼5.7-fold faster, and ∼21-fold faster Ca2+ dissociation rate ( koff), respectively. On the basis of Kd and koff, these results suggest that the Ca2+ association rate to the Tn complex decreased ∼2-fold for I60QTnC and V43QTnC. Constructs were reconstituted into single-skinned rabbit psoas fibers to assess Ca2+ dependence of force development and rate of force redevelopment ( ktr) at 15°C, resulting in sensitization of both force and ktr to Ca2+ for V43QTnC, whereas T70DTnC and I60QTnC desensitized force and ktr to Ca2+, I60QTnC causing a greater desensitization. In addition, T70DTnC and I60QTnC depressed both maximal force (Fmax) and maximal ktr. Although V43QTnC and I60QTnC had drastically different effects on Ca2+ binding properties of TnC, they both exhibited decreases in cooperativity of force production and elevated ktr at force levels <30%Fmax vs. wild-type TnC. However, at matched force levels >30%Fmax ktr was similar for all TnC constructs. These results suggest that the TnC mutants primarily affected ktr through modulating the level of thin filament activation and not by altering intrinsic cross-bridge cycling properties. To corroborate this, NEM-S1, a non-force-generating cross-bridge analog that activates the thin filament, fully recovered maximal ktr for I60QTnC at low Ca2+ concentration. Thus TnC mutants with altered Ca2+ binding properties can control the rate of contraction by modulating thin filament activation without directly affecting intrinsic cross-bridge cycling rates.
Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?
Authors: DeLorey D. S. , Buckwalter J. B. , Mittelstadt S. W. , Anton M. M. , Kluess H. A. , Clifford P. S.
Published: August 2010

We tested the hypothesis that tonic adrenergic and nonadrenergic receptor-mediated sympathetic vasoconstriction would increase at rest and during exercise with advancing age. Young ( n = 6; 22 ± 1 mo; means ± SE) and old ( n = 6; 118 ± 9 mo) beagles were studied. Selective antagonists for alpha-1, alpha-2, neuropeptide Y (NPY), and purinergic (P2x) receptors were infused at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade. Prazosin produced similar increases in vascular conductance in young and old beagles at rest (Young: 158 ± 34%; Old: 98 ± 19%) and during exercise at 2.5 mph (Young: 80 ± 10%; Old: 58 ± 12%) and 4 mph and 2.5% grade (Young: 57 ± 5%; Old: 26 ± 4%). Rauwolscine caused similar ( P > 0.05) increases in vascular conductance in old compared with young dogs at rest (Young: 119 ± 25%; Old: 64 ± 22%) and at 2.5 mph (Young: 86 ± 13%; Old: 60 ± 7%) and 4 mph with 2.5% grade (Young: 61 ± 5%; Old: 43 ± 7%). N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-d-arginine amide (BIBP) caused a smaller increase ( P < 0.05) in vascular conductance in old compared with young dogs at rest (Young: 179 ± 44%; Old: 91 ± 22%), whereas similar increases ( P > 0.05) of experimental limb vascular conductance in young and old dogs occurred following BIBP during exercise at 2.5 mph (Young: 56 ± 16%; Old: 50 ± 12%) and 4 mph and 2.5% grade (Young: 45 ± 10%; Old: 25 ± 7%). Pyridoxal-phosphate-6-azophenyl-2′-4′-disulfonic acid infusion produced a larger increase in vascular conductance in old compared with young beagles at rest (Young: 88 ± 14%; Old: 191 ± 58%), whereas similar increases were observed at 2.5 mph (Young: 47 ± 18%; Old: 31 ± 11%) and 4 mph with 2.5% grade (Young: 26 ± 13%; Old: −18 ± 8%). At rest, NPY receptor-mediated restraint of skeletal muscle blood flow was reduced with advancing age, whereas P2xreceptor-mediated restraint of skeletal muscle blood flow was increased. During exercise, the magnitude of adrenergic and nonadrenergic sympathetic vasoconstriction was not different between young and old dogs. Overall, these data demonstrate that adrenergic receptor-mediated vasoconstriction was not elevated at rest, but nonadrenergic sympathetic vasoconstriction was altered under basal conditions in aged beagles.
Effects of dietary K on cell-surface expression of renal ion channels and transporters
Authors: Frindt Gustavo , Palmer Lawrence G.
Published: August 2010

