bluuebunny/crossref_metadata_2025 huggingface dataset:
Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder
Authors: Sprossmann Franz , Pankert Patrick , Sausbier Ulrike , Wirth Angela , Zhou Xiao‐Bo , Madlung Johannes , Zhao Hong , Bucurenciu Iancu , Jakob Andreas , Lamkemeyer Tobias , Neuhuber Winfried , Offermanns Stefan , Shipston Michael J. , Korth Michael , Nordheim Alfred , Ruth Peter , Sausbier Matthias
Published: February 2009

The large‐conductance, voltage‐dependent and Ca2+‐dependent K+(BK) channel links membrane depolarization and local increases in cytosolic free Ca2+to hyperpolarizing K+outward currents, thereby controlling smooth muscle contractility. Constitutive deletion of the BK channel in mice (BK−/−) leads to an overactive bladder associated with increased intravesical pressure and frequent micturition, which has been revealed to be a result of detrusor muscle hyperexcitability. Interestingly, time‐dependent and smooth muscle‐specific deletion of the BK channel (SM‐BK−/−) caused a more severe phenotype than displayed by constitutive BK−/−mice, suggesting that compensatory pathways are active in the latter. In detrusor muscle of BK−/−but not SM‐BK−/−mice, we found reduced L‐type Ca2+current density and increased expression of cAMP kinase (protein kinase A; PKA), as compared with control mice. Increased expression of PKA in BK−/−mice was accompanied by enhanced β‐adrenoceptor/cAMP‐mediated suppression of contractions by isoproterenol. This effect was attenuated by about 60–70% in SM‐BK−/−mice. However, the Rp isomer of adenosine‐3′,5′‐cyclic monophosphorothioate, a blocker of PKA, only partially inhibited enhanced cAMP signaling in BK−/−detrusor muscle, suggesting the existence of additional compensatory pathways. To this end, proteome analysis of BK−/−urinary bladder tissue was performed, and revealed additional compensatory regulated proteins. Thus, constitutive and inducible deletion of BK channel activity unmasks compensatory mechanisms that are relevant for urinary bladder relaxation.
Synergistic co‐operation of signal transducer and activator of transcription 5B with activator protein 1 in angiotensin II‐induced angiotensinogen gene activation in vascular smooth muscle cells
Authors: Han Mei , Li Ai‐Ying , Meng Fang , Dong Li‐Hua , Zheng Bin , Hu Hai‐Juan , Nie Lei , Wen Jin‐Kun
Published: February 2009

The binding sequences for signal transducer and activator of transcription (STAT) and activator protein 1 have been found in the promoter region of the angiotensinogen gene. We examined whether the elements for activator protein 1 and STAT5B function in angiotensinogen gene activation induced by angiotensin II in vascular smooth muscle cells. Stimulation with angiotensin II increased the level of angiotensinogen mRNA by 2.1‐fold in vascular smooth muscle cells. The increased level of angiotensinogen mRNA occurred with concurrent elevations in the levels of STAT5B and c‐Jun phosphorylation after stimulation with angiotensin II. Likewise, angiotensin II resulted in similar enhancements of the DNA‐binding activity of STAT5B and c‐Jun in angiotensin II‐induced angiotensinogen expression. Notably, the STAT5B–DNA complex interacted with the c‐Jun–DNA complex by forming a stable quaternary complex in angiotensin II‐induced angiotensinogen expression. Our findings support a model in which co‐operative interaction of STAT5B and activator protein 1 bound to the the promoter region provides maximal activation of angiotensinogen expression by angiotensin II in vascular smooth muscle cells.
Engineering thermal stability of l‐asparaginase by in vitro directed evolution
Authors: Kotzia Georgia A. , Labrou Nikolaos E.
Published: February 2009

l‐Asparaginase (EC 3.5.1.1, l‐ASNase) catalyses the hydrolysis of l‐Asn, producing l‐Asp and ammonia. This enzyme is an anti‐neoplastic agent; it is used extensively in the chemotherapy of acute lymphoblastic leukaemia. In this study, we describe the use of in vitro directed evolution to create a new enzyme variant with improved thermal stability. A library of enzyme variants was created by a staggered extension process using the genes that code for the l‐ASNases from Erwinia chrysanthemi and Erwinia carotovora. The amino acid sequences of the parental l‐ASNases show 77% identity, but their half‐inactivation temperature (Tm) differs by 10 °C. A thermostable variant of the E. chrysamthemi enzyme was identified that contained a single point mutation (Asp133Val). The Tm of this variant was 55.8 °C, whereas the wild‐type enzyme has a Tm of 46.4 °C. At 50 °C, the half‐life values for the wild‐type and mutant enzymes were 2.7 and 159.7 h, respectively. Analysis of the electrostatic potential of the wild‐type enzyme showed that Asp133 is located at a neutral region on the enzyme surface and makes a significant and unfavourable electrostatic contribution to overall stability. Site‐saturation mutagenesis at position 133 was used to further analyse the contribution of this position on thermostability. Screening of a library of random Asp133 mutants confirmed that this position is indeed involved in thermostability and showed that the Asp133Leu mutation confers optimal thermostability.
Constant interest rate projections without the curse of indeterminacy: A note
Authors: Galí Jordi
Published: February 2009

Constant interest rate projections are often criticized on the grounds that they are inconsistent with the existence of a unique equilibrium in a variety of forward‐looking models. This note shows how to construct constant interest rate projections that are not subject to that criticism, using a standard New Keynesian model as a reference framework.
The covering factor of high-redshift damped Lyman-α systems
Authors: Kanekar N. , Lane W. M. , Momjian E. , Briggs F. H. , Chengalur J. N.
Published: February 2009

We have used the Very Long Baseline Array to image 18 quasars with foreground damped Lyman-α systems (DLAs) at 327, 610 or 1420 MHz, to measure the covering factor f of each DLA at or near its redshifted H i 21 cm line frequency. Including six systems from the literature, we find that none of 24 DLAs at 0.09 < z < 3.45 has an exceptionally low covering factor, with f∼ 0.45–1 for the 14 DLAs at z > 1.5 and f∼ 0.41–1 for the 10 systems at z < 1, and consistent covering factor distributions in the two subsamples. The observed paucity of detections of H i 21 cm absorption in high-z DLAs thus cannot be explained by low covering factors and is instead likely to arise due to a larger fraction of warm H i in these absorbers.
Discovery of two distinct red clumps in NGC 419: a rare snapshot of a cluster at the onset of degeneracy
Authors: Girardi Léo , Rubele Stefano , Kerber Leandro
Published: February 2009

Colour–magnitude diagrams (CMDs) of the Small Magellanic Cloud (SMC) star cluster NGC 419, derived from Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) data, reveal a well-delineated secondary clump located below the classical compact red clump typical of intermediate-age populations. We demonstrate that this feature belongs to the cluster itself, rather than to the underlying SMC field. Then, we use synthetic CMDs to show that it corresponds very well to the secondary clump predicted to appear as a result of He-ignition in stars just massive enough to avoid e--degeneracy settling in their H-exhausted cores. The main red clump instead is made of the slightly less massive stars which passed through e- degeneracy and ignited He at the tip of the red giant branch. In other words, NGC 419 is the rare snapshot of a cluster while undergoing the fast transition from classical to degenerate H-exhausted cores. At this particular moment of a cluster's life, the colour distance between the main-sequence turn-off and the red clump(s) depends sensitively on the amount of convective core overshooting, Λc. By coupling measurements of this colour separation with fits to the red clump morphology, we are able to estimate simultaneously the cluster mean age (1.35+0.11-0.04 Gyr) and overshooting efficiency (Λc= 0.47+0.14-0.04). Therefore, clusters like NGC 419 may constitute important marks in the age scale of intermediate-age populations. After eye inspection of other CMDs derived from HST/ACS data, we suggest that the same secondary clump may also be present in the Large Magellanic Cloud clusters NGC 1751, 1783, 1806, 1846, 1852 and 1917.
Direct numerical simulations of the galactic dynamo in the kinematic growing phase
Authors: Gissinger Christophe , Fromang Sebastien , Dormy Emmanuel
Published: February 2009

We present kinematic simulations of a galactic dynamo model based on the large-scale differential rotation and the small-scale helical fluctuations due to supernova explosions. We report for the first time direct numerical simulations of the full galactic dynamo using an unparametrized global approach. We argue that the scale of helicity injection is large enough to be directly resolved rather than parametrized. While the actual superbubble characteristics can only be approached, we show that numerical simulations yield magnetic structures which are close to both the observations and the previous parametrized mean field models. In particular, the quadrupolar symmetry and the spiraling properties of the field are reproduced. Moreover, our simulations show that the presence of a vertical inflow plays an essential role to increase the magnetic growth rate. This observation could indicate an important role of the downward flow (possibly linked with galactic fountains) in sustaining galactic magnetic fields.
The mass and velocity anisotropy of the Carina, Fornax, Sculptor and Sextans dwarf spheroidal galaxies
Authors: Łokas Ewa L.
Published: February 2009

We model the large kinematic data sets for the four Milky Way dwarf spheroidal (dSph) satellites: Carina, Fornax, Sculptor and Sextans, recently published by Walker et al. The member stars are selected using a reliable dynamical interloper removal scheme tested on simulated data. Our member selection is more restrictive than the one based on metallicity indicators as it removes not only contamination due to Milky Way stars but also the unbound stars from the tidal tails. We model the cleaned data sets by adjusting the solutions of the Jeans equations to the profiles of the projected velocity dispersion and kurtosis. The data are well reproduced by models where mass follows light and the best-fitting stellar orbits are isotropic to weakly tangential, as expected from the tidal stirring scenario. The Fornax dwarf, with more than 2400 member stars, is a dSph galaxy with the most accurately determined mass to date: its 1σ error following from the sampling errors of the velocity moments is below 5 per cent. With mass-to-light ratio of 97 solar units, Sextans seems to be the most dark matter dominated of the four dSph galaxies.
A turbulent model of gamma-ray burst variability
Authors: Narayan Ramesh , Kumar Pawan
Published: February 2009

A popular paradigm to explain the rapid temporal variability observed in gamma-ray burst (GRB) light curves is the internal shock model. We propose an alternative model in which the radiating fluid in the GRB shell is relativistically turbulent with a typical eddy Lorentz factor γt. In this model, all pulses in the gamma-ray light curve are produced at roughly the same distance R from the centre of the explosion. The burst duration is ∼R/cΓ2, where Γ is the bulk Lorentz factor of the expanding shell, and the duration of individual pulses in the light curve is ∼R/cΓ2γ2t. The model naturally produces highly variable light curves with ∼γ2t individual pulses. Even though the model assumes highly inhomogeneous conditions, nevertheless the efficiency for converting jet energy to radiation is high.
Nurse practitioner practice patterns for exercise counseling
Authors: Tompkins Tawnya Horsley , Belza Basia , Brown Marie‐Annette
Published: February 2009

Purpose:  To describe nurse practitioner (NP) practice patterns for exercise counseling for adults.

