bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Heading Direction for Recreating the Horizontal Alignment of an Existing Road
Authors: Camacho‐Torregrosa Francisco J. , Pérez‐Zuriaga Ana M. , Campoy‐Ungría José M. , García Alfredo , Tarko Andrew P.
Published: February 2015

This article proposes a new method for fitting the horizontal alignment of a road to a set of (x, y) points. Those points can be obtained from digital imagery or GPS‐data collection. Unlike current methods that represent road alignment through its curvature, the proposed method describes the horizontal alignment as a sequence of headings. An analytic–heuristic approach is introduced. The proposed method produces unique solutions even for complex horizontal alignments. Some examples and a case study are presented. This solution may not be accurate enough for road redesign, but it allows researchers and departments of transportation to obtain accurate geometric features.
Clostridium difficile surface proteins are anchored to the cell wall using CWB2 motifs that recognise the anionic polymer PSII
Authors: Willing Stephanie E. , Candela Thomas , Shaw Helen Alexandra , Seager Zoe , Mesnage Stéphane , Fagan Robert P. , Fairweather Neil F.
Published: February 2015

Gram‐positive surface proteins can be covalently or non‐covalently anchored to the cell wall and can impart important properties on the bacterium in respect of cell envelope organisation and interaction with the environment. We describe here a mechanism of protein anchoring involving tandem CWB2 motifs found in a large number of cell wall proteins in the Firmicutes. In the Clostridium difficile cell wall protein family, we show the three tandem repeats of the CWB2 motif are essential for correct anchoring to the cell wall. CWB2 repeats are non‐identical and cannot substitute for each other, as shown by the secretion into the culture supernatant of proteins containing variations in the patterns of repeats. A conserved Ile Leu Leu sequence within the CWB2 repeats is essential for correct anchoring, although a preceding proline residue is dispensable. We propose a likely genetic locus encoding synthesis of the anionic polymer PSII and, using RNA knock‐down of key genes, reveal subtle effects on cell wall composition. We show that the anionic polymer PSII binds two cell wall proteins, SlpA and Cwp2, and these interactions require the CWB2 repeats, defining a new mechanism of protein anchoring in Gram‐positive bacteria.
Association between endothelial and platelet function markers and adiponectin in renal transplanted recipients on cyclosporine and tacrolimus immunosuppression based therapy
Authors: Sahin Garip , Akay Olga Meltem , Uslu Sema , Bal Cengiz , Yalcin Ahmet Ugur , Gulbas Zafer
Published: February 2015

Aim

Coagulation abnormalities, endothelial dysfunction and arteriosclerosis play a key role in cardiovascular disease state observed in transplanted patients. Plasma adiponectin levels are lower following kidney transplantation. However, there is still a debate about this topic in the literature. This study evaluated, adiponectin levels associated with markers of endothelial dysfunction and platelet function in renal transplant patients.

Methods

Sixty‐six renal transplant patients were studied. Patients were grouped according to immunosuppression regimen. Group 1 (n = 36) were treated with cyclosporine A based regimes and group 2 (n = 30) were treated with tacrolimus based regimes. Plasma adiponectin, asymmetric dimethyl arginine (ADMA), sP‐selectin levels and platelet aggregation tests were studied and were compared with those in control group (n = 15, group 3).

Results

Adiponectin, sP‐selectin and ADMA levels were higher in group 1 and statistically significant differences were observed compared with those of group 2 and group 3, respectively (P < 0.001, P < 0.05, P < 0.05). Platelet aggregation values induced by agonists were lower in group 1 than group 2 and group 3, but the difference did not reach statistical significance (P > 0.05).

Conclusion

Adiponectin levels are elevated in line with ADMA and sP‐selectin levels. Since CsA induces higher adiponectin levels, platelet activation and endothelial dysfunction. These changes may be responsible for the increased risk of post‐transplant cardiovascular events in renal transplant patients.
Measurements of transpiration isotopologues and leaf water to assess enrichment models in cotton
Authors: Song Xin , Loucos Karen E. , Simonin Kevin A. , Farquhar Graham D. , Barbour Margaret M.
Published: February 2015

The two‐pool and Péclet effect models represent two theories describing mechanistic controls underlying leaf water oxygen isotope composition at the whole‐leaf level (δ18OL).

To test these models, we used a laser spectrometer coupled to a gas‐exchange cuvette to make online measurements of δ18O of transpiration (δ18Otrans) and transpiration rate (E) in 61 cotton (Gossypium hirsutum) leaves. δ18Otrans measurements permitted direct calculation of δ18O at the sites of evaporation (δ18Oe) which, combined with values of δ18OL from the same leaves, allowed unbiased estimation of the proportional deviation of enrichment of δ18OL from that of δ18Oe (f) under both steady‐state (SS) and non‐steady‐state (NSS) conditions.

Among all leaves measured, f expressed relative to both δ18O of transpired water (ftrans) and source water (fsw) remained relatively constant with a mean ± SD of 0.11 ± 0.05 and 0.13 ± 0.05, respectively, regardless of variation in E spanning 0.8–9.1 mmol m−2 s−1. Neither ftrans nor fsw exhibited a significant difference between the SS and NSS leaves at the P < 0.05 level.

