bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of puromycin‐sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) mutant tau
Authors: YANAGI Kentaro , TANAKA Toshihisa , KATO Kiyoko , SADIK Golam , MORIHARA Takashi , KUDO Takashi , TAKEDA Masatoshi
Published: March 2010

In tauopathies, tau protein is hyperphosphorylated, ubiquitinated, and accumulated in the brain; however, the mechanisms underlying this accumulation remain unclear. To gain an understanding of the role of proteases in the metabolism of tau protein, in the present study we evaluated the effects of protease inhibitors in SH‐SY5Y human neuroblastoma cells and COS‐7 cells transfected with the tau gene. When cells were treated with 0.1–10 µmol/L of lactacystin and 1.0–20 µmol/L of MG‐132 (inhibitors of proteasome), 0.1–10 µmol/L of CA‐074Me (a cathepsin inhibitor), and 0.1–2 µmol/L of puromycin (a puromycin‐sensitive aminopeptidase (PSA) inhibitor) for up to 24 h, there were no significant changes in tau protein levels. However, pulse‐chase experiments demonstrated that the proteolysis of tau protein in SH‐SY5Y cells was attenuated following treatment of cells with 200 nmol/L puromycin. Increased tau protein levels were also observed in SH‐SY5Y cells treated with short interference (si) RNA to PSA to inhibit the expression of PSA. These data suggest that PSA is a protease that catalyses tau protein predominantly in SH‐SY5Y cells. The protein metabolism of tau‐containing mutations of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) was also investigated using pulse‐chase experiments. The results indicate attenuated proteolysis of tau in cells transfected with mutant tau genes after 48 h. Further immunocytochemical analysis and subcellular fractionation experiments revealed that the mutations did not alter the intracellular distribution of tau and suggested that impaired accessibility of tau to PSA is unlikely to account for the attenuated proteolysis of tau protein. Western blotting with phosphorylation‐dependent antibodies revealed that phosphorylation levels of tau at Thr231, Ser396, and Ser409 were increased in cells transfected with V337M, R406W, and R406W mutant tau genes, respectively. Together, the data suggest that attenuated proteolysis of FTDP‐17 mutant tau may be explained by increased phosphorylation levels, resulting in resistance to proteolysis.
A Matrix‐Calibrated Species‐Area Model for Predicting Biodiversity Losses Due to Land‐Use Change
Authors: KOH* LIAN PIN , GHAZOUL JABOURY
Published: March 2010

Abstract:  Application of island biogeography theory to prediction of species extinctions resulting from habitat loss is based on the assumption that the transformed landscape matrix is completely inhospitable to the taxa considered, despite evidence demonstrating the nontrivial influence of matrix on populations within habitat remnants. The island biogeography paradigm therefore needs refining to account for specific responses of taxa to the area of habitat “islands” and to the quality of the surrounding matrix. We incorporated matrix effects into island theory by partitioning the slope (z value) of species–area relationships into two components: γ, a constant, and σ, a measure of taxon‐specific responses to each component of a heterogeneous matrix. We used our matrix‐calibrated model to predict extinction and endangerment of bird species resulting from land‐use change in 20 biodiversity hotspots and compared these predictions with observed numbers of extinct and threatened bird species. We repeated this analysis with the conventional species–area model and the countryside species–area model, considering alternative z values of 0.35 (island) or 0.22 (continental). We evaluated the relative strength of support for each of the five candidate models with Akaike's information criterion (AIC). The matrix‐calibrated model had the highest AIC weight (wi = 89.21%), which means the weight of evidence in support of this model was the optimal model given the set of candidate models and the data. In addition to being a valuable heuristic tool for assessing extinction risk, our matrix‐calibrated model also allows quantitative assessment of biodiversity benefits (and trade‐offs) of land‐management options in human‐dominated landscapes. Given that processes of secondary regeneration have become more widespread across tropical regions and are predicted to increase, our matrix‐calibrated model will be increasingly appropriate for practical conservation in tropical landscapes.
Effect of Aging Time on the Stability of Aqueous Y‐α‐SiAlON Precursor Powder Suspensions
Authors: Pereira Catarina , Olhero Susana , Ferreira José M.F.
Published: March 2010

A temporarily stable aqueous slip of Y‐α‐SiAlON precursors powders (Si3N4, Al2O3, Y2O3, and AlN powders) was successfully prepared using an AlN powder thermo‐chemically treated against hydrolysis (AlN‐TC). Aqueous suspensions of AlN‐TC and an Si3N4‐based powders' mixture (Si3N4/Y2O3/Al2O3) proved to have long‐term stability under separate deagglomeration by ball milling. However, the kinetic stability decreased when the two suspensions were mixed in the required proportion to obtain a precursor Y‐α‐SiAlON composition. This work aims at understanding better the aging phenomena and evaluating the feasibility of using aqueous processing to fabricate Y‐α‐SiAlON ceramics. The pH and rheological behavior of the suspensions were monitored along the time. The effects of drying conditions (room temperature or humidity‐controlled chamber) of slip‐cast samples on the crystalline phases and oxygen contents before and after sintering were evaluated. Drying under a moisture‐rich atmosphere favored hydrolysis of AlN and the appearance of β‐SiAlON as the main phase after sintering. The results allowed concluding that there is a time frame within which Y‐α‐SiAlON ceramics can be fabricated from aqueous suspensions.
Effects of Bi2O3 and Yb2O3 on the Curie Temperature in BaTiO3‐Based Ceramics
Authors: Yao Guofeng , Wang Xiaohui , Yang Yang , Li Longtu
Published: March 2010

