bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of fine particulate matter concentrations to changes of emissions and temperature in Europe
Authors: Megaritis A. G. , Fountoukis C. , Charalampidis P. E. , Pilinis C. , Pandis S. N.
Published: April 2012

Abstract. PMCAMx-2008, a three dimensional chemical transport model (CTM), was applied in Europe to quantify the changes in fine particle (PM2.5) concentration in response to different emission reductions as well as to temperature increase. A summer and a winter simulation period were used, to investigate the seasonal dependence of the PM2.5 response to 50% reductions of SO2, NH3, NOx, anthropogenic VOCs and anthropogenic OA emissions and also to temperature increases of 2.5 and 5 K. Reduction of NH3 emissions seems to be the most effective control strategy for reducing PM2.5, in both periods, resulting in a decrease of PM2.5 up to 5.1 μg m−3 and 1.8 μg m−3 (5.5% and 4% on average) during summer and winter respectively, mainly due to reduction of NH4NO3 (20% on average in both periods). The reduction of SO2 emissions decreases PM2.5 in both periods having a significant effect over the Balkans (up to 1.6 μg m−3) during summer, mainly due to decrease of sulfate (30% on average over the Balkans). The anthropogenic OA control strategy reduces total OA by 15% during winter and 8% in the summer. The reduction of total OA is higher in urban areas close to its emissions sources. A slight decrease of OA (8% in summer and 4% in winter) is also predicted after a 50% reduction of VOCs emissions due to the decrease of anthropogenic SOA. The reduction of NOx emissions reduces PM2.5 (up to 3.4 μg m−3) during the summer, due a decrease of NH4NO3, causing although an increase of ozone concentration in major urban areas and over Western Europe. Additionally, the NOx control strategy actually increases PM2.5 levels during the winter. The increase of temperature results in a decrease of PM2.5 in both periods over Central Europe, mainly due to a decrease of NH4NO3 during summer (18%) and fresh POA during winter (35%). Significant increases of OA are usually predicted during summer due mainly to the increase of biogenic VOC emissions. On the contrary, OA is predicted to decrease in the winter due to the dominance of fresh POA reduction and the small biogenic SOA contribution to OA. The resulting increase of oxidant levels from the temperature rise lead to an increase of sulfate levels in both periods, mainly over North Europe and the Atlantic Ocean. The substantial reduction of PM2.5 components due to emissions reductions of their precursors in conjunction with significant changes of PM after increasing the temperature indicate that both emissions and temperature need to be of significant concern for improving air quality.
Increasing cloud cover in the 20th century: review and new findings in Spain
Authors: Sanchez-Lorenzo A. , Calbó J. , Wild M.
Published: April 2012

Abstract. Visual observations of clouds have been performed since the establishment of meteorological observatories during the early instrumental period, and have become more systematic and reliable after the mid-19th century due to the establishment of the first national weather services. During the last decades a large number of studies have documented the trends of the total cloud cover (TCC) and cloudy types; most of these studies are focused on the trends since the second half of the 20th century. Due to the lower reliability of former observations, and the fact that most of this data is not accessible in digital format, there is a lack of studies focusing on the trends of cloudiness since the mid-19th century. In the first part, this work attempts to review the previous studies analyzing TCC changes with information covering at least the first half of the 20th century. Then, the study analyses a database of cloudiness observations in Southern Europe (Spain) since the second third of the 19th century. Specifically, monthly TCC series were reconstructed since 1866 by means of a so-called parameter of cloudiness, calculated from the number of cloudless and overcast days. This estimated TCC series show a high interannual and decadal correlation with the observed TCC series originally measured in oktas. After assessing the temporal homogeneity of the estimated TCC series, the mean annual and seasonal series for the whole of Spain and several subregions were calculated. The mean annual TCC shows a general tendency to increase from the beginning of the series until the 1960s; at this point, the trend becomes negative. The linear trend for the annual mean series, estimated over the 1866–2010 period, is a highly remarkable (and statistically significant) increase of +0.44% per decade, which implies an overall increase of more than +6% during the analyzed period. These results are in line with the major part of the previous trends observed at many areas of the World, especially for the records before the 1950s, when a widespread increase of TCC can been considered as a common feature.
Spatial variation of shallow and deep soil moisture in the semi-arid loess hilly area, China
Authors: Yang L. , Wei W. , Chen L. , Jia F. , Mo B.
Published: April 2012

Abstract. Soil moisture in deep soil layers is the only relatively stable water resource for introduced vegetation in the semi-arid Loess Plateau of China. Characterizing the spatial variation of deep soil moisture is significant for vegetation restoration with respect to the topographic conditions. In this study, we focused on analyzing the spatial variations and influencing factors of soil moisture content (SMC) in shallow (0–2 m) and deep (2–8 m) soil layers based on soil moisture observation in the Longtan watershed. The vegetation type of each sampling site for each comparison is same, while varies with slope position, slope gradient, or slope aspect. The following results are found: (1) compared with shallow SMC, slope position and slope aspect may affect shallow soil moisture more, rather than deep layers. Slope gradient however, affect both shallow and deep soil moisture significantly. It indicates that high difference of deep soil hydrological processes between shallow and deep soil moisture remains, which can be attributed to the introduced vegetation and topography. (2) The vegetation growth condition has significant negative relation with deep soil moisture. This result indicates that plants under different growth conditions may consume soil moisture differently, thus causing higher spatial variation of deep soil moisture. (3) The dynamic role of slope position and slope aspect on deep SMC has been changed by introduced vegetation in semi-arid environment. Consequently, vegetation growth condition and slope gradient may be the major factor contributing to the spatial variation of deep soil moisture.
Towards an integrated soil moisture drought monitor for East Africa
Authors: Anderson W. B. , Zaitchik B. F. , Hain C. R. , Anderson M. C. , Yilmaz M. T. , Mecikalski J. , Schultz L.
Published: April 2012

Abstract. Drought in East Africa is a recurring phenomenon with significant humanitarian impacts. Given the steep climatic gradients, topographic contrasts, general data scarcity, and, in places, political instability that characterize the region, there is a need for spatially distributed, remotely derived monitoring systems to inform national and international drought response. At the same time, the very diversity and data scarcity that necessitate remote monitoring also make it difficult to evaluate the reliability of these systems. Here we apply a suite of remote monitoring techniques to characterize the temporal and spatial evolution of the 2010–2011 Horn of Africa drought. Diverse satellite observations allow for evaluation of meteorological, agricultural, and hydrological aspects of drought, each of which is of interest to different stakeholders. Focusing on soil moisture, we apply triple collocation analysis (TCA) to three independent methods for estimating soil moisture anomalies to characterize relative error between products and to provide a basis for objective data merging. The three soil moisture methods evaluated include microwave remote sensing using the Advanced Microwave Scanning Radiometer – Earth Observing System (AMSR-E) sensor, thermal remote sensing using the Atmosphere-Land Exchange Inverse (ALEXI) surface energy balance algorithm, and physically-based land surface modeling using the Noah land surface model. It was found that the three soil moisture monitoring methods yield similar drought anomaly estimates in areas characterized by extremely low or by moderate vegetation cover, particularly during the below-average 2011 long rainy season. Systematic discrepancies were found, however, in regions of moderately low vegetation cover and high vegetation cover, especially during the failed 2010 short rains. The merged, TCA-weighted soil moisture composite product takes advantage of the relative strengths of each method, as judged by the consistency of anomaly estimates across independent methods. This approach holds potential as a remote soil moisture-based drought monitoring system that is robust across the diverse climatic and ecological zones of East Africa.
Treatment of Medically Refractory Hypercalcemic Crisis
Authors: Au Selena , Dunham Michael , Godinez Tomas
Published: April 2012

Introduction:

A 58-year-old patient was admitted to the intensive care unit for severe hypercalcemia (total Ca 5.30 mmol/L) complicated with status epilepticus, hypertensive crisis and acute renal failure. Renal replacement therapy was explored as a method for treating medically refractory hypercalcemia.

Methods:

Because of hemodynamic instability during intermittent hemodialysis (IHD), continuous venovenous hemofiltration (CVVH) with high rates of calcium-free replacement fluids was instituted. Epoprostenol rather than citrate was used as anticoagulation to ensure adequate extracorporeal anticoagulation.

Results:

CVVH was continued for 40 hours total during which ionized calcium decreased from 2.19 to 1.07 mmol/L. The etiology of the hypercalcemia was from autoinfarction of a parathyroid adenoma.

Conclusions:

This is the first case of hypercalcemia treated with CVVH with epoprostenol anticoagulation. This method avoids some of the pitfalls of using intermittent hemodialysis. It is also a rare example of hypercalcemia induced posterior reversible encephalopathy syndrome (PRES).
Artificial Liver Support System Reduces Intracranial Pressure More Effectively than Bioartificial System: An Experimental Study
Authors: Ryska Ondrej , Pantoflicek Tomas , Laszikova Eva , Prazak Josef , Koblihova Eva , Ryska Miroslav
Published: April 2012

Objectives:

Extracorporeal liver support (ELS) may play a role in bridging therapy in patients with acute liver failure (ALF). The aim of this study was to compare the influence of nonbiological and biological methods on intracranial pressure (ICP) in an animal model of ALF.

Methods:

A surgical devascularization model of ALF in pigs (35–40 kg) was used. Elimination therapy started after the onset of hypoglycemia. Biochemical parameters (bilirubin, ammonia, lactate, etc.) as well as ICP and cerebral perfusion pressure (CPP) were monitored for 12 hours. Of the total 31 pigs with ALF, 14 animals were treated by fractionated plasma separation and absorption (FPSA), 10 were treated with a bioartificial liver (BAL), and 7 animals were used as a control group.

Results:

FPSA and BAL treatment started on average 3 hours 17 minutes and 2 hours 21 minutes, after devascularization and lasted for 5 hours 54 minutes and 5 hours 43 minutes, respectively. Ammonia levels were lower in the FPSA group, and bilirubin levels differed significantly in both the FPSA and BAL groups compared with controls. However, ICP values were reduced more effectively in pigs treated by FPSA: 19.1 vs. 27.0 mm Hg at 9 hours, 22.5 vs. 28.7 mm Hg at 11 hours, and 24.0 vs. 33.0 mm Hg at 12 hours (p<0.05).

Conclusions:

The artificial liver support system FPSA reduced ICP values more effectively than the Performer O. Liver RanD BAL system. Compared with this BAL system, the nonbiological elimination method of FPSA is a simpler application with the advantage that it can be applied in a more continuous way.
Trenchless technologies: Innovative solutions for water main renewal
Authors: Matthews John C.
Published: April 2012

The disparity between available funding and the need to invest in renewal of the water infrastructure in the United States has necessitated the use of innovative techniques to extend the life of pipe assets.
Caregiver Burden Among Informal Caregivers Assisting People with Multiple Sclerosis
Authors: Buchanan Robert J. , Radin Dagmar , Huang Chunfeng
Published: April 2012

Multiple sclerosis (MS) burdens not only patients but also their informal or family caregivers. This study was conducted to identify characteristics of caregivers, caregiving, and MS patients receiving informal care that are associated with caregiving burden. Data were collected through a national survey of informal MS caregivers and analyzed using an ordered logistic regression model to identify factors associated with burden. Burden was found to be significantly greater among male caregivers than among female caregivers. Moreover, greater burden was associated with more frequent patient bladder dysfunction, more hours per week spent providing assistance, and greater restriction on the caregiver's ability to perform daily activities because of caregiving responsibilities. A strong association was found between the mental health status of the caregiver and burden. Health professionals should be sensitive to the impact of caregiving on the mental health of MS caregivers. The results of this study suggest that treating patient bladder dysfunction and facilitating respite care may reduce burden and improve the mental health of informal caregivers of people with MS. Future research should identify programs and services designed specifically to reduce burden experienced by male caregivers.
Monitoring My Multiple Sclerosis
Authors: Gulick Elsie E. , Namey Marie , Halper June
Published: April 2012

Optimal health of people with multiple sclerosis (MS) can be promoted by patients' sharing of health information gained through periodic self-monitoring with their health-care providers. The purpose of this study was to develop a valid and reliable self-administered scale to obtain information about MS patients' health status and the impact of the disease on their daily lives. We named this scale “Monitoring My Multiple Sclerosis” (MMMS). A cross-sectional survey was conducted of 171 MS patients who completed the MMMS and Patient-Determined Disease Steps (PDDS) scales and provided information on their MS disease classification and demographic characteristics. Data analysis included several parametric procedures. Factor analysis of the 26-item MMMS resulted in four factors with satisfactory α reliability coefficients for the total scale (0.90) and factored subscales: Physical (0.85), Relationships (0.80), Energy (0.70), and Cognitive/Mental (0.67). Analysis of variance demonstrated that the total scale and the Physical subscale, but not the Relationships subscale, showed significantly worse functioning for patients with either moderate or severe disability as measured by the PDDS than for patients with mild disability (P < .001). The Cognitive/Mental subscale showed significantly worse functioning for patients with moderate disability than for patients with mild disability (P < .05). However, the Energy subscale showed significantly worse functioning among moderately disabled patients than among severely disabled patients (P < .01). Independent t tests demonstrated that patients classified as having secondary progressive multiple sclerosis had significantly worse scores on the total MMMS (P < .05) and the Physical subscale (P < .001) than those classified as having relapsing-remitting multiple sclerosis. The MMMS demonstrated satisfactory reliability and validity and is recommended for use by MS patients and their health-care providers as a mechanism to promote the sharing of health information, to the benefit of both patients and providers.
Perceived Met and Unmet Health-Care Needs in a Community Population with Multiple Sclerosis
Authors: Patten Scott B. , Williams Jeanne V.A. , Lavorato Dina H. , Terriff David , Metz Luanne M. , Berzins Sandy , Bulloch Andrew G.M.
Published: April 2012

Community-based studies are required to accurately describe the supportive services needed by people with multiple sclerosis (MS). Characteristics that influence (or result from) care-seeking may introduce bias into other types of studies. The Participation and Activity Limitation Survey (PALS) was a post-census survey conducted by Statistics Canada in association with a 2006 national census. The PALS collected data from a sample of 22,513 respondents having health-related impairments according to their census forms. The survey collected self-reported diagnostic data and obtained ratings for items assessing impairment as well as perceived met and unmet needs for care and support. It identified 245 individuals with MS, leading to an estimated (weighted) population prevalence of 0.2% (200 per 100,000). As expected, those with MS reported more-severe health problems than did those with other types of disability, particularly in the areas of mobility, dexterity, and cognition; they were also more likely to report having multiple caregivers. People with MS also reported more unmet health-care needs than did those with other forms of disability, particularly with respect to meal preparation, housework, shopping, and chores. Despite their more negative health status and greater reliance on caregivers, people with MS reported participation in society comparable to that of people without MS. Thus, people with MS report greater needs than do people with other forms of health-related disability and utilize supportive services more often. However, they also report higher levels of unmet needs. The substantial needs of people with MS are only partially addressed by existing services.
World of Similitude: The Metamorphosis of Iranian Architecture
Authors: Farahi Farshad
Published: April 2012

How can an ancient architectural heritage become a rich resource for inspiration rather than a burden or a limitation? Moving away from a conventional formal analysis of historic architecture, which identifies particular periods with specific styles or characteristics, Farshad Farahi suggests an approach that unites the contemporary philosophically and spiritually with its past ‐ by seeking out an imaginary dimension or ‘World of Similitude’.
Assimilating the Authentic with the Contemporary: The Work of Hadi Mirmiran 1945–2006
Authors: Sayar Saman
Published: April 2012

Hadi Mirmiran formulated a third way for Iranian architecture. During the 1980s he created an influential shift in thinking and practice by developing an alternative approach, which neither directly imitated Western Modernism nor copied traditional building forms. As Saman Sayar explains, Mirmiran developed a uniquely Iranian treatment that owed as much to the geometrical purity and simplicity of the 17th‐century Bridge of 33 Arches in Isfahan as to Mies van der Rohe.
Functionalized Poly(γ‐Glutamic Acid) Fibrous Scaffolds for Tissue Engineering
Authors: Gentilini Cristina , Dong Yixiang , May Jessica R. , Goldoni Silvia , Clarke David E. , Lee Boon‐Heng , Pashuck E. Thomas , Stevens Molly M.
Published: April 2012

Poly(γ‐glutamic acid) (γ‐PGA) is a biocompatible, enzymatically‐degradable, natural polymer with a higher resistance to hydrolysis than polyesters commonly used for tissue engineering scaffolds such as poly(L‐lactide) (PLLA). Notably, γ‐PGA's free carboxyl side groups allow for simple chemical functionalization, making it a versatile candidate for producing scaffolds. Here, a series of water‐resistant fibrous scaffolds were engineered from ethyl (Et), propyl (Pr) and benzyl (Bn) esterifications of γ‐PGA. All scaffolds were non‐cytotoxic and γ‐PGA‐Bn showed an increase in cell adhesion of hMSCs compared to γ‐PGA‐Et and γ‐PGA‐Pr. Moreover, cells on γ‐PGA‐Bn showed three‐fold higher viability at day 14 and significantly higher adhesion when compared with PLLA scaffolds, despite having a similar hydrophobicity. Cell attachment decreased by 40% when the polymer was only partially modified with benzyl groups (γ‐PGA‐Bn‐77%), but was restored when integrin‐binding RGD peptide was conjugated to the remaining free carboxylic groups, indicating the peptide was accessible and able to bind integrins. The mechanism behind the cell‐material interactions on γ‐PGA‐Bn scaffolds was further investigated through protein adsorption and fibronectin conformation experiments. These results, in addition to the cell‐adhesion studies, suggest an inherent effect of the benzyl modification in the mechanism of cell attachment to γ‐PGA‐Bn scaffolds. Finally, γ‐PGA‐Bn scaffolds cultured in osteogenic media were also efficient in supporting hMSCs differentiation towards an osteogenic lineage as determined by alkaline phosphatase and Runx2 gene expression. Taken together these data suggest that esterified γ‐PGA polymer scaffolds are new and versatile candidates for tissue engineering applications and that, intriguingly, aromatic functionality plays a key role in the cell‐scaffold interaction.
Materials for Diabetes Therapeutics
Authors: Bratlie Kaitlin M. , York Roger L. , Invernale Michael A. , Langer Robert , Anderson Daniel G.
Published: April 2012

This review is focused on the materials and methods used to fabricate closed‐loop systems for type 1 diabetes therapy. Herein, we give a brief overview of current methods used for patient care and discuss two types of possible treatments and the materials used for these therapies–(i) artificial pancreases, comprised of insulin producing cells embedded in a polymeric biomaterial, and (ii) totally synthetic pancreases formulated by integrating continuous glucose monitors with controlled insulin release through degradable polymers and glucose‐responsive polymer systems. Both the artificial and the completely synthetic pancreas have two major design requirements: the device must be both biocompatible and be permeable to small molecules and proteins, such as insulin. Several polymers and fabrication methods of artificial pancreases are discussed: microencapsulation, conformal coatings, and planar sheets. We also review the two components of a completely synthetic pancreas. Several types of glucose sensing systems (including materials used for electrochemical, optical, and chemical sensing platforms) are discussed, in addition to various polymer‐based release systems (including ethylene‐vinyl acetate, polyanhydrides, and phenylboronic acid containing hydrogels).
Endoscopic neural blockade for rhinogenic headache and facial pain: 2011 update
Authors: Rodman Regina , Dutton Jay
Published: April 2012

Background:

Over 45 million Americans suffer from recurrent headaches, and an estimated $11.9 million was spent on doctor's visits for rhinogenic pain last year. Sphenopalatine blocks have been described for various facial pain syndromes, but their use and the type of blockade agents remain controversial. The objective of this study was to demonstrate that endoscopic nerve blocks, using a mixture of bupivicaine and triamcinolone‐40, injected into the anterior ethmoid or sphenopalatine regions, can be a relative safe and effective option for refractory pain.

Methods:

The charts of all patients undergoing endoscopic neural blockade, in a private practice setting from 1998 to 2008 were retrospectively reviewed. A 1:1 mixture of 0.5% bupivicaine and triamcinolone acetonide injectable suspension was injected into the patients' anterior ethmoid or sphenopalatine neural distribution, or both, depending on the pain distribution. Charts were reviewed to assess outcomes and any adverse events from nerve blocks.

Results:

A total of 882 nerve blocks were administered to 147 patients, over the course of 431 office visits. Four mild complications, 2 moderate complications, and no severe or permanent complications were noted. No permanent visual complications were observed. Of all the charts, 85% had documented effects of the nerve block at follow‐up. Of those, 81.3% claimed improvement, 17.9% reported feeling the same, and 0.79% stated they had worse pain.

Conclusion:

Endoscopic neural blockade appears to be a relatively safe and viable option in the treatment of refractory headache and facial pain with a rhinogenic component. © 2012 ARS‐AAOA, LLC.
Association between bone mineral density and C‐reactive protein in a large population‐based sample
Authors: de Pablo Paola , Cooper Mark S. , Buckley Christopher D.
Published: April 2012

Objective

Several studies suggest that bone mineral density (BMD) is reduced in chronic inflammatory diseases. Higher serum levels of C‐reactive protein (CRP) have been associated with lower BMD in women and older adults. However, it is not clear whether this association holds in a representative sample of the general population. The purpose of this study was to examine the relationship between BMD and CRP level in a large representative US population‐based sample from the National Health and Nutrition Examination Survey (NHANES).

Methods

We included participants age ≥20 years with BMD (total and subregions) measured by dual x‐ray absorptiometry scans and complete information on covariates from NHANES. The association between CRP level and BMD was evaluated using multivariate linear regression models, adjusting for potential confounders and further adjusting for comorbid diseases, medications, and serum vitamin D levels.

Results

The study sample included 10,475 participants (53% Caucasian, 22% Mexican American, 18% African American, and 7% other races). Men had higher BMD and lower CRP concentrations than women. BMD (total body BMD as well as subtotal BMD and BMD of the extremities, ribs, and trunk subregions) was inversely associated with quintiles of CRP concentration both in men and in women in a dose‐dependent manner (for total BMD, P for trend < 0.0001 for men, P for trend = 0.0005 for women). The associations were independent of medications, comorbidities, and other potential confounders. The results remained largely unchanged with further adjustment for serum vitamin D levels.

Conclusion

Among men and women in a large representative population‐based sample, the CRP level was inversely and independently associated with total BMD in a dose‐dependent manner.
Brief Report: Inhibition of interleukin‐6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis
Authors: Samson Maxime , Audia Sylvain , Janikashvili Nona , Ciudad Marion , Trad Malika , Fraszczak Jennifer , Ornetti Paul , Maillefert Jean‐Francis , Miossec Pierre , Bonnotte Bernard
Published: April 2012

Objective

From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti–interleukin‐6 (anti–IL‐6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL‐6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL‐6 blockade on the balance between Th17 cells and Treg cells in patients with active RA.

Methods

Patients with active RA for whom TCZ had been prescribed by a rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed, and the Disease Activity Score in 28 joints (DAS28) was assessed. Serum cytokine levels and other parameters of inflammation were measured before the first infusion and after the third infusion of TCZ (8 mg/kg).

Results

Compared to controls, levels of Th17 cells (CD4+IL‐17+) were increased and Treg cells (CD4+CD25highFoxP3+) were decreased in the peripheral blood of patients with active RA. The suppressive function of circulating Treg cells was not impaired in patients with active RA. TCZ treatment induced a significant decrease in the DAS28 associated with a significant decrease in the percentage of Th17 cells (from a median of 0.9% to 0.45%; P = 0.009) and an increase in the percentage of Treg cells (from a median of 3.05% to 3.94%; P = 0.0039) in all patients.

Conclusion

This study demonstrates for the first time that inhibition of IL‐6 function by TCZ corrects the imbalance between Th17 cells and Treg cells in patients with RA.
Dkk‐1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice
Authors: Oh Hwanhee , Chun Churl‐Hong , Chun Jang‐Soo
Published: April 2012

Objective

Dkk is a family of canonical Wnt antagonists with 4 members (Dkk‐1, Dkk‐2, Dkk‐3, and Dkk‐4). We undertook this study to explore the roles of Dkk‐1 and Dkk‐2 in osteoarthritic (OA) cartilage destruction in mice.

Methods

Expression of Dkk and other catabolic factors was determined at the messenger RNA and protein levels in human and mouse OA cartilage. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) or by intraarticular injection of Epas1 adenovirus (AdEPAS‐1). The role of Dkk in OA pathogenesis was examined by intraarticular injection of AdDkk‐1 or by using chondrocyte‐specific Dkk1 (Col2a1‐Dkk1)–transgenic mice and Dkk2 (Col2a1‐Dkk2)–transgenic mice. Primary culture mouse chondrocytes were also treated with recombinant Dkk proteins.

Results

We found opposite patterns of Dkk1 and Dkk2 expression in human and mouse experimental OA cartilage: Dkk1 was up‐regulated and Dkk2 was down‐regulated. Overexpression of Dkk1 by intraarticular injection of AdDkk‐1 significantly inhibited DMM‐induced experimental OA. DMM‐induced OA was also significantly inhibited in Col2a1‐Dkk1–transgenic mice compared with their wild‐type littermates. However, Col2a1‐Dkk2–transgenic mice showed no significant difference in OA pathogenesis. Wnt‐3a, which activates the canonical Wnt pathway, induced Mmp13 and Adamts4 expression in primary culture chondrocytes, an effect that was significantly inhibited by Dkk‐1 pretreatment or Dkk1 overexpression.

Conclusion

Our findings indicate that expression of Dkk1, but not Dkk2, in chondrocytes inhibits OA cartilage destruction. The protective effect of Dkk‐1 appears to be associated with its capacity to inhibit Wnt‐mediated expression of catabolic factors, such as Mmp13, providing evidence that Dkk‐1 might serve as a therapeutic target for OA treatment.
Antiinflammatory functions of p38 in mouse models of rheumatoid arthritis: Advantages of targeting upstream kinases MKK‐3 or MKK‐6
Authors: Guma Monica , Hammaker Deepa , Topolewski Katharyn , Corr Maripat , Boyle David L. , Karin Michael , Firestein Gary S.
Published: April 2012

Objective

Inhibitors of p38 demonstrate limited benefit in rheumatoid arthritis (RA), perhaps due to the antiinflammatory functions of p38α. This study was performed to determine if selective deletion of p38α in macrophages affects the severity of arthritis and whether blocking upstream kinases in the p38 pathway, such as MKK‐3 or MKK‐6, avoids some of the limitations of p38 blockade.

Methods

Wild‐type (WT) mice and mice with selective deletion of p38α in macrophages (p38αΔLysM) were injected with K/BxN sera. Antigen‐induced arthritis was also induced in p38αΔLysM mice. Mouse joint extracts were evaluated by enzyme‐linked immunosorbent assay, quantitative polymerase chain reaction (qPCR), and Western blot analysis. Bone marrow–derived macrophages (BMMs) were stimulated with lipopolysaccharide (LPS) and were evaluated by qPCR and Western blotting. Bone marrow chimeras were generated using MKK‐3−/− and MKK‐6−/− mice, and K/BxN serum was administered to induce arthritis.

Results

Compared to WT mice, p38αΔLysM mice had increased disease severity and delayed resolution of arthritis, which correlated with higher synovial inflammatory mediator expression and ERK phosphorylation. In contrast to WT BMMs cultured in the presence of a p38α/β inhibitor, LPS‐stimulated MKK‐6– and MKK‐3–deficient BMMs had suppressed LPS‐mediated interleukin‐6 (IL‐6) expression but had normal IL‐10 production, dual‐specificity phosphatase 1 expression, and MAPK phosphorylation. WT chimeric mice with MKK‐6– and MKK‐3–deficient bone marrow had markedly decreased passive K/BxN arthritis severity.

Conclusion

Inhibiting p38α in a disease that is dominated by macrophage cytokines, such as RA, could paradoxically suppress antiinflammatory functions and interfere with clinical efficacy. Targeting an upstream kinase that regulates p38 could be more effective by suppressing proinflammatory cytokines while preventing decreased IL‐10 expression and increased MAPK activation.
An examination of multisession web tasks
Authors: MacKay Bonnie , Watters Carolyn
Published: April 2012

Today, people perform many types of tasks on the web, including those that require multiple web sessions. In this article, we build on research about web tasks and present an in‐depth evaluation of the types of tasks people perform on the web over multiple web sessions. Multisession web tasks are goal‐based tasks that often contain subtasks requiring more than one web session to complete. We will detail the results of two longitudinal studies that we conducted to explore this topic. The first study was a weeklong web‐diary study where participants self‐reported information on their own multisession tasks. The second study was a monthlong field study where participants used a customized version of Firefox, which logged their interactions for both their own multisession tasks and their other web activity. The results from both studies found that people perform eight different types of multisession tasks, that these tasks often consist of several subtasks, that these lasted different lengths of time, and that users have unique strategies to help continue the tasks which involved a variety of web and browser tools such as search engines and bookmarks and external applications such as Notepad or Word. Using the results from these studies, we have suggested three guidelines for developers to consider when designing browser‐tool features to help people perform these types of tasks: (a) to maintain a list of current multisession tasks, (b) to support multitasking, and (c) to manage task‐related information between sessions.
Synthesis of Optically Pure Norcantharidin Analogue NCA‐01, a Highly Selective Protein Phosphatase 2B Inhibitor, and its Derivatives
Authors: Shimizu Tadashi , Iizuka Masato , Matsukura Hiroko , Hashizume Daisuke , Sodeoka Mikiko
Published: April 2012

An efficient synthetic route to optically pure norcantharidin analogue NCA‐01, a highly selective inhibitor of protein phosphatase 2B (PP2B; calcineurin), has been developed. The absolute stereochemistry of the enantiomers was determined by X‐ray crystallographic analysis. Optically pure NCA derivatives that had various substituents at the C1 position were synthesized in a similar manner. The PP2B‐inhibitory activities of NCA‐01 and its derivatives were independent of the enantiomeric form. NCA‐01 dimethyl ester potently inhibited IL‐2 production in Jurkat cells.
Dietary zinc status reversibly alters both the feeding behaviors of the rats and gene expression patterns in diencephalon
Authors: Okada Shinji , Abuyama Moe , Yamamoto Ryo , Kondo Takashi , Narukawa Masataka , Misaka Takumi
Published: April 2012

Nutritional status influences feeding behaviors, food preferences, and taste sensations. For example, zinc‐deficient rats have been reported to show reduced and cyclic food intake patterns with increased preferences for NaCl. Although some impairments of the central nervous and endocrine systems have been speculated to be involved in these phenomena, the effects of short‐term zinc deficiency on the brain have not been well examined to date. In this study, we performed a comprehensive analysis of the gene expression patterns in the rat diencephalon, which is a portion of the brain that includes the hypothalamus and thalamus, after short‐term zinc deficiency and also during zinc recovery. The rats showed reduced and cyclic food intake patterns with increased salt preferences after a 10‐day dietary zinc deficiency. A comparative analysis of their diencephalons using cDNA microarrays revealed that approximately 1% of the genes expressed in the diencephalons showed significantly altered expression levels. On the other hand, a 6‐day zinc supplementation following the deprivation allowed for the recovery to initial food intake behaviors and salt preferences. The expression levels of most of the genes that had been altered by exposure to zinc deficient conditions were also recovered. These results show that feeding behaviors, taste preferences and gene expression patterns in the diencephalon respond quickly to changing zinc levels.
Beneficial effect of (–)Schisandrin B against 3‐nitropropionic acid‐induced cell death in PC12 cells
Authors: Lam Philip Y. , Ko Kam Ming
Published: April 2012

Huntington's disease (HD) is characterized by the dysfunction of mitochondrial energy metabolism, which is associated with the functional impairment of succinate dehydrogenase (mitochondrial complex II), and pyruvate dehydrogenase (PDH). Treatment with 3‐nitropropionic acid (3‐NP), a potent irreversible inhibitor of succinate dehydrogenase, replicates most of the pathophysiological features of HD. In the present study, we investigated the effect of (–)schisandrin B [(–)Sch B, a potent enantiomer of schisandrin B] on 3‐NP‐induced cell injury in rat differentiated neuronal PC12 cells. The 3‐NP caused cell necrosis, as assessed by lactate dehydrogenase (LDH) leakage, and mitochondrion‐dependent cell apoptosis, as assessed by caspase‐3 and caspase‐9 activation, in differentiated PC12 cells. The cytotoxicity induced by 3‐NP was associated with a depletion of cellular reduced glutathione (GSH) as well as the activation of redox‐sensitive c‐Jun N‐terminal kinase (JNK) pathway and the inhibition of PDH. (‐)Sch B pretreatment (5 and 15 μM) significantly reduced the extent of necrotic and apoptotic cell death in 3‐NP‐challenged cells. The cytoprotection afforded by (–)Sch B pretreatment was associated with the attenuation of 3‐NP‐induced GSH depletion as well as JNK activation and PDH inhibition. (–)Sch B pretreatment enhanced cellular glutathione redox status and ameliorated the 3‐NP‐induced cellular energy crisis, presumably by suppressing the activated JNK‐mediated PDH inhibition, thereby protecting against necrotic and apoptotic cell death in differentiated PC12 cells.
Synthesis of Fragrance Ingredients by Tandem Hydroformylation‐Cyclization of Limonene Catalyzed by Rhodium Complexes and Pyridinium p‐Toluenesulphonate
Authors: Vieira Camila G. , de Freitas Marina C. , dos Santos Eduardo N. , Gusevskaya Elena V.
Published: April 2012

The rhodium‐catalyzed hydroformylation of limonene (1) in the presence of PPh3 or P(O‐o‐tBuPh)3 as auxiliary ligands and pyridinium p‐toluenesulfonate, as an acid co‐catalyst, gave two diasteroisomers of 4,8‐dimethyl‐bicyclo[3.3.1]non‐7‐en‐2‐ol (3) in nearly quantitative yield. Limonene is a cheap natural product obtained commercially from citrus fruits, in particular, as a sub‐product of the orange juice industry; whereas alcohol 3 is an expensive perfume ingredient. Alcohol 3 is formed through the hydroformylation of 1 giving a corresponding aldehyde (2) followed by the intramolecular carbonyl ene reaction resulting in cyclization of the aldehyde. The cyclization step is highly stereoselective with only one diasteroisomer of 3 being formed from each of two diasteroisomers of 2. The use of the P(O‐o‐tBuPh)3 ligand not only remarkably accelerates the hydroformylation step compared to the system with PPh3, but also increases significantly the cyclization activity of the catalytic system.
Ion Exchange Adsorption Studies of Miglitol in a Fixed Bed
Authors: Zhang J. , Zhang X. L. , Li H. , Zhao B.
Published: April 2012

The adsorption of miglitol on the D001 resin in a fixed bed was studied at different flow rates, temperatures, and height‐to‐diameter ratios (H/D). The exhaustion time decreased and the height of the mass transfer zone (HMTZ) increased with increasing flow rate. The surface area of the adsorbent increased with decreasing solution flow rate. Breakthrough curves at different flows were described by the Thomas, Yoon–Nelson, and Adams‐Bohart models. The rate constants for the kinetic models increased with increasing flow rate. The theoretical and experimental times required for 50 % adsorbate breakthrough slightly differed at varying flow rates. The change trend in the values of the maximum volumetric adsorption capacity was the same as that of the values at the maximum adsorption capacity of the D001 resin. The temperature did not obviously affect the breakthrough curves. The slope of the breakthrough curve decreased and the HMTZ increased with increasing H/D ratio. The adsorption capacities of the fixed bed for H/D = 7.6 and 0.7 were greater than that for H/D = 1.5.
ChemInform Abstract: The Effect of the N‐Mesityl Group in NHC‐Catalyzed Reactions.
Authors: Mahatthananchai Jessada , Bode Jeffrey W.
Published: April 2012

The majority of the NHC‐catalyzed reactions occurs more rapidly with N‐mesityl substituents, whereas less hindered derivatives such as N‐C6F5 are preferred for benzoin and Stetter type reactions.
ChemInform Abstract: Aromatic Hydroxyl Group — A Hydrogen Bonding Activator in Bifunctional Asymmetric Organocatalysis.
Authors: Chauhan Pankaj , Chimni Swapandeep Singh
Published: April 2012

