bluuebunny/crossref_metadata_2025 huggingface dataset:
Palladium‐Catalyzed Insertion of Ethylene and 1,1‐Disubstituted Difunctional Olefins: An Experimental and Computational Study
Authors: Gaikwad Shahaji R. , Patel Ketan , Deshmukh Satej S. , Mote Nilesh R. , Birajdar Rajkumar S. , