bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of wind turbine gear micropitting under variable load and speed conditions using ISO/TR 15144-1: 2010
Authors: Al-Tubi Issa S , Long Hui
Published: December 2012

Wind turbine gearbox operates under a wide array of highly fluctuating and dynamic load conditions caused by the stochastic nature of wind and operational wind turbine controls. Micropitting damage is one of failure modes commonly observed in wind turbine gearboxes. This article investigates gear micropitting of high-speed stage gears of a wind turbine gearbox operating under nominal and varying load and speed conditions. Based on the ISO standard of gear micropitting (ISO/TR 15144-1:2010) and considering the operating load and speed conditions, a theoretical study is carried out to assess the risk of gear micropitting by determining the contact stress, sliding parameter, local contact temperature and lubricant film thickness along the line of action of gear tooth contact. The non-uniform distributions of temperature and lubricant film thickness over the tooth flank are observed due to the conditions of torque and rotational speed variations and sliding contact along the gear tooth flanks. The lubricant film thickness varies along the tooth flank and is at the lowest when the tip of the driving gear engages with the root of the driven gear. The lubricant film thickness increases with the increase of rotational speed and decreases as torque and sliding increase. It can be concluded that micropitting is most likely to initiate at the addendum of driving gear and the dedendum of driven gear. The lowest film thickness occurs when the torque is high and the rotational speed is at the lowest which may cause direct tooth surface contact. At the low-torque condition, the varying rotational speed condition may cause a considerable variation of lubricant film thickness thus interrupting the lubrication which may result in micropitting.
The Busy Social Brain
Authors: Spunt Robert P. , Lieberman Matthew D.
Published: December 2012

Much social-cognitive processing is believed to occur automatically; however, the relative automaticity of the brain systems underlying social cognition remains largely undetermined. We used functional MRI to test for automaticity in the functioning of two brain systems that research has indicated are important for understanding other people’s behavior: the mirror neuron system and the mentalizing system. Participants remembered either easy phone numbers (low cognitive load) or difficult phone numbers (high cognitive load) while observing actions after adopting one of four comprehension goals. For all four goals, mirror neuron system activation showed relatively little evidence of modulation by load; in contrast, the association of mentalizing system activation with the goal of inferring the actor’s mental state was extinguished by increased cognitive load. These results support a dual-process model of the brain systems underlying action understanding and social cognition; the mirror neuron system supports automatic behavior identification, and the mentalizing system supports controlled social causal attribution.
The Characteristics of Unsuccessful E-Mentoring Relationships for Youth With Disabilities
Authors: Shpigelman Carmit-Noa , Gill Carol J.
Published: December 2012

Recently, researchers have focused on the benefits of e-mentoring for young people with disabilities, such as greater access to sources of information and support. Relatively few researchers have explored the problem of unsuccessful e-mentoring relationships, i.e., mentors and mentored individuals who withdraw from an e-mentoring program before completion. Our findings promote understanding of the dynamics of unsuccessful vs. successful e-mentoring relationships for youth with disabilities. Using qualitative methods, we focused primarily on negative online experiences. We compared the e-mentoring process of six “unsuccessful” pairs of mentors and mentored students who withdrew from an e-mentoring program with three exemplary “successful” pairs who fully completed the program. Our findings revealed different communication patterns in the two groups. Whereas the unsuccessful pairs used a more formal style and distant tone, the successful pairs used an informal and supportive style. We discuss these differences, including the components that are essential to success.
The management of dental anxiety and impact of psychosomatic factors on dentistry: Is recent scientific research translated into German dental practices?
Authors: Diercke Katja , Bürger Gila D , Bermejo Justo L , Lux Christopher J , Brunner Monika
Published: December 2012

This study investigated the dentists’ knowledge about psychosomatic medicine. Anxiolytic techniques, considerations about psychosomatic medicine, and referrals to psychotherapists were examined by a questionnaire. Overall, 65 percent felt negatively affected by patients with dental fear. Few dentists used relaxation techniques and hypnosis. The relationship between psychosomatic factors and pain perception was well known, but not their impact on wound healing. The frequency of continuing education courses correlated with a broader range of treatment techniques and less difficulties in treatment. Research evidence about the impact of psychological factors on dental treatment has not been translated into dental practice.
Bio-child: Human sciences and governing through freedom
Authors: McCallum David
Published: December 2012

This article provides an account of the rise of a bio-politics of governing families and children in Australia and its relations with liberal political reason. Drawing on Foucault’s lectures on Security, Territory, Population it maps out the ways in which forms of liberal governing seek to define the nature and scope of norms and freedoms in a population through the practices of the human sciences. Bio-politics is shown to introduce new ways of calculating and intervening upon certain parts of the population and to create normalizing tensions with sovereign or judicial forms of governing.
Novo Nordisk v.. Caraco: Who defines the use code narrative?
Authors: Rein Frederick H , Crystal Joseph B
Published: December 2012

In Novo Nordisk A/S et al. v. Caraco Pharma. Labs., Ltd. et al., 688 F.3d 766 (Fed. Cir. 2012), the Federal Circuit addressed the scope of the injunction issued by the District Court in light of the Supreme Court's decision in Caraco Pharmaceutical Laboratories Ltd. et al. v. Novo Nordisk A/S et al. (U.S. 2012). The Federal Circuit found that the District Court had abused its discretion in issuing its injunction and modified the injunction accordingly. This case report presents the arguments made to the Federal Circuit by the parties and how the Federal Circuit addressed those issues.
Overview of the biosimilars: Strategic considerations of various issues
Authors: Kudrin Alex
Published: December 2012

Compared to well-established generic medicines that are routinely developed using the bioequivalence approach and identical drug substances, biosimilars are developed using a step-wise comparability exercise aimed at demonstrating similar but not identical quality, non-clinical and clinical attributes. Biosimilar development is not intended to demonstrate the clinical benefits of the product as millions years of exposure data are currently available for the many originator monoclonal antibodies but rather to demonstrate a high degree of similarity against the reference using analytical and non-analytical state-of-the-art quality, non-clinical and clinical tools. It is therefore assumed that biosimilar development will be strongly based on the well-studied safety profiles of the originator product. The scope and size of the biosimilar safety database will be propelled by a risk-driven evaluation of biosimilarity and immunogenicity-attributed risks. The first driver for biosimilars is the expiry of patents for several originator biologic products with a significant revenue stream. Secondly, many stakeholders, especially payers and patients, need earlier and expanded access to affordable biologics, and biosimilars could provide substantial budget savings. With a more mature and defined regulatory framework surrounding biosimilars, a number of biosimilar players have emerged in the last few years including contract research organizations (Parexel, Quintiles), generic (Sandoz, Teva, Hospira), innovative companies (Merck Ventures, Merck & Serono, GSK, Pfizer, etc.) and even some companies with no prior pharmaceutical expertise who are moving into the biosimilar business (Samsung, LG Life Sciences, Fuji Pharma). The objective of this article is to highlight some important commercial, regulatory and developmental trends relating to biosimilars, across developed and emerging markets.
The role of B7 family molecules in hematologic malignancy
Authors: Greaves Paul , Gribben John G.
Published: December 2012

The B7 family consists of structurally related, cell-surface proteins that regulate immune responses by delivering costimulatory or coinhibitory signals through their ligands. Eight family members have been identified to date including CD80 (B7-1), CD86 (B7-2), CD274 (programmed cell death-1 ligand [PD-L1]), CD273 (programmed cell death-2 ligand [PD-L2]), CD275 (inducible costimulator ligand [ICOS-L]), CD276 (B7-H3), B7-H4, and B7-H6. B7 ligands are expressed on both lymphoid and nonlymphoid tissues. The importance of the B7 family in regulating immune responses is clear from their demonstrated role in the development of immunodeficiency and autoimmune diseases. Manipulation of the signals delivered by B7 ligands shows great potential in the treatment of cancers including leukemias and lymphomas and in regulating allogeneic T-cell responses after stem cell transplantation.
A urine biomarker for severe obstructive sleep apnoea patients: lipocalin-type prostaglandin D synthase
Authors: Chihara Yuichi , Chin Kazuo , Aritake Kosuke , Harada Yuka , Toyama Yoshiro , Murase Kimihiko , Yoshimura Chikara , Hitomi Takefumi , Oga Toru , Mishima Michiaki , Urade Yoshihiro
Published: December 2012

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of prostaglandin D2, has been reported to have a close connection with cardiovascular disease and sleep regulation. This study aimed to test the hypothesis that the L-PGDS level is a useful marker to identify patients with obstructive sleep apnoea.

64 subjects were enrolled in this prospective study. Urinary concentrations of L-PGDS were measured in the morning. Measurements were made every 4 h in 25 of the 64 patients. Endothelial function was assessed by the reactive hyperaemia peripheral arterial tone index.

Circadian variations in L-PGDS concentrations had a significant time-dependent fluctuation (p = 0.0002). L-PGDS was higher in the subjects with severe obstructive sleep apnoea (median 784.7 ng per mg of creatinine, n = 23) than in control subjects (262.1 ng per mg of creatinine, n = 16; p = 0.004) and in those with moderate obstructive sleep apnoea (371.7 ng per mg of creatinine, n = 25; p = 0.0008). After 2 days of continuous positive airway pressure treatment, L-PGDS concentrations in severe obstructive sleep apnoea subjects (n = 12) decreased significantly (p = 0.02) to levels present in control subjects whereas endothelial function did not change significantly. Morning urinary L-PGDS concentrations had significant correlations with the apnoea/hypopnoea index (R2= 13.9%) and serum high-density lipoprotein cholesterol (R2= 6.2%), but not with sleepiness.

Urinary L-PGDS might be a moderately useful marker to identify patients with severe obstructive sleep apnoea.
Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by gamma/delta T cells
Authors: Wozniak Karen L , Kolls Jay K , Wormley Floyd L
Published: December 2012

Protective responses in mice immunized with an interferon-gamma producing strain ofCryptococcus neoformans, H99γ, are associated with IL-17A production by neutrophils. Neutrophil depletion in H99γ-immunized mice did not affect pulmonary fungal burden, indicating that neutrophils are not required for clearance. However, we observed an increase in IL-17A in the lungs of neutrophil-depleted H99γ infected mice, which corresponded to an increase in IL-17A+γδ+T cells. Moreover, we observed increased IL-17A+/ CD3+cells and IL-17A+/γδ+cells, but decreased IL-17A+/Ly6G+neutrophils in the lungs of IL-17 receptor (R)A deficient mice compared to wild-type mice. Increased production of IL-17A in neutropenic mice coincided with increased IL-6 and CXCL1, but not Th17 inducing cytokines TGF-β, IL-21 and IL-23. Concurrent depletion of neutrophils and γδ+T cells reduced IL-17A levels. Our results suggest that γδ+T cells mediate significant IL-17A production in neutropenic mice during the protective response toC.neoformansinfection.
Alternative splicing of the neurofibromatosis type 1 pre-mRNA is regulated by the muscleblind-like proteins and the CUG-BP and ELAV-like factors
Authors: Fleming Victoria A , Geng Cuiyu , Ladd Andrea N , Lou Hua
Published: December 2012

Background

Alternative splicing is often subjected to complex regulatory control that involves many protein factors and cis-acting RNA sequence elements. One major challenge is to identify all of the protein players and define how they control alternative expression of a particular exon in a combinatorial manner. The Muscleblind-like (MBNL) and CUG-BP and ELAV-Like family (CELF) proteins are splicing regulatory proteins, which function as antagonists in the regulation of several alternative exons. Currently only a limited number of common targets of MBNL and CELF are known that are antagonistically regulated by these two groups of proteins.

Results

Recently, we identified neurofibromatosis type 1 (NF1) exon 23a as a novel target of negative regulation by CELF proteins. Here we report that MBNL family members are positive regulators of this exon. Overexpression of MBNL proteins promote exon 23a inclusion in a low MBNL-expressing cell line, and simultaneous siRNA-mediated knockdown of MBNL1 and MBNL2 family members in a high MBNL-expressing cell line promotes exon 23a skipping. Importantly, these two groups of proteins antagonize each other in regulating inclusion of exon 23a. Furthermore, we analyzed the binding sites of these proteins in the intronic sequences upstream of exon 23a by UV cross-linking assays. We show that in vitro, in addition to the previously identified preferred binding sequence UGCUGU, the MBNL proteins need the neighboring sequences for optimal binding.

Conclusion

This study along with our previous work that demonstrated roles for Hu, CELF, and TIA-1 and TIAR proteins in the regulation of NF1 exon 23a establish that this exon is under tight, complex control.
Plant growth strategies are remodeled by spaceflight
Authors: Paul Anna-Lisa , Amalfitano Claire E , Ferl Robert J
Published: December 2012

Background

Arabidopsis plants were grown on the International Space Station within specialized hardware that combined a plant growth habitat with a camera system that can capture images at regular intervals of growth. The Imaging hardware delivers telemetric data from the ISS, specifically images received in real-time from experiments on orbit, providing science without sample return. Comparable Ground Controls were grown in a sister unit that is maintained in the Orbital Environment Simulator at Kennedy Space Center. One of many types of biological data that can be analyzed in this fashion is root morphology. Arabidopsis seeds were geminated on orbit on nutrient gel Petri plates in a configuration that encouraged growth along the surface of the gel. Photos were taken every six hours for the 15 days of the experiment.

Results

In the absence of gravity, but the presence of directional light, spaceflight roots remained strongly negatively phototropic and grew in the opposite direction of the shoot growth; however, cultivars WS and Col-0 displayed two distinct, marked differences in their growth patterns. First, cultivar WS skewed strongly to the right on orbit, while cultivar Col-0 grew with little deviation away from the light source. Second, the Spaceflight environment also impacted the rate of growth in Arabidopsis. The size of the Flight plants (as measured by primary root and hypocotyl length) was uniformly smaller than comparably aged Ground Control plants in both cultivars.

Conclusions

Skewing and waving, thought to be gravity dependent phenomena, occur in spaceflight plants. In the presence of an orienting light source, phenotypic trends in skewing are gravity independent, and the general patterns of directional root growth typified by a given genotype in unit gravity are recapitulated on orbit, although overall growth patterns on orbit are less uniform. Skewing appears independent of axial orientation on the ISS – suggesting that other tropisms (such as for oxygen and temperature) do not influence skewing. An aspect of the spaceflight environment also retards the rate of early Arabidopsis growth.
Incidence and predictors of immediate complications following perioperative non-obstetric epidural punctures
Authors: Meyer-Bender Andreas , Kern Andrea , Pollwein Bernhard , Crispin Alexander , Lang Philip M
Published: December 2012

Background

Epidural Anesthesia (EA) is a well-established procedure. The aim of the present study was to evaluate the incidence of immediate complications following epidural puncture, such as sanguineous puncture, accidental dural perforation, unsuccessful catheter placement or insufficient analgesia and to identify patient and maneuver related risk factors.

Methods

A total of 7958 non-obstetrical EA were analyzed. The risk of each complication was calculated according to the preconditions and the level of puncture. For probabilistic evaluation we used a logistic regression model with forward selection.

Results

The risk of sanguineous puncture (n = 247, 3.1%) increases with both the patient’s age (P = 0.013) and the more caudal the approach (P < 0.01). Dural perforation (n = 123, 1.6%) was found to be influenced only by advanced age (P = 0.019). Unsuccessful catheter placement (n = 68, 0.94%) occurred more often in smaller individuals (P < 0.001) and at lower lumbar sites (P < 0.01). Amongst all cases with successful catheter placement a (partial) insufficient analgesia was found in 692 cases (8.8%). This risk of insufficient analgesia decreased with patient’s age (P <0 .01), being least likely for punctures of the lower thoracic spine (P < 0.001).

Conclusions

Compared to more cranial levels, EA of the lower spine is associated with an increased risk of sanguineous and unsuccessful puncture. Insufficient analgesia more often accompanies high thoracic and low lumbar approaches. The risk of a sanguineous puncture increases in elderly patients. Gender, weight and body mass index seem to have no influence on the investigated complications.
Identification of prostaglandin receptors in human ureters
Authors: Oll Matthias , Baumann Claudia , Behbahani Turang E , Ruecker Alexander von , Müller Stefan C , Ellinger Jörg
Published: December 2012

Background

Prostaglandins play an important role in ureteral obstruction, but the detailed expression profiles of the prostaglandin receptors (PTGER1, PTGER2, PTGER3, PTGER4, PTGFR) remain unknown in the different parts of the human ureter.

Methods

The expression pattern of PTGER1, PTGER2, PTGER3, PTGER4 and PTGFR was determined in human distal, mid and proximal ureter and renal pelvis samples using immunohistochemistry (protein levels) and quantitative real-time PCR (mRNA).

Results

PTGER1 was highly expressed in most samples irrespective of the ureteral localization; however, urothelial cells had higher levels of PTGER1 than smooth muscle cells. PTGFR was also moderately to strongly expressed in urothelial and smooth muscle cells. In comparison, PTGER2-4 expression was mostly unexpressed or weakly expressed in urothelial and smooth cells in all regions.

Conclusions

Our data indicate high levels of PTGER1 in ureters.
The cardioprotective effect of danshen and gegen decoction on rat hearts and cardiomyocytes with post-ischemia reperfusion injury
Authors: Hu Fan , Koon Chi-Man , Chan Judy Yuet-Wa , Lau Kit-Man , Fung Kwok-Pui
Published: December 2012

Background

Danshen (Salviae Miltiorrhizae Radix) and Gegen (Puerariae Lobatae Radix) have been used for treating heart disease for several thousand years in China. It has been found that a Danshen and Gegen decoction (DG) exhibiting an anti-atherosclerosis effect, which improves the patients’ heart function recovery. Pre-treatment with DG was reported to have protective effects on myocardium against ischemia/reperfusion injury. In the present study, we aim to investigate the post-treatment effect of DG on ischemic-reperfusion injuriesex vivoorin vitroand the underlying mechanisms involved.

Methods

The rat heart function in an ischemia and reperfusion (I/R) model was explored by examining three parameters including contractile force, coronary flow rate and the release of heart specific enzymes within the heart perfusate.In vitromodel of hypoxia and reoxygenation (H/R), the protective effect of DG on damaged cardiomyocytes was investigated by examining the cell structure integrity, the apoptosis and the functionality of mitochondria.

Results

Our results showed that DG significantly improved rat heart function after I/R challenge and suppressed the release of enzymes by damaged heart muscles in a dose-dependent manner. DG also significantly inhibited the death of cardiomyocytes, H9c2 cells, with a H/R challenge. It obviously decreased cell apoptosis, protected the mitochondrial function and cell membrane skeleton integrity on H9c2 cells. The cardio-protection was also found to be related to a decrease in intracellular calcium accumulation within H9c2 cells after I/R challenge.

Conclusion

The potential application of DG in treating rat hearts with an I/R injury has been implied in this study. Our results suggested that DG decoction could act as an anti-apoptotic and anti-ion stunning agent to protect hearts against an I/R injury.
High-density surface EMG maps from upper-arm and forearm muscles
Authors: Rojas-Martínez Monica , Mañanas Miguel A , Alonso Joan F
Published: December 2012

Background

sEMG signal has been widely used in different applications in kinesiology and rehabilitation as well as in the control of human-machine interfaces. In general, the signals are recorded with bipolar electrodes located in different muscles. However, such configuration may disregard some aspects of the spatial distribution of the potentials like location of innervation zones and the manifestation of inhomogineties in the control of the muscular fibers. On the other hand, the spatial distribution of motor unit action potentials has recently been assessed with activation maps obtained from High Density EMG signals (HD-EMG), these lasts recorded with arrays of closely spaced electrodes. The main objective of this work is to analyze patterns in the activation maps, associating them with four movement directions at the elbow joint and with different strengths of those tasks. Although the activation pattern can be assessed with bipolar electrodes, HD-EMG maps could enable the extraction of features that depend on the spatial distribution of the potentials and on the load-sharing between muscles, in order to have a better differentiation between tasks and effort levels.

Methods

An experimental protocol consisting of isometric contractions at three levels of effort during flexion, extension, supination and pronation at the elbow joint was designed and HD-EMG signals were recorded with 2D electrode arrays on different upper-limb muscles. Techniques for the identification and interpolation of artifacts are explained, as well as a method for the segmentation of the activation areas. In addition, variables related to the intensity and spatial distribution of the maps were obtained, as well as variables associated to signal power of traditional single bipolar recordings. Finally, statistical tests were applied in order to assess differences between information extracted from single bipolar signals or from HD-EMG maps and to analyze differences due to type of task and effort level.

Results

Significant differences were observed between EMG signal power obtained from single bipolar configuration and HD-EMG and better results regarding the identification of tasks and effort levels were obtained with the latter. Additionally, average maps for a population of 12 subjects were obtained and differences in the co-activation pattern of muscles were found not only from variables related to the intensity of the maps but also to their spatial distribution.

Conclusions

Intensity and spatial distribution of HD-EMG maps could be useful in applications where the identification of movement intention and its strength is needed, for example in robotic-aided therapies or for devices like powered- prostheses or orthoses. Finally, additional data transformations or other features are necessary in order to improve the performance of tasks identification.
Kinetics of IgG antibody to cytomegalovirus (CMV) after birth and seroprevalence of anti-CMV IgG in Chinese children
Authors: Chen Jie , Hu Lingqing , Wu Meiling , Zhong Tianying , Zhou Yi-Hua , Hu Yali
Published: December 2012

Background

Prevalence of cytomegalovirus (CMV) infection is 90–100% in developing countries; however, the kinetics of anti-CMV IgG in infants remains elusive.

Methods

Sera from 112 mother-newborn pairs and longitudinal samples from 41 infants up to 2-year old were tested for anti-CMV IgG and IgM. Additionally, samples from 837 healthy children were included.

Results

Of 112 mothers, 108 (96.4%) were anti-CMV IgG positive; their 108 newborns were also seropositive. In a 2-year follow-up among 40 infants of positive mothers, anti-CMV IgG level in 8 individuals decreased with time and became undetectable by age of 3.5–8 months, and that in 32 others decreased at 1- and 3.5-month old, and then increased. Based on the positive IgM, rising IgG levels, and low anti-CMV IgG avidity index, 76.7% of the primary infections were demonstrated to occur during 1–3.5 months of age. The overall seroprevalence of anti-CMV in 837 children was 82.4%, which was generally constant from 2 to 8 years old (χ2 = 3.150, p = 0.790).

Conclusions

The maternally acquired anti-CMV IgG in infants disappears before 8-month old. Primary CMV infection in Chinese children mostly occurs during 1–3.5 months of age. Whether the relatively lower seroprevalence of anti-CMV in Chinese children found in this survey may reflect the positive rate in child-bearing age women in the future remains to be further studied.
Luminal B tumors are the most frequent molecular subtype in breast cancer of North African women: an immunohistochemical profile study from Morocco
Authors: El Fatemi Hinde , Chahbouni Sanae , Jayi Sofia , Moumna Kaoutar , Melhouf My Abdelilah , Bannani Abdelaziz , Mesbahi Omar , Amarti Afaf
Published: December 2012

Background

Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC) characteristics. The aim of our study is to show the molecular profile characteristic of breast cancer in the North African population of Morocco. This work showed preliminary results and correlations with clinicopathological and histological parameters. Three hundred and ninety primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, CK8/18 and Ki67 using paraffin tissue.

Methods

We reviewed 390 cases of breast cancer diagnosed on January 2008 to December 2011 at the Department of pathology, Hassan II teaching hospital, Fez, Morocco. Age, size tumor, metastatic profile, node involvement profile, histological type and immunohistochemical profile were studied.

Results

The average age was 46 years; our patients were diagnosed late with a high average tumor size. Luminal B subtype was more prevalent (41.8%), followed by luminal A (30.5%), basal-like (13, 6%), Her2-overexpressing (9, 2%), and unclassified subtype (4.9%).

Conclusion

This study showed that molecular classification and biological profile may be different according to geographical distribution, to encourage further studies to know the genomic profile of tumors and the environment.

Virtual slide

http://www.diagnosticpathology.diagnomx.eu/vs/1675272504826544
COG5-CDG: expanding the clinical spectrum
Authors: Rymen Daisy , Keldermans Liesbeth , Race Valérie , Régal Luc , Deconinck Nicolas , Dionisi-Vici Carlo , Fung Cheuk-wing , Sturiale Luisa , Rosnoblet Claire , Foulquier François , Matthijs Gert , Jaeken Jaak
Published: December 2012

Background

The Conserved Oligomeric Golgi (COG) complex is involved in the retrograde trafficking of Golgi components, thereby affecting the localization of Golgi glycosyltransferases. Deficiency of a COG-subunit leads to defective protein glycosylation, and thus Congenital Disorders of Glycosylation (CDG). Mutations in subunits 1, 4, 5, 6, 7 and 8 have been associated with CDG-II. The first patient with COG5-CDG was recently described (Paesold-Burda et al. Hum Mol Genet 2009; 18:4350–6). Contrary to most other COG-CDG cases, the patient presented a mild/moderate phenotype, i.e. moderate psychomotor retardation with language delay, truncal ataxia and slight hypotonia.

Methods

CDG-IIx patients from our database were screened for mutations in COG5. Clinical data were compared. Brefeldin A treatment of fibroblasts and immunoblotting experiments were performed to support the diagnosis.

