bluuebunny/crossref_metadata_2025 huggingface dataset:
Di(2‐ethylhexyl) phthalate (DEHP) [MAK Value Documentation, 2015]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the mechanism of action, the effects after inhalation, the toxicity to fertility, the genotoxicity and carcinogenicity of di(2‐ethylhexyl) phthalate (DEHP). The literature has been searched for new studies relevant to the evaluation of these endpoints. Prenatal toxicity is not included in this evaluation.

A MAK value of 2 mg/m
3
for the inhalable fraction has been calculated by toxicokinetic extrapolation from the lowest oral NOAEL of 3.7 mg DEHP/kg body weight and day (90‐day rat study). At the LOAEL (38 mg/kg body weight and day) vacuolization of Sertoli cells was observed. The MAK value is markedly below the NOAEC of 50 mg/m
3
in a 28‐day rat inhalation study. The larynx was not investigated in this study. Although it might have been a possible target organ, because the structurally related dibutyl phthalate caused low grade squamous metaplasia in the larynx, this effect is regarded as adaptive.

As systemic toxicity is critical, DEHP is classified in Peak Limitation Category II. The effects are more likely attributable to monoethylhexyl phthalate (MEHP) or its further metabolites. As the initial half‐life of MEHP of 1.9 hours is decisive for the peak concentrations in the blood, an excursion factor of 2 has been established.

DEHP induced hepatocellular adenomas and carcinomas in rats and mice, as well as tumours originating from the enterochromaffin cells of the stomach and from the acinar and islet cells of the pancreas. A new long term study with male rats confirms the data. Since the documentation from 2002 no new mechanistic data or genotoxicity studies have become available which call into question the previous carcinogenicity evaluation. The classification in Carcinogen Category 4 is therefore retained.

As available data for DEHP and its metabolites in vitro and in vivo do not provide any clear evidence of genotoxic effects, DEHP is not classified in one of the categories for germ cell mutagens.

Dermal absorption can provide a relevant contribution to systemic toxicity. DEHP is therefore designated with an “H”. The substance is not sensitising to skin or airways.
N‐Cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt [MAK Value Documentation, 2013]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. A gavage study with rats given daily doses of the substance for 3 months yielded a NOAEL of 25 mg/kg body weight and day; effects on the blood and liver and mortality occurred at 50 mg/kg body weight and day. Based on this NOAEL, a MAK value of 10 mg/m
3
has been established for the inhalable fraction of N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt. The MAK value was derived from a systemic NOAEL; therefore, N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt is classified in Peak Limitation Category II with a default excursion factor of 2 as sufficient toxicokinetic data are not available. Calculations of dermal absorption based on in vitro studies show that dermal absorption would contribute substantially to the systemic toxicity. Therefore, N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt has been designated with an “H”. N‐Cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt is not genotoxic or carcinogenic and limited data show no sensitizing potential in mice. Because there are no studies on developmental toxicity of N‐cyclohexylhydroxy‐diazene‐1‐oxide, potassium salt, it is assigned to Pregnancy Risk Group D.
Dimethylsulfoxid [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

Dimethyl sulfoxide

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration of dimethyl sulfoxide at the workplace (MAK value) of 50 ml/m
3
, considering the endpoints local and systemic toxicity as well as developmental toxicity. In a 13‐week inhalation study the olfactory and respiratory epithelia and the pharynx of rats were the target tissues, and reduction of body weight gain, possibly secondary to the irritation, was seen. The NOAEC for these effects is 964 mg/m
3
(297 ml/m
3
, vapour). Since 2014 the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, a MAK value of 50 ml/m
3
can be calculated from this study, taking into account that a lower NOAEC has to be expected with chronic exposure. Therefore, the previous MAK value is retained. As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 2 are retained. The borderline increase in incidences of pups with dilated renal pelvis seen in the developmental toxicity study was not confirmed in a screening study with rats according to OECD Test Guideline 421. However, in rabbits dimethyl sulfoxide causes kidney malformations with a NOAEL of 300 mg/kg bw. Therefore, damage to the embryo or foetus cannot be excluded even when the MAK value is observed and dimethyl sulfoxide is assigned to Pregnancy Risk Group B.
Multiple Ionization of Free Ubiquitin Molecular Ions in Extreme Ultraviolet Free‐Electron Laser Pulses
Authors: Schlathölter Thomas , Reitsma Geert , Egorov Dmitrii , Gonzalez‐Magaña Olmo , Bari Sadia , Boschman Leon , Bodewits Erwin , Schnorr Kirsten , Schmid Georg , Schröter Claus Dieter , Moshammer Robert , Hoekstra Ronnie
Published: July 2016

The fragmentation of free tenfold protonated ubiquitin in intense 70 femtosecond pulses of 90 eV photons from the FLASH facility was investigated. Mass spectrometric investigation of the fragment cations produced after removal of many electrons revealed fragmentation predominantly into immonium ions and related ions, with yields increasing linearly with intensity. Ionization clearly triggers a localized molecular response that occurs before the excitation energy equilibrates. Consistent with this interpretation, the effect is almost unaffected by the charge state, as fragmentation of sixfold deprotonated ubiquitin leads to a very similar fragmentation pattern. Ubiquitin responds to EUV multiphoton ionization as an ensemble of small peptides.
Developing evasive action‐based indicators for identifying pedestrian conflicts in less organized traffic environments
Authors: Tageldin Ahmed , Sayed Tarek
Published: July 2016