Changes in apical surface expression of ion channels and transporters in the superficial rat renal cortex were assessed using biotinylation and immunoblotting during alterations in dietary K intake. A high-K diet increased, and a low-K diet decreased, both the overall and surface abundance of the β- and γ-subunits of the epithelial Na channel (ENaC). In the case of γ-ENaC, the effect was specific for the 65-kDa cleaved form of the protein. The overall amount of α-ENAC was also increased with increasing K intake. The total expression of the secretory K+channels (ROMK) increased with a high-K diet and decreased with a low-K diet. The surface expression of ROMK increased with high K intake but was not significantly altered by a low-K diet. In contrast, the amounts of total and surface protein representing the thiazide-sensitive NaCl cotransporter (NCC) decreased with increasing K intake. We conclude that modulation of K+secretion in response to changes in dietary K intake involves changes in apical K+permeability through regulation of K+channels and in driving force subsequent to alterations in both Na delivery to the distal nephron and Na+uptake across the apical membrane of the K+secretory cells.
Strength–Duration Relationship for Extracellular Neural Stimulation: Numerical and Analytical Models
Authors: Boinagrov David , Loudin Jim , Palanker Daniel
Published: August 2010

The strength–duration relationship for extracellular stimulation is often assumed to be similar to the classical intracellular stimulation model, with a slope asymptotically approaching 1/τ at pulse durations shorter than chronaxy. We modeled extracellular neural stimulation numerically and analytically for several cell shapes and types of active membrane properties. The strength–duration relationship was found to differ significantly from classical intracellular models. At pulse durations between 4 μs and 5 ms stimulation is dominated by sodium channels, with a slope of −0.72 in log-log coordinates for the Hodgkin–Huxley ion channel model. At shorter durations potassium channels dominate and slope decreases to −0.13. Therefore the charge per phase is decreasing with decreasing stimulus duration. With pulses shorter than cell polarization time (∼0.1–1 μs), stimulation is dominated by polarization dynamics with a classical −1 slope and the charge per phase becomes constant. It is demonstrated that extracellular stimulation can have not only lower but also upper thresholds and may be impossible below certain pulse durations. In some regimes the extracellular current can hyperpolarize cells, suppressing rather than stimulating spiking behavior. Thresholds for burst stimuli can be either higher or lower than that of a single pulse, depending on pulse duration. The modeled thresholds were found to be comparable to published experimental data. Electroporation thresholds, which limit the range of safe stimulation, were found to exceed stimulation thresholds by about two orders of magnitude. These results provide a biophysical basis for understanding stimulation dynamics and guidance for optimizing the neural stimulation efficacy and safety.
Influence of Near Threshold Visual Distractors on Perceptual Detection and Reaching Movements
Authors: Deplancke A. , Madelain L. , Chauvin A. , Cardoso-Leite P. , Gorea A. , Coello Y.
Published: August 2010

Providing evidence against a dissociation between conscious vision for perception and unconscious vision for action, recent studies have suggested that perceptual and motor decisions are based on a unique signal but distinct decisional thresholds. The aim of the present study was to provide a direct test of this assumption in a perceptual-motor dual task involving arm movements. In 300 trials, 10 participants performed speeded pointing movements toward a highly visible target located at 10° from the fixation point and ±45° from the body midline. The target was preceded by one or two close to threshold distractor(s) (80 ms stimulus onset asynchrony) presented ±30° according to the target location. After each pointing movement, participants judged whether the distractor was present or not on either side of the target. Results showed a robust reaction time facilitation effect and a deviation toward the distractor when the distractor was both present and consciously perceived (Hit). A small reaction time facilitation was also observed when two distractors were physically present but undetected (double-miss)—this facilitation being highly correlated with the physical contrast of the distractors. These results are compatible with the theory proposing that perceptual and motor decisions are based on a common signal but emerge from a contrast dependent fixed threshold for motor responses and a variable context dependent criterion for perceptual responses. This paper thus extends to arm movement control previous findings related to oculomotor control.
Pathology of Macular Foveoschisis Associated with Degenerative Myopia
Authors: Tang Johnny , Rivers Michael B. , Moshfeghi Andrew A. , Flynn Harry W. , Chan Chi-Chao
Published: August 2010

