bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural analysis of dihydrofolate reductases enables rationalization of antifolate binding affinities and suggests repurposing possibilities
Authors: Bhosle Amrisha , Chandra Nagasuma
Published: January 2016

Antifolates are competitive inhibitors of dihydrofolate reductase (DHFR), a conserved enzyme that is central to metabolism and widely targeted in pathogenic diseases, cancer and autoimmune disorders. Although most clinically used antifolates are known to be target specific, some display a fair degree of cross‐reactivity with DHFRs from other species. A method that enables identification of determinants of affinity and specificity in target DHFRs from different species and provides guidelines for the design of antifolates is currently lacking. To address this, we first captured the potential druggable space of a DHFR in a substructure called the ‘supersite’ and classified supersites of DHFRs from 56 species into 16 ‘site‐types’ based on pairwise structural similarity. Analysis of supersites across these site‐types revealed that DHFRs exhibit varying extents of dissimilarity at structurally equivalent positions in and around the binding site. We were able to explain the pattern of affinities towards chemically diverse antifolates exhibited by DHFRs of different site‐types based on these structural differences. We then generated an antifolate–DHFR network by mapping known high‐affinity antifolates to their respective supersites and used this to identify antifolates that can be repurposed based on similarity between supersites or antifolates. Thus, we identified 177 human‐specific and 458 pathogen‐specific antifolates, a large number of which are supported by available experimental data. Thus, in the light of the clinical importance of DHFR, we present a novel approach to identifying differences in the druggable space of DHFRs that can be utilized for rational design of antifolates.
Relationships between sarcopenia and household status and locomotive syndrome in a community‐dwelling elderly women in Japan
Authors: Momoki Chika , Habu Daiki , Ogura Juri , Tada Arisa , Hasei Ai , Sakurai Kotone , Watanabe Hatsumi
Published: January 2016

Aim

The aim of the present study was to identify factors associated with sarcopenia in community‐dwelling elderly women in Japan.

Methods

A total of 186 women aged over 65 years attending preventive care classes were enrolled in the study. Muscle mass was assessed using bioelectrical impedance analysis. Sarcopenia was defined as low muscle mass and low muscle strength in accord with the consensus report of the Asian Working Group for Sarcopenia. Data regarding household status (living alone, with a spouse, or with children and/or grandchildren), calf circumference and the presence of locomotive syndrome were obtained, as well as dietary variety score, Tokyo Metropolitan Institute of Gerontology Index of Competence and Mini‐Nutritional Assessment short form, and 10‐item Eating Assessment Tool scores.

Results

Sarcopenia was identified in 21.0% of participants. Participants with sarcopenia were older, had a lower body mass index and calf circumference, and were more likely to have locomotive syndrome, and living with children and/or grandchildren. In multivariate analysis, age, body mass index <18.5 and locomotive syndrome were significantly associated with sarcopenia, as were associated living alone (OR 1.69, 95% CI 0.45–6.41), and living with children and/or grandchildren (OR 2.46, 95% CI 0.71–8.54) and dietary variety score ≥9 (OR 4.98, 95% CI 0.97–25.56).

Conclusions

Age, body mass index, dietary variety score, locomotive syndrome and household status were associated with sarcopenia. Early interventions are required for older adults identified as having a higher risk of sarcopenia to prevent its adverse health consequences. Geriatr Gerontol Int 2017; 17: 54–60.
Effectiveness of a multidisciplinary home‐based medication review program in reducing healthcare utilization among older adult Singaporeans
Authors: Ong Kheng Yong , Cheen Mcvin Hua Heng , Chng Joanne Swee Gek , Chen Li Li , Ng Sock Mui , Lim Seng Han , Lim Paik Shia , Chang Wei Terk
Published: January 2016

Aim

The study aimed to: (i) evaluate the effectiveness of a multidisciplinary home‐based medication review (HBMR) program in reducing hospital admissions and emergency department (ED) visits, cost of hospital admissions and length of stay (LOS); and (ii) determine the prevalence of drug‐related problems (DRP) in elderly Singaporeans.

Methods

A retrospective observational study was carried out at an academic medical center in Singapore. Patients referred between 1 March 2011 and 31 December 2012 were included. Frequency of hospital admissions and ED visits, cost of hospital admissions, and LOS 6 months before and after HBMR, number of DRP, their categories, and their outcomes (i.e. resolved/ unresolved) were recorded.

Results

The analysis included 107 patients with a mean (SD) age of 75.6 years (7.6 years). HBMR resulted in a 41% reduction in risk for hospital admissions (Incidence rate ratio 0.59, 95% CI 0.47–0.73, P < 0.001). The same magnitude of reduction was observed for ED visits. The mean (SD) cost of hospital admissions reduced from $16 957.77 ($16 118.35) before HBMR to $7488.76 ($12 773.40) after (P < 0.001). Among 62 patients with hospital admissions before and after HBMR, the mean (SD) LOS decreased from 26.5 days (22.4 days) to 17.6 days (17.8 days; P = 0.010). The team identified 525 DRP from 1353 medications reviewed. Of these, 34 (6.7%) and 174 (34.1%) were resolved with and without physician involvement, respectively. The most common DRP identified were failure to receive drug (n = 163, 31.0%) and untreated indication (n = 140, 26.7%).

Conclusions

The multidisciplinary HBMR program was associated with reduced ED visits, hospital admissions, LOS and costs in older adult Singaporeans with multiple DRP. Geriatr Gerontol Int 2017; 17: 302–307.
Inhibition of blood vessel formation in tumors by IL‐18‐polarized M1 macrophages
Authors: Xing Yanjiang , Tian Yijun , Kurosawa Takamasa , Matsui Sayaka , Touma Maki , Wu Qiong , Sugimoto Kenkichi
Published: January 2016

We previously showed that interleukin (IL)‐18 produced by NFSA cells induced the M1 type of macrophages in NFSA tumors, caused the destruction of endothelial cells in vitro and may have resulted in the necrosis of NFSA tumors by enhancing macrophage phagocytosis and cytotoxicity. However, the effect of IL‐18 on blood vessel formation in vivo has not been elucidated. MS‐K cells do not express il‐18, and they form tumors with well‐developed blood vessels. Here, we established IL‐18‐over‐expressing MS‐K cell clones (MS‐K‐IL‐18) to address the roles of IL‐18 in angiogenesis. The over‐expression of IL‐18 inhibited the proliferation rate of the MS‐K‐IL‐18 cells in vitro and blood vessel formation in the MS‐K‐IL‐18 tumors. Interestingly, CD14‐positive cells from the MS‐K‐IL‐18 tumor had up‐regulated expression of the M1‐type macrophage marker il‐6 and down‐regulated expression of interferon (ifn)‐γ. Furthermore, FACS analysis showed more accumulation of CD11b+/CD80+ M1 macrophages in the MS‐K‐IL‐18 tumors than in the parental MS‐K tumor. Moreover, an in vitro coculture assay showed that MS‐K‐IL‐18‐conditioned medium (CM) stimulated macrophages to induce the apoptosis of endothelial cells. Cumulatively, our data showed that IL‐18 inhibited tumor blood vessel formation in vivo.
Blurring Public and Private: The Pragmatic Desegregation Politics of an Elite Private School in Atlanta
Authors: Purdy Michelle A.
Published: January 2016

The school desegregation narrative often references historically white public schools as sites of massive resistance and historically white private schools as segregationist academies. Yet some historically white elite private schools or independent schools, such as The Westminster Schools (plural in name only), established in 1951 in Atlanta, Georgia, chose to desegregate. Such elite institutions, which have served as one catalyst for the creation and maintenance of social and cultural capital, became more accessible after Brown v. Board of Education through a combination of private and public decisions galvanized by larger social, political, and federal forces. Westminster's 1965 decision to consider all applicants regardless of race was emblematic of the pragmatic desegregation politics of Atlanta's city leaders during the civil rights movement and a national independent school agenda focused on recruiting black students. Drawing on institutional, local, regional, and national archival records and publications, this article examines the import of schools like Westminster to civic and business leaders, to the politics of race and desegregation occurring in large cities, and to the range of educational opportunities available in metropolitan areas. This examination yields an analysis of the leadership and politics of a southern historically white elite private school that black students desegregated in 1961.
Between the School and the Academy: The Struggle to Promote Teacher Research at Columbia University's Lincoln School, 1917–1935
Authors: Perrillo Jonna
Published: January 2016

This essay examines the development of a research faculty and culture at the Lincoln School, a laboratory school founded in 1917 by the Rockefeller General Education Board (GEB) at Teachers College, Columbia University. The school was dedicated to the production of education research by practicing teachers. The essay focuses in particular on the role played by the two men first charged by the GEB to organize and administrate the school, Abraham Flexner and Otis Caldwell, and some of the school's teachers. Flexner and Caldwell promoted a working environment marked by experimentation, academic freedom, and faculty collaboration. This leadership model created tensions between Flexner and Caldwell and some Teachers College faculty over the use of Lincoln School classrooms as a resource for education research. Over the twenty-four years of the school's existence, Lincoln School teachers published hundreds of studies and textbooks focusing on curriculum development, child development, teaching techniques, and democratic school administration. In a profession where members are expected to be consumers rather than creators of knowledge, and practitioners rather than “experts,” the teachers and administrators of the Lincoln School defied many of the most foundational premises that have guided schools and the production of education research alike.
Maternal transfer of androgens in eggs is affected by food supplementation but not by predation risk
Authors: Morosinotto Chiara , Thomson Robert L. , Ruuskanen Suvi , Korpimäki Erkki , Lehikoinen Esa , Möstl Erich , Laaksonen Toni
Published: January 2016

Mothers may affect the future success of their offspring by varying allocation to eggs and embryos. Allocation may be adaptive based on the environmental conditions perceived during early breeding. We investigated the effects of food supplementation and predation risk on yolk hormone transfer in the pied flycatcher Ficedula hypoleuca. In a food supplementation experiment, females were food‐supplemented prior to and during egg‐laying and androgen concentrations were measured throughout the laying order. Predation risk was investigated in three different studies combining both correlative data, where flycatchers bred in close proximity to two different predator species that prey upon adult flycatchers (either Tengmalm's owl Aegolius funereus or pygmy owl Glaucidium passerinum), and an experimental manipulation, where flycatchers were exposed to cues of a nest predator (least weasel Mustela nivalis). Females receiving food supplementation laid eggs with lower concentrations of androstenedione (A4) than females not receiving food supplements. Yolk testosterone (T) concentration showed the same pattern but the difference was not statically significant. Testosterone (but not A4) concentration increased within clutches, from the first to the last egg, independently of the food supplementation. Females breeding under high predation risk did not differ from control females in their yolk androgen levels (A4, T or progesterone). However, concentrations of A4 tended to be lower in the proximity of pygmy owls, which could indirectly increase offspring survival after fledging. Food supplementation during egg‐laying seems to have a stronger impact on maternal transfer of androgens than predation risk. Food availability and predation risk could differentially affect the trade‐offs of androgen allocation for the offspring when raised in good vs. dangerous environments.
Prevalence and Determinants of Chronic Kidney Disease Among Hypertensive Cameroonians According to Three Common Estimators of the Glomerular Filtration Rate
Authors: Kaze Francois Folefack , Kengne Andre‐Pascal , Magatsing Carine Tchendjou , Halle Marie‐Patrice , Yiagnigni Euloge , Ngu Kathleen Blackett
Published: January 2016

Hypertension is a risk factor for renal diseases, which, in turn, are precursors of hypertension. The authors assessed the prevalence and determinants of chronic kidney disease (CKD) among 336 hypertensive adult Cameroonians (mean age, 60.9±11.3 years; 63.4% women) at Yaoundé. Any participant with an estimated glomerular filtration rate <60 mL/min/1.73 m2 regardless of the equation used (Cockcroft‐Gault [CG], Modification of Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD‐EPI]) and/or dipstick proteinuria was reviewed 3 months later. Participants presented a high prevalence of diabetes (18.5%), dyslipidemia (17.6%), gout/hyperuricemia (10.7%), overweight/obesity (68.8%), self‐medication (37.5%), and alcohol consumption (33.3%). Hypertension was uncontrolled in 265 patients (78.9%). The prevalence of CKD was 49.7%, 50.0%, and 52.1% according to MDRD, CKD‐EPI, and CG equations, respectively. Advanced age, adiposity, and severity of hypertension were determinants of CKD. Nearly half of the hypertensive patients had CKD regardless of the estimators used, predicted by well‐known risk factors.
Synergistic Antimicrobial Effects of Organic Acids in Combination with Carvacrol Against Shigella Sonnei
Authors: Chai Changhoon , Lee Soyeon , Kim Jinhee , Oh Se‐Wook
Published: January 2016

This study aimed to investigate the antimicrobial activities of organic acids, carvacrol and their combination against Shigella sonnei. Shigella sonnei at a density of approximately 7.4 log cfu/mL in tryptic soy broth (TSB) was barely inactivated by 0.5% w/v acetic or citric acid; however, the number of S. sonnei were reduced to 4.53 and 3.25 log cfu/mL by 0.5% w/v malic and lactic acid, respectively, after the treatment for 9 h. Shigella sonnei was completely inactivated by 0.02 and 0.03% w/v carvacrol within 70 and 20 min, respectively. Furthermore, the treatment with the combination of 0.5% w/v lactic acid and 0.02% w/v carvacrol completely inactivate S. sonnei at 6.52 log cfu/mL in TSB within 10 min. The number of S. sonnei inactivated by the combination was greater than the sum of those inactivated by 0.5% w/v lactic acid and 0.02% w/v carvacrol, indicating the synergistic effect of the combination.

Practical Applications

The synergistic inactivation against Shigella sonnei by the combination of an organic acid and carvacrol demonstrated in this study is directly applicable to fresh food processing, and these findings could be useful for the development of new means to keep food safety from S. sonnei infection.
Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis
Authors: Slocum C. , Kramer C. , Genco C. A.
Published: January 2016

Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti‐inflammatory therapies for this chronic disease.
Travel distances by Wisconsin Medicaid enrollees who visit emergency departments for dental care
Authors: Okunseri Christopher , Vanevenhoven Rabeea , Chelius Thomas , Beyer Kirsten M. M. , Okunseri Elaye , Lobb William K. , Szabo Aniko
Published: January 2016

Objectives

Prior studies document increased numbers of nontraumatic dental condition (NTDC) visits to U.S. emergency departments (EDs). However, the influence of travel distance on ED use for NTDCs, particularly for Medicaid enrollees has hitherto received little attention. The authors examined the effect of travel distance on Wisconsin Medicaid enrollees’ NTDC visits to EDs after adjustment for covariates.

Methods

NTDC‐related visits claims data for Wisconsin Medicaid (2001‐2009) was analyzed. For each enrollee, travel distance to the nearest of 130 EDs in Wisconsin was determined. The number of NTDC visits per person‐year was aggregated by ZIP+4 of residence. Negative binomial regression adjusting for the expected number of visits based on race, sex, age of the residents and calendar year was used to evaluate the effect of travel distance, urbanicity, and dentist‐population ratio on rate of visits.

Results

Enrollees residing in rural counties, entire dental health professional shortage areas, areas with dentist population ratios >20,000: 1 and non‐Hispanic Whites travelled the furthest, compared to nearest mean ED distance of 2.9 miles. Enrollees residing 3 miles away or further had significantly lower rates of NTDC visits to EDs.

Conclusions

This study demonstrates that distance is a barrier to making NTDC‐related visits to EDs. Rates of NTDC visits decreased as travel distance to the nearest ED increased for Medicaid enrollees.
Fossil leaves of Populus from the Middle Miocene of Yunnan, SW China
Authors: Liang Xiao‐Qing , Ferguson David K. , Su Tao , Zhou Zhe‐Kun
Published: January 2016

Today southern Yunnan, SW China, has a tropical or subtropical climate and seasonal rainforests. In the past, some temperate elements were also present. In this paper, a new species of Populus is reported from the Middle Miocene deposits in Zhenyuan. Its leaves are ovate or ovate‐suborbicular, with serrate margins. They have a shallowly cordate to cuneate base without glands, short acuminate apex, and salicoid teeth with spherical glands. The veins are glabrous but unicellular hair bases occur on the lower epidermis of the lamina. Stomata are confined to the lower epidermis. The presence of Populus in the Middle Miocene of the region indicates an expansion of the genus into low‐latitude Asia in the late Cenozoic and a more complicated history of vegetational change in southern Yunnan than has so far been assumed.
The redox control of photorespiration: from biochemical and physiological aspects to biotechnological considerations
Authors: Keech Olivier , Gardeström Per , Kleczkowski Leszek A. , Rouhier Nicolas
Published: January 2016

Photorespiration is a complex and tightly regulated process occurring in photosynthetic organisms. This process can alter the cellular redox balance, notably via the production and consumption of both reducing and oxidizing equivalents. Under certain circumstances, these equivalents, as well as reactive oxygen or nitrogen species, can become prominent in subcellular compartments involved in the photorespiratory process, eventually promoting oxidative post‐translational modifications of proteins. Keeping these changes under tight control should therefore be of primary importance. In order to review the current state of knowledge about the redox control of photorespiration, we primarily performed a careful description of the known and potential redox‐regulated or oxidation sensitive photorespiratory proteins, and examined in more details two interesting cases: the glycerate kinase and the glycine cleavage system. When possible, the potential impact and subsequent physiological regulations associated with these changes have been discussed. In the second part, we reviewed the extent to which photorespiration contributes to cellular redox homeostasis considering, in particular, the set of peripheral enzymes associated with the canonical photorespiratory pathway. Finally, some recent biotechnological strategies to circumvent photorespiration for future growth improvements are discussed in the light of these redox regulations.
Demographic, Social Support, and Community Differences in Predictors of African‐American and White Men Receiving Prostate Cancer Screening in the United States
Authors: Dickey Sabrina L. , Cormier Eileen M. , Whyte James , Graven Lucinda , Ralston Penny A.
Published: January 2016

Objective

To examine demographic, social support, and community factors from a national dataset that influence African‐American (AA) and White men to receive prostate cancer screening (PCS) via the Digital Rectal Exam (DRE) or Prostate Specific Antigen Test (PSA).

Design and Sample

A cross‐sectional secondary analysis from the National Health and Nutrition Examination Survey (NHANES) provided the sample of AA (N = 377) and White (N = 971) men over the age of 40 years. Regression analysis with confidence intervals was utilized to examine the factors associated with AA and White men receiving PCS. The Social Ecological Model provided the theoretical framework.

Measures

Questionnaires from the NHANES dataset provided data for this study. Results: Age, education, and access to health care was associated with AA and White men receiving the DRE. Income and church attendance was only associated with White men receiving the DRE. Only White men had an association of income with receiving the PSA test and only AA men had an association of marital status with receiving the PSA test.

Conclusions

Cultural evaluations of PCS behaviors among AA men are necessary to decrease the health disparity of prostate cancer among the AA population.
Non‐Scale Endogenous Growth with R&D and Human Capital
Authors: Day Creina
Published: January 2016

This paper examines the conditions under which increasing knowledge, encapsulated in ideas for new technology through R&D and embodied in human capital through education, sustains economic growth. A general model is developed where, consistent with recent literature, growth is non‐scale (not increasing in population size) and endogenous (generated by factors within R&D and education). Recent models feature the counterfactual assumption of constant returns to existing knowledge and restrict the substitutability of inputs within R&D and education. We find that non‐scale endogenous growth is possible under less stringent conditions. The findings reconcile sustained economic growth with evidence of diminishing marginal returns in education and R&D, which suggests an ambiguous role for R&D policy.
Circulating let‐7g is down‐regulated in Bernese Mountain dogs with disseminated histiocytic sarcoma and carcinomas – a prospective study
Authors: Børresen B. , Nielsen L. N. , Jessen L. R. , Kristensen A. T. , Fredholm M. , Cirera S.
Published: January 2016

