bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic variation in fruit volatiles emitted by the hawthorn Crataegus mollis and its consequences for host race formation in the apple maggot fly, Rhagoletis pomonella
Authors: Cha Dong H. , Powell Thomas H. Q. , Feder Jeffrey L. , Linn Charles E.
Published: May 2012

The shift of the apple (AP) maggot fly, Rhagoletis pomonella (Walsh) (Diptera: Tephritidae), from its ancestral host downy hawthorn, Crataegus mollis (DH) (Torr. & A. Gray) Scheele, to introduced domesticated AP, Malus domestica Borkh. (both Rosaceae), is a model for ecological divergence and incipient sympatric speciation with gene flow. However, a portion of the variation contributing to the sympatric host shift from DH to AP appears to have a different biogeographic history, pre‐dating the shift. One potential source of standing variation may trace to a number of different native hawthorn species infested by R. pomonella in the southern USA, where the AP‐attacking race is absent. Herein, we investigate this possibility for the southern red hawthorn (SR) endemic to Texas, Crataegus mollis var. texana (Buckl.), which has been described as a member of the Molles series that includes the more northern distributed DH. We report results from chemical analyses of host fruit volatiles, fly behavioural responses to synthetic fruit blends, and microsatellite surveys of fly populations, implying that R. pomonella infesting SR may behaviourally and genetically represent a native host race differing from the DH‐infesting fly. No fly reared from SR responded to AP fruit volatiles in flight tunnel assays. However, coupled gas chromatographic‐electroantennographic detection (GC‐EAD) profiles for SR fruit contain all five of the component esters that comprise the standard AP volatile blend inducing behavioural orientation for AP‐infesting flies, compounds that appear to be largely missing from volatile profiles for DH fruit. Thus, SR‐infesting flies do not represent a source for a preassembled AP‐accepting phenotype. However, they may help explain why the ancestral DH race that shifted to AP in the northeastern USA had the ability to recognize AP fruit esters, potentially enabling the shift to AP. Our results highlight how categorizing speciation into different geographic modes may not adequately describe the evolutionary origins of important genetic variation fuelling adaptive radiation and the genesis of new biodiversity.
Limited prognostic value of tissue protein expression levels of cyclinEinDanish ovarian cancer patients: from theDanish ‘MALOVA’ ovarian cancer study
Authors: Heeran Mel C. , Høgdall Claus K. , Kjaer Susanne K. , Christensen Lise , Blaakaer Jan , Christensen Ib Jarle , Hogdall Estrid V. S.
Published: May 2012

The primary objective of this study was to assess the expression of cyclin E in tumour tissues from 661 patients with epithelial ovarian tumours. The second was to evaluate whether cyclinEtissue expression levels correlate with clinico‐pathological parameters and prognosis of the disease. Using tissue arrays (TA), we analysed the cyclin E expression levels in tissues from 168 women with borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a 10% cut‐off level for cyclinEoverexpression, 20% of theBOTs were positive with a higher proportion of serous than mucinous tumours. Sixty‐two per cent of theOCs were positive for cyclin E expression with the highest percentage found in clear cell carcinomas. Results based on univariate and multivariate survival analyses with a 10% cut‐off value showed that cyclinEhad no independent prognostic value. In conclusion, we found cyclinEexpression in tumour tissue to be of limited prognostic value toDanishOCpatients.
Bioactive oligopeptides in dermatology: Part II
Authors: Reddy Bobby Y. , Jow Tiffany , Hantash Basil M.
Published: May 2012

Peptides are central to the regulation and modulation of the chemical reactions and biological responses that occur in nature. Many physiological processes are affected by the interactions of these peptides, including cell proliferation and migration, inflammation, melanogenesis, angiogenesis and innate immunity. Thus, biologically active peptides offer a great potential medically and therapeutically. Moreover, the ability to generate synthetic peptides with attention to specifically modulating their pharmacokinetics and properties for increased potency, delivery and stability has spurred much interest in this rapidly growing field of research. In this review, we focus on the therapeutic uses of bioactive peptides as antimicrobials and effectors of neurotransmitter release. We also highlight the advantages and challenges associated with this new technology and discuss methods for improving oligopeptide transdermal delivery.
Bioactive oligopeptides in dermatology: Part I
Authors: Reddy Bobby , Jow Tiffany , Hantash Basil M.
Published: May 2012

Short sequence amino acids or oligopeptides represent a relatively new and promising area of dermatology. Oligopeptides are defined as peptide sequences ranging from 2 to 20 amino acids. This class of proteins includes potent biologically active compounds, which can modulate various cellular and molecular processes. The medical potential of short sequence peptides was initially characterized many decades ago with the identification of biological mediators such as angiotensin, vasopressin, oxytocin and bradykinin. However, the role of oligopeptides in affecting biological activity within the skin has only recently been explored. Currently, the dermatologic use of protein peptide fragments is a rapidly growing field of research. Recent studies suggest that treatment with various biologically active peptides can result in favourable clinical outcomes such as for the treatment of hyperpigmentation disorders with tyrosinase inhibitors and the use of collagen synthesis modulators to diminish skin laxity. In this review, we explore the roles of biologically active short sequence peptides as potential therapeutics through the modulation of collagen, elastin and melanin synthesis.
Up‐regulation of melanin synthesis by the antidepressant fluoxetine
Authors: Liao Sha , Shang Jing , Tian Xiaoli , Fan Xueqi , Shi Xiupu , Pei Siran , Wang Qian , Yu Boyang
Published: May 2012

Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase (TYR) activity, enhances the protein levels of microphthalmia‐associated transcription factor (MITF), TYR and tyrosinase‐related protein‐1 (TRP‐1) and eventually leads to a dramatic increase in melanin production in both murine B16F10 melanoma cells and normal human melanocytes (NHMCs). In well‐characterized C57BL/6 mouse models, systemic application of fluoxetine increased hair pigmentation by up‐regulating hair follicular MITF, TYR, TRP‐1 and tyrosinase‐related protein‐2 (TRP‐2) protein levels. Using a serotonin 1A receptor (SR1A) antagonist and RNA interference (RNAi) technique, we revealed that SR1A appears to be one of the involved pathways in the fluoxetine‐induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR1A may serve as a novel target in modulating melanogenesis.
CREB1 modulates the influence of childhood sexual abuse on adult's anger traits
Authors: Hasler R. , Perroud N. , Baud P. , Olié E. , Guillaume S. , Malafosse A. , Courtet P.
Published: May 2012

Childhood maltreatment and genes underlie vulnerability to suicidal behaviours (SB), possibly by affecting the constitution of endophenotypes such as anger traits. The CREB protein has been implicated in antidepressant response, suicide and mood disorders in general. The aim of this study was to investigate if CREB1 gene is associated with SB and/or anger‐related traits and if these associations are modulated by childhood maltreatment. Five hundred and thirty‐four male suicide attempters and 357 male non‐suicide attempters were genotyped for several polymorphisms within CREB1 gene. Four hundred and thirty‐seven (156 non‐suicide attempters and 281 suicide attempters) completed the State‐Trait Anger Expression Inventory (STAXI) and 288 (265 suicide attempters and 23 controls) fulfilled the Childhood Trauma Questionnaire (CTQ). In total, 72 males had experienced childhood sexual abuse. Our results did not show any significant association between CREB1 and suicide behaviour. We found a significant interaction showing that CREB1 rs4675690 polymorphism modulated the effect of childhood sexual abuse on adulthood anger‐out levels (P = 0.003). Sexually abused subjects carrying the CC genotype showed higher anger‐out scores than T allele carriers, whereas no difference was observed in non‐sexually abused subjects. CREB1 rs4675690 polymorphism modulates the association between childhood sexual abuse and adulthood anger‐trait level. This is, to our knowledge, the first study to show such an interaction and to highlight the main effect of this gene on modulating the effect of child abuse on psychopathologies and warrant further investigation on this topic.
A Democratic Account of the Right to Rule in Global Governance
Authors: Wheatley Steven
Published: May 2012

Abstract:  The objective of this article is to examine the extent to which a democratic conception of legitimate political authority can be applied to global regulatory regimes. The analysis is both a response to the concerns around the putative ‘democratic deficit’ at the domestic level that results from the globalization of governance functions and the need for global regulators to demonstrate a ‘right to rule’ in conditions in which it is no longer meaningful to speak about ‘sovereignty’ as legitimating the exercise of political power in world society. The essay draws on the work of Joseph Raz and Jürgen Habermas to develop a conceptual framework for understanding the idea of legitimate political authority – as it applies to democratic societies – before going on to consider the complexities that emerge from the recognition of multiple overlapping regimes, all of which can make a plausible claim to democratic legitimacy and a right to rule on the issue under consideration.
Legitimacy in Global Governance: International, Transnational and Private Institutions Compared
Authors: Take Ingo
Published: May 2012

Abstract: How to generate legitimate forms of governance beyond the nation state is often considered a central question in contemporary world politics (Moravcsik 2004: 336). To proceed in theory‐building, scholars need to systematically assign the theory‐driven assumptions on legitimate forms of governance beyond the nation‐state with the various, already observable, forms of global governance. This article aims to conduct a comparative appraisal of the legitimatory quality of different patterns of governance by applying a framework of indicators for their assessment. The indicators are selected from the scholarly debate within International Relations on the legitimacy of global governance arrangements and structured by a multi‐dimensional concept of legitimacy (input‐, throughput‐ and output‐dimension). This framework is then applied to international, transnational and private forms of global governance in three policy fields in order to show how each of them try to produce and maintain legitimacy, which strategies they apply and in how they interact with their stakeholders.
The EU, the IMF, and the Representative Turn: Addressing the Challenge of Legitimacy
Authors: Guastaferro Barbara , Moschella Manuela
Published: May 2012

Abstract:  Over time, international organizations have adopted different strategies to redress their legitimacy deficits. Among them, two strategies stand out: expanding participation of relevant stakeholders and improving output. By analyzing the application of these strategies in the European Union (EU) and in the International Monetary Fund (IMF), we argue that these efforts at legitimization have not been satisfying because they have been implemented as supplements, rather than complements, of representation. Interestingly, then, the most recent efforts at legitimizing the two international bodies have started emphasizing the issue of representation. We illustrate our argument by reviewing and comparing the legitimacy‐enhancing strategies that have been adopted in the EU and the IMF.
Monoamniotic twin pregnancy
Authors: Dias Tiran , Thilaganathan Basky , Bhide Amar
Published: May 2012

Key content

Monoamniotic twins are believed to account for 1–5% of all monozygotic conceptions, with an estimated annual incidence of 30–150 pregnancies in the UK.

High perinatal loss rates in monoamniotic twins have been attributed mainly to umbilical cord entanglement, inter‐twin transfusion syndrome, discordant fetal abnormality or fetal growth restriction.

Management of monoamniotic twin pregnancy is aimed at preventing antenatal fetal death and optimising timing of delivery.

Despite the paucity of robust data on the incidence and causes of perinatal loss, elective delivery at 32–34 weeks of gestation has been proposed.

Most obstetric units use caesarean birth as the preferred mode of delivery for monoamniotic twins to prevent intrapartum cord complications.

Learning objectives

To understand the aetiology, incidence and diagnosis of monoamnionicity.

To be able to identify the type and prevalence of complications in monoamniotic twins.

To be aware of the current evidence on the antenatal management and optimal timing of delivery of monoamniotic twin pregnancy.

Ethical issues

Can we justify elective preterm delivery and its subsequent complications without a robust evidence base demonstrating a reduction in perinatal morbidity and mortality?
New‐onset hypertension in pregnancy: a review of the long‐term maternal effects
Authors: Green Amanda , Loughna Pamela , Pipkin Fiona Broughton
Published: May 2012

Key content

Women with a history of new‐onset hypertension in pregnancy have an increased risk of future hypertension and cardiovascular disease; women who deliver preterm (before 34 weeks of gestation) are at even higher risk.

In this group of women, cardiovascular disease often occurs at a much earlier age.

Follow‐up after pregnancy is vital to ensure that ongoing disease is appropriately investigated and managed.

Simple lifestyle changes may help reduce these risks.

Learning objectives

To have increased awareness of the future risks of hypertensive pregnancy.

To be able to quantify the risk of future disease from current evidence in the literature.

To be able to counsel women and discuss lifestyle changes.

Ethical issues

Do we counsel women adequately about the long‐term risk of disease after hypertensive pregnancy?

Are we missing opportunities for disease prevention?
Mayer–Rokitansky–Küster–Hauser syndrome: diagnosis and management
Authors: Valappil Saudabi , Chetan Uma , Wood Nick , Garden Anne
Published: May 2012

Key content

In Mayer–Rokitansky–Küster–Hauser syndrome (müllerian agenesis) there is congenital absence of the upper two‐thirds of the vagina and the uterus is absent or rudimentary.

A common presentation is primary amenorrhoea in a female with 46,XX karyotype and normal secondary sexual characteristics.

There may be associated abnormalities of the kidneys, skeletal system, heart and auditory system.

Magnetic resonance imaging is a useful diagnostic tool with which to assess the anatomical abnormalities.

Management involves psychological support and creation of a neovagina for sexual function.

Objectives

To understand the anatomical abnormalities of this entity.

To learn about the clinical presentation and differential diagnosis.

To understand the management issues.

Ethical issues

If, in the future, uterine transplantation becomes safe and effective, will it be ethical for a woman to donate her uterus to her daughter?

With many children awaiting adoption, should women with Mayer–Rokitansky–Küster–Hauser syndrome be encouraged to adopt rather than undergo surrogacy?

Who should pay for assisted reproduction treatment, given the constraints of health service budgets?

Should women with Mayer–Rokitansky–Küster–Hauser syndrome be managed in selected centres of excellence?
Management of borderline ovarian tumours
Authors: Bagade Pallavi , Edmondson Richard , Nayar Anitha
Published: May 2012

Key content

Borderline ovarian tumours are a heterogeneous group of tumours often seen in younger women.

Many are only diagnosed after primary surgery has already taken place for a presumed benign lesion.

The subsequent management often causes confusion.

Complete surgical staging is the cornerstone of management, but conservative surgery is an acceptable alternative in those keen to retain their fertility.

The role of long‐term follow‐up is controversial.

Learning objectives

To gain an overview of the pathology and biology of borderline ovarian tumours.

To understand the principles of surgical management in young women and the importance of a multidisciplinary team approach.

To appreciate the value of following up these women.

Ethical issues

Can we reduce the morbidity of radical surgery in a young woman wishing to retain her fertility?

Is a more conservative approach a safe alternative regarding cancer prognosis?
Bullying in the workplace: recognition and management
Authors: Kumar Geeta , Jain Arpana , Kumar Bidyut
Published: May 2012

Key content

The definition of bullying is wide and relies on individual perception.

Bullying has significant consequences: bullied healthcare workers report higher levels of job‐induced stress, depression and anxiety and lower levels of job satisfaction.

There have been several surveys on bullying of healthcare workers.

Deaneries must formulate strategies to support all those involved in allegations of bullying.

Learning objectives

To appreciate the difficulties of defining bullying.

To be able to distinguish constructive supervision from bullying behaviour.

To be aware of the resources available to manage bullying behaviour.

Ethical issues

In implementing effective and appropriate remedial measures there is the potential for breaching confidentiality.
Exploring the Relationship Among ADHD, Stimulants, and Substance Abuse
Authors: Nelson Andrea , Galon Patricia
Published: May 2012

TOPIC:  There is an ongoing debate among prescribers concerning the risk of inadvertently contributing to the initiation of substance abuse (SA) in children and adolescents through the use of stimulants in the treatment of attention‐deficit/hyperactivity disorder (ADHD). Psychiatric nurses at all levels of practice must be informed about this important discourse in order to provide accurate and timely interventions to clients and their families.

PURPOSE:  This literature review explores the current state of prescriptive stimulant use for ADHD and the possible links to SA. Developmental, genetic, and neuro‐chemical theories of the disorder that may contribute to SA as well as the burden of comorbidity are considered. The impact of gender, cultural, legal, and ethical influences on diagnostic and treatment recommendations is also included.

SOURCE:  U.S. and other English language articles were identified through PubMed and the Cumulated Index of Nursing and Allied Health Literature. These sources were used to determine the current practice of stimulant prescription and the prevalence of SA as a comorbidity to other child psychiatric disorders including ADHD. Textbooks were consulted for information regarding relevant neurochemistry, genetics, and psychopharmacology.

CONCLUSIONS:  The authors conclude that the use of stimulants is appropriate for children and adolescents with ADHD when opportunities for screening, family and child education, and counseling concerning SA are consistently integrated into the ongoing treatment regimen.
Tomato plants transformed with the inhibitor‐of‐virus‐replication gene are partially resistant to several pathogenic fungi
Authors: Elad Y. , Rav‐David D. , Leibman D. , Vintal H. , Vunsh R. , Moorthy H. , Gal‐On A. , Loebenstein G.
Published: May 2012

The inhibitor‐of‐virus replication (IVR) gene associated with the local lesion response to Tobacco mosaic virus in tobacco codes for a putative protein with a molecular mass of 22 kDa. Earlier work revealed that when tomato (Solanum lycopersicum) cv. VF36 plants are transformed with a cDNA clone encoding this gene, they become partially resistant to Botrytis cinerea infection. The transformation of tomatoes with the IVR gene induced partial resistance to in vitro seedling infection by Alternaria alternata, Pythium aphanidermatum and Rhizoctonia solani and faster seedling growth. Resistance to damping‐off was observed in transgenic seedlings planted in soil infested with R. solani and P. aphanidermatum. Early blight (Alternaria solani) and powdery mildew (Oidium neolycopersici) were also partially controlled in mature transgenic tomato plants.
CONTROLLING OTHER PEOPLE'S CHILDREN: RACIALIZED VIEWS OF DELINQUENCY AND WHITES’ PUNITIVE ATTITUDES TOWARD JUVENILE OFFENDERS*
Authors: PICKETT JUSTIN T. , CHIRICOS TED
Published: May 2012

The juvenile justice system was founded on, and until recently developed around, the idea that society should afford delinquents more leniency and rehabilitative care than adult criminals because of their lower levels of physical and cognitive development and, thus, diminished culpability for law violations and higher amenability to treatment. The past four decades, however, have witnessed a sustained movement to recriminalize delinquency through the enactment of policies that treat juvenile offenders more like their adult counterparts.Feld (1999a)and others have argued that this punitive turn in juvenile justice is in part a result of the racialization of delinquency and violent victimization in the post–Civil Rights era. This study provides the first test of the key assumption underlying this thesis, namely, that Whites’ support for getting tough with juvenile offenders is in part tied to racialized views of youth crime. Drawing on data from a recent national survey, we examine the extent to which relative racial typifications about delinquency and victimization, as well as racial resentment, are associated with general punitiveness toward juvenile offenders as well as support for lower minimum ages of criminal justice jurisdiction. Regression results show that Whites who hold such typifications and those who are more racially resentful are both more likely to embrace punitive youth justice policies and favor transfers for younger offenders. The implications of the findings are discussed.
Body heat storage during physical activity is lower with hot fluid ingestion under conditions that permit full evaporation
Authors: Bain A. R. , Lesperance N. C. , Jay O.
Published: May 2012

Aim

To assess whether, under conditions permitting full evaporation, body heat storage during physical activity measured by partitional calorimetry would be lower with warm relative to cold fluid ingestion because of a disproportionate increase in evaporative heat loss potential relative to internal heat transfer with the ingested fluid.

Methods

Nine males cycled at 50% VO2max for 75 min at 23.6 ± 0.6 °C and 23 ± 11% RH while consuming water of either 1.5 °C, 10 °C, 37 °C or 50 °C in four 3.2 mL kg−1 boluses. The water was administered 5 min before and 15, 30 and 45 min following the onset of exercise.

Results

No differences in metabolic heat production, sensible or respiratory heat losses (all P > 0.05) were observed between fluid temperatures. However, while the increased internal heat loss with cold fluid ingestion was paralleled by similar reductions in evaporative heat loss potential at the skin (Esk) with 10 °C (P = 0.08) and 1.5 °C (P = 0.55) fluid, the increased heat load with warm (50 °C) fluid ingestion was accompanied by a significantly greater Esk (P = 0.04). The resultant calorimetric heat storage was lower with 50 °C water ingestion in comparison to 1.5 °C, 10 °C and 37 °C (all P < 0.05). In contrast, heat storage derived conventionally using thermometry yielded higher values following 50 °C fluid ingestion compared to 1.5 °C (P = 0.025).

Conclusion

Under conditions permitting full sweat evaporation, body heat storage is lower with warm water ingestion, likely because of disproportionate modulations in sweat output arising from warm‐sensitive thermosensors in the esophagus/stomach. Local temperature changes of the rectum following fluid ingestion exacerbate the previously identified error of thermometric heat storage estimations.
Steps towards an early warning model for flood forecasting in Durazno city in Uruguay
Authors: Silveira L. , López G. , Chreties C. , Crisci M.
Published: May 2012

A hydrologic–hydrodynamic model of the Yi River basins in Uruguay has been developed as a support tool to the Emergency Coordination Centre of Durazno city. The purpose was to improve the existing decision support system and the emergency planning by providing information on gauge height and its permanence in time, and the risk of flooded areas. Four past flood events of high return period were used for calibration and validation with accurate results. The input data to the operational model in real time are hourly observed rainfall and gauge height, as well as rainfall forecasts by several international sources. The use of predictions from numerical weather forecasts allows for the generation of pre‐alert scenarios with larger lead time. These scenarios can warn the emergency coordinators, and thus are of great value to premanage a probable emergency. Operation of a meteorological weather alert issued by the National Meteorological Board is discussed.
Characterization of two novel small molecules targeting melanocyte development in zebrafish embryogenesis
Authors: Chen Lu , Ren Xi , Liang Fang , Li Song , Zhong Hanbing , Lin Shuo
Published: May 2012

Melanocytes are pigment cells that are closely associated with many skin disorders, such as vitiligo, piebaldism, Waardenburg syndrome, and the deadliest skin cancer, melanoma. Through studies of model organisms, the genetic regulatory network of melanocyte development during embryogenesis has been well established. This network also seems to be shared with adult melanocyte regeneration and melanoma formation. To identify chemical regulators of melanocyte development and homeostasis, we screened a small‐molecule library of 6000 compounds using zebrafish embryos and identified five novel compounds that inhibited pigmentation. Here we report characterization of two compounds, 12G9 and 36E9, which disrupted melanocyte development. TUNEL assay indicated that these two compounds induced apoptosis of melanocytes. Furthermore, compound 12G9 specifically inhibited the viability of mammalian melanoma cells in vitro. These two compounds should be useful as chemical biology tools to study melanocytes and could serve as drug candidates against melanocyte‐related diseases.
CARDIORENAL MEDICINE IN THE CHANGING HEALTH SYSTEM
Authors: Mahadevan Kalaivani , Kalra Paul
Published: May 2012

The phenomenon of Cardiorenal Syndrome is complex, well recognised and poses challenges to all levels of global healthcare. Ongoing research in this area continually manifests new ideas and theories with respect to the pathophysiology and clinical management of this condition. The 6th Cardiorenal Forum held in London on 7th October 2011 discussed some of the latest ideas and advances in this field of medicine.
Lagerstroemia menglaensis sp. nov. (Lythraceae) from Xishuangbanna, Yunnan Province, China
Authors: Gu Cui‐Hua , Ji Meng‐Cheng , Ma Dan‐Dan
Published: May 2012

Lagerstroemia menglaensis C. H. Gu, M. C. Ji & D. D. Ma, a new species of Lythraceae from Xishuangbanna, Yunnan, China is described and illustrated. The morphological characteristics of the new species and two morphologically similar species (L. guilinensis and L. venusta) are compared, and a key to distinguish between them is provided.
The ubiquitin proteasome system and efficacy of proteasome inhibitors in diseases
Authors: Chitra Selvarajan , Nalini Ganesan , Rajasekhar Gopalakrishnan
Published: May 2012

In eukaryotes the ubiquitin proteasome pathway plays an important role in cellular homeostasis and also it exerts a critical role in regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription and immune response. Defects in these pathways have been implicated in a number of human pathologies. Inhibition of the ubiquitin proteasome pathway by proteasome inhibitors may be a rational therapeutic approach for various diseases, such as cancer and inflammatory diseases. Many of the critical cytokine and chemokine mediators of the progression of rheumatoid arthritis are regulated by nuclear factor kappa B (NF‐κB). In peptidoglycan/polysaccharide‐induced polyarthritis, proteasome inhibitors limit the overall inflammation, reduce NF‐κB activation, decrease cellular adhesion molecule expression, inhibit nitric oxide synthase, attenuate circulating levels of proinflammatory cytokine interleukin‐6 and reduce the arthritis index and swelling in the joints of the animals. Since proteasome inhibitors exhibit anti‐inflammatory and anti proliferative effects, diseases characterized by both of these processes such as rheumatoid arthritis might also represent clinical opportunities for such drugs. The regulation of the proteasomal complex by proteasome inhibitors also has implications and potential benefits for the treatment of rheumatoid arthritis. This review summarizes the ubiquitin proteasome pathway, the structure of 26S proteasomes and types of proteasome inhibitors, with their actions, and clinical applications of proteasome inhibitors in various diseases.
Oral Histories in Meteoritics and Planetary Science – XVII: Joseph Goldstein
Authors: SEARS Derek W. G.
Published: May 2012

Abstract– In this interview, Joseph Goldstein (Fig. 1) recounts how he became interested in meteorites during his graduate studies working with Robert Ogilvie at MIT. By matching the Ni profiles observed across taenite fields in the Widmanstätten structure of iron meteorites with profiles he computed numerically he was able to determine cooling rates as the meteorites cooled through 650–400 °C. Upon graduating, he worked with a team of meteorite researchers led by Lou Walter at Goddard Space Flight Center where for 4 years he attempted to understand metallographic structures by reproducing them in the laboratory. Preferring an academic environment, Joe accepted a faculty position in the rapidly expanding metallurgy department at Lehigh University where he was responsible for their new electron microprobe. He soon became involved in studying the metal from lunar soils and identifying the metallic component from its characteristic iron and nickel compositions. Over the next two decades he refined these studies of Ni diffusion in iron meteorites, particularly the effect of phosphorus in the process, which resulted in superior Fe‐Ni‐P phase diagrams and improved cooling rates for the iron meteorites. After a period as vice president for research at Lehigh, in 1993 he moved to the University of Massachusetts to serve as dean of engineering, but during these administrative appointments Joe produced a steady stream of scientific results. Joe has served as Councilor, Treasurer, Vice President, and President of the Meteoritical Society. He received the Leonard Medal in 2005, the Sorby Award in 1999, and the Dumcumb Award for in 2008.

 Joseph Goldstein.

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Prevalence of oral mucosal lesions in adults undergoing highly active antiretroviral therapy in Hong Kong
Authors: Perera Mahendra , Tsang Peter Chiu Shun , Samaranayake Lakshman , Lee Man Po , Li Patrick
Published: May 2012

Aim:  Highly active antiretroviral therapy (HAART) has altered the prevalence and incidence of oral mucosal lesions of HIV infection. Recent reports show a variation in the prevalence of oral mucosal lesions in different population groups. Understanding the prevalence of these lesions is of paramount importance in the efficient delivery of dental care to such cohorts. The aim of the present study was to investigate the prevalence of oral mucosal lesions and salivary parameters during HAART in an ethnic Chinese cohort in Hong Kong.

Methods:  A cross‐sectional estimation of the prevalence of oral mucosal lesions was carried out in 101 HIV‐infected ethnic Chinese in Hong Kong using the European Community–Clearinghouse classification.

Results:  The prevalence of oral mucosal lesions was more common in patients who were classified at baseline as Centers for Disease Control (CDC) C3 category than CDC A2, A3, B2, and B3 (P < 0.05). An overall prevalence of 1.98% was observed for oral Kaposi’s sarcoma. Additionally, the HIV group on HAART (0.37 ± 0.23 mL/min) had significantly lower salivary flow rates (P < 0.01) compared with the healthy group (0.49 ± 0.15 mL/min).

Conclusions:  Although HAART appears to markedly reduce the prevalence of oral mucosal lesions during the course of HIV disease, regular systematic oral screening is still warranted for such populations for the early diagnosis and management of pathologies, such as Kaposi’s sarcoma.
Simapse – simulation maps for ecological niche modelling
Authors: Tarroso Pedro , Carvalho Sílvia B. , Brito José Carlos
Published: May 2012

1. Artificial neural networks (ANNs) are known for their powerful predictive power in the analysis of both linear and nonlinear relationships. They have been successfully applied to several fields including ecological modelling and predictive species’ distributions.

2. Here we present Simapse – Simulation Maps for Ecological Niche Modelling, a free and open‐source application written in Python and available to the most common platforms. It uses ANNs with back‐propagation to build spatially explicit distribution models from species data (presence/absence, presence‐only and abundance).

3. The main features include the automatic production of replicates with different sub‐sampling methods and total control of ANN structure and learning parameters.

4. Simapse uses common text formats as main input and output and provides assessment of variable importance and behaviour and measurement of model fitness.
Characterising surface energy of pharmaceutical powders by inverse gas chromatography at finite dilution
Authors: Das Shyamal C , Stewart Peter J
Published: May 2012

Objectives

The objectives of this project were the use of surface energy distributions in: distinguishing the effects of magnesium stearate on the surface energy of lactose processed by two methods: mixing in a Turbula and mechanofusion; characterising surface energy of materials before and after micronisation; and understanding surface energy changes of micronised lactose before and after storage at high relative humidity (RH).

Methods

Heptane, octane and nonane were used to determine nonpolar surface energy, and dichloromethane and ethyl acetate were used to determine polar surface energy in inverse gas chromatography at finite dilution.

Key findings

The total surface energy of lactose decreased more after mechanofusion with magnesium stearate than mixing in Turbula. The nonpolar surface energy of indometacin increased while polar and total surface energies decreased after micronisation. The nonpolar, polar and total surface energies and work of cohesion of micronised lactose decreased after storage at 75%RH for three months.

