bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial ranking strategy and enhanced peripheral vision discrimination optimize performance and efficiency of visual sequential search
Authors: Veneri Giacomo , Pretegiani Elena , Fargnoli Francesco , Rosini Francesca , Vinciguerra Claudia , Federighi Pamela , Federico Antonio , Rufa Alessandra
Published: June 2014

Visual sequential search might use a peripheral spatial ranking of the scene to put the next target of the sequence in the correct order. This strategy, indeed, might enhance the discriminative capacity of the human peripheral vision and spare neural resources associated with foveation. However, it is not known how exactly the peripheral vision sustains sequential search and whether the sparing of neural resources has a cost in terms of performance. To elucidate these issues, we compared strategy and performance during an alpha‐numeric sequential task where peripheral vision was modulated in three different conditions: normal, blurred, or obscured. If spatial ranking is applied to increase the peripheral discrimination, its use as a strategy in visual sequencing should differ according to the degree of discriminative information that can be obtained from the periphery. Moreover, if this strategy spares neural resources without impairing the performance, its use should be associated with better performance. We found that spatial ranking was applied when peripheral vision was fully available, reducing the number and time of explorative fixations. When the periphery was obscured, explorative fixations were numerous and sparse; when the periphery was blurred, explorative fixations were longer and often located close to the items. Performance was significantly improved by this strategy. Our results demonstrated that spatial ranking is an efficient strategy adopted by the brain in visual sequencing to highlight peripheral detection and discrimination; it reduces the neural cost by avoiding unnecessary foveations, and promotes sequential search by facilitating the onset of a new saccade.
Family Relationships and Adolescents' Health Attitudes and Weight: The Understudied Role of Sibling Relationships
Authors: Senguttuvan Umadevi , Whiteman Shawn D. , Jensen Alexander C.
Published: June 2014

Family relationships are important predictors of adolescents' diet, physical activity, and health issues including obesity. Despite their prominence in the family, siblings have received little attention on how they may influence these health‐related behaviors. Addressing this gap, this study examined associations between sibling relationship qualities and adolescents' health attitudes, exercise behaviors, and weight controlling for other family relationship qualities. Participants included one parent and two adolescent siblings (ages 12–19) from 326 families. Multilevel models indicated that net of parent–adolescent relationship qualities and adolescents' personal characteristics, sibling intimacy was related to healthy attitudes and greater exercise behaviors, whereas sibling conflict was associated with increased risk of being overweight. Links between sibling conflict and weight status, however, were further qualified by gender composition of the sibling dyad. Results highlight the significance of sibling relationships in adolescents' everyday health attitudes and behaviors and implications for intervention efforts are discussed.
Transitioning to Postdivorce Family Life: A Grounded Theory Investigation of Resilience in Coparenting
Authors: Jamison Tyler B. , Coleman Marilyn , Ganong Lawrence H. , Feistman Richard E.
Published: June 2014

Court‐ordered shared physical and legal custody has led to greater numbers of couples that must coparent following divorce. We conducted a grounded theory study to examine resilience processes in postdivorce coparenting. Data were collected through in‐depth interviews from 47 divorced mothers and fathers. The analysis revealed that successfully transitioning from married to divorced coparenting required intrapersonal changes (i.e., how participants thought and felt about their ex‐partners) as well as behavioral changes (e.g., avoiding conflict). Parents who reported focusing on children, regulating their emotional responses, and choosing battles about time and money were more effective than those who had difficulty letting go of divorce anger or engaged in frequent conflicts. Implications for parent educators and clinicians are discussed.
Conformation‐dependent backbone geometry restraints set a new standard for protein crystallographic refinement
Authors: Moriarty Nigel W. , Tronrud Dale E. , Adams Paul D. , Karplus P. Andrew
Published: May 2014

Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common use today have been designed on the assumption that each type of bond or angle has a single ideal value that is independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and, as a first step towards using such information to build more accurate models, ultra‐high‐resolution protein crystal structures have been used to derive a conformation‐dependent library (CDL) of restraints for the protein backbone [Berkholz et al. (2009) Structure 17, 1316–1325]. Here, we report the introduction of this CDL into the phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the CDL yields models that have substantially better agreement with ideal main‐chain bond angles and lengths and, on average, a slightly enhanced fit to the X‐ray data. No disadvantages of using the backbone CDL are apparent. In phenix, use of the CDL can be selected by simply specifying the cdl = True option. This successful implementation paves the way for further aspects of the context dependence of ideal geometry to be characterized and applied to improve experimental and predictive modeling accuracy.
Laboratory evolution of adenylyl cyclase independent learning in Drosophila and missing heritability
Authors: Cressy M. , Valente D. , Altick A. , Kockenmeister E. , Honegger K. , Qin H. , Mitra P. P. , Dubnau J.
Published: May 2014

Gene interactions are acknowledged to be a likely source of missing heritability in large‐scale genetic studies of complex neurological phenotypes. However, involvement of rare variants, de novo mutations, genetic lesions that are not easily detected with commonly used methods and epigenetic factors also are possible explanations. We used a laboratory evolution study to investigate the modulatory effects of background genetic variation on the phenotypic effect size of a null mutation with known impact on olfactory learning. To accomplish this, we first established a population that contained variation at just 23 loci and used selection to evolve suppression of the learning defect seen with null mutations in the rutabaga adenylyl cyclase. We thus biased the system to favor relatively simplified outcomes by choosing a Mendelian trait and by restricting the genetic variation segregating in the population. This experimental design also assures that the causal effects are among the known 23 segregating loci. We observe a robust response to selection that requires the presence of the 23 variants. Analyses of the underlying genotypes showed that interactions between more than two loci are likely to be involved in explaining the selection response, with implications for the missing heritability problem.
Temperate extinction in squamate reptiles and the roots of latitudinal diversity gradients
Authors: Pyron R. Alexander
Published: June 2014

Aim

Many ecological and evolutionary hypotheses have been proposed to explain latitudinal diversity gradients. However, any mechanistic explanation must include factors that change at least one of the three processes that can directly affect species richness: speciation, extinction and dispersal. I hypothesize that higher extinction in temperate areas, higher speciation in tropical areas and reduced dispersal into temperate regions drives latitudinal diversity gradients in squamates, and that these processes may be common in other groups.

Location

World‐wide.

Methods

I test for these processes using phylogenetic methods that can untangle speciation and extinction with respect to latitudinal position (GeoSSE), using a dated phylogeny containing c. 45% of all squamates (4161 species) with data on their geographic occurrence.

Results

I find that lineages in the tropics have high speciation and low extinction, but that temperate lineages have even higher speciation and extinction, leading to lower net diversification and higher turnover in temperate areas, with much higher rates of dispersal into the tropics from temperate areas than the reverse.

Main conclusions

Recent empirical studies using dated molecular phylogenies appear to be consistent in supporting a similar set of simple and intuitive results for processes driving latitudinal gradients in species richness: higher net diversification rates in the tropics, higher relative extinction fractions in temperate regions and reduced dispersal out of the tropics. I suggest that higher temperate extinction represents a dominant force for the origin and maintenance of latitudinal gradients, particularly in groups with ancient temperate clades.
Asp68His mutation in the A1 domain of human factor V causes impaired secretion and ineffective translocation
Authors: Liu H.‐C. , Shen M.‐C. , Eng H.‐L. , Wang C.‐H. , Lin T.‐M.
Published: June 2014

Congenital factor V (FV) deficiency is a rare inherited disorder. We determined the mechanism of a missense mutation, Asp68His, in the A1 domain of the FV protein, is associated with severe FV deficiency. We characterized the mutant FV‐Asp68His protein using in vitro expression studies by using specific secretion and degradation pathway inhibitors and analysed the intracellular translocation of the mutant protein by immunofluorescence staining. The Asp68His mutation caused very low levels of FV protein in the conditioned media, with normal specific FV activity. Similar mRNA degradation rates between FV‐wild‐type (wt) and FV‐Asp68His mRNA showed that the Asp68His mutation does not affect FV expression at the transcriptional level. A specific secretion pathway inhibitor, brefeldin A, was used to demonstrate that the lower efficiency of transport to the outside of the cell for FV‐Asp68His mutant protein compared with that of the FV‐wt protein. Furthermore, we showed that the Asp68His mutation resulted in increased intracellular degradation through a MG132‐mediated proteasomal degradation pathway. In the transfected cell lysates, FV‐wt protein had multiple posttranslational modified forms, but the FV‐Asp68His protein was not completely glycosylated. We further observed that the FV‐Asp68His protein was retrieved in the endoplasmic reticulum only and did not undergo transport to the Golgi apparatus, leading to impaired secretion. These results strongly suggest that the Asp68His mutation may result in intracellular defective trafficking and enhanced degradation, and impaired secretion of FV protein.
Erythropoietin‐stimulating agents in the management of anemia of end‐stage renal disease patients on regular hemodialysis: A prospective randomized comparative study from Qatar
Authors: Al‐Ali Fadwa Saqr , El‐Sayed Abdelfattah Mohamed , Fawzy Ashraf Ahmed , Hamdy Ahmed Farouk , Abdulla Aisha Elsayed
Published: June 2014

Despite extensive use, to the best of our knowledge, no trial has simultaneously compared the three currently used erythropoietin‐stimulating agents (ESAs) in a prospective manner in the treatment of anemia of end‐stage renal disease patients. All hemodialysis patients in Qatar who were treated with short‐acting epoetin alfa or beta have been screened. Eligible patients had been prospectively randomized, either to continue on the previous regimen of epoetin or to receive darbepoetin alfa or continuous erythropoietin receptor activator (CERA) for a total period of 40 weeks. All groups were assessed at the end of the study for safety and efficacy parameters. A total of 327 eligible patients were randomized. Mean hemoglobin concentration remained constant within the recommended target range (11–12 g/dL) throughout the study in the three studied groups. The percentage of patients who reached the target range was constantly above 50% in the second half of the study among CERA group patients who also had significantly lower mean number of dose adjustments as compared with the other two groups (P = 0.001). Similarly, the number of discontinuations of ESA among epoetin, darbepoetin, and CERA groups was 17, 19, and 9, respectively (P = 0.042). The frequencies of adverse events were similar in all groups. This study has specifically compared the effect of ESA type on the variability of serum hemoglobin levels in hemodialysis patients. Furthermore, it confirmed the efficacy and safety of once monthly CERA for maintaining tight hemoglobin control within recommended target ranges.
Fibroblast growth factor receptor (FGFR) gene amplifications are rare events in bladder cancer
Authors: Fischbach Anna , Rogler Anja , Erber Ramona , Stoehr Robert , Poulsom Richard , Heidenreich Axel , Schneevoigt Birte‐Swantje , Hauke Sven , Hartmann Arndt , Knuechel Ruth , Veeck Jürgen , Gaisa Nadine T
Published: June 2014

Aims

Activating point mutations and protein overexpression of fibroblast growth factor receptors (FGFRs), especially FGFR3, are frequent events in bladder cancer. Little is known about gene amplifications, therefore we characterized amplification of FGFR1‐3 by fluorescence in‐situ hybridization (FISH).

Methods and results

Tumours of 153 patients (n = 65 pTa low‐grade, n = 15 pTa high‐grade, n = 37 pT1, n = 20 pT2, n = 10 pT3, n = 6 pT4) were analysed by FISH for FGFR1‐3 copy numbers and screened for FGFR3 mutations and immunohistochemical protein expression. Amplifications of FGFR1 were found in 1.6% (two of 122), FGFR2 in 0.8% (one of 121) and FGFR3 in 3.4% (five of 145). All amplifications were high‐level amplifications, not overlapping with polysomy. Amplifications were found in papillary/papillary‐invasive tumour parts, and predominantly in tumours with enhanced Ki67 index (>10%), aberrant CK20 expression, and low p53 expression. All FGFR3‐amplified samples showed concomitant FGFR3 mutations and FGFR3 protein overexpression. FGFR amplifications were not associated significantly with gender, age, grade or stage in statistical analyses.

Conclusions

FGFR amplifications are rare events in bladder cancer, with FGFR3 amplification being the most prevalent (3.4% of cases). Concomitant FGFR3 mutations and protein overexpression indicate that FGFR3‐mediated signalling in these tumours would probably be highly active. This patient subgroup may be particularly suited to FGFR‐targeted pharmacotherapy.
Etidronate causes minimal changes in the ability of sodium hypochlorite to dissolve organic matter
Authors: Tartari T. , Guimarães B. M. , Amoras L. S. , Duarte M. A. H. , Silva e Souza P. A. R. , Bramante C. M.
Published: June 2014

Aim

To evaluate the effect of individual and combined use of sodium hypochlorite (NaOCl), etidronate (HEDP) and ethylenediaminetetraacetic acid (EDTA) in tissue dissolution.

Methodology

Sixty fragments of bovine muscle tissue were prepared and their weights determined on a precision scale. The samples were then distributed in the following groups (n = 10): G1 – saline solution (control); G2 – 17% EDTA; G3 – 18% HEDP; G4 – 2.5% NaOCl; G5 – mixture of 5% NaOCl + 17% EDTA; and G6 – mixture of 5% NaOCl + 18% HEDP. The specimens in each group were immersed in the solutions for 5, 10 and 15 min and reweighted at each time period. Analysis of variance (anova) and Tukey's multiple‐comparison tests (α<0.05) were applied to identify the intragroup and intergroup differences.

Results

G1, G2, G3 and G5 did not dissolve the organic matter. G4 and G6 significantly reduced the weights of specimens at all periods. Amongst the groups, the difference in ability to dissolve organic matter was greater and significant in the following order G4 = G6 > G5 = G3 = G2 = G1 after 5 min of immersion and G4 > G6 > G5 = G3 = G2 = G1 after 10 and 15 min of immersion.

Conclusion

The only solution capable of dissolving organic matter was NaOCl. In the mixtures analysed, this ability was arrested by EDTA; however, it was minimally affected by the HEDP, proving that this combination, if used during the biomechanical preparation, is able to dissolve of organic matter.
Pilonidal sinus surgery: could we predict postoperative complications?
Authors: Milone Marco , Di Minno Matteo ND , Bianco Paolo , Coretti Guido , Musella Mario , Milone Francesco
Published: June 2014

Pilonidal sinus surgery could, as of now, be considered a surgery tailored more to the surgeon than to the patient. In an attempt to give to surgeons an objective instrument of decision, we have evaluated which variables could be considered predictive of postoperative complications after pilonidal sinus surgery. A prospective electronic database of all patients treated for sacrococcygeal pilonidal disease was analysed. Sex, age, obesity, smoking, recurrent disease, the presence of multiple orifices and the distance between the most lateral orifice and midline were recorded and correlated with the occurrence of postoperative complications (infection and recurrence); 1006 patients were evaluated. Excision with primary mid‐line closure was performed on all the patients. Mean follow‐up was 7·3 ± 3·6 years. A total of 158 patients with postoperative complications (infection and/or recurrence) were recorded during this period. A multivariate analysis showed that, after adjusting for major clinical and demographic characteristics, only a recurrent disease [odds ratio (OR): 3·41, 95% confidence interval (CI): 1·89–6·15, P < 0·001] and the distance of lateral orifice from midline (OR: 26·3, 95% CI: 12·2–56·7, P < 0·001) were independent predictors of overall postoperative complications. Focussing on the distance from midline, the receiver operative characteristic (ROC) analysis showed that the distance of lateral orifice from midline predicted 79·2% of complications and the Youden's test identified the best cut‐off as 2·0 cm for this variable. An evidence‐based tool for deciding on the type of surgical intervention could be developed and validated by further ad hoc prospective studies evaluating our results in comparison to other different types of surgical techniques. Our results support the use of these variables as an effective way to tailor pilonidal sinus surgery to the patient, so as to obtain the best results in patient care.
Evidence for sex‐specific selection in brain: a case study of the nine‐spined stickleback
Authors: Herczeg G. , Välimäki K. , Gonda A. , Merilä J.
Published: June 2014

Theory predicts that the sex making greater investments into reproductive behaviours demands higher cognitive ability, and as a consequence, larger brains or brain parts. Further, the resulting sexual dimorphism can differ between populations adapted to different environments, or among individuals developing under different environmental conditions. In the nine‐spine stickleback (Pungitius pungitius), males perform nest building, courtship, territory defence and parental care, whereas females perform mate choice and produce eggs. Also, predation‐adapted marine and competition‐adapted pond populations have diverged in a series of ecologically relevant traits, including the level of phenotypic plasticity. Here, we studied sexual dimorphism in brain size and architecture in nine‐spined stickleback from marine and pond populations reared in a factorial experiment with predation and food treatments in a common garden experiment. Males had relatively larger brains, largertelencephala,cerebellaandhypothalami(6–16% divergence) than females, irrespective of habitat. Females tended to have largerbulbi olfactoriithan males (13%) in the high food treatment, whereas no such difference was found in the low food treatment. The strong sexual dimorphism in brain architecture implies that the different reproductive allocation strategies (behaviourvs. egg production) select for different investments into the costly brains between males and females. The lack of habitat dependence in brain sexual dimorphism suggests that the sex‐specific selection forces on brains differ only negligibly between habitats. Although significance of the observed sex‐specific brain plasticity in the size ofbulbus olfactoriusremains unclear, it demonstrates the potential for sex‐specific neural plasticity.
Androgen Deficiency as a Biological Determinant of Frailty: Hope or Hype?
Authors: Afilalo Jonathan
Published: June 2014

The role of androgen deficiency as a biological determinant of frailty has received considerable attention. Cross‐sectional studies have shown that low bioavailable testosterone (BT) is associated with prevalent frailty. High levels of luteinizing hormone and sex hormone binding globulin are also associated with prevalent frailty. Longitudinal studies have had mixed results, suggesting, for the most part, that a decline in BT over time is associated with progression of frailty. A number of potential biases were found in the current body of evidence, including misclassification bias (due to testosterone assays that were insensitive in lower ranges), selection bias (due to preferential inclusion of healthier individuals), and residual confounding (due to correlation of low testosterone with several disease states and adverse health characteristics). Consideration of these biases is vital to ensure that future epidemiological studies and interventional trials generate valid conclusions.
Teachers' Duty to Report Child Abuse and Neglect and the Paradox of Noncompliance: Relational Theory and “Compliance” in the Human Services
Authors: Gallagher‐Mackay Kelly
Published: June 2014

Based on in‐depth interviews with thirty‐eight individuals on the front line of child welfare (educators, mothers, and child protection workers) this study analyzes the attitudes behind educators' acknowledged noncompliance with mandatory reporting of child abuse and neglect by teachers. Regulatory theory posits that “compliance” is affected by a mix of sanctions, capacity, motivation, and the perceptions of legitimacy and moral purpose associated with particular rules. Paradoxically, while the educators in this study were knowledgeable and supportive of the rule in principle, their accounts of reporting decision making were highly contextualized and ambivalent. The interview data suggests that existing theories of compliance may be usefully supplemented with an explicitly relational approach that better accounts for decision making in the contexts of care and dependency that characterize regulatory fields of human services such as education and child welfare.
West versus East Mediterranean Sea: origin and genetic differentiation of the sea cucumber Holothuria polii
Authors: Valente Sara , Serrão Ester A. , González‐Wangüemert Mercedes
Published: June 2014

We studied the genetic structure of the sea cucumber Holothuria (Roweothuria) polii (Delle Chiaje 1823) by analysing the mitochondrial DNA variation in two fragments of cytochrome oxidase I (COI) and 16S genes. Individuals were collected in seven locations along the Mediterranean Sea, which cover a wide range of the species distribution. We found high haplotype diversity for COI and moderate diversity for 16S, and low nucleotide diversity for both genes. Our results for the COI gene showed many recent and exclusive haplotypes with few mutational changes, suggesting recent or ongoing population expansion. The Western and Eastern Mediterranean populations exhibited slight but significant genetic differentiation (COI gene) with higher genetic diversity in the East. The most ancient haplotype was not present in the westernmost sampling location (SE Spain). The oldest expansion time was observed in Turkey, corresponding to mid‐Pleistocene. Turkey had also the highest genetic diversity (number of total and exclusive haplotypes, polymorphisms, haplotype and nucleotide diversity). This suggests that this region could be the origin of the subsequent colonizations through the Mediterranean Sea, a hypothesis that should be assessed with nuclear markers in future research.
Spectrum of renal disease in diabetes
Authors: Teng Jessie , Dwyer Karen M , Hill Prue , See Emily , Ekinci Elif I , Jerums George , MacIsaac Richard J
Published: June 2014

The spectrum of renal disease in patients with diabetes encompasses both diabetic kidney disease (including albuminuric and non‐albuminuric phenotypes) and non‐diabetic kidney disease. Diabetic kidney disease can manifest as varying degrees of renal insufficiency and albuminuria, with heterogeneity in histology reported on renal biopsy. For patients with diabetes and proteinuria, the finding of non‐diabetic kidney disease alone or superimposed on the changes of diabetic nephropathy is increasingly reported. It is important to identify non‐diabetic kidney disease as some forms are treatable, sometimes leading to remission. Clinical indications for a heightened suspicion of non‐diabetic kidney disease and hence consideration for renal biopsy in patients with diabetes and nephropathy include absence of diabetic retinopathy, short duration of diabetes, atypical chronology, presence of haematuria or other systemic disease, and the nephrotic syndrome.
S‐acylation anchors remorin proteins to the plasma membrane but does not primarily determine their localization in membrane microdomains
Authors: Konrad Sebastian S. A. , Popp Claudia , Stratil Thomas F. , Jarsch Iris K. , Thallmair Veronika , Folgmann Jessica , Marín Macarena , Ott Thomas
Published: June 2014

Remorins are well‐established marker proteins for plasma membrane microdomains. They specifically localize to the inner membrane leaflet despite an overall hydrophilic amino acid composition. Here, we determined amino acids and post‐translational lipidations that are required for membrane association of remorin proteins.

We used a combination of cell biological and biochemical approaches to localize remorin proteins and truncated variants of those in living cells and determined S‐acylation on defined residues in these proteins.

S‐acylation of cysteine residues in a C‐terminal hydrophobic core contributes to membrane association of most remorin proteins. While S‐acylation patterns differ between members of this multi‐gene family, initial membrane association is mediated by protein–protein or protein–lipid interactions. However, S‐acylation is not a key determinant for the localization of remorins in membrane microdomains.

Although remorins bind via a conserved mechanism to the plasma membrane, other membrane‐resident proteins may be involved in the recruitment of remorins into membrane domains. S‐acylation probably occurs after an initial targeting of the proteins to the plasma membrane and locks remorins in this compartment. As S‐acylation is a reversible post‐translational modification, stimulus‐dependent intracellular trafficking of these proteins can be envisioned.
Phenological shifts assist colonisation of a novel environment in a range‐expanding raptor
Authors: Martin Rowan O. , Sebele Lovelater , Koeslag Ann , Curtis Odette , Abadi Fitsum , Amar Arjun
Published: June 2014

In a rapidly changing world understanding the capacity of populations to adapt to novel environments is increasingly urgent. Timing of breeding can be a highly flexible trait and adjustments in this trait can potentially buffer populations from climate change and facilitate the colonisation of new environments. Recent range‐expansions into novel climatic regimes provide a valuable opportunity to investigate the implications of plasticity in timing of breeding for population processes. Black sparrowhawks have recently colonised the Cape Peninsula of South Africa where they experience dramatically different weather patterns to those in their historical range. These include a total reversal in the rainfall regime, with the majority of rain falling in the winter as opposed to the summer months. We investigate the breeding phenology of black sparrowhawks in relation to both regional and local climate variation and, using a long‐term dataset, explore the implications of phenological shifts for reproductive success and population growth following colonisation. In the recently colonised Cape Peninsula the breeding season began up to three months earlier than within their historical range and these early breeding attempts produced more offspring. Population models suggested that this adjustment assisted the colonisation of the Cape Peninsula, reducing the probability of extinction by 23%. Contrary to expectations, we found little support for the hypothesis that black sparrowhawks were responding to local variation in rainfall. We suggest that shifts in breeding phenology may be driven in part by other novel processes, such as interspecific competition for nest sites and lower temperatures during late summer. These results provide insight into the processes that facilitated the colonisation of a novel climatic regime highlighting the potential role of a diverse range of factors.
Misconceptions about Value‐Added and Retail Sales Taxes: Are They Barriers to Sensible Tax Policy?
Authors: Mikesell John L.
Published: June 2014

Retail sales and value‐added taxes both aim to tax consumption, but lawmakers, the public, and academics view them differently. Several American states have sought increased retail sales tax (RST) reliance, some have argued for a national RST, but a value‐added tax (VAT) remains anathema. Conversely, international observers strongly reject the RST in favor of the VAT. This paper examines these views from the standpoints of administration, transparency, rate increases, and breadth to see how misconceptions might be involved.
Refractory Pyoderma Gangrenosum in an Infant
Authors: Etzler Chloe , Cannon Sarah , Hyde Patrice
Published: June 2014

We present a rare case of infantile pyoderma gangrenosum with an extended course and limited response to treatment. Despite extensive examination for an underlying disorder, the case remains idiopathic.
Successful treatment of fulminant Wilson's disease without liver transplantation
Authors: Motobayashi Mitsuo , Fukuyama Tetsuhiro , Nakayama Yoshiko , Sano Kenji , Noda Shunsuke , Hidaka Yoshihiko , Amano Yoshiro , Ikeda Shu‐ichi , Koike Kenichi , Inaba Yuji
Published: June 2014

Fulminant Wilson's disease (WD) is life‐threatening. The revised WD prognostic index (RWPI) has been used to predict the severity of the disease, with a score ≥11 indicating fatal outcome without liver transplantation (LTx). We here report the case of a 10‐year‐old female patient with fulminant WD (RWPI, 16) who recovered fully after plasma exchange and continuous hemodiafiltration, followed by treatment with copper chelate agents. To the best of our knowledge, there have been five fulminant WD patients with RWPI ≥ 11 including the present patient, in whom LTx was not done. Based on the therapeutic modalities in these five cases, non‐surgical treatment (blood purification and copper chelate agents) may be able to avoid LTx in fulminant WD even with very high RWPI, although preparation for LTx is necessary.
Three‐dimensional to two‐dimensional cross‐strata transition in the lower Pleistocene Catanzaro tidal strait transgressive succession (southern Italy)
Authors: Longhitano Sergio G. , Chiarella Domenico , Muto Francesco
Published: June 2014

Sandstone tidal cross‐strata are the predominant sedimentary feature of strait‐fill stratigraphic successions. However, although widely described in numerous studies, tidal strait‐fill two‐dimensional and three‐dimensional cross‐strata have rarely been reported to occur in discrete intervals which are laterally adjacent or vertically stacked, and the meaning of this stratigraphic architecture has not yet been fully investigated. Understanding of the processes responsible for changes in the internal features of modern and ancient tidal bedforms is essential in order to predict lateral and vertical heterogeneities in analogous reservoir strata. This facies‐based study aims to interpret the three‐dimensional to two‐dimensional cross‐strata transition observed in the lower Pleistocene mixed siliciclastic/bioclastic sandstone filling the Catanzaro Strait, in southern Italy, during a continuous phase of tectonically driven marine transgression. Tidal cross‐strata disappear in the uppermost interval of the studied succession, where mudstone strata prevail. This stratigraphic trend is interpreted as the evidence of an important change in the tidal strait hydrodynamics due to a phase of relative sea‐level rise. At the beginning of the transgression, three‐dimensional tidal dunes migrated throughout the ca 3 to 4 km wide and ca 30 km long, WNW–ESE‐oriented Catanzaro Strait, due to strong tidal currents amplified through the seaway and flowing in semi‐diurnal phase opposition. As the intermediate phase of transgression enlarged the seaway width, the tidal current strength decreased as tidal water exchange occurred over a larger cross‐sectional area. The progressive reduction of the bed shear stress modified three‐dimensional tidal dunes into an extensive two‐dimensional bedform field. At the end of the transgression, the further widening of the Catanzaro Strait into a ca 10 to 12 km wide marine passageway changed the tidally dominated strait into a non‐tidal open shelf. The results of this research suggest the presence of a ‘critical cross‐sectional area’ in the narrowest strait‐centre zone which controls the activation and deactivation of tidal current amplification along a marine seaway.
Region‐Urbanicity Differences in Locus of Control: Social Disadvantage, Structure, or Cultural Exceptionalism?
Authors: Shifrer Dara , Sutton April
Published: June 2014

People with internal rather than external locus of control experience better outcomes in multiple domains. Previous studies on spatial differences in control within America only focused on the South, relied on aggregate level data or historical evidence, or did not account for other confounding regional distinctions (such as variation in urbanicity). Using data from the National Education Longitudinal Study, we find differences in adolescents' loci of control depending on their region and urbanicity are largely attributable to differences in their social background, and only minimally to structural differences (i.e., differences in the qualities of adolescents' schools). Differences that persist net of differences across adolescents and their schools suggest the less internal control of rural Southern adolescents, and the more internal control of rural and urban Northeastern adolescents, may be due to cultural distinctions in those areas. Results indicate region is more closely associated than urbanicity with differences in locus of control, with Western and Northeastern cultures seemingly fostering more internal control than Midwestern and Southern cultures. These findings contribute to research on spatial variation in a variety of psychological traits.
PLCγ1–PKCγ Signaling‐Mediated Hsp90α Plasma Membrane Translocation Facilitates Tumor Metastasis
Authors: Yang Jian , Song Xiaomin , Chen Yang , Lu Xin‐an , Fu Yan , Luo Yongzhang
Published: June 2014

The 90‐kDa heat shock protein (Hsp90α) has been identified on the surface of cancer cells, and is implicated in tumor invasion and metastasis, suggesting that it is a potentially important target for tumor therapy. However, the regulatory mechanism of Hsp90α plasma membrane translocation during tumor invasion remains poorly understood. Here, we show that Hsp90α plasma membrane expression is selectively upregulated upon epidermal growth factor (EGF) stimulation, which is a process independent of the extracellular matrix. Abrogation of EGF‐mediated activation of phospholipase (PLCγ1) by its siRNA or inhibitor prevents the accumulation of Hsp90α at cell protrusions. Inhibition of the downstream effectors of PLCγ1, including Ca2+ and protein kinase C (PKCγ), also blocks the membrane translocation of Hsp90α, while activation of PKCγ leads to increased levels of cell‐surface Hsp90α. Moreover, overexpression of PKCγ increases extracellular vesicle release, on which Hsp90α is present. Furthermore, activation or overexpression of PKCγ promotes tumor cell motility in vitro and tumor metastasis in vivo, whereas a specific neutralizing monoclonal antibody against Hsp90α inhibits such effects, demonstrating that PKCγ‐induced Hsp90α translocation is required for tumor metastasis. Taken together, our study provides a mechanistic basis for the role for the PLCγ1–PKCγ pathway in regulating Hsp90α plasma membrane translocation, which facilitates tumor cell motility and promotes tumor metastasis.
Storage of volume‐reduced washed platelets in M‐sol additive solution for 7 days
Authors: Hirayama Junichi , Fujihara Mitsuhiro , Akino Mitsuaki , Kojima Shunsuke , Yanagisawa Ryu , Homma Chihiro , Kato Toshiaki , Ikeda Hisami , Azuma Hiroshi , Shimodaira Shigetaka , Takamoto Shigeru
Published: June 2014

Background

Volume‐reduced washed platelets (VR‐wPLTs), which are prepared by concentrating platelets (PLTs) into a smaller volume of additive solution (AS), may prevent not only circulatory overload, but also adverse reactions caused by plasma components. Although VR‐wPLTs may be quickly degraded due to high PLT concentrations, few studies have examined the effects of storage on VR‐wPLTs. We examined here the in vitro properties of VR‐wPLTs prepared with M‐sol AS during their storage for 7 days.

Study Design and Methods

Platelet concentrates (PCs) were divided into two equal aliquots (control group and test group). After the centrifugation of both aliquots and removal of as much supernatant as possible, the pellet of the control group was resuspended in 160 mL of M‐sol while that of the test group was resuspended in 80 or 40 mL of M‐sol. The wPLTs of both groups were stored in polyolefin bags with agitation at 20 to 24°C for 7 days.

Results

The pH values of both groups were maintained at higher than 7.0 during the 7‐day storage. Differences in %disk, CD62P, annexin V, percent hypotonic shock response, and aggregation values between the test group and control group were small for at least 2 days after washing.

Conclusions

The in vitro properties of VR‐wPLTs were not markedly degraded for at least 2 days. Therefore, the storage properties of PLTs may be maintained in VR‐wPLTs prepared at blood centers until they are administered to patients in hospitals.
Optimizing isolation culture and freezing methods to preserve Wharton's jelly's mesenchymal stem cell (MSC) properties: an MSC banking protocol validation for the Hellenic Cord Blood Bank
Authors: Chatzistamatiou Theofanis K. , Papassavas Andreas C. , Michalopoulos Efstathios , Gamaloutsos Christos , Mallis Panagiotis , Gontika Ioanna , Panagouli Effrosyni , Koussoulakos Stauros L. , Stavropoulos‐Giokas Catherine
Published: June 2014

Background

Mesenchymal stem or stromal cells (MSCs) are a heterogeneous population that can be isolated from many tissues including umbilical cord Wharton's jelly (UC‐WJ). Although initially limited in studies such as a hematopoietic stem cell transplantation adjuvant, an increasing number of clinical trials consider MSCs as a potential anti‐inflammatory or a regenerative medicine agent. It has been proposed that creating a repository of MSCs would increase their availability for clinical applications. The aim of this study was to assess the optimal isolation and cryopreservation procedures to facilitate WJ MSC banking.

Study Design and Methods

Cells were isolated from UC‐WJ using enzymatic digestion or plastic adhesion methods. Their isolation efficacy, growth kinetics, immunophenotype, and differentiation potential were studied, as well as the effects of freezing. Flow cytometry for common MSC markers was performed on all cases and differentiation was shown with histocytochemical staining. Finally, the isolation efficacy on cryopreserved WJ tissue fragments was tested.

Results

MSC isolation was successful using both isolation methods on fresh UC‐WJ tissue. However, UC‐WJ MSC isolation from frozen tissue fragments was impossible. Flow cytometry analysis revealed that only MSC markers were expressed on the surface of the isolated cells while differentiation assays showed that they were capable of trilinear differentiation. All the above characteristics were also preserved in isolated UC‐WJ MSCs over the cryopreservation study period.

Conclusion

These data showed that viable MSCs can only be isolated from fresh UC‐WJ tissue, setting the foundation for clinical‐grade banking.
The human carotid body releases acetylcholine, ATP and cytokines during hypoxia
Authors: Kåhlin Jessica , Mkrtchian Souren , Ebberyd Anette , Hammarstedt‐Nordenvall Lalle , Nordlander Britt , Yoshitake Takashi , Kehr Jan , Prabhakar Nanduri , Poellinger Lorenz , Fagerlund Malin Jonsson , Eriksson Lars I.
Published: May 2014

New Findings

What is the central question of this study?

Data on human carotid body (CB) function are limited. The aim of this study was therefore to investigate whether the human CB releases acetylcholine, ATP or cytokines during hypoxia.

What is the main finding and its importance?

Using human CBs, we demonstrate hypoxia‐induced acetylcholine and ATP release, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. Moreover, the human CB releases cytokines upon hypoxia and expresses cytokine receptors as well as hypoxia‐inducible factor proteins HIF‐1α and HIF‐2α in glomus cells, indicating their role in immune signalling and oxygen sensing, respectively, in accordance with previous animal data.

Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)‐1β, IL‐4, IL‐6, IL‐8 and IL‐10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia‐inducible factor‐1α and hypoxia‐inducible factor‐2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information suggesting that the carotid body may play a role in detecting inflammation, providing a link between the immune system and the nervous system.
Modular Bearing Designs to Cope With the New Engine Designs Demanding High Performance, Lead-Free Solutions, and Robustness
Authors: Aufischer Rainer , Walker Rick , Offenbecher Martin , Hager Gunther
Published: May 2014

Engine development, driven by environmental considerations outlined in the different emission regulations, fuel economy, and fuel availability in combination with economical boundary conditions, needs new approaches in bearing material and design. Since gas engines are gaining market share and firing pressures increase in diesel engines in order to fulfill fuel economy, a special focus has also been taken to tailor-made bearings for these applications. This complex task has to consider lining compound material strength and stability under different conditions like oil condition and dilution. Thin overlays with long-term wear resistance and mixed friction capabilities as well as robust design for extraordinary events like dirt shock loading or adaptations at the engine start are necessary. To fulfill all these requirements, different tasks have to be considered: (1) bearing lining and steel shell compound to fulfill assembly requirements to combine a safe bearing seat with antifretting and high strength with base tribological characteristics, (2) design and use of different layers to compensate weakness of the one layer with the strength of another layer, (3) incorporation of special running conditions and cost reduction approaches in the layer design like polymer coatings for start stop and shaft designs with rougher surface finishes, and (4) bearing design incorporating special shapes to cope better with deflections and geometric deficiencies of a special engine design or application In this publication, existing and new lining compound approaches, including lead-free designs, a variety of different overlays from electroplated, polymer and sputtered ones, are briefly described. Additionally, it is explained how these layers are combined and how they work together to improve bearing performance. Testing of the bearing components and designs on bearing test rigs with new test conditions considering dirt shock and misalignment and their confirmation by engine running experiences are given for a gas engine and a high speed diesel engine applications. A special outlook on how this approach can be extended to other applications for the sake of robustness, cost reduction, or performance increase will summarize the paper.
Laminar Natural Convection Between a Vertical Surface With Uniform Heat Flux and Pseudoplastic and Dilatant Fluids
Authors: Capobianchi Massimo , Aziz A.
Published: May 2014

This paper reports the average Nusselt number for steady, laminar natural convection between a vertical surface and otherwise quiescent pseudoplastic and dilatant fluids under a constant and uniform surface heat flux boundary condition. Models for the fluids' apparent viscosity were utilized that are valid in all five regions of the flow curve. The results are thus applicable for whatever shear rates may exist within the flow field and a dimensionless shear rate parameter was identified that quantifies the shear rate region where the given system is operating. The data indicate that the average Nusselt numbers approach the corresponding Newtonian values when the shear rates are predominantly in either the zero or the infinite shear rate Newtonian regions. However, power law values are approached only when both of the following two conditions are met: (1) the shear rates are principally in the power law region and (2) the fluid's limiting zero and infinite shear rate Newtonian viscosities differ sufficiently, by approximately 4 orders of magnitude or more. For all other cases, the average Nusselt number was found to reside between the Newtonian and the power law asymptotes. Results are provided in both graphical and tabular form over a broad range of system parameters.
Design of a Compact Robotic Manipulator for Single-Port Laparoscopy
Authors: Quaglia Claudio , Petroni Gianluigi , Niccolini Marta , Caccavaro Sebastiano , Dario Paolo , Menciassi Arianna
Published: May 2014

This paper presents the mechanical design of a novel surgical robotic platform, specifically developed for single-port laparoscopy (SPL). The greatest constraint is the small size of the skin incision through which the robot must operate. Several technical and technological challenges have been tackled to meet the stringent requirements imposed by the surgical procedure at hand. In this paper, a detailed mechanical description of the system is provided, fulfilling the necessary design requirements. The main outcome of this work is a compact, light-weight (total weight approximately 6 kg) and highly dexterous bimanual robot capable of overcoming the current drawbacks experienced in SPL when using traditional medical devices. The system has been assessed in terms of tracking accuracy, resulting in satisfactory and promising performance.