bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mir-144 selectively regulates embryonic α-hemoglobin synthesis during primitive erythropoiesis
Authors: Fu Yan-Fang , Du Ting-Ting , Dong Mei , Zhu Kang-Yong , Jing Chang-Bin , Zhang Yong , Wang Lei , Fan Hong-Bo , Chen Yi , Jin Yi , Yue Gui-Ping , Chen Sai-Juan , Chen Zhu , Huang Qiu-Hua , Jing Qing , Deng Min , Xi Liu Ting 
Published: October 2008

AbstractPrecise transcriptional control of developmental stage-specific expression and switching of α- and β-globin genes is significantly important to understand the general principles controlling gene expression and the pathogenesis of thalassemia. Although transcription factors regulating β-globin genes have been identified, little is known about the microRNAs and trans-acting mechanism controlling α-globin genes transcription. Here, we show that an erythroid lineage-specific microRNA gene, miR-144, expressed at specific developmental stages during zebrafish embryogenesis, negatively regulates the embryonic α-globin, but not embryonic β-globin, gene expression, through physiologically targeting klfd, an erythroid-specific Krüppel-like transcription factor. Klfd selectively binds to the CACCC boxes in the promoters of both α-globin and miR-144 genes to activate their transcriptions, thus forming a negative feedback circuitry to fine-tune the expression of embryonic α-globin gene. The selective effect of the miR-144-Klfd pathway on globin gene regulation may thereby constitute a novel therapeutic target for improving the clinical outcome of patients with thalassemia.
In silico microarray probe design for diagnosis of multiple pathogens
Authors: Vijaya Satya Ravi , Zavaljevski Nela , Kumar Kamal , Bode Elizabeth , Padilla Susana , Wasieloski Leonard , Geyer Jeanne , Reifman Jaques 
Published: October 2008

Abstract

Background
With multiple strains of various pathogens being sequenced, it is necessary to develop high-throughput methods that can simultaneously process multiple bacterial or viral genomes to find common fingerprints as well as fingerprints that are unique to each individual genome. We present algorithmic enhancements to an existing single-genome pipeline that allows for efficient design of microarray probes common to groups of target genomes. The enhanced pipeline takes advantage of the similarities in the input genomes to narrow the search to short, nonredundant regions of the target genomes and, thereby, significantly reduces the computation time. The pipeline also computes a three-state hybridization matrix, which gives the expected hybridization of each probe with each target.

Results
Design of microarray probes for eight pathogenic Burkholderia genomes shows that the multiple-genome pipeline is nearly four-times faster than the single-genome pipeline for this application. The probes designed for these eight genomes were experimentally tested with one non-target and three target genomes. Hybridization experiments show that less than 10% of the designed probes cross hybridize with non-targets. Also, more than 65% of the probes designed to identify all Burkholderia mallei and B. pseudomallei strains successfully hybridize with a B. pseudomallei strain not used for probe design.

Conclusion
The savings in runtime suggest that the enhanced pipeline can be used to design fingerprints for tens or even hundreds of related genomes in a single run. Hybridization results with an unsequenced B. pseudomallei strain indicate that the designed probes might be useful in identifying unsequenced strains of B. mallei and B. pseudomallei.
Persistent expression of BMP-4 in embryonic chick adrenal cortical cells and its role in chromaffin cell development
Authors: Huber Katrin , Franke Aylin , Brühl Barbara , Krispin Shlomi , Ernsberger Uwe , Schober Andreas , Halbach Oliver von Bohlen und , Rohrer Hermann , Kalcheim Chaya , Unsicker Klaus 
Published: October 2008

Abstract
Background
Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs) emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate.

Results
We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of 'chromaffin' granules were significantly increased.

