bluuebunny/crossref_metadata_2025 huggingface dataset:
Social and biophysical vulnerability of prehistoric societies to Rapid Climate Change
Authors: Clare Lee , Weninger Bernhard
Published: October 2011

Previous studies of the impact of Rapid Climate Change (RCC) on prehistoric com- munities have often been restricted in their explanatory power due to the lack of an appropriate analytical tool capable of combining palaeoclimate data with archaeological culture. In this paper, we seek to remedy this shortfall by introducing theoretical-methodological concepts adapted from modern vulnerability and risk studies. Using this approach, our focus shifts from climate proxies to prehistoric cultures themselves.
The archaeology of death: from ‘social personae’ to ‘relational personhood’
Authors: Budja Mihael
Published: October 2011

In order to understand rituals in the past, archaeology has long relied on theories and concepts developed in other disciplines. This paper presents concepts concerning burial practices and funeral rituals, ancestors, personhood, and individual and dividual identities.
The manipulation of death: a burial area at the Neolithic Settlement of Avgi, NW Greece
Authors: Stratouli Georgia , Triantaphyllou Sevi , Bekiaris Tasos , Katsikaridis Nikos
Published: October 2011

In the Neolithic of Northern Greece the disposal of the deceased is strongly related to the community of the living, and in most cases to the built environment. Burials often occur in close proximity to, or underneath ‘domestic’ structures. The constant association of dead ancestors with the living social environment may indicate a particular desire by Neolithic people to negotiate their past by incorporating it into their own present. This paper addresses such issues, based on new evidence from the Neolithic settlement of Avgi, NW Greece. A group of cremations were recently located inside ten small pots buried in an open space in the Neolithic village. The burials consisted of tiny amounts of heavily burnt human bones and, in two cases, were accompanied by carbonized seeds. This paper will discuss the occurrence of the burial pots and the associated cremations as tokens of memory and of special links to the past represented by the dead ancestors.
Modeling of on Shore Propagation of Random Water Waves
Authors: Fassieh K. M. , Fahmy O. , El-Shabrawy M. M. , Zaki M. A.
Published: October 2011

Two numerical models are investigated to model random water waves (RWWs) transformation due to mild depth variation. Modelling of steady on-shore propagation of small-amplitude RWWs is based on superposition principle of waves of different heights and directions. Each component is simulated through either the parabolic model (PM) or the elliptic model (EM). PM simulates weak refraction, diffraction, shoaling, and wave breaking. EM simulates strong refraction, diffraction, and shoaling. Both models neglect wave reflection. Comparison between PM and EM, in test cases that are experimentally measured, proved that both models give good results for unidirectional and narrow-directional RWW. However, EM is more accurate in modelling broad-directional RWWs.
Effects of Multicomponent Exercise Training on Physical Functioning among Institutionalized Elderly
Authors: Justine Maria , Hamid Tengku Aizan , Mohan Vikram , Jagannathan Madhanagopal
Published: October 2011

This quasiexperimental study aimed to measure the effects of 12-week multicomponent exercise training on physical functioning among institutionalized elderly. Forty-three participants (age = 70.88 ± 7.82 years) were self-assigned to an intervention (n=23) or control (n=20) group. Before and after training, cardiorespiratory endurance, arm curl strength, grip strength, lower limb strength, upper and lower limb flexibility, balance, and mobility were assessed. The training included aerobic, resistance, balance and flexibility exercises, performed 3 times per week. Significant increases (P<0.05) were observed in the exercise group on cardiorespiratory endurance (41.79%), right arm curl strength (25%), left arm curl strength (30.79%), right hand grip strength (13.65%), left hand grip strength (9.93%), lower limb strength (46.19%), balance (49.58%), and mobility (26.37%). Measures of flexibility in the exercise group also showed improvement (right lower limb (63.57%), left lower limb (44.17%), right upper limb (36.67%), and left upper limb (63.1%)) but were not statistically significant (all,P>0.05). The control group did not show any significant changes (P>0.05) in any variables. The data suggested that 12-week multicomponent exercise training may improve physical functioning among institutionalized elderly.
Art Education and the Emergence of Radical Art Movements in Egypt: The Surrealists and the Contemporary Arts Group, 1938–1951
Authors: KANE PATRICK
Published: October 2011

So it wasn’t the aim of the artist to just toss out a work of art. A tradition of the exhibition of the natural, and its meaning was not that it fled from life, but that it had penetrated and plunged into reality. Its meaning was not a prescription or plain exercise in the taste of the sublime, or harmony of forms and charming scenes; and its meaning was not as a decoration of life; it was in its expression of what life inspires in us to give back.

—Henry Moore, as quoted by Ramses Yunan, in “The Aim of the Contemporary Artist”1

In these crucial days of difficulty, the artists in this country live in tall aristocratic towers…. For this peasant has an art of his own that sustains him, and it is not that art of the educated class.

—Kamil Al-Tilmisani (c. 1941-1942)
Geographies of Desire: Postsocial Urban Space and Historical Revision in the Films of Martin Scorsese
Authors: HAENNI SABINE
Published: October 2011

I was stupid … New York meant freedom to me.

-Ellen Olenska in The Age of Innocence (1993)
La simulación basada en agentes: una nueva forma de explorar los fenómenos sociales
Authors: García-Valdecasas Medina Juan Ignacio
Published: October 2011

La simulación basada en agentes es un nuevo método de investigaciónque permite tratar de manera sencilla la complejidad, la emergencia y lano-linealidad típica de muchos fenómenos sociales. En este artículo definiremosla simulación basada en agentes —presentando sus distintasvariedades—, ilustrándola a partir de un ejemplo clásico: el modelo desegregación urbana de Schelling, que intenta explicar cómo es posibleque surjan guetos en ciudades cuyos habitantes no tienen prejuiciosétnicos. Finalmente, se consideran algunas de sus posibles aplicaciones:desarrollar, formalizar y evaluar teorías sociológicas; decidir entreteorías diferentes sobre un mismo fenómeno; integrar teorías en un mismomarco común; explicar dinámicas sociales a través de sus micromecanismos;realizar experimentos virtuales; evaluar políticas sociales ysus resultados a priori; y predecir algunos fenómenos sociales.
Trauma-associated hyperfibrinolysis
Authors: Voelckel W. , Maegele M. , Solomon C. , Schöchl H.
Published: October 2011

Trauma-induced coagulopathy (TIC) has been considered for a long time as being due to depletion of coagulation factors secondary to blood loss, dilution and consumption. Dysfunction of the remaining coagulation factors due to hypothermia and acidosis is assumed to additionally contribute to TIC. Recent data suggest that hyperfibrinolysis (HF) represents an additional important confounder to the disturbed coagulation process. Severe shock and major tissue trauma are the main drivers of this HF. The incidence of HF is still speculative. According to visco-elastic testing of trauma patients upon emergency room admission, HF is present in approximately 2.5–7% of all trauma patients. However, visco-elastic tests provide information on severe forms of HF only. Occult HF seems to be much more common but diagnosis is still challenging. Results from a recent randomized, placebo-controlled trial suggest that the early treatment of trauma patients with tranexamic acid may result in a significant reduction of trauma-associated mortality.
A Literature Review of Self Adjusting File
Authors: ADIGÜZEL Özkan
Published: October 2011

A primary aim of root canal treatment is to completely clean and shape the root canal system. Various instruments are available for endodontic instrumentation. Although rotary systems do prepare many canals without major procedural errors, they do not address canal types with long-oval or flat cross sections. A newly developed self-adjusting file (SAF) was designed to address the shortcomings of traditional rotary files by adjusting itself to the canal cross section. This instrument consists of a compressible opened NiTi tube that, on placement into a root canal, will exert pressure against the canal Wall. The SAF is used in an in-and-out motion powered by a handpiece and under constant irrigation. The aim of this review was to describe instrument design, usage parameters and features of Self Adjusting File.
How to cite this article: Adıgüzel Ö. A Literature Review of Self Adjusting File. Int Dent Res 2011;1:18-25.
Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.
Diagnosis and Treatment Modalities of Internal and External Cervical Root Resorptions: Review of the Literature with Case Reports
Authors: YİĞİT ÖZER Senem
Published: October 2011

The clinical presentation of internal and external cervical lesions vary considerably, and detection of lesions is often made incidentally. Accurate diagnosis is the most important step of the treatment plan because these pathologies are quite different from each other concerning their treatment procedures. This paper gives a literature review of internal and external root resorptions with respect of their etiology and addresses the difference in treatment modalities. 

How to cite this article: Yiğit Özer S. Diagnosis and Treatment Modalities of Internal and External Cervical Root Resorptions:  Review of the Literature with Case Reports Int Dent Res 2011;1:32-37.

Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.
Association of magnetic resonance imaging–based knee cartilage T2 measurements and focal knee lesions with knee pain: Data from the Osteoarthritis Initiative
Authors: Baum Thomas , Joseph Gabby B. , Arulanandan Ahilan , Nardo Lorenzo , Virayavanich Warapat , Carballido‐Gamio Julio , Nevitt Michael C. , Lynch John , McCulloch Charles E. , Link Thomas M.
Published: October 2011

Objective

To evaluate the association of magnetic resonance imaging (MRI)–based knee cartilage T2 measurements and focal knee lesions with knee pain in knees without radiographic osteoarthritis (OA) among subjects with OA risk factors.

Methods

We studied the right knees of 126 subjects from the Osteoarthritis Initiative database. We randomly selected 42 subjects ages 45–55 years with OA risk factors, right knee pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain score ≥5), no left knee pain (WOMAC pain score 0), and no radiographic OA (Kellgren/Lawrence [K/L] score ≤1) in the right knee. We also selected 2 comparison groups: 42 subjects without knee pain in either knee and 42 with bilateral knee pain. Both groups were frequency matched to subjects with right knee pain only by sex, age, body mass index, and K/L score. All of the subjects underwent 3T MRI of the right knee. Focal knee lesions were assessed and cartilage T2 measurements were performed.

Results

Prevalences of meniscal, bone marrow, and ligamentous lesions and joint effusion were not significantly different between the groups (P > 0.05), while cartilage lesions were more frequent in subjects with right knee pain only compared to subjects without knee pain (P < 0.05). T2 values averaged over all of the compartments were similar in subjects with right knee pain only (mean ± SD 34.4 ± 1.8 msec) and in subjects with bilateral knee pain (mean ± SD 34.7 ± 4.7 msec), but were significantly higher compared to subjects without knee pain (mean ± SD 32.4 ± 1.8 msec; P < 0.05).

Conclusion

These results suggest that elevated cartilage T2 values are associated with findings of pain in the early phase of OA, whereas among morphologic knee abnormalities only knee cartilage lesions are significantly associated with knee pain status.
Scleroderma digital ulcers complicated by infection with fecal pathogens
Authors: Giuggioli Dilia , Manfredi Andreina , Colaci Michele , Lumetti Federica , Ferri Clodoveo
Published: October 2011

Objective

Digital ulcers represent one of the most frequent complications of systemic sclerosis (SSc; scleroderma); they are very painful, scarcely responsive to treatment, and often responsible for marked limitations on daily activities, including patient self‐care. Infectious complications may severely compromise the outcome of skin lesions in a significant percentage of patients. Numerous pathogens of different origin may be involved, including bacteria from patient endogenous flora. Here we evaluated the possible involvement of fecal pathogens in scleroderma digital ulcers.

Methods

Among a series of 82 SSc patients with digital ulcers, we retrospectively analyzed 42 subjects with clinical signs of local bacterial infection. All digital ulcers with suspected infection have been investigated by microbiologic examinations.

Results

Bacterial infection was confirmed in all 42 patients investigated; in particular, Staphylococcus aureus were the most frequently found (50%). Interestingly, 11 (26%) of 42 patients showed digital ulcers infected with intestinal bacteria; specifically, 7 patients were positive for Escherichia coli and 4 for Enterococcus faecalis. Diffuse cutaneous SSc patients were more numerous in this subgroup versus the other 31 patients (Fisher's P = 0.011).

Conclusion

A number of effective measures involving health care personnel and hospital environment are essential in the management of digital ulcers and prevention of infectious complications. In addition, the prevalence of fecal pathogens in one‐quarter of cases, never reported previously, suggests an important role of a patient's self‐care limitations, mainly during intercurrent home medications. Consequently, methodical education on hand hygiene of both patients and relatives, frequently involved in ulcer medications, is mandatory to avoid such deleterious complications.
Use of disease‐modifying medications for rheumatoid arthritis by race and ethnicity in the National Ambulatory Medical Care Survey
Authors: Solomon Daniel H. , Ayanian John Z. , Yelin Ed , Shaykevich Tamara , Brookhart M. Alan , Katz Jeffrey N.
Published: October 2011

Objective

Disease‐modifying antirheumatic drugs (DMARDs) are recommended for virtually all patients with rheumatoid arthritis (RA). We investigated the use of DMARDs in patients with RA in a nationally representative sample of visits to US physicians in the National Ambulatory Care Medical Survey (NAMCS).

Methods

We analyzed the NAMCS visit data from 1996 through 2007 if the physician noted a diagnosis of RA. DMARD utilization was based on the medications listed by the physician. We used generalized linear models to examine the adjusted associations between DMARD use and potential predictors.

Results

Of the 859 visits with a diagnosis code of RA identified over the study period, 404 visits (47%; 95% confidence interval [95% CI] 44–50%) had an associated DMARD. The percentage of RA visits with DMARDs increased slightly over the 12 years (P = 0.048), with biologic DMARDs increasing to 20% of visits after their introduction (P for trend <0.001). In fully adjusted models, African American race was associated with a 30% reduction in DMARD prescribing (risk ratio [RR] 0.70, 95% CI 0.48–1.00). A visit to a rheumatologist was the strongest correlate of DMARD prescribing (RR 2.33, 95% CI 1.89–2.86). Among visits to nonrheumatologists, African Americans were significantly less likely than whites to receive a DMARD (RR 0.39, 95% CI 0.17–0.92), but not among visits with rheumatologists (RR 0.81, 95% CI 0.52–1.27).

Conclusion

In the NAMCS, most visits coded with RA did not have an associated DMARD prescription. African Americans were less likely to receive DMARDs than whites, particularly when visiting nonrheumatologists.
Work productivity in scleroderma: Analysis from the University of California, Los Angeles scleroderma quality of life study
Authors: Singh Manjit K. , Clements Philip J. , Furst Daniel E. , Maranian Paul , Khanna Dinesh
Published: October 2011

Objective

To examine the productivity of patients with scleroderma (systemic sclerosis [SSc]) both outside of and within the home in a large observational cohort.

Methods

One hundred sixty‐two patients completed the Work Productivity Survey. Patients indicated whether or not they were employed outside of the home, how many days per month they missed work (employment or household work) due to SSc, and how many days per month productivity was decreased by ≥50%. Patients also completed other patient‐reported outcome measures. We developed binomial regression models to assess the predictors of days missed from work (paid employment or household activities). The covariates included: type of SSc, education, physician and patient global assessments, Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy–Fatigue, and Center of Epidemiologic Studies Depression Scale Short Form.

Results

The mean age of patients was 51.8 years and 52% had limited cutaneous SSc. Of the 37% of patients employed outside of the home, patients reported missing 2.6 days per month of work and had 2.5 days per month of productivity reduced by half. Of the 102 patients who were not employed, 39.4% were unable to work due to their SSc. When we assessed patients for household activities (n = 162), patients missed an average of 8 days of housework per month and had productivity reduced by an average of 6 days per month. In the regression models, patients with lower education and poor assessment of overall health by a physician were more likely to miss work outside of the home. Patients with limited cutaneous SSc and high HAQ DI scores were more likely to miss work at home.

