bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do I Lower Pressure in My Distribution System?
Authors: Gimson Mark , Duque Alejandro
Published: April 2016

If pressure fed into a zone needs to be lowered, traditionally the method used is to install a pressure‐reducing valve (PRV). Such a valve will limit a valve's outlet pressure to a preset pressure regardless of the flow rate and the inlet pressure.
High rates of virological failure and drug resistance in perinatally HIV‐1‐infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo
Authors: Salou Mounerou , Dagnra Anoumou Y , Butel Christelle , Vidal Nicole , Serrano Laetitia , Takassi Elom , Konou Abla A , Houndenou Spero , Dapam Nina , Singo‐Tokofaï Assetina , Pitche Palokinam , Atakouma Yao , Prince‐David Mireille , Delaporte Eric , Peeters Martine
Published: April 2016

Introduction

Antiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV‐1‐infected children and adolescents receiving ART in Togo.

Methods

HIV viral load (VL) testing was consecutively proposed to all children and adolescents who were on ART for at least 12 months when attending HIV healthcare services for their routine follow‐up visit (June to September 2014). Plasma HIV‐1 VL was measured using the m2000 RealTime HIV‐1 assay (Abbott Molecular, Des Plaines, IL, USA). Genotypic drug resistance was done for all samples with VL>1000 copies/ml.

Results and discussion

Among 283 perinatally HIV‐1‐infected children and adolescents included, 167 (59%) were adolescents and 116 (41%) were children. The median duration on ART was 48 months (interquartile range: 28 to 68 months). For 228 (80.6%), the current ART combination consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine and lamivudine) and one non‐nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine or efavirenz). Only 28 (9.9%) were on a protease inhibitor (PI)‐based regimen. VL was below the detection limit (i.e. 40 copies/ml) for 102 (36%), between 40 and 1000 copies/ml for 35 (12.4%) and above 1000 copies/ml for 146 (51.6%). Genotypic drug‐resistance testing was successful for 125/146 (85.6%); 110/125 (88.0%) were resistant to both NRTIs and NNRTIs, 1/125 (0.8%) to NRTIs only, 4/125 (3.2%) to NNRTIs only and three harboured viruses resistant to reverse transcriptase and PIs. Overall, 86% (108/125) of children and adolescents experiencing VF and successfully genotyped, corresponding thus to at least 38% of the study population, had either no effective ART or had only a single effective drug in their current ART regimen.

Conclusions

Our study provided important information on virological outcome on lifelong ART in perinatally HIV‐1‐infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow‐up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource‐limited countries can have dramatic long‐term outcomes and illustrate that paediatric ART receives inadequate attention.
Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain
Authors: He Shuning , Mansour Marc R , Zimmerman Mark W , Ki Dong Hyuk , Layden Hillary M , Akahane Koshi , Gjini Evisa , de Groh Eric D , Perez-Atayde Antonio R , Zhu Shizhen , Epstein Jonathan A , Look A Thomas
Published: April 2016

Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1’s role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical “developmental tumor”, NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation.
A lysin to kill
Authors: Gaca Anthony O , Gilmore Michael S
Published: April 2016

An enzyme produced by a bacteriophage can enter human cells and kill intracellular Streptococcus pyogenes.
Separation of large DNA molecules by size exclusion chromatography-based microchip with on-chip concentration structure
Authors: Azuma Naoki , Itoh Shintaro , Fukuzawa Kenji , Zhang Hedong
Published: April 2016

The separation of DNA molecules according to their size represents a fundamental bioanalytical procedure. Here, we report the development of a chip-sized device, consisting of micrometer-sized fence structures fabricated in a microchannel, for the separation of large DNA molecules (over 10 kbp) based on the principle of size exclusion chromatography (SEC). In order to achieve separation, two approaches were utilized: first, the DNA samples were concentrated immediately prior to separation using nanoslit structures, with the aim of improving the resolution. Second, a theoretical model of SEC-based separation was established and applied in order to predict the optimal voltage range for separation. In this study, we achieved separation of λ DNA (48.5 kbp) and T4 DNA (166 kbp) using the present SEC-based microchip.
Chlorinated biphenyls (PCBs) [Air Monitoring Methods, 2014]
Authors: Tschickardt M. , Breuer D. , Hebisch R. , Hartwig A. ,   MAK Commission
Published: April 2016

This analytical method is a validated measurement procedure for the determination of chlorinated biphenyls (PCBs) in the gaseous state and bound to particles in workplace air for monitoring their MAK value at workplaces. Sampling is performed by drawing a defined volume of air through a quartz fibre filter located in the sampling head with an adsorption tube filled with Tenax TA connected downstream using a suitable pump. The flow rate is adjusted either to 0.5; 1.0 or 2.0 L per minute according to the used conical inlet listed in DIN EN 481. The collected PCBs are thermally desorbed and then analysed by means of gas chromatography‐mass spectrometry (GC‐MS). Quantitative evaluation is based on a 5‐point calibration using PCB 209 as internal standard. The limit of quantification (LOQ) is determined on the basis of ten standard solutions in the lower concentration range. The relative LOQ is 36 ng/m3, which is the sum of the collected PCBs on both the sorbent Tenax TA and the filter. The LOQ for the individual PCB congener per analysis sample is 0.17 to 0.56 ng (absolute). The expanded uncertainty for these parameters is between 15.4 and 16.4% for the individual PCB congeners.
N‐Alkyl‐2‐pyrrolidones (N‐methyl‐2‐pyrrolidone, N‐ethyl‐2‐pyrrolidone), vapour [Air Monitoring Methods, 2014b]
Authors: Rosenberger W. , Breuer D. , Hebisch R. , Hartwig A. ,   MAK Commission
Published: April 2016

This analytical method is a validated measurement procedure for the determination of gaseous
N
‐methyl‐2‐pyrrolidone (NMP) and N‐ethyl‐2‐pyrrolidone (NEP) and for monitoring their Occupational Exposure Limits (OELs) or MAK values at workplaces. Both personal and stationary sampling can be performed for assessment of workplaces. Sampling is carried out by drawing air through a silica gel tube spiked with d
9
‐NMP as internal standard using a suitable flow‐regulated pump. The flow rate is set to approx. 0.33 L/min with a recommended air sample volume of 40 litres. For sample preparation the collected NMP and/or NEP are desorbed from the silica gel with methanol. The sample solutions are analysed by means of gas chromatography‐mass spectrometry (GC‐MS). The quantitative determination is based on calibration functions obtained by means of multiple‐point calibrations. The limit of quantification is 0.15 mg/m
3
for NMP and 0.3 mg/m
3
for NEP with an expanded uncertainty of approx. 20%.
Cadmium and its inorganic compounds [BAT Value Documentation, 1983]
Authors: Lehnert G. , Drexler H. , Hartwig A. ,   MAK Commission
Published: April 2016

Cadmium

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated cadmium and its inorganic compounds and derived 1983 a biological tolerance value at the work place (BAT value)considering cadmium in blood and urine to characterize the internal exposure. Available publications are described in detail. The evaluation of the BAT value is based on the nephrotoxic effects of cadmium. A number of epidemiological studies in workers chronically exposed to cadmium showed that, in workers without signs of kidney damage, a urinary cadmium excretion of 10–13.5 μg/g creatinine corresponded to a renal cadmium concentration of 162–221 mg/kg (Roels et al. 1981). According to other investigations in 148 workers exposed to cadmium and 88 persons of a control group, it can be assumed that a cadmium exposure of 1 μg/100 ml whole blood in the group can be tolerated without kidney damage (Buchet et al. 1980). Assuming a critical cadmium concentration in the renal cortex of 200–250 mg/ kg wet weight (Roels et al. 1981) and considering the results of occupational epidemiological investigations, BAT values of 15 μg cadmium/l blood* and 15 μg cadmium/l urine* were established. The sampling time is not fixed.The BAT values do not apply for CdCl2 and cadmium compounds of a comparable solubility.
Addendum to Cadmium and its inorganic compounds [BAT Value Documentation, 2011]
Authors: Drexler H. , Lämmlein P. , Nasterlack M. , Reuter U. , Hartwig A. ,   MAK Commission
Published: April 2016

Cadmium

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated cadmium and its inorganic compounds in 2010. The former BLW is withdrawn and Biological reference values (BAR) are established for cadmium in blood and urine. Available publications are described in detail.Studies of occupationally exposed persons show that tubular proteinuria can lead to glomerular damage and a reduced glomerular filtration rate, even after relatively low exposure levels of 4 μg cadmium/g creatinine (Järup et al. 1995). Moreover, studies of environmental exposure indicate that reduced glomerular filtration rates can occur at low cadmium concentrations similar to those at which tubular damage has been observed (Akesson et al. 2005; Suwazono et al. 2006). In a large study, the authors concluded that the probability of unusually high values for RBP, NAG, β2M, amino acids and calcium is 10% at cadmium concentrations of around 1–2 μg/g creatinine (Buchet et al. 1990). Considering the early tubular effects, the long half‐life of more than 10 years and the accumulation of cadmium comparable to a permanent body burden and irreversibility, the former BLW of 7 μg cadmium/l urine is withdrawn.Using the database of the environmental survey from 1990/92 (Becker et al. 2002 b; Krause et al. 1996) and 1998 (Becker et al. 2002 a, b) the Human Biomonitoring Commission established a reference value for cadmium of 1.0 μg/l blood for adults (non‐smokers, now 18–69 years old) (UBA 2003; Wilhelm et al. 2004). On this basis a BAR has been set for the non‐smoking population of 1 μg cadmium/l bloodfor adults. The sampling time is not fixed.On the basis of the environmental survey from 1998 (Becker et al. 2002 and 2003) a BAR of 0.8 μg cadmium/l urine* for adults was established. The sampling time is not fixed.Cadmium concentrations in the blood and urine of smokers are higher than in non‐smokers.
Addendum to Cobalt and cobalt compounds [BAT Value Documentation, 2007]
Authors: Angerer J. , Drexler H. , Hartwig A. ,   MAK Commission
Published: April 2016

Cobalt

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the exposure equivalents for carcinogenic substances (EKA) for cobalt and cobalt compounds in 2006. Available publications are described in detail. Cobalt is potentially carcinogenic and mutagenic and has a sensitizing effect. This metal has an effect on the bronchopulmonary system, the heart and blood. Most of the recent studies on occupational exposure to cobalt contained data on concentrations in air and urine, only in some cases also in blood. As the concentration of cobalt in urine is about 10 times higher than that in blood, the detection of cobalt in urine both diagnostically and analytically is more reliable and the method is not invasive, the EKA between cobalt in air and cobalt in blood is withdrawn. The relationships between the concentration of cobalt in air and that in urine derived from the more recent studies show results that agree with comparable relationships derived in 1989. The Commission therefore retains the correlation already derived in 1986 between the concentration of cobalt in ambient air and that in urine, and extends this to include lower concentrations. The correlation contains air concentrations from 0.01 to 0.5 mg cobalt/m
3
and concentrations of cobalt in urine from 6 to 300 µg/L. The sampling time is at the end of the exposure or shift, for long‐term exposures after several shifts.
N‐Isopropyl‐N′‐phenyl‐p‐phenylenediamine [MAK Value Documentation, 2011]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

N‐Isopropyl‐N′‐phenyl‐p‐phenylenediamine is used mainly as a stabilizer (antioxidant) in the rubber industry. The main field of application is the tyre manufacturing sector. In addition, antiozonization agents such asN‐isopropyl‐N′‐phenyl‐p‐phenylenediamine are found also in other rubber products.N‐isopropyl‐N′‐phenyl‐p‐phenylenediamine is non irritating to the skin. The skin‐sensitizing effects ofN‐isopropyl‐N′‐phenyl‐p‐phenylenediamine are sufficiently documented, both as a result of clinical observations in humans and the findings in animal studies.N‐Isopropyl‐N′‐phenyl‐p‐phenylenediamine is therefore given the designation “Sh” (for substances which cause sensitization of the skin). As there are no data available for sensitizing effects on the airways, the substance is not designated with “Sa”.
Diethylamin [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

Diethylamine

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of 5 ml/m
3
for diethylamine, considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of diethylamine is atrophy of the olfactory mucosa in rats and mice in a 2‐year study. 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. A NOAEC for atrophy of the olfactory mucosa was not obtained in the 2‐year study. A benchmark concentration of 4 ml/m
3
(BMDL
05
) as a substitute for a NOAEC is calculated from the data of the mouse, the most sensitive species. Therefore, the MAK value for diethylamine is lowered to 2 ml/m
3
. The chronic NOAEC for systemic toxicity is judged to be 16 ml/m
3
. As local effects are critical, the assignment to Peak Limitation Category I is confirmed. The excursion factor of 2 is set with a read‐across to cyclohexylamine. The momentary value is lowered to 5 ml/m
3
. Because there are no studies on developmental toxicity, the assignment to Pregnancy Risk Group D is confirmed as well. Diethylamine is not genotoxic and not carcinogenic. Skin contact may contribute significantly to systemic toxicity and diethylamine is designated with an “H” notation. Sensitization is not expected from the limited data.
Di‐(2‐ethylhexyl)phthalat (DEHP) [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the developmental toxicity of di(2‐ethylhexyl) phthalate (DEHP). In 2014, the maximum concentration at the workplace (MAK value) of DEHP was set to 2 mg/m
3
for the inhalable fraction.

In some studies, a correlation between prenatal DEHP exposure and effects on anogenital distance of male newborns, birth weight and pregnancy duration in humans is found; however, the results are not consistent.

Teratogenicity is observed in rats only at maternally toxic doses of 1000 mg/kg bw and day and above, in mice at 91 mg/kg bw and day. NOAELs for teratogenicity are 200 mg/kg bw and day for rats and 44 mg/kg bw and day for mice, the latter corresponding to 29 mg/m
3
after scaling to a concentration at the workplace. In contrast to mouse and marmoset, the rat is very sensitive to the effects of DEHP on the male reproductive organs. From a three‐generation study, the Commission deduces a NOAEL for pre‐ and postnatal developmental toxicity to the male reproductive organs and for foetotoxicity of 46 mg/kg bw and day for rats, corresponding to 54 mg/m
3
after scaling to a concentration at the workplace. The Commission does not consider the reported effects – small testes, reduced absolute weights of testis and epididymis – to be adverse because they do not show correlating consequences for the next generation, there is no dose‐response relationship to changes in relative organ weights and histopathological correlates are not observed. Germ cell organization, mRNA expression and protein level of StAR („steroidogenic acute regulatory protein“) in testes are affected after in utero exposure to 100 mg/kg bw and day and above. These effects resulted in a NOAEL for prenatal developmental effects of the male reproductive organs of 30 mg/kg bw and day for rats, corresponding to 35 mg/m
3
. For mice a NOAEL for foetotoxicity as well as prenatal developmental toxicity of 48 mg/kg bw and day is derived in prenatal developmental studies, corresponding to 32 mg/m
3
. Thus, damage to the embryo or foetus is unlikely when the MAK value is observed and DEHP is classified in Pregnancy Risk Group C.
Pentanole [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

