bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomics-Driven Oncology: Framework for an Emerging Paradigm
Authors: Garraway Levi A.
Published: April 2013

A majority of cancers are driven by genomic alterations that dysregulate key oncogenic pathways influencing cell growth and survival. However, the ability to harness tumor genetic information for its full clinical potential has only recently become manifest. Over the past several years, the convergence of discovery, technology, and therapeutic development has created an unparalleled opportunity to test the hypothesis that systematic knowledge of genomic information from individual tumors can improve clinical outcomes for many patients with cancer. Rigorous evaluation of this genomics-driven cancer medicine hypothesis will require many logistic innovations that are guided by overarching conceptual advances in tumor genomic profiling, data interpretation, clinical trial design, and the ethical return of genetic results to oncologists and their patients. The results of these efforts and the rigor with which they are implemented will determine whether and how comprehensive tumor genomic information may become incorporated into the routine care of patients with cancer.
Clinical Analysis and Interpretation of Cancer Genome Data
Authors: Van Allen Eliezer M. , Wagle Nikhil , Levy Mia A.
Published: April 2013

The scale of tumor genomic profiling is rapidly outpacing human cognitive capacity to make clinical decisions without the aid of tools. New frameworks are needed to help researchers and clinicians process the information emerging from the explosive growth in both the number of tumor genetic variants routinely tested and the respective knowledge to interpret their clinical significance. We review the current state, limitations, and future trends in methods to support the clinical analysis and interpretation of cancer genomes. This includes the processes of genome-scale variant identification, including tools for sequence alignment, tumor–germline comparison, and molecular annotation of variants. The process of clinical interpretation of tumor variants includes classification of the effect of the variant, reporting the results to clinicians, and enabling the clinician to make a clinical decision based on the genomic information integrated with other clinical features. We describe existing knowledge bases, databases, algorithms, and tools for identification and visualization of tumor variants and their actionable subsets. With the decreasing cost of tumor gene mutation testing and the increasing number of actionable therapeutics, we expect the methods for analysis and interpretation of cancer genomes to continue to evolve to meet the needs of patient-centered clinical decision making. The science of computational cancer medicine is still in its infancy; however, there is a clear need to continue the development of knowledge bases, best practices, tools, and validation experiments for successful clinical implementation in oncology.
Leveraging Cancer Genome Information in Hematologic Malignancies
Authors: Rampal Raajit , Levine Ross L.
Published: April 2013

The use of candidate gene and genome-wide discovery studies in the last several years has led to an expansion of our knowledge of the spectrum of recurrent, somatic disease alleles, which contribute to the pathogenesis of hematologic malignancies. Notably, these studies have also begun to fundamentally change our ability to develop informative prognostic schema that inform outcome and therapeutic response, yielding substantive insights into mechanisms of hematopoietic transformation in different tissue compartments. Although these studies have already had important biologic and translational impact, significant challenges remain in systematically applying these findings to clinical decision making and in implementing new technologies for genetic analysis into clinical practice to inform real-time decision making. Here, we review recent major genetic advances in myeloid and lymphoid malignancies, the impact of these findings on prognostic models, our understanding of disease initiation and evolution, and the implication of genomic discoveries on clinical decision making. Finally, we discuss general concepts in genetic modeling and the current state-of-the-art technology used in genetic investigation.
A young patient of hereditary renal hypouricaemia presenting with exercise-induced rhabdomyolysis and acute kidney injury
Authors: Chakraborty Sutirtha , Sural Saubhik
Published: April 2013

Hereditary renal hypouricaemia (HRH) is a genetic disorder commonly associated with exercise-induced acute kidney injury (AKI). We report the case of a 19-year-old man who was admitted to hospital with exercise-induced AKI and who was subsequently shown to have HRH. We believe this to be the first description of a case of HRH co-presenting with rhabdomyolysis.
Elevated cardiac markers are associated with higher mortality in patients after transjugular intrahepatic portosystemic shunt insertion
Authors: Vasatova Martina , Pudil Radek , Safka Vaclav , Fejfar Tomas , Buchler Tomas , Hulek Petr , Palicka Vladimir
Published: April 2013

Background

Transjugular intrahepatic portosystemic shunts (TIPSs) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess the value of cardiac markers before and after TIPS insertion for the prediction of one-year mortality in cirrhotic patients.

Methods

The study population consisted of 55 patients (38 men and 17 women, aged 55.6 ± 8.9 y, range 37-74) with liver cirrhosis treated with transjugular portosystemic shunting. Biochemical markers were measured before and 24 h after TIPS. High-sensitivity cardiac troponin T (hs-cTnT) was tested by high-sensitivity immunoassay for Elecsys analyser (Roche Diagnostics). Concentrations of creatine kinase MB isoenzyme, myoglobin (MYO), glycogenphosphorylase BB isoenzyme (GPBB) and heart type of fatty acid binding protein (FABP) were measured by the Evidence Investigator protein biochip system (Randox Laboratories).

Results

In patients before TIPS insertion, hs-cTnT was increased above the cut-off (0.014 μg/L) in 39.2% of patients. Higher hs-cTnT and FABP concentrations were associated with poor survival in patients before TIPS (hs-cTnT: P = 0.018; FABP: P = 0.016). Twenty-four hours after the TIPS procedure, we found a significant elevation in serum GPBB in comparison with preprocedural values ( P < 0.001). There was an association between postprocedural concentrations of cardiac markers (MYO, hs-cTnT, FABP) and overall survival.

Conclusions

Measurement of cardiac markers, mainly hs-cTnT and FABP, may be useful for mortality prediction in cirrhotic patients after TIPS. Cardiac markers are better mortality predictors than other risk factors such as age, gender or Child-Pugh score.
Association between C-reactive protein, pro-oxidant-antioxidant balance and traditional cardiovascular risk factors in an Iranian population
Authors: Razavi Akramosadat , Baghshani Mohammad Reza , Rahsepar Amir Ali , Ardabili Hossein Mohaddes , Andalibi Mohammad Sobhan Sheikh , Parizadeh Seyyed Mohammad Reza , Tavallaie Shima , Mousavi Somayeh , Ghayour-Mobarhan Majid , Ferns Gordon
Published: April 2013

Background

Inflammatory states are known to cause an imbalance in the redox status. We aimed to study the possible associations between pro-oxidant-antioxidant balance (PAB) and serum high-sensitive C-reactive protein (hs-CRP) concentrations and traditional cardiovascular disease (CVD) risk factors in an unselected Iranian population and in groups of individuals with specific disease.

Methods

The study was conducted among an unselected population of 758 male subjects. Biochemical markers, including hs-CRP and PAB values, were measured.

Results

Serum hs-CRP concentrations were positively associated with serum PAB values (r = 0.260, P ≤ 0.001). Univariate analysis showed that PAB values were statistically higher in individuals who were obese or smokers compared with non-obese and non-smokers individuals (P < 0.01). While serum hs-CRP concentrations were significantly higher in older subjects, subjects with obesity, diabetes mellitus, metabolic syndrome, central obesity, hypertriglyceridaemia, higher low-density lipoprotein cholesterol concentrations, positive history of CVD and lower physical activity than subjects without these risk factors (P < 0.05). Comparing hs-CRP and PAB values in different CVD risk score subgroups showed a significant incremental rise in both parameters as CVD risk score increased (P < 0.05). Using multiple linear regression analysis we found a strong association between PAB values and hs-CRP concentrations.

Conclusions

This study showed that among Iranian subjects, the inflammatory marker, hs-CRP, was strongly and positively associated with a marker of oxidative stress and also with several traditional risk factors of CVD. Moreover, the impact of traditional cardiovascular risk factors on hs-CRP concentrations and PAB values differed.
Clinical biochemistry of dihydrotestosterone
Authors: Marchetti Paula M , Barth Julian H
Published: April 2013

Dihydrotestosterone (DHT) is the most potent natural androgen in humans. There has been an increasing interest in this androgen and its role in the development of primary and secondary sexual characteristics as well as its potential roles in diseases ranging from prostate and breast cancer to Alzheimer's disease. Despite the range of pathologies shown to involve DHT there is little evidence for measurement of serum DHT in the management of these diseases. In this review we describe the physiology of DHT production and action, summarize current concepts in the role of DHT in the pathogenesis of various disorders of sexual development, compare current methods for the measurement of DHT and conclude on the clinical utility of DHT measurement. The clinical indications for the measurement of DHT in serum are: investigation of 5a reductase deficiency in infants with ambiguous genitalia and palpable gonads; men with delayed puberty and/or undescended testes; and to confirm the presence of active testicular tissue. Investigation is aided by the use of human chorionic gonadotrophin stimulation. Due to paucity of published data on this procedure, it is important to follow guidelines prescribed by the laboratory performing the analysis to ensure accurate interpretation.
Helix B surface peptide administered after insult of ischemia reperfusion improved renal function, structure and apoptosis through beta common receptor/erythropoietin receptor and PI3K/Akt pathway in a murine model
Authors: Yang Cheng , Zhao Tian , Lin Miao , Zhao Zitong , Hu Linkun , Jia Yichen , Xue Yinjia , Xu Ming , Tang Qunye , Yang Bin , Rong Ruiming , Zhu Tongyu
Published: April 2013

Erythropoietin (EPO) has been well recognized as a tissue protective agent by inhibiting apoptosis and inflammation. The tissue protective effect of EPO, however, only occurs at a high dosage, which may elicit severe side-effects at the meantime. Helix B surface peptide (HBSP), a novel peptide derived from the non-erythropoietic helix B of EPO, plays a specific role in tissue protection. We investigated effects of HBSP and the expression of its heterodimeric receptor, beta common receptor (βcR)/EPO receptor (), in a murine renal ischemia reperfusion (IR) injury model. HBSP significantly ameliorated renal dysfunction and tissue damage, decreased apoptotic cells in the kidney and reduced activation of caspase-9 and 3. The βcR/EPOR in the kidney was up-regulated by IR, but down-regulated by HBSP. Further investigation revealed that the expression and phosphorylation of Akt was dramatically enhanced by HBSP, but strongly reversed by wortmannin, the PI3K inhibitor. Wortmannin intervention improved βcR/EPOR expression, promoted caspase-9 and 3 activation, and increased active caspase-3 positive cells, while renal function and structure, and apoptotic cell counts scarcely changed. This result indicates a significant contribution of PI3K/Akt signaling pathway in the renoprotection of HBSP. The therapeutic effects of HBSP in this study suggest that HBSP could be a better candidate for renal protection.
Remodeling of elastic layer of aortic artery after training by swimming in spontaneously hypertensive rats
Authors: Andrade Geisielle Pereira , Cintra Mariana Molinar Mauad , Alves Polyanna Miranda , Neto Octávio Barbosa , Silva Renata Calciolari Rossi E , Da Silva Valdo José Dias , Dos Reis Marlene Antônia , Abate Débora Tavares De Resende E Silva
Published: April 2013

