bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Polymorphisms in Genes Encoding for Insulin-Like Growth Factor (IGF)-I, Insulin, and IGF-Binding Protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 Levels in Umbilical Cord Plasma
Authors: Landmann Eva , Kollerits Barbara , Kreuder Joachim Gerhard , Blum Werner Friedrich , Kronenberg Florian , Rudloff Silvia
Published: June 2012

Background/Aims: In postnatal life, polymorphisms in the promoter region of IGFBP3 were associated with insulin-like growth factor binding protein (IGFBP)-3 plasma levels. Whether these associations exist in utero has not been studied yet. Polymorphisms in the IGF1 promoter (polymorphic CA-repeat) and the insulin gene variable number tandem repeats locus (INS VNTR) are further polymorphisms of interest, because associations with birth weight have been reported. We aimed to investigate associations between polymorphisms in the promoter regions of IGF1 (wild type 192 bp), IGFBP3 (rs2854744; rs13241830), and INS VNTR (rs689) with cord plasma levels of IGF-I, IGF-II, and IGFBP-3. Methods: We measured IGF-I, IGF-II, and IGFBP-3 concentrations in cord blood from 677 neonates and genotyped the selected polymorphisms. Results: Carriers of the minor allele of both polymorphisms in the IGFBP3 gene had, on average, 4–5% lower IGFBP-3 levels per copy of the respective minor allele (p = 0.002 and p = 0.028) when compared to wild type carriers. The IGF1 promoter and the INS VNTR polymorphisms were not associated with IGF-I, IGF-II, or IGFBP-3 levels. Conclusions: Our data show associations of cord plasma IGFBP-3 levels and the IGFBP3 gene variants but not of IGF1 promoter and INS VNTR polymorphisms with IGF-I, IGF-II, or IGFBP-3 levels in utero.
Bronchoscopic Intervention Obviates the Need for Continued Mechanical Ventilation in Patients with Airway Obstruction and Respiratory Failure from Inoperable Non-Small-Cell Lung Cancer
Authors: Murgu Septimiu , Langer Stephanie , Colt Henri
Published: June 2012

Background: Patients with advanced non-small-cell lung cancer (NSCLC) and acute respiratory failure (ARF) from central airway obstruction (CAO) may be offered end-of-life care rather than intensive care treatment and palliative bronchoscopic intervention. Objectives: To determine whether bronchoscopic intervention could be immediately successful in restoring airway patency and obviate the need for continued mechanical ventilation in a homogeneous group of inoperable mechanically ventilated patients with ARF and CAO from NSCLC. Methods: A retrospective study of 12 consecutive intubated and mechanically ventilated patients with inoperable or unresectable CAO from NSCLC referred for therapeutic bronchoscopic intervention between January 2003 and December 2008. Outcome measures included time-to-postintervention extubation and survival. Procedural success was defined as successful restoration of airway patency, extubation and removal from mechanical ventilation within 24 h after bronchoscopic intervention. Results: Twelve intubated and mechanically ventilated patients were admitted to the ICU during the 6-year study period. Airway patency was restored in 11/12 (91%) patients. Bronchoscopic intervention resulted in immediate extubation and discontinuation of mechanical ventilation in 9/12 (75%) patients. Overall median survival was 228 days (range 6–927). For the 9 patients extubated within 24 h after intervention, however, median survival was 313 days (range 6–927). Conclusions: Intubated patients with respiratory failure caused by CAO from NSCLC can be successfully and rapidly removed from mechanical ventilation after bronchoscopic interventions aimed at restoring airway patency. Median survival greater than 10 months justifies ICU hospitalization and referral for bronchoscopic treatment.
Analysis of Vitamin D Receptor Gene Polymorphisms in Vitiligo
Authors: Aydıngöz İkbal Esen , Bingül İlknur , Doğru-Abbasoğlu Semra , Vural Pervin , Uysal Müjdat
Published: June 2012

Background: Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Vitamin D has both stimulatory and protective effects on melanocytes and acts through its nuclear vitamin D receptor (VDR) on target cells. Aim: The aim of this study was to investigate the association between VDR gene polymorphisms and susceptibility to vitiligo. Methods: 98 patients with vitiligo and 216 age- and sex-matched controls recruited from dermatology outpatients attending the same department were included in the study. Genomic DNA was extracted from peripheral blood leukocytes using a DNA isolation kit. The VDR polymorphisms of BsmI, ApaI, TaqI, FokI and Cdx2 were investigated by rapid capillary PCR with melting curve analysis. Differences in genotype distributions and allele frequencies in vitiligo cases versus controls were compared for statistical significance using χ2 test. Results: Subjects with TaqI polymorphism had a 2.23-fold increased risk of developing vitiligo. Furthermore, a haplotype analysis showed that BsmI/ApaI/TaqI/FokI/Cdx2 GCCCG was significantly overrepresented in the vitiligo patients in comparison with controls (p = 0.031). Conclusion: This study showed that VDR TaqI gene polymorphism and the haplotype BsmI/ApaI/ TaqI/FokI/Cdx2 GCCCG may be considered as novel risk factors in vitiligo.
Interest of High-Dose Pulse Corticosteroid Therapy Combined with Methotrexate for Severe Alopecia Areata: A Retrospective Case Series
Authors: Droitcourt Catherine , Milpied Brigitte , Ezzedine Khaled , Hubiche Thomas , Belin Emilie , Akpadjan Fabrice , Taïeb Alain , Seneschal Julien
Published: June 2012

Background: The combination of systemic pulse corticosteroids and methotrexate in the treatment of severe alopecia areata has never been reported. Objective: The objective of this work was to give arguments for the efficacy and safety of this combined treatment. Methods: This was a retrospective case series of patients treated with intravenous 500 mg methylprednisolone per day for 3 consecutive days monthly during 3 months plus methotrexate initiated at the end of the second pulse regimen. We reviewed all case notes of patients who received this regimen between January 1 2007 and December 1 2010. Results: Twenty patients were treated. Data on hair regrowth at month 12 were available for all patients; 14 patients were still receiving the treatment on December 1 2010, 2 patients were lost of follow-up, and 4 patients had stopped the treatment. Of the 14 patients who were still receiving the treatment regimen at month 18, 10 (10/20, 50%) had total hair regrowth and 4 (4/20, 20%) had incomplete but satisfactory hair regrowth. The treatment was well tolerated. Conclusion: The initial treatment by pulse intravenous corticosteroids may influence the overall response. This approach should be evaluated in a larger series of patients.
A Case Series of Paediatric Hearing Preservation Cochlear Implantation: A New Treatment Modality for Children with Drug-Induced or Congenital Partial Deafness
Authors: Kuthubutheen J. , Hedne C.N. , Krishnaswamy J. , Rajan G.P.
Published: June 2012

Objective: To investigate the use of hearing preservation cochlear implantation in children with partial deafness. Patients and Methods: Five children with either drug-induced or congenital partial deafness were enrolled in a pilot study. The patients ranged in age from 13 months to 14 years. Implantation was performed using a hearing preservation technique. A Flex EAS electrode (MED-EL, Innsbruck, Austria) was used in all full insertions. Results: Low frequency hearing was preserved in all patients with postoperative bone conduction within 10 dB of the preoperative hearing levels. These changes were preserved over the follow-up period of 12 months. There were significant improvements in speech perception. Conclusion: Hearing preservation cochlear implantation is a new effective modality in children with partial deafness.
Association of Race with Cumulative Exposure to Statins in Dialysis
Authors: Wetmore James B. , Mahnken Jonathan D. , Rigler Sally K. , Ellerbeck Edward F. , Mukhopadhyay Purna , Hou Qingjiang , Shireman Theresa I.
Published: June 2012

Background: Patients on dialysis have high rates of cardiovascular disease and are frequently treated with HMG-CoA reductase inhibitors. Given that these patients have insurance coverage for medications as well as regular contact with health care providers, differences by race in exposure to statins over time should be minimal among patients who are candidates for the drug. Methods: We created a cohort of incident dialysis patients who were dually eligible for Medicare and Medicaid services. We determined the proportion of days covered (or PDC, a marker of cumulative medication exposure) by a statin prescription over a mean of 2.0 ± 1.4 years. Ordinary least squares regression was used to determine the factors associated with cumulative drug exposure. Results: Of the 18,727 patients who filled at least one prescription for a statin, mean PDC was 0.57 ± 0.32. The unadjusted PDC was higher for Caucasians (0.63 ± 0.31) than for African-Americans (0.51 ± 0.32), Hispanics (0.54 ± 0.31), and individuals of other race/ethnicity (0.58 ± 0.32). In multivariable modeling, Caucasian race was independently associated with greater exposure to statins. Relative to Caucasians, the adjusted odds ratios for the PDC for African-Americans was 0.47 (95% confidence interval, CI, 0.43–0.50), for Hispanics 0.52 (0.48–0.56) and for others, 0.72 (0.64–0.81). Conclusions: Despite insurance coverage, regular contact with health care providers, and at least one prescription for a statin, there are large differences by race in statin exposure over time. The provider- and patient-associated factors related to this phenomenon should be further examined.
Intragastric Balloon Left in the Stomach for More than a Year: Two Case Reports
Authors: Sioulas Athanasios D. , Polymeros Dimitrios , Kourikou Anastasia , Papanikolaou Ioannis S. , Triantafyllou Konstantinos
Published: June 2012

Objective: Intragastric balloon (IGB) is often used to achieve short-term weight reduction in morbidly obese patients. It is placed endoscopically for a 6-month-period either in the pre-bariatric surgery setting and also in cases where no bariatric surgery is planned. Prolonged implantation may be accompanied by serious complications. Case Reports: We herein report two cases of extraction of intact IGBs long time after their placement. Conclusion: Although no adverse events were observed, adherence to manufacturers’ recommendations is definitely suggested.
The Rise of the Region in Global Environmental Politics
Authors: Conca Ken
Published: June 2012

This essay examines some of the reasons for the upsurge in interest in regional approaches to global environmental challenges. One reason is a growing sense of obstruction and drift at the global level. With the rate of formation of new global environmental agreements lagging, with many existing agreements seemingly stalled, and with the momentum of global summitry having faded, regions may seem a more pragmatic scale at which to promote the diffusion of ideas, the development of institutions, and social mobilization for change. Beyond political pragmatism, there are also conceptually interesting—if still debatable—arguments that regions hold promise for strengthening global environmental governance. The regional scale may offer superior conditions to the global for common-property resource management—although the historical track record seems mixed at best, and formidable barriers to collective action remain. Regions may be more conducive to promoting norm diffusion—although the causal direction appears to be more strongly global-to-regional than vice versa. However the conceptual promise of the regional scale plays out in practice, there is also a compelling ethical argument for a regional focus, as mitigation failures at the global level condemn particular locales to formidable challenges of adaptation.
Characterizing Responses of Translation-Invariant Neurons to Natural Stimuli: Maximally Informative Invariant Dimensions
Authors: Eickenberg Michael , Rowekamp Ryan J. , Kouh Minjoon , Sharpee Tatyana O.
Published: June 2012

The human visual system is capable of recognizing complex objects even when their appearances change drastically under various viewing conditions. Especially in the higher cortical areas, the sensory neurons reflect such functional capacity in their selectivity for complex visual features and invariance to certain object transformations, such as image translation. Due to the strong nonlinearities necessary to achieve both the selectivity and invariance, characterizing and predicting the response patterns of these neurons represents a formidable computational challenge. A related problem is that such neurons are poorly driven by randomized inputs, such as white noise, and respond strongly only to stimuli with complex high-order correlations, such as natural stimuli. Here we describe a novel two-step optimization technique that can characterize both the shape selectivity and the range and coarseness of position invariance from neural responses to natural stimuli. One step in the optimization is finding the template as the maximally informative dimension given the estimated spatial location where the response could have been triggered within each image. The estimates of the locations that triggered the response are updated in the next step. Under the assumption of a monotonic relationship between the firing rate and stimulus projections on the template at a given position, the most likely location is the one that has the largest projection on the estimate of the template. The algorithm shows quick convergence during optimization, and the estimation results are reliable even in the regime of small signal-to-noise ratios. When we apply the algorithm to responses of complex cells in the primary visual cortex (V1) to natural movies, we find that responses of the majority of cells were significantly better described by translation-invariant models based on one template compared with position-specific models with several relevant features.
Microphysical Structure of the Marine Boundary Layer under Strong Wind and Spray Formation as Seen from Simulations Using a 2D Explicit Microphysical Model. Part II: The Role of Sea Spray
Authors: Shpund J. , Zhang J. A. , Pinsky M. , Khain A.
Published: June 2012

The effect of sea spray on the thermodynamics and microphysical structure of the lowest 400-m layer under strong wind speeds is investigated using a 2D hybrid Lagrangian–Eulerian model with spectral bin microphysics. A large number of adjacent and interacting Lagrangian parcels move within a turbulent-like flow with the largest vortices being interpreted as large eddies (LE) with characteristic velocity of a few meters per second.

It is shown that sea spray effect strongly depends on the environmental conditions, and largely on relative humidity (RH). When RH < ~90%, spray evaporates and contributes to moistening and cooling of the boundary layer, as well as to an increase in surface fluxes. When RH > ~90% the effects of spray on the BL thermodynamics substantially decrease. Spray leads to formation of drizzle by collisions with droplets formed on background aerosols.

It is also shown that LE transport about 20% of large spray drops with radius exceeding 150 μm to the upper levels of the atmospheric mixed layer. It is hypothesized that this effect is of much importance with regard to the spray effect on the microphysics and dynamics of deep convective clouds typical of a hurricane eyewall.
Mean Biases, Variability, and Trends in Air–Sea Fluxes and Sea Surface Temperature in the CCSM4
Authors: Bates Susan C. , Fox-Kemper Baylor , Jayne Steven R. , Large William G. , Stevenson Samantha , Yeager Stephen G.
Published: June 2012

Air–sea fluxes from the Community Climate System Model version 4 (CCSM4) are compared with the Coordinated Ocean-Ice Reference Experiment (CORE) dataset to assess present-day mean biases, variability errors, and late twentieth-century trend differences. CCSM4 is improved over the previous version, CCSM3, in both air–sea heat and freshwater fluxes in some regions; however, a large increase in net shortwave radiation into the ocean may contribute to an enhanced hydrological cycle. The authors provide a new baseline for assessment of flux variance at annual and interannual frequency bands in future model versions and contribute a new metric for assessing the coupling between the atmospheric and oceanic planetary boundary layer (PBL) schemes of any climate model. Maps of the ratio of CCSM4 variance to CORE reveal that variance on annual time scales has larger error than on interannual time scales and that different processes cause errors in mean, annual, and interannual frequency bands. Air temperature and specific humidity in the CCSM4 atmospheric boundary layer (ABL) follow the sea surface conditions much more closely than is found in CORE. Sensible and latent heat fluxes are less of a negative feedback to sea surface temperature warming in the CCSM4 than in the CORE data with the model’s PBL allowing for more heating of the ocean’s surface.
Variations in Tropical Cyclone Genesis Factors in Simulations of the Holocene Epoch
Authors: Korty Robert L. , Camargo Suzana J. , Galewsky Joseph
Published: June 2012