Our results suggest that the simpler two‐pool model is adequate for predicting cotton leaf water enrichment at the whole‐leaf level. We discuss the implications of adopting a two‐pool concept for isotopic applications in ecological studies.
Lipid anchoring of Arabidopsis phototropin 1 to assess the functional significance of receptor internalization: should I stay or should I go?
Authors: Preuten Tobias , Blackwood Lisa , Christie John M. , Fankhauser Christian
Published: February 2015

The phototropin 1 (phot1) blue light receptor mediates a number of adaptive responses, including phototropism, that generally serve to optimize photosynthetic capacity. Phot1 is a plasma membrane‐associated protein, but upon irradiation, a fraction is internalized into the cytoplasm. Although this phenomenon has been reported for more than a decade, its biological significance remains elusive. Here, we use a genetic approach to revisit the prevalent hypotheses regarding the functional importance of receptor internalization.

Transgenic plants expressing lipidated versions of phot1 that are permanently anchored to the plasma membrane were used to analyse the effect of internalization on receptor turnover, phototropism and other phot1‐mediated responses.

Myristoylation and farnesylation effectively prevented phot1 internalization. Both modified photoreceptors were found to be fully functional in Arabidopsis, rescuing phototropism and all other phot1‐mediated responses tested. Light‐mediated phot1 turnover occurred as in the native receptor. Furthermore, our work does not provide any evidence of a role of phot1 internalization in the attenuation of receptor signalling during phototropism.

Our results demonstrate that phot1 signalling is initiated at the plasma membrane. They furthermore indicate that release of phot1 into the cytosol is not linked to receptor turnover or desensitization.
Temperate radiations and dying embers of a tropical past: the diversification of Viburnum
Authors: Spriggs Elizabeth L. , Clement Wendy L. , Sweeney Patrick W. , Madriñán Santiago , Edwards Erika J. , Donoghue Michael J.
Published: February 2015

We used a near‐complete phylogeny for the angiosperm clade Viburnum to assess lineage diversification rates, and to examine possible morphological and ecological factors driving radiations.

Maximum‐likelihood and Bayesian approaches identified shifts in diversification rate and possible links to character evolution. We inferred the ancestral environment for Viburnum and changes in diversification dynamics associated with subsequent biome shifts.

Viburnum probably diversified in tropical forests of Southeast Asia in the Eocene, with three subsequent radiations in temperate clades during the Miocene. Four traits (purple fruits, extrafloral nectaries, bud scales and toothed leaves) were statistically associated with higher rates of diversification. However, we argue that these traits are unlikely to be driving diversification directly. Instead, two radiations were associated with the occupation of mountainous regions and a third with repeated shifts between colder and warmer temperate forests.

Early‐branching depauperate lineages imply that the rare lowland tropical species are ‘dying embers’ of once more diverse lineages; net diversification rates in Viburnum likely decreased in these tropical environments after the Oligocene. We suggest that ‘taxon pulse’ dynamics might characterize other temperate plant lineages.
The promise of ketamine for treatment‐resistant depression: current evidence and future directions
Authors: DeWilde Kaitlin E. , Levitch Cara F. , Murrough James W. , Mathew Sanjay J. , Iosifescu Dan V.
Published: February 2015

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments for MDD primarily consist of monoamine‐targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant in MDD. We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with the NIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants.
Multi‐component molecular‐level body composition reference methods: evolving concepts and future directions
Authors: Heymsfield S. B. , Ebbeling C. B. , Zheng J. , Pietrobelli A. , Strauss B. J. , Silva A. M. , Ludwig D. S.
Published: February 2015

Excess adiposity is the main phenotypic feature that defines human obesity and that plays a pathophysiological role in most chronic diseases. Measuring the amount of fat mass present is thus a central aspect of studying obesity at the individual and population levels. Nevertheless, a consensus is lacking among investigators on a single accepted ‘reference’ approach for quantifying fat mass in vivo. While the research community generally relies on the multi‐component body volume class of ‘reference’ models for quantifying fat mass, no definable guide discerns among different applied equations for partitioning the four (fat, water, protein and mineral mass) or more quantified components, standardizes ‘adjustment’ or measurement system approaches for model‐required labelled water dilution volumes and bone mineral mass estimates, or firmly establishes the body temperature at which model physical properties are assumed. The resulting differing reference strategies for quantifying body composition in vivo leads to small, but under some circumstances, important differences in the amount of measured body fat. Recent technological advances highlight opportunities to expand model applications to new subject groups and measured components such as total body protein. The current report reviews the historical evolution of multi‐component body volume‐based methods in the context of prevailing uncertainties and future potential.
Genetic engineering of the Xa10 promoter for broad‐spectrum and durable resistance to Xanthomonas oryzae pv. oryzae
Authors: Zeng Xuan , Tian Dongsheng , Gu Keyu , Zhou Zhiyun , Yang Xiaobei , Luo Yanchang , White Frank F. , Yin Zhongchao
Published: February 2015

Many pathovars of plant pathogenic bacteria Xanthomonas species inject transcription activator‐like (TAL) effectors into plant host cells to promote disease susceptibility or trigger disease resistance. The rice TAL effector‐dependent disease resistance gene Xa10 confers narrow‐spectrum race‐specific resistance to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight disease in rice. To generate broad‐spectrum and durable resistance to Xoo, we developed a modified Xa10 gene, designated as Xa10E5. Xa10E5 has an EBE‐amended promoter containing 5 tandemly arranged EBEs each responding specifically to a corresponding virulent or avirulent TAL effector and a stable transgenic rice line containing Xa10E5 was generated in the cultivar Nipponbare. The Xa10E5 gene was specifically induced by Xoo strains that harbour the corresponding TAL effectors and conferred TAL effector‐dependent resistance to the pathogens at all developmental stages of rice. Further disease evaluation demonstrated that the Xa10E5 gene in either Nipponbare or 9311 genetic backgrounds provided broad‐spectrum disease resistance to 27 of the 28 Xoo strains collected from 11 countries. The development of Xa10E5 and transgenic rice lines provides new genetic materials for molecular breeding of rice for broad‐spectrum and durable disease resistance to bacterial blight.
Photocatalytic Activity of LaSr2AlO5:Eu Ceramic Powders
Authors: García Carlos R. , Oliva Jorge , Díaz‐Torres Luis A.
Published: February 2015

The photocatalytic activity, of undoped and Europium‐doped LaSr2AlO5 powders, has been investigated by degrading methylene blue dye in water solutions. Those powders were fabricated by a combustion method and an annealing treatment in air. All samples showed a tetragonal single phase according to by X‐ray diffraction measurements (XRD). Scanning electron microscopy (SEM) revealed irregular semi‐oval grains with sizes in the range of 3.5–4.27 μm. Photoluminescence spectrum showed sharp emission peaks at 588 nm and at 617 nm which are associated with 7F1,7F2→ 5D0 Eu3+ ion forbidden transitions, respectively, under UV light excitation of 322 nm. The methylene blue (MB) degradation under UV light (254 nm) was studied by monitoring changes in the absorbance peak of MB at 665 nm. Finally, LaSr2AlO5:Eu powders were used three times and the efficiency for the degradation of MB decreased from 100 to 61% after the third cycle of use.
Do the Causes of Infertility Play a Direct Role in the Aetiology of Preterm Birth?
Authors: Messerlian Carmen , Platt Robert W. , Ata Baris , Tan Seang‐Lin , Basso Olga
Published: February 2015

Background

It is well established that singletons born of assisted reproductive technology are at higher risk of preterm birth and other adverse outcomes. What remains unclear is whether the increased risk is attributable to the effects of the treatment alone or whether the underlying causes of infertility also play a role. The aim of this study was to examine whether any of the six categories of causes of infertility were associated with a direct effect on preterm birth using causal mediation analysis.

Methods

We assembled a hospital‐based cohort of births delivered at a large tertiary care hospital in Montreal, Canada between 2001 and 2007. Causes of infertility were ascertained through a clinical database and medical chart abstraction. We employed marginal structural models (MSM) to estimate the controlled direct effect of each cause of infertility on preterm birth compared with couples without the cause under examination.

Results

The final study cohort comprised 18 598 singleton and twin pregnancies, including 1689 in couples with ascertained infertility. MSM results suggested no significant direct effect for any of the six categories of causes. However, power was limited in smaller subgroup analyses, and a possible direct effect for uterine abnormalities (e.g. fibroids and malformations) could not be ruled out.

Conclusion

In this cohort, most of the increased risk of preterm birth appeared to be explained by maternal characteristics (such as age, body mass index, and education) and by assisted reproduction. If these findings are corroborated, physicians should consider these risks when counselling patients.
Is integrated multitrophic aquaculture the solution to the sectors’ major challenges? – a review
Authors: Granada Luana , Sousa Nádia , Lopes Sofia , Lemos Marco F. L.
Published: February 2015

The growing demand for fish products and the dwindling productivity of marine fish stocks due to the overexploitation of fisheries place the aquaculture industry as a key contributor to the global fish supply. The intensive development of aquaculture has raised a range of environmental concerns such as effluent discharge, excessive use of resources and dependence on commercial feed. In this context, the development of sustainable aquaculture systems is becoming the cornerstone for long‐term aquaculture expansion, and to achieve environmental sustainability. Integrated multitrophic aquaculture (IMTA) is regarded as a suitable approach to limit aquaculture nutrients and organic matter outputs through biomitigation. The cocultured species are used as biofilters, and each level has its own independent commercial value, providing both economic and environmental sustainability. Here, environmental issues of aquaculture and the current status of IMTA are reviewed and its future prospects discussed. Also, the opportunities to expand this systems’ complexity with increased added‐value and trophic levels are introduced.
Fundamental movement skills and physical fitness as predictors of physical activity: A 6‐year follow‐up study
Authors: Jaakkola T. , Yli‐Piipari S. , Huotari P. , Watt A. , Liukkonen J.
Published: February 2015

The purpose of this study was to examine the extent to which fundamental movement skills and physical fitness scores assessed in early adolescence predict self‐reported physical activity assessed 6 years later. The sample comprised 333 (200 girls, 133 boys; M age = 12.41) students. The effects of previous physical activity, sex, and body mass index (BMI) were controlled in the main analyses. Adolescents’ fundamental movement skills, physical fitness, self‐report physical activity, and BMI were collected at baseline, and their self‐report energy expenditure (metabolic equivalents: METs) and intensity of physical activity were collected using the International Physical Activity Questionnaire 6 years later. Results showed that fundamental movement skills predicted METs, light, moderate, and vigorous intensity physical activity levels, whereas fitness predicted METs, moderate, and vigorous physical activity levels. Hierarchical regression analyses also showed that after controlling for previous levels of physical activity, sex, and BMI, the size of the effect of fundamental movement skills and physical fitness on energy expenditure and physical activity intensity was moderate (R2 change between 0.06 and 0.15), with the effect being stronger for high intensity physical activity.
Severe infections after single umbilical cord blood transplantation in adults with or without the co‐infusion ofCD34+cells from a third‐party donor: results of a multicenter study from the Grupo Español de Trasplante Hematopoyético (GETH)
Authors: Martino R. , Bautista G. , Parody R. , García I. , Esquirol A. , Rovira M. , Cabrera J.R. , Regidor C. , Fores R. , García‐Marco J.A. , Serrano D. , Barba P. , Heras I. , Marquez‐Malaver F.J. , Sánchez‐Ortega I. , Duarte R. , Saavedra S. , Sierra J. , Vazquez L. ,   the Infectious/Non‐infectious Complications Subcommittee of the Grupo Español de Trasplante Hematopoyético (GETH)
Published: February 2015

Background

Umbilical cord blood transplantation (CBT) is an established alternative source of stem cells in the setting of unrelated transplantation. When compared with other sources, single‐unitCBT(sCBT) is associated with a delayed hematologic recovery, which may lead to a higher infection‐related mortality (IRM). Co‐infusion with thesCBTofCD34+peripheral blood stem cells from a third‐party donor (TPD) (sCBT + TPDCD34+) has been shown to markedly accelerate leukocyte recovery, potentially reducing theIRM. However, to our knowledge, no comparative studies have focused on severe infections andIRMwith these 2sCBTstrategies.

Methods

A total of 148 consecutivesCBT(2000–2010, median follow‐up 4.5 years) were included in a multicenter retrospective study to analyze the incidence and risk factors ofIRMand severe viral and invasive fungal infections (IFIs). Neutrophil engraftment occurred in 90% ofsCBT(n = 77) and 94%sCBT + TPDCD34+(n = 71) recipients at a median of 23 and 12 days post transplantation, respectively (P < 0.01).

Results

The 4‐yearIRMwas 24% and 20%, respectively (P = 0.7), with no differences at day +30 (5% and 4%, respectively) and day +100 (10% and 8%, respectively). In multivariate analysis early status of the underlying malignancy, cytomegalovirus (CMV)‐seronegative recipient and highCD34+cell content in the cord blood unit before cryostorage (≥1.4 × 105/kg) were protective ofIRM. Among the causes ofIRM, bacterial infections andIFIs were more common insCBT(15% vs. 4%), whileCMVdisease and parasitic infections were more common in thesCBT + TPDCD34+cohort (5% vs. 16%).

Conclusion

These data show thatsCBTsupported withTPDCD34+cells results in much shorter periods of post‐transplant leukopenia, but the short‐ and long‐term rates ofIRMwere comparable to those ofsCBT, presumably because immune recovery is equally delayed in both graft types.
Metabolic and photosynthetic consequences of blocking starch biosynthesis in the green alga Chlamydomonas reinhardtii sta6 mutant
Authors: Krishnan Anagha , Kumaraswamy G. Kenchappa , Vinyard David J. , Gu Huiya , Ananyev Gennady , Posewitz Matthew C. , Dismukes G. Charles
Published: February 2015

Upon nutrient deprivation, microalgae partition photosynthate into starch and lipids at the expense of protein synthesis and growth. We investigated the role of starch biosynthesis with respect to photosynthetic growth and carbon partitioning in the Chlamydomonas reinhardtii starchless mutant, sta6, which lacks ADP‐glucose pyrophosphorylase. This mutant is unable to convert glucose‐1–phosphate to ADP‐glucose, the precursor of starch biosynthesis. During nutrient‐replete culturing, sta6 does not re‐direct metabolism to make more proteins or lipids, and accumulates 20% less biomass. The underlying molecular basis for the decreased biomass phenotype was identified using LC–MS metabolomics studies and flux methods. Above a threshold light intensity, photosynthetic electron transport rates (water → CO2) decrease in sta6 due to attenuated rates of NADPH re‐oxidation, without affecting photosystems I or II (no change in isolated photosynthetic electron transport). We observed large accumulations of carbon metabolites that are precursors for the biosynthesis of lipids, amino acids and sugars/starch, indicating system‐wide consequences of slower NADPH re‐oxidation. Attenuated carbon fixation resulted in imbalances in both redox and adenylate energy. The pool sizes of both pyridine and adenylate nucleotides in sta6 increased substantially to compensate for the slower rate of turnover. Mitochondrial respiration partially relieved the reductant stress; however, prolonged high‐light exposure caused accelerated photoinhibition. Thus, starch biosynthesis in Chlamydomonas plays a critical role as a principal carbon sink influencing cellular energy balance however, disrupting starch biosynthesis does not redirect resources to other bioproducts (lipids or proteins) during nutrient‐replete culturing, resulting in cells that are susceptible to photochemical damage caused by redox stress.
Evaluation of the protection of primates transfused with variant Creutzfeldt‐Jakob disease–infected blood products filtered with prion removal devices: a 5‐year update
Authors: Lescoutra‐Etchegaray Nathalie , Jaffré Nina , Sumian Chryslain , Durand Valérie , Correia Evelyne , Mikol Jacqueline , Luccantoni‐Freire Sophie , Culeux Audrey , Deslys Jean‐Philippe , Comoy Emmanuel E.
Published: February 2015