This is a clinicopathological paper on the histologic findings in myopia-associated macular foveoschisis. The findings on ophthalmic pathological study of a 73-year-old woman with high myopia are reviewed. Multiple retinoschisis cavities involving both the macula and retinal periphery were disclosed. Our paper offers tissue evidence and supports recent ocular coherence tomography reports of eyes with high myopia and associated macular foveoschisis.
Vitamin D and Serum Cytokines in a Randomized Clinical Trial
Authors: Yusupov Eleanor , Li-Ng Melissa , Pollack Simcha , Yeh James K. , Mikhail Mageda , Aloia John F.
Published: August 2010

Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines.Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 μg/d(2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-γ, TNF-α) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group.Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (−62.9%,P<.0001), IFN-γ(−38.9%,P<.0001), IL-4 (−50.8%,P=.001), IL-8 (−48.4%,P<.0001), and IL-10 (−70.4%,P<.0001). In the placebo group, there were significant declines for GM-CSF (−53.2%,P=.0007) and IFN-γ(−34.4%,P=.0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of64.3±25.4 nmol/L to88.5±23.2 nmol/L.Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.
Battery Recharging Issue for a Two‐Power‐Level Flywheel System
Authors: Gonçalves de Oliveira Janaína , Bernhoff Hans
Published: August 2010

A novel battery recharging system for an all‐electric driveline comprising a flywheel with a permanent magnet double wound synchronous machine (motor/generator) is presented. The double winding enables two voltage levels and two different power levels. This topology supersedes other all‐electric drivelines. The battery operates in a low‐power regime supplying the average power whereas the flywheel delivers and absorbs power peaks, which are up to a higher order of magnitude. The topology presents new challenges for the power conversion system, which is the focus of this investigation. The main challenge is the control of the power flow to the battery when the vehicle is parked despite the decay of the flywheel machine voltage; which is dependent on its charge state, that is, rotational speed. The design and simulation of an unidirectional DC/DC buck/boost converter for a variable rotational speed flywheel is presented. Conventional power electronic converters are used in a new application, which can maintain a constant current or voltage on the battery side. Successful PI current control has been implemented and simulated, together with the complete closed loop system.
Cryptanalysis and Improvement of a Block Cipher Based on Multiple Chaotic Systems
Authors: He Jun , Qian Haifeng , Zhou Yuan , Li Zhibin
Published: August 2010

Wang and Yu proposed a block cipher scheme based on dynamic sequences generated
by multiple chaotic systems, which overcomes the problem of periodical degradation on
random sequences due to computational precision. Their scheme has a feature that a
plaintext is encrypted by a keystream created from several one‐dimensional chaotic maps.
However, this feature results in some weaknesses of the encryption algorithm. We show
three kinds of attacks in this paper, through which one can recover the plaintext from
a given ciphertext without the secret key. We also present an improvement on their
scheme, which prevents the three attacks mentioned above. Security of the enhanced
cipher is presented and analyzed, which shows that our improved scheme is secure under
the current attacks.
The Cost Efficiency of the Brazilian Electricity Distribution Utilities: A Comparison of Bayesian SFA and DEA Models
Authors: Pereira de Souza Marcus Vinicius , Diallo Madiagne , Castro Souza Reinaldo , Baidya Tara Keshar Nanda
Published: August 2010