Effects of doping Bi2O3 and Yb2O3 into BaTiO3‐based ceramics were investigated. The Curie temperature shifted to a higher point with an increasing BiYbO3. Yb plays a major role and Bi has no influence on the Curie point, but Bi2O3 is important because it can hinder the diffusion of other dopants and avoid the destruction of the “core–shell” structure. Moreover, the excess Bi2O3 addition enhances the effect of Yb2O3 on shifting Tc. X‐ray diffraction analysis indicated that the c/a ratio increased with the increasing of BiYbO3. The rise of the Curie temperature is attributed to an internal stress caused by the lattice mismatch between grain cores and grain shells. The dielectric properties can also be explained by the “core–shell” structure.
Doping of BiScO3–PbTiO3 Ceramics for Enhanced Properties
Authors: Sehirlioglu Alp , Sayir Ali , Dynys Fred
Published: March 2010

Compositional modification of ferroelectric BiScO3–PbTiO3 (BS–PT) ceramics was investigated by ZrSc• doping as a function of temperature and electric field. Zr doping decreased the Curie temperature; yet depoling temperature was higher as determined from the weak field measurements. Weight change measurements explain the difference in sintering behavior, emphasizing the effects of sacrificial powder on the defect structure. Possible mechanisms are discussed in collaboration with the crystal structure analysis. Pb′Bi replacement was shown as a possible charge balance mechanism. Pb′Bi is supported by the weight loss data, crystal structure analysis and the weak‐field electrical and electromechanical measurements. However, high field measurements contradicted the postulated Pb′Bi mechanism. Unipolar and bipolar high field polarization, strain and dielectric constant measurements indicated that the donor doping creates A‐site vacancies; a similar observation to Pb(Zr,Ti)O3 (PZT)‐based ceramics. At higher temperatures, the property dependence on the composition decreased suggesting that thermally assisted domain motion eliminated the dependence of the domain wall mobility on the extrinsic contributions (i.e., defect structure induced by doping). Effect of ZrSc• doping on electrical and electromechanical properties are reported and discussed as a function of temperature.
Changes in gingival crevicular fluid inflammatory mediator levels during the induction and resolution of experimental gingivitis in humans
Authors: Offenbacher Steven , Barros Silvana , Mendoza L. , Mauriello S. , Preisser J. , Moss K. , De Jager Marko , Aspiras Marcelo
Published: March 2010

Offenbacher S, Barros S, Mendoza L, Mauriello S, Preisser J, Moss K, de Jager M, Aspiras M. Changes in gingival crevicular fluid inflammatory mediator levels during the induction and resolution of experimental gingivitis in humans. J Clin Periodontol 2010; 37: 324–333. doi: 10.1111/j.1600‐051X.2010.01543.x

Aim: The goal of this study is to characterize the changes in 33 biomarkers within the gingival crevicular fluid during the 3‐week induction and 4‐week resolution of stent‐induced, biofilm overgrowth mediated, experimental gingivitis in humans.

Methods: Experimental gingivitis was induced in 25 subjects for 21 days followed by treatment with a sonic powered toothbrush for 28 days. Clinical indices and gingival crevicular fluids were collected weekly during induction and biweekly during resolution. Samples were analysed using a bead‐based multiplexing analysis for the simultaneous measurements of 33 biomarkers within each sample including cytokines, matrix‐metalloproteinases (MMPs) and adipokines. Prostaglandin‐E2 was measured by enzyme‐linked immunoadsorbant assay. Statistical testing using general linear models with structured covariance matrices were performed to compare stent to contralateral (non‐stent) changes in clinical signs and in biomarker levels over time.

Results: Gingivitis induction was associated with a significant 2.6‐fold increase in interleukin 1‐β (IL‐β), a 3.1‐fold increase in IL‐1α and a significant decrease in multiple chemokines as well as MMPs‐1, ‐3 and 13. All changes in clinical signs and mediators rebounded to baseline in response to treatment in the resolution phase.

Conclusions: Stent‐induced gingivitis is associated with marked, but reversible increases in IL‐αa and IL‐1β with suppression of multiple chemokines as well as selected MMPs.
SMS pain diary: a method for real‐time data capture of recurrent pain in childhood
Authors: Alfvén Gösta
Published: March 2010

Objectives:  To capture recurrent pain in children aged 9–15 years reported by short message service (SMS) and to test the compliance of such reporting in a pilot study.

Methods:  After instructions, 15 children reported their pain six times a day on SMS for a week and the compatibility of the reporting was evaluated. The pain was expressed and reported on three variables: intensity captured using a numeric rating scale (NRS‐11), duration in minutes and a verbal pain‐related disability scale with six alternatives (0–5). The validity of this scale was tested in 37 children, and the reliability in a test–retest procedure in 20 children.

Results:  Good compliance reporting the three variables intensity and duration of pain as well as pain‐related disability on SMS was indicated. Support for construct validity and reliability of the verbal instrument for pain‐related disability was achieved.

