bluuebunny/crossref_metadata_2025 huggingface dataset:
P-wave of hydrate-bearing sand under temperature cycling
Authors: Li Dongliang , Wang Dong , Liang Deqing
Published: January 2011

P-wave velocity was used to study the formation of gas hydrates that were formed from methane, [Formula: see text], and propane in the pores of sand particles under temperature cycling. During the temperature-cycling tests, additional hydrate or ice formation can be demonstrated by investigating the velocities and amplitude of the P-wave. The experiments indicated that temperature cycling can accelerate hydrate accumulation in the pore space of sediments. Although most of the water in the pore space of sand can transform into gas hydrate after several temperature cycles, the formation of propane hydrate was slower than that of methane hydrate or [Formula: see text] hydrate. To estimate the hydrate saturation, an effective-medium theory was used. The results corroborated the validity of the contact model that the hydrate acted as a mineral grain to support the sediment frame. According to the calculation results, the methane-hydrate saturation can be up to 0.85 after three temperature cycles. The evaluation results accord with those of some natural hydrates in sand layers.
Management of Seminomatous Testicular Cancer: A Binational Prospective Population-Based Study From the Swedish Norwegian Testicular Cancer Study Group
Authors: Tandstad Torgrim , Smaaland Rune , Solberg Arne , Bremnes Roy M. , Langberg Carl W. , Laurell Anna , Stierner Ulrika K. , Ståhl Olof , Cavallin-Ståhl Eva K. , Klepp Olbjørn H. , Dahl Olav , Cohn-Cedermark Gabriella
Published: January 2011

Purpose

A binational, population-based treatment protocol was established to prospectively treat and follow patients with seminomatous testicular cancer. The aim was to standardize care for all patients with seminoma to further improve the good results expected for this disease.

Patients and Methods

From 2000 to 2006, a total of 1,384 Norwegian and Swedish patients were included in the study. Treatment in clinical stage 1 (CS1) was surveillance, adjuvant radiotherapy, or adjuvant carboplatin. In metastatic disease, recommended treatment was radiotherapy in CS2A and cisplatin-based chemotherapy in CS2B or higher.

Results

At a median follow-up of 5.2 years, 5-year cause-specific survival was 99.6%. In CS1, 14.3% (65 of 512) of patients relapsed following surveillance, 3.9% (seven of 188) after carboplatin, and 0.8% (four of 481) after radiotherapy. We could not identify any factors predicting relapse in CS1 patients who were subjected to surveillance only. In CS2A, 10.9% (three of 29) patients relapsed after radiotherapy compared with no relapses in CS2A/B patients (zero of 73) treated with chemotherapy (P = .011).

Conclusion

An international, population-based treatment protocol for testicular seminoma is feasible with excellent results. Surveillance remains a good option for CS1 patients. No factors predicted relapse in CS1 patients on surveillance. Despite resulting in a lower rate of relapse than with adjuvant carboplatin, adjuvant radiotherapy has been abandoned in the Swedish and Norwegian Testicular Cancer Project (SWENOTECA) as a recommended treatment option because of concerns of induction of secondary cancers. The higher number of relapses in radiotherapy-treated CS2A patients when compared with chemotherapy-treated CS2A/B patients is of concern. Late toxicity of cisplatin-based chemotherapy versus radiotherapy must be considered in CS2A patients.
Understanding Surgical Decision Making in Early Hepatocellular Carcinoma
Authors: Nathan Hari , Bridges John F.P. , Schulick Richard D. , Cameron Andrew M. , Hirose Kenzo , Edil Barish H. , Wolfgang Christopher L. , Segev Dorry L. , Choti Michael A. , Pawlik Timothy M.
Published: January 2011

Purpose

The choice between liver transplantation (LT), liver resection (LR), and radiofrequency ablation (RFA) as initial therapy for early hepatocellular carcinoma (HCC) is controversial, yet little is known about how surgeons choose therapy for individual patients. We sought to quantify the impact of both clinical factors and surgeon specialty on surgical decision making in early HCC by using conjoint analysis.

Methods

Surgeons with an interest in liver surgery were invited to complete a Web-based survey including 10 case scenarios. Choice of therapy was then analyzed by using regression models that included both clinical factors and surgeon specialty (non-LT v LT).

Results

When assessing early HCC occurrences, non-LT surgeons (50% LR; 41% LT; 9% RFA) made significantly different recommendations compared with LT surgeons (63% LT; 31% LR; 6% RFA; P < .001). Clinical factors, including tumor number and size, type of resection required, and platelet count, had significant effects on the choice between LR, LT, and RFA. After adjusting for clinical factors, non-LT surgeons remained more likely than LT surgeons to choose LR compared with LT (relative risk ratio [RRR], 2.67). When the weight of each clinical factor was allowed to vary by surgeon specialty, the residual independent effect of surgeon specialty on the decision between LR and LT was negligible (RRR, 0.93).