Conclusion

SSc has a major impact on productivity at home and at work. Nearly 40% of patients reported disability due to their SSc.
Mesoporous Silicon‐PLGA Composite Microspheres for the Double Controlled Release of Biomolecules for Orthopedic Tissue Engineering
Authors: Fan Dongmei , De Rosa Enrica , Murphy Matthew B. , Peng Yang , Smid Christine A. , Chiappini Ciro , Liu Xuewu , Simmons Paul , Weiner Bradley K. , Ferrari Mauro , Tasciotti Ennio
Published: October 2011

In this study, poly(dl‐lactide‐co‐glycolide)/porous silicon (PLGA/pSi) composite microspheres, synthesized by a solid‐in‐oil‐in‐water (S/O/W) emulsion method, are developed for the long‐term controlled delivery of biomolecules for orthopedic tissue engineering applications. Confocal and fluorescent microscopy, together with material analysis, show that each composite microsphere contained multiple pSi particles embedded within the PLGA matrix. The release profiles of fluorescein isothiocyanate (FITC)‐labeled bovine serum albumin (FITC‐BSA), loaded inside the pSi within the PLGA matrix, indicate that both PLGA and pSi contribute to the control of the release rate of the payload. Protein stability studies show that PLGA/pSi composite can protect BSA from degradation during the long term release. We find that during the degradation of the composite material, the presence of the pSi particles neutralizes the acidic pH due to the PLGA degradation by‐products, thus minimizing the risk of inducing inflammatory responses in the exposed cells while stimulating the mineralization in osteogenic growth media. Confocal studies show that the cellular uptake of the composite microspheres is avoided, while the fluorescent payload is detectable intracellularly after 7 days of co‐incubation. In conclusion, the PLGA/pSi composite microspheres offer an additional level of controlled release and could be ideal candidates as drug delivery vehicles for orthopedic tissue engineering applications.
Quantitative Analysis of Bulk Heterojunction Films Using Linear Absorption Spectroscopy and Solar Cell Performance
Authors: Turner Sarah T. , Pingel Patrick , Steyrleuthner Robert , Crossland Edward J. W. , Ludwigs Sabine , Neher Dieter
Published: October 2011

A fundamental understanding of the relationship between the bulk morphology and device performance is required for the further development of bulk heterojunction organic solar cells. Here, non‐optimized (chloroform cast) and nearly optimized (solvent‐annealed o‐dichlorobenzene cast) P3HT:PCBM blend films treated over a range of annealing temperatures are studied via optical and photovoltaic device measurements. Parameters related to the P3HT aggregate morphology in the blend are obtained through a recently established analytical model developed by F. C. Spano for the absorption of weakly interacting H‐aggregates. Thermally induced changes are related to the glass transition range of the blend. In the chloroform prepared devices, the improvement in device efficiency upon annealing within the glass transition range can be attributed to the growth of P3HT aggregates, an overall increase in the percentage of chain crystallinity, and a concurrent increase in the hole mobilities. Films treated above the glass transition range show an increase in efficiency and fill factor not only associated with the change in chain crystallinity, but also with a decrease in the energetic disorder. On the other hand, the properties of the P3HT phase in the solvent‐annealed o‐dichlorobenzene cast blends are almost indistinguishable from those of the corresponding pristine P3HT layer and are only weakly affected by thermal annealing. Apparently, slow drying of the blend allows the P3HT chains to crystallize into large domains with low degrees of intra‐ and interchain disorder. This morphology appears to be most favorable for the efficient generation and extraction of charges.
Nonisocyanate polyurethane/silica hybrid coatings via a sol–gel route
Authors: Hosgor Z. , Kayaman‐Apohan N. , Karatas S. , Gungor A. , Menceloglu Y.
Published: October 2011

Polyurethane/silica hybrids by a nonisocyanate route were prepared by reacting cyclic carbonate‐modified bis(4‐glycidyloxy phenyl)phenyl phosphine oxide (BGPPO), and poly(propyleneglycol)diglycidyl ether (PPG‐DGE) with hexamethylene diamine. The incorporation of silica was achieved via a sol–gel method. The effect of silica and phosphine oxide moiety on polyurethane coating properties was studied by physical, mechanical, and thermal tests. Modulus and hardness of the coatings were enhanced by increasing the amount of silica and phosphine oxide based resin. The improvement in flame retardancy and thermal stability of nanocomposites was proved with increased char yield values and decomposition temperatures in thermogravimetric analyses. © 2011 Wiley Periodicals, Inc. Adv Polym Techn 31: 390–400, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.20262
Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate
Authors: Li Ling , Zhu Gui‐quan , Meng Tian , Shi Jia‐yu , Wu Jun , Xu Xue , Shi Bing
Published: October 2011

The noncoding SNP rs7205289, located in the microRNA‐140 gene has been associated with cleft palate risk. MiR‐140 was found to regulate zebrafish palatal development in vivo and its expression level be reduced by environmental smoke exposure in vitro. Therefore, we sought to investigate whether the A allele of rs7205289 and maternal smoke exposure during the first trimester might contribute to cleft palate risk by regulating microRNA‐140. We used in situ hybridization to explore the microRNA‐140 expression pattern. A luciferase reporting system and Western blot were used to validate the target of microRNA‐140. Mouse palatal mesenchymal cells (MPMC) were transfected with microRNA‐140 expression vectors, or treated with cigarette smoke extract. In addition, we performed a hospital‐based case–control study in 169 patients with nonsyndromic cleft palate and 306 unaffected controls. We demonstrated microRNA‐140 expression in mouse palatal shelves from embryonic days 12 to 15. Pdgfrα was the target of microRNA‐140 in MPMC. When these cells were transfected with the minor allele vector or exposed to cigarette smoke extract, they showed a decrease in microRNA‐140 expression. Epidemiological analyses showed that infants with CA/AA genotypes and exposed to maternal passive smoking during pregnancy had evidence of synergistic interaction in contributing to cleft palate risk. We concluded that infants with CA/AA genotypes at rs7205289 and maternal passive smoking during the first trimester may synergistically contribute to cleft palate risk by decreasing microRNA‐140 during palatal development. © 2011 Wiley Periodicals, Inc.
Origins of electromagnetic hypersensitivity to 60 Hz magnetic fields: A provocation study
Authors: Kim Deok Won , Choi Jae Lim , Nam Ki Chang , Yang Dong In , Kwon Min Kyung
Published: October 2011

With increasing electrical device usage, social concerns about the possible effects of 60 Hz electromagnetic fields on human health have increased. The number of people with self‐attributed electromagnetic hypersensitivity (EHS) who complain of various subjective symptoms such as headache and insomnia has also increased. However, it is unclear whether EHS results from physiological or other origins. In this double‐blinded study, we simultaneously investigated physiological changes (heart rate, respiration rate, and heart rate variability), subjective symptoms, and perception of the magnetic field to assess origins of the subjective symptoms. Two volunteer groups of 15 self‐reported EHS and 16 non‐EHS individuals were tested with exposure to sham and real (60 Hz, 12.5 µT) magnetic fields for 30 min. Magnetic field exposure did not have any effects on physiological parameters or eight subjective symptoms in either group. There was also no evidence that the EHS group perceived the magnetic field better than the non‐EHS group. In conclusion, the subjective symptoms did not result from the 60 Hz, 12.5 µT magnetic field exposures but from other non‐physiological factors. Bioelectromagnetics 33:326–333, 2012. © 2011 Wiley Periodicals, Inc.
Complex permittivity of representative biological solutions in the 2–67 GHz range
Authors: Zhadobov Maxim , Augustine Robin , Sauleau Ronan , Alekseev Stanislav , Di Paola Alessandra , Le Quément Catherine , Mahamoud Yonis Soubere , Le Dréan Yves
Published: October 2011

The main purpose of this study is to provide experimental data on the complex permittivity of some biological solutions in the 2–67 GHz range at room and human body temperatures. The permittivity measurements are performed using an open‐ended coaxial probe. Permittivity spectra of several representative monomolecular solutions of proteins, amino acids, nucleic acids, and carbohydrates are analyzed and compared. Furthermore, measurements have also been performed for complex biomolecular solutions, including bovine serum albumin (BSA)–DNA–glucose mixture, culture medium, and yeast extract solution. The results demonstrate that for concentrations below 1%, the permittivity spectra of the solutions do not substantially differ from that of distilled water. Measurements carried out for 4% and 20% BSA solutions show that the presence of proteins results in a decrease in permittivity. For highly concentrated RNA solutions (3%), a slight increase in the imaginary part of the permittivity is observed below 10 GHz. Experimental data show that free water permittivity can be used for modeling of the culture medium above 10 GHz. However, at lower frequencies a substantial increase in the imaginary part of the permittivity due to ionic conductivity should be carefully taken into account. A similar increase has also been observed for the yeast extract solution in the lower frequency region of the considered spectrum. Above 10 GHz, the high concentration of proteins and other low‐permittivity components of the yeast extract solution results in a decrease in the complex permittivity compared to that of water. Obtained data are of utmost importance for millimeter‐wave dosimetry studies. Bioelectromagnetics 33:346–355, 2012. © 2011 Wiley Periodicals, Inc.
Mitochondrial dysfunction and Down's syndrome: Is there a role for coenzyme Q10?
Authors: Tiano Luca , Busciglio Jorge
Published: October 2011

Structural changes and abnormal function of mitochondria have been documented in Down's syndrome (DS) cells, patients, and animal models. DS cells in culture exhibit a wide array of functional mitochondrial abnormalities including reduced mitochondrial membrane potential, reduced ATP production, and decreased oxido‐reductase activity. New research has also brought to central stage the prominent role of oxidative stress in this condition. This review focuses on recent advances in the field with a particular emphasis on novel translational approaches involving the utilization of coenzyme Q10 (CoQ10) to treat a variety of clinical phenotypes associated with DS that are linked to increased oxidative stress and energy deficits. CoQ10 has already provided promising results in several different conditions associated with altered energy metabolism and oxidative stress in the CNS. Two studies conducted in Ancona investigated the effect of CoQ10 treatment on DNA damage in DS patients. Although the effect of CoQ10 was evidenced only at single cell level, the treatment affected the distribution of cells according to their content in oxidized bases. In fact, it produced a strong negative correlation linking cellular CoQ10 content and the amount of oxidized purines. Results suggest that the effect of CoQ10 treatment in DS not only reflects antioxidant efficacy, but likely modulates DNA repair mechanisms.
Albumin handling by renal tubular epithelial cells in a microfluidic bioreactor
Authors: Ferrell Nicholas , Ricci Kevin B. , Groszek Joseph , Marmerstein Joseph T. , Fissell William H.
Published: October 2011

Epithelial cells in the proximal tubule of the kidney reclaim and metabolize protein from the glomerular filtrate. Proteinuria, an overabundance of protein in the urine, affects tubular cell function and is a major factor in the progression of chronic kidney disease. By developing experimental systems to study tubular protein handling in a setting that simulates some of the environmental conditions of the kidney tubule in vivo, we can better understand how microenviromental conditions affect cellular protein handling to determine if these conditions are relevant in disease. To this end, we used two in vitro microfluidic models to evaluate albumin handling by renal proximal tubule cells. For the first system, cells were grown in a microfluidic channel and perfused with physiological levels of shear stress to evaluate the effect of mechanical stress on protein uptake. In the second system, a porous membrane was used to separate an apical and basolateral compartment to evaluate the fate of protein following cellular metabolism. Opossum kidney (OK) epithelial cells were exposed to fluorescently labeled albumin, and cellular uptake was determined by measuring the fluorescence of cell lysates. Confocal fluorescence microscopy was used to compare uptake in cells grown under flow and static conditions. Albumin processed by the cells was examined by size exclusion chromatography (SEC) and SDS–PAGE. Results showed that cellular uptake and/or degradation was significantly increased in cells exposed to flow compared to static conditions. This was confirmed by confocal microscopy. Size exclusion chromatography and SDS–PAGE showed that albumin was broken down into small molecular weight fragments and excreted by the cells. No trace of intact albumin was detectable by either SEC or SDS–PAGE. These results indicate that fluid shear stress is an important factor mediating cellular protein handling, and the microfluidic bioreactor provides a novel tool to investigate this process. Biotechnol. Bioeng. 2012; 109:797–803. © 2011 Wiley Periodicals, Inc.
Removal versus fragmentation of amyloid‐forming precursors via membrane filtration
Authors: Posada David , Tessier Peter M. , Hirsa Amir H.
Published: October 2011

The presence of even minute amounts of protein aggregates in solution can significantly alter the kinetics of amyloid formation. Removal of such pre‐existing aggregates is critical for reproducible analysis of amyloid formation. Here we examine the effects of membrane filtration on insulin fibrillization. We find that filtration of insulin with large pore membranes (≥100 nm) generally slows fibril formation relative to unfiltered solutions by removing pre‐aggregated protein. Unexpectedly, filtration with small pore membranes (<100 nm) showed no beneficial effect and, in some cases, accelerated insulin fibril formation. This effect may be due to fragmentation of pre‐existing aggregates during filtration through small pore membranes, which can increase the number of amyloid‐forming precursors. These findings reveal the complexity of removing protein aggregates via filtration and suggest optimal filtration protocols for conducting fibril formation analysis of insulin and similar amyloidogenic proteins. Biotechnol. Bioeng. 2012; 109:840–845. © 2011 Wiley Periodicals, Inc.
Preventing spontaneous genetic rearrangements in the transgene cassettes of adenovirus vectors
Authors: Cottingham Matthew G. , Carroll Fionnadh , Morris Susan J. , Turner Alison V. , Vaughan Aisling M. , Kapulu Melissa C. , Colloca Stefano , Siani Loredana , Gilbert Sarah C. , Hill Adrian V.S.
Published: October 2011

First‐generation, E1/E3‐deleted adenoviral vectors with diverse transgenes are produced routinely in laboratories worldwide for development of novel prophylactics and therapies for a variety of applications, including candidate vaccines against important infectious diseases, such as HIV/AIDS, tuberculosis, and malaria. Here, we show, for two different transgenes (both encoding malarial antigens) inserted at the E1 locus, that rare viruses containing a transgene‐inactivating mutation exhibit a selective growth advantage during propagation in E1‐complementing HEK293 cells, such that they rapidly become the major or sole species in the viral population. For one of these transgenes, we demonstrate that viral yield and cytopathic effect are enhanced by repression of transgene expression in the producer cell line, using the tetracycline repressor system. In addition to these transgene‐inactivating mutations, one of which occurred during propagation of the pre‐viral genomic clone in bacteria, and the other after viral reconstitution in HEK293 cells, we describe two other types of mutation, a small deletion and a gross rearranging duplication, in one of the transgenes studied. These were of uncertain origin, and the effects on transgene expression and viral growth were not fully characterized. We demonstrate that, together with minor protocol modifications, repression of transgene expression in HEK293 cells during viral propagation enables production of a genetically stable chimpanzee adenovirus vector expressing a malarial antigen which had previously been impossible to derive. These results have important implications for basic and pre‐clinical studies using adenoviral vectors and for derivation of adenoviral vector products destined for large‐scale amplification during biomanufacture. Biotechnol. Bioeng. 2012; 109:719–728. © 2011 Wiley Periodicals, Inc.
Collisional fragmentation of central carbon metabolites in LC‐MS/MS increases precision of 13C metabolic flux analysis
Authors: Rühl Martin , Rupp Beat , Nöh Katharina , Wiechert Wolfgang , Sauer Uwe , Zamboni Nicola
Published: October 2011

Experimental determination of fluxes by 13C‐tracers relies on detection of 13C‐patterns in metabolites or by‐products. In the field of 13C metabolic flux analysis, the most recent developments point toward recording labeling patterns by liquid chromatography (LC)‐mass spectrometry (MS)/MS directly in intermediates in central carbon metabolism (CCM) to increase temporal resolution. Surprisingly, the flux studies published so far with LC‐MS measurements were based on intact metabolic intermediates—thus neglected the potential benefits of using positional information to improve flux estimation. For the first time, we exploit collisional fragmentation to obtain more fine‐grained 13C‐data on intermediates of CCM and investigate their impact in 13C metabolic flux analysis. For the case study of Bacillus subtilis grown in mineral medium with 13C‐labeled glucose, we compare the flux estimates obtained by iterative isotopologue balancing of 13C‐data obtained either by LC‐MS/MS for solely intact intermediates or LC‐MS/MS for intact and fragmented intermediates of CCM. We show that with LC‐MS/MS data, fragment information leads to more precise estimates of fluxes in pentose phosphate pathway, glycolysis, and to the tricarboxylic acid cycle. Additionally, we present an efficient analytical strategy to rapidly acquire large sets of 13C‐patterns by tandem MS, and an in‐depth analysis of the collisional fragmentation of primary intermediates. In the future, this catalogue will enable comprehensive in silico calculability analyses to identify the most sensitive measurements and direct experimental design. Biotechnol. Bioeng. 2012; 109:763–771. © 2011 Wiley Periodicals, Inc.
Effect of various factors on ethanol yields from lignocellulosic biomass by Thermoanaerobacterium AK17
Authors: Almarsdottir Arnheidur Ran , Sigurbjornsdottir Margret Audur , Orlygsson Johann
Published: October 2011

The ethanol production capacity from sugars and lignocellulosic biomass hydrolysates (HL) by Thermoanaerobacterium strain AK17 was studied in batch cultures. The strain converts various carbohydrates to, acetate, ethanol, hydrogen, and carbon dioxide. Ethanol yields on glucose and xylose were 1.5 and 1.1 mol/mol sugars, respectively. Increased initial glucose concentration inhibited glucose degradation and end product formation leveled off at 30 mM concentrations. Ethanol production from 5 g L−1 of complex biomass HL (grass, hemp, wheat straw, newspaper, and cellulose) (Whatman paper) pretreated with acid (0.50% H2SO4), base (0.50% NaOH), and without acid/base (control) and the enzymes Celluclast® and Novozyme 188 (0.1 mL g−1 dw; 70 and 25 U g−1 of Celluclast and Novozyme 188, respectively) was investigated. Highest ethanol yields (43.0 mM) were obtained on cellulose but lowest on hemp leafs (3.6 mM). Chemical pretreatment increased ethanol yields substantially from lignocellulosic biomass but not from cellulose. The influence of various factors (HL, enzyme, and acid/alkaline concentrations) on end‐product formation from 5 g L−1 of grass and cellulose was further studied to optimize ethanol production. Highest ethanol yields (5.5 and 8.6 mM ethanol g−1 grass and cellulose, respectively) were obtained at very low HL concentrations (2.5 g L−1); with 0.25% acid/alkali (v/v) and 0.1 mL g−1 enzyme concentrations. Inhibitory effects of furfural and hydroxymethylfurfural during glucose fermentation, revealed a total inhibition in end product formation from glucose at 4 and 6 g L−1, respectively. Biotechnol. Bioeng. 2012; 109:686–694. © 2011 Wiley Periodicals, Inc.
Construction of BAC‐based physical map and analysis of chromosome rearrangement in chinese hamster ovary cell lines
Authors: Cao Yihua , Kimura Shuichi , Itoi Takayuki , Honda Kohsuke , Ohtake Hisao , Omasa Takeshi
Published: October 2011

Chinese hamster ovary (CHO) cells have frequently been used in biotechnology for many years as a mammalian host cell platform for cloning and expressing genes of interest. A detailed physical chromosomal map of the CHO DG44 cell line was constructed by fluorescence in situ hybridization (FISH) imaging using randomly selected 303 BAC clones as hybridization probes (BAC‐FISH). The two longest chromosomes were completely paired chromosomes; other chromosomes were partly deleted or rearranged. The end sequences of 624 BAC clones, including 287 mapped BAC clones, were analyzed and 1,119 informative BAC end sequences were obtained. Among 303 mapped BAC clones, 185 clones were used for BAC‐FISH analysis of CHO K1 chromosomes and 94 clones for primary Chinese hamster lung cells. Based on this constructed physical map and end sequences, the chromosome rearrangements between CHO DG44, CHO K1, and primary Chinese hamster cells were investigated. Among 20 CHO chromosomes, eight were conserved without large rearrangement in CHO DG44, CHO K1, and primary Chinese hamster cells. This result suggested that these chromosomes were stable and essential in CHO cells and supposedly conserved in other CHO cell lines. Biotechnol. Bioeng. 2012; 109:1357–1367. © 2011 Wiley Periodicals, Inc.
Rapid determination of syringyl: Guaiacyl ratios using FT‐Raman spectroscopy
Authors: Sun Lan , Varanasi Patanjali , Yang Fan , Loqué Dominique , Simmons Blake A. , Singh Seema
Published: October 2011