The purpose of this study is to evaluate the efficiency indices for 60 Brazilian electricity distribution utilities. These scores are obtained by DEA (Data Envelopment Analysis) and Bayesian Stochastic Frontier Analysis models, two techniques that can reduce the information asymmetry and improve the regulator′s skill to compare the performance of the utilities, a fundamental aspect in incentive regulation schemes. In addition, this paper also addresses the problem of identifying outliers and influential observations in deterministic nonparametric DEA models.
Temperature Cooling and Warming Rates in Three Different Built Environments within Nairobi City, Kenya
Authors: Makokha George Lukoye , Shisanya Chris Allan
Published: August 2010

Urban canyon, urban park, and suburban surface air temperature data for hot‐wet, hot‐dry, cool‐dry, and warm‐wet periods in Nairobi city were analyzed to detect differences in the cooling and warming rates. Measurement of temperature for thirty continuous days was done at each of the three sites for each of the above periods. The cooling and warming rates were computed on an hourly basis beginning at 6.00 P.M., the approximate time of sunset. The results of the study showed that the largest cooling and warming rates were generally experienced during the hot‐dry period while the lowest during the cool‐dry period. Cooling and warming rates were also found to be the highest at the suburban site and the lowest at the urban canyon site. The differences in the conditions of the built environment at the three sites could explain the cause of the differential cooling and warming rates. The study recommends proper planning of the built environment to ameliorate the problem of excessive nocturnal heat loads within the built environment.
Porcine Cysticercosis and Risk Factors in The Gambia and Senegal
Authors: Secka Arss , Marcotty Tanguy , De Deken Redgi , Van Marck Eric , Geerts Stanny
Published: August 2010

During a stratified cross-sectional survey, 1705 pigs were sampled from 279 randomly selected households, 63 randomly selected communities and villages, from four study areas in The Gambia and Senegal during the period October 2007 to January 2008. Porcine cysticercosis prevalence detected by tongue inspection at animal level per study area ranged from 0.1% to 1.0%. Using an antigen-detection ELISA the seroprevalence of cysticercosis at both community/village and animal levels for the four selected study areas is: Western region 80.0% (95%CI: 52.4%–93.6%) and 4.8% (95%CI: 3.4%–6.5%), Bignona 86.7% (95%CI: 59.8%–96.6%) and 8.9% (95%CI: 5.0%–15.5%), Kolda 82.4% (95%CI: 46.8%–96.1%) and 13.2% (95%CI: 10.8%–16.0%), and Ziguinchor 81.3% (95%CI: 43.5%–96.1%) and 6.4% (95%CI: 4.0%–10.1%), respectively. No risk factors for cysticercosis were found significant in this study. This study proved that porcine cysticercosis is endemic and distributed widely in the study areas though its incidence might be suppressed by the generalised use of toilets and latrines in the study areas.
Therapeutic Implications of PPARγin Cardiovascular Diseases
Authors: Hasegawa Hiroshi , Takano Hiroyuki , Komuro Issei
Published: August 2010

Peroxisome proliferator-activated receptor-γ(PPARγ) is the members of the nuclear receptor superfamily as a master transcriptional factor that promotes differentiation of preadipocytes by activating adipose-specific gene expression. Although PPARγis expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPARγis also present in a variety of cell types including vascular cells and cardiomyocytes. Activation of PPARγsuppresses production of inflammatory cytokines, and there is accumulating data that PPARγligands exert antihypertrophy of cardiomyocytes and anti-inflammatory, antioxidative, and antiproliferative effects on vascular wall cells and cardiomyocytes. In addition, activation of PPARγis implicated in the regulation of endothelial function, proliferation and migration of vascular smooth muscle cells, and activation of macrophages. Many studies suggest that PPARγligands not only ameliorate insulin sensitivity, but also have pleiotropic effects on the pathophysiology of atherosclerosis, cardiac hypertrophy, ischemic heart, and myocarditis.
Normal and Osculating Planes of Δ‐Regular Curves
Authors: Paşalı Atmaca Sibel
Published: August 2010

We present the normal and osculating planes of the curves parameterized by a compact subinterval of a time scale.
A Rational Self-Sacrificing Template Route toLiMn2O4Nanotubes and Nanowires
Authors: Yang Baojun , Yuan Xinsong , Chai Duoli
Published: August 2010

Single-crystallineLiMn2O4nanotubes and nanowires have been synthesized via a low-temperature molten salt synthesis method, using the preparedβ-MnO2nanotubes andα-MnO2nanowires as the precursors and self-sacrificing template. The materials were investigated by a variety of techniques, including X-ray powder diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and high-resolution transmission electron microscopy (HRTEM). The results indicate that the preparedLiMn2O4nanotube and nanowire samples are both spinel phase, have lengths up to several micrometers and diameters of hundreds and tens of nanometers, respectively.
Water-Soluble Chitosan Nanoparticles Inhibit Hypercholesterolemia Induced by Feeding a High-Fat Diet in Male Sprague-Dawley Rats
Authors: Tao Yi , Zhang Hongliang , Gao Bing , Guo Jiao , Hu Yinming , Su Zhengquan
Published: August 2010

Chitosan, a deacetylated product of chitin, has been demonstrated to lower cholesterol in humans and animals. However, chitosan is not fully soluble in water which would influence absorption in the human intestine. In addition, water-soluble chitosan (WSC) has higher reactivity compared to chitosan. The present study was designed to clarify the effects of WSC and water-soluble chitosan nanoparticles (WSC-NPs) on hypercholesterolemia induced by feeding a high-fat diet in male Sprague-Dawley rats. WSC-NPs were prepared by the ionic gelation method and the spray-drying technique. The nanoparticles were spherical in shape and had a smooth surface. The mean size of WSC-NPs was 650 nm variing from 500 to 800 nm. Results showed that WSC-NPs reduced the blood lipids and plasma viscosity significantly and increased the serum superoxide dismutase (SOD) activities significantly. This paper is the first report of the lipid-lowering effects of WSC-NPs suggesting that the WSC-NPs could be used for the treatment of hypercholesterolemia.
Image-Guided Breast Tumor Therapy Using a Small Interfering RNA Nanodrug
Authors: Kumar Mohanraja , Yigit Mehmet , Dai Guangping , Moore Anna , Medarova Zdravka
Published: August 2010

Iron oxide nanoparticles offer a feasible tool for combined imaging and delivery of small interfering RNA (siRNA) to tumors, stimulating active interest in exploring different imaging and delivery platforms suitable for detection by a variety of modalities. In this study, we describe the synthesis and testing of a tumor-targeted nanodrug (MN-EPPT-siBIRC5) that is designed to specifically shuttle siRNA to human breast tumors. The nanodrug binds the tumor-specific antigen uMUC-1, which is found in >90% of human breast adenocarcinomas. MN-EPPT-siBIRC5 consists of superparamagnetic iron oxide nanoparticles [for magnetic resonance imaging (MRI)], the dye Cy5.5 (for near-IR optical imaging), peptides (EPPT) that specifically target uMUC-1, and a synthetic siRNA that targets the tumor-specific antiapoptotic gene BIRC5. Nanodrug uptake by human breast adenocarcinoma cells resulted in a significant downregulation of BIRC5. Following i.v. delivery into subcutaneous mouse models of breast cancer, the nanodrug showed a preferential tumor uptake, which could be visualized by MRI and near-IR optical imaging. Furthermore, MRI could be used to quantitatively monitor nanodrug bioavailability in the tumor tissue throughout the course of treatment. Intravenous injection of the agent once a week over 2 weeks resulted in the induction of considerable levels of necrosis and apoptosis in the tumors, translating into a significant decrease in tumor growth rate. Our strategy permits the simultaneous tumor-specific delivery of siRNA to tumors and the imaging of the delivery process. More generally, it illustrates the potential to apply this approach to many human cancer studies, including for basic tumor biology and therapy. Cancer Res; 70(19); 7553–61. ©2010 AACR.