There has been a growing interest in using surrogate safety measures such as traffic conflicts to analyse road safety from a broader perspective than collision data alone. This growing interest has been aided by recent advances in automated video‐based traffic conflict analysis. The automation enables accurate calculation of various conflict indicators such as time‐to‐collision and post‐encroachment time. These indicators rely on road users getting within specific temporal and spatial proximity from each other and therefore assume that proximity is a surrogate for conflict severity. However, this assumption may not be valid in many driving environments where close interactions between road users are common. The objective of this paper is to investigate the applicability of time proximity conflict indicators for evaluating pedestrian safety in less‐organized traffic environments with a high mix of road users. Several alternative behavioural conflict indicators based on detecting pedestrian evasive actions are recommended to better measure traffic conflicts in such traffic environments. These indicators represent variations in the spatio‐temporal gait parameters (step length, step frequency and walk ratio) immediately before the conflict point. A highly congested shared intersection in Shanghai, China, with frequent pedestrian conflicts is used as a case study. Traffic conflicts are analysed with the use of automated video‐based analysis techniques. The results showed that evasive action‐based indicators have higher potential to identify pedestrian conflicts and measure their severity in high mix less organized traffic environments than time proximity measures such as time‐to‐collision and post‐encroachment time. Copyright © 2016 John Wiley & Sons, Ltd.
New Ways of Looking at Democracy
Authors: Hennig Brett
Published: July 2016

Dr. Brett Hennig is the cofounder and director of the Sortition Foundation (http://www.sortitionfoundation.org/). This is an edited extract from his new book, The End of Politicians, to be published by Unbound in late 2016 (https://unbound.co.uk/books/the‐end‐of‐politicians/).
Solidarity and Reciprocity Between People With and Without Disabilities
Authors: Bredewold Femmianne , Tonkens Evelien , Trappenburg Margo
Published: July 2016

Governments of contemporary welfare states call upon citizens to care for people with psychiatric or intellectual disabilities. This is deemed sensible and morally just. However, social–psychological theory suggests that stereotyping may stand in the way of engaging into contact. Sociological theory suggests that the giving of help is based on either balanced or generalized reciprocity. Balanced reciprocity depends on one's ability to ‘pay back’, which people with disabilities may have trouble doing. Generalized reciprocity depends on close social bonds, while people with disabilities often have fewer social bonds than other citizens. The current study aimed to find out whether citizens—despite socio‐psychological and sociological theories expecting otherwise—enter into supporting relationships with people with intellectual or psychiatric disabilities. Although we found socio‐psychological and sociological theory to be largely correct, we also found people to be more creative than theory assumes. A smile can be experienced as a return gift, thus including people with intellectual disabilities in the web of balanced reciprocity. Some people create new social bonds to include people with disabilities: they feel close to them because they had a job in the healthcare sector or because they had a family member with a disability. In disadvantaged neighbourhoods, recognition of each other's problems can create feelings of similarity and concomitant reciprocity. Copyright © 2016 John Wiley & Sons, Ltd.
Iridoid Glycosides from Tabebuia avellanedae
Authors: Suo Mao‐Rong , Yan Sheng‐Ying
Published: July 2016

Five novel iridoid glycosides, avellanedaesides A‐E (1 – 5) were isolated from the H2O extract of Tabebuia avellanedae. Their structures were determined on the basis of NMR and MS analysis. Isolated compounds suppressed inflammatory cytokine, tumor‐necrosis factor‐α and interleukin‐1β production in cultured human myeloma THP‐1 cells co‐stimulated with lipopolysaccharide (LPS). In addition, the study revealed iridoid glycosides inhibited the activity of cytochrome CYP3A4 enzyme.
Diversification of ortho‐Fused Cycloocta‐2,5‐dien‐1‐one Cores and Eight‐ to Six‐Ring Conversion by σ Bond C−C Cleavage
Authors: Eccleshare Lee , Lozada‐Rodríguez Leticia , Cooper Phillippa , Burroughs Laurence , Ritchie John , Lewis William , Woodward Simon
Published: July 2016

Sequential treatment of 2‐C6H4Br(CHO) with LiC≡CR1 (R1=SiMe3, tBu), nBuLi, CuBr⋅SMe2 and HC≡CCHClR2 [R2=Ph, 4‐CF3Ph, 3‐CNPh, 4‐(MeO2C)Ph] at −50 °C leads to formation of an intermediate carbanion (Z)‐1,2‐C6H4{CA(=O)C≡CBR1}{CH=CH(CH−)R2} (4). Low temperatures (−50 °C) favour attack at CB leading to kinetic formation of 6,8‐bicycles containing non‐classical C‐carbanion enolates (5). Higher temperatures (−10 °C to ambient) and electron‐deficient R2 favour retro σ‐bond C−C cleavage regenerating 4, which subsequently closes on CA providing 6,6‐bicyclic alkoxides (6). Computational modelling (CBS‐QB3) indicated that both pathways are viable and of similar energies. Reaction of 6 with H+ gave 1,2‐dihydronaphthalen‐1‐ols, or under dehydrating conditions, 2‐aryl‐1‐alkynylnaphthlenes. Enolates 5 react in situ with: H2O, D2O, I2, allylbromide, S2Me2, CO2 and lead to the expected C‐E derivatives (E=H, D, I, allyl, SMe, CO2H) in 49–64 % yield directly from intermediate 5. The parents (E=H; R1=SiMe3, tBu; R2=Ph) are versatile starting materials for NaBH4 and Grignard C=O additions, desilylation (when R1=SiMe) and oxime formation. The latter allows formation of 6,9‐bicyclics via Beckmann rearrangement. The 6,8‐ring iodides are suitable Suzuki precursors for Pd‐catalysed C−C coupling (81–87 %), whereas the carboxylic acids readily form amides under T3P® conditions (71–95 %).
Delirium frequency among advanced cancer patients presenting to an emergency department: A prospective, randomized, observational study
Authors: Elsayem Ahmed F. , Bruera Eduardo , Valentine Alan D. , Warneke Carla L. , Yeung Sai‐Ching J. , Page Valda D. , Wood Geri L. , Silvestre Julio , Holmes Holly M. , Brock Patricia A. , Todd Knox H.
Published: July 2016

