bluuebunny/crossref_metadata_2025 huggingface dataset:
Muju virus, a novel hantavirus harboured by the arvicolid rodent Myodes regulus in Korea
Authors: Song Ki-Joon , Baek Luck Ju , Moon Sungsil , Ha Si Jung , Kim Sang Hyun , Park Kwang Sook , Klein Terry A. , Sames William , Kim Heung-Chul , Lee John S. , Yanagihara Richard , Song Jin-Won
Published: October 2007

Acute-phase sera from >5 % of cases of haemorrhagic fever with renal syndrome occurring annually in Korea have been found to exhibit a fourfold or higher antibody titre to Puumala virus (PUUV) than to Hantaan virus (HTNV) by double-sandwich IgM ELISA, suggesting the existence of a PUUV-related hantavirus. Based on the phylogenetic relationships among arvicolid rodents, the royal vole (Myodes regulus) was targeted as a likely reservoir host of hantavirus. Using RT-PCR, a genetically distinct hantavirus, designated Muju virus (MUJV), was detected in lung tissue of royal voles, captured in widely separated geographical regions in Korea during 1996–2007. Pairwise analysis of the full-length S (1857 nt) and M (3634 nt) segments of MUJV indicated approximately 77 % sequence similarity with PUUV. At the amino acid level, MUJV differed from PUUV by 5.5–6.9 % (nucleocapsid) and 10.0–11.6 % (Gn and Gc envelope glycoproteins). Interstrain variation of MUJV sequences from royal voles captured in different regions suggested geographic-specific clustering. Neutralizing antibody titres against PUUV were two- to sixfold higher than to HTNV in sera of MUJV-infectedMyodes regulus. Although virus isolation attempts were unsuccessful, the collective data indicate that MUJV is a distinct hantavirus species.
Species B adenovirus serotypes 3, 7, 11 and 35 share similar binding sites on the membrane cofactor protein CD46 receptor
Authors: Fleischli Christoph , Sirena Dominique , Lesage Guillaume , Havenga Menzo J. E. , Cattaneo Roberto , Greber Urs F. , Hemmi Silvio
Published: October 2007

We recently characterized the domains of the human cofactor protein CD46 involved in binding species B2 adenovirus (Ad) serotype 35. Here, the CD46 binding determinants are mapped for the species B1 Ad serotypes 3 and 7 and for the species B2 Ad11. Ad3, 7 and 11 bound and transduced CD46-positive rodent BHK cells at levels similar to Ad35. By using antibody-blocking experiments, hybrid CD46–CD4 receptor constructs and CD46 single point mutants, it is shown that Ad3, 7 and 11 share many of the Ad35-binding features on CD46. Both CD46 short consensus repeat domains SCR I and SCR II were necessary and sufficient for optimal binding and transgene expression, provided that they were positioned at an appropriate distance from the cell membrane. Similar to Ad35, most of the putative binding residues of Ad3, 7 and 11 were located on the same glycan-free, solvent-exposed face of the SCR I or SCR II domains, largely overlapping with the binding surface of the recently solved fiber knob Ad11–SCR I–II three-dimensional structure. Differences between species B1 and B2 Ads were documented with competition experiments based on anti-CD46 antibodies directed against epitopes flanking the putative Ad-binding sites, and with competition experiments based on soluble CD46 protein. It is concluded that the B1 and B2 species of Ad engage CD46 through similar binding surfaces.
Internalization and intracellular retention of CD4 are two separate functions of the human immunodeficiency virus type 1 Nef protein
Authors: Giolo Giorgia , Neri Francesca , Casartelli Nicoletta , Potestà Marina , Belleudi Francesca , Torrisi Maria Rosaria , Doria Margherita
Published: October 2007

The pathogenic Nef protein of the human immunodeficiency virus type 1 (HIV-1) downregulates CD4 by inducing its endocytosis and by inhibiting the transport of the receptor to the cell membrane. By means of in vivo-selected mutations, we show that L37, P78 and E177 residues of Nef are required for its effect on CD4 internalization and recycling but dispensable for Nef-induced retention and degradation of intracellular CD4. Of note, the function of Nef on the anterograde transport of newly synthesized CD4 molecules is irrelevant in cells with a slow constitutive CD4 turnover such as T cell lines. Moreover, we show that a mutated CD4 that is unresponsive to Nef-mediated endocytosis, CD4LL144AA, is retained intracellularly and degraded by Nef like wild-type CD4. Thus, Nef's abilities to enhance endocytosis and induce intracellular retention of CD4 are mediated by separate protein surfaces and occur through distinct mechanisms.
Identification and characterization of two novel human papillomaviruses (HPVs) by overlapping PCR: HPV102 and HPV106
Authors: Chen Zigui , Schiffman Mark , Herrero Rolando , Burk Robert D.
Published: October 2007

Complete genomes of HPV102 (8078 bp) and HPV106 (8035 bp) were PCR amplified and cloned from cervicovaginal cells of a 49-year-old Hispanic female with reactive changes on her Pap test and a 42-year-old Hispanic female with a Pap test diagnosis of atypical squamous cells of unknown significance (ASCUS), respectively. The nucleotide sequence similarity of the complete L1 open reading frame (ORF) determined that HPV102 and HPV106 are most closely related to HPV83 (84.1 % identity) and HPV90 (83.5 % identity), respectively, placing them in the genital HPV groups, papillomaviruses species α3 and α15. HPV102 and HPV106 contain five early genes (E6, E7, E1, E2, and E4) and two late genes (L2 and L1), and both lack an E5 ORF. On the basis of phylogenetic analyses and available clinical information, these two novel HPV types expand the heterogeneity of HPVs detected in the lower genital tract.
Inhibitory role of CXCR4 glycan in CD4-independent X4-tropic human immunodeficiency virus type 1 infection and its abrogation in CD4-dependent infection
Authors: Kubo Yoshinao , Yokoyama Masaru , Yoshii Hiroaki , Mitani Chiho , Tominaga Chika , Tanaka Yuetsu , Sato Hironori , Yamamoto Naoki
Published: October 2007

CXCR4 functions as an infection receptor of X4 human immunodeficiency virus type 1 (HIV-1) . CXCR4 is glycosylated at the N-terminal extracellular region, which is important for viral envelope (Env) protein binding. We compared the effects of CXCR4 glycan on the CD4-dependent and –independent infections in human cells by X4 viruses. We found that transduction mediated by Env proteins of CD4-independent HIV-1 strains increased up to 5.5-fold in cells expressing unglycosylated CXCR4, suggesting that the CXCR4 glycan inhibits CD4-independent X4 virus infection. Co-expression of CD4 on the target cell surface or pre-incubation of virus particles with soluble CD4 abrogates the glycan-mediated inhibition of X4 virus infection, suggesting that interaction of Env protein with CD4 counteracts the inhibition. These findings indicate that it will be advantageous for X4 HIV-1 to remain CD4-dependent. A structural model that explains the glycan-mediated inhibition is discussed.
In vivo footprint of a picornavirus internal ribosome entry site reveals differences in accessibility to specific RNA structural elements
Authors: Fernández-Miragall Olga , Martínez-Salas Encarnación
Published: October 2007

Internal ribosome entry site (IRES) elements were described in picornaviruses as an essential region of the viral RNA. Understanding of IRES function requires a detailed knowledge of each step involved in the internal initiation process, from RNA folding and IRES–protein interaction to ribosome recruitment. Thus, deciphering IRES accessibility to external agents due to RNA structural features, as well as RNA–protein protection within living cells, is of primary importance. In this study, two chemical reagents, dimethylsulfate (DMS) and aminomethylpsoralen, have been used to footprint the entire IRES of foot-and-mouth disease virus (FMDV) in living cells; these reagents enter the cell membrane and interact with nucleic acids in a structure-dependent manner. For FMDV, as in other picornaviruses, viral infection is dependent on the correct function of the IRES; therefore, the IRES region itself constitutes a useful target of antiviral drugs. Here, thein vivofootprint of a picornavirus IRES element in the context of a biologically active mRNA is shown for the first time. The accessibility of unpaired adenosine and cytosine nucleotides in the entire FMDV IRES was first obtainedin vitroby DMS probing; subsequently, this information was used to interpret the footprint data obtainedin vivofor the mRNA encompassing the IRES element in the intercistronic space. The results of DMS accessibility and UV–psoralen cross-linking studies in the competitive cellular environment provided evidence for differences in RNA structure from data obtainedin vitro, and provided essential information to identify appropriate targets within the FMDV IRES aimed at combating this important pathogen.
Distinct gamma interferon-production pathways in mice infected with lactate dehydrogenase-elevating virus
Authors: Le-Thi-Phuong Thao , Thirion Gaëtan , Coutelier Jean-Paul
Published: October 2007

Two distinct pathways of gamma interferon (IFN-γ) production have been found in mice infected with lactate dehydrogenase-elevating virus. Both pathways involve natural killer cells. The first is mostly interleukin-12-independent and is not controlled by type I interferons. The second, which is suppressed by type I interferons, leads to increased levels of IFN-γ production and requires the secretion of interleukin-12. This regulation of IFN-γ production by type I interferons may help to control indirect pathogenesis induced by this cytokine.
Trio’s Rho-specific GEF domain is the missing Gαq effector in C. elegans
Authors: Williams Stacey L. , Lutz Susanne , Charlie Nicole K. , Vettel Christiane , Ailion Michael , Coco Cassandra , Tesmer John J.G. , Jorgensen Erik M. , Wieland Thomas , Miller Kenneth G.
Published: October 2007

The Gαq pathway is essential for animal life and is a central pathway for driving locomotion, egg laying, and growth in Caenorhabditis elegans, where it exerts its effects through EGL-8 (phospholipase Cβ [PLCβ]) and at least one other effector. To find the missing effector, we performed forward genetic screens to suppress the slow growth and hyperactive behaviors of mutants with an overactive Gαq pathway. Four suppressor mutations disrupted the Rho-specific guanine-nucleotide exchange factor (GEF) domain of UNC-73 (Trio). The mutations produce defects in neuronal function, but not neuronal development, that cause sluggish locomotion similar to animals lacking EGL-8 (PLCβ). Strains containing null mutations in both EGL-8 (PLCβ) and UNC-73 (Trio RhoGEF) have strong synthetic phenotypes that phenocopy the arrested growth and near-complete paralysis of Gαq-null mutants. Using cell-based and biochemical assays, we show that activated C. elegans Gαq synergizes with Trio RhoGEF to activate RhoA. Activated Gαq and Trio RhoGEF appear to be part of a signaling complex, because they coimmunoprecipitate when expressed together in cells. Our results show that Trio’s Rho-specific GEF domain is a major Gαq effector that, together with PLCβ, mediates the Gαq signaling that drives the locomotion, egg laying, and growth of the animal.
Phosphorylation of histone H3 at Ser10 facilitates RNA polymerase II release from promoter-proximal pausing in Drosophila
Authors: Ivaldi M. Soledad , Karam Caline S. , Corces Victor G.
Published: October 2007

The Drosophila JIL-1 kinase is known to phosphorylate histone H3 at Ser10 (H3S10) during interphase. This modification is associated with transcriptional activation, but its function is not well understood. Here we present evidence suggesting that JIl-1-mediated H3S10 phosphorylation is dependent on chromatin remodeling by the brahma complex and is required during early transcription elongation to release RNA polymerase II (Pol II) from promoter-proximal pausing. JIL-1 localizes to transcriptionally active regions and is required for activation of the E75A ecdysone-responsive and hsp70 heat-shock genes. The heat-shock transcription factor, the promoter-paused form of Pol II (Pol IIoser5), and the pausing factor DSIF (DRB sensitivity-inducing factor) are still present at the hsp70 loci in JIL-1-null mutants, whereas levels of the elongating form of Pol II (Pol IIoser2) and the P-TEFb kinase are dramatically reduced. These observations suggest that phosphorylation of H3S10 takes place after transcription initiation but prior to recruitment of P-TEFb and productive elongation. Western analyses of global levels of both forms of Pol II further suggest that JIL-1 plays a general role in early elongation of a broad range of genes. Taken together, the results introduce H3S10 phosphorylation by JIL-1 as a hallmark of early transcription elongation in Drosophila.
The ArabidopsisDESPERADO/AtWBC11Transporter Is Required for Cutin and Wax Secretion
Authors: Panikashvili David , Savaldi-Goldstein Sigal , Mandel Tali , Yifhar Tamar , Franke Rochus B. , Höfer René , Schreiber Lukas , Chory Joanne , Aharoni Asaph
Published: October 2007

The cuticle fulfills multiple roles in the plant life cycle, including protection from environmental stresses and the regulation of organ fusion. It is largely composed of cutin, which consists of C16-18 fatty acids. While cutin composition and biosynthesis have been studied, the export of cutin monomers out of the epidermis has remained elusive. Here, we show that DESPERADO (AtWBC11) (abbreviated DSO), encoding a plasma membrane-localized ATP-binding cassette transporter, is required for cutin transport to the extracellular matrix. The dso mutant exhibits an array of surface defects suggesting an abnormally functioning cuticle. This was accompanied by dramatic alterations in the levels of cutin monomers. Moreover, electron microscopy revealed unusual lipidic cytoplasmatic inclusions in epidermal cells, disappearance of the cuticle in postgenital fusion areas, and altered morphology of trichomes and pavement cells. We also found that DSO is induced by salt, abscisic acid, and wounding stresses and its loss of function results in plants that are highly susceptible to salt and display reduced root branching. Thus, DSO is not only essential for developmental plasticity but also plays a vital role in stress responses.
The F-Box Protein MAX2 Functions as a Positive Regulator of Photomorphogenesis in Arabidopsis
Authors: Shen Hui , Luong Phi , Huq Enamul
Published: October 2007

Light is vital for plant growth and development. To respond to ambient light signals, plants are equipped with an array of photoreceptors, including phytochromes that sense red (R)/far-R (FR) regions and cryptochromes and phototropins that respond to the ultraviolet-A/blue (B) region of the light spectrum, respectively. Several positively and negatively acting components in light-signaling pathways have been identified using genetic approaches; however, the pathways are not saturated. Here, we characterize a new mutant named pleiotropic photosignaling (pps), isolated from a genetic screen under continuous R light. pps has longer hypocotyls and slightly smaller cotyledons under continuous R, FR, and B light compared to that of the wild type. pps is also hyposensitive to both R and FR light-induced seed germination. Although photosynthetic marker genes are constitutively expressed in pps in the dark at high levels, the expression of early light-regulated genes is reduced in the pps seedlings compared to wild-type seedlings under R light. PPS encodes MAX2/ORE9 (for MORE AXILLARY BRANCHES2/ORESARA9), an F-box protein involved in inflorescence architecture and senescence. MAX2 is expressed ubiquitously in the seedling stage. However, its expression is restricted to vascular tissues and meristems at adult stages. MAX2 is also localized to the nucleus. As an F-box protein, MAX2 is predicted to be a component of the SCF (for SKP, Cullin, and F-box protein) complex involved in regulated proteolysis. These results suggest that SCFMAX2 plays critical roles in R, FR, and B light-signaling pathways. In addition, MAX2 might regulate multiple targets at different developmental stages to optimize plant growth and development.
Cell Wall Proteome in the Maize Primary Root Elongation Zone. II. Region-Specific Changes in Water Soluble and Lightly Ionically Bound Proteins under Water Deficit
Authors: Zhu Jinming , Alvarez Sophie , Marsh Ellen L. , LeNoble Mary E. , Cho In-Jeong , Sivaguru Mayandi , Chen Sixue , Nguyen Henry T. , Wu Yajun , Schachtman Daniel P. , Sharp Robert E.
Published: October 2007

Previous work on the adaptation of maize (Zea mays) primary roots to water deficit showed that cell elongation is maintained preferentially toward the apex, and that this response involves modification of cell wall extension properties. To gain a comprehensive understanding of how cell wall protein (CWP) composition changes in association with the differential growth responses to water deficit in different regions of the elongation zone, a proteomics approach was used to examine water soluble and loosely ionically bound CWPs. The results revealed major and predominantly region-specific changes in protein profiles between well-watered and water-stressed roots. In total, 152 water deficit-responsive proteins were identified and categorized into five groups based on their potential function in the cell wall: reactive oxygen species (ROS) metabolism, defense and detoxification, hydrolases, carbohydrate metabolism, and other/unknown. The results indicate that stress-induced changes in CWPs involve multiple processes that are likely to regulate the response of cell elongation. In particular, the changes in protein abundance related to ROS metabolism predicted an increase in apoplastic ROS production in the apical region of the elongation zone of water-stressed roots. This was verified by quantification of hydrogen peroxide content in extracted apoplastic fluid and by in situ imaging of apoplastic ROS levels. This response could contribute directly to the enhancement of wall loosening in this region. This large-scale proteomic analysis provides novel insights into the complexity of mechanisms that regulate root growth under water deficit conditions and highlights the spatial differences in CWP composition in the root elongation zone.
Proteome Analysis ofArabidopsisLeaf Peroxisomes Reveals Novel Targeting Peptides, Metabolic Pathways, and Defense Mechanisms
Authors: Reumann Sigrun , Babujee Lavanya , Ma Changle , Wienkoop Stephanie , Siemsen Tanja , Antonicelli Gerardo E. , Rasche Nicolas , Lüder Franziska , Weckwerth Wolfram , Jahn Olaf
Published: October 2007

We have established a protocol for the isolation of highly purified peroxisomes from mature Arabidopsis thaliana leaves and analyzed the proteome by complementary gel-based and gel-free approaches. Seventy-eight nonredundant proteins were identified, of which 42 novel proteins had previously not been associated with plant peroxisomes. Seventeen novel proteins carried predicted peroxisomal targeting signals (PTS) type 1 or type 2; 11 proteins contained PTS-related peptides. Peroxisome targeting was supported for many novel proteins by in silico analyses and confirmed for 11 representative full-length fusion proteins by fluorescence microscopy. The targeting function of predicted and unpredicted signals was investigated and SSL>, SSI>, and ASL> were established as novel functional PTS1 peptides. In contrast with the generally accepted confinement of PTS2 peptides to the N-terminal domain, the bifunctional transthyretin-like protein was demonstrated to carry internally a functional PTS2. The novel enzymes include numerous enoyl-CoA hydratases, short-chain dehydrogenases, and several enzymes involved in NADP and glutathione metabolism. Seven proteins, including β-glucosidases and myrosinases, support the currently emerging evidence for an important role of leaf peroxisomes in defense against pathogens and herbivores. The data provide new insights into the biology of plant peroxisomes and improve the prediction accuracy of peroxisome-targeted proteins from genome sequences.
User‐Centered Design in a Large‐Scale Naval Ship Design Program: Usability Testing of Complex Military Systems—DDG 1000
Authors: QUINTANA VINCE , HOWELLS ROBERT A. , HETTINGER LAWRENCE
Published: October 2007

The US Navy is currently developing a new class of surface combatant ships referred to as DDG 1000. Unlike past ship designs, DDG 1000 is explicitly focused on the execution of a user‐centered approach—one that captures the requirements, capabilities, and limitations of sailors expected to operate the ship. Additionally, DDG 1000 presents a number of significant human factors and challenges related to its greatly reduced crew size (compared with similar legacy ships) and high reliance on automated systems. Usability testing and usability assessments (UT and UAs) for the purpose of validation of human systems integration (HSI) principles, and the validation of the DDG 1000 Sailor Systems Specification (S3), play a key role in the DDG 1000 Human‐Centered Design (HCD). Through the use of summative and formative design analysis and design verification events, UT/UA is critical in identifying and rectifying issues early in the design process, and verifying system functionality later in the design process. For the DDG 1000 program, the Human Systems Integration—Design Verification Integrated Product Team (HSI‐DV‐IPT) has also combined its efforts with both the DDG 1000 Safety and Training Cross Product Teams to realize the economies of scale associated with conducting these tests to obtain data for the needs of all three HCD disciplines. Through the course of the DDG 1000 detailed design phase, UTs and UAs have become a defined procedural process, which is governed by both the DDG 1000 Human Systems Integration Plan and as an extension of the total testing plan for the DDG 1000 ship. Almost all DDG 1000 HSI‐DV‐IPT evolutions combine the efforts of system engineering and design teams with HSI engineers and fleet users to ensure that the combined test output product has received a “cut” from the entire chain of influence from concept to end user. To date, over 30 user interaction and test events employing 1,100 users have been conducted to verify the utility of aspects of the DDG 1000 design, from the most sophisticated to the most mundane systems and processes. In addition, a series of tools that includes 3D visualization aids for modeling and simulation, and weighted assessment systems like NASA‐TLX have been included in the DDG 1000 HSI test engineers' tool bag to provide the best of breed solutions to HCD‐oriented testing. The test results obtained to date provided valuable insight into the validity of the DDG 1000 HCD and provided feedback that led to optimization of both crew and ship as its HCD objectives intended, in addition to providing cost‐effective and timely feedback into the DDG 1000 design.
The High‐Speed Navy: Vessel Motion Influences on Human Performance
Authors: McCAULEY MICHAEL E. , PIERCE ERIC C. , MATSAGAS PANAYIOTIS
Published: October 2007

This paper presents the recent results from an ongoing analysis of the effects of high‐speed naval operations on the performance, comfort, and safety of crew and passengers. A 127‐m trimaran, the Benchijigua Express, which is similar in hull design to the General Dynamics Littoral Combat Ship (LCS) vessel, was investigated for motion‐induced interruptions, motion sickness, and biodynamic feed‐through to manual tasks. Data were obtained on two 2‐hour transits per day for a total of 86 transits during February and March 2006. Survey questionnaires were obtained from nearly 2,000 passengers. The motion effects on manual dexterity were negligible, but motion sickness symptoms were reported by a majority of the passengers. The capability to manage the motion sickness issue for unadapted passengers may be important for the effective use of LCS to transport ground combatants and for Sea Basing concepts.
Importance of Addressing Human Systems Integration Issues Early in the Science and Technology Process
Authors: WALLACE DANIEL F. , ROBERT BOST J. , THURBER JAMES B. , HAMBURGER PATRICIA S.
Published: October 2007

Historically, human systems integration (HSI) and other operational issues are not addressed during the science and technology (S&T) phase because the focus is on technology development. That view is to solve the “tough science” first, and the rest is simple application by a program office or operational forces. An imbalance between technology development efforts and total system performance considerations, e.g., total ownership cost, workload, manning, training, operational concept, skills, and human performance, leads to suboptimal solutions at best, and at worst prevents the technology's benefits from transitioning out of S&T at all. If HSI is not addressed during the S&T phase, the responsibility falls to the acquisition programs to ensure that operator, maintainer, and total system performance are optimized in the final design. By this point, cost and schedule constraints can make this prohibitive, limiting the options to either using a legacy system or accepting the technology with suboptimal performance and high life‐cycle costs (because design problems lead to manpower, training, and human error problems). However, if the S&T community uses HSI in their technology readiness level evaluation criteria, the Department of Defense can reduce its out‐year costs and recapitalize that funding to buy required weapons systems and platforms while still reaping the tactical benefits that a new technology offers.
Human Systems Integration in Education and Training: A Grassroots Effort to Obtain Total Systems Performance at an Affordable Cost
Authors: LINDBERG ROBERT M. , CARR LARRY A.
Published: October 2007

Human systems integration (HSI) requires highly qualified practitioners who can effectively and affordably integrate human capabilities into new and existing weapons systems. Over the past few years, Congressional support of National Defense Act (HR1522) for HSI continues as evident by this statement, “The committee recognizes HSI initiatives as a means for reducing total ownership costs of weapons programs, and continues to support efforts to more formally consider HSI issues earlier in the acquisition cycle.” To do so, organizations must focus attention within the Joint Capabilities Integration and Development System (CJCSI 3170.01) and the Department of Defense (DoD) acquisition framework (DoDI 5000.2) processes. More specifically, HSI practitioners center attention on total system performance by integrating trade‐offs within and across the HSI domains of manpower, personnel, training, human factors engineering, environment, safety, occupational health, survivability, and habitability. By conducting system‐level integration from concept inception to operational employment to eventual disposal, HSI practitioners can enable optimized total systems performance and reduce life‐cycle costs. Because very few qualified HSI practitioners are available and/or affordable, three critical ingredients need to be addressed: (1) greater demand for HSI as a result of better HSI requirements, (2) senior leadership and organizational motivation of subject matter experts to become HSI practitioners, and (3) availability of comprehensive education and training programs across the spectrum for new personnel to become HSI practitioners and existing practitioners to maintain proficiency and currency with changing technology. Education and training opportunities need to be cohesive and coherent across the spectrum of learning: initial qualification, continuing education, professional development, advanced credentials, and ultimately professional certification. These opportunities should be sufficient to create a near‐term DoD and industry certification standard and process that will support the growing demand for HSI in DoD systems acquisition and the industries that support the process.
Avoiding a Second Hollow Force: The Case for Including Crew Endurance Factors in the Afloat Staffing Policies of the US Navy
Authors: MILLER NITA LEWIS , FIREHAMMER ROBERT
Published: October 2007

In order to meet its obligations for prompt and sustained combat at sea, the US Navy relies on sailors to perform relentlessly while underway in highly stressful combat environments. The Navy currently uses an afloat staffing policy that is calculated using a 70‐hour workweek per sailor metric. However, this construct fails to factor in an individual sailor's capacity to sustain performance and is based instead on a notional Navy standard workweek. Part of the inadequacy of the current staffing policy results from its failure to consider an inviolable and basic physiological requirement for adequate sleep and rest for sailors. Research indicates a strong causal relationship between sleep and performance. When deprived of sleep, either chronically or acutely, human performance suffers in a dramatic and predictable manner. These performance decrements have even been equated to the effects of alcohol. If the US Navy is to deliver the combat capability demanded by our government and stated in Navy governing documents, sleep and rest requirements must be accounted for in staffing methodologies. To achieve full combat capability, the Navy must change its culture and adopt programs that promote crew endurance. Human system integration can provide a means to accomplish this goal.
Applying Human Systems Integration to the Rapid Acquisition Process
Authors: MACK DEMETRIUS D. , HIGGINS LEON A. , SHATTUCK LAWRENCE G.
Published: October 2007

The rapidly changing complexity of the Global War on Terrorism has changed the approach to equipping forward‐deployed military forces. Combatant Commanders conducting operations now require timely materiel solutions to enhance mission capabilities and reduce the risk for individual soldiers. To address this challenge, the US Army established the Rapid Equipping Force to assess emerging requirements, to propose solutions to those requirements, and to implement those solutions in an expedient time frame. Unfortunately, the REF lacks a consistent analytical methodology for assessing alternative materiel solutions. To address the need for a human systems integration (HSI) analysis method, the authors developed an Assessment‐Based Rapid Acquisition HSI Analysis Method (ABRAHAM) capable of generating tailored surveys and evaluating these surveys for unacceptable risks to soldiers. To validate ABRAHAM's concept and content, ABRAHAM was showcased in three Department of Defense settings: the Human Factors Engineering Technical Advisory Group, the REF, and the US Marine Corps' Operational Test and Evaluation Activity. The ABRAHAM appears to fill a gap in the current library of HSI tools. Based on the feedback provided during the product showcases, there is sufficient interest and technological maturity to further develop ABRAHAM to serve both the traditional and rapid acquisition processes.
A Human–Automation Interface Model to Guide Automation Design of System Functions
Authors: KENNEDY JOSHUA S. , McCAULEY MICHAEL E.
Published: October 2007

A major component of the US Army's Future Combat Systems (FCS) will be a fleet of eight different manned ground vehicles (MGV). There are promises that “advanced automation” will accomplish many of the tasks formerly performed by soldiers in legacy vehicle systems. However, the current approach to automation design does not relieve the soldier operator of tasks; rather, it changes the role of the soldiers and the work they must do, often in ways unintended and unanticipated. This paper proposes a coherent, top‐down, overarching approach to the design of a human–automation interaction model. First, a qualitative model is proposed to drive the functional architecture and human–automation interface scheme for the MGV fleet. Second, the proposed model is applied to a portion of the functional flow of the common crew station on the MGV fleet. Finally, the proposed model is demonstrated quantitatively via a computational task‐network modeling program (Improved Performance Research and Integration Tool). The modeling approach offers insights into the impacts on human task‐loading, workload, and human performance. Implications for human systems integration domains are discussed, including Manpower and Personnel, Human Factors Engineering, Training, System Safety, and Soldier Survivability. The proposed model gives engineers and scientists a top‐down approach to explicitly define and design the interactions between proposed automation schemes and the human crew. Although this paper focuses on the Army's FCS MGV fleet, the model and analytical processes proposed, or similar approaches, are appropriate for many manned systems in multiple domains (aviation, space, maritime, ground transportation, manufacturing, etc.).
The unfalsifiability of cladograms and its consequences
Authors: Vogt L.
Published: October 2007

Popper's falsificationism provides the normative reference system in recent discussions regarding theory and methodology of systematics. According to Popper, the falsifiability of a hypothesis represents a necessary precondition for its corroborability. It is shown that cladograms, independent of “strict”, “methodological” or “sophisticated” falsification, are not falsifiable in principle. No present observation is prohibited by any tree hypothesis and, thus, no Popperian test of cladograms exists. It is shown that the congruence test, which is commonly said to represent a Popperian test of cladograms, instead tests sets of apomorphy hypotheses. Three different strategies that have been proposed to circumvent this problem are discussed and refuted: (1) referring to Popper's convention to renouncead hocmaneuvers; (2) referring to Popper's treatment of probability hypotheses; and (3) decoupling corroboration from falsification. As a consequence, within a Popperian framework the unfalsifiability of cladograms implies that cladograms cannot explain any present day observation and, thus, represent metaphysical hypotheses.

However, Popper's falsificationism has been criticized and questioned by many philosophers before and it seems to be about time that phylogeneticists develop their own philosophy of phylogenetics that meets their specific requirements of a historical science that is not seeking for universal laws and regularities, but instead reconstructing particular historical events.

© The Willi Hennig Society 2007.
Phylogenetic placement of the Tasmanian spider Acrobleps hygrophilus (Araneae, Anapidae) with comments on the evolution of the capture web in Araneoidea
Authors: Lopardo Lara , Hormiga Gustavo
Published: October 2007

This paper studies the family‐level phylogenetic placement of the conflicting Tasmanian spider genus Acrobleps using both morphological and behavioral data. We also provide a formal taxonomic revision of Acrobleps, including information on its web architecture and natural history, as well as detailed morphological information for A. hygrophilus, its only species. Acrobleps hygrophilus lacks the typical mysmenid features. Furthermore A. hygrophilus does have all typical and diagnostic characteristics of Anapidae, except for the labral spur. We also discuss two noteworthy morphological features of Acrobleps: the pore bearing depressions of the carapace and the granulated cuticle of the spinnerets. Variation in the latter feature might provide a useful phylogenetic character. Based on the results of cladistic analyses we propose the transfer of Acrobleps from the Mysmenidae to its original placement within the Anapidae. We also propose a new lineage, informally labeled as the “clawless female clade”, which includes synaphrids, cyatholipids and “symphytognathoids.” The secondary absence of the female palpal claw provides support for the “clawless female clade.” We discuss the evolution of the orb web within anapids and other symphytognathoids based on the results of our cladistic analyses. The identical bi‐dimensional webs of the anapid Elanapis and of symphytognathids have evolved independently. Finally, we comment on the implications of one of our analyses regarding araneoid web evolution. We conclude that the taxon sample included in the previous orbicularian data matrix (modified and used in this study) is adequate to test the phylogenetic placement of Acrobleps in Anapidae but insufficient to significantly assess web evolution within Araneoidea.

© The Willi Hennig Society 2007.
Cladistic analysis of Echinodorus (Alismataceae): simultaneous analysis of molecular and morphological data
Authors: Lehtonen Samuli , Myllys Leena
Published: October 2007

Echinodorus is the second largest genus in the aquatic plant family Alismataceae. The genus is naturally distributed in the New World, but many species are known world‐wide as popular aquarium plants. The views upon species delimitation and infrageneric classification of the genus have been controversial. Phenotypic plasticity of aquatic plants combined with reduced and presumably convergent morphological structures pose serious problems to classification, emphasizing the need for molecular‐level data. A simultaneous cladistic analysis of molecular and morphological data was conducted to resolve the phylogeny of the genus. The results showed Echinodorus (as it is currently circumscribed) to be polyphyletic. None of the currently proposed infrageneric classifications of the genus were supported in the light of phylogenetic evidence. Also, many species and subspecies level rankings were found to be unnatural. Monophyly of Echinodorus is ascertained by separating Helanthium and the monotypic genus Albidella from Echinodorus. As a result, two new combinations (Helanthium bolivianum and H. zombiense) are made, and a detailed description of the genus Helanthium is provided.

© The Willi Hennig Society 2007.
Internal Audit Departments: Adoption and Characteristics in Italian Companies
Authors: Arena Marika , Azzone Giovanni
Published: October 2007

This article analyses the adoption and characteristics of internal audit departments in Italian companies, in the light of recent changes in the economic and political environment following the big financial scandals which occurred both in Italy and abroad. The research framework is informed by new institutional theory, driving the definition of a conceptual model. The research approach comprises two steps: first, a preliminary in‐depth case study to support the research design (assessment of relevant variables and questionnaire's construction); second, an extensive survey involving 364 Italian companies, with a response rate of 63%. The article highlights an actual diffusion of internal audit structures among Italian companies. Data collected show increasing attention towards internal audit activities, resources and competencies and highlight the relevance of isomorphic pressures in influencing companies' support of internal auditing.
Reporting Internal Control Deficiencies in the Post‐Sarbanes‐Oxley Era: The Role of Auditors and Corporate Governance
Authors: Krishnan Gopal V. , Visvanathan Gnanakumar
Published: October 2007

This study addresses the role of audit committees and auditors in the reporting of internal control deficiencies after the passage of the Sarbanes‐Oxley Act (SOX). We find that a higher number of meetings of the audit committee, lesser proportion of ‘financial experts’ in the audit committee, and more auditor changes characterize firms that report weaknesses in their internal controls compared to firms with no weaknesses. Prior restatements of financial statements are also higher for firms that report weaknesses in internal controls. These results obtain after controlling for a variety of firm characteristics such as complexity of operations, profitability, and growth. Our results underscore the importance of governance characteristics beyond general firm characteristics in examining the reporting of internal control weaknesses.
Meeting Challenges and Expectations of Continuous Auditing in the Context of Independent Audits of Financial Statements
Authors: Du Hui , Roohani Saeed
Published: October 2007

This paper proposes a continuous auditing model that provides external auditors the opportunity to audit clients continuously or on a more frequent basis while reducing the possibility of compromising auditor independence. The model requires the auditor's system to be separated from the auditee's system so that the two systems do not interfere with each other. The auditor's system must also communicate smoothly and effectively with the auditee's system to continuously process data captured from that system. We show how the new technology using XML (eXtensible Markup Language) and CORBA (Common Object Request Broker Architecture) can help effectively connect the auditor's system to the auditee's system, thereby supporting smooth communication between the two independent systems. We also introduce the concept of continuous auditing cycle, which helps define the engagement period between client and auditor and makes the audit within each cycle continuous.
Molecular analysis of the pathophysiological binding of the platelet aggregation‐inducing factor podoplanin to the C‐type lectin‐like receptor CLEC‐2
Authors: Kato Yukinari , Kaneko Mika Kato , Kunita Akiko , Ito Hiromi , Kameyama Akihiko , Ogasawara Satoshi , Matsuura Nana , Hasegawa Yasushi , Suzuki‐Inoue Katsue , Inoue Osamu , Ozaki Yukio , Narimatsu Hisashi
Published: October 2007

The mucin‐type sialoglycoprotein podoplanin (aggrus) is involved in tumor cell‐induced platelet aggregation and tumor metastasis. C‐type lectin‐like receptor‐2 (CLEC‐2) was recently identified as an endogenous receptor of podoplanin on platelets. However, the pathophysiological importance and function of CLEC‐2 have not been elucidated. Here we clarified the pathophysiological interaction between podoplanin and CLEC‐2 in vitro and in vivo. Using several deletion mutants of CLEC‐2 expressed as Fc chimeras, we first identified an important podoplanin‐recognition domain in CLEC‐2. Furthermore, the podoplanin–CLEC‐2 interaction was confirmed using several deletion mutants of podoplanin expressed as Fc chimeras. Not only the disialyl‐core1‐attached glycopeptide but also the stereostructure of the podoplanin protein was found to be critical for the CLEC‐2‐binding activity of podoplanin. We next synthesized various glycopeptides of podoplanin that included both the platelet aggregation‐stimulating domain and O‐glycan on Thr52. Interestingly, a disialyl‐core1‐attached glycopeptide was recognized specifically by CLEC‐2. Moreover, the anti‐podoplanin monoclonal antibody NZ‐1 suppressed both the podoplanin–CLEC‐2 interaction and podoplanin‐induced pulmonary metastasis, suggesting that CLEC‐2 is the first pathophysiological receptor of podoplanin to be identified. In summary, we clarified the molecular interaction in vitro and in vivo between a platelet aggregation‐inducing factor, podoplanin, and its specific pathophysiological receptor on platelets, CLEC‐2. Podoplanin and CLEC‐2 might represent promising therapeutic targets in cancer metastasis. (Cancer Sci 2008; 99: 54–61)
Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology
Authors: Dores Graça M. , Anderson William F. , Curtis Rochelle E. , Landgren Ola , Ostroumova Evgenia , Bluhm Elizabeth C. , Rabkin Charles S. , Devesa Susan S. , Linet Martha S.
Published: October 2007

The 2001 World Health Organization classification scheme considers B‐cell chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in an aggregate category (CLL/SLL) because of shared clinicopathological features. We have estimated age‐adjusted incidence rates (IRs) of CLL and SLL in the population‐based Surveillance, Epidemiology and End Results Program in the United States to analyse patterns of CLL and SLL separately and jointly. Age‐standardized to the 2000 US population, overall IRs were 3·83 per 100 000 person‐years for CLL (n = 15 676) and 1·31 for SLL (n = 5382) during 1993–2004. Incidence of the combined entity, CLL/SLL, was 90% higher among males compared to females, and the male:female IR ratio was significantly higher for CLL (1·98) than for SLL (1·67). CLL/SLL IRs were 25% and 77% lower among Blacks and Asian/Pacific Islanders, respectively, compared to Whites. A significant reporting delay was evident for CLL but not for SLL, so that CLL/SLL temporal trends must be interpreted cautiously. CLL and SLL IRs increased exponentially with age among all gender/race groups, with CLL IRs increasing more steeply with advancing age than SLL. Avenues of future research include assessment of delayed‐ and under‐reporting to cancer registries and exploration of race, gender, and age effects in epidemiological studies.
B‐cell repertoire and clonal analysis in unaffected first degree relatives in familial chronic lymphocytic leukaemia kindred
Authors: Abbasi Fatima , Longo Nancy S. , Lipsky Peter E. , Raveche Elizabeth , Schleinitz Therese A. , Stetler‐Stevenson Maryalice , Caporaso Neil , Marti Gerald
Published: October 2007

Monoclonal B cell lymphocytosis (MBL) was detected in four unaffected first‐degree relatives (FDR) in a familial chronic lymphocytic leukaemia (CLL) kindred. The proband remains untreated and two male siblings have died. The four unaffected siblings have been followed for a five‐year period. All four FDR developed a kappa+CD5+ MBL detected by flow cytometry. Poymerase chain reaction (PCR) for IGHV rearrangement showed evidence of oligoclonality in three of these individuals. Single cell PCR of flow cytometric sorted kappa+ cells combined with Ig kappa light chain gene sequencing revealed further evidence of monoclonality in two of these individuals. Three of these individuals all showed evidence of hyper‐somatic mutations. The B‐cell repertoire in unaffected FDR in familial CLL offers a new area to investigate the interface between the immune system and lymphoid neoplasm.
Acquired immune‐related and inflammatory conditions and subsequent chronic lymphocytic leukaemia
Authors: Landgren Ola , Gridley Gloria , Check David , Caporaso Neil E. , Morris Brown Linda
Published: October 2007

Immune‐mediated pathways have been recognized to be of importance in the pathogenesis of chronic lymphocytic leukaemia (CLL). We assessed a broad variety of immune‐related and inflammatory conditions and subsequent CLL development among 4 million adult male veterans admitted to VA hospitals. We identified 3,680 CLL cases with up to 27 years of follow‐up. Using Poisson regression analyses restricted to immune‐related or inflammatory conditions that occurred more than one year before CLL, we estimated relative risk (RR) and 95% confidence intervals for CLL risk. Elevated CLL risk was found among individuals with prior chronic sinusitis (RR = 1·27, 1·01–1·61). Pneumonia had a borderline (RR = 1·13, 1·00–1·27) association with CLL; the risk was further elevated (RR = 1·35, 1·07–1·72) for latency <5 years. Conversely, chronic non‐rheumatic valvular heart disease was associated with 0·76‐fold (0·58–0·99) decreased risk. Herpes zoster and simplex were associated with increased (RR = 1·98, 1·40–2·79) and borderline increased (RR = 1·69, 0·96–2·98) CLL risk. There was no general association between autoimmunity and CLL; however, autoimmune haemolytic anaemia was associated with 3·86‐fold (1·93–7·74) elevated CLL risk. Individuals with chronic osteoarthritis and prostatitis had 1·14‐fold (1·03–1·25) and 1·64‐fold (1·14–2·37) elevated CLL risk. These association patterns suggest primary focus on infectious agents rather than autoantigens for future aetiologic CLL studies.