Lignin composition in relation to its basic phenylpropanoid units, particularly the syringyl to guaiacyl (S/G) ratio, is an important property for biomass characterization and varies greatly as a function of species, genotype and environment. A rapid screening method is highly desirable to assess lignin composition in a large number of samples. We have developed a nondestructive and label‐free Fourier transform Raman (FT‐Raman) spectroscopic method that is capable of rapidly and reliably measuring the S/G ratio with minimal sample preparation. A variety of feedstocks, including hardwood (Eucalyptus globulus), softwood (Pinus radiata), herbaceous plants (Zea mays, Panicum virgatum, and Sorghum bicolor), and a model dicot (Arabidopsis thaliana) were measured using this technique and the corresponding S/G ratio was calculated after spectral deconvolution based on the S and G bands identified using a known library of model compounds. The results obtained using this technique were successfully validated by pyrolysis‐gas chromatography/mass spectrometry (pyro‐GC/MS). This technique holds significant promise in the rapid screening of engineered feedstocks as part of a comprehensive screening methodology that is correlated with biomass recalcitrance. Biotechnol. Bioeng. 2012; 109:647–656. © 2011 Wiley Periodicals, Inc.
Value of hepatic venous pressure gradient measurement before liver resection for hepatocellular carcinoma
Authors: Stremitzer S , Tamandl D , Kaczirek K , Maresch J , Abbasov B , Payer B A , Ferlitsch A , Gruenberger T
Published: October 2011

Background

Portal hypertension associated with liver cirrhosis increases the risk of postoperative complications after liver resection for hepatocellular carcinoma (HCC). This study assessed the role of preoperative hepatic venous pressure gradient (HVPG) assessment in identifying portal hypertension.

Methods

All patients who underwent liver resection for HCC between January 2000 and December 2009 at the Department of General Surgery, Medical University Vienna, were analysed retrospectively. HVPG was assessed prospectively in a subset of patients before liver resection. The influence of this assessment on postoperative complications was investigated.

Results

A total of 132 patients were enrolled, of whom 39 underwent HVPG measurement. Mean(s.d.) HVPG was 6·4(3·0) and 4·3(1·4) mmHg in patients with and without postoperative complications respectively (P = 0·028). Complication rates differed significantly at a cut-off HVPG value of 5 mmHg: 11 of 21 patients with a gradient of 1–5 mmHg developed complications versus 12 of 14 patients with a higher value (P = 0·045). HVPG exceeding 5 mmHg was associated with worse liver fibrosis (P = 0·004), higher rates of postoperative liver dysfunction (5 of 13 versus 1 of 18; P = 0·022) and ascites (7 of 14 versus 3 of 21; P = 0·022), and a longer hospital stay (median (range) 11 (7–26) versus 8 (4–20) days; P = 0·034). Overall postoperative morbidity did not differ between patients who had preoperative HVPG assessment and those who did not (P = 0·142).

Conclusion

Preoperative HVPG assessment predicted liver fibrosis and postoperative complications.
Mixed handedness is associated with greater age‐related decline in volumes of the hippocampus and amygdala: the PATH through life study
Authors: Cherbuin Nicolas , Sachdev Perminder S. , Anstey Kaarin J.
Published: October 2011

Handedness has been found to be associated with structural and functional cerebral differences. Left handedness and mixed handedness also appear to be associated with an elevated risk of some developmental and immunological disorders that may contribute to pathological processes developing in ageing. Inconsistent reports show that left handedness may be more prevalent in early‐onset as well as late‐onset Alzheimer's disease, but might also be associated with slower decline. Such inconsistencies may be due to handedness being usually modeled as a binary construct while substantial evidence suggests it to be a continuous trait. The aim of this study was to investigate the relationship between brain structures known to be implicated in pathological ageing and strength and direction of handedness. The association between handedness and hippocampal and amygdalar atrophy was investigated in 327 cognitively healthy older individuals. Handedness was measured with the Edinburgh Inventory. Two measures were computed from this index, one reflecting the direction (left = 0/right = 1) and the other the degree of handedness (ranging from 0 to 1). Hippocampal and amygdalar volumes were manually traced on scans acquired 4 years apart. Regression analyses were used to assess the relationship between strength and direction of handedness and incident hippocampal and amygdalar atrophy. Analyses showed that strength but not direction of handedness was a significant predictor of hippocampal (Left: beta = 0.118, P= 0.013; Right: beta = 0.116, P= 0.010) and amygdalar (Right: beta = 0.105, P= 0.040) atrophy. The present findings suggest that mixed but not left handedness is associated with greater hippocampal and amygdalar atrophy. This effect may be due to genetic, environmental, or behavioural differences that will need further investigation in future studies.
NMR Spectroscopic Investigations of the Activated p38α Mitogen‐Activated Protein Kinase
Authors: Nielsen Gerd , Schwalbe Harald
Published: October 2011

Phosphorylation of protein kinases is a central mechanism involved in numerous cellular regulatory circuits, both in prokaryotic and eukaryotic cells. An understanding of the structural and functional consequences of protein phosphorylation is of considerable importance for the design of selective, small‐molecule kinase inhibitors. NMR spectroscopy is a central method to support structure‐based drug design. Here, we present the NMR assignment of the activated p38α kinase and compare it to the NMR assignment of unphosphorylated p38α. Conformational changes in solution induced by activation can be located to the activation loop, an adjacent loop, and an insert part of the polypeptide chain that is specific for the family of mitogen‐activated kinases. Deuterium‐exchange experiments additionally revealed differences in exchange behavior for two residues in an alanine‐rich helix–loop motif that becomes more flexible upon binding of an ATP analogue and a substrate peptide.