Results and conclusion

We identified five new patients with proven COG5 deficiency. We conclude that the clinical picture is not always as mild as previously described. It rather comprises a broad spectrum with phenotypes ranging from mild to very severe. Interestingly, on a clinical basis some of the patients present a significant overlap with COG7-CDG, a finding which can probably be explained by subunit interactions at the protein level.
Kinetics and mechanism of jack bean urease inhibition by Hg2+
Authors: Du Nana , Chen Mingming , Liu Zhaodi , Sheng Liangquan , Xu Huajie , Chen Shuisheng
Published: December 2012

Background

Jack bean urease (EC 3.5.1.5) is a metalloenzyme, which catalyzes the hydrolysis of urea to produce ammonia and carbon dioxide. The heavy metal ions are common inhibitors to control the rate of the enzymatic urea hydrolysis, which take the Hg2+ as the representative. Hg2+ affects the enzyme activity causing loss of the biological function of the enzyme, which threatens the survival of many microorganism and plants. However, inhibitory kinetics of urease by the low concentration Hg2+ has not been explored fully. In this study, the inhibitory effect of the low concentration Hg2+ on jack bean urease was investigated in order to elucidate the mechanism of Hg2+ inhibition.

Results

According to the kinetic parameters for the enzyme obtained from Lineweaver–Burk plot, it is shown that the K
m is equal to 4.6±0.3 mM and V
m is equal to 29.8±1.7 μmol NH3/min mg. The results show that the inhibition of jack bean urease by Hg2+ at low concentration is a reversible reaction. Equilibrium constants have been determined for Hg2+ binding with the enzyme or the enzyme-substrate complexes (K
i =0.012 μM). The results show that the Hg2+ is a noncompetitive inhibitor. In addition, the kinetics of enzyme inhibition by the low concentration Hg2+ has been studied using the kinetic method of the substrate reaction. The results suggest that the enzyme first reversibly and quickly binds Hg2+ and then undergoes a slow reversible course to inactivation. Furthermore, the rate constant of the forward reactions (k
+0) is much larger than the rate constant of the reverse reactions (k
-0). By combining with the fact that the enzyme activity is almost completely lost at high concentration, the enzyme is completely inactivated when the Hg2+ concentration is high enough.

Conclusions

These results suggest that Hg2+ has great impacts on the urease activity and the established inhibition kinetics model is suitable.
Probabilistic failure modelling of reinforced concrete structures subjected to chloride penetration
Authors: Nogueira Caio Gorla , Leonel Edson Denner , Coda Humberto Breves
Published: December 2012

Structural durability is an important criterion that must be evaluated for every type of structure. Concerning reinforced concrete members, chloride diffusion process is widely used to evaluate durability, especially when these structures are constructed in aggressive atmospheres. The chloride ingress triggers the corrosion of reinforcements; therefore, by modelling this phenomenon, the corrosion process can be better evaluated as well as the structural durability. The corrosion begins when a threshold level of chloride concentration is reached at the steel bars of reinforcements. Despite the robustness of several models proposed in literature, deterministic approaches fail to predict accurately the corrosion time initiation due the inherent randomness observed in this process. In this regard, structural durability can be more realistically represented using probabilistic approaches. This paper addresses the analyses of probabilistic corrosion time initiation in reinforced concrete structures exposed to chloride penetration. The chloride penetration is modelled using the Fick's diffusion law. This law simulates the chloride diffusion process considering time-dependent effects. The probability of failure is calculated using Monte Carlo simulation and the first order reliability method, with a direct coupling approach. Some examples are considered in order to study these phenomena. Moreover, a simplified method is proposed to determine optimal values for concrete cover.
The effect of Link N on differentiation of human bone marrow-derived mesenchymal stem cells
Authors: Antoniou John , Wang Hong Tian , Alaseem Abdulrahman M , Haglund Lisbet , Roughley Peter J , Mwale Fackson
Published: December 2012

Introduction

We previously showed that Link N can stimulate extracellular matrix biosynthesis by intervertebral disc (IVD) cells, both in vitro and in vivo, and is therefore a potential stimulator of IVD repair. The purpose of the present study was to determine how Link N may influence human mesenchymal stem cell (MSC) differentiation, as a prelude to using Link N and MSC supplementation in unison for optimal repair of the degenerated disc.

Methods

MSCs isolated from the bone marrow of three osteoarthritis patients were cultured in chondrogenic or osteogenic differentiation medium without or with Link N for 21 days. Chondrogenic differentiation was monitored by proteoglycan staining and quantitation by using Alcian blue, and osteogenic differentiation was monitored by mineral staining and quantitation by using Alzarin red S. In addition, proteoglycan secretion was monitored with the sulfated glycosaminoglycan (GAG) content of the culture medium, and changes in gene expression were analyzed with real-time reverse transcription (RT) PCR.

Results

Link N alone did not promote MSC chondrogenesis. However, after MSCs were supplemented with Link N in chondrogenic differentiation medium, the quantity of GAG secreted into the culture medium, as well as aggrecan, COL2A1, and SOX9 gene expression, increased significantly. The gene expression of COL10A1 and osteocalcin (OC) were downregulated significantly. When MSCs were cultured in osteogenic differentiation medium, Link N supplementation led to a significant decrease in mineral deposition, and alkaline phosphatase (ALP), OC, and RUNX2 gene expression.

Conclusions

Link N can enhance chondrogenic differentiation and downregulate hypertrophic and osteogenic differentiation of human MSCs. Therefore, in principle, Link N could be used to optimize MSC-mediated repair of the degenerated disc.
A network module-based method for identifying cancer prognostic signatures
Authors: Wu Guanming , Stein Lincoln
Published: December 2012

Discovering robust prognostic gene signatures as biomarkers using genomics data can be challenging. We have developed a simple but efficient method for discovering prognostic biomarkers in cancer gene expression data sets using modules derived from a highly reliable gene functional interaction network. When applied to breast cancer, we discover a novel 31-gene signature associated with patient survival. The signature replicates across 5 independent gene expression studies, and outperforms 48 published gene signatures. When applied to ovarian cancer, the algorithm identifies a 75-gene signature associated with patient survival. A Cytoscape plugin implementation of the signature discovery method is available at http://wiki.reactome.org/index.php/Reactome_FI_Cytoscape_Plugin
Biological Inquiry: A New Course and Assessment Plan in Response to the Call to Transform Undergraduate Biology
Authors: Goldey Ellen S. , Abercrombie Clarence L. , Ivy Tracie M. , Kusher Dave I. , Moeller John F. , Rayner Doug A. , Smith Charles F. , Spivey Natalie W.
Published: December 2012

We transformed our first-year curriculum in biology with a new course, Biological Inquiry, in which >50% of all incoming, first-year students enroll. The course replaced a traditional, content-driven course that relied on outdated approaches to teaching and learning. We diversified pedagogical practices by adopting guided inquiry in class and in labs, which are devoted to building authentic research skills through open-ended experiments. Students develop core biological knowledge, from the ecosystem to molecular level, and core skills through regular practice in hypothesis testing, reading primary literature, analyzing data, interpreting results, writing in disciplinary style, and working in teams. Assignments and exams require higher-order cognitive processes, and students build new knowledge and skills through investigation of real-world problems (e.g., malaria), which engages students’ interest. Evidence from direct and indirect assessment has guided continuous course revision and has revealed that compared with the course it replaced, Biological Inquiry produces significant learning gains in all targeted areas. It also retains 94% of students (both BA and BS track) compared with 79% in the majors-only course it replaced. The project has had broad impact across the entire college and reflects the input of numerous constituencies and close collaboration among biology professors and students.
Developing a Test of Scientific Literacy Skills (TOSLS): Measuring Undergraduates’ Evaluation of Scientific Information and Arguments
Authors: Gormally Cara , Brickman Peggy , Lutz Mary
Published: December 2012

Life sciences faculty agree that developing scientific literacy is an integral part of undergraduate education and report that they teach these skills. However, few measures of scientific literacy are available to assess students’ proficiency in using scientific literacy skills to solve scenarios in and beyond the undergraduate biology classroom. In this paper, we describe the development, validation, and testing of the Test of Scientific Literacy Skills (TOSLS) in five general education biology classes at three undergraduate institutions. The test measures skills related to major aspects of scientific literacy: recognizing and analyzing the use of methods of inquiry that lead to scientific knowledge and the ability to organize, analyze, and interpret quantitative data and scientific information. Measures of validity included correspondence between items and scientific literacy goals of the National Research Council and Project 2061, findings from a survey of biology faculty, expert biology educator reviews, student interviews, and statistical analyses. Classroom testing contexts varied both in terms of student demographics and pedagogical approaches. We propose that biology instructors can use the TOSLS to evaluate their students’ proficiencies in using scientific literacy skills and to document the impacts of curricular reform on students’ scientific literacy.
Peer Learning and Support of Technology in an Undergraduate Biology Course to Enhance Deep Learning
Authors: Tsaushu Masha , Tal Tali , Sagy Ornit , Kali Yael , Gepstein Shimon , Zilberstein Dan
Published: December 2012

This study offers an innovative and sustainable instructional model for an introductory undergraduate course. The model was gradually implemented during 3 yr in a research university in a large-lecture biology course that enrolled biology majors and nonmajors. It gives priority to sources not used enough to enhance active learning in higher education: technology and the students themselves. Most of the lectures were replaced with continuous individual learning and 1-mo group learning of one topic, both supported by an interactive online tutorial. Assessment included open-ended complex questions requiring higher-order thinking skills that were added to the traditional multiple-choice (MC) exam. Analysis of students’ outcomes indicates no significant difference among the three intervention versions in the MC questions of the exam, while students who took part in active-learning groups at the advanced version of the model had significantly higher scores in the more demanding open-ended questions compared with their counterparts. We believe that social-constructivist learning of one topic during 1 mo has significantly contributed to student deep learning across topics. It developed a biological discourse, which is more typical to advanced stages of learning biology, and changed the image of instructors from “knowledge transmitters” to “role model scientists.”
Teaching Neuroscience to Science Teachers: Facilitating the Translation of Inquiry-Based Teaching Instruction to the Classroom
Authors: Roehrig G. H. , Michlin M. , Schmitt L. , MacNabb C. , Dubinsky J. M.
Published: December 2012

In science education, inquiry-based approaches to teaching and learning provide a framework for students to building critical-thinking and problem-solving skills. Teacher professional development has been an ongoing focus for promoting such educational reforms. However, despite a strong consensus regarding best practices for professional development, relatively little systematic research has documented classroom changes consequent to these experiences. This paper reports on the impact of sustained, multiyear professional development in a program that combined neuroscience content and knowledge of the neurobiology of learning with inquiry-based pedagogy on teachers’ inquiry-based practices. Classroom observations demonstrated the value of multiyear professional development in solidifying adoption of inquiry-based practices and cultivating progressive yearly growth in the cognitive environment of impacted classrooms.
Joyce's Census: Character, Demography, and the Problem of Population inUlysses
Authors: Alexander Sam
Published: December 2012

This article proposes that the narratological problem of character in Joyce's Ulysses is inseparable from the biopolitical problem of population. More important than the presentation or ontological status of any individual character in Joyce's novel is the sheer number of characters who populate Ulysses as a whole. Drawing attention to Joyce's use of reproductive metaphors for character-creation, the author argues that this proliferation of fictional characters compensates for a very real sense of demographic deficit in the wake of the Irish Famine. By refusing to abide depopulation within his novel, Joyce transforms a realist character-system based on the premises of scarcity and an overpopulation of characters. The search for a more inclusive and democratic mode of representing population leads him (via the street directory that he used to plan Ulysses) to the Irish census. After examining the census's influence on episodes such as “Ithaca” and “Wandering Rocks,” the author argues that Joyce embraces a key assumption of the statistical movement that gave rise to the census: the idea that individuals are quantifiable, and thus commensurate, almost to the point of being interchangeable. The preoccupation with “enume ration” in Ulysses points to an expansive vision of population that extends the census's egalitarian logic beyond the quantifying unit of the household. In his own “census,” Joyce presents his characters in demographic detail, confounding the distinctions between flat and round, major and minor, that usually frame discussions of character.
The Spending and Debt Response to Minimum Wage Hikes
Authors: Aaronson Daniel , Agarwal Sumit , French Eric
Published: December 2012

Immediately following a minimum wage hike, household income rises on average by about $250 per quarter and spending by roughly $700 per quarter for households with minimum wage workers. Most of the spending response is caused by a small number of households who purchase vehicles. Furthermore, we find that the high spending levels are financed through increases in collateralized debt. Our results are consistent with a model where households can borrow against durables and face costs of adjusting their durables stock. (JEL D12, D14, D91, J38)
Pricing and Welfare in Health Plan Choice
Authors: Bundorf M. Kate , Levin Jonathan , Mahoney Neale
Published: December 2012

Premiums in health insurance markets frequently do not reflect individual differences in costs, either because consumers have private information or because prices are not risk rated. This creates inefficiencies when consumers self-select into plans. We develop a simple econometric model to study this problem and estimate it using data on small employers. We find a welfare loss of 2–11 percent of coverage costs compared to what is feasible with risk rating. Only about one-quarter of this is due to inefficiently chosen uniform contribution levels. We also investigate the reclassification risk created by risk rating individual incremental premiums, finding only a modest welfare cost. (JEL G22, I13, I18)
Diagnosing Consumer Confusion and Sub-Optimal Shopping Effort: Theory and Mortgage-Market Evidence
Authors: Woodward Susan E , Hall Robert E
Published: December 2012

Mortgage loans are leading examples of transactions where experts on one side of the market take advantage of consumers' lack of knowledge and experience. We study the compensation that borrowers pay to mortgage brokers for assistance from application to closing. Two findings support the conclusion that confused borrowers overpay for brokers' services: (i) A model of effective shopping shows that borrowers sacrifice at least $1,000 by shopping from too few brokers. (ii) Borrowers who compensate their brokers with both cash and a commission from the lender pay twice as much as similar borrowers who pay no cash. (JEL D12, D14, G21)
Imperfect Public Monitoring with Costly Punishment: An Experimental Study
Authors: Ambrus Attila , Greiner Ben
Published: December 2012

This paper experimentally investigates the effects of a costly punishment option on cooperation and social welfare in long, finitely repeated public good contribution games. In a perfect monitoring environment, increasing the severity of the potential punishment monotonically increases average net payoffs. In a more realistic imperfect monitoring environment, we find a U-shaped relationship. Access to a standard punishment technology in this setting significantly decreases net payoffs, even in the long run. Access to a severe punishment technology leads to roughly the same payoffs as with no punishment option, as the benefits of increased cooperation offset the social costs of punishing. (JEL C92, H41, K42)
Who Matters in Coordination Problems?
Authors: Sákovics József , Steiner Jakub
Published: December 2012

Agents face a coordination problem akin to the adoption of a network technology. A principal announces investment subsidies that, at minimal cost, attain a given likelihood of successful coordination. Optimal subsidies target agents who impose high externalities on others and on whom others impose low externalities. Based on the analysis of the role of strategic uncertainty in coordination processes, we provide a methodology that can be used to find the optimal targets for a variety of interventions in a large class of coordination problems with heterogeneous agents. (JEL D81, D82, D83, O33)