Conclusion

The impact of surgeon specialty on choice of therapy for early HCC is stronger than that of some clinical factors. However, the influence of surgeon specialty does not merely reflect an across-the-board preference for one therapy over another. Rather, certain clinical factors are weighed differently by surgeons in different specialties.
Prognostic Importance of Histone MethyltransferaseMLL5Expression in Acute Myeloid Leukemia
Authors: Damm Frederik , Oberacker Tina , Thol Felicitas , Surdziel Ewa , Wagner Katharina , Chaturvedi Anuhar , Morgan Michael , Bomm Karoline , Göhring Gudrun , Lübbert Michael , Kanz Lothar , Fiedler Walter , Schlegelberger Brigitte , Heil Gerhard , Schlenk Richard F. , Döhner Konstanze , Döhner Hartmut , Krauter Jürgen , Ganser Arnold , Heuser Michael
Published: January 2011

Purpose

To assess the prognostic importance of mixed lineage leukemia 5 (MLL5) expression in acute myeloid leukemia (AML).

Patients and Methods

MLL5 transcript levels from 509 patients with AML who were treated in multicenter trials AML SHG 0199 and AML SHG 0295 and 48 healthy volunteers were analyzed by real-time reverse-transcription polymerase chain reaction in the context of other molecular markers (NPM1, FLT3, CEBPA, IDH1/IDH2, NRAS, KIT, MN1, BAALC, ERG, and WT1).

Results

Patients with high (n = 127) compared with low (n = 382) MLL5 expression had a higher complete response rate in multivariate analysis (odds ratio, 1.87; 95% CI, 1.08 to 3.24; P = .026). In multivariate analysis, high MLL5 expression was a favorable prognostic marker for overall survival (OS; hazard ratio [HR], 0.66; 95% CI, 0.49 to 0.89; P = .007) and relapse-free survival (RFS; HR, 0.72; 95% CI, 0.52 to 1.01; P = .057). Patient characteristics, cytogenetic aberrations, and gene mutations were similarly distributed between patients with high and low MLL5 expression except for a higher platelet count in those with high MLL5 expression. MLL5 expression independently predicted prognosis in cytogenetically normal AML patients (n = 268; OS: HR, 0.53; 95% CI, 0.33 to 086; P = .011; RFS: HR, 0.61; 95% CI, 0.38 to 0.99; P = .05) and in patients with core-binding factor leukemias (n = 81; OS: HR, 0.12; 95% CI, 0.02 to 0.91; P = .04; RFS: HR, 0.18; 95% CI, 0.04 to 0.77; P = .02). The prognostic importance of high MLL5 expression was independently validated in 167 patients treated in the AMLSG 07/04 trial (OS: HR, 0.5; 95% CI, 0.27 to 0.92; P = .023; RFS: HR, 0.49; 95% CI, 0.25 to 0.96; P = .033).

Conclusion

High MLL5 expression levels are associated with a favorable outcome and may improve risk and treatment stratification in AML.
Physical Activity and Survival After Prostate Cancer Diagnosis in the Health Professionals Follow-Up Study
Authors: Kenfield Stacey A. , Stampfer Meir J. , Giovannucci Edward , Chan June M.
Published: January 2011

Purpose

To determine whether higher physical activity after prostate cancer (PCa) diagnosis decreases risk of overall and PCa-specific death.

Patients and Methods

We evaluated physical activity in relation to overall and PCa mortality among 2,705 men in the Health Professionals Follow-Up Study diagnosed with nonmetastatic PCa observed from 1990 to 2008. Proportional hazards models were used to evaluate physical activity and time to overall and PCa-specific death.

Results

Among men who lived at least 4 years after their postdiagnosis physical activity assessment, we documented 548 deaths, 20% of which were a result of PCa. In multivariable analysis, men who were physically active had lower risk of all-cause mortality (Ptrend < .001) and PCa mortality (Ptrend = .04). Both nonvigorous activity and vigorous activity were associated with significantly lower overall mortality. Those who walked ≥ 90 minutes per week at a normal to very brisk pace had a 46% lower risk of all-cause mortality (hazard ratio [HR] 0.54; 95% CI, 0.41 to 0.71) compared with shorter durations at an easy walking pace. Men with ≥ 3 hours per week of vigorous activity had a 49% lower risk of all-cause mortality (HR, 0.51; 95% CI, 0.36 to 0.72). For PCa-specific mortality, brisk walking at longer durations was suggestively inverse but not statistically significant. Men with ≥ 3 hours per week of vigorous activity had a 61% lower risk of PCa death (HR, 0.39, 95% CI, 0.18 to 0.84; P = .03) compared with men with less than 1 hour per week of vigorous activity. Men exercising vigorously before and after diagnosis had the lowest risk.

Conclusion

In men with PCa, physical activity was associated with lower overall mortality and PCa mortality. A modest amount of vigorous activity such as biking, tennis, jogging, or swimming for ≥ 3 hours a week may substantially improve PCa-specific survival.
Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in Muscle-Invasive Bladder Cancer
Authors: Choudhury Ananya , Swindell Ric , Logue John P. , Elliott P. Anthony , Livsey Jacqueline E. , Wise Marcus , Symonds Paul , Wylie James P. , Ramani Vijay , Sangar Vijay , Lyons Jeanette , Bottomley Ian , McCaul Damian , Clarke Noel W. , Kiltie Anne E. , Cowan Richard A.
Published: January 2011

Purpose

The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX).

Patients and Methods

Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m2 on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival.

Results

All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%.

Conclusion

Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.
Congestive Heart Failure Risk in Patients With Breast Cancer Treated With Bevacizumab
Authors: Choueiri Toni K. , Mayer Erica L. , Je Youjin , Rosenberg Jonathan E. , Nguyen Paul L. , Azzi Georges R. , Bellmunt Joaquim , Burstein Harold J. , Schutz Fabio A.B.
Published: January 2011

Purpose

Bevacizumab is a treatment option in patients with metastatic breast cancer. Congestive heart failure (CHF) has been reported, although the overall incidence and relative risk (RR) of this complication remains unclear. We performed an up-to-date, comprehensive meta-analysis to determine the risk of serious CHF in patients with breast cancer receiving bevacizumab.

Methods

The databases of Medline were searched for articles from 1966 to March 2010. Abstracts presented at the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium meetings were also searched for relevant clinical trials. Eligible studies include randomized trials with bevacizumab in patients with breast cancer. Adequate reporting of safety profile data was required for inclusion. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% CIs by using random-effects models.

Results

A total of 3,784 patients were included. Overall incidence results for high-grade CHF in bevacizumab- and placebo-treated patients were 1.6% (95% CI, 1.0% to 2.6%) and 0.4% (95% CI, 0.2% to 1.0%), respectively. The RR of CHF in bevacizumab-treated patients was 4.74 (95% CI, 1.66 to 11.18; P = .001) compared with placebo-treated ones. In subgroup analyses, there were no significant differences in CHF incidence or risk between patients treated with low-dose (2.5 mg/kg) versus high-dose (5 mg/kg) bevacizumab or among patients treated with different chemotherapy regimens. No evidence of publication bias was observed.

Conclusion

This is the first comprehensive report to show that bevacizumab is associated with an increased risk of significant heart failure in patients with breast cancer.
A Ruthenium-Catalyzed Hydrosilane-Induced Polymerization of 3-Alkyl-3-hydroxymethyloxetane Derivatives: Facile Access to Functionalized Polyoxetanes by Virtue of Organosilyl Groups
Authors: Harada Nari-aki , Yasuhara Jushiro , Motoyama Yukihiro , Fujimura Osamu , Tsuji Tetsuro , Takahashi Takeshi , Takahashi Yoshiaki , Nagashima Hideo
Published: December 2010

Ring-opening polymerization of 3-alkyl-3-alkoxymethyl- or 3-alkyl-3-siloxymethyloxetanes is catalyzed by a triruthenium cluster, [Ru3{μ3-(η2,η3,η5-C12H8)}(CO)7], in the presence of trialkylsilanes, providing a novel accessible method for functionalized polyoxetanes of Mn = 103–105. Oxetanes having alkoxy-, fluoroalkoxy-, triethyleneglycoloxy-, and trialkylsiloxy functions undergo polymerization and copolymerization. Consumption rates of two monomers in the copolymerization of 3-benzyloxymethyl- and 3-trimethylsiloxymethyl-3-alkyloxetanes are almost the same, indicating formation of random copolymers. The organosilyl group in the polymer and copolymers with siloxymethyl side chains is converted to CH2OH or CH2OCOR groups by hydrolysis or silyl/acyl exchange. These protocols give the way to access polymers or copolymers bearing OH and OCOR side chains. A ruthenium-catalyzed reaction of 3-ethyl-3-hydroxymethyloxetane with trialkylsilanes results in dehydrogenative silylation to give 3-ethyl-3-siloxymethyloxetane, which is followed by ring-opening polymerization. Combination of tandem dehydrogenative silylation/ring-opening polymerization/the silyl/acyl exchange realizes one-pot synthesis of polymers with CH2OCOR side chains from 3-ethyl-3-hydroxymethyloxetane. DSC analyses of the formed polymers provided Tg and Tm data, which are a good example showing that the polymer properties are controlled by appropriate selection of functional groups at the side chain.
Physician Perceptions About Generic Drugs
Authors: Shrank William H , Liberman Joshua N , Fischer Michael A , Girdish Charmaine , Brennan Troyen A , Choudhry Niteesh K
Published: January 2011

Background

With constrained health-care resources, there is a need to understand barriers to cost-effective medication use.

Objective

To study physician perceptions about generic medications.

Methods

Physicians used 5-point Likert scales to report perceptions about cost-related medication nonadherence, the efficacy and quality of generic medications, preferences for generic use, and the implications of dispensing medication samples. Descriptive statistics were used to assess physician perceptions and logistic regression models were used to evaluate predictors of physician perceptions.

Results:

Among the invited sample. 839 (30.4%) responded and 506 (18.3%) were eligible and included in the final study population. Over 23% of physicians surveyed expressed negative perceptions about efficacy of generic drugs, almost 50% reported negative perceptions about quality of generic medications, and more than one quarter do not prefer to use generics as first-line medications for themselves or for their family. Physicians over the age of 55 years were 3.3 times more likely to report negative perceptions about generic quality, 5.8 times more likely to report that they would not use generics themselves, and 7.5 times more likely to state that they would not recommend generics for family members (p < 0.05 for all). Physicians reported that pharmaceutical company representatives are the most common (75%) source of information about market entry of a generic medication. Almost half of the respondents expressed concern that free samples may adversely affect subsequent affordability, yet two thirds of respondents provide free samples.

Conclusions:

A meaningful proportion of physicians expressed negative perceptions about generic medications, representing a potential barrier to generic use. Payors and policymakers trying to encourage generic use may consider educational campaigns targeting older physicians.
Elevated International Normalized Ratio from Vitamin K Supplement Discontinuation
Authors: Miesner Andrew R , Sullivan Timothy S
Published: January 2011

Objective

To report a case of a critically elevated international normalized ratio (INR) following discontinuation of a vitamin K supplement in a patient receiving warfarin.

Case Summary:

A 64-year-old man with atrial fibrillation received warfarin for primary stroke prevention. He was initialed on tow-dose vitamin K supplementation therapy secondary to a high level of INR variability. The patient was stabilized on this therapy for approximately 9 months with a mean INR of 2.02 and a warfarin dose ranging from 6.5 to 7.5 mg/week. At a visit with his primary care physician, the patient's INR was subtherapeutic at 1.5. He had not been taking his vitamin K supplement for nearly a week, but had not missed any doses of warfarin. The vitamin K supplement was discontinued and his warfarin dose was increased by 14.3%. Nearly 2 weeks later the patient presented with a critically elevated INR of 8.5, but no acute bleeding. No other factors affecting the INR could be determined. After a dose of 2.5 mg of vitamin K was administered and warfarin was withheld for 2 days, the patient's INR returned to 2.9. Low-dose vitamin K supplementation and warfarin at a lower dose of 7 mg/week were restarted. His INR remained relatively stable, with no ensuing critical INR changes or other sequelae.

Discussion:

Vitamin K supplement removal was believed to be a major contributor to the critically elevated INR. White the warfarin dose had been increased according to the clinic protocol (14.3% for an INR of 1.5), the timing of the INR elevation following supplement removal follows pharmacodynamic expectations of clotting factor synthesis. This case is labeled a category D error.

Conclusions:

Discontinuation of vitamin K supplementation therapy might result in elevation of INR.
Glutamate Receptor Subtypes Mediating Synaptic Activation of Prefrontal Cortex Neurons: Relevance for Schizophrenia
Authors: Rotaru Diana C. , Yoshino Hiroki , Lewis David A. , Ermentrout G. Bard , Gonzalez-Burgos Guillermo
Published: January 2011

Schizophrenia may involve hypofunction of NMDA receptor (NMDAR)-mediated signaling, and alterations in parvalbumin-positive fast-spiking (FS) GABA neurons that may cause abnormal gamma oscillations. It was recently hypothesized that prefrontal cortex (PFC) FS neuron activity is highly dependent on NMDAR activation and that, consequently, FS neuron dysfunction in schizophrenia is secondary to NMDAR hypofunction. However, NMDARs are abundant in synapses onto PFC pyramidal neurons; thus, a key question is whether FS neuron or pyramidal cell activation is more dependent on NMDARs. We examined the AMPAR and NMDAR contribution to synaptic activation of FS neurons and pyramidal cells in the PFC of adult mice. In FS neurons, EPSCs had fast decay and weak NMDAR contribution, whereas in pyramidal cells, EPSCs were significantly prolonged by NMDAR-mediated currents. Moreover, the AMPAR/NMDAR EPSC ratio was higher in FS cells. NMDAR antagonists decreased EPSPs and EPSP–spike coupling more strongly in pyramidal cells than in FS neurons, showing that FS neuron activation is less NMDAR dependent than pyramidal cell excitation. The precise EPSP–spike coupling produced by fast-decaying EPSCs in FS cells may be important for network mechanisms of gamma oscillations based on feedback inhibition. To test this possibility, we used simulations in a computational network of reciprocally connected FS neurons and pyramidal cells and found that brief AMPAR-mediated FS neuron activation is crucial to synchronize, via feedback inhibition, pyramidal cells in the gamma frequency band. Our results raise interesting questions about the mechanisms that might link NMDAR hypofunction to alterations of FS neurons in schizophrenia.
Corticotropin-Releasing Factor Critical for Zebrafish Camouflage Behavior Is Regulated by Light and Sensitive to Ethanol
Authors: Wagle Mahendra , Mathur Priya , Guo Su
Published: January 2011

The zebrafish camouflage response is an innate “hard-wired” behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity ofcrfexpression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.
The Neuronal Basis of Long-Term Sensorimotor Learning
Authors: Mandelblat-Cerf Yael , Novick Itai , Paz Rony , Link Yuval , Freeman Sharon , Vaadia Eilon
Published: January 2011

The brain has a remarkable ability to learn and adjust behavior. For instance, the brain can adjust muscle activation to cope with changes in the environment. However, the neuronal mechanisms behind this adaptation are not clear. To address this fundamental question, this study examines the neuronal basis of long-term sensorimotor learning by recording neuronal activity in the primary motor cortex of monkeys during a long-term adaptation to a force-field perturbation. For 5 consecutive days, the same perturbation was applied to the monkey's hand when reaching to a single target, whereas movements to all other targets were not perturbed. The gradual improvement in performance over these 5 days was correlated to the evolvement in the population neuronal signal, with two timescales of changes in single-cell activity. Specifically, one subgroup of cells showed a relatively fast increase in activity, whereas the other showed a gradual, slower decrease. These adapted patterns of neuronal activity did not involve changes in directional tuning of single cells, suggesting that adaptation was the result of adjustments of the required motor plan by a population of neurons rather than changes in single-cell properties. Furthermore, generalization was mostly expressed in the direction of the required compensatory force during adaptation. Altogether, the neuronal activity and its generalization accord with the adapted motor plan.
Dopamine D2 Receptor Overexpression Alters Behavior and Physiology inDrd2-EGFPMice
Authors: Kramer Paul F. , Christensen Christine H. , Hazelwood Lisa A. , Dobi Alice , Bock Roland , Sibley David R. , Mateo Yolanda , Alvarez Veronica A.
Published: January 2011