Review: ca. 150 refs.
Knowledge Based Design of Piping and Instrumentation Diagrams
Authors: Uzuner Hülya , Schembecker Gerhard
Published: April 2012

Der Designprozess des Rohrleitungs‐ und Instrumentierungsfließbildes (R&I‐Fließbild), das aufgrund seiner auftragsspezifischen Unikaterstellung einen enormen Aufwand und hohe Kosten für jedes Chemieanlagenprojekt bedeutet, bietet ein erhebliches Einsparungspotenzial innerhalb des Planungsprozesses chemischer Anlagen. Der Beitrag thematisiert die Verkürzung von Projektdurchlaufzeiten durch Beschleunigung der Entwicklungsphase von R&I‐Fließbildern. Es wird ein modulbasierter Ansatz zur Erstellung wissensbasierter R&I‐Fließbilder in der frühen Basic‐Engineering‐Phase vorgestellt und gezeigt, wie eine verfahrenstechnische Anlage systematisch aus vorgefertigten, flexiblen Planungseinheiten rechnergestützt zusammengesetzt werden kann.
The dynamic role of bone morphogenetic proteins in neural stem cell fate and maturation
Authors: Bond Allison M. , Bhalala Oneil G. , Kessler John A.
Published: April 2012

The bone morphogenetic proteins (BMPs) are a group of powerful morphogens that are critical for development of the nervous system. The effects of BMP signaling on neural stem cells are myriad and dynamic, changing with each stage of development. During early development inhibition of BMP signaling differentiates neuroectoderm from ectoderm, and BMP signaling helps to specify neural crest. Thus modulation of BMP signaling underlies formation of both the central and peripheral nervous systems. BMPs secreted from dorsal structures then form a gradient which helps pattern the dorsal–ventral axis of the developing spinal cord and brain. During forebrain development BMPs sequentially induce neurogenesis and then astrogliogenesis and participate in neurite outgrowth from immature neurons. BMP signaling also plays a critical role in maintaining adult neural stem cell niches in the subventricular zone (SVZ) and subgranular zone (SGZ). BMPs are able to exert such diverse effects through closely regulated temporospatial expression and interaction with other signaling pathways. © 2012 Wiley Periodicals, Inc. Develop Neurobiol 72: 1068–1084, 2012
Rhodium‐Catalyzed Allylic Substitution Reactions with Indium(III) Organometallics
Authors: Riveiros Ricardo , Tato Rubén , Pérez Sestelo José , Sarandeses Luis A.
Published: April 2012

A novel rhodium‐catalyzed allylic substitution reaction using indium organometallics is reported. Aryl‐ and heteroarylindium reagents reacted in THF at 80 °C with primary and secondary allyl halides and their derivatives under rhodium(I) catalysis to afford the α‐substituted products in good yields and with high regio‐ and stereoselectivity. The reaction takes place with substoichiometric amounts of the triorganoindium reagents, which demonstrates the efficiency of the indium–rhodium transmetallation process in carbon–carbon bond‐forming reactions.
Interaction between the controls on fluvial system development: tectonics, climate, base level and river capture – Rio Alias, Southeast Spain
Authors: Whitfield (née Maher) Elizabeth , Harvey Adrian M.
Published: April 2012

Fluvial systems in uplifting terrain respond to tectonic, climatic, eustatic and local base‐level controls modified by specific local factors, such as river capture. The Rio Alias in southeast Spain is an ephemeral, transverse‐to‐structure fluvial system. The river drains two interconnected Neogene sedimentary basins, the Sorbas and Almeria basins, and crosses two major geological structures, the Sierras de Alhamilla/Cabrera and the Carboneras Fault Zone. Regional epeirogenic uplift resulted in sustained fluvial incision during the Quaternary, punctuated by major climatically driven periods of aggradation and dissection, which created a suite of five river terraces. The river terrace sequence was radically modified in the late Pleistocene by a major river capture (itself a response to regional tectonics), localized tectonic activity and eustatic base‐level change. The Rio Alias is defined by four reaches; within each the climatically‐generated, region‐wide, fluvial response was modified by tectonics, base‐level change or river capture to varying degrees. In the upper part of the basin (Lucainena reach), climate was the dominant control on river development, with limited modification of the sequence by uplift of the Sierra Alhamilla and local drainage reorganization by a local river capture. Downstream of the Sierra Alhamilla in the Polopus reach, the climatic signal is dominant, but its expression is radically modified by the response to a major river capture whereby the Alias system lost up to 70% of its pre‐capture drainage area. In the reach adjacent to the Carboneras Fault Zone (Argamason reach), modification of the terrace sequence by local tectonic activity and a resultant local base‐level fall led to a major local incisional event (propagating c. 3–4 km upstream from the area of tectonic disturbance). At the seaward end of the system (El Saltador reach) Quaternary sea‐level changes modified the patterns of erosion and incision and have resulted in steep incisional terrace profiles. The signals generated by regional tectonics and the Quaternary climate change can be identified throughout the basin but those generated by ongoing local tectonics, river capture and sea‐level change are spatially restricted and define the four reaches. The connectivity of the system from the headwaters to the coast decreased through time as incision progressed, resulting in changes in local coupling characteristics. Copyright © 2012 John Wiley & Sons, Ltd.