bluuebunny/crossref_metadata_2025 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

Precise 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

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

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

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

Objective: 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

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 < 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 < 0.01) and left ventricular ejection fraction less than 45% (hazard ratio 2.52; confidence interval 1.43–4.42; P < 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.
ROCK-mediated contractility, tight junctions and channels contribute to the conversion of a preapical patch into apical surface during isochoric lumen initiation
Authors: Ferrari Aldo , Veligodskiy Alexey , Berge Ulrich , Lucas Miriam S. , Kroschewski Ruth
Published: October 2008

Epithelial cells assemble into three-dimensional aggregates to generate lumen-containing organ substructures. Cells therein contact the extracellular matrix with their basal surface, neighbouring cells with their contact surface and the lumen with their apical surface. We investigated the development of single MDCK cells into aggregates with lumen using quantitative live-cell imaging to identify morphogenetic rules for lumen formation. In two-cell aggregates, membrane insertion into the contact surface established a preapical patch (PAP) characterized by the presence of the apical marker gp135, microvilli and the absence of E-cadherin. This PAP originated from a compartment that had hallmarks of an apical recycling endosome, and matured through Brefeldin-A-sensitive membrane trafficking and the establishment of tight junctions around itself. As a result of the activity of water and ion channels, an optically resolvable lumen formed. Initially, this lumen enlarged without changes in aggregate volume or cell number but with decreasing cell volumes. Additionally, the ROCK1/2-myosin-II pathway counteracted PAP and lumen formation. Thus, lumen formation results from PAP establishment, PAP maturation, lumen initiation and lumen enlargement. These phases correlate with distinct cell surface and volume patterns, which suggests that such morphometric parameters are regulated by trafficking, ROCK-mediated contractility and hydrostatic pressure or vice versa.
A dominant vimentin mutant upregulates Hsp70 and the activity of the ubiquitin-proteasome system, and causes posterior cataracts in transgenic mice
Authors: Bornheim Roland , Müller Martin , Reuter Uschi , Herrmann Harald , Büssow Heinrich , Magin Thomas M.
Published: October 2008

Vimentin is the main intermediate filament (IF) protein of mesenchymal cells and tissues. Unlike other IF–/– mice, vimentin–/– mice provided no evidence of an involvement of vimentin in the development of a specific disease. Therefore, we generated two transgenic mouse lines, one with a (R113C) point mutation in the IF-consensus motif in coil1A and one with the complete deletion of coil 2B of the rod domain. In epidermal keratins and desmin, point mutations in these parts of the α-helical rod domain cause keratinopathies and desminopathies, respectively. Here, we demonstrate that substoichiometric amounts of vimentin carrying the R113C point mutation disrupted the endogenous vimentin network in all tissues examined but caused a disease phenotype only in the eye lens, leading to a posterior cataract that was paralleled by the formation of extensive protein aggregates in lens fibre cells. Unexpectedly, central, postmitotic fibres became depleted of aggregates, indicating that they were actively removed. In line with an increase in misfolded proteins, the amounts of Hsp70 and ubiquitylated vimentin were increased, and proteasome activity was raised. We demonstrate here for the first time that the expression of mutated vimentin induces a protein-stress response that contributes to disease pathology in mice, and hypothesise that vimentin mutations cause cataracts in humans.
Plasma-membrane-anchored growth factor pro-amphiregulin binds A-type lamin and regulates global transcription
Authors: Isokane Mayumi , Hieda Miki , Hirakawa Satoshi , Shudou Masachika , Nakashiro Koichi , Hashimoto Koji , Hamakawa Hiroyuki , Higashiyama Shigeki
Published: October 2008

Amphiregulin (AR), a member of the EGF family, is synthesized as a type I transmembrane protein precursor (proAR) and expressed on the cell surface. Shedding of proAR yields a transmembrane-cytoplasmic fragment (AR-CTF), as well as a soluble AR. Here we demonstrate that the proAR-shedding stimuli trigger endocytosis of both AR-CTF and un-shed proAR. ProAR translocates from the plasma membrane to the inner nuclear membrane, whereas AR-CTF is translocated to the lysosome via retrograde membrane trafficking. Nuclear envelope localization of proAR involves truncation of the C-terminus, which subsequently activates the ER-retrieval signal. The truncated form of proAR interacts with A-type lamin and is retained at the inner nuclear membrane. Heterochromatin formation is then induced and global transcription is transiently suppressed. This study gives new insight into epigenetic chromatin organization in mammalian cells: a plasma-membrane-anchored growth factor is targeted to the inner nuclear membrane where it participates in dynamic chromatin organization and control of transcription.
Across the meiotic divide – CSF activity in the post-Emi2/XErp1 era
Authors: Wu Judy Qiju , Kornbluth Sally
Published: October 2008

Vertebrate eggs are arrested at the metaphase stage of meiosis II. Only upon fertilization will the metaphase-II-arrested eggs exit meiosis II and enter interphase. In 1971, Masui and Markert injected egg extracts into a two-cell-stage embryo and found that the injected blastomere arrested at the next mitosis. On the basis of these observations, they proposed the existence of an activity present in the eggs that is responsible for meiosis-II arrest and can induce mitotic arrest, and named this activity cytostatic factor (CSF). Although the existence of CSF was hypothesized more than 35 years ago, its precise identity remained unclear until recently. The discovery of the Mos-MAPK pathway and characterization of the anaphase-promoting complex/cyclosome (APC/C) as a central regulator of M-phase exit provided the framework for a molecular understanding of CSF. These pathways have now been linked by the discovery and characterization of the protein Emi2, a meiotic APC/C inhibitor, the activity and stability of which are controlled by the Mos-MAPK pathway. Continued investigation into the mechanism of action and mode of regulation of Emi2 promises to shed light not only on CSF function, but also on the general principles of APC/C regulation and the control of protein function by MAPK pathways.
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.
Track vibration analysis for railways with mixed passenger and freight traffic
Authors: Lei X , Rose J G
Published: October 2008

By means of establishing the continuous elastic three layer beam model for track structures with random irregularity of the track vertical profile, a methodology of analysing track vibration by Fourier transform technique is presented. First, the vibration equations of the track structure are transformed by Fourier transform. The vibration displacements in Fourier transform domain are solved with this transformed equation. Then, the vibration responses of the track structure are obtained by performing inverse Fast Fourier Transform. As an application example, vibration analysis of the track for railways with mixed passenger and freight traffic is carried out. Influences of different speeds of passenger and freight trains and different line grades of the track irregularity on track vibration are investigated. The studies show that the worst situation for railways with mixed passenger and freight traffic is from freight trains. The track displacement and the track acceleration as well as the track dynamic forces on the ground resulting from freight traffic are larger by 54—57, 39—47, and 52—56 per cent, respectively than those from the passenger trains when both passenger and freight trains are running at the same speed. Also, the irregularity of the track vertical profile has great impact on track vibration. With the development of track irregularity, dynamic responses induced by freight trains increase more rapidly than those induced by passenger trains.
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.
Influence of gas composition on the combustion and efficiency of a homogeneous charge compression ignition engine system fuelled with methanol reformed gases
Authors: Shudo T
Published: October 2008

A homogeneous charge compression ignition (HCCI) engine system fuelled with dimethyl ether (DME) and methanol-reformed gas (MRG), both produced from methanol by onboard reformers using exhaust heat, has been proposed in previous research. Adjusting the proportions of DME and MRG with different ignition properties effectively controlled the ignition timing and load in HCCI combustion. The use of the single liquid fuel, methanol, also eliminates the inconvenience of carrying two fuels while maintaining the effective ignition control effect. Because reactions producing DME and MRG from methanol are endothermic, a part of the exhaust gas heat energy can be recovered during the fuel reforming. Methanol can be reformed into various compositions of hydrogen, carbon monoxide, and carbon dioxide. The present paper aims to establish the optimum MRG composition for the system in terms of ignition control and overall efficiency. The results show that an increased hydrogen fraction in MRG retards the onset of high-temperature oxidation and permits operation with higher equivalence ratios. However, the MRG composition affects the engine efficiency only a little, and the MRG produced by the thermal decomposition having the best waste-heat recovery capacity brings the highest overall thermal efficiency in the HCCI engine system fuelled with DME and MRG.
Characterizing the cyclic variability of ignition timing in a homogeneous charge compression ignition engine fuelled with n-heptane/iso-octane blend fuels
Authors: Shahbakhti M , Koch C R
Published: October 2008

The cyclic variations of homogeneous charge compression ignition (HCCI) ignition timing is studied for a range of charge properties by varying the equivalence ratio, intake temperature, intake pressure, exhaust gas recirculation (EGR) rate, engine speed, and coolant temperature. Characterization of cyclic variations of ignition timing in HCCI at over 430 operating points on two single-cylinder engines for five different blends of primary reference fuel (PRF), (iso-octane and n-heptane) is performed. Three distinct patterns of cyclic variation for the start of combustion (SOC), combustion peak pressure ( Pmax), and indicated mean effective pressure (i.m.e.p.) are observed. These patterns are normal cyclic variations, periodic cyclic variations, and cyclic variations with weak/misfired ignitions. Results also show that the position of SOC plays an important role in cyclic variations of HCCI combustion with less variation observed when SOC occurs immediately after top dead centre (TDC). Higher levels of cyclic variations are observed in the main (second) stage of HCCI combustion compared with that of the first stage for the PRF fuels studied. The sensitivity of SOC to different charge properties varies. Cyclic variation of SOC increases with an increase in the EGR rate, but it decreases with an increase in equivalence ratio, intake temperature, and coolant temperature.
Pay for performance in Australia: Queensland's new Clinical Practice Improvement Payment
Authors: Duckett Stephen , Daniels Sandra , Kamp Maarten , Stockwell Alexis , Walker Gary , Ward Michael
Published: October 2008

Following a high profile scandal relating to quality and safety of care, the health authority in the Australian state of Queensland introduced a pay for performance (P4P) component into its new hospital prospective payment system. The Clinical Practice Improvement Payment system pays hospitals for achievement of clinical process indicators. Initially the focus is on the quality of clinical processes and outcomes. Using a consensus approach involving consultation with clinicians, seven clinical indicators were adopted for 2007-2008. The first payments using pay for performance were made for work carried out up until June 2008. Although no data exist yet as to the impact of the new system, pay for performance appears to be gaining widespread, if somewhat reluctant, acceptance.
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.
Arnauld’s God
Authors: Nadler Steven
Published: October 2008

In this paper, I argue that Arnauld’s conception of God is more radical than scholars have been willing to allow. It is not the case that, for Arnauld, God acts for reasons, with His will guided by wisdom (much as the God of Malebranche and Leibniz acts), albeit by a wisdom impenetrable to us. Arnauld’s objections to Malebranche are directed not only at the claim that God’s wisdom is transparent to human reason, but at the whole distinction between will and wisdom in God, even if that wisdom were “hidden.” Arnauld’s God, in fact, approaches the extreme voluntarist God of Descartes, and thus transcends practical rational agency altogether.
Poverty, Inequality, and Democracy: Postcommunist Welfare States
Authors: Orenstein Mitchell A.
Published: October 2008

Abstract: Democracy is one of several factors that have determined welfare state spending in the postcommunist countries since the transition, together with geography, history, economic conditions, and international influences. While the more developed, democratic, and Western countries of Central and Eastern Europe have maintained a high level of social protection comparable to the rest of the European Union, the states of the former Soviet Union and Southeastern Europe have experienced a partial disintegration of their social safety nets. Still, most postcommunist states spend a higher proportion of their national product on their welfare states than other developing countries.
Cultural Tenacity within Libraries and Publishers
Authors: Jensen Michael
Published: October 2008

Libraries and book publishers coevolved during the period of information scarcity, and developed cultural traits that are affecting their strategies in the new era of content abundance. Both industries are under threat. The author examines the interdependencies, the similarities, and the different agendas of the two cultures; explores likely speciation within the new ecosystems; and frames reasons for both optimism and concern for the near future.
A Book Publisher's Manifesto for the Twenty-first Century: How Traditional Publishers Can Position Themselves in the Changing Media Flows of a Networked Era
Authors: Lloyd Sara
Published: October 2008

In this challenging call to arms, Sara Lloyd, head of digital publishing at the United Kingdom trade publishing house, Pan Macmillan, explores whether there will be a role for publishers in a digital future and discusses the radical changes in culture and approach publishers will need to make if they are to evolve quickly enough to embrace the change from a linear content creation and delivery chain in which a publisher's role is definitive and fixed, to a circular, networked, Web-based one. This is a broad-ranging piece including coverage of the creative directions in which content creation and delivery might develop, new ways in which publishers will need to engage with authors, readers, and other distributors in the content creation chain and the interface between publishers and nontraditional competitors emerging in the digital marketplace.
A Mass Digitization Primer
Authors: Sutherland Juliet
Published: October 2008

Many people are talking these days about "digitizing books." But what does that really mean? This paper describes different kinds of digitizing, the pros and cons of each, and suggests a layered structure for understanding "digitization."
A Method for Estimating Pan Evaporation for Inland and Coastal Regions of the Southeastern U.S.
Authors: Cooke William H. , Grala Katarzyna , Wax Charles L.
Published: October 2008

Regression models that estimate daily pan evaporation for inland and coastal regions of Southeastern U.S. were developed using observations of wind speed, solar radiation, minimum relative humidity, and maximum temperature. These weather elements are collected in numerous locations where measured pan evaporation records are not available, allowing an estimation of pan evaporation across large regions with higher point pattern density than is available using pan evaporation sites only. Sixteen models were developed and tested. An innovative model selection metric was developed, employing R square, Pearson's correlation coefficient, average difference between estimated and measured evaporation, root mean-squared error, and mean absolute error. Models selected included two validated for use in inland environments and one validated for use in coastal environments.
Ozone Exposure and Potential for Vegetation Injury within the Atlanta, Georgia Metropolitan Area
Authors: Diem Jeremy E. , Styers Diane M.
Published: October 2008

Ozone-induced vegetation injury may be prevalent within metropolitan areas in the southeastern United States. The purpose of this study is to explore the relationship between ozone exposure and potential foliar injury within the Atlanta, Georgia metropolitan statistical area (MSA). The main methods involve calculating seasonal ozone exposure at 11 monitoring stations in the Atlanta MSA for 2000-2005 and measuring ozone-induced visible foliar injury in the eastern portion of the MSA in August 2004. Ozone exposure within the Atlanta MSA probably was high enough to injure only highly sensitive species, and the 2004 survey did reveal foliar injury to highly sensitive species.
BGH, Urteil vom 18. 6. 2007 – II ZR 86/06, Kapitalerhaltungsgebot bei der Veräußerung von GmbH-Anteilen
Authors: Böcker Philipp
Published: October 2008

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)
BGH, Beschluss vom 5. 7. 2007 – IX ZB 305/04, Berechnungsgrundlage für die Vergütung des Insolvenzverwalters
Authors: Keller Ulrich
Published: October 2008

Beschluss vom 5. 7. 2007 – IX ZB 305/04

1. Rechtsanwaltsgebühren für den Einsatz besonderer Sachkunde, die gemäß § 5 InsVV an die Sozietät (GbR) des Insolvenzverwalters, nicht aber an den Insolvenzverwalter persönlich gezahlt werden, sind bei der Bestimmung der Insolvenzmasse zur Berechnung der Vergütung nach § 1 Abs. 2 Nr. 4 Satz 2 Buchst. a InsVV nicht in Abzug zu bringen.

2. Bei der Festsetzung der Insolvenzverwaltervergütung zu berücksichtigen ist ein Massezufluss, der sich nach Einreichung der Schlussrechnung, aber vor dem Schlusstermin ergibt.

(Leitsätze der Redaktion)

(Vorgehend: AG Hamburg, 14. 5. 2004 – 67 c IN 99/01; LG Hamburg, 2. 12. 2004 – 326 T 53/04)
Die Kontrolle der insolvenzbedingten Kündigung nach § 8 Nr. 2 VOB/B am Maßstab des allgemeinen Zivil- und des Insolvenzanfechtungsrechts
Authors: Fritsche Stefan , Kilian Dirk
Published: October 2008

I. Einleitung

Nachdem die Regelungen der VOB/B zwischenzeitlich für den weitaus größten Teil der abgeschlossenen Bauverträge Geltung beanspruchen, stellt sich für die Rechts- und Baupraxis in zunehmenden Maße die Frage, ob die dort getroffenen Vereinbarungen – sei es in ihrer Gesamtheit, sei es in einzelnen Ausschnitten – die Belange der am Bau Beteiligten tatsächlich in jedem Fall angemessen berücksichtigen. Besonders virulent werden derartige Fragestellungen, wenn die Verwirklichung des Bauvorhabens infolge der ökonomischen Schieflage eines Vertragspartners gefährdet ist. Verdichtet sich diese Schieflage zur Insolvenz, so treten neben die immanenten Belange der Vertragsparteien die durch die Vorgaben der Insolvenzordnung zu berücksichtigenden Interessen außenstehender Dritter, namentlich die der jeweiligen Gläubigergemeinschaften. In einem solchen Spannungsfeld bewegt sich auch das (durch die Neufassung der VOB/B vom 4. 9. 2006 erweiterte) insolvenzbedingte Kündigungsrecht aus § 8 Nr. 2 VOB/B, welches dem Auftraggebers unter Absatz 1 die Lösung vom Vertrag gestattet,

»…wenn der Auftragnehmer seine Zahlungen einstellt, von ihm oder zulässigerweise vom Auftraggeber oder einem anderen Gläubiger das Insolvenzverfahren (InsO, § 14 und § 15) beziehungsweise ein vergleichbares gesetzliches Verfahren beantragt ist, ein solches Verfahren eröffnet wird oder dessen Eröffnung mangels Masse abgelehnt wird.«
Gesetzentwurf zur Änderung der Insolvenzordnung – Zur Insolvenzfestigkeit von Lizenzverträgen
Authors: Schleich Thorsten , Götz Florian
Published: October 2008

Das Bundeskabinett hat am 22. 8. 2007 einen durch das Bundesjustizministerium vorgelegten Gesetzentwurf zur Änderung der InsO beschlossen. Die geplanten Gesetzesänderungen sehen u. a. die Einführung eines neuen § 108 a InsO vor, durch welchen zukünftig Lizenzverträge im Falle der Insolvenz des Lizenzgebers insolvenzfest ausgestaltet werden sollen. Nach Auffassung der Bundesregierung ist diese Änderung der bestehenden Rechtslage zur Stärkung des Wirtschafts- und Forschungsstandortes Deutschland notwendig, insbesondere um Wettbewerbsnachteile gegenüber den USA und Japan abzubauen und eine Abwanderung von Unternehmen in diese Länder zu verhindern sowie um Investitionen von Lizenznehmern im Insolvenzfall zu sichern. Der geplante neue § 108 a InsO soll dabei folgenden Wortlaut aufweisen:

»Ein vom Schuldner als Lizenzgeber abgeschlossener Lizenzvertrag über ein Recht am geistigen Eigentum besteht mit Wirkung für die Insolvenzmasse fort. Dies gilt für vertragliche Nebenpflichten nur in dem Umfang, als deren Erfüllung zwingend geboten ist, um dem Lizenznehmer eine Nutzung des geschützten Rechts zu ermöglichen. Besteht zwischen der im Lizenzvertrag vereinbarten Vergütung und einer marktgerechten Vergütung ein auffälliges Missverhältnis, so kann der Insolvenzverwalter eine Anpassung der Vergütung verlangen; in diesem Fall kann der Lizenznehmer den Vertrag fristlos kündigen.«
Zwei Beschlüsse in Sachen »Göttinger Gruppe«
Authors: Smid Stefan
Published: October 2008

In der DZWIR ist unlängst der in Sachen eines Unternehmens der »Göttinger Gruppe« ergangene Eröffnungsbeschluss des AG Göttingen einer kritischen Betrachtung unterzogen worden. Das AG Göttingen hatte sich mit seiner Entscheidung in Gegensatz zum AG Charlottenburg gesetzt, dessen Zuständigkeit es wegen angenommener arglistiger Zuständigkeitserschleichung durch die Organe der Schuldnerin geleugnet hat. Über welches Vermögen es das Verfahren eröffnet, scheint das AG Göttingen nicht so recht gewusst zu haben.
BGH, Urteil vom 9. 7. 2007 – II ZR 62/06, Rückforderung bei verdeckter gemischter Sacheinlage
Authors: Zack Carsten
Published: October 2008

Urteil vom 9. 7. 2007 – II ZR 62/06

1. Eine verdeckte gemischte Sacheinlage (vgl. Sen.Urt. v. 20. 11. 2006 – II ZR 176/05, ZIP 2007, 178) liegt auch dann vor, wenn eine Aktiengesellschaft innerhalb der Zweijahresfrist des § 52 Abs. 1 AktG im Zusammenhang mit einer Barkapitalerhöhung ein Austauschgeschäft mit dem Zeichner der neuen Aktien schließt und das vereinbarte Entgelt den Betrag seiner Einlageverpflichtung (oder auch das Volumen der Kapitalerhöhung) um ein Vielfaches übersteigt.

2. Das gemäß § 183 Abs. 2 Satz 1 AktG unwirksame Austauschgeschäft ist, soweit nicht dingliche Ansprüche des Inferenten (§§ 985, 894 BGB) eingreifen (vgl. BGHZ 155, 329 [= DZWIR 2004, 157 mit Anm. Keil]), nach Bereicherungsrecht (§§ 812, 818 BGB) unter Saldierung der beiderseitigen Bereicherungsansprüche rückabzuwickeln. Das gilt auch im Insolvenzverfahren der Gesellschaft jedenfalls dann, wenn die Voraussetzungen des sinngemäß anzuwendenden § 94 InsO vorliegen.

3. Ein aktienrechtlicher Rückforderungsanspruch der Gesellschaft gemäß § 62 AktG besteht weder in den Fällen der §§ 27 Abs. 3 Satz 1, 183 Abs. 2 Satz 1 AktG noch im Fall der Unwirksamkeit eines Nachgründungsgeschäfts gemäß § 52 Abs. 1 AktG. Unberührt bleibt der Anspruch der Gesellschaft auf (erneute) Zahlung des Ausgabebetrages der Aktien gemäß §§ 27 Abs. 3 Satz 3, 183 Abs. 2 Satz 3 AktG.

4. Auch im Urkundenprozess (§§ 592 ff. ZPO) können die Gesellschaft oder ihr Insolvenzverwalter nicht ohne weiteres das aufgrund des unwirksamen Austauschgeschäfts Geleistete zurückfordern, sondern nur einen Anspruch auf den nach Saldierung verbleibenden Überschuss geltend machen und müssen daher einen entsprechenden Saldo – unter Beachtung ihrer prozessualen Wahrheitspflicht (§ 138 ZPO) – darlegen.

(Vorgehend: LG Frankfurt a. M., 26. 10. 2004 – 2/26 O 293/03; OLG Frankfurt a. M., 10. 2. 2006 – 10 U 265/04)
BGH, Urteil vom 5. 7. 2007 – IX ZR 256/06, Insolvenzanfechtung der Rückzahlung einer Beihilfe
Authors: Cranshaw F. L
Published: October 2008

Urteil vom 5. 7. 2007 – IX ZR 256/06

Der Umstand, dass der Insolvenzgläubiger die dem Schuldner gewährte und von diesem vor Insolvenzeröffnung zurückgezahlte Beihilfe nach einer Entscheidung der Europäischen Kommission zurückzufordern hat, steht der Insolvenzanfechtung der Rückzahlung nicht entgegen; eine Rückgewähr nach §§ 30 ff. GmbHG scheidet dagegen aus.

(Vorgehend: LG Erfurt, 7. 9. 2004 – 1 HKO 260/02; OLG Jena, 30. 11. 2005 – 6 U 906/04)