Pentanols

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of 20 ml/m
3
for pentanols, considering local and systemic toxicity as well as developmental toxicity. Pentanols are irritating to skin and eyes. In rats, the most sensitive effect due to irritation from 2‐methyl‐2‐butanol is lacrimation at 225 ml/m
3
with a NOAEC of 50 ml/m
3
. 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. However, the NOAEC for lacrimation in the absence of histopathological effects cannot be extrapolated to humans and the MAK value of 20 ml/m
3
is confirmed. Peak Limitation Category I is retained due to local effects. The former excursion factor of 4 seems too high and is reduced to 2 as for linear alcohols, whose chain length is inversely associated with their eye irritating capacity, which is assumed to be similar for branched alcohols. Compared with butanols with a peak limit concentration of 100 ml/m
3
and 4‐methyl‐2‐pentanol with a peak limit concentration of 10 ml/m
3
, the irritating potency of pentanols is supposed to be in between. Previous developmental toxicity studies showed no risk for the foetus if the MAK value is observed; as there are no new studies available, Pregnancy Risk Group C is retained.
Destillate (Erdöl), mit Wasserstoff behandelte leichte [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

Distillates (petroleum), hydrotreated light

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of 20 ml/m
3
for hydrotreated light distillates (petroleum), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of hydrotreated light distillates (petroleum) (C9–C16) vapours is presumably CNS depression as is the case with other hydrocarbon mixtures like white spirit. Lung toxicity is assumed to be the critical effect for the aerosol phase. The Commission increased the MAK value for the vapour phase to 50 ml/m
3
in analogy to hydrotreated heavy naphtha (petroleum) (C6–C13), for which behavioural studies with white spirit (C9–C12) in volunteers were used to derive the MAK value. It was shown that white spirit is also representative for hydrotreated light distillates (petroleum) because their C13–C16 components have low vapour pressures and do not contribute much to the concentration in the vapour phase. On the other hand, the aerosol phase comprises mostly these components and they are expected to be deposited as aerosol in the lung. A MAK value of 5 mg/m
3
for the respirable fraction in analogy to white oil is set. As systemic effects are critical, the assignment to Peak Limitation Category II is retained. The excursion factor of 2 for the vapour is confirmed and an excursion factor of 4 for the aerosol is set in analogy to white oil. The assignment to Pregnancy Risk Group C is confirmed, as damage to the embryo or foetus is unlikely when the MAK value is observed. Hydrotreated light distillates are not genotoxic. Malignant skin tumours developed in mice after chronic epicutaneous application of high doses of kerosenes. However, since the relevance for humans of these tumours in this model is not clear, the assignment to Carcinogen Category 3B is retained. Skin contact does not contribute to systemic toxicity and sensitization is not expected.
N,N‐Dimethylformamid [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

Dimethylformamide (DMF)

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated dimethylformamide, considering all toxicity endpoints. Available publications are described in detail.

The critical target organ after exposure to dimethylformamide (DMF) has been shown in humans and rats to be the liver. After chronic exposure via inhalation, DMF induces significant increases of hepatocellular carcinomas in rats after exposure to 800 ml/m
3
and in mice in response to 200 ml/m
3
and higher. Several in vitro and in vivo studies have indicated that DMF is not genotoxic. The results of the long‐term studies reveal that the tumors develop in the liver only after chronic toxic inflammatory and degenerative changes have developed in this organ. The tumors are a result of chronic damage. Therefore it can be assumed that exposure to DMF at concentrations which do not induce necrotic changes is not associated with an increased cancer risk. DMF was classified in Carcinogen Category 4 with a MAK value of 5 ml/m
3
. The MAK value was established in 2006 on the basis of data from a 2‐year study in mice and a BMD and BMLD calculation. The assignment of DMF to Peak Limitation Category II with an excursion factor of 8, also in 2006, is retained. The assignment to Pregnancy Risk Group B in 1989 is confirmed.
Brommethan [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

Methyl bromide

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the developmental toxicity of methyl bromide. Available unpublished study reports and publications are described in detail. The maximum concentration at the workplace (MAK value) of methyl bromide is 1 ml/m
3
, based on the irritant effect on the upper respiratory tract.

NOAECs for prenatal developmental toxicity in rats and rabbits were 70 ml/m
3
and 40 ml/m
3
, respectively. NOAELs of 30 and 10 mg/kg bw and day in rats and rabbits, respectively, were obtained in gavage studies, corresponding to 14 and 8 ml/m
3
after scaling to a concentration at the workplace. Thus, there is an adequate margin between NOAEC/L for developmental toxicity and the MAK value.

However, methyl bromide is a neurotoxin and no data on developmental neurotoxicity exist. In adult mice and rats, neurotoxic symptoms like convulsions and paralysis of the hind limbs are observed. In a two‐generation study the adult F0 and F1 generations do not show such neurotoxic effects at 90 ml/m
3
, which would particularly have been expected in the F1‐animals having a longer exposure time which included complete gestation. It can be inferred that offspring are not more sensitive to the neurotoxicity of methyl bromide than adults. Thus, damage to the embryo or foetus is unlikely when the MAK value is observed and methyl bromide is re‐assigned to Pregnancy Risk Group C.
Hexachlorbutadien [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: April 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated hexachlorobutadiene to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of hexachlorobutadiene is its toxicity and carcinogenicity in the kidney. In a 2‐year feeding study in rats, hexachlorobutadiene caused significantly increased incidences of adenomas and carcinomas of the kidneys only at the highest dose of 20 mg/kg bw, whereas nephrotoxicity was observed from 2 mg/kg bw. From the NOAEL of 0.2 mg/kg bw in this study, a MAK value of 0.02 ml/m
3
is derived. As the critical effect is systemic, Peak Limitation Category II is assigned. The default excursion factor of 2 is set as no half‐life is known. Concerning the carcinogenicity of hexachlorobutadiene, the Commission concluded that a non‐genotoxic mode of action is of prime importance and genotoxic effects play at most a minor part provided the MAK value is observed. Therefore, hexachlorobutadiene was assigned to Category 4 of carcinogenic substances. As the possible genotoxicity of hexachlorobutadiene is specific for the kidney and it has not been shown to reach the germ cells in an active form, hexachlorobutadiene is not classified in any of the categories for germ cell mutagens. The difference between the NOAEL for developmental toxicity in rats of 10 ml/m
3
and the MAK value is sufficiently large, so that damage to the embryo or foetus is unlikely when the MAK value is observed. Thus, the substance is classified in Pregnancy Risk Group C. Skin contact may contribute significantly to systemic toxicity and hexachlorobutadiene continues to be designated with an “H” notation. Sensitization is not expected from the limited data.
Adaptive fault tolerant control against actuator faults
Authors: Shen Qikun , Jiang Bin , Shi Peng
Published: April 2016

This paper investigates the problem of adaptive fault tolerant control for a class of dynamic systems with unknown un‐modeled actuator faults. The fault model is assumed to be an unknown nonlinear function of control input, not in the traditional form in which the faults can be described as gain and/or bias faults. Using the property of the basic function of neural networks and the implicit function theorem, a novel neural networks‐based fault tolerant controller is designed. Finally, the lateral dynamics of a front‐wheeled steered vehicle is used to demonstrate the efficiency of the proposed design techniques. Copyright © 2016 John Wiley & Sons, Ltd.
Manipulation of Irradiative Defects at MnSe and ZnSe Dopant–Host Interface
Authors: Wang Chunlei , Xu Jingkun , Wang Yanbin , Xu Shuhong , Qi Zhengqing , Lu Changgui , Cui Yiping
Published: April 2016

In the past few decades, trap emission was always believed hardly manipulated to luminescent quantum dots (QDs). Actually, not all trap emissions are useless. This work shows that the interface between MnSe dopant and ZnSe host could be used for manipulating irradiative defects with a controllable manner. This study focuses on three basic challenges for manipulating interface defects, including (i) how to introduce irradiative defects at the dopant–host interface, (ii) how to control the intensity of the interface trap emission, and (iii) how to tune QD emission color via the interface trap emission. Finally, this study shows the application of dopant–host interface defects in ratiometric optical thermometry.
Viruses, Artificial Viruses and Virus‐Based Structures for Biomedical Applications
Authors: van Rijn Patrick , Schirhagl Romana
Published: April 2016

Nanobiomaterials such as virus particles and artificial virus particles offer tremendous opportunities to develop new biomedical applications such as drug‐ or gene‐delivery, imaging and sensing but also improve understanding of biological mechanisms. Recent advances within the field of virus‐based systems give insights in how to mimic viral structures and virus assembly processes as well as understanding biodistribution, cell/tissue targeting, controlled and triggered disassembly or release and circulation times. All these factors are of high importance for virus‐based functional systems. This review illustrates advances in mimicking and enhancing or controlling these aspects to a high degree toward delivery and imaging applications.
Osteoanabolic Implant Materials for Orthopedic Treatment
Authors: Ding Yun‐Fei , Li Rachel W. , Nakai Masaaki , Majumdar Trina , Zhang Dong‐Hai , Niinomi Mitsuo , Birbilis Nick , Smith Paul N. , Chen Xiao‐Bo
Published: April 2016

Osteoporosis is becoming more prevalent due to the aging demographics of many populations. Osteoporotic bone is more prone to fracture than normal bone, and current orthopedic implant materials are not ideal for the osteoporotic cases. A newly developed strontium phosphate (SrPO4) coating is reported herein, and applied to Ti‐29Nb‐13Ta‐4.6Zr (wt%), TNTZ, an implant material with a comparative Young's modulus to that of natural bone. The SrPO4coating is anticipated to modulate the activity of osteoblast (OB) and osteoclast (OC) cells, in order to promote bone formation. TNTZ, a material with excellent biocompatibility and high bioinertness is pretreated in a concentrated alkaline solution under hydrothermal conditions, followed by a hydrothermal coating growth process to achieve complete SrPO4surface coverage with high bonding strength. Owing to the release of Sr ions from the SrPO4coating and its unique surface topography, OB cells demonstrate increased proliferation and differentiation, while the cellular responses of OC are suppressed, compared to the control case, i.e., bare TNTZ. This TNTZ implant with a near physiologic Young's modulus and a functional SrPO4coating provides a new direction in the design and manufacture of implantable devices used in the management of orthopedic conditions in osteoporotic individuals.
Graphene/h‐BN Heterostructures: Recent Advances in Controllable Preparation and Functional Applications
Authors: Song Xiuju , Sun Jingyu , Qi Yue , Gao Teng , Zhang Yanfeng , Liu Zhongfan
Published: April 2016

Vertical heterostructures based on two‐dimensional (2D) layered materials such as graphene and hexagonal boron nitride have emerged as a new paradigm of functional materials. Representing the thinnest and most commonplace 2D heterostructures, graphene/h‐BN, have recently attracted considerable attentions due to their remarkable morphological, electrical, and thermal properties. Herein, this research news highlights recent advances in the preparation of graphene/h‐BN heterostructures, especially via two representative routes involving the one‐batch chemical vapor deposition and co‐segregation growth methods. Furthermore, several promising applications of such heterostructures in energy‐efficient nanoelectronics, energy conversion as well as energy harvesting are also introduced. The existing challenges and future directions with respect to the controllable preparation and the related applications of such graphene/h‐BN heterostructures are finally proposed.
Molecular and clinical analyses with neuropsychological assessment of a case of del(10)(q26.2qter) without intellectual disability: Genomic and transcriptomic combined approach and review of the literature
Authors: Laudier Béatrice , Epiais Tiphanie , Pâris Arnaud , Menuet Arnaud , Briault Sylvain , Ozsancak Canan , Perche Olivier
Published: April 2016

Terminal deletion of the long arm of the chromosome 10 is a rare but well known abnormality, with a large phenotypic variability. Very few data are available about subtelomeric deletion 10q26 patients without intellectual disability. Herein, we report the case of a young adult with a classical 10q26.2qter deletion. She exhibited mainly short stature at birth and in childhood/adulthood without intellectual disability or behavioral problems. After clinical and neuropsychological assessments, we performed genomic array and transcriptomic analysis and compared our results to the data available in the literature. The patient presents a 6.525 Mb heterozygous 10q26.2qter deletion, encompassed 48 genes. Among those genes, DOCK1, C10orf90, and CALY previously described as potential candidate genes for intellectual disability, were partially or completed deleted. Interestingly, they were not deregulated as demonstrated by transcriptomic analysis. This allowed us to suggest that the mechanism involved in the deletion 10qter phenotype is much more complex that only the haploinsufficiency of DOCK1 or other genes encompassed in the deletion. Genomic and transcriptomic combined approach has to be considered to understand this pathogenesis. © 2016 Wiley Periodicals, Inc.
A de novo 10p11.23‐p12.1 deletion recapitulates the phenotype observed in WAC mutations and strengthens the role of WAC in intellectual disability and behavior disorders
Authors: Abdelhedi Fatma , El Khattabi Laila , Essid Nouha , Viot Geraldine , Letessier Dominique , Lebbar Aziza , Dupont Jean‐Michel
Published: April 2016

Chromosomal microarray analysis has become a powerful diagnostic tool in the investigation of patients with intellectual disability leading to the discovery of dosage sensitive genes implicated in the manifestation of various genomic disorders. Interstitial deletions of the short arm of chromosome 10 represent rare genetic abnormalities, especially those encompassing the chromosomal region 10p11‐p12. To date, only 10 postnatal cases with microdeletion of this region have been described, and all patients shared a common phenotype, including intellectual disability, abnormal behavior, distinct dysmorphic features, visual impairment, and cardiac malformations. WAC was suggested to be the main candidate gene for intellectual disability associated with 10 p11‐p12 deletion syndrome. Here, we describe a new case of de novo 10p11.23‐p12.1 microdeletion in a patient with intellectual disability, abnormal behavior, and distinct dysmorphic features. Our observation allows us to redefine the smallest region of overlap among patients reported so far, with a size of 80 Kb and which contains only the WAC gene. These findings strengthen the hypothesis that haploinsufficency of WAC gene might be likely responsible for intellectual disability and behavior disorders. Our data also led us to propose a clinical pathway for patients with this recognizable genetic syndrome depending on the facial dysmorphisms. © 2016 Wiley Periodicals, Inc.
Boron Nitride Nanosheets Improve Sensitivity and Reusability of Surface‐Enhanced Raman Spectroscopy
Authors: Cai Qiran , Mateti Srikanth , Yang Wenrong , Jones Rob , Watanabe Kenji , Taniguchi Takashi , Huang Shaoming , Chen Ying , Li Lu Hua
Published: April 2016

Surface enhanced Raman spectroscopy (SERS) is a useful multidisciplinary analytic technique. However, it is still a challenge to produce SERS substrates that are highly sensitive, reproducible, stable, reusable, and scalable. Herein, we demonstrate that atomically thin boron nitride (BN) nanosheets have many unique and desirable properties to help solve this challenge. The synergic effect of the atomic thickness, high flexibility, stronger surface adsorption capability, electrical insulation, impermeability, high thermal and chemical stability of BN nanosheets can increase the Raman sensitivity by up to two orders, and in the meantime attain long‐term stability and extraordinary reusability not achievable by other materials. These advances will greatly facilitate the wider use of SERS in many fields.
Hierarchical Proteinosomes for Programmed Release of Multiple Components
Authors: Liu Xiaoman , Zhou Pei , Huang Yudong , Li Mei , Huang Xin , Mann Stephen
Published: April 2016

A facile route to hierarchically organized multicompartmentalized proteinosomes based on a recursive Pickering emulsion procedure using amphiphilic protein–polymer nanoconjugate building blocks is described. The number of incarcerated guest proteinosomes within a single host proteinosome is controlled, and enzymes and genetic polymers encapsulated within targeted subcompartments to produce chemically organized multi‐tiered structures. Three types of spatiotemporal response—retarded concomitant release, synchronous release or hierarchical release of dextran and DNA—are demonstrated based on the sequential response of the host and guest membranes to attack by protease, or through variations in the positioning of disulfide‐containing cross‐links in either the host or guest proteinosomes integrated into the nested architectures. Overall, our studies provide a step towards the construction of hierarchically structured synthetic protocells with chemically and spatially integrated proto‐organelles.
Diamond Quantum Devices in Biology
Authors: Wu Yuzhou , Jelezko Fedor , Plenio Martin B , Weil Tanja
Published: April 2016

The currently available techniques for molecular imaging capable of reaching atomic resolution are limited to low temperatures, vacuum conditions, or large amounts of sample. Quantum sensors based on the spin‐dependent photoluminescence of nitrogen‐vacancy (NV) centers in diamond offer great potential to achieve single‐molecule detection with atomic resolution under ambient conditions. Diamond nanoparticles could also be prepared with implanted NV centers, thereby generating unique nanosensors that are able to traffic into living biological systems. Therefore, this technique might provide unprecedented access and insight into the structure and function of individual biomolecules under physiological conditions as well as observation of biological processes down to the quantum level with atomic resolution. The theory of diamond quantum sensors and the current developments from their preparation to sensing techniques have been critically discussed in this Minireview.
A comparison between PARAMICS and VISSIM in estimating automated field‐measured traffic conflicts at signalized intersections
Authors: Essa Mohamed , Sayed Tarek
Published: April 2016

The main objective of this study is to investigate the relationship between field‐measured conflicts and simulated conflicts estimated from microsimulation model (PARAMICS) using the surrogate safety assessment model. An urban signalized intersection was selected for analysis. Automated video‐based computer vision techniques were used to identify field conflicts. The applicability of a two‐step model calibration procedure applied to VISSIM in a recent study was investigated using PARAMICS. In the first calibration step, the PARAMICS model was calibrated to ensure that the simulation gives reasonable results of average delay times. The second calibration step used a genetic algorithm procedure to calibrate PARAMICS parameters to enhance the correlation between simulated and field‐measured conflicts. Finally, the results obtained from PARAMICS were compared with results obtained from VISSIM. The comparison included three aspects: (i) the car‐following model and safety‐related parameters; (ii) the correlation between simulated and field‐measured conflicts; and (iii) the conflict spatial distributions. The results show that the default simulation model parameters give poor correlation with the field‐measured data, and therefore, using simulation models without a proper calibration should be avoided. Overall, good correlation between field‐measured and simulated conflicts was obtained after calibration for both models, especially at higher time‐to‐collision (TTC) values. At TTC threshold of 1.5 s, PARAMICS overestimates the number of conflicts and VISSIM underestimates it. Both models overestimated the number of conflicts at TTC threshold of 3.00 s. There were major differences between field‐measured and simulated conflicts spatial distributions for both simulation models. This indicates that despite the good correlation obtained from the calibration process, both PARAMICS and VISSIM do not capture the actual conflict occurrence mechanism. Copyright © 2016 John Wiley & Sons, Ltd.
Analysis of past experimental data in literature to determine conditions for high performance in biodiesel production
Authors: Alper Tapan N. , Yıldırım Ramazan , Erdem Günay M.
Published: April 2016

In this study, published experimental works on catalytic transesterification were analyzed to determine the most important variables affecting fatty acid conversion and the most suitable ranges of these variables for high performance. A database of 1324 data points was constructed from the experimental results in 31 representative papers published between 2008 and 2014, and this database was analyzed using artificial neural network (ANN) and decision tree (DT) techniques. It was found from ANN analysis that the most important variable for high fatty acid conversion was reaction time (with about 40% relative importance) followed by catalyst loading, alcohol:oil molar ratio, operating temperature, and support type with similar relative importance (about 10% each). DT analysis revealed 14 combinations of conditions leading to high performance, and some of these seemed to be generalizable for the use for the future studies; some heuristics were also derived from these generalizable conditions. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Enzymatic conjugation of multiple proteins on a DNA aptamer in a tail‐specific manner
Authors: Takahara Mari , Hayashi Kounosuke , Goto Masahiro , Kamiya Noriho
Published: April 2016

Conjugation of single‐strand DNA aptamers and enzymes has been of great significance in bioanalytical and biomedical applications because of the unlimited functions provided by DNA aptamer direction. Therefore, we developed efficient tailing of a DNA aptamer, with end‐specific conjugation of multiple enzymes, through enzymatic catalysis. Terminal deoxynucleotidyl transferase (TdT) added multiple Z‐Gln‐Gly (Z‐QG) moieties to the 3′‐end of a DNA aptamer via the addition of Z‐QG‐modified deoxyuridine triphosphate (Z‐QG‐dUTP) and deoxynucleoside triphosphates (dNTPs). The resultant (Z‐QG)m‐(dN)l‐aptamer, whose Z‐QGs with dN spacers served as stickers for microbial transglutaminase (MTG), were crosslinked between the Z‐QGs on the DNA and a substrate peptide sequence containing lysine (K), fused to a recombinant enzyme (i.e. bacterial alkaline phosphatase; BAP) by MTG. The incorporation efficiency of Z‐QG moieties on the aptamer tail and the subsequent conjugation efficiency with multiple enzyme molecules were dramatically altered by the presence of dNTPs, revealing that a combination of Z‐QG‐dUTP/dTTP comprised the best labeling efficiency and corresponding properties during analytical performance. Thus, a novel optimized platform for designing (BAP)n‐(dT)l‐DNA aptamers was demonstrated for the first time in this article, offering unique opportunities for tailoring new types of covalent protein‐nucleic acid conjugates in a controllable way.
Novel materials based on DNA‐CTMA and lanthanide (Ce3+, Pr3+)
Authors: Lazar Cosmina Andreea , Kajzar François , Mihaly Maria , Rogozea Adina Elena , Petcu Adina Roxana , Olteanu Nicoleta Liliana , Rau Ileana
Published: April 2016

New, deoxyribonucleic acid (DNA) based compounds, functionalized with hexadecyltrimethylammonium chloride (CTMA) and lanthanide hydroxide nanoparticles were synthesized. The spectral measurements suggest that between the DNA‐CTMA complex and the lanthanide (III) ions a chemical interaction takes place. The obtained materials exhibit an improved fluorescence efficiency, showing a potential interest for application in photonics, and more particularly, in light emitting devices. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 613–617, 2016.
Is peripheral paraneoplastic neurological syndrome possible in primary brain tumors?
Authors: Koszewicz Magdalena , Michalak Slawomir , Bilinska Malgorzata , Budrewicz Slawomir , Zaborowski Mikolaj , Slotwinski Krzysztof , Podemski Ryszard , Ejma Maria
Published: April 2016

Introduction

Systemic malignant diseases cause the induction of autoimmunity, for example, paraneoplastic syndromes. There are no proofs of paraneoplastic syndromes in primary brain tumors. The aim of the study was to evaluate the involvement of the peripheral nervous system, together with an assessment of onconeuronal and antineural antibodies as indicators of humoral immune response against nervous system in patients with primary brain tumors.

Materials and Methods

Clinical examinations, electrophysiological studies of peripheral nerves (motor and sensory conduction velocity studies, conduction velocity distribution tests, thermal and vibratory quantitative sensory tests, and sympathetic skin response tests) and muscles, blood sampling collection (assessment of onconeuronal, and antineural antibodies) were performed on 33 patients with newly recognized primary brain tumors within 2–4 days after their admission to our department.

Results

We revealed statistically significant changes of peripheral nerves, more pronounced in the peroneal nerve in standard and conduction velocity distribution tests, as well as in sympathetic skin responses. We revealed significantly higher vibratory thresholds, and pain thresholds for cold and warm in the upper and lower limbs in the study group than in the controls. In five patients, we have identified anti‐neuroendothelium, anti‐GFAP, anti‐MAG, anti‐PCNA, and anti‐Ro52 antibodies.

Conclusions

In patients with primary brain tumors, electrophysiological changes in peripheral nerves, together with the presence of the antineural antibodies suggest an autoimmune humoral response, and make the diagnosis of paraneoplastic neurological syndrome possible.