bluuebunny/crossref_metadata_2025 huggingface dataset:
Naive antibody gene-segment frequencies are heritable and unaltered by chronic lymphocyte ablation
Authors: Glanville Jacob , Kuo Tracy C. , von Büdingen H.-Christian , Guey Lin , Berka Jan , Sundar Purnima D. , Huerta Gabriella , Mehta Gautam R. , Oksenberg Jorge R. , Hauser Stephen L. , Cox David R. , Rajpal Arvind , Pons Jaume
Published: November 2011

A diverse antibody repertoire is essential for an effective adaptive immune response to novel molecular surfaces. Although past studies have observed common patterns of V-segment use, as well as variation in V-segment use between individuals, the relative contributions to variance from genetics, disease, age, and environment have remained unclear. Using high-throughput sequence analysis of monozygotic twins, we show that variation in naive VHand DHsegment use is strongly determined by an individual's germ-line genetic background. The inherited segment-use profiles are resilient to differential environmental exposure, disease processes, and chronic lymphocyte depletion therapy. Signatures of the inherited profiles were observed in class switched germ-line use of each individual. However, despite heritable segment use, the rearranged complementarity-determining region-H3 repertoires remained highly specific to the individual. As it has been previously demonstrated that certain V-segments exhibit biased representation in autoimmunity, lymphoma, and viral infection, we anticipate our findings may provide a unique mechanism for stratifying individual risk profiles in specific diseases.
Dividing a supercoiled DNA molecule into two independent topological domains
Authors: Leng Fenfei , Chen Bo , Dunlap David D.
Published: November 2011

Both prokaryotic and eukaryotic chromosomes are organized into many independent topological domains. These topological domains may be formed through constraining each DNA end from rotating by interacting with nuclear proteins; i.e., DNA-binding proteins. However, so far, evidence to support this hypothesis is still elusive. Here we developed two biochemical methods; i.e., DNA-nicking and DNA-gyrase methods to examine whether certain sequence-specific DNA-binding proteins are capable of separating a supercoiled DNA molecule into distinct topological domains. Our approach is based on the successful construction of a series of plasmid DNA templates that contain many tandem copies of one or two DNA-binding sites in two different locations. With these approaches and atomic force microscopy, we discovered that several sequence-specific DNA-binding proteins; i.e.,
lac
repressor,
gal
repressor, and
λ
O protein, are able to divide a supercoiled DNA molecule into two independent topological domains. These topological domains are stable under our experimental conditions. Our results can be explained by a topological barrier model in which nucleoprotein complexes confine DNA supercoils to localized regions. We propose that DNA topological barriers are certain nucleoprotein complexes that contain stable toroidal supercoils assembled from DNA-looping or tightly wrapping DNA around DNA-binding proteins. The DNA topological barrier model may be a general mechanism for certain DNA-binding proteins, such as histone or histone-like proteins, to modulate topology of chromosome DNA in vivo.
Cosmochemistry: Understanding the Solar System through analysis of extraterrestrial materials
Authors: MacPherson Glenn J. , Thiemens Mark H.
Published: November 2011

Cosmochemistry is the chemical analysis of extraterrestrial materials. This term generally is taken to mean laboratory analysis, which is the cosmochemistry gold standard because of the ability for repeated analysis under highly controlled conditions using the most advanced instrumentation unhindered by limitations in power, space, or environment. Over the past 40 y, advances in technology have enabled telescopic and spacecraft instruments to provide important data that significantly complement the laboratory data. In this special edition, recent advances in the state of the art of cosmochemistry are presented, which range from instrumental analysis of meteorites to theoretical–computational and astronomical observations.
Molecular basis of dihydrouridine formation on tRNA
Authors: Yu Futao , Tanaka Yoshikazu , Yamashita Keitaro , Suzuki Takeo , Nakamura Akiyoshi , Hirano Nagisa , Suzuki Tsutomu , Yao Min , Tanaka Isao
Published: November 2011

Dihydrouridine (D) is a highly conserved modified base found in tRNAs from all domains of life. Dihydrouridine synthase (Dus) catalyzes the D formation of tRNA through reduction of uracil base with flavin mononucleotide (FMN) as a cofactor. Here, we report the crystal structures of
Thermus thermophilus
Dus (
Tth
Dus), which is responsible for D formation at positions 20 and 20a, in complex with tRNA and with a short fragment of tRNA (D-loop). Dus interacts extensively with the D-arm and recognizes the elbow region composed of the kissing loop interaction between T- and D-loops in tRNA, pulling U20 into the catalytic center for reduction. Although distortion of the D-loop structure was observed upon binding of Dus to tRNA, the canonical D-loop/T-loop interaction was maintained. These results were consistent with the observation that Dus preferentially recognizes modified rather than unmodified tRNAs, indicating that Dus introduces D20 by monitoring the complete L-shaped structure of tRNAs. In the active site, U20 is stacked on the isoalloxazine ring of FMN, and C5 of the U20 uracil ring is covalently cross linked to the thiol group of Cys93, implying a catalytic mechanism of D20 formation. In addition, the involvement of a cofactor molecule in uracil ring recognition was proposed. Based on a series of mutation analyses, we propose a molecular basis of tRNA recognition and D formation catalyzed by Dus.
Evolutionary erosion of yeast sex chromosomes by mating-type switching accidents
Authors: Gordon Jonathan L. , Armisén David , Proux-Wéra Estelle , ÓhÉigeartaigh Seán S. , Byrne Kevin P. , Wolfe Kenneth H.
Published: November 2011