Data sources:  Using a cross‐sectional design, participants completed a self‐administered questionnaire that ascertained barriers and facilitators encountered when providing exercise counseling. Participants included 398 NPs, who averaged 11 years in practice (SD = 7.9) and worked in a variety of practice areas.

Conclusions:  In a given week, about half (48%) of the NPs counseled more than 50% of their patients for exercise. The majority of participants (84%) agreed that exercise counseling is as valuable an intervention as prescribed medication. More than half (59%) of the participants exercised regularly. Barriers and facilitators to exercise counseling were predominately a patient’s lack of interest and the length of the patient visit. Specific strategies were identified for older adults and individuals residing in rural areas who may require more tailored exercise counseling. Participants demonstrated strong values about exercise counseling and observed that exercise had clear benefits for their patients. NP respondents offered recommendations focused on safety and adherence that can be used to improve exercise counseling.

Clinical implications:  Exercise is a crucial component of preventative health care. Studies have shown that healthcare provider recommendations can be effective in helping patients increase their exercise and activity.
The effectiveness of a peer‐mentored older adult fitness program on perceived physical, mental, and social function
Authors: Dorgo Sandor , Robinson Kristynia M , Bader Julia
Published: February 2009

Purpose:  The purpose of this research was to compare changes in perceived physical, mental, and social function measured by the Short Form‐36 (SF36vr2) in a group of older adults who were trained by peer mentors (PMs) versus a similar group trained by qualified kinesiology student mentors (SMs).

Data sources:  We conducted a two‐arm repeated measures longitudinal intervention and collected data for 87 PM and 44 SM participants. Pre‐ and post‐training subscale scores were computed for all eight subscales and the two summary physical and mental component scores. The percentage differences in the 10 scores were used as the response variables.

Conclusions:  After a 14‐week physical fitness intervention, perceived physical, mental, and social functioning improved significantly (p < .05) for the PM group, but not for the SM group (p > .06). Thus, older adults who participated in a physical fitness program with peer support perceived (a) overall improvement in physical and mental well‐being; (b) better social functioning, (c) enhanced ability to carry out physical and emotional roles, (d) improved general health, and (e) increased level of vitality. Thus, we conclude that peer‐mentored exercise programs for older adults are superior to programs mentored by young professionals and may lead to increased adherence.

Implications for practice:  Nurse practitioners routinely prescribe exercise while educating older adults about the benefits of an active lifestyle; however, older adults often remain sedentary and exhibit poor adherence to exercise. One potential solution is to use peer support. Two factors that can improve adherence are availability of structured exercise programs for the older adult and peer mentoring.
Good manufacturing practices
Authors: Ahmed A.
Published: February 2009

GMP introduces the application of Quality assurance principles in all steps involved in the collection, preparation, testing and distribution activities. GMP resulting in an increase of the availability of blood products.
Efficacy of different plasma sources in the treatment of thrombotic thrombocytopenic purpura
Authors: Pereira A.
Published: February 2009

Plasma exchange (PE) with fresh frozen plasma (FFP) is the treatment of choice for thrombotic thrombocytopenic purpura (TTP). Since TTP patients are exposed to a large number of plasma donors, they would benefit from any additional measure of plasma safety. Several such measures have been implemented but doubts remain as to whether the new types of plasma are as effective as FFP or whether some plasma fraction may be more effective.

 Cryoprecipitate‐poor plasma (CCP) was introduced in the therapeutics of TTP as a superior alternative to FFP. However, a clinical trial by the Canadian Apheresis Group failed to confirm the therapeutic superiority of CPP over FFP. Quarantine FFP (qFFP) is as effective as chemically modified plasma in the prevention of HIV, HBV and HCV transmission. Since qFFP has not been chemically manipulated, it must be regarded as equivalent to FFP both in terms of protein composition and therapeutic efficacy. Solvent/detergent (SD) plasma has long been used in the treatment of TTP and seems to be as effective as FFP. However, the only formal proof of efficacy consist in a small trial involving only 26 patients. Methylene blue‐photoinactivated plasma (MBPIP) is used in some regions in Spain and other European countries. A recent multicentric, ‘quasi experimental’ trial involving 102 cases of idiopathic TTP has shown that MBPIP is less effective than qFFP. Patient in the MBPIP arm required twice as many PE procedures and more adjuvant therapies to achieve remission and had a higher risk of TTP recrudescence. There is only one randomized trial comparing psoralen‐photoinactivated plasma to FFP. Though no difference was found in the rate of TTP remission, the trial recruited only 35 patients and was therefore severely underpowered. Levels of ADAMTS13 activity, as measured by the current laboratory assays, are similar in the various plasma sources despite some (i.e. MBPIP) are clinically less effective.

 In conclusion, FFP and qFFP are the plasma sources of choice for PE in TTP. CPP is probably as effective as FFP. MBPIP should be avoided because it is less effective. There is no proof that SD‐plasma and psoralen‐photoinactivated plasma are therapeutically equivalent to FFP. Normal levels of ADAMTS13 in therapeutic plasma seem not to be an accurate proxy of clinical effectiveness.
International Rare Blood Donor Centre
Authors: Nance S.
Published: February 2009

When a patient needs a rare blood type not present or identified routinely, immediate assistance is needed from the facility capable of supplying the product. If this reserve is not available domestically, patient care is in jeopardy. This presentation will discuss fundamentals of establishing an International Rare Blood Donor Center.
Hypoxia, melanocytes and melanoma – survival and tumor development in the permissive microenvironment of the skin
Authors: Bedogni Barbara , Powell Marianne Broome
Published: February 2009

The tissue microenvironment plays a critical role in cell survival and growth and can contribute to cell transformation and tumor development. Cellular interactions with the stroma and with other cells provide key signals that control cellular arrest or division, survival or death, and entrance or exit from a quiescent state. Together, these decisions are essential for maintenance of tissue homeostasis. Tissue oxygenation is an important component of the microenvironment that can acutely alter the behavior of a cell through the direct regulation of genes involved in cell survival, apoptosis, glucose metabolism, and angiogenesis. Loss of tissue homeostasis due to, for example, oncogene activation leads to the disruption of these signals and eventually can lead to cell transformation and tumor development. Here we review the role of tissue oxygenation, and in particular physiologic skin hypoxia, on cell survival and senescence and how it contributes to melanocyte transformation and melanoma development.
Five‐year incidence of visual impairment and blindness in older Icelanders: the Reykjavik Eye Study
Authors: Gunnlaugsdottir Elin , Arnarsson Arsaell , Jonasson Fridbert
Published: February 2009

Purpose:  This study examined age, sex and cause‐specific 5‐year incidence of visual impairment and blindness in a middle‐aged and elderly Icelandic population.

Methods:  The study cohort consisted of a population‐based, random sample of citizens aged ≥ 50 years. Of 1379 eligible subjects, 1045 underwent a baseline examination in 1996; 846 of the 958 survivors (88.2%) underwent a 5‐year follow‐up examination in 2001. All participants underwent an extensive ophthalmological examination including best corrected visual acuity (BCVA) using a Snellen chart. We used World Health Organization (WHO) criteria, which define visual impairment as BCVA in the better eye of < 6/18 and ≥ 3/60 and blindness as BCVA in the better eye of < 3/60. We also used US criteria, which consider BCVA of < 6/12 and > 6/60 in the better eye to represent visual impairment and BCVA of ≤ 6/60 in the better eye to represent blindness. The causes of incident visual loss in either eye were determined. Deterioration or improvement in vision were defined as a loss or gain of ≥ 2 Snellen lines.

Results:  According to WHO criteria, 5‐year incidence of bilateral visual impairment and blindness were 1.07% (95% confidence interval [CI] 0.37–1.76) and 0.35% (95% CI 0.00–0.76), respectively. Using US criteria, equivalent incidence of bilateral visual impairment and blindness were 3.49% (95% CI 2.24–4.74) and 0.95% (95% CI 0.29–1.60), respectively. Age‐related macular degeneration and cataract were the major causes of incident visual impairment and blindness.

Conclusions:  Incidences of visual impairment and blindness increased significantly with age. Age‐related macular degeneration, present in 75% of affected persons, was the most common cause of 5‐year incident legal blindness in this middle‐aged and elderly Icelandic population.
Distinct Brain Volume Changes Correlating with Clinical Stage, Disease Progression Rate, Mutation Size, and Age at Onset Prediction as Early Biomarkers of Brain Atrophy in Huntington's Disease
Authors: Squitieri Ferdinando , Cannella Milena , Simonelli Maria , Sassone Jenny , Martino Tiziana , Venditti Eugenio , Ciammola Andrea , Colonnese Claudio , Frati Luigi , Ciarmiello Andrea
Published: February 2009

Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross‐sectional and longitudinal rate of brain atrophy, quantitatively measured by fully‐automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene‐positive subjects with presymptomatic to advanced HD, and age‐matched healthy controls. Each of the three brain compartments we studied (WM, GM, and CSF) had a diverse role and their time courses differed in the development of HD. GM volume decreased early in life. Its decrease was associated with decreased serum brain‐derived‐neurotrophic‐factor and started even many years before onset symptoms, then decreased slowly in a nonlinear manner during the various symptomatic HD stages. WM volume loss also began in the presymptomatic stage of HD a few years before manifest symptoms appear, rapidly decreasing near to the zone‐of‐onset. Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG‐based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R2= 0.25, P < 0.0001).
Clinical Evaluation of the Daily Assessment of Symptoms‐Anxiety (DAS‐A): A New Instrument to Assess the Onset of Symptomatic Improvement in Generalized Anxiety Disorder
Authors: Feltner Douglas E. , Harness Jane , Brock Jerri , Sambunaris Angelo , Cappelleri Joseph C. , Morlock Robert
Published: February 2009

Introduction: Rapid onset of symptomatic improvement is a desirable characteristic of new generalized anxiety disorder (GAD) treatments. A validated rating scale is needed to assess GAD symptoms during the first days of treatment.

Aims: To provide clinical data to support the validation of the Daily Assessment of Symptoms‐Anxiety (DAS‐A), a new instrument to assess onset of symptomatic improvement in GAD.

Methods: We assessed the ability of the DAS‐A to detect onset of symptomatic improvement during the first week of therapy in 169 GAD patients randomized to paroxetine 20 mg/day, lorazepam 4.5 mg/day, or placebo for 4 weeks.

Results: On the primary outcome measure, average change from baseline over the first 6 days of DAS‐A assessments, lorazepam (−14.5 ± 1.8 [LS mean, SE]; P= 0.006 vs. placebo) showed a significant improvement versus placebo (−7.85 ± 1.7), whereas paroxetine (−8.3 ± 1.7; P= 0.83 vs. placebo) did not. Lorazepam produced a significant treatment effect on the DAS‐A at 24 h (P= 0.0004), whereas paroxetine did not (P= 0.5666). Both active drugs produced statistically significant improvement versus placebo on the DAS‐A total change score (last‐observation carried forward method; LOCF, endpoint). On the DAS‐A total change score (observed cases analysis), lorazepam produced statistically significant improvement versus placebo at weeks 1, 2, and 4 (P < 0.05; no week 3 visit), whereas paroxetine, separated from placebo at weeks 2 and 4 (P < 0.05). Both active drugs produced results on the Hamilton Anxiety Rating Scale (HAM‐A) at weeks 1 through 4 that were similar to those found on the DAS‐A.

Conclusions: These data indicate that the DAS‐A can detect symptomatic improvement in GAD patients treated with lorazepam during the first week of treatment, and, in a secondary analysis, as early as 24 h.
Congenital Dilatation of the Bile Ducts (Caroli's Disease) in Young Dogs
Authors: Görlinger S. , Rothuizen J. , Bunch S. , van den Ingh T.S.G.A.M.
Published: February 2009

We describe 8 young dogs with congenital dilatation of the intra‐ and extrahepatic bile ducts and diffuse cystic kidney disease, compatible with Caroli's disease in humans. The dogs were referred between 1980 and 2000 because of chronic disease at an age of 6 months to 3 years. These dogs included 3 Collies, 2 Frisian Stabyhouns, 2 Jack Russell Terriers, and 1 mixed‐breed dog. The most common signs were vomiting (6/6), polyuria and polydipsia (4/6), and anorexia (4/6). Ascites was a common finding (4/6). Clinicopathologic abnormalities were available for 6 dogs. All had increased plasma alkaline phosphatase activity and fasting bile acids; increased alanine aminotransferase activity and urea and creatinine concentrations were present in 50% of dogs. Ultrasound examination of the liver showed severely dilated bile ducts without evidence of obstruction, and calcification in all cases but 1. Postmortem examination revealed severe dilatation of the larger intra‐ and extrahepatic bile ducts. The common bile duct and gall bladder were normal, and the bile system was patent. The ducts contained a clear viscid fluid often with calcified material. Microscopically, marked portal fibrosis was present, often with abnormally structured dilated bile ducts lined with columnar or cuboid epithelium and regularly small calcifications. The lesion was complicated by ascending cholangitis in 1 dog. The kidneys showed marked cortical and medullary fibrosis with a diffuse radial cystic pattern; only slight renal fibrosis was found in the oldest dog. Seven dogs were euthanized without treatment; the oldest dog was alive and well 5 months after diagnosis and was maintained on a protein‐restricted diet.
Evaluation of the Effects of Clomipramine on Canine Thyroid Function Tests
Authors: Gulikers Keven P. , Panciera David L.
Published: February 2009

To evaluate the effect of long‐term clomipramine administration on the hypothalamic‐pituitary‐thyroid axis in healthy dogs, 14 healthy adult dogs were enrolled in a prospective study. Clomipramine (3 mg/kg PO q12h) was administered to all dogs beginning on day 0, and continued for 112 days. Serum total thyroxine (T4), free thyroxine (fT4), 3,5,3'‐triiodothyronine (T3), 3,3',5'‐triiodothyronine (reverse T3; rT3), and thyroid‐stimulating hormone (TSH) were measured on days 0, 7, 28, 42, 56, and 112. Thyrotropin‐releasing hormone (TRH) response tests were performed concurrently. Significant decreases were noted in serum T4, fT4, and rT3concentrations beginning on day 28 through the end of the study period. The lowest mean (ÆM) concentrations of T4(26 ± 1.2 to 17 ± 0.5 nmol/L) and rT3(1.21 ± 0.13 to 0.83 ± 0.08 nmol/L) occurred at day 112, whereas the lowest mean fT4(29 ± 2.4 to 18 ± 1.7 pmol/L) was found on day 56 of clomipramine treatment. The effect of treatment over time on serum T3concentration also was significant, but the deviation in T3from baseline was variable. No significant effect of clomipramine treatment was noted on either pre‐ or post‐TRH TSH concentrations. The 35 and 38% decreases in serum T4and fT4concentrations, respectively, during clomipramine administration may lead to a misdiagnosis of hypothyroidism. Although no evidence of hypothyroidism was noted in this study population, subclinical hypothyroidism may have occurred. A longer duration of treatment might further suppress thyroid function, and concurrent illness or other drug administration might exacerbate clomipramine's effects.
Influence of Host Factors on Survival in Dogs with Malignant Mammary Gland Tumors
Authors: Philibert Jeffrey C. , Snyder Paul W. , Glickman Nita , Glickman Larry T. , Knapp Deborah W. , Waters David J.
Published: February 2009

The purpose of our study was to determine if specific host factors, such as age at diagnosis, obesity, and hormone status, influence the prognosis of canine mammary gland carcinomas and to confirm if previously reported risk factors (ie, histologic subtype, tumor size, and World Health Organization [WHO] stage) were important in a large series of affected dogs. Ninety‐nine female dogs with mammary gland carcinomas, no previous therapy, an excisional biopsy, and known cause of death were studied. No significant association with survival was noted for age at diagnosis (chronologic or physiologic), obesity, or hormone status (ie, spayed versus intact, regardless of time of being spayed). Of the tumor factors analyzed, the histologic subtype anaplastic carcinoma (P= .02), WHO stage I (P= .01), evidence of metastasis at the time of diagnosis (P= .004), and tumor size of 3 cm or smaller (P= .005) all significantly influenced survival. Dogs that were classified as having tumor‐related mortality had a shorter postoperative survival compared to dogs that died of other causes (14 months versus 23 months;P= .03). In conclusion, histologic subtype, WHO stage, and tumor size remain important prognostic factors in canine mammary gland tumors. Further study of other prognostic factors is needed to determine which tumors are adequately addressed with local therapy only and which dogs may require adjuvant treatment with chemotherapy.
Management of Pneumothorax in Cattle by Continuous‐Flow Evacuation
Authors: Peek Simon F. , Slack J.A. , McGuirk Sheila M.
Published: February 2009

Pneumothorax in cattle can develop subsequent to acute or chronic pulmonary disease, and if unresolved may lead to respiratory distress and death due to hypoxia and compression and collapse of cardiac and thoracic great vessels. Therapeutic evacuation of free air within the pleural space can provide acute relief and improve chances of survival. This article descibes the adaptation and use of a continuous flow evacuation device to resolve pneumothorax in 3 cattle with pneumothorax associated with infectious lower airway disease.
A balloon lens: Acoustic scattering from a penetrable sphere
Authors: Thomas Derek C. , Gee Kent L. , Turley R. Steven
Published: February 2009

A balloon filled with a gas that has a different sound speed than that of air has been used as an acoustic lens. One purpose of the lens is to show refraction of sound waves in an analogy to geometric optics. We discuss the physics of the balloon lens demonstration. To determine the validity of a gas-filled balloon as a classroom demonstration of an acoustic lens and to understand the corresponding phenomena, its physics is considered analytically, numerically, and experimentally. Our results show that although a geometric analogy is a good first-order approximation, scattering theory is required to fully understand the observed phenomena. Thus this demonstration can be adapted to a wide range of students, from those learning the basic principles of refraction to advanced students studying scattering.
The harmonic oscillator in quantum mechanics: A third way
Authors: Marsiglio F.
Published: February 2009

Courses on undergraduate quantum mechanics usually focus on solutions of the Schrödinger equation for several simple one-dimensional examples. When the notion of a Hilbert space is introduced, only academic examples are used, such as the matrix representation of Dirac’s raising and lowering operators or the angular momentum operators. We introduce some of the same one-dimensional examples as matrix diagonalization problems, with a basis that consists of the infinite set of square well eigenfunctions. Undergraduate students are well equipped to handle such problems in familiar contexts. We pay special attention to the one-dimensional harmonic oscillator. This paper should equip students to obtain the low lying bound states of any one-dimensional short range potential.
Sequencing and Analyses of All Known Human Rhinovirus Genomes Reveal Structure and Evolution
Authors: Palmenberg Ann C. , Spiro David , Kuzmickas Ryan , Wang Shiliang , Djikeng Appolinaire , Rathe Jennifer A. , Fraser-Liggett Claire M. , Liggett Stephen B.
Published: February 2009

Infection by human rhinovirus (HRV) is a major cause of upper and lower respiratory tract disease worldwide and displays considerable phenotypic variation. We examined diversity by completing the genome sequences for all known serotypes (
n
= 99). Superimposition of capsid crystal structure and optimal-energy RNA configurations established alignments and phylogeny. These revealed conserved motifs; clade-specific diversity, including a potential newly identified species (HRV-D); mutations in field isolates; and recombination. In analogy with poliovirus, a hypervariable 5′ untranslated region tract may affect virulence. A configuration consistent with nonscanning internal ribosome entry was found in all HRVs and may account for rapid translation. The data density from complete sequences of the reference HRVs provided high resolution for this degree of modeling and serves as a platform for full genome-based epidemiologic studies and antiviral or vaccine development.
Equilibrium Iron Isotope Fractionation at Core-Mantle Boundary Conditions
Authors: Polyakov Veniamin B.
Published: February 2009

The equilibrium iron isotope fractionation between lower mantle minerals and metallic iron at core-mantle boundary conditions can be evaluated from the high-pressure
57
Fe partial vibrational density of states determined by synchrotron inelastic nuclear resonant x-ray scattering spectroscopy using a diamond anvil. Ferropericlase [(Mg,Fe)O] and (Fe,Mg)SiO
3
–post-perovskite are enriched in heavy iron isotopes relative to metallic iron at ultrahigh pressures, as opposed to the equilibrium iron isotope fractionation between these compounds at low pressure. The enrichment of Earth and Moon basalts in heavy iron isotopes relative to those from Mars and asteroid Vesta can be explained by the equilibrium iron isotope fractionation during the segregation of Earth's core and the assumption that Earth was already differentiated before the Moon-forming “giant impact.”
The Dynamic Control of Kiss-And-Run and Vesicular Reuse Probed with Single Nanoparticles
Authors: Zhang Qi , Li Yulong , Tsien Richard W.
Published: February 2009

Vesicular secretion of neurotransmitter is essential for neuronal communication. Kiss-and-run is a mode of membrane fusion and retrieval without the full collapse of the vesicle into the plasma membrane and de novo regeneration. The importance of kiss-and-run during efficient neurotransmission has remained in doubt. We developed an approach for loading individual synaptic vesicles with single quantum dots. Their size and pH-dependent photoluminescence change allowed us to distinguish kiss-and-run from full-collapse fusion and to track single vesicles through multiple rounds of kiss-and-run and reuse, without perturbing vesicle cycling. Kiss-and-run dominated at the beginning of stimulus trains, reflecting the preference of vesicles with high release probability. Its incidence was increased by rapid firing, a response appropriate to shape the kinetics of neurotransmission during a wide range of firing patterns.
Observation of Unconventional Quantum Spin Textures in Topological Insulators
Authors: Hsieh D. , Xia Y. , Wray L. , Qian D. , Pal A. , Dil J. H. , Osterwalder J. , Meier F. , Bihlmayer G. , Kane C. L. , Hor Y. S. , Cava R. J. , Hasan M. Z.
Published: February 2009

A topologically ordered material is characterized by a rare quantum organization of electrons that evades the conventional spontaneously broken symmetry–based classification of condensed matter. Exotic spin-transport phenomena, such as the dissipationless quantum spin Hall effect, have been speculated to originate from a topological order whose identification requires a spin-sensitive measurement, which does not exist to this date in any system. Using Mott polarimetry, we probed the spin degrees of freedom and demonstrated that topological quantum numbers are completely determined from spin texture–imaging measurements. Applying this method to Sb and Bi
1–x
Sb
x
, we identified the origin of its topological order and unusual chiral properties. These results taken together constitute the first observation of surface electrons collectively carrying a topological quantum Berry's phase and definite spin chirality, which are the key electronic properties component for realizing topological quantum computing bits with intrinsic spin Hall–like topological phenomena.
Singing in the Brain
Authors: Salwiczek Lucie H.
Published: February 2009

Neuroscience of Birdsong
.
H. Philip Zeigler and Peter Marler, Eds.
. Cambridge University Press, Cambridge, 2008. 568 pp. $160, £80. ISBN 9780521869157.

The contributors offer advanced graduates and researchers a thorough survey of our current understanding of birdsong neurobiology.
A comparative QSAR study of SVM and PPR in the correlation of lithium cation basicities
Authors: Katritzky Alan R. , Ren Yueying , Slavov Svetoslav H. , Karelson Mati
Published: February 2009

Correlation of gas-phase lithium cation basicities (LCB) of 259 diverse compounds extends the published datasets utilizing multilinear, support vector machine (SVM) and projection pursuit regression (PPR) modeling. The best multiple linear regression (BMLR) method implemented in CODESSA was used to: (i) build multiparameter linear QSPR models and (ii) select set of descriptors for further treatment by the SVM and PPR. The external predictivity and the performance of each of the above methods was estimated and compared to those of the other techniques. The PPR method produced results superior to SVM, which in turn outperformed MLR. The physico-chemical interpretation of each of the descriptors provides new insight into the mechanism of LCB interactions.
Relationship between vitamin D, calcium and parathyroid hormone in Cape Town
Authors: Haarburger D , Hoffman M , Erasmus R T , Pillay T S
Published: February 2009

Aim:

The aim of this study was to test the hypothesis that vitamin D deficiency is associated with abnormal levels of calcium and parathyroid hormone (PTH).

Methods:

Vitamin D requests at a tertiary hospital in South Africa over 2 years were retrospectively analysed along with calcium and PTH levels.

Results:

Only when the 25-hydroxyvitamin D (25(OH)D) level dropped below 25 nmol/l, was there a significant rise in PTH. A subnormal 25(OH)D level was also not always related to hypocalcaemia, as more than half of patients with their 25(OH)D level below 25 nmol/l had calcium levels in the reference range. However, all patients with calcium levels below 1.8 mmol/l were shown to have vitamin D insufficiency.

Conclusion:

Hypovitaminosis D may co-exist with a blunted PTH response. Therefore, assumptions about vitamin D status should not be made based on PTH and calcium values. 25(OH)D measurements should be requested when vitamin D deficiency is clinically suspected, irrespective of biochemical results.
A sequential Bayesian methodology to estimate movement and exploitation rates using electronic and conventional tag data: application to Atlantic bluefin tuna (Thunnus thynnus)
Authors: Kurota Hiroyuki , McAllister Murdoch K. , Lawson Gareth L. , Nogueira Jacob I. , Teo Steven L.H. , Block Barbara A.
Published: February 2009

This paper presents a Bayesian methodology to estimate fishing mortality rates and transoceanic migration rates of highly migratory pelagic fishes that integrates multiple sources of tagging data and auxiliary information from prior knowledge. Exploitation rates and movement rates for Atlantic bluefin tuna ( Thunnus thynnus ) are estimated by fitting a spatially structured model to three types of data obtained from pop-up satellite, archival, and conventional tags for the period 1990–2006 in the western North Atlantic. A sequential Bayesian statistical approach is applied in which the key components of the model are separated and fitted sequentially to data sets pertinent to each component with the posterior probability density function (pdf) of parameters from one analysis serving as the prior pdf for the next. The approach sequentially updates the estimates of age-specific fishing mortality rates (F) and transoceanic movement rates (T). Estimates of recent F are higher than the estimated rate of natural mortality and higher in the east than in the west. Estimates of annual T from the west to the east are higher for larger fish (6% for ages 0–3 to 16% for ages 9+). These estimates are also higher than those obtained from tagging studies before the 1990s and could be associated with changes in stock composition.
Gene flow increases temporal stability of Chinook salmon (Oncorhynchus tshawytscha) populations in the Upper Fraser River, British Columbia, Canada
Authors: Walter Ryan P. , Aykanat Tutku , Kelly David W. , Shrimpton J. Mark , Heath Daniel D.
Published: February 2009

Temporal instability in population genetic structure has significant implications for management and conservation decisions. Here, we evaluate temporal stability in five populations of Chinook salmon ( Oncorhynchus tshawytscha ) from the Upper Fraser River, British Columbia, Canada, based on estimates of temporal allelic variance and effective population size (Ne) at 11 microsatellite loci. Significant temporal variation in allele frequencies was found within individual populations sampled at 5- to 12-year intervals. Removal of migrant fish or correcting for migrants resulted in higher allelic variance or reduced Ne. Populations with higher levels of temporally consistent gene flow show reduced temporal allelic variance (i.e., reduced genetic drift) and higher Ne. This study is an important empirical example of the effect of gene flow on genetic stability and Ne. In salmonids, low straying levels may have evolved to favor local adaptation; however, we show that even such low levels of gene flow can elevate effective population sizes and preserve genetic variability. This study highlights the importance of considering gene flow acting to temporally stabilize populations, particularly small ones, and should migration be interrupted, Nelevels may decline with no obvious change in census population sizes.
Case study of a piled raft foundation constructed using a reverse construction method and its post-analysis
Authors: Sonoda Ryuuichi , Matsumoto Tatsunori , Kitiyodom Pastsakorn , Moritaka Hideo , Ono Toshihiro
Published: February 2009

A building and its foundation were constructed in sandy ground using a reverse construction method. The main difference between a reverse construction method and a conventional construction method is that the piles are cast in place and are partially loaded by the superstructure early during the construction process. It is only later that the raft (mat foundation) is constructed to combine with the piles to bear the full building load. Therefore, the foundation is regarded as a pile group in early stages of construction, while the foundation behaves as a piled raft after completion of the raft construction. A simple conservative design approach was used for the design of the foundation. To examine the validity of the design method, settlements of the foundation were observed during construction. The measured settlements were smaller than those predicted in the design stage, satisfying the design requirements for the building. Post-analysis of the deformation of the foundation was carried out using the results of the pile load test at the construction site, and the results of the analysis are compared with the observed settlements of the foundation, aiming at an improvement in pile foundation design.
The Generalized Failure of an Ottawa Valley Champlain Sea Clay
Authors: Mitchell R. J. , Wong K. K.
Published: February 2009

Fully drained strengths of specimens trimmed from block samples of Champlain Sea Clay from the Ottawa area were measured in triaxial compression, triaxial extension, and plane strain. Various effective stress paths were followed and the results of about 50 strength tests are included in this paper. Under very low average stresses (confining pressures) failure points were found to agree with the Mohr–Coulomb failure criterion. At average stresses in excess of the preconsolidation pressure, p′c, good agreement was obtained with the Mohr–Coulomb predictions. Over a significant range of stresses less than p′c the strength data do not agree with any of the classical failure criteria due to apparent strength anisotropy. Practical implications of these findings are discussed.
The Influence of Anchor Inclination on Pull-out Resistance of Clays
Authors: Hanna T. H.
Published: February 2009

A theoretical model is described that was used to examine the influence of anchor inclination on pull-out capacity. Use was made of previous general findings for pile shaft adhesion prediction in stiff clays. It is shown that the adhesion available at the anchor shaft – clay interface depends on: (1) the in situ stress state in the ground; (2) anchor inclination; and (3) the initial shear stress existing in the ground in the direction of the anchor shaft. The possible importance of the reported trends is considered.
A catalyst-free protocol for the green and efficient condensation of indoles with aldehydes in ionic liquids
Authors: Zare Abdolkarim , Parhami Abolfath , Moosavi-Zare Ahmad Reza , Hasaninejad Alireza , Khalafi-Nezhad Ali , Beyzavi Mohammad Hassan
Published: February 2009

Indoles are efficiently condensed with aromatic and aliphatic aldehydes in the absence of any catalyst in ionic liquid 1-butyl-3-methylimidazolium bromide {bmim]Br} under microwave irradiation to afford bis(indolyl)methanes in good to excellent yields and in short reaction times.