BACKGROUND

The frequency of delirium among patients with cancer presenting to the emergency department (ED) is unknown. The purpose of this study was to determine delirium frequency and recognition by ED physicians among patients with advanced cancer presenting to the ED of The University of Texas MD Anderson Cancer Center.

METHODS

The study population was a random sample of English‐speaking patients with advanced cancer who presented to the ED and met the study criteria. All patients were assessed with the Confusion Assessment Method (CAM) to screen for delirium and with the Memorial Delirium Assessment Scale (MDAS) to measure delirium severity (mild, ≤15; moderate, 16‐22; and severe, ≥23). ED physicians were also asked whether their patients were delirious.

RESULTS

Twenty‐two of the 243 enrolled patients (9%) had CAM‐positive delirium, and their median MDAS score was 14 (range, 9‐21 [30‐point scale]). The median age of the enrolled patients was 62 years (range, 19‐89 years). Patients with delirium had a poorer performance status than patients without delirium (P < .001); however, the 2 groups did not differ in other characteristics. Ten of the 99 patients who were 65 years old or older (10%) had CAM‐positive delirium, whereas 12 of the 144 patients younger than 65 years (8%) did (P = .6). According to the MDAS scores, delirium was mild in 18 patients (82%) and moderate in 4 patients (18%). Physicians correctly identified delirium in 13 of the CAM‐positive delirious patients (59%).

CONCLUSIONS

Delirium is relatively frequent and is underdiagnosed by physicians in patients with advanced cancer who are visiting the ED. Further research is needed to identify the optimal screening tool for delirium in ED. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2918–2924. © 2016 American Cancer Society
Autoantibodies to post‐translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus
Authors: Rizzo Paola , Pitocco Dario , Zaccardi Francesco , Di Stasio Enrico , Strollo Rocky , Rizzi Alessandro , Scavone Giuseppe , Costantini Federica , Galli Marco , Tinelli Giovanni , Flex Andrea , Caputo Salvatore , Pozzilli Paolo , Landolfi Raffaele , Ghirlanda Giovanni , Nissim Ahuva
Published: July 2016

Aims

Charcot neuroarthropathy (CN) is a disabling complication, culminating in bone destruction and involving joints and articular cartilage with high inflammatory environment. Its real pathogenesis is as yet unknown. In autoinflammatory diseases, such as rheumatoid arthritis, characterized by inflammation and joint involvement, autoantibodies against oxidative post‐translationally modified (oxPTM) collagen type I (CI) and type II (CII) were detected. Therefore, the aim of our study was to assess the potential involvement of autoimmunity in charcot neuroarthropathy, investigating the presence of autoantibodies oxPTM‐CI and oxPTM‐CII, in participants with charcot neuroarthropathy.

Methods

In this case‐control study, we enrolled 124 participants with type 2 diabetes mellitus (47 with charcot neuroarthropathy, 37 with diabetic peripheral neuropathy without charcot neuroarthropathy, and 40 with uncomplicated diabetes), and 32 healthy controls. The CI and CII were modified with ribose and other oxidant species, and the modifications were evaluated with sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Binding of sera from the participants was analyzed with enzyme‐linked immunosorbent assay.

Results

Age, body mass index, waist and hip circumferences, and lipid profile were similar across the 4 groups, as well as glycated hemoglobin and duration of diabetes among people with diabetes. An increased binding to both native and all oxidation‐modified forms of CII was found in participants with CN and diabetic neuropathy. Conversely, for CI, an aspecific increased reactivity was noted.

Conclusions

Our results detected the presence of autoantibodies against oxidative post‐translational modified collagen, particularly type 2 collagen, in participants with charcot neuroarthropathy and diabetic neuropathy, suggesting the possible involvement of autoimmunity. Further studies are required to understand the role of autoimmunity in the pathogenesis of charcot neuroarthropathy.
Adiponectin protects against incident hypertension independent of body fat distribution: observations from the Dallas Heart Study
Authors: Peri‐Okonny Poghni A. , Ayers Colby , Maalouf Naim , Das Sandeep R. , de Lemos James A. , Berry Jarett D. , Turer Aslan T. , Neeland Ian J. , Scherer Philipp E. , Vongpatanasin Wanpen
Published: July 2016

Background

Excess adipose tissue has been implicated in the pathogenesis of insulin resistance and atherosclerosis and is a key risk factor for blood pressure (BP) elevation. However, circulating levels of adiponectin, a protein produced by adipose tissue and widely implicated in the pathogenesis of insulin resistance and atherosclerosis, are inversely proportional to adiposity. The relationship between adiponectin and incident hypertension has not been determined in the general US population.

Methods

Normotensive participants (n = 1233) enrolled in the Dallas Heart Study, a multiethnic, probability‐based population sample of Dallas County adults were followed for median of 7 years. Retroperitoneal, intraperitoneal, visceral, and subcutaneous adipose tissue were measured at baseline by magnetic resonance imaging. Liver fat content was measured by 1H‐magnetic resonance spectroscopy. Relative risk regression was used to determine the association of adiponectin with incident hypertension after adjustment for age, race, sex, BMI, smoking, diabetes, baseline systolic BP, total cholesterol, and regional fat depot.

Results

Of the 1233 study participants (median age 40 years, 40% black, and 56% women), 391 (32%) had developed hypertension over a median follow‐up of 7 years. Adiponectin levels were associated with reduced risk of incident hypertension (RR 0.81, 95% CI [0.68‐0.96]) in the fully adjusted model, which included liver fat. Similar results were observed after adjustment for subcutaneous or visceral fat depots when tested individually or simultaneously in the model.

Conclusion

Our study suggested a protective role of adiponectin against incident hypertension independent of body fat distribution.
Highly Selective and Modular Synthesis of 3‐Aryl‐4‐(arylethynyl)‐2H‐chromen‐2‐ones from 2‐Iodoaryl 2‐Arylacetates through a Carbonylative Sonogashira Coupling–Intramolecular Aldol Cascade Reaction
Authors: Chandrasekhar Attoor , Ramkumar Venkatachalam , Sankararaman Sethuraman
Published: July 2016

A modular method for the synthesis of 3‐aryl‐4‐(arylethynyl)‐2H‐chromen‐2‐ones from 2‐iodoaryl 2‐arylacetates and arylacetylenes has been developed. The carbonylative Sonogashira coupling–intramolecular aldol casade reaction was carried out in the presence of Pd(PPh3)2(Cl)2 as the catalyst. The one‐pot approach that involves the in situ formation of the 2‐iodoaryl 2‐arylacetates from the corresponding 2‐iodophenols and 2‐arylacetyl chlorides followed by the palladium‐catalyzed carbonylative annulation in the presence of the arylacetylene has also been described for the formation of the 3‐aryl‐4‐(arylethynyl)‐2H‐chromen‐2‐ones.
Stereoretentive H/D Exchange via an Electroactivated Heterogeneous Catalyst at sp3 C–H Sites Bearing Amines or Alcohols
Authors: Bhatia Souful , Spahlinger Greg , Boukhumseen Nehal , Boll Quentin , Li Zhenglong , Jackson James E.
Published: July 2016

This report describes a mild, aqueous‐phase strategy that enables stereoretentive C–H activation at sp3 C–H sites bearing amine or alcohol groups. The transformation utilizes D2O to replace the hydrogen with deuterium while retaining stereochemistry. Electroactivated ruthenium particles, which are supported by an activated carbon cloth (Ru/ACC), catalyze this reaction on a timescale of minutes to hours. This yields optimal results at low current density and mild temperature.
Sensitive Electroanalytical Detection on GCE: the Case of Lipoic Acid and its Interaction with N‐acetylcysteine and Glutathione
Authors: Santos Ana Caroline F. , Moura Fabiana A. , Tanaka Auro A. , Luz Rita C. S. , Damos Flavio S. , Kubota Lauro T. , Goulart Marilia O. F.
Published: July 2016

A simple and sensitive electrochemical method was developed for the determination of N‐Acetylcysteine (NAC) and Glutathione (GSH), on glassy carbon electrode. The results indicate that α‐lipoic acid (LipS2) is oxidized at the electrode, but is regenerated by thiols, suggesting a redox catalytic effect. Under optimized conditions, the analytical curves for NAC and GSH were obtained in the range of 1 up to 10 µM and 1 up to 60 µM, respectively. The quantification can be performed in a single assay with high sensitivity, reproducibility and low detection limit of 0.27 and 0.67 µM for NAC and GSH, respectively. This method was successfully applied to the determination of NAC and GSH in artificial saliva and human urine samples, with excellent recovery results.
Altered anterior‐posterior connectivity through the arcuate fasciculus in temporal lobe epilepsy
Authors: Takaya Shigetoshi , Liu Hesheng , Greve Douglas N. , Tanaka Naoaki , Leveroni Catherine , Cole Andrew J. , Stufflebeam Steven M.
Published: July 2016

How the interactions between cortices through a specific white matter pathway change during cognitive processing in patients with epilepsy remains unclear. Here, we used surface‐based structural connectivity analysis to examine the change in structural connectivity with Broca's area/the right Broca's homologue in the lateral temporal and inferior parietal cortices through the arcuate fasciculus (AF) in 17 patients with left temporal lobe epilepsy (TLE) compared with 17 healthy controls. Then, we investigated its functional relevance to the changes in task‐related responses and task‐modulated functional connectivity with Broca's area/the right Broca's homologue during a semantic classification task of a single word. The structural connectivity through the AF pathway and task‐modulated functional connectivity with Broca's area decreased in the left midtemporal cortex. Furthermore, task‐related response decreased in the left mid temporal cortex that overlapped with the region showing a decrease in the structural connectivity. In contrast, the region showing an increase in the structural connectivity through the AF overlapped with the regions showing an increase in task‐modulated functional connectivity in the left inferior parietal cortex. These structural and functional changes in the overlapping regions were correlated. The results suggest that the change in the structural connectivity through the left frontal–temporal AF pathway underlies the altered functional networks between the frontal and temporal cortices during the language‐related processing in patients with left TLE. The left frontal–parietal AF pathway might be employed to connect anterior and posterior brain regions during language processing and compensate for the compromised left frontal–temporal AF pathway. Hum Brain Mapp 37:4425–4438, 2016. © 2016 Wiley Periodicals, Inc.
OH, THE HUMANITY! THE CONTROL SIDE OF SYSTEM SECURITY
Authors: Narkevicius J. M. , Harris S. D.
Published: July 2016

In 1951, Fitts observed that humans are better than machines at inductive reasoning while machines excel at deductive reasoning. Meanwhile, system security users' needs unrepresented in design, require high‐load deductive tasks such as unaided recall of passwords. The purpose of system security is to control access; therefore, security should be approached from the perspective of control theory. Intelligent control theory incorporates critical components of security and structures the diagnostic process in the form of a logical induction. A control theoretic perspective that purports to apply to system security must account for induction in the control loop and automation is often proposed for these solutions. But, there are no fully automated systems. Human users are components of a control process. Modern security systems are almost exclusively logical systems, have hybrid intelligence (hybridized from users and software) and exhibit Emergent Behaviors (EB) that cannot be known a priori. Emergence in complex systems is readily apparent in most failures and frequently labeled latent human error. Human‐system integration‐induced EB must be accounted for because as a source of major vulnerability. The only viable strategy is suggested by control theory and incorporates embedded simulation as a critical component. A human‐centered design perspective is required.
YOUR FUTURE AT RISK – ARE YOU PREPARED?
Authors: deLamare Michael , Walker Loren Mark , Juhasz John
Published: July 2016

Critical infrastructures are highly vulnerable to a variety of threat scenarios. Three specific threats are known to endanger critical infrastructure so pervasively that a large‐scale incident could make vital services unavailable for a period of a month or more — possibly much more. These threats include Electro‐Magnetic Pulse (EMP) weapons, Geo‐Magnetic Disturbances (GMD) and cyber incidents in information technology and industrial control systems. These threats, sometimes referred to as the “triple threats” can cause damage from regional to continental or even global scales such that obtaining help from neighboring regions is unlikely since all neighboring regions may be equally and significantly damaged. The seriousness of the threats are so severe, as the EMP Commission reported to the US Congress that power outages could last a year or more, resulting in substantial loss of life. Let that warning sink in for a moment. Agile system principles evolved via INCOSE methods and other organizations are considered instrumental in planning for resiliency and recovery from catastrophic events. Agile systems use multiple independent encapsulated modules as the principle system components. Each module is highly cohesive internally, loosely coupled with the other modules, yet they cooperate toward a shared common purpose. These principles would be applicable to social units of organization during a recovery process, and are considered a vital step in contingency pre‐planning for such threat scenarios. This article provides background on the triple threats and explores the application of specific core agile principles applied to social organizing for achieving resiliency.
AGILE VETTING OF AUTONOMOUS SYSTEMS
Authors: Ring Jack
Published: July 2016

Autonomous systems are already coping with complex, unpredictable situations. Some of these are raising red flags about unanticipated behaviors and unintended consequences (Miley 2015). Systems engineering practitioners must respond with new ways and means for creating and vetting autonomous systems. Systems have become so complex that most of their caretakers do not understand them. This means the system must be protected not only from cyber attacks by others but also from its own caretakers. Eventually every new line of code introduced into a system must be considered a cyber attack until proven otherwise. This article explores the challenges in vetting autonomous systems for sustainable system life, and offers a checklist for agile vetting throughout the lifecycle.
SYSTEMS SECURITY ENGINEERING: WHOSE JOB IS IT ANYWAY?
Authors: Nejib Perri , Beyer Dawn
Published: July 2016

This article delivers a look at current and evolving policy, guidance, and standards surrounding security activities in the systems engineering lifecycle. Emphasis is placed on systems security engineering (SSE) and how application of systems engineering concepts and processes in an agile manner (agile systems engineering) throughout the lifecycle is the way to deal with the dynamic and diverse world of cyber threats to a system (Dove 2014). This paper is a follow‐on to “Response to Cyber Security Demands for Agility” (Nejib‐Beyer 2014) published in the International Council on Systems Engineering (INCOSE) INSIGHT in 2014. The focus of that research was bringing attention to cyber security and the importance of other disciplines towards contributing to secure systems. Since that time many of these domains have further developed their own standards, processes, and guidance in the area of cyber security. What we require now is a way to take these domain‐focused concepts and integrate them into and across a systems lifecycle. The best way to achieve this is as part of the systems engineering function. Designing and building secure systems requires a seamless integration of security into systems engineering processes and agile methodologies adopted to constantly revisit, reevaluate, and re‐design as part of a risk management process. The framework that will be discussed in this paper will focus on taking currently evolving guidance in SSE and breaking that down into products and tools for systems engineers to easily determine the relationship and value between SSE and systems engineering. In addition, quick reference guides will further enhance and enable successful development and integration of SSE artifacts into systems engineering artifacts. One of the companion pieces needed in the existing SSE documentation is a mapping of work products/artifacts generated during the lifecycle/technical processes and the responsible and contributing parties. Critical to the success of the new guidance, such as the National Institute of Standards and Technology (NIST) Special Publication (SP) 800‐160, Systems Security Engineering, is a clear accountability and acceptance of all disciplines on their contributions and influence towards developing a secure system. We present an SSE roles and responsibilities framework concept for consideration. The framework is an implementation tool to be used along with existing guidance in the area of SSE and systems engineering to clearly demonstrate that program protection is not the responsibility of any one person or discipline, it is the responsibility of an entire team of individuals planning, developing, deploying, operating & maintaining (O&M), and retiring a system. SSE is the “glue” that binds all of this together during the systems engineering lifecycle to enhance system security.
A FOUNDATION FOR DEVELOPING SUSTAINABLY SECURE SYSTEMS
Authors: Khou Stephen , Mailloux Logan O. , McEvilley Michael
Published: July 2016

This article is intended to introduce and familiarize systems engineers with ongoing developments in the field of systems security engineering and particularly the effort to develop NIST Special Publication 800‐160 Systems Security Engineering, which provides security considerations for engineering trustworthy secure systems.
A compact fiber‐optic probe‐based singlet oxygen luminescence detection system
Authors: Gemmell Nathan R. , McCarthy Aongus , Kim Michele M. , Veilleux Israel , Zhu Timothy C. , Buller Gerald S. , Wilson Brian C. , Hadfield Robert H.
Published: July 2016

This paper presents a novel compact fiberoptic based singlet oxygen near‐infrared luminescence probe coupled to an InGaAs/InP single photon avalanche diode (SPAD) detector. Patterned time gating of the single‐photon detector is used to limit unwanted dark counts and eliminate the strong photosensitizer luminescence background. Singlet oxygen luminescence detection at 1270 nm is confirmed through spectral filtering and lifetime fitting for Rose Bengal in water, and Photofrin in methanol as model photosensitizers. The overall performance, measured by the signal‐to‐noise ratio, improves by a factor of 50 over a previous system that used a fiberoptic‐coupled superconducting nanowire single‐photon detector. The effect of adding light scattering to the photosensitizer is also examined as a first step towards applications in tissue in vivo.

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The nature of structure and bonding between transition metal and mixed Si‐Ge tetramers: A 20‐electron superatom system
Authors: Li Xiaojun , Yan Zhijun , Li Shuna
Published: July 2016

A novel superatom species with 20‐electron system, SixGeyM+ (x + y = 4; M = Nb, Ta), was properly proposed. The trigonal bipyramid structures for the studied systems were identified as the putative global minimum by means of the density functional theory calculations. The high chemical stability can be explained by the strong p‐d hybridization between transition metal and mixed Si‐Ge tetramers, and closed‐shell valence electron configuration [1S21P62S21D10]. Meanwhile, the chemical bondings between metal atom and the tetramers can be recognized by three localized two‐center two‐electron (2c‐2e) and delocalized 3c‐2e σ‐bonds. For all the doped structures studied here, it was found that the π‐ and σ‐electrons satisfy the 2(N + 1)2 counting rule, and thus these clusters possess spherically double (π and σ) aromaticity, which is also confirmed by the negative nucleus‐independent chemical shifts values. Consequently, all the calculated results provide a further understanding for structural stabilities and electronic properties of transition metal‐doped semiconductor clusters. © 2016 Wiley Periodicals, Inc.
Cytoskeleton Aberrations in Alkaptonuric Chondrocytes
Authors: Geminiani Michela , Gambassi Silvia , Millucci Lia , Lupetti Pietro , Collodel Giulia , Mazzi Lucia , Frediani Bruno , Braconi Daniela , Marzocchi Barbara , Laschi Marcella , Bernardini Giulia , Santucci Annalisa
Published: July 2016

Alkaptonuria (AKU) is an ultra‐rare autosomal genetic disorder caused by a defect in the activity of the enzyme homogentisate 1,2‐dioxygenase (HGD) that leads to the accumulation of homogentisic acid (HGA) and its oxidized product, benzoquinone acetic acid (BQA), in the connective tissues causing a pigmentation called “ochronosis.” The consequent progressive formation of ochronotic aggregates generate a severe condition of oxidative stress and inflammation in all the affected areas. Experimental evidences have also proved the presence of serum amyloid A (SAA) in several AKU tissues and it allowed classifying AKU as a secondary amyloidosis. Although AKU is a multisystemic disease, the most affected system is the osteoarticular one and articular cartilage is the most damaged tissue. In this work, we have analyzed for the first time the cytoskeleton of AKU chondrocytes by means of immunofluorescence staining. We have shown the presence of SAA within AKU chondrocytes and finally we have demonstrated the co‐localization of SAA with three cytoskeletal proteins: actin, vimentin, and β‐tubulin. Furthermore, in order to observe the ultrastructural features of AKU chondrocytes we have performed TEM analysis, focusing on the Golgi apparatus structure and, to demonstrate that pigmented areas in AKU cartilage are correspondent to areas of oxidation, 4‐HNE presence has been evaluated by means of immunofluorescence. J. Cell. Physiol. 232: 1728–1738, 2017. © 2016 Wiley Periodicals, Inc.
Sex Differences in Pain
Authors: Sorge Robert E. , Totsch Stacie K.
Published: July 2016

