bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiviral Activity of Salmonid Gamma Interferon against Infectious Pancreatic Necrosis Virus and Salmonid Alphavirus and Its Dependency on Type I Interferon
Authors: Sun Baojian , Skjæveland Ingrid , Svingerud Tina , Zou Jun , Jørgensen Jorunn , Robertsen Børre
Published: June 2011

We investigated the antiviral activity and gene induction properties of interferon gamma (IFN-γ) compared to type I IFN (IFNa1) in Atlantic salmon. IFN-γ protected salmon cells against infectious pancreatic necrosis virus (IPNV)-induced cytopathic effect (CPE), reduced virus titers, and inhibited the synthesis of the viral structural protein VP3. Moreover, IFN-γ showed potent antiviral activity against salmonid alphavirus 3 (SAV3) measured as a reduction in virus nsP1 transcripts. IFN-γ (a type II IFN) had less specific antiviral activity against IPNV than IFNa1, showing a half-maximal effective concentration of 1.6 ng/ml versus 31 pg/ml determined in the CPE reduction assay. Compared to IFNa1, IFN-γ was a more effective inducer of the antiviral protein GBP, several interferon regulatory transcription factors (IRFs), and the chemokine IP-10. The antiviral activity of IFN-γ may also in part be ascribed to upregulation of Mx, ISG15, and viperin. These are typical type I IFN-induced genes in mammals and were also more strongly induced by IFNa1 than by IFN-γ in salmon cells. Fish and mammalian IFN-γ thus show strikingly similar gene induction properties. Interestingly, the antiviral activity of IFN-γ against IPNV and SAV3 and its ability to induce Mx and ISG15 markedly decreased in the presence of neutralizing antiserum against IFNa1. In contrast, antiIFNa1 had no effect on the induction of IRF-1 and IP-10 by IFN-γ. This suggests that the antiviral activity of IFN-γ is partially dependent on IFNa induction. However, because antiIFNa1 could not abolish the IFN-γ-mediated induction of Mx and ISG15 completely, IFN-γ may possibly also induce such genes directly.
Adenovirus Type 5 Early Region 1B 55K Oncoprotein-Dependent Degradation of Cellular Factor Daxx Is Required for Efficient Transformation of Primary Rodent Cells
Authors: Schreiner Sabrina , Wimmer Peter , Groitl Peter , Chen Shuen-Yuan , Blanchette Paola , Branton Philip E. , Dobner Thomas
Published: June 2011

Early region 1B 55K (E1B-55K) from adenovirus type 5 (Ad5) is a multifunctional regulator of lytic infection and contributesin vitroto complete cell transformation of primary rodent cells in combination with Ad5 E1A. Inhibition of p53 activated transcription plays a key role in processes by which E1B-55K executes its oncogenic potential. Nevertheless, additional functions of E1B-55K or further protein interactions with cellular factors of DNA repair, transcription, and apoptosis, including Mre11, PML, and Daxx, may also contribute to the transformation process. In line with previous results, we performed mutational analysis to define a Daxx interaction motif within the E1B-55K polypeptide. The results from these studies showed that E1B-55K/Daxx binding is not required for inhibition of p53-mediated transactivation or binding and degradation of cellular factors (p53/Mre11). Surprisingly, these mutants lost the ability to degrade Daxx and showed reduced transforming potential in primary rodent cells. In addition, we observed that E1B-55K lacking the SUMO-1 conjugation site (SCS/K104R) was sufficient for Daxx interaction but no longer capable of E1B-55K-dependent proteasomal degradation of the cellular factor Daxx. These results, together with the observation that E1B-55K SUMOylation is required for efficient transformation, provides evidence for the idea that SUMO-1-conjugated E1B-55K-mediated degradation of Daxx plays a key role in adenoviral oncogenic transformation. We assume that the viral protein contributes to cell transformation through the modulation of Daxx-dependent pathways. This further substantiates the assumption that further mechanisms for efficient transformation of primary cells can be separated from functions required for the inhibition of p53-stimulated transcription.
The E7 Open Reading Frame Acts in
cis
and in
trans
To Mediate Differentiation-Dependent Activities in the Human Papillomavirus Type 16 Life Cycle
Authors: Bodily Jason M. , Mehta Kavi P. M. , Cruz Linda , Meyers Craig , Laimins Laimonis A.
Published: June 2011

Human papillomaviruses (HPVs) are the causative agents of several important genital and other mucosal cancers. The HPV16 E7 gene encodes a viral oncogene that is necessary for the continued growth of cancer cells, but its role in the normal, differentiation-dependent life cycle of the virus is not fully understood. The function of E7 in the viral life cycle was examined using a series of mutations of E7 created in the context of the complete HPV16 genome. The effect of these E7 mutations on key events of the viral life cycle, including immortalization, episomal maintenance, late promoter activation, and infectious virion synthesis, was examined. Our studies show that the pRb binding domain is indispensable for early viral activities, whereas the C-terminal zinc finger domain contributed primarily to very late events. Mutations of the casein kinase II phosphorylation site caused a complex phenotype involving both the function of E7 protein and a
cis
element necessary for the activation of the late promoter, identifying for the first time a promoter element important for late promoter function in the context of the viral genome. All mutant genomes tested showed reduced viral titers following growth in organotypic raft cultures. These studies clarify the role of E7 as a regulator of late events in the differentiation-dependent HPV life cycle.
Alteration of the Chronic Wasting Disease Species Barrier byIn VitroPrion Amplification
Authors: Kurt Timothy D. , Seelig Davis M. , Schneider Jay R. , Johnson Christopher J. , Telling Glenn C. , Heisey Dennis M. , Hoover Edward A.
Published: June 2011