Conclusion:  The study supports the hypothesis that pain experience expressed as intensity, duration and pain‐related disability can be captured in real time by SMS in an inexpensive and compliant way in children aged 9–15 years. Validity and reliability was indicated for the constructed verbal pain‐related disability scale. Further studies are needed to further confirm these findings.
Psoriasiform skin lesion and supprative acrodermatitis associated with Kawasaki disease followed by the treatment with infliximab: a case report
Authors: Kishimoto S , Muneuchi J , Takahashi Y , Izu K , Nakano R , Joo K
Published: March 2010

A 4‐month‐old boy was diagnosed with Kawasaki disease. The ordinary treatments with intravenous gammaglobulin and metylpredonisolone were not effective. Infliximab (5 mg/kg) was administrated on 13th day of illness which led to defeverscence and improvement of clinical manifestations. On 23 days of illness, however, desquamative papules and plaques developed on both the extensor surfaces of the forearms and legs. In addition, typical subungual desquamations of fingers and toes followed crusted hyperkeratosis which resembled supprative acrodermatitis. Skin biopsy from the forearm showed inflammatory dyskeratosis with marked hyperkeratosis, epithelial parakeratotsis, loss of granular layer and dominant infiltration of CD8 + T‐cells. Local treatment of steroid followed improvement of skin lesions within a few weeks.

Conclusion:  Although previous reports described the beneficial effects of infliximab in patients with Kawasaki disease, it is possible that the administration of infliximab modify psoriasiform skin lesion associated with Kawasaki disease.
Incidence of necrotizing enterocolitis in very‐low‐birth‐weight infants related to the use of Lactobacillus GG
Authors: Luoto R , Matomäki J , Isolauri E , Lehtonen L
Published: March 2010

Background:  One of the five level III neonatal intensive care units (NICU) in Finland has used prophylactic Lactobacillus GG (LGG) for very‐low‐birth‐weight (VLBW) infants since 1997.

Aim:  To examine retrospectively the incidence of necrotizing enterocolitis (NEC) in all five university hospital NICUs in Finland in relation to the use of LGG during the years each unit has belonged to the Vermont Oxford Network (VON).

Methods:  The incidence of NEC was analysed from the national database and from the VON databases separately in all five level III NICUs and additionally in three groups according to the probiotic practice in the hospitals: prophylactic LGG group, probiotics ‘on demand’ group and no probiotics group.

Results:  The incidence of NEC was 4.6% vs. 3.3% vs. 1.8% in the prophylactic LGG group, the probiotics ‘on demand’ group and the no probiotics group, respectively; p = 0.0090, chi‐square. LGG had no influence on the clinical course of NEC.

Conclusions:  The results of this retrospective report failed to show that LGG prophylaxis protects VLBW infants from the occurrence of NEC, in contrast to previously published results. Our results call for more research regarding effective ways to administer probiotics, including data on appropriate bacteria, strain, dose and timing of administration to achieve clinically robust effects.
Sodium pump α1 and α3 subunit isoforms mediate distinct responses to ouabain and are both essential for survival of human neuroblastoma
Authors: Karpova Larisa , Eva Alexander , Kirch Ulrike , Boldyrev Alexander , Scheiner‐Bobis Georgios
Published: March 2010

Using SK‐N‐AS human neuroblastoma cells, which co‐express the α1 and α3 isoforms of the sodium pump α subunit, we selectively silenced either the α1 or α3 subunit by means of transfection with small interfering RNA, and investigated cell survival and the cellular response to ouabain. We found that both of the α subunits are essential for cell survival, indicating that substitution of one subunit for the other is not sufficient. In the presence of both α subunits, ouabain causes sustained activation of extracellular signal‐regulated kinases 1 and 2 (Erk1/2). This activation is not affected when the α1 subunit is silenced. However, when α3 expression is silenced, ouabain‐induced activation of Erk1/2 does not occur, even at a high concentration of ouabain (1 μm). Thus, ouabain‐induced Erk1/2 activation is mediated in SK‐N‐AS cells by α3 only, and α1 does not participate in this event. This is a clear demonstration of selective involvement of a specific sodium pump α subunit isoform in ouabain‐induced signaling.
Clinical and pathological evaluation of patients with early and late recurrence of colorectal cancer
Authors: AGHILI Mahdi , IZADI Shahrzad , MADANI Hossein , MORTAZAVI Hossein
Published: March 2010

Aim:  To compare the characteristics of primary cancer between patients with early recurrence and those with late recurrence of colorectal cancer.

Methods:  Overall 535 patients with primary colorectal cancer were reviewed and of these 130 patients with demonstrated recurrence were evaluated. Of the 130 patients, 91 had early recurrence (less than 2 years after surgery) and 39 had late recurrence (2 years or more after surgery). The clinical and pathological characteristics of primary cancer in these two groups were compared.

Results:  The rate of late recurrence was 30% of total recurrences (39/130). On average, patients with early recurrence were younger than patients with late recurrence (mean age 48 vs 54 years, p = 0.027). Adjacent organ involvement and Dukes stage C was more prevalent in the early recurrence group than in the late group. The liver was the main site of distant recurrence in the early recurrence group (64% of distant recurrences), whereas bone and peritoneum were the most frequent sites of metastases in the late recurrence group (58%). In Dukes C colon cancer patients the disease‐free interval was significantly longer in those who received both adjuvant therapies than in those who received either radiotherapy or chemotherapy or neither of them.

Conclusion:  This study showed that factors such as primary clinical signs, stage of primary tumor, and adjacent organ involvement are significant with respect to the time for recurrence of colorectal cancer. It is important to take these characteristics into account in patient care management after curative resection for colorectal cancer.
Clinical characteristics and prognostic factors for primary appendiceal carcinoma
Authors: KO Yoon Ho , PARK Se Hoon , JUNG Chan‐Kwon , WON Hye Sung , HONG Sook Hee , PARK Ji Chan , ROH Sang Young , WOO In Sook , KANG Jin Hyoung , HONG Young Seon , BYUN Jae Ho
Published: March 2010

Aim:  Primary adenocarcinoma of the appendix is a rare malignancy. This study assessed prognostic factors affecting the clinical outcome in patients with appendiceal neoplasms.

Methods:  We performed a retrospective analysis of patients who had appendectomies between 1991 and 2007 at five centers in South Korea.

Results:  Overall 55 patients (19 men, 36 women, median age 61 years) were identified. Of these, 37 (67.3%) were mucinous adenocarcinomas, 14 (25.5%) were intestinal‐type adenocarcinomas, and four (7.3%) were signet ring cell carcinomas. The distribution of stages was: 26 (47.3%) with localized disease, five (9.1%) with regional disease, and 24 (43.6%) with distant metastatic disease. The overall 3‐ and 5‐year survival rates among all patients were 72.2% and 64.0%, respectively, with 20 deaths during the follow‐up period. In a multivariate analysis, high histological grade (hazard ratio [HR]vs low grade 15.7; P = 0.001) and pathological stage (distant vs loco‐regional, HR 6.2; P = 0.021) were independent predictors of overall survival. Of the 34 patients who underwent curative resections of primary appendiceal carcinomas, the 3‐ and 5‐year disease‐free survival rates were 66.4% and 53.3%, respectively. The recurrence rate was higher in patients with regional lymph node metastasis (HR vs node negative disease 23.4; P = 0.005) and high‐grade tumors (HR vs low grade 6.3; P = 0.029). Additionally, a right hemicolectomy reduced the risk of recurrence (HR vs lesser procedures 0.05; P = 0.005).

Conclusion:  High tumor grade and advanced stage were significantly predictive of poor survival outcome in patients with primary appendiceal carcinomas.
New systemic treatment options for metastatic renal‐cell carcinoma in the era of targeted therapies
Authors: TAN Thean Hsiang , PRANAVAN Ganesalingam , HAXHIMOLLA Hodo Z , YIP Desmond
Published: March 2010

Advances in understanding the biology and genetics of renal‐cell carcinomas have led to the development of novel targeted therapies for the treatment of metastatic renal‐cell cancer. Previously the systemic approaches were limited to cytokine therapies that were modest in their clinical benefits and at the expense of significant toxicities. Investigational treatments with allogeneic bone marrow transplantation were equally toxic and resulted in significant morbidity and mortality. The development of targeted therapy has revolutionized the treatment of metastatic renal‐cell cancer with more meaningful outcomes. This review aims to provide a detailed discussion of the clinical benefits of targeted therapies such as sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab, and some of the newer agents in clinical trial development. The efficacy of these compounds in terms of response, survival and clinical benefit are explored as well as their toxicities. The role of surgery in metastatic renal‐cell carcinoma is reviewed in the context of cytoreductive therapy and resection of solitary and oligometastatic disease. Ongoing studies in the adjuvant setting following curative resection are also reviewed. The availability of targeted therapies has led to their rapid adoption as frontline therapy over traditional cytokine therapy, thus bringing more optimistic and hopeful therapeutic options in a condition where historically, systemic treatments have been relatively unsatisfactory and disappointing.
Off‐Farm Work Participation of Israeli Farm Couples: the Importance of Farm Work Participation Status
Authors: Kimhi Ayal
Published: March 2010

This article claims that coefficients of off‐farm work participation equations for farm residents might be estimated inconsistently if selectivity based on farm participation is ignored. Participation equations will be different for farm residents who do not work on farm, especially with respect to the dependence of reservation wages on farm attributes. I estimate an endogenous switching regression model in which farm and off‐farm participation equations are estimated jointly while the off‐farm participation coefficients are different for those who work on farm and those who don't. Using the 1981 Israeli Census of Agriculture data, I reject the hypothesis of insignificant selection bias and the hypothesis of equal coefficients in the two subsamples.
Clinicopathological pattern and HER 2/neu status in patients presenting with different histological grades of colorectal carcinomas
Authors: Anwar Sadia , Nagi A H , Naseem Nadia , Saqib Muhammad , Sami Waqas
Published: March 2010

Background and aims: Colorectal carcinoma is among the most frequently observed malignancies in Pakistan. The HER 2/neu protein is intimately involved in tumorigenesis and its receptor has been demonstrated as a therapeutic target in several carcinomas. This study was designed to assess the clinico‐pathological pattern and the HER 2/neu immunohistochemical score with respect to the histological grades of colorectal carcinoma in our population. Methods: Tissue biopsies from 100 patients, with detailed documentation of their clinical account, were subjected to immunohistochemistry utilizing monoclonal anti‐HER 2/neu antibody. Positive expression was assigned a score from 0–3+. Results: A distinct positive HER 2/neu scoring pattern was observed in n= 42 cases of non‐mucinous, mucinous and signet ring cell adenocarcinomas, all with a specific histological grade. An inverse correlation (P= 0.001) was observed between the two parameters. Conclusion: Colorectal carcinoma is a growing malignancy, even in the younger population and HER 2/neu protein is credibly expressed in colonic cancer cells in our patients especially where the histological grade is low or moderate. Therefore, it may be applied as a reasonably reliable immunohistochemical marker and a target for a new adjuvant monoclonal antibody‐based immunotherapy.
Proliferative activity of cells from remaining dental pulp in response to treatment with dental materials
Authors: Lutfi AN , Kannan TP , Fazliah MN , Jamaruddin MA , Saidi J
Published: March 2010

Background:  The biological examination of pulp injury, repair events and response of dental pulp stem cells to dental restorative materials is important to accomplish restorative treatment, especially to commonly used dental materials in paediatric dentistry, such as glass ionomer cement (GIC) and calcium hydroxide (Ca(OH)2) lining cement.