Females greatly outnumber males as sufferers of chronic pain. Although social and psychological factors certainly play a role in the differences in prevalence and incidence, biological differences in the functioning of the immune system likely underlie these observed effects. This Review examines the current literature on biological sex differences in the functioning of the innate and adaptive immune systems as they relate to pain experience. With rodent models, we and others have observed that male mice utilize microglia in the spinal cord to mediate pain, whereas females preferentially use T cells in a similar manner. The difference can be traced to differences in cell populations, differences in suppression by hormones, and disparate cellular responses in males and females. These sex differences also translate into human cellular responses and may be the mechanism by which the disproportionate chronic pain experience is based. Recognition of the evidence underlying sex differences in pain will guide development of treatments and provide better options for patients that are tailored to their physiology. © 2016 Wiley Periodicals, Inc.
Assessing the uncertainty of CESM‐LE in simulating the trends of mean and extreme temperature and precipitation over China
Authors: Li Juan , Zhu Zhiwei , Dong Wenjie
Published: July 2016

Climate change affects mean and extreme temperature and precipitation, increasing the risk of related disasters. Assessing the performance of current models in simulating these aspects is therefore crucial to future projection and policymaking. Based on a large ensemble (LE; 30 members) of the Community Earth System Model (CESM‐LE), this study seeks to answer the following two questions: (1) Are the simulated trends of mean and extreme temperature and precipitation over China consistent with observations? (2) What is the range of model uncertainty due to internal variability? The results show that CESM‐LE can capture the trends of observed annul mean temperature and extremely low temperature days (ELD) over 16–26% of China, but has difficulty in reproducing the observed trends in extremely high temperature days (EHD). For precipitation, CESM‐LE demonstrates similar capability in reproducing the observed trends in annual mean precipitation and extreme precipitation days (EPD). For consecutive dry days (CDD), the decreasing trends over part of northwestern China can be captured, but the increasing trends over northern China cannot be reproduced by CESM‐LE. Regarding the uncertainty of the model resulting from natural internal variability, because all 30 ensemble members of CESM use the same model and external forcing, CESM‐LE's spread (uncertainty) is mainly due to internal variability. Larger uncertainty in simulated trends is found over northern China and the Tibetan Plateau for annual mean temperature, over northeastern China and the Huang‐Huai region for ELD, and over the Tibetan Plateau for EHD. The trends in annual mean precipitation show uniform uncertainty over nearly all of China, except for the northwest. Larger uncertainty trends appear over southern and northwestern China for EPD, and over the Tibetan Plateau and northern China for CDD.
Asymptotic behavior of solutions to a class of nonlinear wave equations of sixth order with damping
Authors: Wang Yu‐Zhu , Wang Yinxia
Published: July 2016

We investigate the initial value problem for a class of nonlinear wave equations of sixth order with damping. The decay structure of this equation is of the regularity‐loss type, which causes difficulty in high‐frequency region. By using the Fourier splitting frequency technique and energy method in Fourier space, we establish asymptotic profiles of solutions to the linear equation that is given by the convolution of the fundamental solutions of heat and free wave equation. Moreover, the asymptotic profile of solutions shows the decay estimate of solutions to the corresponding linear equation obtained in this paper that is optimal under some conditions. Finally, global existence and optimal decay estimate of solutions to this equation are also established. Copyright © 2016 John Wiley & Sons, Ltd.
High efficiency coronary MR angiography with nonrigid cardiac motion correction
Authors: Pang Jianing , Chen Yuhua , Fan Zhaoyang , Nguyen Christopher , Yang Qi , Xie Yibin , Li Debiao
Published: July 2016

Purpose

To improve the coronary visualization quality of four‐dimensional (4D) coronary MR angiography (MRA) through cardiac motion correction and iterative reconstruction.

Methods

A contrast‐enhanced, spoiled gradient echo sequence with 3D radial trajectory and self‐gating was used for 4D coronary MRA data acquisition at 3 Tesla. A whole‐heart 16‐phase cine series was reconstructed with respiratory motion correction. Nonrigid registration was performed between the identified quiescent phases and a reference. The motion information of all included phases was then used along with the corresponding k‐space data to iteratively reconstruct the final image. Healthy volunteer studies (N = 13) were conducted to compare the proposed method with the conventional strategy, which accepts data from a single, contiguous window out of the original 16‐phase data. Apparent signal‐to‐noise ratio (aSNR) and coronary sharpness were used as the image quality metrics.

Results

The proposed method significantly improved aSNR (11.89 ± 3.76 to 13.97 ± 5.21; P = 0.005) and scan efficiency (18.8% ± 6.0% to 40.9% ± 9.7%; P < 0.001), compared with the conventional strategy. Sharpness of left main (P = 0.002), proximal (P = 0.04), and middle (P = 0.02) right coronary artery, and proximal left anterior descending (P = 0.04) was also significantly improved.

Conclusion

The proposed cardiac motion‐corrected reconstruction significantly improved the achievable quality of coronary visualization from 4D coronary MRA. Magn Reson Med 76:1345–1353, 2016. © 2016 International Society for Magnetic Resonance in Medicine
Test–retest analysis of multiple 31P magnetization exchange pathways using asymmetric adiabatic inversion
Authors: Pouymayou Bertrand , Buehler Tania , Kreis Roland , Boesch Chris
Published: July 2016

Purpose

A 31P‐MR inversion transfer (IT) method with a short adiabatic inversion pulse is proposed and its test–retest reliability was evaluated for two spectral fitting strategies.

Methods

Assessment in a test–retest design (3 Tesla, vastus muscles, 12 healthy volunteers, 14 inversion times, 22 ms asymmetric adiabatic inversion pulse, adiabatic excitation); spectral fitting in Fitting Tool for Interrelated Arrays of Datasets (FitAID) and Java Magnetic Resonance User Interface (jMRUI); least squares solution of the Bloch‐McConnell‐Solomon matrix formalism including all 14 measured time‐points with equal weighting.

Results

The cohort averages of k[PCr→γ‐ATP] (phosphocreatine, PCr; adenosine triphosphate, ATP) are 0.246 ± 0.050s−1 versus 0.254 ± 0.050s−1, and k[Pi→γ‐ATP] 0.086 ± 0.033s−1 versus 0.066 ± 0.034s−1 (average ± standard deviation, jMRUI versus FitAID). Coefficients of variation of the differences between test and retest are lowest (9.5%) for k[PCr→γ‐ATP] fitted in FitAID, larger (15.2%) for the fit in jMRUI, and considerably larger for k[Pi→γ‐ATP] fitted in FitAID (43.4%) or jMRUI (47.9%). The beginning of the IT effect can be observed with magnetizations above 92% for noninverted lines while inversion of the ATP resonances is better than −72%.

Conclusion

The performance of the asymmetric adiabatic pulse allows an accurate observation of IT effects even in the early phase; the least squares fit of the Bloch‐McConnell‐Solomon matrix formalism is robust; and the type of spectral fitting can influence the results significantly. Magn Reson Med 78:33–39, 2017. © 2016 International Society for Magnetic Resonance in Medicine
In Brief: Mitophagy: mechanisms and role in human disease
Authors: Springer Maya Z , Macleod Kay F
Published: July 2016

Mitophagy is a selective form of macro‐autophagy in which mitochondria are specifically targeted for autophagic degradation. Mitophagy plays an important role in cellular homeostasis by eliminating dysfunctional mitochondria and reducing mitochondrial mass as an adaptive response to stress. Cells execute mitophagy through several non‐redundant mechanisms, including the PINK1/Parkin partnership, which modulates turnover of depolarized mitochondria, and stress‐induced BNIP3, NIX, and FUNDC1 molecular adaptors, which interact directly with LC3 to promote mitophagy. These pathways are deregulated in human diseases, including cancer, neurodegeneration, metabolic disorders, muscle atrophy, ageing, and inflammation, reflecting the importance of mitophagy as a cellular housekeeping function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The stability and dielectric performance of BiNbO4 prepared by citrate method assisting sintering process
Authors: Zhai Haifa , Chen Bei , Luo Hongying , Li Haiqin , Zheng Liuyang , Yang Jien , Liu Hairui , Liu Zhiyong
Published: July 2016

Low‐temperature β phase BiNbO4 powders (denoted as Low‐β) were prepared by a citrate method using home‐made water‐soluble niobium precursors. The stability of Low‐β was systematically investigated from the aspects including calcination temperature, incubation time, and stress existing in pellets. Pure Low‐β can be obtained between 700 and 750 °C and the crystal evolution of Low‐β has not completed yet, compared with high‐temperature β phase. Low‐β is kinetically stable and no phase transition occurs when increasing the incubation time below 750 °C. Above 750 °C, both the calcination temperature and incubation time can induce the abnormal phase transition from Low‐β to α phase; also, stress existing in pellets can effectively activate the phase transition of Low‐β. We can conclude that the Low‐β is thermodynamically unstable, while in kinetics, Low‐β is stable. The dielectric properties of BiNbO4 ceramics were investigated to analyze the influence of phase of BiNbO4 powders precursors, especially the effect of phase transition of Low‐β. It's found that BiNbO4 powders firstly calcined at 700 °C is the best precursor to prepare dense ceramics with uniform grain size and the dielectric permittivity and dielectric loss of BiNbO4 ceramics prepared at 1000 °C is 56.6 and 0.001 at 10 kHz, respectively.
Rookies and seasoned recruits: How experience in different levels, firms, and industries shapes strategic renewal in top management
Authors: Williams Charles , Chen Pao‐Lien , Agarwal Rajshree
Published: July 2016

Research summary: This study explores the effect of knowledge integration on strategic renewal. In particular, it examines how executives from different levels and sources influence renewal when added to top management teams (TMT). In contrast to prior work, the study hypothesizes and finds that new outside rookies—those new to top management and the firm—are associated with higher firm growth than other types of executives. We also find that seasoned outsiders—those with prior TMT experience outside the focal industry—contribute to growth only when the existing TMT has a long tenure. The results suggest that the ability of the TMT to integrate new members varies by executive type and has an important effect on incremental strategic renewal.

Managerial summary: Conventional wisdom holds that firms are better off hiring those who can demonstrate prior experience and skill in tasks as close as possible to the job. In the realm of the top management team (TMT), however, we find that many firms benefit from hiring rookies from other firms who are new to the top management team level. These candidates bring useful knowledge of the operations of competitors and other firms, and they are easier to socialize and integrate with the existing team. While more experienced senior leaders may bring valuable strategic knowledge, this study suggests that only top management teams with long shared experience can weather the disruption that they cause to realize the potential benefits. Copyright © 2016 John Wiley & Sons, Ltd.