bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailored Profiles Made of Tailor Rolled Strips by Roll Forming – Part 1 of 2
Authors: Hirt Gerhard , Dávalos‐Julca Daniel H.
Published: November 2011

To fully exploit the potential of sheet and profiles, various technologies to produce tailored blanks and profiles have been developed [1,2]. In earlier work [3] it has been shown that Strip Profile Rolling (SPR) can be used to produce metal strips with a predefined thickness distribution across the width of the strip. Building upon this knowledge, in two subsequent papers the extended goal of the project is presented. Therein is demonstrated that Strip Profile Rolling can be applied very effectively using a combination of roll forming (part 1) as well as further processing by roll forming (see part 2) to allow for the production of profiles with varying wall thickness in their cross section. To achieve the goal of part 1, a numerical model describing SPR was developed and used to study the influencing process parameters on spread and bulge formation. As a result of this parametric study, an optimized roll design and rolling sequence was developed to produce a demonstrator strip on a 12 stand roll forming mill manufactured by the company Dreistern [4]. Starting with a conventional strip out of DC01 steel (width 170 mm, thickness 2.5 mm), 29 rolling passes were necessary to achieve the desired geometry (width 186 mm, thickness 2.5 mm with a longitudinal groove being 64 mm wide where the thickness is reduced to 1.5 mm). In the second part of the process chain the coils produced by Strip Profile Rolling were successfully roll formed into a circular tube of 60 mm.
Status of Genomic Imprinting in Epigenetically Distinct Pluripotent Stem Cells
Authors: Sun Bowen , Ito Mitsuteru , Mendjan Sasha , Ito Yoko , Brons I. Gabrielle M. , Murrell Adele , Vallier Ludovic , Ferguson-Smith Anne C. , Pedersen Roger A.
Published: November 2011

Mouse epiblast stem cells (EpiSCs) derived from postimplantation embryos are developmentally and functionally different from embryonic stem cells (ESCs) generated from blastocysts. EpiSCs require Activin A and FGF2 signaling for self-renewal, similar to human ESCs (hESCs), while mouse ESCs require LIF and BMP4. Unlike ESCs, EpiSCs have undergone X-inactivation, similar to the tendency of hESCs. The shared self-renewal and X-inactivation properties of EpiSCs and hESCs suggest that they have an epigenetic state distinct from ESCs. This hypothesis predicts that EpiSCs would have monoallelic expression of most imprinted genes, like that observed in hESCs. Here, we confirm this prediction. By contrast, we find that mouse induced pluripotent stem cells (iPSCs) tend to lose imprinting similar to mouse ESCs. These findings reveal that iPSCs have an epigenetic status associated with their pluripotent state rather than their developmental origin. Our results also reinforce the view that hESCs and EpiSCs are in vitro counterparts, sharing an epigenetic status distinct from ESCs and iPSCs.

Disclosure of potential conflicts of interest is found at the end of this article.
Risikoberechnungen beim X-chromosomal rezessiven Erbgang
Authors: Grimm T. , Fischer C.
Published: November 2011

Am Beispiel der Muskeldystrophie Duchenne werden Risikoberechnungen beim X-chromosomal rezessiven Erbgang mithilfe des Bayesschen Rechentableaus durchgeführt und dabei demonstriert, wie sich auch komplexe genetische Modelle berücksichtigen lassen und auf das Risiko auswirken.
Les ombres portées et la Renaissance Un trait culturel peut-il revivre ?
Authors: Jacquesson François
Published: November 2011

La représentation des ombres portées est un fait très rare dans l’histoire des arts: d’abord en Grèce et dans l’Empire gréco-romain, ensuite à partir du XVe siècle en Europe, avec une éclipse médiévale. Jamais en Asie, ni ailleurs. Ce trait caractéristique, qui est souvent passé inaperçu et n’a (durant ces deux périodes) pas donné lieu à théorisation, crée ainsi un lien spécifique entre la Renaissance et l’Antiquité qu’elle voulait revivre. On peut se demander s’il existe ainsi des« marqueurs culturels» et quel genre d’existence ils mènent.
Deccan Volcanism Linked to the Cretaceous-Tertiary Boundary Mass Extinction: New Evidence from ONGC Wells in the Krishna-Godavari Basin
Authors: Keller G. , Bhowmick P.K. , Upadhyay H. , Dave A. , Reddy A.N. , Jaiprakash B.C. , Adatte T.
Published: November 2011

A scientific challenge is to assess the role of Deccan volcanism in the Cretaceous-Tertiary boundary (KTB) mass extinction. Here we report on the stratigraphy and biologic effects of Deccan volcanism in eleven deep wells from the Krishna-Godavari (K-G) Basin, Andhra Pradesh, India. In these wells, two phases of Deccan volcanism record the world’s largest and longest lava mega-flows interbedded in marine sediments in the K-G Basin about 1500 km from the main Deccan volcanic province. The main phase-2 eruptions (~80% of total Deccan Traps) began in C29r and ended at or near the KTB, an interval that spans planktic foraminiferal zones CF1-CF2 and most of the nannofossil Micula prinsii zone, and is correlative with the rapid global warming and subsequent cooling near the end of the Maastrichtian. The mass extinction began in phase-2 preceding the first of four mega-flows. Planktic foraminifera suffered a 50% drop in species richness. Survivors suffered another 50% drop after the first mega-flow, leaving just 7 to 8 survivor species. No recovery occurred between the next three mega-flows and the mass extinction was complete with the last phase-2 mega-flow at the KTB. The mass extinction was likely the consequence of rapid and massive volcanic CO2 and SO2 gas emissions, leading to high continental weathering rates, global warming, cooling, acid rains, ocean acidification and a carbon crisis in the marine environment.

Deccan volcanism phase-3 began in the early Danian near the C29R/C29n boundary correlative with the planktic foraminiferal zone P1a/P1b boundary and accounts for ~14% of the total volume of Deccan eruptions, including four of Earth’s longest and largest mega-flows. No major faunal changes are observed in the intertrappeans of zone P1b, which suggests that environmental conditions remained tolerable, volcanic eruptions were less intense and/or separated by longer time intervals thus preventing runaway effects. Alternatively, early Danian assemblages evolved in adaptation to high-stress conditions in the aftermath of the mass extinction and therefore survived phase-3 volcanism. Full marine biotic recovery did not occur until after Deccan phase-3. These data suggest that the catastrophic effects of phase-2 Deccan volcanism upon the Cretaceous planktic foraminifera were a function of both the rapid and massive volcanic eruptions and the highly specialized faunal assemblages prone to extinction in a changing environment. Data from the K-G Basin indicates that Deccan phase-2 alone could have caused the KTB mass extinction and that impacts may have had secondary effects.
Light Hydrocarbons Geochemistry of Surface Sediments from Pranhita-Godavari Basin, Andhra Pradesh
Authors: Anu Radha B. , Rasheed M. A. , Srinivasa Rao P.L. , Kalpana M.S. , Dayal A. M.
Published: November 2011

A geochemical study of surface sediments from Pranhita-Godavari Basin, Andhra Pradesh, India was carried out using light hydrocarbon compounds to assess the hydrocarbon potential of the basin. Suite of 80 soil samples were collected from the depth of 2.5 m and analyzed for adsorbed light gaseous hydrocarbons namely methane (CH4), ethane (C2H6) and propane (C3H8) in Gas chromatograph. Compound specific Carbon isotope ratios for CH4 and C2H6 were also determined using GC-C IRMS (Gas Chromatograph Combustion Isotope Mass Spectrometer). The presence of moderate to low concentrations of methane (CCH4: 1 to 138 ppb), ethane (CC2H6: 1 to 35 ppb) and propane (CC3H8: 1 to 20 ppb) was measured in the soil samples. Carbon isotopic composition of δ13CCH4 ranges between -27.9 to -47.1 ‰ and δ13CC2H6 ranged between -36.9 to -37.2 ‰ (V-PDB) indicating that these gases are of thermogenic origin. Study of soil samples suggests the area has good potential for hydrocarbon.
Flow-types and Lava Emplacement History of Rajahmundry Traps, West of River Godavari, Andhra Pradesh
Authors: Sen Bibhas , Sabale A. B.
Published: November 2011

Rajahmundry Traps has been under geo-scientific investigations for over half a century; yet sketchy information is available on morphology and internal architecture of lavas. This study bridges this gap by describing the morphology of lava pile of Duddukuru area following Hawaiian scheme that relates a lava-type with a particular emplacement style.

The lowest flow (Flow 1) at Duddukuru, overlying an infra-trappean bed is a thick pahoehoe sheet lobe with intermittent basal hummocky, P-type pahoehoe lobes representing slow, sub-aerial emplacement of lava parcels. Some of them also have cherty intercalations and morphology suggestive of possible interaction of lava with water or water-laden sediments. Hummocky lobes were over-ridden by subaerial emplacement of voluminous sheet lava, which developed multi-tier columnar joints probably due to inundation of lava-surface by water. Inter-trappean sediments were deposited above Flow 1 in the ensuing period of volcanic quiescence. The eruptive history of Duddukuru ended with sub-aerial outpouring of two consecutive a’a flows (Flows 2 and 3) separated by a thin red bole horizon.

As pahoehoe lavas are known to travel long distances due to emplacement through thermally efficient mechanism of endogenous inflation and insulated melt transport whereas a’a lavas, in contrast, are cooling-limited flows which rarely attain lengths covered by pahoehoe lavas; it is probable that the pahoehoe and a’a flows of Duddukuru have not traveled comparable distances. A’a flows of Rajahmundry Traps traveling from far-off vents are, therefore, more unlikely despite temporal and chemical similarity of this lava-pile with upper parts of Western Deccan Basalt Group.
Middleware for social computing: a roadmap
Authors: Capra Licia , Quercia Daniele
Published: November 2011

Social computing broadly refers to supporting social behaviours using computational systems. In the last decade, the advent of Web 2.0 and its social networking services, wikis, blogs, and social bookmarking has revolutionised social computing, creating new online contexts within which people interact socially (socialnetworking). With the pervasiveness of mobile devices and embedded sensors, we stand at the brink of another major revolution, where the boundary between online and offline social behaviours blurs, providing opportunities for (re)defining social conventions and contexts once again. But opportunities come with challenges: can middleware foster the engineering of social software? We identify threesocietalgrand challenges that are likely to drive future research in social computing and elaborate on how the middleware community can help address them.
Out of Sight, Out of Mind: Including Group Quarters Residents With Household Residents Can Change What We Know About Working-Age People With Disabilities
Authors: Stapleton David , Honeycutt Todd , Schechter Bruce
Published: November 2011

Information about residents of institutional and noninstitutional group quarters (GQ), particularly those with disabilities, has been limited by gaps in survey data, and statistics based on data that exclude some or all GQ residents are biased as estimates of total population statistics. We used the 2006 and 2007 American Community Survey (ACS) to identify the distribution of working-age populations with and without disabilities by major residence type and to assess the sensitivity of disability statistics to GQ residence. Our findings show that (1) of those with disabilities, about 1 in 13 males and 1 in 33 females live in GQ; (2) GQ rates are higher for individuals reporting mental, self-care, or go-outside-the-home disabilities than for those reporting sensory, physical, or employment disabilities; (3) younger males with disabilities are more likely to reside there, particularly at institutional GQ, reflecting their relatively high incarceration rate; (4) individuals with and without disabilities who are black, American Indian, were never married, or have less than a high school education have higher GQ residence rates; (5) 40% of male and 62% of female GQ residents have a disability; (6) adding GQ residents to household residents increases estimated disability prevalence for males by 6%, and the estimated difference between disability prevalence rates by gender nearly disappears; and (7) inclusion of the GQ population substantially lowers employment rate estimates for young males, blacks, and American Indians.
Lower Limb Ischaemia Complicating Total Hip Arthroplasty
Authors: Shiu-Wai Chan , Hing-Cheong Wong , Kam-Yiu Wong
Published: November 2011

This article is about two patients having vascular injuries complicating total hip arthroplasty because of intraoperative indirect injuries. One patient had a delayed presentation of acute lower limb ischaemia, in which he required amputation of his left second toe because of ischaemic gangrene. The other patient had acute lower limb ischaemia leading to permanent muscle and nerve damage because of delayed recognition. Both patients had vascular interventions for the indirect vascular injuries. Preoperative workup for suspicious underlying peripheral vascular disease, intraoperative precautions, and perioperative period of vascular status monitoring are essential for prevention and early detection of such sinister events.
Relationship of Acetabular Dysplasia and Femoroacetabular Impingement to Hip Osteoarthritis: A Focused Review
Authors: Harris‐Hayes Marcie , Royer Nathaniel K.
Published: November 2011

Hip osteoarthritis (OA) leads to significant functional limitations and economic burden. If modifiable risk factors for hip OA are identified, it may be possible to implement preventative measures. Bony abnormalities associated with acetabular dysplasia (AD) and femoroacetabular impingement have been recently implicated as risk factors for hip OA. The purpose of this focused review is to summarize the available evidence describing the relationship between bony abnormalities and hip OA. A librarian‐assisted database search with PubMed, Embase, and CENTRAL was performed. Relevant articles were identified and assessed for inclusion criteria. The authors reviewed cohort and case‐control studies that reported on the association between abnormal hip morphology and hip OA. The available literature suggests that an association exists between bony abnormalities found in AD and femoroacetabular impingement and hip OA, and preliminary evidence suggests that AD is a risk factor for OA; however, these conclusions are based on limited evidence. Prospective, longitudinal studies are needed to confirm the causal relationship between abnormal hip morphology and the future development of hip OA.
The annulled Tax state: Schumpeterian Prolegomena to the study of postcommunist fiscal sociology
Authors: Ganev Venelin I.
Published: November 2011

How was a new infrastructure of revenue-collection instituted after the collapse of Soviet-type regimes in Eastern Europe? This article suggests that currently available answers to this question are unsatisfactory. Building upon insights derived from the literature on fiscal sociology and from Joseph Schumpeter’s analysis of modern “tax states,” it outlines a new approach to the study of various phenomena related to revenue-collection in postcommunism. More specifically, I examine a set of empirical and theoretical issues related to the reemergence of a taxpayer as having a cultural role, the reconfiguration of the bureaucratic apparatuses bequeathed by the old regime, and the recreation of trustworthy national currencies. Having identified important gaps in our understanding of the transformative processes that engulfed the region after 1989, the paper introduces a more comprehensive research program focused on the context-specific challenges inherent in the attempt to re-establish tax states in the formerly communist countries.
Chlorophyll aalgorithms for oligotrophic oceans: A novel approach based on three‐band reflectance difference
Authors: Hu Chuanmin , Lee Zhongping , Franz Bryan
Published: November 2011

A new empirical algorithm is proposed to estimate surface chlorophyll a (Chl) concentrations in the global ocean for Chl ≤ 0.25 mg m−3(∼78% of the global ocean area). The algorithm is based on a color index (CI), defined as the difference between remote‐sensing reflectance (Rrs, sr−1) in the green and a reference formed linearly between Rrsin the blue and red. For low‐Chl waters, in situ data showed a tighter (and therefore better) relationship between CI and Chl than between traditional band ratios and Chl, which was further validated using global data collected concurrently by ship‐borne and Sea‐viewing Wide Field‐of‐view Sensor (SeaWiFS) and Moderate Resolution Imaging Spectroradiometer (MODIS)/Aqua instruments. Model simulations showed that for low‐Chl waters, compared with the band‐ratio algorithm, the CI‐based algorithm (CIA) was more tolerant to changes in chlorophyll‐specific backscattering coefficient and performed similarly for different relative contributions of nonphytoplankton absorption. Simulations using existing atmospheric correction approaches further demonstrated that the CIA was much less sensitive than band‐ratio algorithms to various errors induced by instrument noise and imperfect atmospheric correction (including sun glint and whitecap corrections). Image and time series analyses of SeaWiFS and MODIS/Aqua data also showed improved performance in terms of reduced image noise, more coherent spatial and temporal patterns, and better consistency between the two sensors. The reduction in noise and other errors is particularly useful to improve the detection of various ocean features such as eddies. Preliminary tests over Medium‐Resolution Imaging Spectrometer and Coastal Zone Color Scanner data indicate that the new approach should be generally applicable to all past, current, and future ocean color instruments.
Eyjafjallajökull ash concentrations derived from both lidar and modeling
Authors: Chazette Patrick , Bocquet Marc , Royer Philippe , Winiarek Victor , Raut Jean‐Christophe , Labazuy Philippe , Gouhier Mathieu , Lardier Mélody , Cariou Jean‐Pierre
Published: November 2011

Following the eruption of the Icelandic volcano Eyjafjallajökull on the 14 April 2010, ground‐based N2‐Raman lidar (GBL) measurements were used to trace the temporal evolution of the ash plume from 16 to 20 April 2010 above the southwestern suburb of Paris. The nighttime overpass of the Cloud‐Aerosol LIdar with Orthogonal Polarization onboard Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observation satellite (CALIPSO/CALIOP) on 17 April 2010 was an opportunity to complement GBL observations. The plume shape retrieved from GBL has been used to assess the size range of the particles size. The lidar‐derived aerosol mass concentrations (PM) have been compared with model‐derived PM concentrations held in the Eulerian model Polair3D transport model, driven by a source term inferred from the SEVIRI sensor onboard Meteosat satellite. The consistency between model and ground‐based wind lidar and CALIOP observations has been checked. The spatial and temporal structures of the ash plume as estimated by each instrument and by the Polair3D simulations are in agreement. The ash plume was associated with a mean aerosol optical thickness of 0.1 ± 0.06 and 0.055 ± 0.053 for GBL (355 nm) and CALIOP (532 nm), respectively. Such values correspond to ash mass concentrations of ∼400 ± 160 and ∼720 ± 670 μg m−3, respectively, within the ash plume, which was lower than 0.5 km in width. The relative uncertainty is ∼75% and mainly due to the assessment of the specific cross‐section assuming an aerosol density of 2.6 g cm−3. The simulated ash plume is smoother leading to integrated mass of the same order of magnitude (between 50 and 250 mg m−2).
The cost of noncooperation in international river basins
Authors: Tilmant A. , Kinzelbach W.
Published: November 2011

In recent years there has been a renewed interest for water supply enhancement strategies in order to deal with the exploding demand for water in some regions, particularly in Asia and Africa. Within such strategies, reservoirs, especially multipurpose ones, are expected to play a key role in enhancing water security. This renewed impetus for the traditional supply‐side approach to water management may indeed contribute to socioeconomic development and poverty reduction if the planning process considers the lessons learned from the past, which led to the recommendations by the World Commission on Dams and other relevant policy initiatives. More specifically, the issues dealing with benefit sharing within an efficient and equitable utilization of water resources are key elements toward the successful development of those river basins. Hence, there is a need for improved coordination and cooperation among water users, sectors, and riparian countries. However, few studies have explicitly tried to quantify, in monetary terms, the economic costs of noncooperation, which we believe to be important information for water managers and policy makers, especially at a time when major developments are planned. In this paper we propose a methodology to assess the economic costs of noncooperation when managing large‐scale water resources systems involving multiple reservoirs, and where the dominant uses are hydropower generation and irrigated agriculture. An analysis of the Zambezi River basin, one of the largest river basins in Africa that is likely to see major developments in the coming decades, is carried out. This valuation exercise reveals that the yearly average cost of noncooperation would reach 350 million US$/a, which is 10% of the annual benefits derived from the system.
Assimilation of terrestrial water storage from GRACE in a snow‐dominated basin
Authors: Forman B. A. , Reichle R. H. , Rodell M.
Published: November 2011

Terrestrial water storage (TWS) information derived from gravity recovery and climate experiment (GRACE) measurements is assimilated into a land surface model over the Mackenzie River basin located in northwest Canada. Assimilation is conducted using an ensemble Kalman smoother (EnKS). Model estimates with and without assimilation are compared against independent observational data sets of snow water equivalent (SWE) and runoff. For SWE, modest improvements in mean difference (MD) and root‐mean‐square difference (RMSD) are achieved as a result of the assimilation. No significant differences in temporal correlations of SWE resulted. Runoff statistics of MD remain relatively unchanged while RMSD statistics, in general, are improved in most of the sub‐basins. Temporal correlations are degraded within the most upstream sub‐basin, but are, in general, improved at the downstream locations, which are more representative of an integrated basin response. GRACE assimilation using an EnKS offers improvements in hydrologic state/flux estimation, though comparisons with observed runoff would be enhanced by the use of river routing and lake storage routines within the prognostic land surface model. Further, GRACE hydrology products would benefit from the inclusion of better constrained models of postglacial rebound, which significantly affects GRACE estimates of interannual hydrologic variability in the Mackenzie River basin.
The Role of Proteolytically Inactive Serine Proteases from Sarcoptes scabiei in Complement Evasion
Authors: Reynolds Simone , Fischer Katja
Published: November 2011

Infestation of skin by the parasitic itch mite Sarcoptes scabiei afflicts 300 million people worldwide, and there is a need for novel and efficient therapies. We have identified a multigene family of serine proteases comprising multiple catalytically inactive members (Scabies Mite Inactivated Protease Paralogues—SMIPP-Ss), which are secreted into the gut of S. scabiei. SMIPPs are located in the mite gut and in feces excreted into the upper epidermis. Scabies mites feed on epidermal protein, including host plasma; consequently, they are exposed to host defense mechanisms both internally and externally. Two recombinantly expressed SMIPP-Ss inhibited all three pathways of the human complement system due to binding of C1q, mannose-binding lectin, and properdin. Immunohistochemical staining demonstrated the presence of C1q in the gut of scabies mites in skin burrows. We propose that SMIPP-Ss minimize complement-mediated gut damage and thus create a favorable environment for the scabies mites.
Discovery of the Cysteine Protease Cathepsin B as a Drug Target for Alzheimer's Disease
Authors: Hook Vivian , Kindy Mark , Hook Gregory
Published: November 2011

Protease enzymes represent logical drug targets in human diseases. Alzheimer's disease (AD) is a devastating neurodegenerative disease resulting in severe loss of memory during advanced aging. Development of AD involves the accumulation of neurotoxic β-amyloid (Aβ) peptides in brains of AD patients, which represents a primary factor in the progressive memory loss observed in animal models of AD. Beta-amyloid peptides are produced by proteases that cleave the amyloid precursor protein (APP) at the β- and γ-secretase sites of APP flanking the N- and C-termini of β-amyloid peptide sequences, respectively, to generate Aβ(1–40) and Aβ(1–42). The strategy to identify and inhibit the protease(s) cleaving at the β-secretase site can reduce production of both forms of Aβ peptides. The majority of AD patients express APP with the normal wild-type β-secretase site, and a few patients express APP with the Swedish mutation at the β-secretase site. The search for proteolytic activity that cleaves the wild-type β -secretase site led to identification of cathepsin B that produces Aβ in regulated secretory vesicles which provide a major portion of extracellular Aβ. Inhibitors of cathepsin B effectively reduce brain Aβ and improve memory in mouse models expressing human APP with the wild-type β-secretase site, but not in mice expressing APP with the Swedish mutant β-secretase site. The specificity of cathepsin B for cleaving the wild-type β-secretase site, but not the Swedish mutant site, provides the basis for the pharmacogenetic differences in drug responses in the two different genetic AD animal models. In contrast to cathepsin B, the BACE1 β-secretase prefers to cleave the Swedish mutant site. Discussion of BACE1 data in the field indicates that they do not preclude cathepsin B as another β-secretase. Cathepsin B and BACE1 may participate jointly as β-secretases. Significantly, the majority of AD patients express WT APP, and therefore, inhibitors of cathepsin B represent candidate drugs for AD.
Plasmodium falciparum Neutral Aminopeptidases: Development of Novel Anti-Malarials by Understanding Enzyme Structure
Authors: Gardiner Donald , Dalton John , McGowan Sheena
Published: November 2011

Malaria is the world's most prevalent human parasitic disease. Because of the rapid spread of drug resistance in the parasite, there is an urgent need to identify new diverse drug targets. Within the complex intra-erythrocytic life-cycle of the parasite, the activity of two neutral metalloaminopeptidases is essential to the parasite's growth and development. Inhibition of the combined activity of the m1 alanyl aminopeptidase and the m17 leucyl aminopeptidase prevents the growth of Plasmodium falciparum parasites in culture, and protects mice from infection with the rodent malaria species P. c. chabaudi, providing strong support for considering them as targets for which a new class of anti-malarial drugs can be developed. The high-resolution X-ray crystal structures of both enzymes have been elucidated and provide valuable structural and mechanistic detail to facilitate the development of compounds in future rational drug-design programs.
Blood-Feeding Human Hookworm Proteases
Authors: Loukas A. , Ranjit N. , Pickering D. A. , Pearson M. S.
Published: November 2011

Proteases are pivotal to parasitism, mediating biological processes crucial to the survival of parasitic helminth (worms). Hookworms live in the small intestine of their mammalian hosts, and bury their anterior ends under the mucosa where they rupture the capillaries and feed on the extravasated blood. A suite of proteases are expressed in the intestine of the hookworm, where they act to degrade host hemoglobin and serum proteins as part of the feeding process. These proteases are exposed to components of the host's immune system when the worms ingest blood, and therefore present as targets for the development of anti-helminth vaccines and prophylactic drugs. The protective effects of current vaccine antigens against hookworms and related nematodes of livestock (barber's pole worm) are based on hemoglobin-degrading intestinal proteases and act largely due to the neutralization of these proteases by antibodies that are ingested with the blood meal. In this chapter, we survey the current status of hookworm and proteases that show promise as vaccines and describe their vital contribution to a parasitic existence.
Pharmacological Targeting of Human Tissue Kallikrein-Related Peptidases
Authors: Pampalakis Georgios , Sotiropoulou Georgia
Published: November 2011

Kallikreins are important enzymes historically known for their participation in the generation of the vasoactive peptides kinins. They are distinguished into plasma kallikrein and the tissue kallikreins, recently renamed kallikrein-related peptidases (KLKs). KLKs constitute the largest serine protease gene family within the human genome that comprises 15 members. It is now well established that KLKs acting individually or in complex tissue-specific proteolytic cascades regulate important physiological processes (i.e., skin desquamation, semen liquefaction, CNS physiology), while their deregulation has been implicated in pathological conditions, including asthma, neurodegeneration, and cancer promotion or inhibition. Therefore, KLKs represent new important targets for pharmacological intervention. The present overview describes the development of different classes of novel inhibitors (or activators) of KLKs that were either designed based on known substrate specificity and protease inhibitor bioscaffolds or isolated by phage display or library screening. These include peptides, engineered protease inhibitors, small organic molecules, and human monoclonal antibodies. These molecules were tested in various animal models for skin disorders, cancer, or asthma, and were found to exhibit potency and efficacy. It is expected that such compounds will enter the market, in the near future, for the treatment of severe diseases some, currently, without alternative therapy.
Structural Mechanisms of Inactivation in Proteolytically Inactive Serine Proteases from Sarcoptes scabiei
Authors: Fischer Katja , Irving James A. , Pike Robert , Buckle Ashley M.
Published: November 2011

The scabies mite (Sarcoptes scabiei) is a parasitic mite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. The scabies mite produces 33 proteins that are closely related to the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalytically inactive. These molecules are thus termed Scabies Mite Inactivated Protease Paralogues (SMIPPs). The precise function of SMIPPs remains unclear. However, it has been suggested that these proteins may function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. The high-resolution crystal structures of two members of the SMIPP family have been solved and provide insight into how SMIPPs have lost the ability to bind substrates in a classical ‘canonical’ fashion, and instead have evolved alternative functions in the lifecycle of the Scabies mite.
The Aspartic Proteinases from the Malaria Parasite: Structure and Function of the Plasmepsins
Authors: Dunn Ben M.
Published: November 2011

Malaria remains a devastating disease in the developing world with nearly a half billion people infected each year by the bite of a mosquito that carries the parasite, Plasmodium falciparum, which causes the disease. There is a desperate need to develop new compounds to combat malaria as the parasite has developed resistance against the classic drugs primaquine and chloroquine. The proteolytic enzymes of the parasite have been identified as potential targets for drug discovery due to the known requirement of the digestion of hemoglobin in the parasite digestive vacuole. Among the proteolytic enzymes found in P. falciparum, the aspartic proteinases, known as plasmepsins, are discussed in this chapter. The completion of the sequencing of the genome of P. falciparum revealed a total of ten enzymes in the aspartic proteinase class, with seven of these being found in the stage of the parasite that can be found in the erythrocyte of infected humans. The current information on these seven enzymes is presented and the possibility of identifying one or more key enzymes as targets for drug discovery is discussed.
Source Gases that Affect Stratospheric Ozone
Authors: Montzka Stephen A.
Published: November 2011

This chapter on source gas trends describes past changes in atmospheric concentrations of ozone-depleting chemicals and discusses their implications for Earth's ozone layer. The observed atmospheric changes provide evidence of an atmosphere responding to international policy decisions given that natural contributions are relatively small and fairly constant. The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer has been successful at causing an initial decrease in the concentrations of ozone-depleting substances and the threat they pose to stratospheric ozone. Despite this success, full recovery of the ozone layer is not expected until mid- to late-century. Other non-halogenated gases, such as methane, nitrous oxide, hydrofluorocarbons, and sulfur-containing chemicals also influence stratospheric ozone and climate and are discussed. Observed changes in the atmospheric concentrations of both ozone-depleting substances and non-halogenated chemicals provide a basis for understanding trends in stratospheric ozone discussed in subsequent chapters.
Impact of Geo-engineering on Stratospheric Ozone and Climate
Authors: Tilmes Simone , Garcia Rolando R.
Published: November 2011

The distribution of stratospheric ozone in the early 21st century is strongly influenced by large-scale anthropogenic emissions of chlorofluorocarbons that occurred in the last half of the 20th century. Further, continuously increasing greenhouse gases have a significant impact on the composition of the atmosphere and the ozone layer, as discussed in earlier chapters. For the future, there might be another important factor influencing ozone and climate, the potential deployment of “geo-engineering” or “climate engineering” schemes, understood as “the deliberate large-scale manipulation of the planetary environment to counteract anthropogenic climate change”. This chapter introduces some basic concepts of geo-engineering, and further focuses on the impact of one of the most discussed geo-engineering schemes, the injection of particles into the stratosphere to counteract global warming by increasing the Earth's albedo. This approach is analogous to large-scale volcanic eruptions, which have been shown to produce transient cooling of the Earth's surface. To date, only limited studies, based on more or less simplified models, have been performed to quantify the effectiveness and also the side-effects and uncertainties of this type of geo-engineering, including its significant impact on the ozone layer.
Traitement orthodontique des adultes avec un parodonte réduit : principes biomécaniques et applications cliniques
Authors: Cacciafesta Vittorio , Luebberink Gudrun , Kanter Daniel
Published: November 2011

Au cours des dernières années, le nombre d’adultes qui bénéficient d’un traitement orthodontique global a considérablement augmenté. En pratique, la prise en charge des adultes peut différer sensiblement de celle de la plupart des adolescents. En effet, les adultes présentent plus souvent que les adolescents des dents plus ou moins délabrées au cours du temps, ce qui peut conduire à modifier la planification classique du traitement. Une usure excessive, des dents manquantes ou compromises font partie des particularités observées. Pour des patients adultes qui ont subi une perte d’attache et d’os suite à une maladie parodontale, de nouvelles considérations biomécaniques permettent de générer les mouvements dentaires souhaités pour le traitement orthodontique. Concevoir un traitement et un dispositif orthodontiques convenables pour des adultes présentant plusieurs dents manquantes peut demander un certain niveau de créativité pour s’adapter à des malocclusions singulières et pour développer un système de forces approprié. Cet article présente l’application clinique actuelle de ces principes biomécaniques, en insistant sur la prise en charge orthodontique de dentures sévèrement délabrées.
Neuroborreliose bei einer Patientin mit vermeintlich kryptogenen zerebralen Infarkten
Authors: Lerch-Riedl T. , Rohringer E. , Brenneis C. , Feuchtinger J.
Published: November 2011

Es handelt sich um den Fall einer 55-jährigen Patientin, welche zweimal einen zerebralen Infarkt erlitt, ohne dass primär eine Ursache festgestellt werden konnte. Durch eine Lumbalpunktion wurde eine aktive Neuroborreliose diagnostiziert. Eine zweiwöchige antibiotische Therapie mit Ceftriaxon führte zu einem klaren Rückgang der entzündlichen Liquorveränderungen. Ein neuerlicher Insult trat bis zum heutigen Tag nicht auf.
Knowledge Management Governance: The Road to Continuous Benefits Realization
Authors: Zyngier Suzanne , Burstein Frada
Published: November 2011

Investment in knowledge management (KM) programmes is often contentious due to the challenge of meeting the need for continuous and sustainable benefits realization. In KM, the word ‘sustainable’ describes how programmes of strategies to leverage organizational knowledge remain productive over time: that they deliver strategic value to the organization. The focus of this paper falls on the constructs of the governance of KM and on its leadership, in KM strategy devopment and implementation, including risk management, financial controls and transparent evaluation mechanisms for continuous benefits realization. This paper presents a KM governance model and explores its recent validation through six case studies of large, distributed, multinational organizations, and through these introduces the granular constructs of KM governance. Exploration of the impact of KM governance on developing and implementing KM programmes in each case study organization demonstrates that there is a clear nexus between strategic KM governance and benefits realized from those programmes.
Threading-dislocation blocking by stacking faults formed in an undoped GaN layer on a patterned sapphire substrate
Authors: Bo Lee Sung , Kwon Tae-Wan , Lee Sung-Hak , Park Jungwon , Choi Won-Jin
Published: November 2011

The microstructure of an undoped GaN grown on a hemisphere-patterned sapphire substrate is characterized by transmission electron microscopy. Interestingly, basal-plane stacking faults are formed in GaN at the height of hemispheres, leading to a substantial reduction in threading-dislocation density. It is believed that the formation of the stacking faults is characteristic of the lateral growth mode. This study looks at an unexplored feature of the lateral growth behavior that both so-called epitaxial lateral overgrowth mechanism and stacking faults function to reduce the dislocation density for the GaN growth on hemisphere-patterned sapphire substrates.
Asymmetric stochastic localization in geometry controlled kinetics
Authors: Mondal Debasish , Ray Deb Shankar
Published: November 2011

We consider the motion of Brownian particles confined in a two-dimensional symmetric bilobal enclosure with uneven cross section. Varying cross section of the confinement results in an effective entropic potential in reduced dimension. By employing two external noise forces, one additive and another multiplicative along x direction, we demonstrate that a correlation between them causes a symmetry breaking of entropic stability, i.e., a difference in relative stability of two lobes. This leads to an asymmetric localization of population in the stationary state. A two-state model is proposed to explain the asymmetric localization of population due to entropic diffusion.
The role of surface currents in plasma confinement
Authors: Webster Anthony J.
Published: November 2011

During plasma instabilities, “surface currents” can flow at the interface between the plasma and the surrounding vacuum, and in most cases, they are a harmless symptom of the instability that is causing them. Large instabilities can lead to “disruptions,” an abrupt termination of the plasma with the potential to damage the machine in which it is contained. For disruptions, the correct calculation of surface currents is thought to be essential for modelling disruptions properly. Recently, however, there has been debate and disagreement about the correct way to calculate surface currents. The purpose of this paper is to clarify as simply as possible the role of surface currents for plasma confinement and to show that a commonly used representation for surface currents σ→ with σ→=∇I∧n→, I a scalar function, and n→ the unit normal to the plasma surface, is only appropriate for the calculation of surface currents that are in magnetohydrodynamic equilibrium. Fortunately, this is the situation thought to be of most relevance for disruption calculations.
On the early evolution in the transient Bénard–Marangoni problem
Authors: Weidenfeld M. , Frankel I.
Published: November 2011

We focus on the early evolution of small (linear) perturbations following the sudden (step-function) exposure of a liquid layer to a cold adjacent atmosphere. On a time scale short relative to that characterizing thermal relaxation across the liquid layer, the temperature distribution is nonlinear and highly transient. Thus, the conduction reference state may not be regarded quasi steady. We accordingly consider the initial-value problem and obtain a Volterra-type integral equation governing the evolution of surface-temperature perturbations. Assuming an O(1) Biot number we study the effects on perturbations evolution of the wavenumber, the Prandtl number (Pr) and the effective Marangoni number (Ma¯, which, from the dominant balance in the thermal perturbation equation, is based on the current values of the width of the thermal boundary layer and the temperature difference across it, respectively). Explicit results are first presented in the limit of Pr>>1 wherein the hydrodynamic perturbation problem is quasi steady. The dominant perturbations correspond to large wavenumbers and convection effectively confined to the thermal boundary layer. Typical of the results is the nonmonotonic temporal evolution of perturbations which initially diminish and only after some finite delay time start to grow. These trends are rationalized in terms of the Marangoni mechanism by observing that while the magnitude of the reference-state temperature gradients remain essentially constant, they extend over a widening thermal boundary layer allowing for enhanced convective effects. Thus, since perturbations may be introduced at all positive times, those evolving on the favourable background of further developed (wider) thermal boundary layers may take over perturbations introduced earlier. This suggests the existence of a nonzero “optimal” appearance time of perturbations which will eventually dominate the instability process. We study the effects of finite O(1) values of Pr on the evolution of the hydrodynamic perturbation problem which is no longer quasi steady. Increasing Pr at a constant Ma¯ is destabilizing which reflects the dual role of liquid viscosity in the transient Bénard-Marangoni problem. It is further demonstrated that with increasing wavenumber convergence to the asymptotic Pr>>1 limit is practically achieved at smaller Pr.
Ultrafast decay of hot phonons in an AlGaN/AlN/AlGaN/GaN camelback channel
Authors: Leach J. H. , Wu M. , Morkoç H. , Liberis J. , Šermukšnis E. , Ramonas M. , Matulionis A.
Published: November 2011

A bottleneck for heat dissipation from the channel of a GaN-based heterostructure field-effect transistor is treated in terms of the lifetime of nonequilibrium (hot) longitudinal optical phonons, which are responsible for additional scattering of electrons in the voltage-biased quasi-two-dimensional channel. The hot-phonon lifetime is measured for an Al0.33Ga0.67N/AlN/Al0.1Ga0.9N/GaN heterostructure where the mobile electrons are spread in a composite Al0.1Ga0.9N/GaN channel and form a camelback electron density profile at high electric fields. In accordance with plasmon-assisted hot-phonon decay, the parameter of importance for the lifetime is not the total charge in the channel (the electron sheet density) but rather the electron density profile. This is demonstrated by comparing two structures with equal sheet densities (1 × 1013 cm−2), but with different density profiles. The camelback channel profile exhibits a shorter hot-phonon lifetime of ∼270 fs as compared with ∼500 fs reported for a standard Al0.33Ga0.67N/AlN/GaN channel at low supplied power levels. When supplied power is sufficient to heat the electrons > 600 K, ultrafast decay of hot phonons is observed in the case of the composite channel structure. In this case, the electron density profile spreads to form a camelback profile, and hot-phonon lifetime reduces to ∼50 fs.
Replica exchange and expanded ensemble simulations as Gibbs sampling: Simple improvements for enhanced mixing
Authors: Chodera John D. , Shirts Michael R.
Published: November 2011

The widespread popularity of replica exchange and expanded ensemble algorithms for simulating complex molecular systems in chemistry and biophysics has generated much interest in discovering new ways to enhance the phase space mixing of these protocols in order to improve sampling of uncorrelated configurations. Here, we demonstrate how both of these classes of algorithms can be considered as special cases of Gibbs sampling within a Markov chain Monte Carlo framework. Gibbs sampling is a well-studied scheme in the field of statistical inference in which different random variables are alternately updated from conditional distributions. While the update of the conformational degrees of freedom by Metropolis Monte Carlo or molecular dynamics unavoidably generates correlated samples, we show how judicious updating of the thermodynamic state indices—corresponding to thermodynamic parameters such as temperature or alchemical coupling variables—can substantially increase mixing while still sampling from the desired distributions. We show how state update methods in common use can lead to suboptimal mixing, and present some simple, inexpensive alternatives that can increase mixing of the overall Markov chain, reducing simulation times necessary to obtain estimates of the desired precision. These improved schemes are demonstrated for several common applications, including an alchemical expanded ensemble simulation, parallel tempering, and multidimensional replica exchange umbrella sampling.