Methods:  Healthy patients aged between 9 to 11 years with carious primary molars without pulp exposure were selected and divided into two groups: Group 1 (teeth restored with GIC) and Group 2 (teeth lined using Ca(OH)2 and restored with GIC). The proliferative activity of stem cells of teeth between these two groups was compared using colourimetric cell proliferation reagent, alamarBlue. Immunocytochemistry and flow cytometry confirmation were performed using mesenchymal stem cell markers, CD105 and CD166.

Results:  The proliferative activity using alamarBlue™ assay showed that cells derived from the remaining dental pulp of exfoliated deciduous teeth were positive for CD105 and CD166 and exhibited no difference between the two groups.

Conclusions:  It can be concluded that the use of Ca(OH)2 or GIC as a lining material in indirect pulp capping procedures has the same effect on cells derived from the remaining dental pulp of exfoliated deciduous teeth which have responded favourably to the restorative treatments.
A primer on the application of Markov chains to the study of wildlife disease dynamics
Authors: Zipkin Elise F. , Jennelle Christopher S. , Cooch Evan G.
Published: March 2010

1. For wildlife researchers, disease specialists and policy analysts unfamiliar with the mathematical/statistical language of disease models, translation of probability statements into meaningful terms for disease research and control may be challenging. Markov chain models are powerful tools, applicable to the study of disease dynamics that allow straightforward calculations of easily interpretable metrics of interest including probabilities of infection/recovery, expected times to initial infection, duration of illness and life expectancies for susceptible and infected individuals.

2. We present the basic principles and assumptions behind Markov chain modelling with an intuitive interpretation of parameter estimates and a step‐by‐step guide (including software code) for implementing this approach in the study of wildlife diseases. We also include an explanation of the estimation process necessary to implement Markov chain modelling (i.e. estimating the probability of state transitions between consecutive time steps) from typical survey data.

3. We demonstrate the usefulness and ease of calculation of Markov chains through an example using a house finchCarpodacus mexicanus–Mycoplasma gallisepticum(MG) system. Our results show how semi‐weekly transition estimates of susceptible and infected individuals can be used to estimate a wide array of seasonal disease‐associated metrics.

4. Markov chain modelling can provide a basic understanding of parameters estimated from wildlife disease studies, and can aid in understanding the implications of disease on wildlife populations and in evaluation of control measures. We envision this paper serving as an entry point into the extensive literature and potential applications of Markov chains in epidemiological modelling.
The K+–Cl−cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampus
Authors: Viitanen Tero , Ruusuvuori Eva , Kaila Kai , Voipio Juha
Published: March 2010

GABAergic excitatory [K+]otransients can be readily evoked in the mature rat hippocampus by intense activation of GABAAreceptors (GABAARs). Here we show that these [K+]oresponses induced by high‐frequency stimulation or GABAAagonist application are generated by the neuronal K+–Cl−cotransporter KCC2 and that the transporter‐mediated KCl extrusion is critically dependent on the bicarbonate‐driven accumulation of Cl−in pyramidal neurons. The mechanism underlying GABAergic [K+]otransients was studied in CA1 stratum pyramidale using intracellular sharp microelectrodes and extracellular ion‐sensitive microelectrodes. The evoked [K+]otransients, as well as the associated afterdischarges, were strongly suppressed by 0.5–1 mmfurosemide, a KCl cotransport inhibitor. Importantly, the GABAAR‐mediated intrapyramidal accumulation of Cl−, as measured by monitoring the reversal potential of fused IPSPs, was unaffected by the drug. It was further confirmed that the reduction in the [K+]otransients was not due to effects of furosemide on the Na+‐dependent K+‐Cl−cotransporter NKCC1 or on intraneuronal carbonic anhydrase activity. Blocking potassium channels by Ba2+enhanced [K+]otransients whereas pyramidal cell depolarizations were attenuated in further agreement with a lack of contribution by channel‐mediated K+efflux. The key role of the GABAAR channel‐mediated anion fluxes in the generation of the [K+]otransients was examined in experiments where bicarbonate was replaced with formate. This anion substitution had no significant effect on the rate of Cl−accumulation, [K+]oresponse or afterdischarges. Our findings reveal a novel excitatory mode of action of KCC2 that can have substantial implications for the role of GABAergic transmission during ictal epileptiform activity.
Local Ca2+ releases enable rapid heart rates in developing cardiomyocytes
Authors: Korhonen Topi , Rapila Risto , Ronkainen Veli‐Pekka , Koivumäki Jussi T. , Tavi Pasi
Published: March 2010

The ability to generate homogeneous intracellular Ca2+ oscillations at high frequency is the basis of the rhythmic contractions of mammalian cardiac myocytes. While the specific mechanisms and structures enabling homogeneous high‐frequency Ca2+ signals in adult cardiomyocytes are well characterized, it is not known how these kind of Ca2+ signals are produced in developing cardiomyocytes. Here we investigated the mechanisms reducing spatial and temporal heterogeneity of cytosolic Ca2+ signals in mouse embryonic ventricular cardiomyocytes. We show that in developing cardiomyocytes the propagating Ca2+ signals are amplified in cytosol by local Ca2+ releases. Local releases are based on regular 3‐D sarcoplasmic reticulum (SR) structures containing SR Ca2+ uptake ATPases (SERCA) and Ca2+ release channels (ryanodine receptors, RyRs) at regular intervals throughout the cytosol. By evoking [Ca2+]i‐induced Ca2+ sparks, the local release sites promote a 3‐fold increase in the cytosolic Ca2+ propagation speed. We further demonstrate by mathematical modelling that without these local release sites the developing cardiomyocytes lose their ability to generate homogeneous global Ca2+ signals at a sufficiently high frequency. The mechanism described here is robust and indispensable for normal mammalian cardiomyocyte function from the first heartbeats during the early embryonic phase till terminal differentiation after birth. These results suggest that local cytosolic Ca2+ releases are indispensable for normal cardiomyocyte development and function of developing heart.
Characterisation of bipolar cell synaptic transmission in goldfish retina using paired recordings
Authors: Palmer Mary J.
Published: March 2010

Direct recordings from the large axon terminals of goldfish retinal bipolar cells (BCs) have revealed detailed information about the properties and regulation of exocytosis at this ribbon‐type synapse. However, the relationship between BC exocytosis and evoked postsynaptic responses in amacrine and ganglion cells is not known. To address this, I have made paired recordings from BC terminals (BCTs) and neurons in the ganglion cell layer (GCL) in goldfish retinal slices. BCT depolarisation evoked short‐latency, AMPA/kainate receptor‐mediated EPSCs in connected GCL neurons. NMDA receptors contributed to the response at +40 mV but not at −60 mV. Evoked EPSCs contained multiple temporal components that differed in their relative amplitudes between pairs. Changing the duration or amplitude of the presynaptic stimulus affected the size and kinetics of the EPSC, with weaker stimuli slowing the EPSC activation rate. Paired‐pulse stimulation caused greater depression of fast than slow EPSC components. A linear relationship was found between the amount of BCT exocytosis, measured via changes in membrane capacitance, and the charge of evoked EPSCs, whether they were mediated by AMPA/kainate receptors alone or in combination with NMDA receptors. In addition, analysis of miniature EPSCs in GCL neurons provided estimates of the quantal content of evoked EPSCs. The results demonstrate the feasibility of using this paired recording system to study synaptic transfer at ribbon synapses, and indicate that both the rapid and sustained phases of BC exocytosis are encoded in the postsynaptic response.
Regulation of Kv channel expression and neuronal excitability in rat medial nucleus of the trapezoid body maintained in organotypic culture
Authors: Tong Huaxia , Steinert Joern R. , Robinson Susan W. , Chernova Tatyana , Read David J. , Oliver Douglas L. , Forsythe Ian D.
Published: March 2010

Principal neurons of the medial nucleus of the trapezoid body (MNTB) express a spectrum of voltage‐dependent K+conductances mediated by Kv1–Kv4 channels, which shape action potential (AP) firing and regulate intrinsic excitability. Postsynaptic factors influencing expression of Kv channels were explored using organotypic cultures of brainstem prepared from P9–P12 rats and maintained in either low (5 mm, low‐K) or high (25 mm, high‐K) [K+]omedium. Whole cell patch‐clamp recordings were made after 7–28 daysin vitro. MNTB neurons cultured in high‐K medium maintained a single AP firing phenotype, while low‐K cultures had smaller K+currents, enhanced excitability and fired multiple APs. The calyx of Held inputs degenerated within 3 days in culture, having lost their major afferent input; this preparation of calyx‐free MNTB neurons allowed the effects of postsynaptic depolarisation to be studied with minimal synaptic activity. The depolarization caused by the high‐K aCSF only transiently increased spontaneous AP firing (<2 min) and did not measurably increase synaptic activity. Chronic depolarization in high‐K cultures raised basal levels of [Ca2+]i, increased Kv3 currents and shortened AP half‐widths. These events relied on raised [Ca2+]i, mediated by influx through voltage‐gated calcium channels (VGCCs) and release from intracellular stores, causing an increase in cAMP‐response element binding protein (CREB) phosphorylation. Block of VGCCs or of CREB function suppressed Kv3 currents, increased AP duration, and reduced Kv3.3 and c‐fosexpression. Real‐time PCR revealed higher Kv3.3 and Kv1.1 mRNA in high‐K compared to low‐K cultures, although the increased Kv1.1 mRNA was mediated by a CREB‐independent mechanism. We conclude that Kv channel expression and hence the intrinsic membrane properties of MNTB neurons are homeostatically regulated by [Ca2+]i‐dependent mechanisms and influenced by sustained depolarization of the resting membrane potential.
Transient release kinetics of rod bipolar cells revealed by capacitance measurement of exocytosis from axon terminals in rat retinal slices
Authors: Oltedal Leif , Hartveit Espen
Published: March 2010