BACKGROUND

Analysis of archived appendix samples reveals that one in 2000 individuals in the United Kingdom may carry the infectious prion protein associated with variant Creutzfeldt‐Jakob disease (vCJD), raising questions about the risk of transfusion transmission from apparently healthy carriers. Blood leukoreduction shows limited efficiency against prions. Therefore, in absence of antemortem diagnostic tests, prion removal filters, including the P‐Capt filter were designed to improve blood transfusion safety.

STUDY DESIGN AND METHODS

We evaluated the performances of two filters, the P‐Capt and one prototype (PMC#005), with blood‐borne infectivity in two independent experiments. Blood was drawn twice from prion‐infected macaques. Corresponding RBCCs were prepared according to two different procedures: in Study A, the leukoreduction step was followed by the filtration through the P‐Capt. In Study B, the leukoreduction and prion removal were performed simultaneously through the PMC#005. For each study, two groups of three animals were transfused twice with samples before or after filtration.

RESULTS

Among the six macaques transfused with nonfiltered samples, five developed neurologic signs but only four exhibited peripheral detectable protease‐resistant prion protein (PrPres) accumulation. In Study A, the three animals transfused with P‐Capt–filtered samples remain asymptomatic and devoid of PrPres in lymph node biopsies 6 years after the transfusion. In Study B, one animal transfused with PMC#005‐filtered samples developed vCJD.

CONCLUSION

After 5 to 6 years of progress, this ongoing study provides encouraging results on the prion blood removal performances of the P‐Capt filter in macaques, an utmost relevant model for human prion diseases.
Collection of peripheral blood progenitor cells on Day 4 is feasible and effective while reducing granulocyte–colony‐stimulating factor exposure to healthy donors
Authors: Flommersfeld Sabine , Sohlbach Kristina , Jaques Gabriele , Bein Gregor , Hoffmann Jörg , Kostrewa Philippe , Sachs Ulrich J.
Published: February 2015

BACKGROUND

Peripheral blood progenitor cells (PBPCs) are the most common stem cell source for allogeneic transplantations. Analysis of our collection data obtained with a Spectra Optia device (Terumo) for apheresis demonstrated collection efficacies (CEs) exceeding our internal target levels of 5 × 106 CD34+ cells/kg body weight of the recipient when collected on Day 5. We thus aimed to investigate whether collection on Day 4 would lead to adequate amounts of PBPCs while minimizing granulocyte–colony‐stimulating factor (G‐CSF) exposure in healthy donors.

STUDY DESIGN AND METHODS

We compared feasibility and effectiveness of Day 5 versus Day 4 collections with data obtained from 23 and 18 allogeneic procedures, respectively.

RESULTS

Both groups were comparable with regard to donor and collection characteristics. Product characteristics as well as platelet loss, CE, throughput, and collection rate did not differ between both protocols. A higher contamination with white blood cells (WBCs; ×109/L) was observed in products collected on Day 5 compared to Day 4 (231 [range, 181‐299] vs. 203 [range, 165‐239]; p = 0.004). A second apheresis procedure was required in three of 23 patients and three of 18 patients, respectively (p = 0.6) to obtain the required PBPC dose.

CONCLUSIONS

PBPC apheresis on Day 4 seems as feasible and effective as collection on Day 5. Collection on Day 4 produces lower WBC content in the product and allows a reduction in G‐CSF exposure to healthy donors.
Blood utilization at a national referral hospital in sub‐Saharan Africa
Authors: Butler Elissa K. , Hume Heather , Birungi Isaac , Ainomugisha Brenda , Namazzi Ruth , Ddungu Henry , Kajja Isaac , Nabadda Susan , McCullough Jeffrey
Published: February 2015

BACKGROUND

A safe and adequate supply of blood is critical to improving health care systems in sub‐Saharan Africa, where little is known about the current use of blood. The aim of this study was to comprehensively describe the use of blood at a tertiary care hospital to inform future efforts to strengthen blood programs in resource‐limited settings.

STUDY DESIGN AND METHODS

Data were collected from blood bank documentation for all units issued at Mulago Hospital Complex in Kampala, Uganda, from mid‐January to mid‐April 2014.

RESULTS

A total of 6330 units (69% whole blood, 32% red blood cells, 6% platelets, 2% plasma) were issued over the 3‐month study period to 3662 unique patients. Transfusion recipients were 58% female and median age was 27 years (interquartile range [IQR], 14–41). Median pretransfusion hemoglobin was 5.6 g/dL (IQR, 4.0–7.2 g/dL, n = 1090). Strikingly, cancer was the top indication for transfusion (33.5%), followed by pregnancy‐related complications (12.4%) and sickle cell disease (6.9%).

CONCLUSION

This study provides a comprehensive picture of blood use at a national referral hospital in sub‐Saharan Africa. Noncommunicable diseases, particularly oncologic conditions, represent a large proportion of demand for transfusion services.
Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008–2013
Authors: Duffy D. , Selmic L. E. , Kendall A. R. , Powers B. E.
Published: February 2015

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non‐mammary and non‐thyroidal soft tissue and visceralEOSin dogs. Thirty‐three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0–458 days) versus median survival time of 13 days (range: 0–20 days)]. The use of surgery should be considered in the management of dogs with non‐mammary and non‐thyroidal soft tissue and visceralEOS.
Helical Flow Disturbances in a Multinozzle Combustor
Authors: Aguilar Michael , Malanoski Michael , Adhitya Gautham , Emerson Benjamin , Acharya Vishal , Noble David , Lieuwen Tim
Published: February 2015

This paper describes an experimental investigation of a transversely forced, swirl stabilized combustor. Its objective is to compare the unsteady flow structures in single and triple nozzle combustors and determine how well a single nozzle configuration emulates the characteristics of a multinozzle one. The experiment consists of a series of velocity field measurements captured on planes normal to the jet axis. As expected, there are differences between the single and triple nozzle flow fields, but the differences are not large in the regions upstream of the jet merging zone. Direct comparisons of the time-averaged flow fields reveal a higher degree of nonaxisymmetry for the flow fields of nozzles in a multinozzle configuration. Azimuthal decompositions of the velocity fields show that the transverse acoustic forcing has an important influence on the dynamics, but that the single and multinozzle configurations have similar forced response dynamics near the dump plane. Specifically, the axial dependence of the amplitude in the highest energy axisymmetric and helical flow structures is quite similar in the two configurations. Thus, upstream of the jet merging zone, the hydrodynamic influence of one swirling jet on the other is minimal. As such, that jet–jet interactions in this configuration do not have a significant influence on the unsteady flow structures.
Effect of Potting Technique on the Measurement of Six Degree-of-Freedom Viscoelastic Properties of Human Lumbar Spine Segments
Authors: Amin Dhara B. , Lawless Isaac M. , Sommerfeld Dana , Stanley Richard M. , Ding Boyin , Costi John J.
Published: February 2015

Polymethyl methacrylate (PMMA) and Wood's Metal are fixation media for biomechanical testing; however, the effect of each potting medium on the measured six degree-of-freedom (DOF) mechanical properties of human lumbar intervertebral discs is unknown. The first aim of this study was to compare the measured 6DOF elastic and viscoelastic properties of the disc when embedded in PMMA compared to repotting in Wood's Metal. The second aim was to compare the surface temperature of the disc when potted with PMMA and Wood's Metal. Six human lumbar functional spinal units (FSUs) were first potted in PMMA, and subjected to overnight preload in a saline bath at 37 °C followed by five haversine loading cycles at 0.1 Hz in each of 6DOF loading directions (compression, left/right lateral bending, flexion, extension, left/right axial rotation, anterior/posterior, and lateral shear). Each specimen was then repotted in Wood's Metal and subjected to a 2-h re-equilibrating preload followed by repeating the same 6DOF tests. Outcome measures of stiffness and phase angle were calculated from the final loading cycle in each DOF and were expressed as normalized percentages relative to PMMA (100%). Disc surface temperatures (anterior, left/right lateral) were measured during potting. Paired t-tests (with alpha adjusted for multiple DOF) were conducted to compare the differences in each outcome parameter between PMMA and Wood's Metal. No significant differences in stiffness or phase angle were found between PMMA and Wood's Metal. On average, the largest trending differences were found in the shear DOFs for both stiffness (approximately 35% greater for Wood's Metal compared to PMMA) and phase angle (approximately 15% greater for Wood's Metal). A significant difference in disc temperature was found at the anterior surface after potting with Wood's Metal compared to PMMA, which did not exceed 26 °C. Wood's Metal is linear elastic, stiffer than PMMA and may reduce measurement artifact of potting medium, particularly in the shear directions. Furthermore, it is easier to remove than PMMA, reuseable, and cost effective.
A Novel Lattice Model on a Gradient Road With the Consideration of Relative Current
Authors: Cao Jin-Liang , Shi Zhong-Ke
Published: February 2015

In this paper, a novel lattice model on a single-lane gradient road is proposed with the consideration of relative current. The stability condition is obtained by using linear stability theory. It is shown that the stability of traffic flow on the gradient road varies with the slope and the sensitivity of response to the relative current: when the slope is constant, the stable region increases with the increasing of the sensitivity of response to the relative current; when the sensitivity of response to the relative current is constant, the stable region increases with the increasing of the slope in uphill and decreases with the increasing of the slope in downhill. A series of numerical simulations show a good agreement with the analytical result and show that the sensitivity of response to the relative current is better than the slope in stabilizing traffic flow and suppressing traffic congestion. By using nonlinear analysis, the Burgers, Korteweg–de Vries (KdV), and modified Korteweg–de Vries (mKdV) equations are derived to describe the triangular shock waves, soliton waves, and kink–antikink waves in the stable, metastable, and unstable region, respectively, which can explain the phase transitions from free traffic to stop-and-go traffic, and finally to congested traffic. One conclusion is drawn that the traffic congestion on the gradient road can be suppressed efficiently by introducing the relative velocity.
Geometric Error Modeling, Separation, and Compensation of Tilted Toric Wheel in Fewer-Axis Grinding for Large Complex Optical Mirrors
Authors: Jiang Zhenhua , Yin Yuehong , Chen Xing
Published: February 2015

In ultraprecision grinding, especially for large complex optical mirrors, the geometric accuracy of grinding wheel plays a vital role and almost dominates the success of the entire grinding process. In this paper, a complete set of geometric error modeling, separation, and compensation methods of tilted toric wheel is established for fewer-axis grinding of large complex optical mirrors. Based on the kinematic equations with the assumptions of virtual axes for toric wheel, a mirror surface error model including all wheel error components is established, providing an error prediction for mirror surface. By linearizing the mirror surface error model and using the error information of mirror surface, solving and separating wheel error components are achieved. Then, the mirror surface with highly improved accuracy is obtained after the compensation of wheel trajectories with calculated wheel error components. Finally, the above method is well verified by the simulation.
Invasion of the T tubules
Authors: Gough Nancy R.
Published: February 2015

Directed secretion of the chemoattractant growth factor FGF enables the targeted growth of tracheal branches into flight muscle T tubules.
Thermosensitive and Mucoadhesive Pluronic-Hydroxypropylmethylcellulose Hydrogel Containing the Mini-CD4 M48U1 Is a Promising Efficient Barrier against HIV Diffusion through Macaque Cervicovaginal Mucus
Authors: Bouchemal Kawthar , Aka-Any-Grah Armelle , Dereuddre-Bosquet Nathalie , Martin Loïc , Lievin-Le-Moal Vanessa , Le Grand Roger , Nicolas Valérie , Gibellini Davide , Lembo David , Poüs Christian , Koffi Armand , Ponchel Gilles
Published: February 2015

To be efficient, vaginal microbicide hydrogels should form a barrier against viral infections and prevent virus spreading through mucus. Multiple particle tracking was used to quantify the mobility of 170-nm fluorescently labeled COOH-modified polystyrene particles (COOH-PS) into thermosensitive hydrogels composed of amphiphilic triblock copolymers with block compositions EO

n

-PO

m

-EO

n

(where EO refers to ethylene oxide and PO to propylene oxide) containing mucoadhesive hydroxypropylmethylcellulose (HPMC). COOH-PS were used to mimic the size and the surface charge of HIV-1. Analysis of COOH-PS trajectories showed that particle mobility was decreased by Pluronic hydrogels in comparison with cynomolgus macaque cervicovaginal mucus and hydroxyethylcellulose hydrogel (HEC; 1.5% by weight [wt%]) used as negative controls. Formulation of the peptide mini-CD4 M48U1 used as an anti-HIV-1 molecule into a mixture of Pluronic F127 (20 wt%) and HPMC (1 wt%) did not affect its anti-HIV-1 activity in comparison with HEC hydrogel. The 50% inhibitory concentration (IC
50
) was 0.53 μg/ml (0.17 μM) for M48U1-HEC and 0.58 μg/ml (0.19 μM) for M48U1-F127-HPMC. The present work suggests that hydrogels composed of F127-HPMC (20/1 wt%, respectively) can be used to create an efficient barrier against particle diffusion in comparison to conventional HEC hydrogels.
Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing
Authors: Singh B. N. , Upreti D. K. , Singh B. R. , Pandey G. , Verma S. , Roy S. , Naqvi A. H. , Rawat A. K. S.
Published: February 2015

Quorum sensing (QS) regulates group behaviors of
Candida albicans
such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by
C. albicans
, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of
C. albicans
infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (
Usnea
longissima
), can be implemented as a sensitizing agent for FCZ-resistant
C. albicans
NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons—biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of
C. albicans
infections.
Autophagy Regulates Colistin-Induced Apoptosis in PC-12 Cells
Authors: Zhang Ling , Zhao Yonghao , Ding Wenjian , Jiang Guozheng , Lu Ziyin , Li Li , Wang Jinli , Li Jian , Li Jichang
Published: February 2015

Colistin is a cyclic cationic polypeptide antibiotic with activity against multidrug-resistant Gram-negative bacteria. Our recent study demonstrated that colistin induces apoptosis in primary chick cortex neurons and PC-12 cells. Although apoptosis and autophagy have different impacts on cell fate, there is a complex interaction between them. Autophagy plays an important role as a homeostasis regulator by removing excessive or unnecessary proteins and damaged organelles. The aim of the present study was to investigate the modulation of autophagy and apoptosis regulation in PC-12 cells in response to colistin treatment. PC-12 cells were exposed to colistin (125 to 250 μg/ml), and autophagy was detected by visualization of monodansylcadaverine (MDC)-labeled vacuoles, LC3 (microtubule-associated protein 1 light chain 3) immunofluorescence microscopic examination, and Western blotting. Apoptosis was measured by flow cytometry, Hoechst 33258 staining, and Western blotting. Autophagosomes were observed after treatment with colistin for 12 h, and the levels of LC3-II gene expression were determined; observation and protein levels both indicated that colistin induced a high level of autophagy. Colistin treatment also led to apoptosis in PC-12 cells, and the level of caspase-3 expression increased over the 24-h period. Pretreatment of cells with 3-methyladenine (3-MA) increased colistin toxicity in PC-12 cells remarkably. However, rapamycin treatment significantly increased the expression levels of LC3-II and beclin 1 and decreased the rate of apoptosis of PC-12 cells. Our results demonstrate that colistin induced autophagy and apoptosis in PC-12 cells and that the latter was affected by the regulation of autophagy. It is very likely that autophagy plays a protective role in the reduction of colistin-induced cytotoxicity in neurons.
The Mycobacterium tuberculosis Outer Membrane Channel Protein CpnT Confers Susceptibility to Toxic Molecules
Authors: Danilchanka Olga , Pires David , Anes Elsa , Niederweis Michael
Published: February 2015

Mycobacterium tuberculosis
, the causative agent of tuberculosis, is protected from toxic solutes by an effective outer membrane permeability barrier. Recently, we showed that the outer membrane channel protein CpnT is required for efficient nutrient uptake by
M. tuberculosis
and
Mycobacterium bovis
BCG. In this study, we found that the
cpnT
mutant of
M. bovis
BCG is more resistant than the wild type to a large number of drugs and antibiotics, including rifampin, ethambutol, clarithromycin, tetracycline, and ampicillin, by 8- to 32-fold. Furthermore, the
cpnT
mutant of
M. bovis
BCG was 100-fold more resistant to nitric oxide, a major bactericidal agent required to control
M. tuberculosis
infections in mice. Thus, CpnT constitutes the first outer membrane susceptibility factor in slow-growing mycobacteria. The dual functions of CpnT in uptake of nutrients and mediating susceptibility to toxic molecules are reflected in macrophage infection experiments: while loss of CpnT was detrimental for
M. bovis
BCG in macrophages that enable bacterial replication, presumably due to inadequate nutrient uptake, it conferred a survival advantage in macrophages that mount a strong bactericidal response. Importantly, the
cpnT
gene showed a significantly higher density of nonsynonymous mutations in drug-resistant clinical
M. tuberculosis
strains, indicating that CpnT is under selective pressure in human tuberculosis and/or during chemotherapy. Our results indicate that the CpnT channel constitutes an outer membrane gateway controlling the influx of nutrients and toxic molecules into slow-growing mycobacteria. This study revealed that reducing protein-mediated outer membrane permeability might constitute a new drug resistance mechanism in slow-growing mycobacteria.
Experimental Resistance to Drug Combinations in Leishmania donovani: Metabolic and Phenotypic Adaptations
Authors: Berg Maya , García-Hernández Raquel , Cuypers Bart , Vanaerschot Manu , Manzano José I. , Poveda José A. , Ferragut José A. , Castanys Santiago , Dujardin Jean-Claude , Gamarro Francisco
Published: February 2015

Together with vector control, chemotherapy is an essential tool for the control of visceral leishmaniasis (VL), but its efficacy is jeopardized by growing resistance and treatment failure against first-line drugs. To delay the emergence of resistance, the use of drug combinations of existing antileishmanial agents has been tested systematically in clinical trials for the treatment of visceral leishmaniasis (VL).
In vitro
,
Leishmania donovani
promastigotes are able to develop experimental resistance to several combinations of different antileishmanial drugs after 10 weeks of drug pressure. Using an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach, we identified metabolic changes in lines that were experimentally resistant to drug combinations and their respective single-resistant lines. This highlighted both collective metabolic changes (found in all combination therapy-resistant [CTR] lines) and specific ones (found in certain CTR lines). We demonstrated that single-resistant and CTR parasite cell lines show distinct metabolic adaptations, which all converge on the same defensive mechanisms that were experimentally validated: protection against drug-induced and external oxidative stress and changes in membrane fluidity. The membrane fluidity changes were accompanied by changes in drug uptake only in the lines that were resistant against drug combinations with antimonials, and surprisingly, drug accumulation was higher in these lines. Together, these results highlight the importance and the central role of protection against oxidative stress in the different resistant lines. Ultimately, these phenotypic changes might interfere with the mode of action of all drugs that are currently used for the treatment of VL and should be taken into account in drug development.