Bacteria artificial chromosome (BAC) transgenic mice expressing the reporter protein enhanced green fluorescent protein (EGFP) under the control of the D1 and D2 dopamine receptor promoters (Drd1-EGFPandDrd2-EGFP) have been widely used to study striatal function and have contributed to our understanding of the physiological and pathological functions of the basal ganglia. These tools were produced and promptly made available to address questions in a cell-specific manner that has transformed the way we frame hypotheses in neuroscience. However, these mice have not been fully characterized until now. We found thatDrd2-EGFPmice display an ∼40% increase in membrane expression of the dopamine D2 receptor (D2R) and a twofold increase in D2R mRNA levels in the striatum when compared with wild-type andDrd1-EGFPmice. D2R overexpression was accompanied by behavioral hypersensitivity to D2R-like agonists, as well as enhanced electrophysiological responses to D2R activation in midbrain dopaminergic neurons. Dopamine (DA) transients evoked by stimulation in the nucleus accumbens showed slower clearance in Drd2-EGFP mice, and cocaine actions on DA clearance were impaired in these mice. Thus, it was not surprising to find thatDrd2-EGFPmice were hyperactive when exposed to a novel environment and locomotion was suppressed by acute cocaine administration. All together, this study demonstrates thatDrd2-EGFPmice overexpress D2R and have altered dopaminergic signaling that fundamentally differentiates them from wild-type andDrd1-EGFPmice.
Information Capacity and Transmission Are Maximized in Balanced Cortical Networks with Neuronal Avalanches
Authors: Shew Woodrow L. , Yang Hongdian , Yu Shan , Roy Rajarshi , Plenz Dietmar
Published: January 2011

The repertoire of neural activity patterns that a cortical network can produce constrains the ability of the network to transfer and process information. Here, we measured activity patterns obtained from multisite local field potential recordings in cortex cultures, urethane-anesthetized rats, and awake macaque monkeys. First, we quantified the information capacity of the pattern repertoire of ongoing and stimulus-evoked activity using Shannon entropy. Next, we quantified the efficacy of information transmission between stimulus and response using mutual information. By systematically changing the ratio of excitation/inhibition (E/I)in vitroand in a network model, we discovered that both information capacity and information transmission are maximized at a particular intermediate E/I, at which ongoing activity emerges as neuronal avalanches. Next, we used ourin vitroand model results to correctly predictin vivoinformation capacity and interactions between neuronal groups during ongoing activity. Close agreement between our experiments and model suggest that neuronal avalanches and peak information capacity arise because of criticality and are general properties of cortical networks with balanced E/I.
Differential Expression and Sensitivity of Presynaptic and Postsynaptic Opioid Receptors Regulating Hypothalamic Proopiomelanocortin Neurons
Authors: Pennock Reagan L. , Hentges Shane T.
Published: January 2011

Hypothalamic proopiomelanocortin (POMC) neurons release the endogenous opioid beta-endorphin and POMC neuron activity is inhibited by opioids, leading to the proposal that beta-endorphin acts to provide feedback inhibition. However, both intrinsic properties and synaptic inputs contribute to the regulation of POMC neurons such that attributing an autoregulatory role to opioids must include consideration of opioid receptor localization and sensitivity at both presynaptic and postsynaptic sites. In the present study, whole-cell recordings were made in POMC cells in mouse brain slices and the presynaptic and postsynaptic regulation of POMC neurons was examined using selective agonists for mu, kappa, and delta opioid receptors. Activation of mu, but not kappa or delta, receptors induced a direct postsynaptic outward current. Agonists for each of the receptors inhibited the frequency of spontaneous IPSCs. Mu and kappa, but not delta, agonists reduced the amplitude of evoked IPSCs and appeared to colocalize in a significant portion of GABAergic terminals onto POMC neurons. The presynaptic inhibition caused by the mu agonist DAMGO had an EC50of 80 nm, whereas the EC50was 350 nmwhen measuring the postsynaptic outward current. This differential sensitivity adds an unexpected component of opioid-dependent feedback regulation, where low levels of opioid receptor activation would likely disinhibit POMC neuron activity and higher concentrations would result in an overall inhibition. The results may help explain why it has been difficult to clearly discern the role that opioids play in the regulation of food intake and other processes involving POMC neurons.
The Glutamic Acid-Rich Protein Is a Gating Inhibitor of Cyclic Nucleotide-Gated Channels
Authors: Michalakis Stylianos , Zong Xiangang , Becirovic Elvir , Hammelmann Verena , Wein Thomas , Wanner Klaus T. , Biel Martin
Published: January 2011

The cyclic nucleotide-gated (CNG) cation channel of rod photoreceptors is a heterotetramer consisting of homologous CNGA1 and CNGB1a subunits. While CNGA1 is indispensable for channel activation, the specific role of CNGB1a in this process has remained elusive. Here, we show that the N-terminal glutamic acid-rich protein (GARP) domain of CNGB1a and soluble GARP2, which corresponds to the proximal portion of the GARP domain, act as autoinhibitory domains that decrease the opening probability of the CNG channel. In the presence of mutations that structurally impair the cyclic nucleotide-binding domain (CNBD) of CNGB1a, the GARP domain completely abolishes channel activity. In agreement with an inhibitory function of GARP, the activity of mutant CNG channels could be fully restored by deletion of the GARP domain. We identified two sequences within the GARP domain that confer most of the inhibitory effect and demonstrate that the profound inhibition imposed by the GARP domain is caused by direct and autonomous protein–protein interaction with the CNG channel complex. In wild-type rod CNG channels, this inhibitory effect can be relieved by binding of cGMP to the CNBD of CNGB1a. In conclusion, we propose that the N terminus of CNGB1a and soluble GARPs act as molecular gate keepers that control the activation of heteromeric rod CNG channels. Our results suggest that the GARP domain has evolved in rod photoreceptors to reduce current noise resulting from openings of CNG channels in the absence of cGMP.
μ-Opioid Receptors in the Nucleus Accumbens Shell Region Mediate the Effects of Amphetamine on Inhibitory Control But Not Impulsive Choice
Authors: Wiskerke Joost , Schetters Dustin , van Es Inge E. , van Mourik Yvar , den Hollander Bjørnar R. O. , Schoffelmeer Anton N. M. , Pattij Tommy
Published: January 2011

Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of impulsivity, the five-choice serial reaction time task and the delayed-reward task, providing measures of inhibitory control and impulsive choice, respectively. We focused on the role of opioid receptor activation in amphetamine-induced impulsivity as there is ample evidence indicating an important role for endogenous opioids in several behavioral and neurochemical effects of amphetamine. Results showed that amphetamine-induced inhibitory control deficits were dose-dependently attenuated by the preferential μ-opioid receptor antagonist naloxone, but not by the selective δ-opioid receptor antagonist naltrindole or κ-opioid receptor antagonistnor-BNI (nor-binaltorphimine dihydrochloride). In contrast, naloxone did not affect amphetamine-induced improvements in impulsive decision making. Naloxone also completely prevented inhibitory control deficits induced by GBR 12909 [1-(2-[bis(4-fluorophenyl)methoxy] ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride], a selective dopamine transporter inhibitor. Intracranial infusions of naloxone, the selective μ-opioid receptor antagonist CTAP (H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2), morphine, and the selective μ-opioid receptor agonist DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin acetate salt) revealed that μ-opioid receptor activation in the shell rather than the core subregion of the nucleus accumbens (NAc) modulates inhibitory control and subserves the effect of amphetamine thereon. Together, these results indicate an important role for NAc shell μ-opioid receptors in the regulation of inhibitory control, probably via an interaction between these receptors and the mesolimbic dopamine system.
Knockout of Zn Transporters Zip-1 and Zip-3 Attenuates Seizure-Induced CA1 Neurodegeneration
Authors: Qian Jing , Xu Kaiping , Yoo Jong , Chen Tim T. , Andrews Glen , Noebels Jeffrey L.
Published: January 2011

CA1 pyramidal neurons are the final integrators of information flow leaving the hippocampus, yet are singularly vulnerable to activity-dependent cell death. Zinc (Zn) entry into cells may add to this vulnerability. Here, we find thatSlc39a1andSlc39a3, members of theZip(Zrt/Irt-like protein) plasmalemmal Zn transporter family, are predominantly expressed in the hippocampus. We examinedZip-1,3-deficient mice to investigate their role in neurodegeneration following intense synaptic activation. When isolated by blockade of NMDA receptors and voltage-gated calcium channels, the absence of both transporters slowed passive Zn uptake into CA1 neurons measured with intracellular fluorescent Zn dyes.In vivoCA1 cell damage following kainic acid exposure was greatly attenuated. Consistent with the hypothesis that Zn entry contributes to neurodegeneration,Znt-3-deficient mice lacking synaptic Zn also show less hippocampal cell damage following kainic acid injection.Ziptransporters may provide selective therapeutic targets to protect these neurons from early Zn-induced neurodegeneration following injury.
Spielräume kultureller Kontakte im Roman des 16. Jahrhunderts: Der Finckenritter (Straßburg 1560)
Authors: Röcke Werner
Published: January 2011

Das Eigene und das Fremde  die vertraute Welt des christlichen Europa einerseits, die fremden Kulturen Indiens und Ostasiens andererseits  werden im Mittelalter strikt getrennt gedacht. Darstellungsmuster dieser Fremde sind monströse Lebewesen und andere Wunder, die im Osten bis zum Rand der Welt imaginiert werden. Das Erstaunliche des Finckenritter, eines parodistischen Reiseromans des 16. Jhdts. (um 1560), liegt darin, dass er den Dualismus von fremder und eigener Welt aufhebt und die Topoi der Fremde in die Vertrautheit der eigenen Welt verpflanzt. Damit schafft er die Möglichkeit einer Hybridisierung von Eigenem und Fremdem, welche einerseits neue Perspektiven von Kulturkontakten, andererseits ganz neue moments of wonder (Greenblatt) eröffnet: eine prinzipielle Verkehrung von Sinn und Ordnung der Welt, der Wahrnehmung und der sozialen Kommunikation, die jede mögliche Orientierung des Lesers aufhebt.
On the Road Again. Nomadentum, Zugehörigkeit und europäische Staatsbürgerschaft der Wagenburgen in Berlin
Authors: Marsault Ralf
Published: January 2011

Dieser Beitrag versucht zu verstehen, wie die europäische Staatsbürgerschaft in den Wohnwagensiedlungen, die unter dem Namen Berliner Wagenburgen bekannt wurden, erlebt und geträumt wird. Die Ethik der Wagenburg versteht sich als entschlossen auf die Zukunft gerichtet, eine Zukunft, in der Teilen und Teilhabe neu definiert und Produktion, Konsum und respektvoller Umgang mit der Umwelt neu definiert werden müssen, aber Kompromisse und Zweideutigkeit sind ihr Alltag. Als möglicher Ort für das Entstehen von Beziehungen ohne Zwang, die dennoch Intimität zulassen, gibt so die Wagenburg Sicherheit in Bezug auf das, was dem Individuum gerade noch erlaubt sein kann bei dem Versuch, eine Ethik freidenkerischer Inspiration umzusetzen. Zugleich sieht sich diese Art von Kontaktzone mit Problemen ritualisierter Begegnungsabläufe, narzisstischer Projektionen und des Betrachtens des Anderen im Spiegel der eigenen Phantasien konfrontiert.
It′s the Japans. Kontaktzonen im Film zwischen Aneignung und Unverfügbarkeit
Authors: Baisch Martin , Freienhofer Evamaria
Published: January 2011

Ausgehend von Überlegungen zum Konzept der Kontaktzone von der Literaturwissenschaftlerin Mary Louise Pratt analysiert der Beitrag Filmszenen der US-Fernsehserie Shogun von 1980 und Sofia Coppolas Spielfilm Lost in Translation von 2003. Unter dem Begriff der Kontaktzone wird dabei ein Rezeptionsakt verstanden, der seine Geltungsansprüche an fluktuierende Zeichenprozesse knüpft. Eine Kontaktzone entsteht sowohl im Aufeinandertreffen von Akteuren verschiedener Kulturen als auch im Aufeinandertreffen kultureller Produkte und deren Publikum. In den Filmbeispielen erweist sich die Inszenierung von Gesten als zentrales Darstellungsmittel im interkulturellen Kontakt, das (in Lernprozessen) zwischen Aneignung und Unverfügbarkeit oszilliert.
Hyperbolé  Politik, Macht, Potenz
Authors: Marramao Giacomo
Published: January 2011

Ziel dieses Beitrags ist die Untersuchung der Begriffe Politik, Macht und Potenz und die Analyse der zwischen ihnen bestehenden Unterschiede. Unter Bezug auf die antike Philosophie werden zentrale Dimensionen des Begriffs der Politik entwickelt. Davon wird der Begriff der Macht unterschieden und sein unterschiedliches Bedeutungsfeld wird entwickelt. Von beiden Begriffen wird unter Rückgriff auf Spinoza der Begriff der Potenz unterschieden. Ziel der Analyse ist die Rekonstruktion eines komplexen Begriffes der Politik, der Reduktionen vermeidet und den Herausforderungen der heutigen Welt gerecht wird.
Innovations in the rise of the dative-infinitive modal sentence in Russian
Authors: Jung Hakyung
Published: January 2011

It has been widely assumed in the literature that the be-modal construction with dative subject in Indo-European languages developed from the existential/possessive sentence in the form of mihi est ‘meDAT there is.’ This paper offers two types of language-internal evidence in favor of this hypothesis for the dative-infinitive modal construction (DIM) in Russian. The first evidence is the nominative object marking and the OV word order in the DIM in Old North Russian. The other comes from the language-internal variants of the DIM, which share crucial syntactic properties with the DIM. The evolutionary process, reflected in the structure of these constructions, is construed as the reduction of thematic features in overt arguments, triggered by the category shift of purposive verbal noun to infinitive. Under the assumption that be is a functional predicate both in be-possessive and be-modal constructions, the grammaticalization of the DIM is defined as the change of a grammatical item to another grammatical element.
Titoistische Ketzerei: Die Bogomilen als Antizipation des „dritten Weges“ Jugoslawiens
Authors: Zimmermann Tanja
Published: January 2011

Only a few years after Yugoslavia was excluded from the Cominform, Tito and his ideologists adopted the term third way as a keyword to designate the Yugoslav politics between East and West. Originally, the term had been coined by the Soviets to denigrate what they perceived as an impossible compromise between Capitalism and Communism. Soon, Yugoslav politicians turned it into a positive slogan. In 1950, the Croatian writer Miroslav Krlezha organised a monumental exhibition of Yugoslav medieval art in the Palais de Chaillot in Paris. He presented the medieval Bosnian sect of the Bogomils with its special form of “socialism” as anticipation and a historical legitimation of Yugoslav sovereignty. Other theoreticians such as the Serbian writer Oto Bihalji-Merin compared Tito and his partisans to rebellious Bogomils. The essay retraces the development of that myth, touching also on cinema and later phases of political propaganda.
Buchbesprechung
Authors: Waegemans Emmanuel
Published: January 2011