We investigate yeast sex chromosome evolution by comparing genome sequences from 16 species in the family Saccharomycetaceae, including data from genera
Tetrapisispora
,
Kazachstania
,
Naumovozyma
, and
Torulaspora
. We show that although most yeast species contain a mating-type (
MAT
) locus and silent
HML
and
HMR
loci structurally analogous to those of
Saccharomyces cerevisiae
, their detailed organization is highly variable and indicates that the
MAT
locus is a deletion hotspot. Over evolutionary time, chromosomal genes located immediately beside
MAT
have continually been deleted, truncated, or transposed to other places in the genome in a process that is gradually shortening the distance between
MAT
and
HML
. Each time a gene beside
MAT
is removed by deletion or transposition, the next gene on the chromosome is brought into proximity with
MAT
and is in turn put at risk for removal. This process has also continually replaced the triplicated sequence regions, called Z and X, that allow
HML
and
HMR
to be used as templates for DNA repair at
MAT
during mating-type switching. We propose that the deletion and transposition events are caused by evolutionary accidents during mating-type switching, combined with natural selection to keep
MAT
and
HML
on the same chromosome. The rate of deletion accelerated greatly after whole-genome duplication, probably because genes were redundant and could be deleted without requiring transposition. We suggest that, despite its mutational cost, switching confers an evolutionary benefit by providing a way for an isolated germinating spore to reform spores if the environment is too poor.
Common oxytocin receptor gene (
OXTR
) polymorphism and social support interact to reduce stress in humans
Authors: Chen Frances S. , Kumsta Robert , von Dawans Bernadette , Monakhov Mikhail , Ebstein Richard P. , Heinrichs Markus
Published: November 2011

The neuropeptide oxytocin has played an essential role in the regulation of social behavior and attachment throughout mammalian evolution. Because recent studies in humans have shown that oxytocin administration reduces stress responses and increases prosocial behavior, we investigated whether a common single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (
OXTR
) might interact with stress-protective effects of social support. Salivary cortisol samples and subjective stress ratings were obtained from 194 healthy male participants before, during, and after a standardized psychosocial laboratory stress procedure. Participants were randomly assigned either to prepare alone or to receive social support from their female partner or close female friend while preparing for the stressful task. Differential stress responses between the genotype groups were observed depending on the presence or absence of social support. Only individuals with one or two copies of the G allele of rs53576 showed lower cortisol responses to stress after social support, compared with individuals with the same genotype receiving no social support. These results indicate that genetic variation of the oxytocin system modulates the effectiveness of positive social interaction as a protective buffer against a stressful experience.
Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Authors: Pang Wendy W. , Price Elizabeth A. , Sahoo Debashis , Beerman Isabel , Maloney William J. , Rossi Derrick J. , Schrier Stanley L. , Weissman Irving L.
Published: November 2011

In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.
Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3–mediated pathway
Authors: He Sudan , Liang Yuqiong , Shao Feng , Wang Xiaodong
Published: November 2011

We report here that mouse macrophages undergo receptor-interacting kinase-3 (RIP3)-dependent but TNF-α–independent necrosis when Toll-like receptors (TLR) 3 and 4 are activated by poly(I:C) and LPS, respectively. An adaptor protein, Toll/IL-1 receptor domain-containing adapter inducing IFN-β (TRIF/TICAM-1), which is dispensable for TNF-α–induced necrosis, forms a complex with RIP3 upon TLR3/TLR4 activation and is essential for TLR3/TLR4-induced necrosis. Mice without RIP3 or functional TRIF did not show macrophage loss and elevation of inflammatory cytokines when they were exposed to LPS. Necrosis in mouse macrophages induced by either TNFR or TLR3/TLR4 is executed by reactive oxygen species. Taken together, these data indicate that there are multiple upstream necrosis-initiating signaling pathways converging on the RIP3 during an innate immune response to viral and bacterial infections in mammals.
Host innate recognition of an intestinal bacterial pathogen induces TRIF-dependent protective immunity
Authors: Sotolongo John , España Cecilia , Echeverry Andrea , Siefker David , Altman Norman , Zaias Julia , Santaolalla Rebeca , Ruiz Jose , Schesser Kurt , Adkins Becky , Fukata Masayuki
Published: November 2011

Toll-like receptor 4 (TLR4), which signals through the adapter molecules myeloid differentiation factor 88 (MyD88) and toll/interleukin 1 receptor domain-containing adapter inducing IFN-β (TRIF), is required for protection against Gram-negative bacteria. TRIF is known to be important in TLR3-mediated antiviral signaling, but the role of TRIF signaling against Gram-negative enteropathogens is currently unknown. We show that TRIF signaling is indispensable for establishing innate protective immunity against Gram-negative Yersinia enterocolitica. Infection of wild-type mice rapidly induced both IFN-β and IFN-γ in the mesenteric lymph nodes. In contrast, TRIF-deficient mice were defective in these IFN responses and showed impaired phagocytosis in regional macrophages, resulting in greater bacterial dissemination and mortality. TRIF signaling may be universally important for protection against Gram-negative pathogens, as TRIF-deficient macrophages were also impaired in killing both Salmonella and Escherichia coli in vitro. The mechanism of TRIF-mediated protective immunity appears to be orchestrated by macrophage-induced IFN-β and NK cell production of IFN-γ. Sequential induction of IFN-β and IFN-γ leads to amplification of macrophage bactericidal activity sufficient to eliminate the invading pathogens at the intestinal interface. Our results demonstrate a previously unknown role of TRIF in host resistance to Gram-negative enteropathogens, which may lead to effective strategies for combating enteric infections.
Does Regulation of Manure Land Application Work Against Agglomeration Economies? Theory and Evidence from the French Hog Sector
Authors: Gaigné Carl , Le Gallo Julie , Larue Solène , Schmitt Bertrand
Published: November 2011

We examine whether the restrictions on manure land application weaken productivity gains arising from agglomeration in the hog sector. By developing a spatial model of production, we show that while regulating the manure application rate promotes dispersion ceteris paribus, it also prompts farmers to adopt systems of manure treatment that favor the agglomeration of hog production. We estimate a reduced form of the model with a spatial HAC procedure from French data. Our results suggest that land limitations induced by the restrictions on manure application do not favor the dispersion of hog production, and may boost agglomeration economies related to non‐market spatial externalities.
Are fibroblast growth factor 23 concentrations in renal transplant patients different from non‐transplanted chronic kidney disease patients?
Authors: Filler Guido , Liu Daisy , Sharma Ajay Parkash , Grimmer Joanne
Published: November 2011

Filler G, Liu D, Sharma AP, Grimmer J. Are fibroblast growth factor 23 concentrations in renal transplant patients different from non‐transplanted chronic kidney disease patients?  Pediatr Transplantation 2012: 16: 73–77. © 2011 John Wiley & Sons A/S.

Abstract:  To compare the pattern of serum FGF23 levels in pediatric renal transplant recipients and GFR‐matched controls. We performed a cross‐sectional matched pair study in 19 stable pediatric renal transplant recipients and 19 GFR‐matched controls with native CKD. After assessment for normal distribution, demographic and bone metabolism parameters were compared with Student’s t‐test, Wilcoxon’s matched pairs (for non‐normal distribution) test, and correlation analysis. The groups were comparable for anthropometric parameters, cystatin C eGFR (71.10 ± 37.28 vs. 76.11 ± 26.80 mL/min/1.73 m2), cystatin C, urea, creatinine, intact PTH, pH, CRP, alkaline phosphatase, phosphate, calcium, ionized calcium, FGF‐23 (63.44 [IQR 38.42, 76.29], 49.92 [IQR 42.48, 76.97]), albumin, and urinary calcium/creatinine ratio. The renal transplant patients had significantly lower 25‐(OH) vitamin D levels (66.63 ± 17.54 vs. 91.42 ± 29.16 ng/mL), and higher 1,25‐(OH)2 vitamin D levels (95.78 ± 34.54 vs. 67.11 ± 35.90 pm). FGF‐23 levels correlated negatively with cystatin C eGFR (r = −0.3571, p = 0.02770) and positively with PTH (r = 0.5063, p = 0.0026), but not with serum phosphate (r = 0.2651, p = 0.1077). We conclude that the increase in FGF23 levels with GFR decline in pediatric renal transplant patients remains similar to that in the patients with CKD. The relationship between FGF23 and serum vitamin D needs further evaluation.
Adverse interactions between antifungal azoles and vincristine: review and analysis of cases
Authors: Moriyama Brad , Henning Stacey A. , Leung Janice , Falade‐Nwulia Oluwaseun , Jarosinski Paul , Penzak Scott R. , Walsh Thomas J.
Published: November 2011

Triazole and imidazole antifungal agents inhibit metabolism of vincristine, leading to excess vinca alkaloid exposure and severe neurotoxicity. Recent reports of debilitating interactions between vincristine and itraconazole, as well as posaconazole, voriconazole and ketoconazole underscore the need to improve medical awareness of this adverse combination. We, therefore, undertook a comprehensive analysis of reports of adverse drug interactions (ADIs) with the combination of vincristine and azole antifungal agents, established a new classification, and provided a detailed summary of these toxicities. In patients who had sufficient data for analysis, 47 individuals were identified who had an ADI with the combination of vincristine and antifungal azoles. Median age was 8 years (1.3–68 years) with 33(70%) having a diagnosis of acute lymphoblastic leukaemia. Median time to ADI with vincristine was 9.5 days with itraconazole, 13.5 days posaconazole and 30 days voriconazole. The median number of vincristine doses preceding the ADI was 2 doses with itraconazole, 3 doses posaconazole and 2 doses voriconazole. The most common severe ADIs included gastrointestinal toxicity, peripheral neuropathy, hyponatremia/SIADH, autonomic neuropathy and seizures. Recovery from these ADIs occurred in 80.6% of patients. We recommend using alternative antifungal agents if possible in patients receiving vincristine to avoid this serious and potentially life‐threatening drug interaction.
Vertical stratification of subsurface microbial community composition across geological formations at the Hanford Site
Authors: Lin Xueju , Kennedy David , Fredrickson Jim , Bjornstad Bruce , Konopka Allan
Published: November 2011

Microbial diversity in subsurface sediments at the Hanford Site 300 Area near Richland, Washington state (USA) was investigated by analysing 21 samples recovered from depths of 9–52 m. Approximately 8000 near full‐length 16S rRNA gene sequences were analysed across geological strata that include a natural redox transition zone. These strata included the oxic coarse‐grained Hanford formation, fine‐grained oxic and anoxic Ringold Formation sediments, and the weathered basalt group. We detected 1233 and 120 unique bacterial and archaeal OTUs (operational taxonomic units at the 97% identity level) respectively. Microbial community structure and richness varied substantially across the different geological strata. Bacterial OTU richness (Chao1 estimator) was highest (> 700) in the upper Hanford formation, and declined to about 120 at the bottom of the Hanford formation. Just above the Ringold oxic–anoxic interface, richness was about 325 and declined to less than 50 in the deeper reduced zones. The deeper Ringold strata were characterized by a preponderance (c. 90%) of Proteobacteria. The bacterial community in the oxic sediments contained not only members of nine well‐recognized phyla but also an unusually high proportion of three candidate divisions (GAL15, NC10 and SPAM). Additionally, 13 novel phylogenetic orders were identified within the Deltaproteobacteria, a clade rich in microbes that carry out redox transformations of metals that are important contaminants on the Hanford Site.
Exploring dependence between brain signals in a monkey during learning
Authors: Gorrostieta Cristina , Ombao Hernando , Prado Raquel , Patel Shaun , Eskandar Emad
Published: November 2011

Our goal is to investigate dependence between brain wave oscillations in the nucleus accumbens (NAc) and the hippocampus (Hc) regions of a macaque monkey during a learning association task. The classical approach to studying dependence in the spectral domain is via cross‐coherence. It is computed for each frequency (or band) and identifies the frequency bands that drive the linear association between the components in a multi‐variate time series. However, cross‐coherence may not fully capture the complex dependence structure in brain signals such as local field potentials. In this article, we develop new tools for discovering associations between the theta (4–8 Hz) and gamma (32–50 Hz) activities at both contemporaneous blocks and lagged time blocks. We propose a class of piecewise harmonizable processes under which we give a precise definition of these dependence measures and develop simple estimators in the case where the time‐series data are recorded over several replicated trials. Our analysis clearly demonstrates strong dependence between the theta and gamma oscillations in the NAc and the Hc regions of a macaque monkey during learning. Moreover, we determined the lagged dependence that differentiate the ‘correct’ responses (i.e., the monkey was able to identify the correct association) from the ‘incorrect’ responses.
The profile of executive function in very preterm children at 4 to 12 years
Authors: AARNOUDSE‐MOENS CORNELIEKE S H , DUIVENVOORDEN HUGO J , WEISGLAS‐KUPERUS NYNKE , VAN GOUDOEVER JOHANNES B , OOSTERLAAN JAAP
Published: November 2011

Aim  To examine executive functioning in very preterm (gestational age ≤30wks) children at 4 to 12 years of age.

Method  Two‐hundred very preterm (106 males, 94 females; mean gestational age 28.1wks, SD 1.4; mean age 8y 2mo, SD 2y 6mo) and 230 term children (106 males, 124 females; mean gestational age 39.9wks, SD 1.2; mean age 8y 4mo, SD 2y 3mo) without severe disabilities, born between 1996 and 2004, were assessed on an executive function battery comprising response inhibition, interference control, switching, verbal fluency, verbal and spatial working memory, and planning. Multiple regression analyses examined group differences while adjusting for effects of parental education, age, sex, and speed indices.

Results  Relative to children born at term, very preterm children had significant (ps<0.02; where ps represents p‐values) deficits in verbal fluency (0.5 standardized mean differences [SMD]), response inhibition (0.4 SMD), planning (0.4 SMD), and verbal and spatial working memory (0.3 SMD), independent of slow and highly fluctuating processing speed. A significant group by age interaction indicated that group differences for response inhibition decreased between 4 and 12 years.

Interpretation  Very preterm birth is associated with a profile of affected and non‐affected executive functions independent of impaired speed. Deficits are of small to moderate magnitude and persist over time, except for response inhibition for which very preterm children catch up with peers.
Biological characterization of a novel class of toll‐like receptor 7 agonists designed to have reduced systemic activity
Authors: Biffen M , Matsui H , Edwards S , Leishman AJ , Eiho K , Holness E , Satterthwaite G , Doyle I , Wada H , Fraser NJ , Hawkins SL , Aoki M , Tomizawa H , Benjamin AD , Takaku H , McInally T , Murray CM
Published: November 2011

BACKGROUND AND PURPOSE Toll‐like receptor 7 (TLR7) agonists have potential in the treatment of allergic diseases. However, the therapeutic utility of current low molecular weight TLR7 agonists is limited by their systemic activity, resulting in unwanted side effects. We have developed a series of TLR7‐selective ‘antedrugs’, including SM‐324405 and AZ12441970, which contain an ester group rapidly cleaved in plasma to reduce systemic exposure.

EXPERIMENTAL APPROACH Agonist activity at TLR7 of the parent ester and acid metabolite was assessed in vitro in reporter cells and primary cells from a number of species. Pharmacokinetics following a dose to the lungs was assessed in mice and efficacy evaluated in vivo with a mouse allergic airway model.

KEY RESULTS Compounds were selective agonists for TLR7 with no crossover to TLR8 and were metabolically unstable in plasma with the acid metabolite showing substantially reduced activity in a number of assays. The compounds inhibited IL‐5 production and induced IFN‐α, which mediated the inhibition of IL‐5. When dosed into the lung the compounds were rapidly metabolized and short‐term exposure of the ‘antedrug’ was sufficient to activate the IFN pathway. AZ12441970 showed efficacy in a mouse allergic airway model with minimal induction of systemic IFN‐α, consistent with the low plasma levels of compound.

CONCLUSIONS AND IMPLICATIONS The biological and metabolic profiles of these TLR7‐selective agonist ‘antedrug’ compounds are consistent with a new class of compound that could be administered locally for the treatment of allergic diseases, while reducing the risk of systemic side effects.

LINKED ARTICLE This article is commented on by Kaufman and Jacoby, pp. 569–572 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01758.x
Can Intensive Hemodialysis Prevent Loss of Functionality in the Elderly ESRD Patient?
Authors: Cornelis Tom , Kotanko Peter , Goffin Eric , Kooman Jeroen P. , van der Sande Frank M. , Chan Christopher T.
Published: November 2011

Initiation of dialysis may be accompanied by decline in physical and cognitive function and independence, especially in the elderly ESRD patient. Here, we postulate the underlying factors, which may contribute to this observation in the elderly dialysis population, such as increased risk of dialysis‐induced hypotension and associated cerebral and cardiac events, as well as malnutrition, infections, sleep abnormalities, and psychological complications of dialysis initiation. We describe an elderly dialysis patient who did well on nocturnal home hemodialysis (HD), and we hypothesize how intensive HD (i.e., nocturnal HD and/or short daily HD) may reduce the incidence of these dialysis complications and may therefore be considered as an option to attempt to preserve functional status and quality of life, especially early after the transition from predialysis to dialysis. Before general adoption of this strategy, further studies on the etiology of functional loss at the time of dialysis initiation, as well as on the potential advantageous effects of intensive HD in the elderly ESRD patient as compared with conventional HD, peritoneal dialysis and kidney transplantation, are required.
Pregnancy in End Stage Renal Disease
Authors: Hladunewich Michelle , Hercz Adam Engel , Keunen Johannes , Chan Christopher , Pierratos Andreas
Published: November 2011

The ovulatory menstrual cycle is known to be affected on multiple levels in women with advanced renal disease. Menstrual irregularities, sexual dysfunction, and infertility worsen in parallel with the renal disease. Pregnancy in women with ESRD on dialysis is therefore uncommon. Furthermore, when pregnancy does occur, it can prove hazardous to both mother and baby owing to a multitude of potential complications including accelerated hypertension and preeclampsia, poor fetal growth, anemia, and polyhydramnios. Data are emerging, however, to suggest that pregnancy while on intensified renal replacement regimens may result in better pregnancy outcomes, and emerging trends include the decreased rate of therapeutic abortions probably reflecting a change in counseling practices over time. Nevertheless, a pregnant woman on intensive dialysis requires meticulous follow‐up by a dedicated team including nephrology, obstetrics, and a full multidisciplinary staff. In this article, we will address fertility issues in young women with ESRD, review pregnancy outcomes in women on both hemodialysis and peritoneal dialysis, and provide suggestions for the management of the pregnant women on intensive hemodialysis.
FISH for MYC amplification and anti‐MYC immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular proliferations
Authors: Fernandez Anthony P. , Sun Yang , Tubbs Raymond R. , Goldblum John R. , Billings Steven D.
Published: November 2011

Background: Secondary angiosarcoma and benign but microscopically atypical vascular proliferations (herein referred to as atypical vascular lesion or AVL) are rare consequences of radiation therapy and/or chronic lymphedema most commonly seen in breast cancer patients. Differentiating angiosarcoma from AVL can be difficult due to overlapping clinical and microscopic features. Recently, amplification of MYC has been associated with 55–100% of secondary angiosarcomas but is reportedly absent in AVL. We examined a series of secondary angiosarcoma and AVL for MYC amplification by fluorescence in situ hybridization (FISH) and expression by immunohistochemistry to investigate the diagnostic utility for discriminating angiosarcoma from AVL.

Methods: Cases of secondary angiosarcoma (n = 8) and AVL (n = 4) were retrieved from our archives and examined by FISH and immunohistochemistry.

Results: All angiosarcoma cases (8/8 = 100%) demonstrated high‐level MYC amplification by FISH, whereas all AVLs (0/4 = 0%) were negative for MYC amplification. Additionally, all angiosarcoma cases (8/8 = 100%) demonstrated nuclear positivity for MYC, whereas all AVLs (0/4 = 0%) were negative.