Presynaptic transmitter release has mostly been studied through measurements of postsynaptic responses, but a few synapses offer direct access to the presynaptic terminal, thereby allowing capacitance measurements of exocytosis. For mammalian rod bipolar cells, synaptic transmission has been investigated in great detail by recording postsynaptic currents in AII amacrine cells. Presynaptic measurements of the dynamics of vesicular cycling have so far been limited to isolated rod bipolar cells in dissociated preparations. Here, we first used computer simulations of compartmental models of morphologically reconstructed rod bipolar cells to adapt the ‘Sine + DC’ technique for capacitance measurements of exocytosis at axon terminals of intact rod bipolar cells in retinal slices. In subsequent physiological recordings, voltage pulses that triggered presynaptic Ca2+ influx evoked capacitance increases that were proportional to the pulse duration. With pulse durations ≤100 ms, the increase saturated at ∼10 fF, corresponding to the size of a readily releasable pool of vesicles. Pulse durations ≥400 ms evoked additional capacitance increases, probably reflecting recruitment from additional pools of vesicles. By using Ca2+ tail current stimuli, we separated Ca2+ influx from Ca2+ channel activation kinetics, allowing us to estimate the intrinsic release kinetics of the readily releasable pool, yielding a time constant of ∼1.1 ms and a maximum release rate of 2–3 vesicles (release site)−1 ms−1. Following exocytosis, we observed endocytosis with time constants ranging from 0.7 to 17 s. Under physiological conditions, it is likely that release will be transient, with the kinetics limited by the activation kinetics of the voltage‐gated Ca2+ channels.
To the Problem of a Passive Levitation of Bodies in Physical Fields
Authors: Denisov G. G. , Novikov V. V. , Fedorov A. E.
Published: March 2010

A possibility of levitation of a body carrying a point electrical charge in the field of a fixed point charge of the same sign is shown. Stabilization of an unstable equilibrium, when gravity is compensated by Coulomb’s force, is realized using gyroscopic forces generated due to the rotation of the body. A finite range of angular velocity corresponds to conservative stability of the levitating body. It is shown that dissipative and circulation forces introduced into consideration simultaneously can improve the stability of the system to asymptotic. Dependence of the domain of attraction of stable equilibrium on parameters of the system is studied numerically.
The Effect of the Angle of Inclination on the Operation Limiting Heat Flux of Long R-134a Filled Thermosyphons
Authors: Grooten M. H. M. , van der Geld C. W. M.
Published: March 2010

When traditional air-to-air cooling is too voluminous, long thermosyphons may offer a way out. For safe operation of heat exchangers equipped with thermosyphons, the limiting heat flux qlim″ is an important design parameter. Some literatures are found to deal with the operation limiting heat flux of closed two-phase thermosyphons. However, R-134a filled thermosyphons with large length-to-diameter (188) are hardly investigated up to now. Extrapolation of existing correlations to predict qlim″ in this case results in large scatter. The effect of the angle of inclination on qlim″ has not been considered until now. Dedicated experiments with a single thermosyphon with a large length-to-diameter ratio (188) and filled with R-134a are presented and analyzed. Effects of saturation temperature, filling ratio, and angle of inclination β on the operational limiting heat flux have been investigated. The thermosyphon functions properly if β<83 deg, and qlim″ is found to increase with increasing β. With decreasing saturation temperature, qlim″ increases. The filling ratio is found not to be crucial if it exceeds 25%. Correlations are presented to accurately predict the operation limiting heat flux for thermosyphons with a L/d ratio up to 188. Because of the accounting for the above new aspects, these correlations are also relevant for filling refrigerants other than R-134a.
Modeling the Effects of System Rotation on the Turbulent Scalar Fluxes
Authors: Younis B. A. , Weigand B. , Mohr F. , Schmidt M.
Published: March 2010

A proposal for modeling the effects of system rotation on the turbulent scalar fluxes is presented. It is based on extension to rotating frames of an explicit algebraic model derived using tensor-representation theory. The model is formulated to allow for the turbulent scalar fluxes to depend on the details of the turbulence field and on the gradients of both the mean-velocity and the scalar. Such dependence, which is absent from conventional models, is required by the exact equations governing the transport of the scalar fluxes. The model’s performance is assessed, both a priori and by actual computations, by comparisons with results from recent direct numerical simulations (DNS) of flows in heated channels rotated about their streamwise, spanwise, and wall-normal axes. To place the new model’s performance in context, additional comparisons are made with predictions obtained from three alternative models, namely, the conventional gradient-transport model, a model that is implicit in the scalar fluxes derived by simplification of the modeled transport equations for the scalar fluxes, and a differential scalar-flux transport model. The results show that the present model yields predictions that are substantially in better agreement with the DNS results than the algebraic models, and which are indistinguishable from those obtained with the more complex differential model. However, important differences remain and reasons for these are discussed.
Monte
Carlo Study of Phonon Heat Conduction in Silicon Thin Films Including Contributions of Optical
Phonons
Authors: Mittal Arpit , Mazumder Sandip
Published: March 2010

The Monte Carlo method has found prolific use in the solution of the Boltzmann transport equation for phonons for the prediction of nonequilibrium heat conduction in crystalline thin films. This paper contributes to the state-of-the-art by performing a systematic study of the role of the various phonon modes on thermal conductivity predictions, in particular, optical phonons. A procedure to calculate three-phonon scattering time-scales with the inclusion of optical phonons is described and implemented. The roles of various phonon modes are assessed. It is found that transverse acoustic (TA) phonons are the primary carriers of energy at low temperatures. At high temperatures (T>200 K), longitudinal acoustic (LA) phonons carry more energy than TA phonons. When optical phonons are included, there is a significant change in the amount of energy carried by various phonons modes, especially at room temperature, where optical modes are found to carry about 25% of the energy at steady state in silicon thin films. Most importantly, it is found that inclusion of optical phonons results in better match with experimental observations for silicon thin-film thermal conductivity. The inclusion of optical phonons is found to decrease the thermal conductivity at intermediate temperatures (50–200 K) and to increase it at high temperature (>200 K), especially when the film is thin. The effect of number of stochastic samples, the dimensionality of the computational domain (two-dimensional versus three-dimensional), and the lateral (in-plane) dimension of the film on the statistical accuracy and computational efficiency is systematically studied and elucidated for all temperatures.
Vapor Flow Analysis in Flat Plate Heat Pipes Using Homotopy Perturbation Method
Authors: Seyf Hamid Reza , Layeghi Mohammad
Published: March 2010