Cancer is a prevalent cause of mortality in Bernese mountain dogs (BMDs). Circulating microRNAs (miRNAs) are found in blood and have been identified as promising biomarkers in various neoplastic diseases in humans. In the current study, the expression profile of different types of miRNAs was investigated in healthy BMDs and BMDs with cancer. Seven healthy and six non‐treated BMDs with cancer [four with disseminated histiocytic sarcomas (DHS)] were enrolled in this study. Clinical evaluations including physical examination, blood analysis, urinalysis and diagnostic imaging were performed on all dogs. Twenty‐four different miRNAs were profiled from RNA isolated from whole blood preserved in PAXgene® tubes using quantitative real‐time PCR (qPCR). The miRNA let‐7g was significantly down‐regulated in dogs with cancer (P = 0.002) and dogs with DHS (P = 0.011) compared with healthy controls. This miRNA is a known tumour suppressor and further analyses are warranted to assess its value as a non‐invasive biomarker for early detection of different types of cancer in BMDs.
High COX‐2 expression is associated with increased angiogenesis, proliferation and tumoural inflammatory infiltrate in canine malignant mammary tumours: a multivariate survival study
Authors: Carvalho M. I. , Pires I. , Prada J. , Raposo T. P. , Gregório H. , Lobo L. , Queiroga F. L.
Published: January 2016

COX‐2 expression affects mammary tumourigenesis by promoting angiogenesis and cell proliferation, encouraging metastatic spread and tumour‐associated inflammation. Samples of canine mammary tumours (n = 109) were submitted to immunohistochemistry to detect COX‐2, CD31, VEGF, Ki‐67, CD3 and MAC387 expression. Concurrent high expression of COX‐2/CD31, COX‐2/VEGF, COX‐2/Ki‐67, COX‐2/CD3 and COX‐2/MAC was associated with elevated grade of malignancy, presence of intravascular emboli and presence of lymph node metastasis. Tumours with high COX‐2 (P < 0.001) and tumours with concurrent expression of high COX‐2 and high CD31 (P = 0.008); high VEGF (P < 0.001); high Ki‐67 (P < 0.001); high CD3+ T‐lymphocytes (P = 0.002) and elevated MAC387 macrophages (P = 0.024) were associated with shorter overall survival (OS) time. Interestingly the groups with high COX‐2/CD31 and high COX‐2/VEGF retained their significance after multivariate analysis arising as independent predictors of OS. Present data highlight the importance of COX‐2 in canine mammary tumourigenesis.
A Novel Approach to Brachycephalic Syndrome. 1. Evaluation of Anatomical Intranasal Airway Obstruction
Authors: Oechtering Gerhard U. , Pohl Sabine , Schlueter Claudia , Lippert Johanna P. , Alef Michaele , Kiefer Ingmar , Ludewig Eberhard , Schuenemann Riccarda
Published: January 2016

Objective

To evaluate airway obstruction due to abnormal intranasal anatomy in 3 brachycephalic dog breeds using computed tomography and rhinoscopy.

Study Design

Prospective clinical study.

Animals

A total of 132 brachycephalic dogs (66 Pugs, 55 French Bulldogs, and 11 English Bulldogs) with severe respiratory distress due to brachycephalic syndrome.

Methods

Computed tomography and anterior and posterior rhinoscopy were performed to evaluate endonasal obstruction.

Results

All dogs had abnormal conchal growth that obstructed the intranasal airways. Rostral aberrant turbinates (RAT) were common in Pugs (90.9%) but less frequent in French (56.4%) and English (36.4%) Bulldogs. Caudal aberrant turbinates (CAT) obstructing the nasopharyngeal meatus were commonly found in all breeds (66.7%). Deviation of the nasal septum was an almost consistent finding in Pugs (98.5%) but was less common in bulldogs. Obstructing turbinates had multiple points of mucosal contact responsible for obstruction of the intranasal airway. Interconchal and intraconchal mucosal contacts were evident in 91.7% of dogs.

Conclusion

Selective breeding for short head conformation reduces the size of the nasal cavities to such an extent that intranasal structures grow aberrantly and malformed, leading to obstructed air conducting spaces. Intranasal airway obstruction of brachycephalic dogs may contribute to their exercise and heat intolerance because of impaired pulmonary ventilation and compromised thermoregulatory functions of the canine nose. Failure to address intranasal obstruction might be an explanation for lack of therapeutic success after conventional surgery for brachycephalic syndrome. Future consideration should be given to the diagnosis, management, and treatment of this newly described aspect of airway obstruction.
A Novel Approach to Brachycephalic Syndrome. 2. Laser‐Assisted Turbinectomy (LATE)
Authors: Oechtering Gerhard U. , Pohl Sabine , Schlueter Claudia , Schuenemann Riccarda
Published: January 2016

Objective

To introduce a new surgical procedure based on interventional, laser‐assisted removal of obstructing turbinate tissue to improve endonasal airway patency in brachycephalic dogs and to confirm the short and long term results using computed tomography (CT) and rhinoscopy.

Study Design

Prospective clinical study.

Animals

Brachycephalic dogs (n = 158; 70 Pugs, 77 French Bulldogs, 11 English Bulldogs) referred for treatment of severe respiratory distress because of brachycephalic syndrome.

Methods

Computed tomography and anterior and posterior rhinoscopy were performed to evaluate endonasal obstruction. Laser‐assisted turbinectomy (LATE) using a diode laser was performed as part of a multilevel surgery. Nasal conchae that were causing airway obstruction were removed.

Results

The obstructing parts of the conchae were safely and efficiently removed by LATE, shaping a patent nasal airway in all dogs. The newly developed surgical procedure involved 3 steps: turbinectomy of the (1)concha nasalis ventralis; (2) rostral aberrantly growing turbinates (RAT); and (3) caudal aberrantly growing turbinates (CAT). Complications of the procedure included transient intraoperative hemorrhage in 51 of 158 dogs (32.3%); however, a temporary tamponade was necessary in only 2/158 dogs (1.3%). After 6 months, regrowth of turbinates required resection of possibly re‐obstructing tissue in 25/158 dogs (15.8%; 1 Pug and 24 French Bulldogs).

Conclusion

LATE is an effective method for creating a patent nasal airway in brachycephalic dogs with intranasal obstruction.
Morphological and genetic variability of local Echinochloa accessions and the link with herbicide sensitivity
Authors: Claerhout S , Dewaele K , De Riek J , Reheul D , De Cauwer B
Published: January 2016

Echinochloa crus‐galli and Echinochloa muricata are common weeds in Belgian maize fields. Both species are morphologically difficult to distinguish and exhibit high morphological variability. Their response to herbicides varies from field to field. This study investigated whether the considerable morphological polymorphism found among Belgian Echinochloa accessions has a genetic background and whether it is consistently associated with differences in sensitivity to maize herbicides. For this purpose, accessions of E. crus‐galli and E. muricata were compared for morphological and genetic resemblance and tested for herbicide sensitivity. All accessions were planted in the field to examine the morphological traits. A cluster analysis was conducted to assess them for morphological diversity. DNA of leaf material was used for amplified fragment length polymorphism analysis to cluster the accessions genetically. Dose–response pot experiments were conducted in the glasshouse to assess the effectiveness of an acetolactate synthase (nicosulfuron), acetyl‐CoA carboxylase (cycloxydim) and 4‐hydroxyphenyl phosphate dioxygenase (topramezone) inhibiting herbicide. The genetic and morphological clusters were compared with the effective doses obtained from the dose–response bioassays. Morphological variation significantly correlated with genetic variation, but the relation with herbicide sensitivity was weak. Spikelet size and biomass characteristics are reliable discriminating characteristics for (sub)species classification. Intraspecies identification does not seem essential for optimisation of chemical control of E. crus‐galli and E. muricata in the field.
Role of reactive oxygen species in regulation of glucose transport in skeletal muscle during exercise
Authors: Katz Abram
Published: January 2016

Glucose derived from extracellular sources serves as an energy source in virtually all eukaryotic cells, including skeletal muscle. Its contribution to energy turnover increases with exercise intensity up to moderately heavy workloads. However, at very high workloads, the contribution of extracellular glucose to energy turnover is negligible, despite the high rate of glucose transport. Reactive oxygen species (ROS) are involved in the stimulation of glucose transport in isolated skeletal muscle preparations during intense repeated contractions. Consistent with this observation, heavy exercise is associated with significant production of ROS. However, during more mild to moderate stimulation or exercise conditions (in vitro, in situ and in vivo) antioxidants do not affect glucose transport. It is noteworthy that the production of ROS is limited or not observed under these conditions and that the concentration of the antioxidant used was extremely low. The results to date suggest that ROS involvement in activation of glucose transport occurs primarily during intense short‐term exercise and that other mechanisms are involved during mild to moderate exercise. What remains puzzling is why ROS‐mediated activation of glucose transport would occur under conditions where glucose transport is highest and utilization (i.e. phosphorylation of glucose by hexokinase) is low. Possibly ROS production is involved in priming glucose transport during heavy exercise to accelerate glycogen biogenesis during the initial recovery period after exercise, as well as altering other aspects of intracellular metabolism.

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Frequency Analysis of Linearly Coupled Modes of MEMS Arrays
Authors: Kambali Prashant N. , Swain Gyanadutta , Kumar Pandey Ashok
Published: January 2016

Microelectromechanical system (MEMS) based arrays have been employed to increase the bandwidth and sensitivity of many sensors and actuators. In this paper, we present an approximate model to demonstrate the tuning of in-plane and out-of-plane frequencies of MEMS arrays consisting of fixed–fixed beams. Subsequently, we apply the Galerkin's method with single approximate mode to obtain the reduced-order static and dynamic equations. Corresponding to a given direct current (DC) voltage, we first solve the static equations and then obtain corresponding frequencies from the dynamic equation for single beam and arrays of multibeams. We compare the model with available experimental results. Later, we show the influence of different frequency tuning parameters such as the initial tensions, fringing field coefficients and the variable inter beam gaps between the microbeam and electrodes to control the coupling region and different modal frequencies of the beam. Finally, we obtain a compact model which can be used in optimizing the bandwidth and sensitivity of microbeams array.
Yield Maps for Single and Bilayer Thin Films Under Scratch
Authors: Chatterjee Abhish , Beheshti Ali , Polycarpou Andreas A. , Bellon Pascal
Published: January 2016

Finite element (FE) simulations were performed to study yielding in single and bilayer (BL) film systems using a “yield zone map” approach. Onset of yielding was observed at the interface, substrate, surface, and film in HfB2/silicon and HfB2/stainless steel systems. The interface yield zone in HfB2/stainless steel system was found to be larger due to the dominant effect of interfacial stress gradients. Based on the FE simulations, empirical equations were derived for the maximum contact pressure required to initiate yield at the interface. For BL/substrate systems, onset of yield at the lower film/substrate interface occurred when film thickness ratio was in the range 0.5–5. The maximum contact pressure associated with the initial yielding at this interface is minimum compared to other locations. From the design point of view, for a BL system the preferable film thickness ratio was found to be 20, whereas the optimum hardness ratio ranges from 2 to 4. For these values, maximum contact pressure is very high (∼30 GPa), and thus, yield onset can be avoided at lower film/substrate interfaces. In addition, based on the obtained results, the advantages and disadvantages of using a BL film as compared to a single film and their relevance to practical applications are discussed.
Nonthermal ablation of deep brain targets: A simulation study on a large animal model
Authors: Top Can Barış , White P. Jason , McDannold Nathan J.
Published: January 2016

Purpose:

Thermal ablation with transcranial MRI‐guided focused ultrasound (FUS) is currently limited to central brain targets because of heating and other beam effects caused by the presence of the skull. Recently, it was shown that it is possible to ablate tissues without depositing thermal energy by driving intravenously administered microbubbles to inertial cavitation using low‐duty‐cycle burst sonications. A recent study demonstrated that this ablation method could ablate tissue volumes near the skull base in nonhuman primates without thermally damaging the nearby bone. However, blood–brain disruption was observed in the prefocal region, and in some cases, this region contained small areas of tissue damage. The objective of this study was to analyze the experimental model with simulations and to interpret the cause of these effects.

Methods:

The authors simulated prior experiments where nonthermal ablation was performed in the brain in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial MRI‐guided FUS system. Low‐duty‐cycle sonications were applied at deep brain targets with the ultrasound contrast agent Definity. For simulations, a 3D pseudospectral finite difference time domain tool was used. The effects of shear mode conversion, focal steering, skull aberrations, nonlinear propagation, and the presence of skull base on the pressure field were investigated using acoustic and elastic wave propagation models.

Results:

The simulation results were in agreement with the experimental findings in the prefocal region. In the postfocal region, however, side lobes were predicted by the simulations, but no effects were evident in the experiments. The main beam was not affected by the different simulated scenarios except for a shift of about 1 mm in peak position due to skull aberrations. However, the authors observed differences in the volume, amplitude, and distribution of the side lobes. In the experiments, a single element passive cavitation detector was used to measure the inertial cavitation threshold and to determine the pressure amplitude to use for ablation. Simulations of the detector's acoustic field suggest that its maximum sensitivity was in the lower part of the main beam, which may have led to excessive exposure levels in the experiments that may have contributed to damage in the prefocal area.

Conclusions:

Overall, these results suggest that case‐specific full wave simulations before the procedure can be useful to predict the focal and the prefocal side lobes and the extent of the resulting bioeffects produced by nonthermal ablation. Such simulations can also be used to optimally position passive cavitation detectors. The disagreement between the simulations and the experiments in the postfocal region may have been due to shielding of the ultrasound field due to microbubble activity in the focal region. Future efforts should include the effects of microbubble activity and vascularization on the pressure field.
Experiments with a falling rod
Authors: Oliveira Vitor
Published: January 2016

We study the motion of a uniform thin rod released from rest, with the bottom end initially in contact with a horizontal surface. Our focus here is the motion of the bottom end as the rod falls. For small angles of release with respect to the horizontal, the rod falls without the bottom end slipping. For larger angles, the slipping direction depends on the static friction coefficient between the rod and the horizontal surface. Small friction coefficients cause the end to slip initially in one direction and then in the other, while for high coefficients, the end slips in one direction only. For intermediate values, depending on the angle of release, both situations can occur. We find the initial slipping direction to depend on a relation between the angle at which the rod slips, and a critical angle at which the frictional force vanishes. Comparison between experimental data and numerical simulations shows good agreement.
DATA CHECK: Tracking first jobs to measure the impact of research funding
Authors: Mervis Jeffrey
Published: January 2016

Study of recent Ph.D.s at eight Midwestern universities demonstrates value of the new science of science policy.
Montreal institute going ‘open’ to accelerate science
Authors: Owens Brian
Published: January 2016

Experiment aims to show whether forgoing patents and freeing up data can boost neuroscience research.
How Cherenkov radiative losses can improve optical frequency combs
Authors: Akhmediev N. , Devine N.
Published: January 2016

Broader optical frequency combs on a photonic chip can help refine time standards

[Also see Report by

Brasch
et al.

]
Point-Counterpoint: The FDA Has a Role in Regulation of Laboratory-Developed Tests
Authors: Caliendo Angela M. , Hanson Kimberly E.
Published: January 2016

Since the Food and Drug Administration (FDA) released its draft guidance on the regulation of laboratory-developed tests (LDTs) in October 2014, there has been a flurry of responses from commercial and hospital-based laboratory directors, clinicians, professional organizations, and diagnostic companies. The FDA defines an LDT as an “
in vitro
diagnostic device that is intended for clinical use and is designed, manufactured, and used within a single laboratory.” The draft guidance outlines a risk-based approach, with oversight of high-risk and moderate-risk tests being phased in over 9 years. High-risk tests would be regulated first and require premarket approval. Subsequently, moderate-risk tests would require a 510(k) premarket submission to the FDA and low-risk tests would need only to be registered. Oversight discretion would be exercised for LDTs focused on rare diseases (defined as fewer than 4,000 tests, not cases, per year nationally) and unmet clinical needs (defined as those tests for which there is no alternative FDA-cleared or -approved test). There was an open comment period followed by a public hearing in early January of 2015, and we are currently awaiting the final decision regarding the regulation of LDTs. Given that LDTs have been developed by many laboratories and are essential for the diagnosis and monitoring of an array of infectious diseases, changes in their regulation will have far-reaching implications for clinical microbiology laboratories. In this Point-Counterpoint, Angela Caliendo discusses the potential benefits of the FDA guidance for LDTs whereas Kim Hanson discusses the concerns associated with implementing the guidance and why these regulations may not improve clinical care.
Development and Evaluation of a Loop-Mediated Isothermal Amplification Method for Rapid Detection of Aspergillus fumigatus
Authors: Tang Qing , Tian Shuguang , Yu Nong , Zhang Xi , Jia Xiaodong , Zhai Hongyan , Sun Qun , Han Li
Published: January 2016

Aspergillus fumigatus
is a conditional pathogen and the major cause of life-threatening invasive aspergillosis (IA) in immunocompromised patients. The early and rapid detection of
A. fumigatus
infection is still a major challenge. In this study, the new member of the fungal annexin family, annexin C4, was chosen as the target to design a loop-mediated isothermal amplification (LAMP) assay for the rapid, specific, and sensitive detection of
A. fumigatus
. The evaluation of the specificity of the LAMP assay that was developed showed that no false-positive results were observed for the 22 non-
A. fumigatus
strains, including 5 species of the
Aspergillus
genus. Its detection limit was approximately 10 copies per reaction in reference plasmids, with higher sensitivity than that of real-time quantitative PCR (qPCR) at 10
2
copies for the same target. Clinical samples from a total of 69 patients with probable IA (
n =
14) and possible IA (
n
= 55) were subjected to the LAMP assay, and positive results were found for the 14 patients with probable IA (100%) and 34 patients with possible IA (61.82%). When detection using the LAMP assay was compared with that using qPCR in the 69 clinical samples, the LAMP assay demonstrated a sensitivity of 89.19% and the concordance rate for the two methods was 72.46%. Accordingly, we report that a valuable LAMP assay for the rapid, specific, and simple detection of
A. fumigatus
in clinical testing has been developed.
Extensive Positive Selection Drives the Evolution of Nonstructural Proteins in Lineage C Betacoronaviruses
Authors: Forni Diego , Cagliani Rachele , Mozzi Alessandra , Pozzoli Uberto , Al-Daghri Nasser , Clerici Mario , Sironi Manuela
Published: January 2016

Middle East respiratory syndrome-related coronavirus (MERS-CoV) spreads to humans via zoonotic transmission from camels. MERS-CoV belongs to lineage C of betacoronaviruses (betaCoVs), which also includes viruses isolated from bats and hedgehogs. A large portion of the betaCoV genome consists of two open reading frames (ORF1a and ORF1b) that are translated into polyproteins. These are cleaved by viral proteases to generate 16 nonstructural proteins (nsp1 to nsp16) which compose the viral replication-transcription complex. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs. Results indicated widespread positive selection, acting mostly on ORF1a. The proportion of positively selected sites in ORF1a was much higher than that previously reported for the surface-exposed spike protein. Selected sites were unevenly distributed, with nsp3 representing the preferential target. Several pairs of coevolving sites were also detected, possibly indicating epistatic interactions; most of these were located in nsp3. Adaptive evolution at nsp3 is ongoing in MERS-CoV strains, and two selected sites (G720 and R911) were detected in the protease domain. While position 720 is variable in camel-derived viruses, suggesting that the selective event does not represent a specific adaptation to humans, the R911C substitution was observed only in human-derived MERS-CoV isolates, including the viral strain responsible for the recent South Korean outbreak. It will be extremely important to assess whether these changes affect host range or other viral phenotypes. More generally, data herein indicate that CoV nsp3 represents a major selection target and that nsp3 sequencing should be envisaged in monitoring programs and field surveys.

IMPORTANCE
Both severe acute respiratory syndrome coronavirus (SARS-CoV) and MERS-CoV originated in bats and spread to humans via an intermediate host. This clearly highlights the potential for coronavirus host shifting and the relevance of understanding the molecular events underlying the adaptation to new host species. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs and in 87 sequenced MERS-CoV isolates. Results indicated widespread positive selection, stronger in ORF1a than in ORF1b. Several selected sites were found to be located in functionally relevant protein regions, and some of them corresponded to functional mutations in other coronaviruses. The proportion of selected sites we identified in ORF1a is much higher than that for the surface-exposed spike protein. This observation suggests that adaptive evolution in ORF1a might contribute to host shifts or immune evasion. Data herein also indicate that genetic diversity at nonstructural proteins should be taken into account when antiviral compounds are developed.