bluuebunny/crossref_metadata_2025 huggingface dataset:
Graph theory and the Jahn–Teller theorem
Authors: Ceulemans A. , Lijnen E. , Fowler P. W. , Mallion R. B. , Pisanski T.
Published: December 2011

The Jahn–Teller (JT) theorem predicts spontaneous symmetry breaking and lifting of degeneracy in degenerate electronic states of (nonlinear) molecular and solid-state systems. In these cases, degeneracy is lifted by geometric distortion. Molecular problems are often modelled using spectral theory for weighted graphs, and the present paper turns this process around and reformulates the JT theorem for general vertex- and edge-weighted graphs themselves. If the eigenvectors and eigenvalues of a general graph are considered as orbitals and energy levels (respectively) to be occupied by electrons, then degeneracy of states can be resolved by a non-totally symmetric re-weighting of edges and, where necessary, vertices. This leads to the conjecture that whenever the spectrum of a graph contains a set of bonding or anti-bonding degenerate eigenvalues, the roots of the Hamiltonian matrix over this set will show a linear dependence on edge distortions, which has the effect of lifting the degeneracy. When the degenerate level is non-bonding, distortions of vertex weights have to be included to obtain a full resolution of the eigenspace of the degeneracy. Explicit treatments are given for examples of the octahedral graph, where the degeneracy to be lifted is forced by symmetry, and the phenalenyl graph, where the degeneracy is accidental in terms of the automorphism group.
Transposase mediated construction of RNA-seq libraries
Authors: Gertz Jason , Varley Katherine E. , Davis Nicholas S. , Baas Bradley J. , Goryshin Igor Y. , Vaidyanathan Ramesh , Kuersten Scott , Myers Richard M.
Published: December 2011

RNA-seq has been widely adopted as a gene-expression measurement tool due to the detail, resolution, and sensitivity of transcript characterization that the technique provides. Here we present two transposon-based methods that efficiently construct high-quality RNA-seq libraries. We first describe a method that creates RNA-seq libraries for Illumina sequencing from double-stranded cDNA with only two enzymatic reactions. We generated high-quality RNA-seq libraries from as little as 10 pg of mRNA (∼1 ng of total RNA) with this approach. We also present a strand-specific RNA-seq library construction protocol that combines transposon-based library construction with uracil DNA glycosylase and endonuclease VIII to specifically degrade the second strand constructed during cDNA synthesis. The directional RNA-seq libraries maintain the same quality as the nondirectional libraries, while showing a high degree of strand specificity, such that 99.5% of reads map to the expected genomic strand. Each transposon-based library construction method performed well when compared with standard RNA-seq library construction methods with regard to complexity of the libraries, correlation between biological replicates, and the percentage of reads that align to the genome as well as exons. Our results show that high-quality RNA-seq libraries can be constructed efficiently and in an automatable fashion using transposition technology.
Recent Gene Duplication and Subfunctionalization Produced a Mitochondrial GrpE, the Nucleotide Exchange Factor of the Hsp70 Complex, Specialized in Thermotolerance to Chronic Heat Stress in Arabidopsis
Authors: Hu Catherine , Lin Siou-ying , Chi Wen-tzu , Charng Yee-yung
Published: December 2011

The duplication and divergence of heat stress (HS) response genes might help plants adapt to varied HS conditions, but little is known on the topic. Here, we examined the evolution and function of Arabidopsis (Arabidopsis thaliana) mitochondrial GrpE (Mge) proteins. GrpE acts as a nucleotide-exchange factor in the Hsp70/DnaK chaperone machinery. Genomic data show that AtMge1 and AtMge2 arose from a recent whole-genome duplication event. Phylogenetic analysis indicated that duplication and preservation of Mges occurred independently in many plant species, which suggests a common tendency in the evolution of the genes. Intron retention contributed to the divergence of the protein structure of Mge paralogs in higher plants. In both Arabidopsis and tomato (Solanum lycopersicum), Mge1 is induced by ultraviolet B light and Mge2 is induced by heat, which suggests regulatory divergence of the genes. Consistently, AtMge2 but not AtMge1 is under the control of HsfA1, the master regulator of the HS response. Heterologous expression of AtMge2 but not AtMge1 in the temperature-sensitive Escherichia coli grpE mutant restored its growth at 43°C. Arabidopsis T-DNA knockout lines under different HS regimes revealed that Mge2 is specifically required for tolerating prolonged exposure to moderately high temperature, as compared with the need of the heat shock protein 101 and the HS-associated 32-kD protein for short-term extreme heat. Therefore, with duplication and subfunctionalization, one copy of the Arabidopsis Mge genes became specialized in a distinct type of HS. We provide direct evidence supporting the connection between gene duplication and adaptation to environmental stress.
Individual genetic tagging for teleosts: an empirical validation and a guideline for ecologists
Authors: Andreou D. , Vacquie‐Garcia J. , Cucherousset J. , Blanchet S. , Gozlan R. E. , Loot G.
Published: December 2011

The efficiency of individual genetic tagging was determined by using passive integrated transponders (PIT) as a comparative conventional tagging method. Fifty‐five common dace Leuciscus leuciscus were captured in the wild, PIT tagged and fin clipped (for DNA analysis). Thirty fish were recaptured on three occasions and tissue samples were collected. Using 18 microsatellite loci, 79–94% of the recaptures were correctly assigned. Experience with scoring L. leuciscus microsatellites led to more individuals correctly assigned. Allowing matches that differed by one or two alleles resulted in 100% of all recaptures successfully assigned irrespective of the observer. Reducing the set of loci to five to six loci appropriately selected did not affect the assignment rate, demonstrating that costs can be subsequently reduced. Despite their potential benefits, the application of genetic tags for teleosts has been limited. Here, it was demonstrated that genetic tagging could be applied, and a clear guideline (flowchart) is provided on how this method can be developed for teleosts and other organisms, with subsequent practical applications to ecology, evolutionary biology and conservation management.
Aeolian construction and alluvial dismantling of a fault‐bounded intracontinental aeolian dune field (Teruel Basin, Spain); a continental perspective on Late Pliocene climate change and variability
Authors: RODRÍGUEZ‐LÓPEZ JUAN PEDRO , LIESA CARLOS L. , VAN DAM JAN , LAFUENTE PALOMA , ARLEGUI LUIS , EZQUERRO LOPE , DE BOER POPPE L.
Published: December 2011

An aeolian dune field migrating to the east encroached on the toes of alluvial fans in the Teruel Basin (eastern Spain) during a short interval in the Late Pliocene (ca 2·9 to 2·6 Ma), when Northern Hemisphere glaciation and strong glacial–interglacial cycles began. Preservation of the dune field was controlled by syn‐sedimentary activity of a normal fault. Ephemeral water discharge eroded aeolian sands and formed V‐shaped channels in which aeolian sandstone blocks accumulated. The incorporation of loose aeolian sand in wadi waters modified the sediment/water ratio, changing the physical properties of the flows as they penetrated the aeolian dune field. The erosion and cover of aeolian dune foresets by sheetflood deposits suggest that dune‐damming caused the intermittent ponding of water behind the dunes and its flashy release. The arid climate in the Late Pliocene western Mediterranean realm favoured the transport of windblown sediments from northern Africa and western Mediterranean land masses into the Mediterranean. The formation of the studied aeolian dune field (2·9 to 2·6 Ma) and possibly others (for example, the Atacama, Namib and Sahara deserts) correlates with a strong increase of the influence of obliquity, which can be attributed to the combination of a regional expression related to the reduced effect of precession due to a minimum in the long‐period (2·3 Ma) eccentricity cycle and a remote expression of the onset of the Northern Hemisphere glaciation.
Evidence‐based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group
Authors: Cicardi M. , Bork K. , Caballero T. , Craig T. , Li H. H. , Longhurst H. , Reshef A. , Zuraw B. ,   on behalf of HAWK (Hereditary Angioedema International Working Group)
Published: December 2011

To cite this article: Cicardi M, Bork K, Caballero T, Craig T, Li HH, Longhurst H, Reshef A, Zuraw B on behalf of HAWK (Hereditary Angioedema International Working Group). Evidence‐based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy 2012; 67: 147–157.

Angioedema owing to hereditary deficiency of C1 inhibitor (HAE) is a rare, life‐threatening, disabling disease. In the last 2 years, the results of well‐designed and controlled trials with existing and new therapies for this condition have been published, and new treatments reached the market. Current guidelines for the treatment for HAE were released before the new trials and before the new treatments became available and were essentially based on observational studies and expert opinion. To provide evidence‐based HAE treatment guidelines supported by the new studies, a conference was held in Gargnano del Garda, Italy, from September 26 to 29, 2010. The meeting hosted 58 experienced HAE expert physicians, representatives of pharmaceutical companies and representatives of HAE patients’ associations. Here, we report the topics discussed during the meeting and evidence‐based consensus about management approaches for HAE in adult/adolescent patients.
Invasive pulmonary aspergillosis in a patient with seminomatous testicular cancer
Authors: Saleiro Sandra , Rocha Luís
Published: December 2011

In the past years there has been an increasing incidence of invasive fungal infections, particularly in immunocompromised patients. These infections continue to pose a diagnostic and therapeutic challenge. Considering these facts, the authors report a clinical case of invasive pulmonary aspergillosis which illustrates the improved outcomes associated with the extended‐spectrum triazole, voriconazole, used in first‐line therapy.
Clinicopathological features of paediatric renal biopsies in Shanghai over a 31 year period
Authors: ZHENG YIBING , XU HONG , ZHOU LIJUN , CAO QI , SUN LI , SHEN QIAN , GUO WEI , FANG XIAOYAN , LIU HAIMEI , ZHANG JUN , RAO JIA , CHEN JIN
Published: December 2011

Aim:  To identify the variations in paediatric renal biopsy pathology and clinicopathological features during the past 31 years.

Methods:  A retrospective analysis of paediatric renal biopsies performed at a single institution in Shanghai from January 1979 to December 2009 was conducted.

Results:  The major pathologies included minor glomerular abnormalities (MGA, 26.1%), IgA nephropathy (IgAN, 17%) and mesangial proliferative glomerulonephritis (MsPGN) without IgA deposition (11.3%). The major clinical presentations included nephrotic syndrome (NS, 39.4%), haematuria with proteinuria (24.4%) and persistent microscopic haematuria (15.1%). MGA accounted for 46.9% of the cases in NS. IgAN and HSN accounted for 24% and 28.9% of patients with concomitant haematuria and proteinuria, and thin basement membrane nephropathy accounted for 51.2% of cases with persistent microscopic haematuria. The frequency of IgAN (78.6%) was much higher than that of TBMN (29.0%) in patients with persistent microscopic haematuria with abnormal urinary albumin.

Conclusion:  Minor glomerular abnormalities and IgAN were the major renal diseases in our study population, and the focus of our paediatric nephrologists. The high proportion of TBMN suggested that there should be limited use of renal biopsy for patients with persistent microscopic haematuria and renal biopsy should be performed in the presence of proteinuria or abnormal levels of urinary albumin.
Endogenous Changes in Property Rights Regime*
Authors: LEONARD DANIEL , VAN LONG NGO
Published: December 2011

The purpose of this article is to present a model of the endogenous evolution of a society's property rights regime. We use an overlapping‐generations framework in which capital accumulation takes place. Property rights enforcement is costly. Individuals decide collectively in each period the appropriate level of enforcement and pay taxes to finance it. Poor households have less interest in the enforcement of property rights than rich households. We also consider heterogenous households with different tastes. They differ on their choice of law enforcement. As their wealth and numbers evolve, political power may change sides, hence the property rights regime also evolves.
Mapping and Ablation of a Perisinusal Atrial Tachycardia with Noncontact Mapping
Authors: AUGELLO GIUSEPPE , D'ASCIA SALVATORE , SANTAGOSTINO ANDREINA , ORNAGO OMBRETTA
Published: December 2011

Perisinusal atrial tachycardia may represent a challenging situation due to unsustained burst characterizing the arrhythmia, sensitivity to bumping, and potential complications including sinus node ablation. This case describes the use of a noncontact mapping system to map and ablates this arrhythmia. Benefit of this technology is described.

(PACE 2013; 36:e11–e14)
Composite Mg2TiO4(111)/MgO (111) Gate Oxide on GaN (001)
Authors: Hsiao Chu‐Yun , Wu Jhih‐Cheng , Wu Hsuan‐Ta , Shih Chuan‐Feng
Published: December 2011

Mg2TiO4/MgO composite thin films were deposited on GaN (001) as gate oxides. The use of oxygen in sputtering and post‐annealing increased the (111)‐preferring orientation of Mg2TiO4 on GaN (001). Inserting MgO buffer layer slightly decreased the overall dielectric constant, but considerably improved the electrical properties by modifying the band alignment at interface. The relative permittivity, interfacial trap density, and leakage current of the composite layer‐based capacitor were ~17.6, 7.4 × 1011 eV−1·cm−2, and 4.6 × 10−8A/cm2 (at −2 V), respectively, showing potential application to the GaN‐based metal‐oxide‐semiconductor capacitor.
Spatial patterns of functional divergence in old‐field plant communities
Authors: Siefert Andrew
Published: December 2011

Spatial patterns of functional traits have received little attention in community ecology but have the potential to provide insights into the processes that structure communities. In this study, I used semivariograms to describe spatial patterns of functional traits and evaluate processes (niche differentiation, environmental filtering, and dispersal limitation) driving functional divergence in old‐field plant communities. I collected spatially explicit data on key plant functional traits (vegetative height, specific leaf area [SLA], and leaf dry matter content [LDMC]) and environmental variables (soil depth and soil moisture) across a range of spatial scales (< 1–1500 m) in old fields in central New York. All traits displayed nonrandom spatial patterns consistent with the environmental filtering hypothesis, but patterns differed among traits. Height had strong spatial dependence at scales congruent with spatial heterogeneity of soil depth, indicating that soil depth acted as a spatial template for divergence in height. SLA and LDMC had much weaker spatial dependence, with > 90% of total divergence occurring within 1‐m2plots, demonstrating that high levels of functional divergence may occur at very fine spatial scales. Spatial patterns of intraspecific functional divergence differed among four common species (Solidago canadensis,Bromus inermis,Poa pratensisandGalium mollugo), indicating that species differed in their trait responses to environmental variation. This study provides novel descriptions of spatial patterns of functional traits in plant communities and demonstrates how these patterns can help understand the processes driving functional divergence across spatial scales.
Building a Knowledge-Driven Society: Scholar Participation and Governance in Large Public Works Projects
Authors: Yang Lihua
Published: December 2011

Previous studies have found no relationship between scholar participation and public project performance. Building on the work of Lindblom (1977; 1990), I propose a model depicting scholars' roles in social organizations and governance. A study of thirty-two cases of large public works projects in China and seventeen projects in thirteen other countries shows a moderately positive relationship. The study further shows the greatest influence on project success occurs when participating scholars serve as information brokers and entrepreneurial activity organizers. Successful scholar participation occurred through five working principles: (1) there is dispersed and specialized knowledge production; (2) there is dispersed and asymmetric knowledge possession; (3) knowledge-driven volitions and consensus are criteria for knowledge; (4) the satisfaction of diverse and heterogeneous individual needs is realized through knowledge-driven institutional arrangements; and (5) there are multiple methods of knowledge application. In general, scholar participation seems to be more effective in projects in which there is low political intervention, and in village and county projects. The results of the study provide a theoretical and empirical foundation for further research on scholar participation in social organizations.
Oral mucosal involvement in Langerhans’ cell histiocytosis: long‐term follow‐up of a rare case
Authors: Kilic E , Er N , Mavili E , Alkan A , Gunhan O
Published: December 2011

Langerhans’ cell histiocytosis (LCH) is a rare disease where different organs and systems may be affected. Oral involvement generally consists of mucosal ulceration associated with lesions of the underlying bone. Many reports exist about the misdiagnosis of this disease. Various symptoms may lead the clinician to an incorrect diagnosis, especially with multiple organ involvement. Oral manifestations are common, and dentists should be aware of this disease and evaluate intraoral findings accordingly. This study presents an LCH case characterized by oral mucosal ulcerations with no involvement of the underlying bone. A definitive diagnosis was made by open biopsy from the oral mucosa.
Experimental investigation of impacts by solar cell secondary ejecta on silica aerogel and aluminum foil: Implications for the Stardust Interstellar Dust Collector
Authors: BURCHELL Mark J. , COLE Michael J. , PRICE Mark C. , KEARSLEY Anton T.
Published: December 2011

Abstract– We have shown in laboratory experiment that hypervelocity impacts on a solar cell produce ejecta that can be captured on aluminum (Al 1100) foil or in low density (33 kg m−3) aerogel. The origin of the secondary impacts can be determined by either analysis of the residue in the craters in the foils (which preserve an elemental signature of the solar cell components) or by their pointing direction for tracks in the aerogel (which we show align with the impact direction to ± 0.4°). This experimental evidence explains the observations of the NASA Stardust mission which has reported that the majority of tracks in the aerogel collector used to collect interstellar dust actually point at the spacecraft’s solar panels. From our results, we suggest that it should also be possible to recognize secondary ejecta craters in the Stardust mission aluminum foils, also used as dust sampling devices during the mission.
Ionized nitrogen mono‐hydride bands are identified in the presolar and carbonado diamond spectra
Authors: GARAI Jozsef
Published: December 2011

Abstract– None of the well‐established nitrogen‐related IR absorption bands, common in synthetic and terrestrial diamonds, have been identified in the presolar diamond spectra. In the carbonado diamond spectra, only the single nitrogen impurity (C center) is identified and the assignments of the rest of the nitrogen‐related bands are still debated. It is speculated that the unidentified bands in the nitrogen absorption region are not induced by nitrogen, but rather by nitrogen‐hydrides because in the interstellar environment, nitrogen reacts with hydrogen and forms NH+; NH; NH2; NH3. Among these hydrides, the electronic configuration of NH+ is the closest to carbon. Thus, this ionized nitrogen‐mono‐hydride is the best candidate to substitute carbon in the diamond structure. The bands of the substitutional NH+ defect are deduced by redshifting the irradiation‐induced N+ bands due to the mass of the additional hydrogen. The six bands of the NH+ defects are identified in both the presolar and the carbonado diamond spectra. The new assignments identify all of the nitrogen‐related bands in the spectra, indicating that presolar and carbonado diamonds contain only single nitrogen impurities.
Strictification of étale stacky Lie groups
Authors: Trentinaglia Giorgio , Zhu Chenchang
Published: December 2011

We define stacky Lie groups to be group objects in the 2-category of differentiable stacks. We show that every connected and étale stacky Lie group is equivalent to a crossed module of the form (Γ,G) where Γ is the fundamental group of the given stacky Lie group and G is the connected and simply connected Lie group integrating the Lie algebra of the stacky group. Our result is closely related to a strictification result of Baez and Lauda.
Atomic layer deposition fabricated substoichiometric TiOx nanorods as fuel cell catalyst supports
Authors: Phillips Richard , Hansen Paul , Eisenbraun Eric
Published: December 2011

Atomic layer deposition (ALD)-grown substoichiometric TiOx (1< x <2) was investigated as a possible fuel cell catalyst support material. The Magneli or Ti4O7 phase in particular exhibits acombination of high conductivity, stability, and corrosion resistance, which makes this material a promising replacement support structure when considering the inferior corrosion resistance of carbon-based supports. The current work investigates a novel technique for manufacturing conductive high aspect ratio TiOx nanorods using ALD over high aspect ratio anodic aluminum oxide templates and annealing to reduce the degree of oxidation and increase conductivity. The combination of optimized ALD parameters and the inclusion of a post deposition H2 anneal enable the production of a conductive Magneli phase TiOx film at temperatures below 450 °C.
Applying Brainpower to Obesity
Authors: Kiberstis Paula A.
Published: December 2011

Neurons transplanted from healthy donor mice can repair brain circuitry and partially normalize metabolism in obese mice.
The Stressed Brain
Authors: Stern Peter R.
Published: December 2011

Acute stress leads to reorganization of large-scale neural network connectivity in the brain that is driven by noradrenaline.
A REVIEW ON ARTERY WALL SEGMENTATION TECHNIQUES AND INTIMA-MEDIA THICKNESS MEASUREMENT FOR CAROTID ULTRASOUND IMAGES
Authors: YANG XIN , HE WANJI , LI KAITONG , JIN JIAOYING , ZHANG XUMING , YUCHI MING , DING MINGYUE
Published: December 2011

Stroke and heart attack, which could be led by a kind of cerebrovascular and cardiovascular disease named as atherosclerosis, would seriously cause human morbidity and mortality. It is important for the early stage diagnosis and monitoring medical intervention of the atherosclerosis. Carotid stenosis is a classical atherosclerotic lesion with vessel wall narrowing down and accumulating plaques burden. The carotid artery of intima-media thickness (IMT) is a key indicator to the disease. With the development of computer assisted diagnosis technology, the imaging techniques, segmentation algorithms, measurement methods, and evaluation tools have made considerable progress. Ultrasound imaging, being real-time, economic, reliable, and safe, now seems to become a standard in vascular assessment methodology especially for the measurement of IMT. This review firstly attempts to discuss the clinical relevance of measurements in clinical practice at first, and then followed by the challenges that one has to face when approaching the segmentation of ultrasound images. Secondly, the commonly used methods for the IMT segmentation and measurement are presented. Thirdly, discussion and evaluation of different segmentation techniques are performed. An overview of summary and future perspectives is given finally.
Pyrrolidine dithiocarbamate enhances hepatic glycogen synthesis and reduces FoxO1-mediated gene transcription in type 2 diabetic rats
Authors: Zhu Tienian , Zhao Ruijing , Zhang Lizhong , Bernier Michel , Liu Jiankun
Published: December 2011

The aim of the present study was to examine the effects of pyrrolidine dithiocarbamate (PDTC) on hepatic glycogen synthesis and FoxO1 transcriptional activity in type 2 diabetic rats and the mechanism underlying these effects. Fasting blood glucose and glycogen deposition, together with expressions of two key genes related to gluconeogenesis, were studied in the liver of rats fed a normal diet (NC), high-fat diet (HFD)-induced insulin-resistant rats made type 2 diabetic by a single intraperitoneal injection of streptozotocin (DM), and a DM with intervention of PDTC (DM + PDTC) for 1 wk. The phosphorylation of Akt, GSK-3β, and FoxO1 was assessed in liver extracts of fasted rats by Western blot, whereas indirect immunofluorescence staining was performed to determine the cellular distribution of FoxO1. The DM rats exhibited obvious increases in fasting blood glucose as well as decreased hepatic glycogen content compared with the NC group. Activation of the Akt/GSK-3β pathway and inactivating phosphorylation of FoxO1 were reduced greatly in DM rat livers ( P < 0.01). By contrast, PDTC treatment protected DM rats against high fasting blood glucose and hepatic glycogen deposition loss. PDTC also elicited an increase in Akt/GSK-3β signaling and subsequent inactivation and nuclear export of FoxO1 in DM rat livers, which translated into a significant reduction in the expression of two FoxO1 target genes, phospho enolpyruvate carboxykinase and glucose-6-phosphatase. This study suggests that PDTC enhances hepatic glycogen synthesis, whereas it reduces FoxO1 transcriptional activity in DM rats.
Comparing Host Plant Resistance, Engineered Resistance, and Insecticide Treatment for Control of Colorado Potato Beetle and Potato Leafhopper in Potatoes
Authors: Ghidiu Gerald M. , Douches David S. , Felcher Kimberly J. , Coombs Joseph J.
Published: December 2011

The Colorado potato beetle,Leptinotarsa decemlineata(Say) Order Coleoptera and the potato leafhopper,Empoasca fabae(Harris) Order Homoptera, are the major insect pests of potato in eastern North America. In two years of field trials, we compared the effectiveness of three pest management options for the control of Colorado potato beetle and potato leafhopper: natural host plant resistance (glandular trichomes), engineered resistance (Bacillus thuringiensis[Bt] Berlinercry3Agene) and a susceptible potato cultivar (Superior) with an at-planting application of the insecticide thiamethoxam. Similar and acceptable control of the Colorado potato beetle larvae was obtained with theBt-cry3Alines and the thiamethoxam treated “Superior” variety. The glandular trichome cultivar had significantly less Colorado potato beetle damage than did the untreated “Superior” in 2004, although damage was significantly greater than in theBt-cry3Alines and the insecticide-treated potatoes for both years, and was the only treatment that consistently had very little potato leafhopper damage. These data demonstrate that although each type of host plant resistance mechanism (Bt-cry3Aor glandular trichomes) was as effective as the chemical control against one of the insects, neither provides adequate resistance to both Colorado potato beetle and potato leaf hopper.
Long-Term Outcome after Autologous Stem Cell Transplantation with Adequate Peripheral Blood Stem Cell Mobilization Using Plerixafor and G-CSF in Poor Mobilizer Lymphoma and Myeloma Patients
Authors: Moreb Jan S. , Salmasinia Donya , Hsu Jack , Hou Wei , Cline Christina , Rosenau Emma
Published: December 2011

Poor peripheral blood stem cell (PBSC) mobilization predicts worse outcome for myeloma and lymphoma patients post autologous stem cell transplant (ASCT). We hypothesize that PBSC harvest using plerixafor and G-CSF in poor mobilizers may improve long-term outcome. We retrospectively analyzed the data on patients who had second PBSC mobilization using plerixafor and G-CSF as a rescue. Nine lymphoma and 8 multiple myeloma (MM) patients received the drug. A control group of 25 MM and lymphoma patients who were good mobilizers with G-CSF only was used for comparison. Sixteen of the 17 poor mobilizers proceeded to ASCT, and one MM patient had tandem transplants. Length of hospital stay, infection incidence, granulocyte engraftment, and long-term hematopoietic recovery were not significantly different between the two groups. In conclusion, all poor mobilizers were able to obtain adequate stem cells transplant dose and had similar transplant course and long-term outcome to that of the control good mobilizers group.
Genetics: Polymorphisms, Epigenetics, and Something In Between
Authors: Maggert Keith A.
Published: December 2011

At its broadest sense, to say that a phenotype is epigenetic suggests that it occurs without changes in DNA sequence, yet is heritable through cell division and occasionally from one organismal generation to the next. Since gene regulatory changes are oftentimes in response to environmental stimuli and may be retained in descendent cells, there is a growing expectation that one's experiences may have consequence for subsequent generations and thus impact evolution by decoupling a selectable phenotype from its underlying heritable genotype. But the risk of this overbroad use of “epigenetic” is a conflation of genuine cases of heritable non-sequence genetic information with trivial modes of gene regulation. A look at the term “epigenetic” and some problems with its increasing prevalence argues for a more reserved and precise set of defining characteristics. Additionally, questions arising about how we define the “sequence independence” aspect of epigenetic inheritance suggest a form of genome evolution resulting from induced polymorphisms at repeated loci (e.g., the rDNA or heterochromatin).
Low Morbidity and Mortality after Stenting for Malignant Bowel Obstruction
Authors: Driest J.J. , Zwaving H.H. , Ledeboer M. , Eeftinck Schattenkerk M. , Kuipers E.J. , ter Borg F.
Published: December 2011

Background: The difference in mortality between emergency and elective surgery for malignant colonic obstruction is more than 5% in healthy patients below the age of 65 and increases with age to around 20%. Emergency surgery can be avoided by endoscopic placement of a self-expandable metal stent (SEMS). Aim: To evaluate the effectiveness and safety of SEMS as ‘bridge to surgery’. Method: Between January 2001 and July 2008, SEMS were placed for acute malignant colonic obstruction in 45 patients (median age 72 years, range 35–91). Results: The procedure was technically successful in 43 patients (94%) with resolution of obstructive symptoms within 48 h in 87% of the patients. No perforations occurred during the procedure or while awaiting surgery. Two (4%) patients required a second endoscopic procedure. All patients underwent a single-stage surgical procedure. Postoperative mortality was 2.2% (n = 1). Histology showed advanced colorectal cancer (T3–4N1–2M0–1) in 75% of the patients. Conclusion: SEMS placement is a safe and effective procedure as bridge to surgery in patients presenting with colonic obstruction due to colorectal malignancy. This procedure carries a risk of serious complications well below that of the reported difference in mortality between emergency an elective surgery.
Soluble Endoglin and Transforming Growth Factor-β1 and the Development of Vasospasm after Spontaneous Subarachnoid Hemorrhage: A Pilot Study
Authors: Dietmann Anelia , Lackner Peter , Fischer Marlene , Broessner Gregor , Pfausler Bettina , Helbok Raimund , Schmutzhard Erich , Beer Ronny
Published: December 2011

Background:Cerebral vasospasm (CVS) and cerebral infarction due to vasospasm (CIV) are major complications after spontaneous subarachnoid hemorrhage (SAH). Alteration of vasomotor tone has been postulated as an important factor in the pathogenesis of CVS. Members of the transforming growth factor-β (TGF-β) family and their receptors have been implicated in the regulation of vascular tone. Methods:Serum levels of soluble endoglin (sEng) and plasma levels of TGF-β1 of 20 consecutive SAH patients were analyzed within 15 days after SAH using ELISA and correlated with CVS, CIV and outcome. Twenty voluntary age- and sex-matched blood donors served as healthy controls (HCs). Results:SAH patients showed significantly lower sEng serum levels and higher TGF-β1 plasma levels compared to HCs. Patients who developed Doppler sonographic CVS (dCVS) had significantly higher TGF-β1 levels. Patients with CIV and patients with hydrocephalus showed significantly lower sEng levels. On day 3, pSAH sEng levels below 3.88 ng/ml or TGF-β1 levels higher than 7.2 ng/ml had a predictive value for the development of CIV. Low mean sEng levels over the study period were highly predictive of poor long-term functional outcome (modified Rankin Scale ≧2) at 6 months after SAH. Conclusions:Concentrations of the vasoactive factors sEng in serum and TGF-β1 in plasma are significantly altered in SAH patients compared to HCs. The results of this pilot study indicate that sEng could represent a novel prognostic biomarker for the onset of secondary complications and long-term functional outcome after SAH.
Classroom-based and distance learning education and training courses in end-of-life care for health and social care staff: A systematic review
Authors: Pulsford David , Jackson Georgina , O’Brien Terri , Yates Sue , Duxbury Joy
Published: December 2011

Background:

Staff from a range of health and social care professions report deficits in their knowledge and skills when providing end-of-life and palliative care, and education and training has been advocated at a range of levels.

Aims:

To review the literature related to classroom-based and distance learning education and training initiatives for health and social care staff in end-of-life and palliative care, in terms of their target audience, extent, modes of delivery, content and teaching and learning strategies, and to identify the most effective educational strategies for enhancing care.

Design:

A systematic review of the literature evaluating classroom-based and distance learning education and training courses for health and social care staff in end-of-life and palliative care.

Data sources:

Online databases CINAHL, MEDLINE, EMBASE and PSYCHINFO between January 2000 and July 2010. Studies were selected that discussed specific education and training initiatives and included pre-and post-test evaluation of participants’ learning.

Results:

30 studies met eligibility criteria. The majority reported successful outcomes, though there were some exceptions. Level of prior experience and availability of practice reinforcement influenced learning. Participative and interactive learning strategies were predominantly used along with discussion of case scenarios. Multi-professional learning was infrequently reported and service user and carer input to curriculum development and delivery was reported in only one study.

Conclusions:

Classroom-based education and training is useful for enhancing professionals’ skills and perceived preparedness for delivering end-of-life care but should be reinforced by actual practice experience.
Substance Use Disorder and ADHD
Authors: Kousha Maryam , Shahrivar Zahra , Alaghband-rad Javad
Published: December 2011

Objective: To assess the pattern of substance use disorder (SUD) in adolescents with and without history of attention - deficit / hyperactivity disorder (ADHD) using an Iranian sample in the context of a cultural background and drug availability is differing from Western countries. Method: In this case- control study, the participants were interviewed by a child psychiatrist and the measures included: kiddie Schedule for Affective Disorder and Schizophrenia for school age children (K-SADS), Opium Treatment Index (OTI) and Global Assessment Functioning (GAF). Data were analyzed with chi square test and T test and fisher exact test by EPI.6 soft ware. Results: Adolescents with ADHD were younger at the time of starting cigarette smoking, substance use, abuse and dependency (p = 0.0001), a shorter period between their first-time substance use and substance dependence or abuse (p = 0.0001), more severe substance use (for cannabis, heroine, cigarette and drugs such as benzodiazepines p < 0.05) and more functional impairment (p = 0.0007). Average number of co morbid disorders were higher in ADHD group. (p = 0.03) Conclusion: Although the pattern and type of substance use may be different in Iranian culture, our findings about the relationship between ADHD and SUD are similar to other western and non western countries. The presence of ADHD may over-ride cultural barriers and lower availability of drugs to the development of SUD in Iranian adolescents. Early diagnosis and treatment of ADHD may propose with better prognosis of SUD and subsequent decrease in the prevalence of SUD and the costs of SUD-related pathology in this population.
Activation of ATF4 mediates unwanted Mcl-1 accumulation by proteasome inhibition
Authors: Hu Jinsong , Dang Nana , Menu Eline , De Bryune Elke , Xu Dehui , Van Camp Ben , Van Valckenborgh Els , Vanderkerken Karin
Published: December 2011

Myeloid cell leukemia-1 (Mcl-1) protein is an anti-apoptotic Bcl-2 family protein that plays essential roles in multiple myeloma (MM) survival and drug resistance. In MM, it has been demonstrated that proteasome inhibition can trigger the accumulation of Mcl-1, which has been shown to confer MM cell resistance to bortezomib-induced lethality. However, the mechanisms involved in this unwanted Mcl-1 accumulation are still unclear. The aim of the present study was to determine whether the unwanted Mcl-1 accumulation could be induced by the unfolded protein response (UPR) and to elucidate the role of the endoplasmic reticulum stress response in regulating Mcl-1 expression. Using quantitative RT-PCR and Western blot, we found that the translation of activating transcription factor-4 (ATF4), an important effector of the UPR, was also greatly enhanced by proteasome inhibition. ChIP analysis further revealed that bortezomib stimulated binding of ATF4 to a regulatory site (at position −332 to −324) at the promoter of the Mcl-1 gene. Knocking down ATF4 was paralleled by down-regulation of Mcl-1 induction by bortezomib and significantly increased bortezomib-induced apoptosis. These data identify the UPR and, more specifically, its ATF4 branch as an important mechanism mediating up-regulation of Mcl-1 by proteasome inhibition.
Performance of random forests and logic regression methods using mini-exome sequence data
Authors: Kim Yoonhee , Li Qing , Cropp Cheryl D , Sung Heejong , Cai Juanliang , Simpson Claire L , Perry Brian , Dasgupta Abhijit , Malley James D , Wilson Alexander F , Bailey-Wilson Joan E
Published: December 2011

Machine learning approaches are an attractive option for analyzing large-scale data to detect genetic variants that contribute to variation of a quantitative trait, without requiring specific distributional assumptions. We evaluate two machine learning methods, random forests and logic regression, and compare them to standard simple univariate linear regression, using the Genetic Analysis Workshop 17 mini-exome data. We also apply these methods after collapsing multiple rare variants within genes and within gene pathways. Linear regression and the random forest method performed better when rare variants were collapsed based on genes or gene pathways than when each variant was analyzed separately. Logic regression performed better when rare variants were collapsed based on genes rather than on pathways.
Methods for detecting associations between phenotype and aggregations of rare variants
Authors: Yang Fan , Kang Chul Joo , Marjoram Paul
Published: December 2011

Although genome-wide association studies have uncovered variants associated with more than 150 traits, the percentage of phenotypic variation explained by these associations remains small. This has led to the search for the dark matter that explains this missing genetic component of heritability. One potential explanation for dark matter is rare variants, and several statistics have been devised to detect associations resulting from aggregations of rare variants in relatively short regions of interest, such as candidate genes. In this paper we investigate the feasibility of extending this approach in an agnostic way, in which we consider all variants within a much broader region of interest, such as an entire chromosome or even the entire exome. Our method searches for subsets of variant sites using either Markov chain Monte Carlo or genetic algorithms. The analysis was performed with knowledge of the Genetic Analysis Workshop 17 answers.
Old lessons learned anew: family-based methods for detecting genes responsible for quantitative and qualitative traits in the Genetic Analysis Workshop 17 mini-exome sequence data
Authors: Simpson Claire L , Justice Cristina M , Krishnan Mera , Wojciechowski Robert , Sung Heejong , Cai Jerry , Green Tiffany , Lewis Deyana , Behneman Dana , Wilson Alexander F , Bailey-Wilson Joan E
Published: December 2011

Family-based study designs are again becoming popular as new next-generation sequencing technologies make whole-exome and whole-genome sequencing projects economically and temporally feasible. Here we evaluate the statistical properties of linkage analyses and family-based tests of association for the Genetic Analysis Workshop 17 mini-exome sequence data. Based on our results, the linkage methods using relative pairs or nuclear families had low power, with the best results coming from variance components linkage analysis in nuclear families and Elston-Stewart model-based linkage analysis in extended pedigrees. For family-based tests of association, both ASSOC and ROMP performed well for genes with large effects, but ROMP had the advantage of not requiring parental genotypes in the analysis. For the linkage analyses we conclude that genome-wide significance levels appear to control type I error well but that “suggestive” significance levels do not. Methods that make use of the extended pedigrees are well powered to detect major loci segregating in the families even when there is substantial genetic heterogeneity and the trait is mainly polygenic. However, large numbers of such pedigrees will be necessary to detect all major loci. The family-based tests of association found the same major loci as the linkage analyses and detected low-frequency loci with moderate effect sizes, but control of type I error was not as stringent.
Analysis of human mini-exome sequencing data from Genetic Analysis Workshop 17 using a Bayesian hierarchical mixture model
Authors: Bueno Filho Julio S , Morota Gota , Tran Quoc , Maenner Matthew J , Vera-Cala Lina M , Engelman Corinne D , Meyers Kristin J
Published: December 2011

Next-generation sequencing technologies are rapidly changing the field of genetic epidemiology and enabling exploration of the full allele frequency spectrum underlying complex diseases. Although sequencing technologies have shifted our focus toward rare genetic variants, statistical methods traditionally used in genetic association studies are inadequate for estimating effects of low minor allele frequency variants. Four our study we use the Genetic Analysis Workshop 17 data from 697 unrelated individuals (genotypes for 24,487 autosomal variants from 3,205 genes). We apply a Bayesian hierarchical mixture model to identify genes associated with a simulated binary phenotype using a transformed genotype design matrix weighted by allele frequencies. A Metropolis Hasting algorithm is used to jointly sample each indicator variable and additive genetic effect pair from its conditional posterior distribution, and remaining parameters are sampled by Gibbs sampling. This method identified 58 genes with a posterior probability greater than 0.8 for being associated with the phenotype. One of these 58 genes, PIK3C2B was correctly identified as being associated with affected status based on the simulation process. This project demonstrates the utility of Bayesian hierarchical mixture models using a transformed genotype matrix to detect genes containing rare and common variants associated with a binary phenotype.
Analytical Fragility Curves for Ordinary Highway Bridges in Turkey
Authors: Avşar Özgür , Yakut Ahmet , Caner Alp
Published: December 2011

This study focuses on the development of analytical fragility curves for the ordinary highway bridges constructed after the 1990s. Four major bridge classes were employed based on skew angle, number of columns per bent, and span number (only multispan bridges). Nonlinear response-history analyses (NRHA) were conducted for each bridge sample using a detailed 3-D analytical model subjected to earthquake ground motions of varying seismic intensities. A component-based approach that uses several engineering demand parameters was employed to determine the seismic response of critical bridge components. Corresponding damage limit states were defined either in terms of member capacities or excessive bearing displacements. Lognormal fragility curves were obtained by curve fitting the point estimates of the probability of exceeding each specified damage limit state for each major bridge class. Bridges with larger skew angles or single-column bents were found to be the most seismically vulnerable.
Sex Differences in the Metabolic Effects of Testosterone in Sheep
Authors: Clarke Scott D. , Clarke Iain J. , Rao Alexandra , Cowley Michael A. , Henry Belinda A.
Published: December 2011

Adiposity is regulated in a sexually divergent manner. This is partly due to sex steroids, but the differential effects of androgens in males and females are unclear. We investigated effects of testosterone on energy balance in castrated male (n = 6) and female sheep (n = 4), which received 3 × 200 mg testosterone implants for 2 wk or blank implants (controls). Temperature probes were implanted into retroperitoneal fat and skeletal muscle. Blood samples were taken to measure metabolites and insulin. In males, muscle and fat biopsies were collected to measure uncoupling protein (UCP) mRNA and phosphorylation of AMP-activated protein kinase and Akt. Testosterone did not change food intake in either sex. Temperature in muscle was higher in males than females, and testosterone reduced heat production in males only. In fat, however, temperature was higher in the castrate males compared with females, and there was no effect of testosterone treatment in either sex. Preprandial glucose levels were lower, but nonesterified fatty acids were higher in females compared with males, irrespective of testosterone. In males, the onset of feeding increased UCP1 and UCP3 mRNA levels in skeletal muscle, without an effect of testosterone. During feeding, testosterone reduced glucose levels in males only but did not alter the phosphorylation of AMP-activated protein kinase or Akt in muscle. Thus, testosterone maintains lower muscle and fat temperatures in males but not females. The mechanism underlying this sex-specific effect of testosterone is unknown but may be due to sexual differentiation of the brain centers controlling energy expenditure.