The thermodynamic factors related to tropical cyclone genesis are examined in several simulations of the middle part of the Holocene epoch when the precession of Earth’s orbit altered the seasonal distribution of solar radiation and in one transient simulation of the millennium preceding the industrial era. The thermodynamic properties most crucial for genesis display a broad stability across both periods, although both orbital variations during the mid-Holocene (MH) 6000 years ago (6ka) and volcanic eruptions in the transient simulation have detectable effects. It is shown that the distribution of top-of-the-atmosphere radiation 6ka altered the Northern Hemisphere seasonal cycle of the potential intensity of tropical cyclones in addition to slightly increasing the difference between middle tropospheric and boundary layer entropy, a parameter that has been related to the incubation period required for genesis. The Southern Hemisphere, which receives more solar radiation during its storm season today than it did 6ka, displays slightly more favorable thermodynamic properties during the MH than in the preindustrial era control. Surface temperatures over the ocean in both hemispheres respond to radiation anomalies more slowly than those in upper levels, altering the thermal stability.

Volcanism produces a sharp but transient temperature response in the last-millennium simulation that strongly reduces potential intensity during the seasons immediately following a major eruption. Here, too, the differential vertical temperature response is key: temperatures in the lower and middle troposphere cool, while those near the tropopause rise. Aside from these deviations, there is no substantial variation in thermodynamic properties over the 1000-yr simulation.
Effects of Diurnal Cycle on a Simulated Asian Summer Monsoon
Authors: Hong Song-You , Kanamitsu Masao , Kim Jung-Eun , Koo Myung-Seo
Published: June 2012

This study investigates the effects of the diurnal cycle on monsoonal circulations over Asia in summer with a focus on precipitation. To this end, two sets of experiments are designed in a regional climate modeling framework forced by reanalysis data. The control experiment is a normal integration in which radiation is computed hourly, whereas the no-diurnal experiment is an experimental integration in which the daily averaged solar flux is computed once a day. Analysis of the results from the two experiments reveals that the diurnal cycle enhances the daily averaged sensible heat flux over land and the latent flux over oceans, which means that daytime net solar heating exceeds nighttime cooling in terms of the effects in surface climate and monsoonal circulations. Seasonal precipitation increased by about 3% over land and 11% over oceans. The surface hydroclimate over land is strongly influenced by the interaction between land and the atmosphere, and results in cooler surface temperatures except over the Tibetan Plateau. Over oceans, a robust increase in precipitation results from enhanced planetary boundary layer mixing. The diurnal cycle over the Tibetan Plateau region is found to decrease surface albedo by melting snow during the daytime, which contributes to the formation of the thermal low near the surface and the Tibetan high in the upper troposphere. The resultant monsoonal precipitation is modulated by an increase (decrease) in precipitation over northern (southern) India. This modulation results in the summer monsoon over East Asia being shifted northward.
Evidence for Enhanced Land–Atmosphere Feedback in a Warming Climate
Authors: Dirmeyer Paul A. , Cash Benjamin A. , Kinter James L. , Stan Cristiana , Jung Thomas , Marx Lawrence , Towers Peter , Wedi Nils , Adams Jennifer M. , Altshuler Eric L. , Huang Bohua , Jin Emilia K. , Manganello Julia
Published: June 2012

Global simulations have been conducted with the European Centre for Medium-Range Weather Forecasts operational model run at T1279 resolution for multiple decades representing climate from the late twentieth and late twenty-first centuries. Changes in key components of the water cycle are examined, focusing on variations at short time scales. Metrics of coupling and feedbacks between soil moisture and surface fluxes and between surface fluxes and properties of the planetary boundary layer (PBL) are inspected. Features of precipitation and other water cycle trends from coupled climate model consensus projections are well simulated. Extreme 6-hourly rainfall totals become more intense over much of the globe, suggesting an increased risk for flash floods. Seasonal-scale droughts are projected to escalate over much of the subtropics and midlatitudes during summer, while tropical and winter droughts become less likely. These changes are accompanied by an increase in the responsiveness of surface evapotranspiration to soil moisture variations. Even though daytime PBL depths increase over most locations in the next century, greater latent heat fluxes also occur over most land areas, contributing a larger energy effect per unit mass of air, except over some semiarid regions. This general increase in land–atmosphere coupling is represented in a combined metric as a “land coupling index” that incorporates the terrestrial and atmospheric effects together. The enhanced feedbacks are consistent with the precipitation changes, but a causal connection cannot be made without further sensitivity studies. Nevertheless, this approach could be applied to the output of traditional climate change simulations to assess changes in land–atmosphere feedbacks.
A Process-Oriented Small Lake Scheme for Coupled Climate Modeling Applications
Authors: MacKay Murray D.
Published: June 2012

A one-dimensional dynamic lake model is presented as a candidate for simulating small unresolved lakes within the land surface scheme of a regional or global climate model. This model is based largely on well-established process algorithms with some exceptions. The complete nonlinear surface energy balance is computed in a skin layer of arbitrary thickness in order to ensure rapid response times with the atmosphere. Turbulent mixing in the surface mixed layer is achieved through stirring and buoyancy production as well as shear production along the diurnal thermocline. The net effect of Kelvin–Helmholtz instability on thermocline structure is grossly accounted for by computing a linear temperature profile within a thermocline layer. The energetics of billowing is not considered; however, a significant thermocline leakage term is included. The model has been incorporated into the Canadian Land Surface Scheme and used to estimate regional turbulent sensible and latent heat fluxes over the Experimental Lakes Area in the boreal forest of northwestern Ontario—an area about 30% lake covered. It is demonstrated that the presence of open water has a significant effect on the net flux exchange with the atmosphere in this region. Sensible heat flux to the atmosphere is suppressed during the summer stratified period but enhanced in the fall, resulting in an increased accumulation of about 5% by the end of the open water season due to the presence of lakes. Turbulent latent heat flux to the atmosphere is more enhanced during autumn, with a final accumulation about 24% larger.
The Unpredictable Nature of Internal Tides on Continental Shelves
Authors: Nash Jonathan D. , Kelly Samuel M. , Shroyer Emily L. , Moum James N. , Duda Timothy F.
Published: June 2012

Packets of nonlinear internal waves (NLIWs) in a small area of the Mid-Atlantic Bight were 10 times more energetic during a local neap tide than during the preceding spring tide. This counterintuitive result cannot be explained if the waves are generated near the shelf break by the local barotropic tide since changes in shelfbreak stratification explain only a small fraction of the variability in barotropic to baroclinic conversion. Instead, this study suggests that the occurrence of strong NLIWs was caused by the shoaling of distantly generated internal tides with amplitudes that are uncorrelated with the local spring-neap cycle. An extensive set of moored observations show that NLIWs are correlated with the internal tide but uncorrelated with barotropic tide. Using harmonic analysis of a 40-day record, this study associates steady-phase motions at the shelf break with waves generated by the local barotropic tide and variable-phase motions with the shoaling of distantly generated internal tides. The dual sources of internal tide energy (local or remote) mean that shelf internal tides and NLIWs will be predictable with a local model only if the locally generated internal tides are significantly stronger than shoaling internal tides. Since the depth-integrated internal tide energy in the open ocean can greatly exceed that on the shelf, it is likely that shoaling internal tides control the energetics on shelves that are directly exposed to the open ocean.
Assessment of Low-Density Lipoprotein Targets
Authors: Whayne Thomas F.
Published: June 2012

The clinical importance of lowering of total cholesterol and low-density lipoprotein cholesterol (LDL-C) to decrease cardiovascular (CV) risk has been verified over many years starting with significant support in 1984 of the then previous lipid hypothesis. Significant support of this hypothesis began that year with publication of the Lipid Research Clinic study. Since then, multiple other studies including outcomes studies have established the value of LDL-C reduction in decreasing CV risk. In addition, multiple other factors such as inflammation, endothelial dysfunction, nitric oxide, antioxidant properties, and plaque stabilization appear important for modifying CV risk and possible favorable alterations by medications such as statins must be considered. Nevertheless, reduction of LDL-C has well-established value and is being accepted by clinicians as a major guideline for CV disease prevention. However, there are still problems with adherence by many clinicians to CV risk modification. Therefore, abandoning LDL-C reduction as a target, as has been advocated by some, appears premature and contraindicated. A strategy of LDL-C reduction in no way interferes with increased understanding of the complexities of atherosclerosis and new approaches to CV disease prevention as they become supported by outcomes studies.
A Parent-Led Contingent Reward Desensitization Intervention for Children With a Feeding Problem Resulting From Sensory Defensiveness
Authors: Dovey Terence M. , Martin Clarissa I.
Published: June 2012

An anthropomorphic, psychometric and dietary variety assessment was employed to uncover the impact of an intervention for children with a feeding problem due to sensory defensiveness. Parents were trained to deliver a contingent reward desensitization procedure to encourage the child to try food. All children gained weight on their population corrected height and weight over the 6-month intervention. The psychometric measures showed that parents reported fewer feeding problems concomitant with increases in dietary variety. Responsiveness to the intervention was variable within the current study, and this was based on the age of the child at the start of the intervention. Before the intervention, dietary variety was directly proportional to the parents’ reporting of their problems controlling mealtimes. In contrast, dietary variety after the intervention was associated with the child’s problem score. In a group of children who primarily have sensory defensiveness, contingent reward alongside a graduated exposure technique, can improve dietary variety.
Modelling and simulation of A segregates in steel castings using thermal criterion function Part II – Optimisation of real industrial cast part
Authors: Kotas P , Hattel J H
Published: June 2012

The present paper is the second of two papers in which a methodology on how to exploit thermal criteria for modelling and optimising, i.e. minimising, the formation of A segregates in steel castings is presented. The first part of the paper dealt with incorporating one specific thermal criterion into a transient three-dimensional thermal fluid model inside a commercial simulation software package and validating this against experimental data obtained from a manufacturing foundry for a cast forging ram. In the second part of the present paper, the found criterion is then taken one step further by being applied to shape optimise the original casting layout of the forging ram where unknown optimal shapes and sizes of the top riser and chills are sought. This was carried out using genetic algorithms for establishing a better solidification pattern and thermal conditions inside the ram, which would eliminate the likelihood of centreline porosity and A segregates.
Modelling dissolution of precipitates considering overlapping of solute fields
Authors: Zuo Q , Liu F , Guo Y L , Jiang Y H
Published: June 2012

Upon isothermal dissolution of precipitates, the transformation is controlled by solute diffusion, where the overlapping of diffusion fields in front of the precipitate/matrix interface plays an important role. Analogous to a published model for soft impingement in isothermal precipitation, the dissolution process is classified as two stages: one without and one with overlapping of diffusion fields. In the current modelling, linear approximation for the concentration gradient and equilibrium approximation at the interface are assumed, which allow an analytical description for this kinetic process. The model was first demonstrated by numerical calculation. Then, model predictions were performed for θ′ dissolving in Al–3·0 wt-Cu alloy and Al2Cu dissolving in Al–4·2 wt-Cu alloy; good agreement with the published experimental data was achieved.
Investigation on thickness of short time oxide films in Al–1Mg and Al–2Mg alloys
Authors: Azarmehr S A , Divandari M , Arabi H
Published: June 2012

The melts of aluminium alloys are very sensitive to oxidation during casting, and the surface oxide film formed during casting can be folded and entrained into the melt due to melt surface turbulence. In this research, sandwiches of oxide–metal–oxide (OMO) formed in a very short time within the cast during solidification were investigated in order to see the effect of magnesium content (i.e. 1 and 2 wt-) on the oxide film thickness. To form OMO sandwiches within the cast, a certain amount of air was blown into the melt every 0·5 s during casting time by means of a compressor at 0·5 atm pressure. Where bubbles of air collided, they formed a sandwich which later was used for investigating purpose. Both the thickness and the surface of oxide films were studied via SEM. The results showed that the thickness of the short time oxide film varies in the range of 150–250 and 200–300 nm for Al–1Mg and Al–2Mg alloys respectively.
Humans accumulate microsatellite instability with acquired loss of MLH1 protein in hematopoietic stem and progenitor cells as a function of age
Authors: Kenyon Jonathan , Fu Pingfu , Lingas Karen , Thomas Emily , Saurastri Anshul , Santos Guasch Gabriela , Wald David , Gerson Stanton L.
Published: June 2012

Hematopoietic stem and progenitor cells (HPCs) are necessary for long-term survival. Genomic instability and persistent DNA damage may cause loss of adult stem cell function. The mismatch repair (MMR) pathway increases replication fidelity and defects have been implicated in malignant hematopoietic diseases. Little, however, is known about the role MMR pathway failure plays in the aging process of human HPCs. We hypothesized that loss of MMR occurs in HPCs as a process of human aging. We examined microsatellite instability and expression of the MMR genes MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in HPCs and colony-forming cell-derived clones (CFCs) from human donors aged 0 to 86 years. CFCs from donors > 45 years had a greater frequency of microsatellite instability and CD34+ progenitors lacking MLH1 expression and protein than individuals ≤ 45 years. Loss of MSH2 did not correlate with age. Thus, a potentially early event in the normal human aging process is microsatellite instability accumulation in normal human HPCs associated with the loss of MLH1 protein expression.
EGNAS: an exhaustive DNA sequence design algorithm
Authors: Kick Alfred , Bönsch Martin , Mertig Michael
Published: June 2012

Background

The molecular recognition based on the complementary base pairing of deoxyribonucleic acid (DNA) is the fundamental principle in the fields of genetics, DNA nanotechnology and DNA computing. We present an exhaustive DNA sequence design algorithm that allows to generate sets containing a maximum number of sequences with defined properties. EGNAS (Exhaustive Generation of Nucleic Acid Sequences) offers the possibility of controlling both interstrand and intrastrand properties. The guanine-cytosine content can be adjusted. Sequences can be forced to start and end with guanine or cytosine. This option reduces the risk of “fraying” of DNA strands. It is possible to limit cross hybridizations of a defined length, and to adjust the uniqueness of sequences. Self-complementarity and hairpin structures of certain length can be avoided. Sequences and subsequences can optionally be forbidden. Furthermore, sequences can be designed to have minimum interactions with predefined strands and neighboring sequences.

Results

The algorithm is realized in a C++ program. TAG sequences can be generated and combined with primers for single-base extension reactions, which were described for multiplexed genotyping of single nucleotide polymorphisms. Thereby, possible foldback through intrastrand interaction of TAG-primer pairs can be limited. The design of sequences for specific attachment of molecular constructs to DNA origami is presented.

Conclusions

We developed a new software tool called EGNAS for the design of unique nucleic acid sequences. The presented exhaustive algorithm allows to generate greater sets of sequences than with previous software and equal constraints. EGNAS is freely available for noncommercial use athttp://www.chm.tu-dresden.de/pc6/EGNAS.
Potential role for PADI-mediated histone citrullination in preimplantation development
Authors: Kan Rui , Jin Mei , Subramanian Venkataraman , Causey Corey P , Thompson Paul R , Coonrod Scott A
Published: June 2012

Background

The peptidylarginine deiminases (PADIs) convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated.

Results

In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26) were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA) to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17.

Conclusions

Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is permissive for histone acetylation.
Excess of health care use in general practice and of comorbid chronic conditions in cancer patients compared to controls
Authors: Jabaaij Lea , van den Akker Marjan , Schellevis François G
Published: June 2012

Background

The number of cancer patients and the number of patients surviving initial treatments is expected to rise. Traditionally, follow-up monitoring takes place in secondary care. The contribution of general practice is less visible and not clearly defined.

This study aimed to compare healthcare use in general practice of patients with cancer during the follow-up phase compared with patients without cancer. We also examined the influence of comorbid conditions on healthcare utilisation by these patients in general practice.

Methods

We compared health care use of N=8,703 cancer patients with an age and gender-matched control group of patients without cancer from the same practice. Data originate from the Netherlands Information Network of General Practice (LINH), a representative network consisting of 92 general practices with 350,000 enlisted patients. Health care utilisation was assessed using data on contacts with general practice, prescription and referral rates recorded between 1/1/2001 and 31/12/2007. The existence of additional comorbid chronic conditions (ICPC coded) was taken into account.

Results

Compared to matched controls, cancer patients had more contacts with their GP-practice (19.5 vs. 11.9, p<.01), more consultations with the GP (3.5 vs. 2.7, p<.01), more home visits (1.6 vs. 0.4, p<.01) and they got more medicines prescribed (18.7 vs. 11.6, p<.01) during the follow-up phase. Cancer patients more often had a chronic condition than their matched controls (52% vs. 44%, p<.01). Having a chronic condition increased health care use for both patients with and without cancer. Cancer patients with a comorbid condition had the highest health care use.

Conclusion

We found that cancer patients in the follow-up phase consulted general practice more often and suffered more often from comorbid chronic conditions, compared to patients without cancer. It is expected that the number of cancer patients will rise in the years to come and that primary health care professionals will be more involved in follow-up care. Care for comorbid chronic conditions, communication between specialists and GPs, and coordination of tasks then need special attention.
Factors associated with prenatal folic acid and iron supplementation among 21,889 pregnant women in Northern Tanzania: A cross-sectional hospital-based study
Authors: Ogundipe Olukemi , Hoyo Cathrine , Østbye Truls , Oneko Olola , Manongi Rachael , Lie Rolv Terje , Daltveit Anne Kjersti
Published: June 2012

Background

Folate and iron deficiency during pregnancy are risk factors for anaemia, preterm delivery, and low birth weight, and may contribute to poor neonatal health and increased maternal mortality. The World Health Organization recommends supplementation of folic acid (FA) and iron for all pregnant women at risk of malnutrition to prevent anaemia. We assessed the use of prenatal folic acid and iron supplementation among women in a geographical area with a high prevalence of anaemia, in relation to socio-demographic, morbidity and health services utilization factors.

Methods

We analysed a cohort of 21,889 women who delivered at Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania, between 1999 and 2008. Logistic regression models were used to describe patterns of reported intake of prenatal FA and iron supplements.

Results

Prenatal intake of FA and iron supplements was reported by 17.2% and 22.3% of pregnant women, respectively. Sixteen percent of women reported intake of both FA and iron. Factors positively associated with FA supplementation were advanced maternal age (OR = 1.17, 1.02-1.34), unknown HIV status (OR = 1.54, 1.42-1.67), a diagnosis of anaemia during pregnancy (OR = 12.03, 9.66-14.98) and indicators of lower socioeconomic status. Women were less likely to take these supplements if they reported having had a malaria episode before (OR = 0.57, 0.53-0.62) or during pregnancy (OR = 0.45, 0.41-0.51), reported having contracted other infectious diseases (OR = 0.45, 0.42-0.49), were multiparous (OR = 0.73, 0.66-0.80), had preeclampsia/eclampsia (OR = 0.48, 0.38-0.61), or other diseases (OR = 0.55, 0.44-0.69) during pregnancy. Similar patterns of association emerged when iron supplementation alone and supplementation with both iron and FA were evaluated.

Conclusions

FA and iron supplementation are low among pregnant women in Northern Tanzania, in particular among women with co-morbidities before or during pregnancy. Attempts should be made to increase supplementation both in general and among women with pregnancy complications.
Enzyme inhibitory and antioxidant activities of traditional medicinal plants: Potential application in the management of hyperglycemia
Authors: Gulati Vandana , Harding Ian H , Palombo Enzo A
Published: June 2012

Background

Traditional Indian and Australian medicinal plant extracts were investigated to determine their therapeutic potential to inhibit key enzymes in carbohydrate metabolism, which has relevance to the management of hyperglycemia and type 2 diabetes. The antioxidant activities were also assessed.

Methods

The evaluation of enzyme inhibitory activity of seven Australian aboriginal medicinal plants and five Indian Ayurvedic plants was carried out against α-amylase and α-glucosidase. Antioxidant activity was determined by measuring (i) the scavenging effect of plant extracts against 2, 2-diphenyl-1-picryl hydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS) and (ii) ferric reducing power. Total phenolic and total flavonoid contents were also determined.

Results

Of the twelve plant extracts evaluated, the highest inhibitory activity against both α-amylase and α-glucosidase enzymes was exerted bySantalum spicatumandPterocarpus marsupiumwith IC50values of 5.43 μg/ml and 0.9 μg/ml, respectively, and 5.16 μg/ml and 1.06 μg/ml, respectively. However, the extracts ofAcacia ligulata(IC50 = 1.01 μg/ml),Beyeria leshnaultii(0.39 μg/ml),Mucuna pruriens(0.8 μg/ml) andBoerhaavia diffusa(1.72 μg/ml) exhibited considerable activity against α-glucosidase enzyme only. The free radical scavenging activity was found to be prominent in extracts ofAcacia kempeana,Acacia ligulatafollowed byEuphorbia drummondiiagainst both DPPH and ABTS. The reducing power was more pronounced inEuphorbia drummondiiandPterocarpus marsupiumextracts. The phenolic and flavonoid contents ranged from 0.42 to 30.27 μg/mg equivalent of gallic acid and 0.51 to 32.94 μg/mg equivalent of quercetin, respectively, in all plant extracts. Pearson’s correlation coefficient between total flavonoids and total phenolics was 0.796.

Conclusion

The results obtained in this study showed that most of the plant extracts have good potential for the management of hyperglycemia, diabetes and the related condition of oxidative stress.
Algorithmic processing of pressure waveforms to facilitate estimation of cardiac elastance
Authors: Stevenson David , Revie James , Chase J Geoffrey , Hann Christopher E , Shaw Geoffrey M , Lambermont Bernard , Ghuysen Alexandre , Kolh Philippe , Desaive Thomas
Published: June 2012

Background

Cardiac elastances are highly invasive to measure directly, but are clinically useful due to the amount of information embedded in them. Information about the cardiac elastance, which can be used to estimate it, can be found in the downstream pressure waveforms of the aortic pressure (P

ao
) and the pulmonary artery (P

pa
). However these pressure waveforms are typically noisy and biased, and require processing in order to locate the specific information required for cardiac elastance estimations. This paper presents the method to algorithmically process the pressure waveforms.

Methods

A shear transform is developed in order to help locate information in the pressure waveforms. This transform turns difficult to locate corners into easy to locate maximum or minimum points as well as providing error correction.

Results

The method located all points on 87 out of 88 waveforms for P

pa
, to within the sampling frequency. For P

ao
, out of 616 total points, 605 were found within 1%, 5 within 5%, 4 within 10% and 2 within 20%.

Conclusions

The presented method provides a robust, accurate and dysfunction-independent way to locate points on the aortic and pulmonary artery pressure waveforms, allowing the non-invasive estimation of the left and right cardiac elastance.
Structure based sequence analysis & epitope prediction of gp41 HIV1 envelope glycoprotein isolated in Pakistan
Authors: Jafri Syyada Samra , Kiran Saliha , Jamal Syed Babar , Shah Masaud
Published: June 2012

Background

Gp41 is an envelope glycoprotein of human immune deficiency virus (HIV). HIV viral glycoprotein gp41, present in complex with gp120, assists the viral entry into host cell. Over eighty thousands individuals are HIV infected in Pakistan which makes about 0.2% of 38.6 million infected patients worldwide. Hence, HIV gp41 protein sequences isolated in Pakistan were analyzed for the CD4 and CD8 T cells binding epitopes.

Results

Immunoinformatics tools were applied for the study of variant region of HIV gp41envelope protein. The protein nature was analyzed using freely accessible computational software. About 90 gp41 sequences of Pakistani origin were aligned and variable and conserved regions were found. Four segments were found to be conserved in gp41 viral protein. A method was developed, involving the secondary structure, surface accessibility, hydrophobicity, antigenicity and molecular docking for the prediction and location of epitopes in the viral glycoprotein. Some highly conserved CD4 and CD8 binding epitopes were also found using multiple parameters. The predicted continuous epitopes mostly fall in the conserved region of 1–12; 14–22 and 25–46 and can be used as effective vaccine candidates.

Conclusions

The study revealed potential HIV subtype a derived cytotoxic T cell (CTL) epitopes from viral proteome of Pakistani origin. The conserved epitopes are very useful for the diagnosis of the HIV 1 subtype a. This study will also help scientists to promote research for vaccine development against HIV 1 subtype a, isolated in Pakistan.