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids now detected in 19 states of the United States, three Canadian provinces, and South Korea. Whether noncervid species can be infected by CWD and thereby serve as reservoirs for the infection is not known. To investigate this issue, we previously used serial protein misfolding cyclic amplification (sPMCA) to demonstrate that CWD prions can amplify in brain homogenates from several species sympatric with cervids, including prairie voles (Microtus ochrogaster) and field mice (Peromyscusspp.). Here, we show that prairie voles are susceptible to mule deer CWD prionsin vivoand that sPMCA amplification of CWD prions in vole brain enhances the infectivity of CWD for this species. Prairie voles inoculated with sPMCA products developed clinical signs of TSE disease approximately 300 days prior to, and more consistently than, those inoculated with CWD prions from deer brain. Moreover, the deposition patterns and biochemical properties of protease-resistant form of PrP (PrPRES) in the brains of affected voles differed from those in cervidized transgenic (CerPrP) mice infected with CWD. In addition, voles inoculated orally with sPMCA products developed clinical signs of TSE and were positive for PrPRESdeposition, whereas those inoculated orally with deer-origin CWD prions did not. These results demonstrate that transspecies sPMCA of CWD prions can enhance the infectivity and adapt the host range of CWD prions and thereby may be useful to assess determinants of prion species barriers.
SH2-Containing Inositol 5′-Phosphatase Inhibits Transformation of Abelson Murine Leukemia Virus
Authors: Fessler Shawn P. , Rosenberg Naomi , Baughn Linda B.
Published: June 2011

v-Abl protein tyrosine kinase encoded by Abelson murine leukemia virus (Ab-MLV) transforms pre-B cells. Transformation requires the phosphatidylinositol 3-kinase (PI3K) pathway. This pathway is antagonized by SH2-containing inositol 5′-phosphatase (SHIP), raising the possibility that v-Abl modulates PI3K signaling through SHIP. Consistent with this, we show that v-Abl expression reduces levels of full-length p145 SHIP in a v-Abl kinase activity-dependent fashion. This event requires signals from the Abl SH2 domain but not the carboxyl terminus. Forced expression of full-length SHIP significantly reduces Ab-MLV pre-B-cell transformation. Therefore, reduction of SHIP protein by v-Abl is a critical component in Ab-MLV transformation.
Repeated Application of Low-Frequency Electroacupuncture Improves High-Fructose Diet-Induced Insulin Resistance in Rats
Authors: Tominaga Atsushi , Ishizaki Naoto , Naruse Yoshihisa , Kitakoji Hiroshi , Yamamura Yoshiharu
Published: June 2011

Background

Insulin resistance is frequently present in obesity and during the development of type 2 diabetes mellitus.

Objective

The purpose of the present study was to investigate the effect of electroacupuncture (EA) on high-fructose diet (HFD)-induced insulin resistance.

Methods

Male Wistar rats were fed HFD for 4 weeks and developed insulin resistance. Insulin sensitivity was assessed by clamp. The number of animals was seven, eight and seven in the control, HFD and HFD+EA groups, respectively. AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4) in skeletal muscle were measured by Western blotting analysis (n=7 in each group). EA stimulation was carried out 12 times over 4 weeks at an intensity of 1–3 mA and a frequency of 2/15 Hz in a conscious state without restraint.

Results

There was no significant difference in mean body weight and fasting blood glucose concentration between groups at the end of the experiment. The mean glucose infusion rate during the clamp was significantly lower in the HFD group than in controls (p<0.05). There was no significant difference in expression of GLUT4 in skeletal muscle in the control and each group. Phosphorylated AMPKα (Thr172) in skeletal muscle showed a significant increase immediately after the final EA stimulation when compared with the control group (p<0.05).

Conclusion

Repeated application of EA is capable of improving diet-induced insulin resistance, probably through activation of AMPK signalling pathways in skeletal muscle. These results suggest that repeated application of EA may have beneficial effects on diet-induced insulin resistance.
No longer lost in translation: the art and science of sports injury prevention implementation research
Authors: Finch Caroline F
Published: June 2011

It is now understood that sports injury interventions will not have significant public health impact if they are not widely accepted and adopted by target sports participants. Although there has been increasing recognition of the need for intervention studies conducted within the real-world context of sports delivery, very few studies have been conducted in this important area. A major reason for this is that there are significant challenges in conducting implementation research; the more traditional sports medicine approaches may not be fully appropriate and new ways of thinking about how to design, conduct and report such research is needed. Moreover, real-world implementation of sports injury interventions and evaluation of their effectiveness needs to start to take into account the broad ecological context in which they are introduced, as well as considering the best way to translate this knowledge to reach the audiences who most need to benefit from such research. This overview paper provides perspectives and guidance on the design, conduct and evaluation of sports injury intervention implementation studies, including better understanding of the complexity of the ecological settings for intervention delivery. Some conceptual approaches that could be adopted in future implementation studies are discussed; particular emphasis is given to Intervention Mapping as a tool to assist intervention development, Diffusion of Innovations Theory to guide the planning of intervention strategies and the RE-AIM (reach, effectiveness, adoption, implementation and maintenance) framework for programme evaluation and programme design. Finally, a broad agenda for this emerging important field of sports medicine research is outlined.
Predictors of hospitalised patients' preferences for physician-directed medical decision-making
Authors: Chung Grace S , Lawrence Ryan E , Curlin Farr A , Arora Vineet , Meltzer David O
Published: June 2011

Background

Although medical ethicists and educators emphasise patient-centred decision-making, previous studies suggest that patients often prefer their doctors to make the clinical decisions.

Objective

To examine the associations between a preference for physician-directed decision-making and patient health status and sociodemographic characteristics.

Methods

Sociodemographic and clinical information from all consenting general internal medicine patients at the University of Chicago Medical Center were examined. The primary objectives were to (1) assess the extent to which patients prefer an active role in clinical decision-making, and (2) determine whether religious service attendance, the importance of religion, self-rated spirituality, Charlson Comorbidity Index, self-reported health, Vulnerable Elder Score and several demographic characteristics were associated with these preferences.

Results

Data were collected from 8308 of 11 620 possible participants. Ninety-seven per cent of respondents wanted doctors to offer them choices and to consider their opinions. However, two out of three (67%) preferred to leave medical decisions to the doctor. In multiple regression analyses, preferring to leave decisions to the doctor was associated with older age (per year, OR=1.019, 95% CI 1.003 to 1.036) and frequently attending religious services (OR=1.5, 95% CI 1.1 to 2.1, compared with never), and it was inversely associated with female sex (OR=0.6, 95% CI 0.5 to 0.8), university education (OR=0.6, 95% CI 0.4 to 0.9, compared with no high school diploma) and poor health (OR=0.6, 95% CI 0.3 to 0.9).

Conclusions

Almost all patients want doctors to offer them choices and to consider their opinions, but most prefer to leave medical decisions to the doctor. Patients who are male, less educated, more religious and healthier are more likely to want to leave decisions to their doctors, but effects are small.
Innovative surgery: the ethical challenges
Authors: Johnson Jane , Rogers Wendy
Published: June 2011

Innovative surgery raises four kinds of ethical challenges: potential harms to patients; compromised informed consent; unfair allocation of healthcare resources; and conflicts of interest. Lack of adequate data on innovations and lack of regulatory oversight contribute to these ethical challenges. In this paper these issues and the extent to which problems may be resolved by better evidence-gathering and more comprehensive regulation are explored. It is suggested that some ethical issues will be more resistant to resolution than others, owing to special features of both surgery and innovation.
PREVENTIVE MIGRATION VS. PREVENTIVE CHECKPOINTING FOR EXTREME SCALE SUPERCOMPUTERS
Authors: CAPPELLO FRANCK , CASANOVA HENRI , ROBERT YVES
Published: June 2011

An alternative to classical fault-tolerant approaches for large-scale clusters is failure avoidance, by which the occurrence of a fault is predicted and a preventive measure is taken. We develop analytical performance models for two types of preventive measures: preventive checkpointing and preventive migration. We instantiate these models for platform scenarios representative of current and future technology trends. We find that preventive migration is the better approach in the short term by orders of magnitude. However, in the longer term, both approaches have comparable merit with a marginal advantage for preventive checkpointing. We also develop an analytical model of the performance for fault tolerance based on periodic checkpointing and compare this approach to both failure avoidance techniques. We find that this comparison is sensitive to the nature of the stochastic distribution of the time between failures, and that failure avoidance is likely inferior to fault tolerance in the long term. Regardless, our result show that each approach is likely to achieve poor utilization for large-scale platforms (e.g., 220 nodes) unless the mean time between failures is large. We show how bounding parallel job size improves utilization, but conclude that achieving good utilization in future large-scale platforms will require a combination of techniques.
BUDGET ESTIMATION AND CONTROL FOR BAG-OF-TASKS SCHEDULING IN CLOUDS
Authors: OPRESCU ANA-MARIA , KIELMANN THILO , LEAHU HARALAMBIE
Published: June 2011

Commercial cloud offerings, such as Amazon's EC2, let users allocate compute resources on demand, charging based on reserved time intervals. While this gives great flexibility to elastic applications, users lack guidance for choosing between multiple offerings, in order to complete their computations within given budget constraints. In this work, we present BaTS, our budget-constrained scheduler. Using a small task sample, BaTS can estimate costs and makespan for a given bag on different cloud offerings. It provides the user with a choice of options before execution and then schedules the bag according to the user's preferences. BaTS requires no a-priori information about task completion times. We evaluate BaTS by emulating different cloud environments on the DAS-3 multi-cluster system. Our results show that BaTS correctly estimates budget and makespan for the scenarios investigated; the user-selected schedule is then executed within the given budget limitations.
Molecular Beam Epitaxy of In-Doped CdTe
Authors: Sugiyama Koichi
Published: June 2011

This error was made during the printing process. We sincerely apologize to the author, Dr. K. Sugiyama, for any inconvenience caused by the misprinting, and we must also apologize to Drs. K. Nakamura, M. Hikita, H. Asano and A. Terada for erroneously printing the title of their article and their names. We are now carrying out a thorough check of our printing system so as to prevent the possibility of any further errors of this kind. Dr. K. Sugiyama's paper is reprinted from Jpn. J. Appl. Phys. Vol. 21 (Part 1) No. 4 in the following pages, together with the corrected title and author's name.
Vapor Phase Epitaxial Growth of ZnSe Using Zinc and Selenium as Source Materials
Authors: Matsumoto Takashi , Nonaka Hideyuki , Ishida Tetsuro
Published: June 2011

The date of reception of the revised manuscript was omitted from the title page of this paper.
It should be inserted as follws:(Received March 29, 1983; revised manuscript received October 21, 1983; accepted for publication November 26, 1983)
Photoacoustic Imaging for The Melting of Gallium
Authors: Kojima Seiji
Published: June 2011

Figure 2 in the above paper was mistakenly printed in black-and-white in the November 1985, Vol. 24, No. 11. The complete paper with the relevant figure in colour is reporudced here.
Silicon Oxide Film Formation by Focused Ion Beam (FIB)-Assisted Deposition
Authors: Komano Haruki , Ogawa Youji , Takigawa Tadahiro
Published: June 2011

The received date of this paper should be corrected as follows: (Received July 3, 1989; accepted for publication October 12, 1989)
Local Tunneling Barrier Height on Si(111) Reconstructed Surfaces
Authors: Horiguchi Nobuhiro , Yonei Kazunori , Miyano Masahiro
Published: June 2011

The family name of the last author should read Masahiro Miyao
Dielectric and Conduction Properties in Nickel Doped Barium Strontium Titanate Ceramics
Authors: Hafid Mustapsha , Takeoka Shinsuke , Nishida Sousuke , Fukami Tatsuo , Sheng Jianxin
Published: June 2011

The authors and their affiliation should read Mustapsha Hafid, Souhaila Moudden, Chantal Proust1, Elisabeth Husson1, Shinsuke Takeoka2, Sousuke Nishida2, Tatsuo Fukami2and Jianxin Sheng2Faculty of Science, IBN Tofail University, B.P. 133, 14000 Kenitra, Morocco1CRPHT-CNRS, 1 D Avenue de la Recherche Scientifique, 45071 Orleans Cedex 2, Frence2Faculty of Engineering, Shinshu University, 500 Wakasato, Nagano 380, Japan
A Ruby Laser with External Mirrors of Large Spacing
Authors: Shimizu Tadao , Shimizu Fujio , Kawaguti Minato , Shimoda Koichi
Published: June 2011

The date received the paper should be read:(Received February 12, 1965)
Enhanced Ca2+ transport and muscle relaxation in skeletal muscle from sarcolipin-null mice
Authors: Tupling A. Russell , Bombardier Eric , Gupta Subash C. , Hussain Dawar , Vigna Chris , Bloemberg Darin , Quadrilatero Joe , Trivieri Maria G. , Babu Gopal J. , Backx Peter H. , Periasamy Muthu , MacLennan David H. , Gramolini Anthony O.
Published: June 2011

Sarcolipin (SLN) inhibits sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps. To evaluate the physiological significance of SLN in skeletal muscle, we compared muscle contractility and SERCA activity between Sln-null and wild-type mice. SLN protein expression in wild-type mice was abundant in soleus and red gastrocnemius (RG), low in extensor digitorum longus (EDL), and absent from white gastrocnemius (WG). SERCA activity rates were increased in soleus and RG, but not in EDL or WG, from Sln-null muscles, compared with wild type. No differences were seen between wild-type and Sln-null EDL muscles in force-frequency curves or maximum rates of force development (+dF/d t). Maximum relaxation rates (−dF/d t) of EDL were higher in Sln-null than wild type across a range of submaximal stimulation frequencies, but not during a twitch or peak tetanic contraction. For soleus, no differences were seen between wild type and Sln-null in peak tetanic force or +dF/d t; however, force-frequency curves showed that peak force during a twitch and 10-Hz contraction was lower in Sln-null. Changes in the soleus force-frequency curve corresponded with faster rates of force relaxation at nearly all stimulation frequencies in Sln-null compared with wild type. Repeated tetanic stimulation of soleus caused increased (−dF/d t) in wild type, but not in Sln-null. No compensatory responses were detected in analysis of other Ca2+ regulatory proteins using Western blotting and immunohistochemistry or myosin heavy chain expression using immunofluorescence. These results show that 1) SLN regulates Ca2+-ATPase activity thereby regulating contractile kinetics in at least some skeletal muscles, 2) the functional significance of SLN is graded to the endogenous SLN expression level, and 3) SLN inhibitory effects on SERCA function are relieved in response to repeated contractions thus enhancing relaxation rates.
Large-conductance voltage- and Ca2+-activated K+ channels regulate human detrusor smooth muscle function
Authors: Hristov Kiril L. , Chen Muyan , Kellett Whitney F. , Rovner Eric S. , Petkov Georgi V.
Published: June 2011

The large-conductance voltage- and Ca2+-activated K+ (BK) channel is expressed in many smooth muscle types, but its role in human detrusor smooth muscle (DSM) is unclear. With a multidisciplinary approach spanning channel molecules, single-channel activity, freshly isolated human DSM cells, intact DSM preparations, and the BK channel specific inhibitor iberiotoxin, we elucidated human DSM BK channel function and regulation. Native human DSM tissues were obtained during open surgeries from patients with no preoperative history of overactive bladder. RT-PCR experiments on single human DSM cells showed mRNA expression of BK channel α-, β1-, and β4-subunits. Western blot and immunocytochemistry confirmed BK channel α, β1, and β4 protein expression. Native human BK channel properties were described using the perforated whole cell configuration of the patch-clamp technique. In freshly isolated human DSM cells, BK channel blockade with iberiotoxin inhibited a significant portion of the total voltage step-induced whole cell K+ current. From single BK channel recordings, human BK channel conductance was calculated to be 136 pS. Voltage-dependent iberiotoxin- and ryanodine-sensitive transient BK currents were identified in human DSM cells. In current-clamp mode, iberiotoxin inhibited the hyperpolarizing membrane potential transients and depolarized the cell resting membrane potential. Isometric DSM tension recordings revealed that BK channels principally control the contractions of isolated human DSM strips. Collectively, our results indicate that BK channels are fundamental regulators of DSM excitability and contractility and may represent new targets for pharmacological or genetic control of urinary bladder function in humans.
Acamprosate-responsive brain sites for suppression of ethanol intake and preference
Authors: Brager Allison , Prosser Rebecca A. , Glass J. David
Published: June 2011

Acamprosate suppresses alcohol intake and craving in recovering alcoholics; however, the central sites of its action are unclear. To approach this question, brain regions responsive to acamprosate were mapped using acamprosate microimplants targeted to brain reward and circadian areas implicated in alcohol dependence. mPer2 mutant mice with nonfunctional mPer2, a circadian clock gene that gates endogenous timekeeping, were included, owing to their high levels of ethanol intake and preference. Male wild-type (WT) and mPer2 mutant mice received free-choice (15%) ethanol/water for 3 wk. The ethanol was withdrawn for 3 wk and then reintroduced to facilitate relapse. Four days before ethanol reintroduction, mice received bilateral blank or acamprosate-containing microimplants releasing ∼50 ng/day into reward [ventral tegmental (VTA), peduculopontine tegmentum (PPT), and nucleus accumbens (NA)] and circadian [intergeniculate leaflet (IGL) and suprachiasmatic nucleus (SCN)] areas. The hippocampus was also targeted. Circadian locomotor activity was measured throughout. Ethanol intake and preference were greater in mPer2 mutants than in wild-type (WT) mice (27 g·kg−1·day−1vs. 13 g·kg−1·day−1and 70% vs. 50%, respectively; both, P < 0.05). In WTs, acamprosate in all areas, except hippocampus, suppressed ethanol intake and preference (by 40–60%) during ethanol reintroduction. In mPer2 mutants, acamprosate in the VTA, PPT, and SCN suppressed ethanol intake and preference by 20–30%. These data are evidence that acamprosate's suppression of ethanol intake and preference are manifest through actions within major reward and circadian sites.
Local network regulation of orexin neurons in the lateral hypothalamus
Authors: Burt Julia , Alberto Christian O. , Parsons Matthew P. , Hirasawa Michiru
Published: June 2011

Obesity and inadequate sleep are among the most common causes of health problems in modern society. Thus, the discovery that orexin (hypocretin) neurons play a pivotal role in sleep/wake regulation, energy balance, and consummatory behaviors has sparked immense interest in understanding the regulatory mechanisms of these neurons. The local network consisting of neurons and astrocytes within the lateral hypothalamus and perifornical area (LH/PFA), where orexin neurons reside, shapes the output of orexin neurons and the LH/PFA. Orexin neurons not only send projections to remote brain areas but also contribute to the local network where they release multiple neurotransmitters to modulate its activity. These neurotransmitters have opposing actions, whose balance is determined by the amount released and postsynaptic receptor desensitization. Modulation and negative feedback regulation of excitatory glutamatergic inputs as well as release of astrocyte-derived factors, such as lactate and ATP, can also affect the excitability of orexin neurons. Furthermore, distinct populations of LH/PFA neurons express neurotransmitters with known electrophysiological actions on orexin neurons, such as melanin-concentrating hormone, corticotropin-releasing factor, thyrotropin-releasing hormone, neurotensin, and GABA. These LH/PFA-specific mechanisms may be important for fine tuning the firing activity of orexin neurons to maintain optimal levels of prolonged output to sustain wakefulness and stimulate consummatory behaviors. Building on these exciting findings should shed further light onto the cellular mechanisms of energy balance and sleep-wake regulation.
Regional and systemic hemodynamic responses following the creation of a murine arteriovenous fistula
Authors: Kang Lu , Yamada Satsuki , Hernandez Melissa C. , Croatt Anthony J. , Grande Joseph P. , Juncos Julio P. , Vercellotti Gregory M. , Hebbel Robert P. , Katusic Zvonimir S. , Terzic Andre , Nath Karl A.
Published: June 2011

The study of hemodynamic alterations following the creation of an arteriovenous fistula (AVF) is relevant to vascular adaptive responses and hemodialysis access dysfunction. This study examined such alterations in a murine AVF created by anastomosing the carotid artery to the jugular vein. AVF blood flow was markedly increased due to reduced AVF vascular resistance. Despite such markedly increased basal blood flow, AVF blood flow further increased in response to acetylcholine. This AVF model exhibited increased cardiac output and decreased systemic vascular resistance; the kidney, in contrast, exhibited decreased blood flow and increased vascular resistance. Augmentation in AVF blood flow was attended by increased arterial heme oxygenase-1 (HO-1) mRNA and protein expression, the latter localized to smooth muscle cells of the AVF artery; AVF blood flow was substantially reduced in HO-1−/− mice compared with HO-1+/+ mice. Finally, in a murine model of a representative disease known to exhibit impaired hemodynamic responses (sickle cell disease), the creation of an AVF was attended by decreased AVF flow and impaired AVF function. We conclude that this AVF model exhibits markedly increased AVF blood flow, a vasodilatory reserve capacity, increased cardiac output, decreased renal blood flow, and a dependency on intact hemodynamic responses, in general, and HO-1 expression, in particular, in achieving and maintaining AVF blood flow. We suggest that these findings support the utility of this model in investigating the basis for and the consequences of hemodynamic stress, including shear stress, and the pathobiology of hemodialysis AVF dysfunction.
Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons
Authors: Guan D. , Higgs M. H. , Horton L. R. , Spain W. J. , Foehring R. C.
Published: June 2011

After block of Kv1- and Kv2-mediated K+ currents in acutely dissociated neocortical pyramidal neurons from layers II/III of rat somatosensory and motor cortex, the remaining current is slowly activating and persistent. We used whole cell voltage clamp to show that the Kv7 blockers linopirdine and XE-991 blocked a current with similar kinetics to the current remaining after combined block of Kv1 and Kv2 channels. This current was sensitive to low doses of linopirdine and activated more slowly and at more negative potentials than Kv1- or Kv2-mediated current. The Kv7-mediated current decreased in amplitude with time in whole cell recordings, but in most cells the current was stable for several minutes. Current in response to a traditional M-current protocol was blocked by muscarine, linopirdine, and XE-991. Whole cell slice recordings revealed that the Q10 for channel deactivation was ∼2.5. Sharp electrode current-clamp recordings from adult pyramidal cells demonstrated that block of Kv7-mediated current with XE-991 reduced rheobase, shortened the latency to firing to near rheobase current, induced more regular firing at low current intensity, and increased the rate of firing to a given current injection. XE-991 did not affect single action potentials or spike frequency adaptation. Application of XE-991 also eliminated subthreshold voltage oscillations and increased gain for low-frequency inputs (<10 Hz) without affecting gain for higher frequency inputs. These data suggest important roles for Kv7 channels in subthreshold regulation of excitability, generation of theta-frequency subthreshold oscillations, regulation of interspike intervals, and biasing selectivity toward higher frequency inputs.
Inhibitory-excitatory synaptic balance is shifted toward increased excitation in magnocellular neurosecretory cells of heart failure rats
Authors: Potapenko Evgeniy S. , Biancardi Vinicia C. , Florschutz Renea M. , Ryu Pan D. , Stern Javier E.
Published: June 2011

Despite the well-established contribution of neurohumoral activation to morbidity and mortality in heart failure (HF) patients, relatively little is known about the underlying central nervous system mechanisms. In this study, we aimed to determine whether changes in GABAergic inhibitory and glutamatergic excitatory synaptic function contribute to altered hypothalamic magnocellular neurosecretory cell (MNC) activity in HF rats. Patch-clamp recordings were obtained from MNCs in brain slices from sham and HF rats. Glutamate excitatory (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) were simultaneously recorded, and changes in their strengths, as well as their interactions, were evaluated. We found a diminished GABAergic synaptic strength in MNCs of HF rats, reflected as faster decaying IPSCs and diminished mean IPSC charge transfer. Opposite changes were observed in glutamate EPSC synaptic strength, resulting in a shift in the GABA-glutamate balance toward a relatively stronger glutamate influence in HF rats. The prolongation of glutamate EPSCs during HF was mediated, at least in part, by an enhanced contribution of AMPA receptor desensitization to the EPSC decay time course. EPSC prolongation, and consequently increased unitary strength, resulted in a stronger AMPA receptor-mediated excitatory drive to firing discharge in MNCs of HF rats. Blockade of GABAAsynaptic activity diminished the EPSC waveform variability observed among events in sham rats, an effect that was blunted in HF rats. Together, our results suggest that opposing changes in postsynaptic properties of GABAergic and glutamatergic synaptic function contribute to enhanced magnocellular neurosecretory activity in HF rats.
Parental Concerns about the Health of Adolescents with Intellectual Disability: A Brief Report
Authors: Tucker Madonna , Taylor Gomez Miriam , Rey-Conde Therese , Lennox Nicholas
Published: June 2011

Background. Parents of adolescents with intellectual disability are concerned about the future health and well-being needs of their children. Method. Qualitative data was collected as part of a cross-sectional descriptive study and semi-structured interviews were conducted with 32 parents. The results were themed. Results. Most parents discussed areas of their children's health which made them anxious about the future. These concerns were collated into five themes. Conclusion. The health and well-being themes were dependency, general health, challenging behaviours, and increasing support needs.
Nonsurgical Outpatient Therapies for the Management of Female Stress Urinary Incontinence: Long-Term Effectiveness and Durability
Authors: Davila G. Willy
Published: June 2011

Objective. To evaluate long-term effectiveness and safety of conservative and minimally invasive outpatient treatments for female stress urinary incontinence (SUI) through a review of the literature.Methods. PubMed was searched for reports on prospective clinical trials with at least 12-month follow-up of minimally invasive treatments, pelvic floor rehabilitation, or pharmacotherapy in women with SUI. Each report was examined for long-term rates of effectiveness and safety.Results. Thirty-two clinical trial reports were included. Prospective long-term studies of pelvic floor rehabilitation were limited but indicated significant improvements with treatment adherence for at least 12 months. Poor initial tolerability with duloxetine resulted in substantial discontinuation. Most patients receiving transurethral radiofrequency collagen denaturation or urethral bulking agents reported significant long-term improvements, generally good tolerability, and safety.Conclusions. Conservative therapy is an appropriate initial approach for female SUI, but if therapy fails, radiofrequency collagen denaturation or bulking agents may be an attractive intermediate management step or alternative to surgery.
Primary Extranodal, Extralymphatic Hodgkin Lymphoma of the Mandible
Authors: Gonzalez-Fontal Guido Ricardo , Rosales Joaquin D. , Jaramillo Roberto , Henao-Martinez Andres F.
Published: June 2011

Primary extranodal, extralymphatic Hodgkin lymphomas (PEEHLs) are a rare occurrence. When they are encountered, they become diagnostic challenges. We are describing the uniqueness of a case of PEEHL affecting the mandible with his early response to the available chemotherapy.
Vici Syndrome: A Rare Autosomal Recessive Syndrome with Brain Anomalies, Cardiomyopathy, and Severe Intellectual Disability
Authors: Rogers R. Curtis , Aufmuth Bridgette , Monesson Stephanie
Published: June 2011

Purpose. The objective of this study was to present and describe two additional patients diagnosed with Vici syndrome.Methods. Clinical, laboratory, and imaging findings of the two siblings are discussed in detail. The two patients' descriptions are compared with the other eleven patients reported in the literature. We also presented detailed autopsy results on the male sibling, which demonstrated cytoplasmic vacuoles of the cardiomyocytes and confirmed the clinical findings.Results. The patients reported here include the 13th and 14th patients reported with Vici syndrome. The summary of findings present in these patients includes postnatal growth retardation, developmental delay, bilateral cataracts, agenesis of the corpus callosum, cerebellar anomalies, gyral abnormalities, seizures, hypotonia, and cardiomyopathy.Conclusion. Vici syndrome should be suspected in any child with agenesis of the corpus callosum and one of the following findings: cardiomyopathy, cataracts, immune deficiency, or cutaneous hypopigmentation.
Are School Factors Important for Measuring Teacher Effectiveness? A Multilevel Technique to Predict Student Gains through a Value-Added Approach
Authors: Subedi Bidya Raj , Swan Bonnie , Hynes Michael C.
Published: June 2011

This paper investigated the effect of teacher quality, represented by teacher level characteristics, on mathematics gain scores employing a three-level hierarchical linear model (HLM) through value-added model (VAM) approach. The analysis investigated significant predictors at student, teacher, and school levels for predicting students' gain scores and also estimated d-type effect sizes at teacher and school levels. We found the significant effects of teacher's mathematics content certification, teacher experience, and the interaction effects of mathematics content certification with student level predictors. Although school poverty significantly predicted students' gain scores, the school level effect was relatively small.
Exploring Online Synthesis for CGRAs with Specialized Operator Sets
Authors: Döbrich Stefan , Hochberger Christian
Published: June 2011

The design of energy-efficient systems has become a major challenge for engineers over the last decade. One way to save energy is to spread out computations in space rather than in time (as traditional processors do). Unfortunately, this requires to design specialized hardware for each application. Also, the nonrecurring expenses for the manufacturing of chips continuously grow. Implementing the computations on FPGAs and CGRAs solves this dilemma, as the non recurring expenses are shared between many different applications. We believe that online synthesis that takes place during the execution of an application is one way to broaden the applicability of reconfigurable architectures as no expert knowledge of synthesis and technologies is required. In this paper, we give a detailed analysis of the amount and specialization of resources in a CGRA that are required to grant a significant speedup of Java bytecode. In fact, we show that even a relatively small number of specialized reconfigurable resources is sufficient to speed up applications considerably. Particularly, we look at the number of dedicated multipliers and dividers. Also, we discuss the required number of concurrent memory access operations inside the CGRA. Again, it shows that two concurrent memory access operations are sufficient for almost all applications.
A General System for Automatic Biomedical Image Segmentation Using Intensity Neighborhoods
Authors: Chen Cheng , Ozolek John A. , Wang Wei , Rohde Gustavo K.
Published: June 2011

Image segmentation is important with applications to several problems in biology and medicine. While extensively researched, generally, current segmentation methods perform adequately in the applications for which they were designed, but often require extensive modifications or calibrations before being used in a different application. We describe an approach that, with few modifications, can be used in a variety of image segmentation problems. The approach is based on a supervised learning strategy that utilizes intensity neighborhoods to assign each pixel in a test image its correct class based on training data. We describe methods for modeling rotations and variations in scales as well as a subset selection for training the classifiers. We show that the performance of our approach in tissue segmentation tasks in magnetic resonance and histopathology microscopy images, as well as nuclei segmentation from fluorescence microscopy images, is similar to or better than several algorithms specifically designed for each of these applications.
Cytogenetic and Clinical Assessment of a Family with Treacher Collins Syndrome
Authors: Kumar Manoj , Kumar Rakesh , Tanwar Mukesh , Ghose Supriyo , Kaur Jasbir , Dada Rima
Published: June 2011

Treacher Collins syndrome (TCS) is a rare autosomal dominant disorder characterized by craniofacial deformities. It is the most common type of mandibulofacial dysostosis (MFD). The objective of this study is to do cytogenetic analysis of a TCS family. Physical examination and all available medical records were reviewed. 50 GTG-banded metaphases were analysed to detect any structural or numerical chromosomal abnormality. Downward slanting of palpebral fissures, hypoplasia of zygomatic arch complex, and hypoplasia of mandible were present in all. Cytogenetic findings show interstitial deletion in chromosomes 5(q32-q33) and 3(q23–q25). We report four members of three generations of a family having TCS in a unique way that the deletion has been found in 3q and 5q which has not been reported. Mosaicism of deletion on 5q was detected in all affected members whereas 3q deletion was found only in one member (II.2). This finding may represent a more severe manifestation of the TCS. Thus the evaluation and counselling of the TCS patients should be undertaken with caution.
Titanium-Based Biomaterials for Preventing Stress Shielding between Implant Devices and Bone
Authors: Niinomi M. , Nakai M.
Published: June 2011

β-type titanium alloys with low Young's modulus are required to inhibit bone atrophy and enhance bone remodeling for implants used to substitute failed hard tissue. At the same time, these titanium alloys are required to have high static and dynamic strength. On the other hand, metallic biomaterials with variable Young's modulus are required to satisfy the needs of both patients and surgeons, namely, low and high Young's moduli, respectively. In this paper, we have discussed effective methods to improve the static and dynamic strength while maintaining low Young's modulus forβ-type titanium alloys used in biomedical applications. Then, the advantage of low Young's modulus ofβ-type titanium alloys in biomedical applications has been discussed from the perspective of inhibiting bone atrophy and enhancing bone remodeling. Further, we have discussed the development ofβ-type titanium alloys with a self-adjusting Young's modulus for use in removable implants.
Highly Accurate Solution of Limit Cycle Oscillation of an Airfoil in Subsonic Flow
Authors: Zhang Y. P. , Chen Y. M. , Liu J. K. , Meng G.
Published: June 2011

The homotopy analysis method (HAM) is employed to propose a highly
accurate technique for solving strongly nonlinear aeroelastic systems of airfoils in
subsonic flow. The frequencies and amplitudes of limit cycle oscillations (LCOs)
arising in the considered systems are expanded as series of an embedding parameter.
A series of algebraic equations are then derived, which determine the coefficients of
the series. Importantly, all these equations are linear except the first one. Using some
routine procedures to deduce these equations, an obstacle would arise in expanding
some fractional functions as series in the embedding parameter. To this end, an
approach is proposed for the expansion of fractional function. This provides us with a
simple yet efficient iteration scheme to seek very‐high‐order approximations.
Numerical examples show that the HAM solutions are obtained very precisely. At the
same time, the CPU time needed can be significantly reduced by using the presented
approach rather than by the usual procedure in expanding fractional functions.
A New Approach for Solving Fully Fuzzy Linear Systems
Authors: Kumar Amit , Neetu  , Bansal Abhinav
Published: June 2011

Several authors have proposed different methods to find the solution of fully fuzzy linear systems (FFLSs) that is, fuzzy linear system with fuzzy coefficients involving fuzzy variables. But all the existing methods are based on the assumption that all the fuzzy coefficients and the fuzzy variables are nonnegative fuzzy numbers. In this paper a new method is proposed to solve an FFLS with arbitrary coefficients and arbitrary solution vector, that is, there is no restriction on the elements that have been used in the FFLS. The primary objective of this paper is thus to introduce the concept and a computational method for solving FFLS with no non negative constraint on the parameters. The method incorporates the principles of linear programming in solving an FFLS with arbitrary coefficients and is not only easier to understand but also widens the scope of fuzzy linear equations in scientific applications. To show the advantages of the proposed method over existing methods we solve three FFLSs.
A Novel Tumor Antigen Derived from Enhanced Degradation of Bax Protein in Human Cancers
Authors: Nunes Cláudia Trindade , Miners Kelly L. , Dolton Garry , Pepper Chris , Fegan Chris , Mason Malcolm D. , Man Stephen
Published: June 2011

Cancer cells frequently exhibit defects in apoptosis, which contribute to increased survival and chemotherapeutic resistance. For example, genetic mutations or abnormal proteasomal degradation can reduce expression of Bax which limits apoptosis. In cancers where abnormal proteasomal degradation of Bax occurs, we hypothesized that Bax peptides that bind to human leukocyte antigen (HLA) class I molecules would be generated for presentation to CD8+ T cells. To test this hypothesis, we generated T cells against pooled Bax peptides, using the blood of healthy human donors. Although T-cell responses were of low frequency (0.15%), a CD8+ T-cell clone (KSIVB17) was isolated that optimally recognized Bax136–144 peptide (IMGWTLDFL) presented by HLA-A*0201. KSIVB17 was able to recognize and kill a variety of HLA-matched cancer cells including primary tumor cells from chronic lymphocytic leukemia (CLL). No reactivity was seen against HLA-matched, nontransformed cells such as PHA blasts and skin fibroblasts. Furthermore, KSIVB17 reactivity corresponded with the proteasomal degradation patterns of Bax protein observed in cancer cells. Taken together, our findings suggest a new concept for tumor antigens based on regulatory proteins that are ubiquitously expressed in normal cells, but that have abnormally enhanced degradation in cancer cells. Bax degradation products offer candidate immune antigens in cancers such as CLL in which increased Bax degradation correlates with poor clinical prognosis. Cancer Res; 71(16); 5435–44. ©2011 AACR.