In the present study, an analytical solution for 2D vapor flow in flat plate heat pipes is presented. The governing equations are solved analytically using the homotopy perturbation method, and numerically using the finite volume method, based on collocated grids. The analytical results are obtained for nondimensional velocity profiles and axial pressures distribution along the entire length of the heat pipe, and compared with the numerical ones. It is shown that there is a relatively small difference of about 1% in the worst case between the analytical and numerical results. Furthermore, the effects of the Reynolds number and the ratio of condenser to evaporator lengths on the flow variables are discussed.
Self-Contained, Oscillating Flow Liquid Cooling System for Thin Form Factor High Performance Electronics
Authors: Wälchli R. , Brunschwiler T. , Michel B. , Poulikakos D.
Published: March 2010

A self-contained, small-volume liquid cooling system for thin form-factor electronic equipment (e.g., blade server modules) is demonstrated experimentally in this paper. A reciprocating water flow loop absorbs heat using mesh-type microchannel cold plates and spreads it periodically to a larger area. From there, the thermal energy is interchanged via large area, low pressure drop cold plates with a secondary heat transfer loop (air or liquid). Four phase-shifted piston pumps create either a linearly or radially oscillating fluid flow in the frequency range of 0.5–3 Hz. The tidal displacement of the pumps covers 42–120% of the fluid volume, and, therefore, an average flow rate range of 100–800 ml/min is tested. Three different absorber mesh designs are tested. Thermal and fluidic characteristics are presented in a time-resolved and a time-averaged manner. For a fluid pump power of 1 W, a waste heat flux of 180 W/cm2(ΔT=67 K) could be dissipated from a 3.5 cm2 chip. A linear oscillation flow pattern is advantageous over a radial one because of the more efficient heat removal from the chip and lower hydraulic losses. The optimum microchannel mesh density is determined as a combination of low pump losses and high heat transfer rates.
Computational Fluid Dynamics Evaluation of Heat Transfer Correlations for Sodium Flows in a Heat Exchanger
Authors: Choi Seok-Ki , Kim Seong-O , Choi Hoon-Ki
Published: March 2010

A numerical study for the evaluation of heat transfer correlations for sodium flows in a heat exchanger of a fast breeder nuclear reactor is performed. Three different types of flows such as parallel flow, cross flow, and two inclined flows are considered. Calculations are performed for these three typical flows in a heat exchanger changing turbulence models. The tested turbulence models are the shear stress transport (SST) model and the SSG-Reynolds stress turbulence model by Speziale, Sarkar, and Gaski (1991, “Modelling the Pressure-Strain Correlation of Turbulence: An Invariant Dynamical System Approach,” J. Fluid Mech., 227, pp. 245–272). The computational model for parallel flow is a flow past tubes inside a circular cylinder and those for the cross flow and inclined flows are flows past the perpendicular and inclined tube banks enclosed by a rectangular duct. The computational results show that the SST model produces the most reliable results that can distinguish the best heat transfer correlation from other correlations for the three different flows. It was also shown that the SSG-RSTM high-Reynolds number turbulence model does not deal with the low-Prandtl number effect properly when the Peclet number is small. According to the present calculations for a parallel flow, all the old correlations do not match with the present numerical solutions and a new correlation is proposed. The correlations by Dwyer (1966, “Recent Developments in Liquid-Metal Heat Transfer,” At. Energy Rev., 4, pp. 3–92) for a cross flow and its modified correlation that takes into account of flow inclination for inclined flows work best and are accurate enough to be used for the design of the heat exchanger.
Forced Convection Heat Transfer Enhancement by Porous Pin Fins in Rectangular Channels
Authors: Yang Jian , Zeng Min , Wang Qiuwang , Nakayama Akira
Published: March 2010

The forced convective heat transfer in three-dimensional porous pin fin channels is numerically studied in this paper. The Forchheimer–Brinkman extended Darcy model and two-equation energy model are adopted to describe the flow and heat transfer in porous media. Air and water are employed as the cold fluids and the effects of Reynolds number (Re), pore density (PPI) and pin fin form are studied in detail. The results show that, with proper selection of physical parameters, significant heat transfer enhancements and pressure drop reductions can be achieved simultaneously with porous pin fins and the overall heat transfer performances in porous pin fin channels are much better than those in traditional solid pin fin channels. The effects of pore density are significant. As PPI increases, the pressure drops and heat fluxes in porous pin fin channels increase while the overall heat transfer efficiencies decrease and the maximal overall heat transfer efficiencies are obtained at PPI=20 for both air and water cases. Furthermore, the effects of pin fin form are also remarkable. With the same physical parameters, the overall heat transfer efficiencies in the long elliptic porous pin fin channels are the highest while they are the lowest in the short elliptic porous pin fin channels.