Conclusion
BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.
Impaired long-term memory retention and working memory in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia
Authors: Takao Keizo , Toyama Keiko , Nakanishi Kazuo , Hattori Satoko , Takamura Hironori , Takeda Masatoshi , Miyakawa Tsuyoshi , Hashimoto Ryota 
Published: October 2008

Abstract

Background
Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. The dystrobrevin-binding protein 1 (DTNBP1: dysbindin-1) gene is a major susceptibility gene for schizophrenia. Genetic variations in DTNBP1 are associated with cognitive functions, general cognitive ability and memory function, and clinical features of patients with schizophrenia including negative symptoms and cognitive decline. Since reduced expression of dysbindin-1 has been observed in postmortem brains of patients with schizophrenia, the sandy (sdy) mouse, which has a deletion in the Dtnbp1 gene and expresses no dysbindin-1 protein, could be an animal model of schizophrenia. To address this issue, we have carried out a comprehensive behavioral analysis of the sdy mouse in this study.

Results
In a rotarod test, sdy mice did not exhibit motor learning whilst the wild type mice did. In a Barnes circular maze test both sdy mice and wild type mice learned to selectively locate the escape hole during the course of the training period and in the probe trial conducted 24 hours after last training. However, sdy mice did not locate the correct hole in the retention probe tests 7 days after the last training trial, whereas wild type mice did, indicating impaired long-term memory retention. A T-maze forced alternation task, a task of working memory, revealed no effect of training in sdy mice despite the obvious effect of training in wild type mice, suggesting a working memory deficit.

Conclusion
Sdy mouse showed impaired long-term memory retention and working memory. Since genetic variation in DTNBP1 is associated with both schizophrenia and memory function, and memory function is compromised in patients with schizophrenia, the sdy mouse may represent a useful animal model to investigate the mechanisms of memory dysfunction in the disorder.
Effects of Recombinant Human Growth Hormone Therapy in Obesity in Adults: A Metaanalysis
Authors: Mekala Kavya C. , Tritos Nicholas A. 
Published: October 2008

AbstractObjective: To conduct a metaanalysis of human studies examining the efficacy and safety of recombinant human GH (rhGH) as therapy for obesity in adults.Design: A thorough search of the literature (including MEDLINE, EMBASE, and the Cochrane Register) was performed for pertinent studies, which were analyzed and subsequently synthesized in a comprehensive metaanalysis.Results: Administration of rhGH led to significant changes in body composition [weighted mean difference (95% confidence interval)], including fat mass [−0.9 kg (−1.3 to −0.4)], percent body fat [−1% (−1.3 to −0.7)], lean body mass [1.8 kg (0.6–2.9)], visceral adipose area [−22.8 cm2 (−39.8 to −5.7)], and lipid profile, including total cholesterol [−7 mg/dl (−11 to −3)] and low-density lipoprotein-cholesterol [−9 mg/dl (−13 to −5)]. There were increases in fasting plasma glucose [3 mg/dl (1–6)] and insulin [1.9 μU/ml (0.2–3.7)]. The latter finding was found only in shorter-term studies. Adverse effects included [odds ratio (95% confidence interval)] arthralgias [6 (1.9–18.6)], peripheral edema [5 (2.4–10.5)], and paresthesias [6.5 (1.5–27.3)].Conclusions: Our metaanalysis suggests that rhGH therapy leads to decrease in visceral adiposity and increase in lean body mass as well as beneficial changes in lipid profile in obese adults, without inducing weight loss. Administration of rhGH was associated with increases in fasting plasma glucose and insulinemia. Because the rhGH doses used in many studies were supraphysiological, future studies of longer duration, using carefully titrated rhGH protocols, will be needed to fully establish the effects of rhGH therapy in obesity, including effects on cardiovascular morbidity and mortality.
Amiodarone-Induced Thyrotoxicosis Is a Predictor of Adverse Cardiovascular Outcome
Authors: Yiu Kai-Hang , Jim Man-Hong , Siu Chung-Wah , Lee Chi-Ho , Yuen Michele , Mok Maggie , Shea Yet-Fung , Fan Katherine , Tse Hung-Fat , Chow Wing-Hing 
Published: October 2008