Kerstin S. Jobst, Die Perle des Imperiums. Der russische Krim-Diskurs im Zarenreich. Konstanz, Universitätsverlag, 2007, 485 S. (Historische Kulturwissenschaft. Band 11). ISBN 978-3-89669-638-0
The role of the brain in the regulation of metabolism and energy expenditure: the central role of insulin, the insulin resistance of the brain
Authors: Halmos Tamás , Suba Ilona
Published: January 2011

Regulatory role of the brain in energy expenditure, appetite, glucose metabolism, and central effects of insulin has been prominently studied. Certain neurons in the hypothalamus increase or decrease appetite via orexigenes and anorexigenes, regulating energy balance and food intake. Hypothalamus is the site of afferent and efferent stimuli between special nuclei and beta- and alpha cells, and it regulates induction/inhibition of glucose output from the liver. Incretines, produced in intestine and in certain brain cells (brain-gut hormones), link to special receptors in the hypothalamus. Central role of insulin has been proved both in animals and in humans. Insulin gets across the blood-brain barrier, links to special hypothalamic receptors, regulating peripheral glucose metabolism. Central glucose sensing, via “glucose-excited” and “glucose-inhibited” cells have outstanding role. Former are active in hyperglycaemia, latter in hypoglycaemia, via influencing beta– and alpha cells, independently of traditional metabolic pathways. Evidence of brain insulin resistance needs centrally acting drugs, paradigm changes in therapy and prevention of metabolic syndrome, diabetes, cardiovascular and oncological diseases. Orv. Hetil., 2011, 152, 83–91.
Asthma and chronic obstructive pulmonary disease overlap
Authors: Müller Veronika , Gálffy Gabriella , Tamási Lilla
Published: January 2011

Asthma bronchiale and chronic obstructive pulmonary disease are the most prevalent lung diseases characterized by inflammation of the airways. International and Hungarian guidelines privide proper definitions for clinical symptoms, diagnostics and therapy of both diseases. However, in everyday clinical practice, overlap of asthma and chronic obstructive pulmonary disease has become more frequent. As guidelines are mainly based on large, multicenter, randomized, controlled trials that exclude overlap patients, there is a lack of diagnostic and especially therapeutic strategies for these patients. This review summarizes clinical characteristics of asthma and chronic obstructive pulmonary disease overlap, and provides daily practical examples for its management. Orv. Hetil., 2011, 152, 114–118.
A monolithic segmented functional light guide for 2‐D dimming LCD backlight
Authors: Käläntär K.
Published: January 2011

Abstract—An edge‐lit backlight with a thin structure and 2‐D dimming function is a highlighted requirement. To achieve a thin backlight unit for 2‐D dimmable displays, a monolithic functional light‐guide plate (LGP) was segmented by using a recessed U‐groove with graded height as semi‐partitions. The height of the U‐groove controls the cross‐talk between the segments. A single segment was characterized with an array of louver‐shaped micro‐prisms that function as unilateral reflectors for light distributing, directing, and extracting. Arrays of rounded micro‐prisms, and lenticular prisms for in‐ and out‐coupling, are designed on the light injection surface and front surface of the LGP for light‐cone shaping on the BLU. The light guide has a length of 73.0 mm, a width of 40.7 mm, and a thickness of 0.7 mm. The LGP was segmented into 16 segments where the width and graded height of the recessed U‐prism between the segments is 0.020 mm and 0.10–0.50 mm, respectively. By using the monolithic light‐guide plate, the cross‐talk is suppressed to 20% and 4% at the center of first and second neighboring segments, respectively.
Gravity tectonics in the SE Basin (Provence, France) imaged from seismic reflection data
Authors: Rangin Claude , Le Pichon Xavier , Hamon Youri , Loget Nicolas , Crespy Agnès
Published: January 2011

Using industrial seismic data available in the French Southeast Basin in Provence, we put into evidence thin skinned processes that have dominated tectonics in this basin since the Oligocene. These interpretations are then replaced within the regional structural framework of SW France with geological maps and field work. A thick Mesozoic and Cenozoic sedimentary cover is detached on a main décollement frequently localized within the Triassic evaporites. The underlying basement is undeformed. The Mid-Durance fault, the Luberon, Trévaresse, and the Ventoux-Lure thrust zones and the Diois-Baronnies fold and thrust belt are produced by thin-skinned tectonics, the associated structures having no roots within the pre-Triassic basement. This thin-skinned deformation is interpreted as resulting from a regional southward gravity mass flow, induced by the westward Alps extrusion, followed in recent times by radial collapse of the Alps. The incipient stage of this gravity sliding occurred during the Late Oligocene in the Diois-Baronnies (the former Mesozoic Vocontian basin), and then rapidly progressed to the south across the Ventoux-Lure thrust zone in Provence during the Miocene. Southward, this gravity sliding vanishes approaching the E-W trending structural high of the Eocene Pyrénéo-Provençal orogenic belt in southern Provence.