Hypertension is a major risk factor for cardiovascular diseases, in which the elastic properties of arteries are subjected to high pressure levels, and networks of elastic fibers may develop cleft longitudinal, transverse, breaks and fragmentation, and such structural changes (fibrosis and degradation of elastin) may lead to a decrease in the elasticity of the artery. The descending thoracic aortas of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs) subjected to physical training through swimming or those of sedentary rats were prepared with hematoxylin-eosin and Verhoff to assess the artery medial. The images were captured with a videocamera coupled to an ordinary light microscope and the images were analyzed with the same program. SHRs showed a larger area of the medial layer of the thoracic aorta (F = 25,764, P, 0.001), and it was observed that rats submitted to physical training through swimming showed a larger area of the thoracic aorta (t = 3.206, P = 0.011). There was a higher percentage of elastic trained (F = 6.536, P = 0.019). To conclude, this study aimed to determine the elastic component of the aortic artery in animals that underwent exercise when compared with those that did not perform the activity, and analyze the relationship between the area of the aortic wall in trained and sedentary animals. The principal conclusion is that the rigidity of the aorta is not increased in SHRs subjected to physical training compared with that of trained WKY animals; however, when sedentary SHRs were analyzed there was a decrease in the elasticcomponent, which can characterize the aortic arterial stiffness in SHRs.
Flame Color as a Lean Blowout Predictor
Authors: Chaudhari Rajendra R. , Sahu Rakesh Prasad , Ghosh Suvojit , Mukhopadhyay Achintya , Sen Swarnendu
Published: April 2013

The study characterizes the behavior of a premixed swirl stabilized dump plane combustor flame near its lean blow-out (LBO) limit in terms of CH* chemiluminiscence intensity and observable flame color variations for a wide range of equivalence ratio, flow rates and degree of premixing (characterized by premixing length, L fuel). LPG and pure methane are used as fuel. We propose a novel LBO prediction strategy based solely on the flame color. It is observed that as the flame approaches LBO, its color changes from reddish to blue. This observation is found to be valid for different levels of fuel-air premixing achieved by changing the available mixing length of the air and the fuel upstream of the dump plane although the flame dynamics were significantly different. Based on this observation, the ratio of the intensities of red and blue components of the flame as captured by a color CCD camera was used as a metric for detecting the proximity of the flame to LBO. Tests were carried out for a wide range of air flow rates and using LPG and CH4 as fuel. For all the operating conditions and both fuels tested, this ratio was found to monotonically decrease as LBO was approached. Moreover, the value of this ratio was within a small range close to LBO for all the cases investigated. This makes the ratio suitable as a metric for LBO detection at all levels of premixing.
Primeiro registro de Ectopsocus titschacki Jentsch (Psocodea: Psocoptera: Ectopsocidae) para o Estado da Bahia: Uma Prova da Falta de Estudos nessa Ordem de Insecta no Brasil
Authors: Silva Neto Alberto Moreira , Bravo Freddy , García Aldrete Alfonso N.
Published: April 2013

Nesse trabalho realizamos o primeiro registro de Ectopsocus titschacki Jentsch para o Estado da Bahia, incluindo alguns comentários sobre a atual situação do conhecimento e da distribuição dessa ordem de Insecta no Brasil evidenciando a lacuna de conhecimento desse grupo em alguns estados especialmente aqueles pertencentes à região Nordeste.

First Record of Ectopsocus titschacki Jentsch (Psocodea: Psocoptera: Ectopsocidae) in Bahia State: Proof of a Lack of Studies on this Order of Insecta in Brazil

Abstract. In this paper we report the first record of Ectopsocus titschacki Jentsch for the State of Bahia, including some comments on the current state of knowledge and distribution of this order of Insecta in Brazil showing the knowledge gap that group in some states especially those belonging to Northeast.
Aspectos ecológicos de Atta sexdens piriventris Santschi (Hymenoptera: Formicidae) no município de Capinzal, Santa Catarina, Brasil
Authors: Spier Manuelly Sartori , Spier Edson Fernando , Dalavéquia Máira Aparecida , Favretto Mario Arthur
Published: April 2013

Entre as espécies de formigas economicamente importantes, devido aos danos que muitas vezes causam à agricultura, as mais significativas são as formigas-cortadeiras por possuírem o hábito de cortar e transportar fragmentos vegetais diversos para os seus ninhos subterrâneos. O objetivo deste estudo foi caracterizar alguns aspectos ecológicos de Atta sexdens piriventris Santschi no município de Capinzal, estado de Santa Catarina, Sul do Brasil. O material de origem vegetal transportado pelas formigas apresentou como característica folhas verdes/frescas 57%, folhas secas 23%, pedaços de frutos 7%, sementes 7% e flores 3%. Já os de origem animal tiveram uma representação de 3%, e eram compostos por pedaços de insetos. A média de distância percorrida pelas formigas em busca do substrato foi de 12,54 m.

Ecological Aspects of Atta sexdens piriventris Santschi (Hymenoptera: Formicidae) in the Municipality of Capinzal, Santa Catarina, Brazil

Abstract. Among the economically important species of ants, due to the damage they often cause the agriculture the most significant are the leaf-cutting ants because they have the habit of cut and transport various plant fragments to their underground nests. The objective of this study was characterized some ecological aspects of Atta sexdens piriventris Santschi in the municipality of Capinzal, Santa Catarina state, Southern Brazil. The plant material transported by the ants was 57% of green leaves, 23% of dried leaves, 7% of fruits, 7% of seeds, 3% of flowers and only 3% of animal parts, mostly compounds by insect parts. The average distance walked by the ants in search of the substrate was 12.54 m.
Estudo comparativo das sensilas antenais de operárias de Melipona scutellaris (Hymenoptera: Apidae) de diferentes altitudes
Authors: Nascimento Marcília Aparecida , Salomão Tânia Maria Fernandes , Martins Gustavo
Published: April 2013

Sensilas são estruturas sensoriais presentes nas antenas dos insetos e são responsáveis pela higro- quimio-, termo- e mecanorrecepção. No presente trabalho, as sensilas presentes nos três flagelômeros (F) mais distais de Melipona scutellaris Latreille (Hymenopera: Apidae) coletadas em diferentes altitudes (200 e acima de 900m) foram avaliadas qualitativamente e quantitativamente. A identificação, contagem e medição das sensilas foram feitas a partir de imagens da superfície dorsal das antenas que foram obtidas com o auxílio de microscópio eletrônico de varredura. Foram observadas as sensilas placoide, basicônica, celocônica, ampulácea, campaniforme e tricoide reta e curvada. Comparativamente, o grupo localizado a 200m de altitude possui sensilas tricoides retas em maior quantidade nos três flagelômeros, enquanto que o grupo de altitudes acima de 900m apresentou maior quantidade de sensilas tricoides curvadas no F9, sendo as mesmas maiores para o F10. Essas diferenças foram discutidas em função da localização geográfica dos diferentes grupos aqui estudados. Os resultados da investigação da estrutura antenal de M. scutellaris contribuem para um melhor entendimento da biologia dessa espécie.

A Comparative Study of the Antennal Sensilla of Melipona scutellaris Latreille (Hymenoptera: Apidae) Workers From Different Altitudes

Abstract. The sensilla are sensitive structures located in different insect parts including antennae. They are responsible for the hygro- chemo-, thermo- and mechanoreception. In the present work the antennal topography of two different populations of Melipona scutellaris Latreille (Hymenopera: Apidae) from different altitudes (200 and above 900m) were studied considering the last three distal antennal flagelomers (F). Images of the antennal surface were obtained with the aid of the scanning electron microscope (SEM). The SEM analysis showed that the sensilla placodea, basiconic, coeloconic, ampullacea, campaniform and trichodea are present in the dorsal surface of the M. scutellaris antennae. The number of sensilla trichodea of the straight subtype is greater in the last three flagelomers in individuals of 200m altitude, while individuals located above 900m altitude has a greater number of sensilla trichodea of the subtype curved in the F9 and they have greater length in individuals of 900m altitude only in the F10. These differences were discussed according to the geographic location of the different groups studied here. This work represents the first assessment to antennal structure of M. scutellaris and contributes to a better understanding of the biology of this species.
Entomofauna do Oeste do Estado de Santa Catarina, Sul do Brasil
Authors: Favretto Mario Arthur , Dos Santos Emili Bortolon , Geuster Cleiton José
Published: April 2013

No presente trabalho é apresentada uma lista de 1328 espécies de insetos observadas no oeste do Estado de Santa Catarina nas últimas oito décadas, esta riqueza de espécies equivale a 1,47% do total de espécies registradas no Brasil. Foram compilados os registrados em diversas coleções por F. Plaumann, literatura, além de observações pessoais. Foram registradas 17 ordens, sendo que as com maior riqueza de espécies foram Hymenoptera com 382 espécies, sendo que a família Formicidae representou 48,42% das espécies desta ordem e Apidae 19%. Em Coleoptera foram registradas 230 espécies, com Curculionidae representando 22,60% desse total e Coccinelidae 19,13%. Na ordem Lepidoptera foram 199 espécies, a família Nymphalidae representou 37,18% dessa riqueza e Saturniidae 22,11%. A riqueza de espécies aqui apresentada ainda é mínima se comparada ao total registrado para o Brasil, mas é trata-se de uma etapa importante para ampliar os conhecimentos sobre a distribuição geográfica destas espécies.

Entomofauna from West of Santa Catarina State, South of Brazil

Abstract. In this study is presented a list of 1328 insect species observed in west of Santa Catarina State, Brazil, in the last eight decades. The species richness founds corresponds 1.47 % of the total of species registered in Brazil. The data set was compiled from collection records performed by F. Plaumann, in addition to the records from literature and personal observations. Here, we recorded a total of 17 orders of insects. The order Hymenoptera had greatest richness with 382 species. Within Hymenoptera, the family Formicidae represented 48.42% and Apidae, 19%. In order Coleoptera, we found 230 species, with Curculionidae representing 22.60% of this total and Coccinelidae 19.13%. On the order Lepidoptera we recorded 199 species, the Nymphalidae family represented 37.18% of this richness and Saturniidae, 22.11%. The species richness presented here is minimal when compared to the total recorded for Brazil, but it is an important step to improve the knowledge about the geographic distribution of these insects.
Probabilistic Set Covering with Correlations
Authors: Ahmed Shabbir , Papageorgiou Dimitri J.
Published: April 2013

We consider two variants of a probabilistic set covering (PSC) problem. The first variant assumes that there is uncertainty regarding whether a selected set can cover an item, and the objective is to determine a minimum-cost combination of sets so that each item is covered with a prespecified probability. The second variant seeks to maximize the minimum probability that a selected set can cover all items. To date, literature on this problem has focused on the special case in which uncertainties are independent. In this paper, we formulate deterministic mixed-integer programming models for distributionally robust PSC problems with correlated uncertainties. By exploiting the supermodularity of certain substructures and analyzing their polyhedral properties, we develop strong valid inequalities to strengthen the formulations. Computational results illustrate that our modeling approach can outperform formulations in which correlations are ignored and that our algorithms can significantly reduce overall computation time.
Staffing and Control of Instant Messaging Contact Centers
Authors: Luo Jun , Zhang Jiheng
Published: April 2013

In addition to traditional call centers, many companies have started building a new kind of customer contact center, in which agents communicate with customers via instant messaging (IM) over the Internet rather than phone calls. A distinctive feature of the service centers based on IM is that one agent can serve multiple customers in parallel. We choose to model such a center as a server pool consisting of many limited processor-sharing servers. We characterize the underlying stochastic processes by establishing a fluid approximation in the many-server heavy-traffic regime. The limiting behavior of the stochastic processes is shown to involve a stochastic averaging principle, and the fluid approximation provides insights into the optimal staffing and control for such service centers.
An Exact Algorithm for the Two-Echelon Capacitated Vehicle Routing Problem
Authors: Baldacci Roberto , Mingozzi Aristide , Roberti Roberto , Calvo Roberto Wolfler
Published: April 2013

In the two-echelon capacitated vehicle routing problem (2E-CVRP), the delivery to customers from a depot uses intermediate depots, called satellites. The 2E-CVRP involves two levels of routing problems. The first level requires a design of the routes for a vehicle fleet located at the depot to transport the customer demands to a subset of the satellites. The second level concerns the routing of a vehicle fleet located at the satellites to serve all customers from the satellites supplied from the depot. The objective is to minimize the sum of routing and handling costs. This paper describes a new mathematical formulation of the 2E-CVRP used to derive valid lower bounds and an exact method that decomposes the 2E-CVRP into a limited set of multidepot capacitated vehicle routing problems with side constraints. Computational results on benchmark instances show that the new exact algorithm outperforms the state-of-the-art exact methods.
Dynamic Business Share Allocation in a Supply Chain with Competing Suppliers
Authors: Li Hongmin , Zhang Hao , Fine Charles H.
Published: April 2013

This paper studies a repeated game between a manufacturer and two competing suppliers with imperfect monitoring. We present a principal-agent model for managing long-term supplier relationships using a unique form of measurement and incentive scheme. We measure a supplier's overall performance with a rating equivalent to its continuation utility (the expected total discounted utility of its future payoffs), and incentivize supplier effort with larger allocations of future business. We obtain the vector of the two suppliers' ratings as the state of a Markov decision process, and we solve an infinite horizon contracting problem in which the manufacturer allocates business volume between the two suppliers and updates their ratings dynamically based on their current ratings and the current performance outcome.

Our contributions are both theoretical and managerial: we propose a repeated principal-agent model with a novel incentive scheme to tackle a common, but challenging, incentive problem in a multiperiod supply chain setting. Assuming binary effort choices and performance outcomes by the suppliers, we characterize the structure of the optimal contract through a novel fixed-point analysis. Our results provide a theoretical foundation for the emergence of “business-as-usual” (low effort) trapping states and tournament competition (high effort) recurrent states as the long-run incentive drivers for motivating critical suppliers.
‘Never-ending Story’: Public Accountability and Public Administration Reform in Queensland Since 1989
Authors: Wear Rae
Published: April 2013

Soon after Johannes Bjelke-Petersen became Premier of Queensland in 1968, companies in which he held shares were given six-year leases to explore for oil on the Great Barrier Reef. The following year, ministers in his government accepted parcels of Comalco shares. So did senior bureaucrats and the Premier's wife. Criticism at the time was muted because Labor politicians and some journalists had also taken shares (Whitton 1989, p. 19). Bjelke-Petersen was adamant that he had done nothing wrong — a feeling that presumably was shared by other beneficiaries of Comalco's largesse (Wear 2002, p. 93). Because it is inconceivable that a saga of such blatant conflict of interest would be played out in today's Queensland, there is a temptation to tell a simple ‘before and after Fitzgerald’ story of public accountability and administrative reform. Considered analysis suggests, however, that the reality is much more complex. There was progress, but there was also backsliding. Some reforms — such as those to the electoral system — were significant and enduring. Others — such as whistleblower and FOI legislation — were fairly quickly watered down. There was a lack of long-term interest in public administration, parliament retained its usual place on the margins of Queensland's political institutions and executive power remained relatively unconstrained. Cases of corruption continued to emerge.
Messunsicherheit eines sekundären Kalibriersystems mit primär kalibriertem internen Bezugsnormal
Authors: Bühn Uwe
Published: April 2013

Zur Kalibrierung von Schwingungsaufnehmern dienen genaue Primärsysteme mit interferometrischer Messung der Schwingungsgröße aber auch preiswerte Sekundärsysteme mit primär kalibrierten Bezugsnormalen. Dazwischen gibt es Systeme, bei denen das Bezugsnormal fest in die Armatur des Schwingungserregers integriert ist und primär kalibriert wurde. Wird ein solches System zur Vergleichskalibrierung benutzt, dann führt das gegenüber klassischen Systemen zu geringeren Messunsicherheiten, da sich bestimmte Einflussgrößen bereits in der Messunsicherheit des internen Bezugsnormals niedergeschlagen haben.
Comparison of cell types in the rat Leydig cell lineage after ethane dimethanesulfonate treatment
Authors: Guo Jingjing , Zhou Hongyu , Su Zhijian , Chen Bingbing , Wang Guimin , Wang Claire Q F , Xu Yunfei , Ge Ren-Shan
Published: April 2013

The objective of this study was to purify cells in the Leydig cell lineage following regeneration after ethane dimethanesulfonate (EDS) treatment and compare their steroidogenic capacity. Regenerated progenitor (RPLCs), immature (RILCs), and adult Leydig cells (RALCs) were isolated from testes 21, 28 and 56 days after EDS treatment respectively. Production rates for androgens including androsterone and 5α-androstane-17β, 3α-diol (DIOL), testosterone and androstenedione were measured in RPLCs, RILCs and RALCs in media after 3-hin vitroculture with 100 ng/ml LH. Steady-state mRNA levels of steroidogenic enzymes and their activities were measured in freshly isolated cells. Compared to adult Leydig cells (ALCs) isolated from normal 90-day-old rat testes, which primarily produce testosterone (69.73%), RPLCs and RILCs primarily produced androsterone (70.21%) and DIOL (69.79%) respectively. Leydig cells isolated from testes 56 days post-EDS showed equivalent capacity of steroidogenesis to ALCs and primarily produced testosterone (72.90%). RPLCs had cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1 and 17α-hydroxylase but had almost no detectable 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities, while RILCs had increased 17β-hydroxysteroid dehydrogenase 3 and 11β-hydroxysteroid dehydrogenase 1 activities. Because RPLCs and RILCs had higher 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase activities they produced mainly 5α-reduced androgens. Real-time PCR confirmed the similar trends for the expressions of these steroidogenic enzymes. In conclusion, the purified RPLCs, RILCs and RALCs are similar to those of their counterparts during rat pubertal development.
Retrospective View of North American Potato (Solanum tuberosumL.) Breeding in the 20th and 21st Centuries
Authors: Hirsch Candice N , Hirsch Cory D , Felcher Kimberly , Coombs Joseph , Zarka Dan , Van Deynze Allen , De Jong Walter , Veilleux Richard E , Jansky Shelley , Bethke Paul , Douches David S , Buell C Robin
Published: April 2013

Cultivated potato (Solanum tuberosum L.), a vegetatively propagated autotetraploid, has been bred for distinct market classes, including fresh market, pigmented, and processing varieties. Breeding efforts have relied on phenotypic selection of populations developed from intra- and intermarket class crosses and introgressions of wild and cultivated Solanum relatives. To retrospectively explore the effects of potato breeding at the genome level, we used 8303 single-nucleotide polymorphism markers to genotype a 250-line diversity panel composed of wild species, genetic stocks, and cultivated potato lines with release dates ranging from 1857 to 2011. Population structure analysis revealed four subpopulations within the panel, with cultivated potato lines grouping together and separate from wild species and genetic stocks. With pairwise kinship estimates clear separation between potato market classes was observed. Modern breeding efforts have scarcely changed the percentage of heterozygous loci or the frequency of homozygous, single-dose, and duplex loci on a genome level, despite concerted efforts by breeders. In contrast, clear selection in less than 50 years of breeding was observed for alleles in biosynthetic pathways important for market class-specific traits such as pigmentation and carbohydrate composition. Although improvement and diversification for distinct market classes was observed through whole-genome analysis of historic and current potato lines, an increased rate of gain from selection will be required to meet growing global food demands and challenges due to climate change. Understanding the genetic basis of diversification and trait improvement will allow for more rapid genome-guided improvement of potato in future breeding efforts.
Resistance to Germline RNA Interference in a Caenorhabditis elegans Wild Isolate Exhibits Complexity and Nonadditivity
Authors: Pollard Daniel A , Rockman Matthew V
Published: April 2013

Resolving the genetic complexity of heritable phenotypic variation is fundamental to understanding the mechanisms of evolution and the etiology of human disease. Trait variation among isolates from genetically efficient model organisms offers the opportunity to dissect genetic architectures and identify the molecular mechanisms of causation. Here we present a genetic analysis of loss of sensitivity to gene knockdown via exogenous RNA interference in the germline of a wild isolate of the roundworm Caenorhabditis elegans. We find that the loss of RNA interference sensitivity in the wild isolate CB4856 is recessive to the sensitivity of the lab strain N2. A cross of the strains produced F2 with intermediate sensitivities, and the segregation of the trait among F2s strongly deviated from a single locus recessive allele expectation. Linkage analysis in recombinant inbred lines derived from CB4856 and N2 identified a single significant locus on chromosome I that includes the argonaute gene ppw-1. The alleles for ppw-1 were unable to explain the sensitivity of 18 (12.1%) of the recombinant inbred lines. Complementation tests and F2 segregation analysis of these recombinant inbred lines revealed cases of complex epistatic suppression and enhancement of the effects of ppw-1. We conclude that the variation in RNA interference sensitivity between CB4856 and N2 likely involves the nonadditive interactions of eight or more genes in addition to ppw-1.
The Exonuclease Activity of the Yeast Mitochondrial DNA Polymerase γ Suppresses Mitochondrial DNA Deletions Between Short Direct Repeats in Saccharomyces cerevisiae
Authors: Stumpf Jeffrey D , Copeland William C
Published: April 2013

The importance of mitochondrial DNA (mtDNA) deletions in the progeroid phenotype of exonuclease-deficient DNA polymerase γ mice has been intensely debated. We show that disruption of Mip1 exonuclease activity increases mtDNA deletions 160-fold, whereas disease-associated polymerase variants were mostly unaffected, suggesting that exonuclease activity is vital to avoid deletions during mtDNA replication.
Competitive Fitness During Feast and Famine: How SOS DNA Polymerases Influence Physiology and Evolution inEscherichia coli
Authors: Corzett Christopher H , Goodman Myron F , Finkel Steven E
Published: April 2013

Escherichia coli DNA polymerases (Pol) II, IV, and V serve dual roles by facilitating efficient translesion DNA synthesis while simultaneously introducing genetic variation that can promote adaptive evolution. Here we show that these alternative polymerases are induced as cells transition from exponential to long-term stationary-phase growth in the absence of induction of the SOS regulon by external agents that damage DNA. By monitoring the relative fitness of isogenic mutant strains expressing only one alternative polymerase over time, spanning hours to weeks, we establish distinct growth phase-dependent hierarchies of polymerase mutant strain competitiveness. Pol II confers a significant physiological advantage by facilitating efficient replication and creating genetic diversity during periods of rapid growth. Pol IV and Pol V make the largest contributions to evolutionary fitness during long-term stationary phase. Consistent with their roles providing both a physiological and an adaptive advantage during stationary phase, the expression patterns of all three SOS polymerases change during the transition from log phase to long-term stationary phase. Compared to the alternative polymerases, Pol III transcription dominates during mid-exponential phase; however, its abundance decreases to <20% during long-term stationary phase. Pol IV transcription dominates as cells transition out of exponential phase into stationary phase and a burst of Pol V transcription is observed as cells transition from death phase to long-term stationary phase. These changes in alternative DNA polymerase transcription occur in the absence of SOS induction by exogenous agents and indicate that cell populations require appropriate expression of all three alternative DNA polymerases during exponential, stationary, and long-term stationary phases to attain optimal fitness and undergo adaptive evolution.
Incidence of Childhood and Adolescent Melanoma in the United States: 1973–2009
Authors: Wong Jeannette R. , Harris Jenine K. , Rodriguez-Galindo Carlos , Johnson Kimberly J.
Published: April 2013

OBJECTIVE:

Childhood and adolescent melanoma is rare but has been increasing. To gain insight into possible reasons underlying this observation, we analyzed trends in melanoma incidence diagnosed between the ages of 0 and 19 years among US whites by gender, stage, age at diagnosis, and primary site. We also investigated incidence trends by UV-B exposure levels.

METHODS:

By using Surveillance, Epidemiology, and End Results (SEER) program data (1973–2009), we calculated age-adjusted incidence rates (IRs), annual percent changes, and 95% confidence intervals for each category of interest. Incidence trends were also evaluated by using joinpoint and local regression models. SEER registries were categorized with respect to low or high UV-B radiation exposure.

RESULTS:

From 1973 through 2009, 1230 children of white race were diagnosed with malignant melanoma. Overall, pediatric melanoma increased by an average of 2% per year (95% confidence interval, 1.4%–2.7%). Girls, 15- to 19-year-olds, and individuals with low UV-B exposure had significantly higher IRs than boys, younger children, and those living in SEER registries categorized as high UV-B. Over the study period, boys experienced increased IRs for melanoma on the face and trunk, and females on the lower limbs and hip. The only decreased incidence trend we observed was among 15- to 19-year-olds in the high UV-B exposure group from 1985 through 2009. Local regression curves indicated similar patterns.

CONCLUSIONS:

These results may help elucidate possible risk factors for adolescent melanoma, but additional individual-level studies will be necessary to determine the reasons for increasing incidence trends.
Cluster (School) RCT of ParentCorps: Impact on Kindergarten Academic Achievement
Authors: Brotman Laurie Miller , Dawson-McClure Spring , Calzada Esther J. , Huang Keng-Yen , Kamboukos Dimitra , Palamar Joseph J. , Petkova Eva
Published: April 2013

OBJECTIVE:

To evaluate the impact of an early childhood, family-centered, school-based intervention on children’s kindergarten academic achievement.

METHODS:

This was a cluster (school) randomized controlled trial with assessments from pre-kindergarten (pre-k) entry through the end of kindergarten. The setting was 10 public elementary schools with 26 pre-k classes in 2 school districts in urban disadvantaged neighborhoods serving a largely black, low-income population. Participants were 1050 black and Latino, low-income children (age 4; 88% of pre-k population) enrolled in 10 schools over 4 years. Universal intervention aimed to promote self-regulation and early learning by strengthening positive behavior support and effective behavior management at home and school, and increasing parent involvement in education. Intervention included after-school group sessions for families of pre-k students (13 2-hour sessions; co-led by pre-k teachers) and professional development for pre-k and kindergarten teachers. The outcome measures were standardized test scores of kindergarten reading, writing, and math achievement by independent evaluators masked to intervention condition (primary outcome); developmental trajectories of teacher-rated academic performance from pre-k through kindergarten (secondary outcome).

RESULTS:

Relative to children in control schools, children in intervention schools had higher kindergarten achievement test scores (Cohen’s d = 0.18, mean difference = 2.64, SE = 0.90, P = .03) and higher teacher-rated academic performance (Cohen’s d = 0.25, mean difference = 5.65, SE = 2.34, P = .01).

CONCLUSIONS:

Early childhood population-level intervention that enhances both home and school environments shows promise to advance academic achievement among minority children from disadvantaged, urban neighborhoods.
Prediction of the prognosis of breast cancer in routine histologic specimens using a simplified, low-cost gene expression signature
Authors: Szász A. Marcell , Ács Balázs , Ágoston Emese , Sztupinszki Zsófia , Tőkés Anna-Mária , Szittya Liliána , Székely Borbála , Szendrői Miklós , Li Qiyuan , Harsányi László , Tímár József , Szállási Zoltán , Swanton Charles , Győrffy Balázs , Kulka Janina
Published: April 2013

Background: Grade 2 breast carcinomas do not form a uniform prognostic group. Aim: To extend the number of patients and the investigated genes of a previously identified prognostic signature described by the authors that reflect chromosomal instability in order to refine characterization of grade 2 breast cancers and identify driver genes. Methods: Using publicly available databases, the authors selected 9 target and 3 housekeeping genes that are capable to divide grade 2 breast carcinomas into prognostic groups. Gene expression was investigated by polymerase chain reaction in 249 formalin-fixed, paraffin-embedded breast tumors. The results were correlated with relapse-free survival. Results: Histologically grade 2 carcinomas were split into good and a poor prognosis groups. Centroid-based ranking showed that 3 genes, FOXM1, TOP2A and CLDN4 were able to separate the good and poor prognostic groups of grade 2 breast carcinomas. Conclusion: Using appropriately selected control genes, a limited set of genes is able to split prognostic groups of breast carcinomas independently from their grade. Orv. Hetil., 2013, 154, 627–632.
Effect of the ratio Mo/Cr in the precipitation and distribution of carbides in alloyed nodular iron
Authors: Rivero H.D. , García José .A. , Atlatenco E. Cándido , Basso Alejandro D. , Sicora J.
Published: April 2013

This investigation deals with the effect of 2/0, 1/1 and 1/0.5 Cr/Mo ratios on the local fraction, distribution and the comparative size of carbides precipitated in cast nodular iron. “Y” block castings with a thickness of 1.5 cm are cast in green sand molds. Two samples are cut from each casting, one located on the center and another on the wall. The carbide volume fraction is evaluated by a digital analysis system. Each sample is analyzed in three zones: bottom, middle and top. Carbide mappings are generated according to the average local carbide fraction in order to get the distribution of carbides on the casting. Results show that higher volume fractions of carbides precipitate for the ratio 2/0 of Cr/Mo with values between 28.5 and 19.5%. The lowest fraction of carbides is presented in nodular iron alloyed with a Cr/Mo ratio of 1/1 between 6.5 and 4.6%. Also a very heterogeneous distribution of the carbides is observed in the three alloys and massive carbides are observed in the last freezing zone of the castings.
Planar integrated plasmonic mid-IR spectrometer
Authors: Rezaie Farnood K. , Fredericksen Chris J. , Buchwald Walter R. , Cleary Justin W. , Smith Evan M. , Rezadad Imen , Nath Janardan , Figueiredo Pedro , Shahzad Monas , Boroumand Javaneh , Yesiltas Mehmet , Medhi Gautam , Davis Andrew , Peale Robert E.
Published: April 2013

A compact spectrometer-on-a-chip featuring a plasmonic molecular interaction region has been conceived, designed, modeled, and partially fabricated. The silicon-on-insulator (SOI) system is the chosen platform for the integration. The low loss of both silicon and SiO2 between 3 and 4 μm wavelengths enables silicon waveguides on SiO2 as the basis for molecular sensors at these wavelengths. Important characteristic molecular vibrations occur in this range, namely the bond stretching modes C-H (Alkynes), O-H (monomeric alcohols, phenols) and N-H (Amines), as well as CO double bonds, NH2, and CN. The device consists of a broad-band infrared LED, photonic waveguides, photon-to-plasmon transformers, a molecular interaction region, dispersive structures, and detectors. Photonic waveguide modes are adiabatically converted into SPPs on a neighboring metal surface by a tapered waveguide. The plasmonic interaction region enhances optical intensity, which allows a reduction of the overall device size without a reduction of the interaction length, in comparison to ordinary optical methods. After the SPPs propagate through the interaction region, they are converted back into photonic waveguide modes by a second taper. The dispersing region consists of a series of micro-ring resonators with photodetectors coupled to each resonator. Design parameters were optimized via electro-dynamic simulations. Fabrication was performed using a combination of photo- and electron-beam-lithography together with standard silicon processing techniques.