Conclusion: Amplification of MYC and nuclear expression of MYC is present in secondary angiosarcoma but not AVL. These ancillary tests can be useful to distinguish angiosarcoma from AVL in difficult cases.

Fernandez AP, Sun Y, Tubbs RR, Goldblum JR, Billings SD. FISH for MYC amplification and anti‐MYC immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular proliferations.
Partial migration in expanding red deer populations at northern latitudes – a role for density dependence?
Authors: Mysterud Atle , Loe Leif Egil , Zimmermann Barbara , Bischof Richard , Veiberg Vebjørn , Meisingset Erling
Published: November 2011

Partial migration is common in ungulates living in highly seasonal environments. Typically, at higher latitudes, this involves movement between high elevation summer areas used during breeding and lowland areas with less snow used during winter. Snow depth is regarded the main cause of migration to low elevation, but it is less clear why deer migrate to high elevation in spring. The forage maturation hypothesis explains the upward migration due to plant phenology. We here present also an alternative and non‐exclusive hypothesis, that deer migrate uphill in summer to escape competition due to the high density in winter areas (the competition avoidance hypothesis). We also suggest that social fences may play a role at high population density. Based on a unique study of 141 GPS‐marked red deer from seven regions covering the main distribution in Norway, we found that the proportion of migrants in the populations varied from 38% to 100%. Migration was more common in areas with a diverse topography, i.e. for areas with access to high elevation. Further, we found evidence that migration was negatively density dependent, and that fall migration was delayed at high density. We suggest that a combination of avoidance of competition in high density winter ranges, social fencing during summer in addition to the forage maturation and predation risk avoidance hypotheses, is needed to explain migration patterns of northern ungulates.
Partial migration in roe deer: migratory and resident tactics are end points of a behavioural gradient determined by ecological factors
Authors: Cagnacci Francesca , Focardi Stefano , Heurich Marco , Stache Anja , Hewison A. J. Mark , Morellet Nicolas , Kjellander Petter , Linnell John D. C. , Mysterud Atle , Neteler Markus , Delucchi Luca , Ossi Federico , Urbano Ferdinando
Published: November 2011

Ungulate populations exhibiting partial migration present a unique opportunity to explore the causes of the general phenomenon of migration. The European roe deerCapreolus capreolusis particularly suited for such studies due to a wide distribution range and a high level of ecological plasticity. In this study we undertook a comparative analysis of roe deer GPS location data from a representative set of European ecosystems available within the EURODEER collaborative project. We aimed at evaluating the ecological factors affecting migration tactic (i.e. occurrence) and pattern (i.e. timing, residence time, number of migratory trips). Migration occurrence varied between and within populations and depended on winter severity and topographic variability. Spring migrations were highly synchronous, while the timing of autumn migrations varied widely between regions, individuals and sexes. Overall, roe deer were faithful to their summer ranges, especially males. In the absence of extreme and predictable winter conditions, roe deer seemed to migrate opportunistically, in response to a tradeoff between the costs of residence in spatially separated ranges and the costs of migratory movements. Animals performed numerous trips between winter and summer ranges which depended on factors influencing the costs of movement such as between‐range distance, slope and habitat openness. Our results support the idea that migration encompasses a behavioural continuum, with one‐trip migration and residence as its end points, while commuting and multi‐trip migration with short residence times in seasonal ranges are intermediate tactics. We believe that a full understanding of the variation in tactics of temporal separation in habitat use will provide important insights on migration and the factors that influence its prevalence.
Evolutionary genetics of partial migration – the threshold model of migration revis(it)ed
Authors: Pulido Francisco
Published: November 2011

Partial migration is a common and widespread phenomenon in animal populations. Even though the ecological causes for the evolution and maintenance of partial migration have been widely discussed, the consequences of the genetics underlying differences in migration patterns have been little acknowledged. Here, I revise current ideas on the genetics of partial migration and identify open questions, focussing on migration in birds. The threshold model of migration describing the inheritance and phenotypic expression of migratory behaviour is strongly supported by experimental results. As a consequence of migration being a threshold trait, high levels of genetic variation can be preserved, even under strong directional selection. This is partly due to strong environmental canalization. This cryptic genetic variation may explain rapid de novo evolution of migratory behaviour in resident populations and the high prevalence of partial migration in animal populations. To date the threshold model of migration has been tested only under laboratory conditions. For obtaining a more realistic representation of migratory behaviour in the wild, the simple threshold model needs to be extended by considering that the threshold of migration or the liability may be modified by environmental effects. This environmental threshold model is valid for both facultative and obligate migration movements, and identifies genetic accommodation as an important process underlying evolutionary change in migration status. Future research should aim at identifying the major environmental variables modifying migration propensity and at determining reaction norms of the threshold and liability across variation in these variables.
Lower Urinary Tract Function in Spinocerebellar Ataxia 6
Authors: TATENO Fuyuki , SAKAKIBARA Ryuji , SUGIYAMA Megumi , KISHI Masahiko , OGAWA Emina , TAKAHASHI Osamu , YANO Masashi , UCHIYAMA Tomoyuki , YAMAMOTO Tatsuya , TSUYUZAKI Yohei
Published: November 2011

Objective: To investigate lower urinary tract function in spinocerebellar ataxia type 6 (SCA6).

Methods: We recruited, without bias, nine SCA6 patients with a mean cytosine‐adenine‐guanine repeat length of 24.3 (21–26, normal <18). They were four men, five women; mean age 58.6 years; mean disease duration 8.2 years. We performed a urinary symptom questionnaire and a urodynamics.

Results: Urinary symptoms were observed in five of nine patients (56%) and urinary frequency in three of nine patients (33%), and none had urinary retention. Urodynamic abnormalities included detrusor overactivity in one (11%) and weak detrusor on voiding in two, but none had postvoid residual urine. Sphincter electromyography revealed, while mild in degree, neurogenic change in five of the eight patients (63%) on whom the test was performed.

Conclusion: We observed urinary frequency in 33%; detrusor overactivity in only 11%; and neurogenic change in the sphincter electromyography in 63% of our nine SCA6 patients. These findings might be relevant to the cerebellar and spinal cord pathologies of this disease.
Postgraduate education – meeting the needs and expectations of those we serve: The dynamic duo of psychiatric diagnosis and formulation
Authors: Mellsop Graham , Clapham Howard Fiona
Published: November 2011

Service users and those who support them have an expectation that a health diagnosis will offer insight into the cause of their symptoms, and will come with a prognosis that will determine treatment options. However, psychiatric diagnostic systems do not usually provide links to aetiology or prognosis, both of which can be highly individualised. As a result, there is a gap between mental health service users’ expectations and what can be realistically provided by diagnosis alone. However, when paired with a thorough and reflective formulation, diagnosis is placed in a context that leads ineluctably to a comprehensive management or recovery plan. This dynamic combination results in a collaborative plan that is better placed to meet both the needs and the expectations of those we serve.
A Three-Dimensional Shock Loss Model Applied to an Aft-Swept, Transonic Compressor Rotor
Authors: Puterbaugh S. L. , Copenhaver W. W. , Hah C. , Wennerstrom A. J.
Published: November 2011

An analysis of the effectiveness of a three-dimensional shock loss model used in transonic compressor rotor design is presented. The model was used during the design of an aft-swept, transonic compressor rotor. The demonstrated performance of the swept rotor, in combination with numerical results, is used to determine the strengths and weaknesses of the model. The numerical results were obtained from a fully three-dimensional Navier–Stokes solver. The shock loss model was developed to account for the benefit gained with three-dimensional shock sweep. Comparisons with the experimental and numerical results demonstrated that shock loss reductions predicted by the model due to the swept shock induced by the swept leading edge of the rotor were exceeded. However, near the tip the loss model underpredicts the loss because the shock geometry assumed by the model remains swept in this region while the numerical results show a more normal shock orientation. The design methods and the demonstrated performance of the swept rotor are also presented. Comparisons are made between the design intent and measured performance parameters. The aft-swept rotor was designed using an inviscid axisymmetric streamline curvature design system utilizing arbitrary airfoil blading geometry. The design goal specific flow rate was 214.7 kg/s/m2 (43.98 lbm/sec/ft2), the design pressure ratio goal was 2.042, and the predicted design point efficiency was 94.0. The rotor tip speed was 457.2 m/s (1500 ft/sec). The design flow rate was achieved while the pressure ratio fell short by 0.07. Efficiency was 3 points below prediction, though at a very high 91 percent. At this operating condition the stall margin was 11 percent.
Film Effectiveness Over a Flat Surface With Air and CO2 Injection Through Compound Angle Holes Using a Transient Liquid Crystal Image Method
Authors: Ekkad S. V. , Zapata D. , Han J. C.
Published: November 2011

This paper presents detailed film effectiveness distributions over a flat surface with one row of injection holes inclined streamwise at 35 deg for three blowing ratios (M = 0.5, 1.0, 2.0). Three compound angles of 0, 45, and 90 deg with air (D.R. = 0.98) and CO2 (D. R. = 1.46) as coolants are tested at an elevated free-stream turbulence condition (Tu ≈ 8.5 percent). A transient liquid crystal technique is used to measure local heat transfer coefficients and film effectiveness. Detailed film effectiveness results are presented near and around film injection holes. Compound angle injection provides higher film effectiveness than simple angle injection for both coolants. Higher density injectant produces higher effectiveness for simple injection. However, lower density coolant produces higher effectiveness for a large compound angle of 90 deg. The detailed film effectiveness obtained using the transient liquid crystal technique, particularly in the near-hole region, provided a better understanding of the film cooling process in gas turbine components.
Measurements of Heat Transfer Coefficients and Friction Factors in Rib-Roughened Channels Simulating Leading-Edge Cavities of a Modern Turbine Blade
Authors: Taslim M. E. , Li T. , Spring S. D.
Published: November 2011

Leading edge cooling cavities in modern gas turbine blades play an important role in maintaining the leading edge temperature at levels consistent with airfoil design life. These cavities often have a complex cross-sectional shape to be compatible with the external contour of the blade at the leading edge. A survey of many existing geometries shows that, for analytical as well as experimental analyses, such cavities can be simplified in shape by a four-sided polygon with one curved side similar to the leading edge curvature, a rectangle with one semicircular side (often the smaller side) or a trapezoid, the smaller base of which is replaced by a semicircle. Furthermore, to enhance the heat transfer coefficient in these cavities, they are mostly roughened on three sides with ribs of different geometries. Experimental data on friction factors and heat transfer coefficients in such cavities are rare if not nonexistent. A liquid crystal technique was used in this experimental investigation to measure heat transfer coefficients in six test sections representing the leading-edge cooling cavities. Both straight and tapered ribs were configured on the two opposite sidewalls in a staggered arrangement with angles of attack to the mainstream flow, α of 60 and 90 deg. The ribs on the curved surface were of constant cross section with an angle of attack 90 deg to the flow. Heat transfer measurements were performed on the straight sidewalls, as well as on the round surface adjacent to the blade leading edge. Effects such as rib angle of attack to the mainstream flow and constant versus tapered rib cross-sectional areas were also investigated. Nusselt numbers, friction factors, and thermal performances are reported for nine rib geometries in six test sections.
Toward a better understanding of the gamma index: Investigation of parameters with a surface‐based distance methoda)
Authors: Li Heng , Dong Lei , Zhang Lifei , Yang James N. , Gillin Michael T. , Zhu X. Ronald
Published: November 2011

Purpose:

The purpose of this work was to clarify the interactions between the parameters used in the γ index with the surface‐based distance method, which itself can be viewed as a generalized version of the γ index. The examined parameters included the distance to agreement (DTA)/dose difference (DD) criteria, the percentage used as a passing criterion, and the passing percentage for given DTA/DD criteria. The specific aims of our work were (1) to understand the relationships between the parameters used in the γ index, (2) to determine the detection limit, or the minimum detectable error, of the γ index with a given set of parameters, and (3) to establish a procedure to determine parameters that are consistent with the capacity of an IMRT QA system.

Methods:

The surface‐based distance technique with dose gradient factor was derived, and then the relationship between surface‐based distance and γ index was established. The dose gradient factor for plans and measurements of 10 IMRT patients, 10 spine stereotactic radiosurgery (SRS) patients, and 3 Radiological Physics Center (RPC) head and neck phantom were calculated and evaluated. The detection limits of the surface‐based distance and γ index methods were examined by introducing known shifts to the 10 IMRT plans.

Results:

The means of the dose gradient factors were 0.434 mm/% and 0.956 mm/% for the SRS and IMRT plans, respectively. Key quantities (including the mean and 90th and 99th percentiles of the distance distribution) of the surface‐based distance distribution between two dose distributions were linearly proportional to the actual shifts. However, the passing percentage of the γ index for a given set of DTA/DD criteria was not associated with the actual shift. For IMRT, using the standard quality assurance criteria of 3 mm/3% DTA/DD and a 90% passing rate, we found that the detection limit of the γ index in terms of global shift was 4.07 mm/4.07 % without noise.

Conclusions:

Surface‐based distance is a direct measure of the difference between two dose distributions and can be used to evaluate or determine parameters for use in calculating the γ index. The dose gradient factor represents the weighting between spatial and dose shift and should be determined before DTA/DD criteria are set. The authors also present a procedure to determine γ index parameters from measurements.
Serotype Emergence and Genotype Distribution among Macrolide-Resistant Invasive Streptococcus Pneumoniae Isolates in the Postconjugate Vaccine (PCV-7) Era
Authors: Liu Zhenying , Nachamkin Irving , Edelstein Paul H. , Lautenbach Ebbing , Metlay Joshua P.
Published: November 2011

We conducted population-based surveillance for pneumococcal bacteremia within a 5-county region surrounding Philadelphia from October 2001 through September 2008, the period following introduction of the seven-valent pneumococcal conjugate vaccine. Erythromycin resistance increased from 14.7% in 2001-2002 to 20.3% in 2007-2008, while the resistance rate to penicillin (MIC, ≥2 μg/ml) decreased from 7.2% to 4.2% during the same period. The most predominant serotypes associated with erythromycin resistance in 2007-2008 included 19A (29.7%), 15A (29.2%), 6C (10.1%), 3 (5.6%), and 6A (4.5%). The molecular mechanisms for the increasing erythromycin resistance were mainly due to the growing presence of
mef(A)
negative
erm
(B)

+

and
mef(A)

+

erm
(B)

+

genotypes, which increased from 20.0% to 46.1% and from 1.8% to 19.1%, respectively, from 2001-2002 to 2007-2008. However,
mef(A)
-mediated erythromycin resistance decreased from 72.7% in 2001-2002 to 34.8% in 2007-2008. Serotypes related to the
erm
(B) gene were 15A (45.6%), 19A (20.9%), 3 (10.1%), and 6B (6.3%); serotypes related to the
mef(A)
gene were 6A (18.6%), 19A (15.0%), 6C (9.3%), and 14(8.4%); serotypes associated with the presence of both
erm
(B) and
mef(A)
were 19A (81.5%), 15A (7.7%), and 19F (6.2%). Pulsed-field gel electrophoresis analysis demonstrated that erythromycin-resistant isolates within the 19A serotype were genetically diverse and related to several circulating international clones. In contrast, erythromycin-resistant isolates within the 15A serotype consisted of clonally identical or closely related isolates.