Abstract
Background: Amiodarone-induced thyrotoxicosis (AIT) is a clinical condition that is notoriously difficult to manage; the relative risk of adverse cardiovascular events in these patients compared with euthyroid patients is largely unknown.
Objective: We compared the clinical characteristics and major adverse cardiovascular events (MACE) in AIT and euthyroid patients.
Method: Patients at a tertiary referral center who had been prescribed amiodarone for at least 3 months were retrospectively analyzed. Baseline clinical characteristics, laboratory parameters, and outcome events were evaluated. MACE was defined as cardiovascular mortality, myocardial infarction, stroke and heart failure, or ventricular arrhythmias that required hospitalization.
Results: A total of 354 patients (61.8 ± 14.1 yr; 64.7% male) with a mean follow-up of 48.6 ± 26.7 months were studied. AIT, euthyroid status, and amiodarone-induced hypothyroidism were identified in 57 (16.1%), 224 (63.3%), and 73 (20.6%) patients, respectively. No differences in baseline clinical characteristics were observed between AIT and euthyroid patients. Nonetheless AIT patients demonstrated a higher MACE rate (31.6 vs. 10.7%, P &lt; 0.01), mostly driven by a higher rate of ventricular arrhythmias that required admission (7.0 vs. 1.3%, P = 0.03). Cox-regression multivariate analysis revealed that AIT (hazard ratio 2.68; confidence interval 1.53–4.68; P &lt; 0.01) and left ventricular ejection fraction less than 45% (hazard ratio 2.52; confidence interval 1.43–4.42; P &lt; 0.01) were independent predictors of MACE.
Conclusion: In patients prescribed long-term amiodarone therapy, occurrence of AIT is associated with a 2.7-fold increased risk of MACE. Regular and close biochemical surveillance is thus advisable to identify and treat this high-risk group of patients.
Simulation of railway brake plants: An application to SAADKMS freight wagons
Authors: Pugi L , Palazzolo A , Fioravanti D 
Published: October 2008

The UIC railway braking system is a complex pneumatic plant whose performance and reliability are safety relevant. The plant is controlled by the transmission of pneumatic signals; different train compositions involve large parametric variations of plant response. The problem is critical for long freight trains where the delayed plant response involves heavy longitudinal forces between vehicles. Even for simple compositions of 10—15 vehicles, the number of components involved in the plant response is quite high. The distributor valve, a complex pneumo-mechanic device, is devoted to control the brake response on every vehicle and it is perhaps the most difficult component to be simulated. Authors have developed simulation models of the pneumatic plant of the UIC railway brake including libraries of pneumatic submodels that can be parametrically calibrated in order to reproduce different train compositions. In this work, a case study concerning the simulation of a convoy composed by the SAADKMS freight wagon is presented. Simulation results are compared with experimental data kindly supplied by Trenitalia SPA. Model formulation and calibration procedures are shown in order to explain the followed workflow.
Experimental metrics for identifying origins of combustion variability during spark-assisted compression ignition
Authors: Reuss D L , Kuo T-W , Silvas G , Natarajan V , Sick V 
Published: October 2008

Spark-assisted compression ignition, SACI, can be used to control the combustion phasing of compression-ignition gasoline engines. However, implementation of this technique can be confounded by cyclic variability. The purpose of this paper is to define experimental metrics that describe the SACI process and to demonstrate the use of these metrics for identifying the source(s) of cyclic variability during the SACI process. This study focused on a light load condition (7 mg/cycle, 200 kPa i.m.e.p.), where spray-guided direct fuel injection with spark ignition and an exhaust-rebreathing strategy was employed to achieve flame propagation, which led to compression ignition. This study employed a combination of measurements including pressure-based heat-release analysis, spark-discharge voltage/current measurements, and cycle-resolved combustion imaging. Based on these measurements, four distinct combustion periods were identified; namely, the spark discharge, the early kernel growth (EKG), flame propagation, and the compression ignition periods. Metrics were defined to characterize each period and used to identify the contribution of each period to the cyclic variability of the main heat release. For the light load condition studied here, the EKG period had the largest effect on the crank angle (CA) position of 50 per cent mass burned, CA50. The spark-discharge event may affect CA50 indirectly through its influence on EKG. However, this could not be definitively assessed here since the camera was incapable of recording both the spark-discharge event and the flame images during cycles of the same tests.
Open access training material
Authors: Light Kate , Stirk Lisa 
Published: October 2008

One of the main challenges of providing training is producing the content. Even if the subject is the trainer's own area of expertise, distilling years of knowledge and experience into an effective training package is often a daunting and time consuming task. Sourcing content from the Internet can be fraught with difficulties relating to copyright. Luckily there are now many sites that provide open access training materials. If you would like to alert readers to useful web pages or suggest topics for this column, please send details to:
Dispensing with Conscience: A Legal and Ethical Assessment
Authors: Wernow Jerome R , Grant Donald G 
Published: October 2008

Background: For over 30 years, pharmacists have exercised the right to dispense medications in accordance with moral convictions based upon a Judeo-Christian ethic. What many of these practitioners see as an apparent shift away from this time-honored ethic has resulted in a challenge to this right. Objective: To review and analyze pharmacy practice standards, legal proceedings, and ethical principles behind conflicts of conscientious objection in dispensing drugs used for emergency contraception. Data Sources: We first searched the terms conscience and clause and Plan B and contraception and abortion using Google, Yahoo, and Microsoft Networks (2006–September 26, 2008). Second, we used Medscape to search professional pharmacy and other medical journals, restricting our terms to conscience, Plan B, contraceptives, and abortifacients. Finally, we employed Loislaw, an online legal archiving service, and did a global search on the phrase conscience clause to determine the status of the legal discussion. Data Synthesis: To date, conflicts in conscientious objection have arisen when a pharmacist believes that dispensing an oral contraceptive violates his or her moral understanding for the promotion of human life. Up to this time, cases in pharmacy have involved only practitioners from orthodox Christian faith communities, primarily devout Roman Catholics. A pharmacist's right to refuse the dispensing of abortifacients for birth control according to moral conscience over against a woman's right to reproductive birth control has created a conflict that has yet to be reconciled by licensing agents, professional standards, or courts of law. Conclusions: Our analysis of prominent conflicts suggests that the underlying worldviews between factions make compromise improbable. Risks and liabilities are dependent upon compliance with evolving state laws, specific disclosure of a pharmacist's moral objections, and professionalism in the handling of volatile situations. Objecting pharmacists and their employers should have clear policies and procedures in place to minimize workplace conflicts and maximize patient care.
Role of Acetyl-L-Carnitine in the Treatment of Diabetic Peripheral Neuropathy
Authors: Evans Jeffery D , Jacobs Tibb F , Evans Emily W 
Published: October 2008

Objective: To examine the role of acetyl-L-carnitine (ALC) in the treatment of diabetic peripheral neuropathy (DPN). Data Sources: A MEDLINE search (1966–April 2008) of the English-language literature was performed using the search terms carnitine, diabetes, nerve, and neuropathy. Studies identified were then cross-referenced for their citations. Study Selection and Data Extraction: The search was limited to clinical trials, meta-analyses, and reviews addressing the use of ALC for the treatment of DPN. Studies that included other disease states that could cause peripheral neuropathy were excluded. Two large clinical studies that used ALC for the treatment of DPN were identified. No case studies were identified. Data Synthesis: The results from 2 published clinical trials Involving 1679 subjects were included. Subjects who received at least 2 g daily of ALC showed decreases in pain scores. One study showed improvements in electrophysiologic factors such as nerve conduction velocities, while the other did not. Patients who had neuropathic pain reported reductions in pain using a visual analog scale. Nerve regeneration was documented in one trial. The supplement was well tolerated, A proprietary form of ALC was used in both studies. Conclusions: Data on treatment of DPN with ALC support its use. It should be recommended to patients early in the disease process to provide maximal benefit. Further studies should be conducted to determine the effectiveness of ALC in the treatment and prevention of the worsening symptoms of DPN.
Clinical Decision Support Tools: Personal Digital Assistant versus Online Dietary Supplement Databases
Authors: Clauson Kevin A , Polen Hyla H , Peak Amy S , Marsh Wallace A , DiScala Sandra L 
Published: October 2008

Background: Clinical decision support tools (CDSTs) on personal digital assistants (PDAs) and online databases assist healthcare practitioners who make decisions about dietary supplements. Objective: To assess and compare the content of PDA dietary supplement databases and their online counterparts used as CDSTs. Methods: A total of 102 question-and-answer pairs were developed within 10 weighted categories of the most clinically relevant aspects of dietary supplement therapy. PDA versions of AltMedDex. Lexi-Natural, Natural Medicines Comprehensive Database, and Natural Standard and their online counterparts were assessed by scope (percent of correct answers present), completeness (3-point scale), ease of use, and a composite score integrating all 3 criteria. Descriptive statistics and inferential statistics, including a χ2 test, Scheffé's multiple comparison test, McNemar's test, and the Wilcoxon signed rank test were used to analyze data. Results: The scope scores for PDA databases were: Natural Medicines Comprehensive Database 84.3%, Natural Standard 58.8%, Lexi-Natural 50.0%, and AltMedDex 36.3%, with Natural Medicines Comprehensive Database statistically superior (p < 0.01). Completeness scores were; Natural Medicines Comprehensive Database 78.4%, Natural Standard 51.0%, Lexi-Natural 43.5%, and AltMedDex 29.7%. Lexi-Natural was superior in ease of use (p < 0.01). Composite scores for PDA databases were: Natural Medicines Comprehensive Database 79.3, Natural Standard 53.0, Lexi-Natural 48.0, and AltMedDex 32.5, with Natural Medicines Comprehensive Database superior (p < 0.01). There was no difference between the scope for PDA and online database pairs with Lexi-Natural (50.0% and 53.9%, respectively) or Natural Medicines Comprehensive Database (84.3% and 84.3%, respectively) (p > 0.05), whereas differences existed for AltMedDex (36.3% vs 74.5%, respectively) and Natural Standard (50.8% vs 80.4%, respectively) (p < 0.01). For composite scores, AltMedDex and Natural Standard online were better than their PDA counterparts (p < 0.01). Conclusions: Natural Medicines Comprehensive Database achieved significantly higher scope, completeness, and composite scores compared with other dietary supplement PDA CDSTs in this study. There was no difference between the PDA and online databases for Lexi-Natural and Natural Medicines Comprehensive Database, whereas online versions of AltMedDex and Natural Standard were significantly better than their PDA counterparts.
BGH, Urteil vom 18. 6. 2007 – II ZR 86/06, Kapitalerhaltungsgebot bei der Veräußerung von GmbH-Anteilen
Authors: Böcker Philipp 
Published: October 2008

Abstract

Urteil vom 18. 6. 2007 – II ZR 86/06

1. Erwirbt der Gesellschafter einer GmbH von seinen Mitgesellschaftern deren Geschäftsanteile unter der aufschiebenden Bedingung der vollständigen Kaufpreiszahlung und hat die Gesellschaft den Veräußerern in einem Bankdepot befindliche Wertpapiere zur Sicherung der Kaufpreisforderung übertragen, so sind sowohl die Anteilsveräußerer als auch der Erwerber Adressaten des Kapitalerhaltungsgebots des § 30 GmbHG.

2. Haften Anteilsveräußerer und Erwerber bei einem Verstoß gegen das Auszahlungsverbot als Gesamtschuldner auf Rückerstattung (§ 31 GmbHG, § 421 BGB), so kann die Gesellschaft die Leistung grundsätzlich nach ihrem Belieben von jedem der Schuldner ganz oder zu einem Teil – ohne Rücksicht auf etwaige Ausgleichs- und Regresspflichten der Gesamtschuldner im (Innen-)Verhältnis zueinander – fordern.

3. Für die Entstehung des Erstattungsanspruchs nach §§ 31, 30 GmbHG ist bei einer Sicherheitenbestellung in Form der Sicherungsübertragung von in einem Bankdepot befindlichen Wertpapieren nicht der Zeitpunkt der effektiven Auskehr des Verwertungserlöses, sondern bereits derjenige der Verwertung des Sicherungsgutes selbst maßgeblich.

4. Hat der Lauf der Verjährungsfrist des § 31 Abs. 5 Satz 1, Hs. 2GmbHG a. F. (= § 31 Abs. 5 Satz 2GmbHG n. F.) mit der Verwertung des Sicherungsgutes begonnen, so wird durch die anschließende Auszahlung des Erlöses keine neue Verjährungsfrist in Gang gesetzt.

(Vorgehend: LG Potsdam, 2. 12. 2004 – 51 O 146/03; OLG Brandenburg, 14. 2. 2006 – 6 U 157/04)