Conclusions

The surface energy distributions determined at finite dilution successfully distinguished and revealed more information than infinite dilution on surface energy changes in materials undergoing different pharmaceutical processes such as mixing, mechanofusion, micronisation and storage at high RH.
Osteocalcin is independently associated with body mass index in adolescent girls
Authors: Dubnov‐Raz G. , Ish‐Shalom S. , Chodick G. , Rozen G. S. , Giladi A. , Constantini N. W.
Published: May 2012

Objective

Osteocalcin is a bone‐related protein, recently found to correlate with body mass index (BMI), waist circumference, fat percentage and metabolic syndrome in adults. The aim of this study was to determine the relationship between osteocalcin and BMI in adolescence, a time of significant bone accrual, while considering possible confounders related to bone and body composition.

Methods

We analyzed data from 160 female adolescents (mean age 15.1 ± 0.7 years), which were divided into tertiles by osteocalcin levels. Across these three groups, we examined the differences in BMI with relation to age, total daily energy intake, calcium intake, physical activity (PA), total body bone mineral density, parathyroid hormone (PTH), 25(OH)‐vitamin D, bone alkaline phosphatase and body fat percentage.

Results

Mean BMI values differed significantly between participants in the three osteocalcin tertiles, including after adjustment for age, PA, PTH, energy and calcium intakes. Post‐hoc analysis revealed that girls in the highest osteocalcin tertile, had a significantly lower BMI than those in the two lower ones (19.3 ± 2.2 vs. 20.6 ± 3.0 and 20.7 ± 2.9 kg m−2, respectively, P = 0.018). There was no significant difference in energy and calcium intakes, bone mineral density, 25(OH)‐vitamin D levels and PTH between study groups.

Conclusions

In female adolescents, BMI is inversely related to osteocalcin, even after consideration of several factors that may affect bone and fat mass. As bone mineral density, 25(OH)D and PTH did not differ between groups, it is possible that the relation between osteocalcin and BMI could be unrelated to bone tissue itself.
Correlations of Cu(In, Ga)Se2 imaging with device performance, defects, and microstructural properties
Authors: Johnston Steve , Unold Thomas , Repins Ingrid , Kanevce Ana , Zaunbrecher Katherine , Yan Fei , Li Jian V. , Dippo Patricia , Sundaramoorthy Rajalakshmi , Jones Kim M. , To Bobby
Published: May 2012

Camera imaging techniques have been used for the characterization of Cu(In,Ga)Se2 (CIGS) solar cells. Photoluminescence (PL) imaging shows brightness variations after the deposition of the CIGS layer that persist through CdS deposition and subsequent processing steps to finish the devices. PL and electroluminescence imaging on finished cells show a correlation to the devices’ corresponding efficiency and open-circuit voltage (VOC), and dark defect-related spots correspond to bright spots on images from illuminated lock-in thermography (LIT) and forward-bias dark LIT. These image-detected defect areas are weak diodes and shunts. Imaging provides locations of defects detrimental to solar cell performance. Some of these defects are analyzed in more detail by scanning electron microscopy using cross-sectional views.
Ultrasound‐guided identification of cardiac imaging windows
Authors: Liu Garry , Qi Xiu‐Ling , Robert Normand , Dick Alexander J. , Wright Graham A.
Published: May 2012

Purpose:

Currently, the use of cine magnetic resonance imaging (MRI) to identify cardiac quiescent periods relative to the electrocardiogram (ECG) signal is insufficient for producing submillimeter‐resolution coronary MR angiography (MRA) images. In this work, the authors perform a time series comparison between tissue Doppler echocardiograms of the interventricular septum (IVS) and concurrent biplane x‐ray angiograms. Our results indicate very close agreement between the diastasis gating windows identified by both the IVS and x‐ray techniques.

Methods:

Seven cath lab patients undergoing diagnostic angiograms were simultaneously scanned during a breath hold by ultrasound and biplane x‐ray for six to eight heartbeats. The heart rate of each patient was stable. Dye was injected into either the left or right‐coronary vasculature. The IVS was imaged using color tissue Doppler in an apical four‐chamber view. Diastasis was estimated on the IVS velocity curve. On the biplane angiograms, proximal, mid, and distal regions were identified on the coronary artery (CA). Frame by frame correlation was used to derive displacement, and then velocity, for each region. The quiescent periods for a CA and its subsegments were estimated based on velocity. Using Pearson's correlation coefficient and Bland–Altman analysis, the authors compared the start and end times of the diastasis windows as estimated from the IVS and CA velocities. The authors also estimated the vessel blur across the diastasis windows of multiple sequential heartbeats of each patient.

Results:

In total, 17 heartbeats were analyzed. The range of heart rate observed across patients was 47–79 beats per minute (bpm) with a mean of 57 bpm. Significant correlations (R > 0.99; p < 0.01) were observed between the IVS and x‐ray techniques for the identification of the start and end times of diastasis windows. The mean difference in the starting times between IVS and CA quiescent windows was −12.0 ms. The mean difference in end times between IVS and CA quiescent windows was −3.5 ms. In contrast, the correlation between RR interval and both the start and duration of the x‐ray gating windows were relatively weaker: R = 0.63 (p = 0.13) and R = 0.86 (p = 0.01). For IVS gating windows, the average estimated vessel blurs during single and multiple heartbeats were 0.5 and 0.66 mm, respectively. For x‐ray gating windows, the corresponding values were 0.26 and 0.44 mm, respectively.

Conclusions:

In this study, the authors showed that IVS velocity can be used to identify periods of diastasis for coronary arteries. Despite variability in mid‐diastolic rest positions over multiple steady rate heartbeats, vessel blurring of 0.5–1 mm was found to be achievable using the IVS gating technique. The authors envision this leading to a new cardiac gating system that, compared with conventional ECG gating, provides better resolution and shorter scan times for coronary MRA.
Recent Explosive Human Population Growth Has Resulted in an Excess of Rare Genetic Variants
Authors: Keinan Alon , Clark Andrew G.
Published: May 2012

Exponential Growth Effects

Humans are an extraordinarily successful species, as measured by our large population size—approximately 7 billion—much of which can be put down to recent explosive growth. Leveraging human genomic data,
Keinan and Clark
(p.
740
) examined the effects of population growth on our ability to detect rare genetic variants, those hypothesized to be most likely associated with disease. It appears that rapid recent growth increases the load of rare variants and is likely to play an important role in the individual genetic burden of complex disease risk.
Spectroscopic Characterization of Mineralogy and Its Diversity Across Vesta
Authors: De Sanctis M. C. , Ammannito E. , Capria M. T. , Tosi F. , Capaccioni F. , Zambon F. , Carraro F. , Fonte S. , Frigeri A. , Jaumann R. , Magni G. , Marchi S. , McCord T. B. , McFadden L. A. , McSween H. Y. , Mittlefehldt D. W. , Nathues A. , Palomba E. , Pieters C. M. , Raymond C. A. , Russell C. T. , Toplis M. J. , Turrini D.
Published: May 2012

A New Dawn

Since 17 July 2011, NASA's spacecraft Dawn has been orbiting the asteroid Vesta—the second most massive and the third largest asteroid in the solar system (see the cover).

Russell
et al.

(p.
684
) use Dawn's observations to confirm that Vesta is a small differentiated planetary body with an inner core, and represents a surviving proto-planet from the earliest epoch of solar system formation; Vesta is also confirmed as the source of the howardite-eucrite-diogenite (HED) meteorites.

Jaumann
et al.

(p.
687
) report on the asteroid's overall geometry and topography, based on global surface mapping. Vesta's surface is dominated by numerous impact craters and large troughs around the equatorial region.

Marchi
et al.

(p.
690
) report on Vesta's complex cratering history and constrain the age of some of its major regions based on crater counts.

Schenk
et al.

(p.
694
) describe two giant impact basins located at the asteroid's south pole. Both basins are young and excavated enough amounts of material to form the Vestoids—a group of asteroids with a composition similar to that of Vesta—and HED meteorites.

De Sanctis
et al.

(p.
697
) present the mineralogical characterization of Vesta, based on data obtained by Dawn's visual and infrared spectrometer, revealing that this asteroid underwent a complex magmatic evolution that led to a differentiated crust and mantle. The global color variations detailed by

Reddy
et al.

(p.
700
) are unlike those of any other asteroid observed so far and are also indicative of a preserved, differentiated proto-planet.
Recalling Space and Time
How We Remember
Brain Mechanisms of Episodic Memory

by Michael E. Hasselmo

MIT Press, Cambridge, MA, 2012. 378 pp. $40, £27.95. ISBN 9780262016353.
Authors: Colgin Laura Lee
Published: May 2012

In a narrative format that combines experimental results, theory, and personal experience, Hasselmo discusses his quantitative model of the brain mechanisms for encoding and remembering our experiences.
Ancient Maya Astronomical Tables from Xultun, Guatemala
Authors: Saturno William A. , Stuart David , Aveni Anthony F. , Rossi Franco
Published: May 2012

Mayan Astronomy

Mayan Codices are books written on bark in the few centuries before Columbus landed. Several record detailed hieroglyphic calculations of lunar and planetary motions and their relation to the Mayan calendar. Their predecessors have been unclear.

Saturno
et al.

(p.
714
) now describe a room in a Mayan complex in Guatemala dating to several centuries before the Codices that seems to have similar calculations on two of its walls. The east wall contains lunar calculations; the calculations on the north wall are more enigmatic, but may relate to Mars, Mercury, and/or Venus.
Europe Picks Jupiter Probe; Runners-Up Vow to Press On
Authors: Cartlidge Edwin
Published: May 2012

Last week, the European Space Agency announced that it had chosen a €1 billion satellite to study three icy moons of Jupiter as its next major science mission, scheduled to be launched in 2022.
A Foul Problem
Authors: Strain Daniel
Published: May 2012

From mussels to barnacles to algae, studies suggest that "hull-fouling" organisms could pose an invasion threat that is as great as if not greater than that from ballast creatures, researchers say.
High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza
Authors: To Kelvin K. W. , Zhang Anna J. X. , Hung Ivan F. N. , Xu Ting , Ip Whitney C. T. , Wong Rebecca T. Y. , Ng Joseph C. K. , Chan Jasper F. W. , Chan Kwok-Hung , Yuen Kwok-Yung
Published: May 2012

The importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P= 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P= 0.004 andP= 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P< 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P< 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes.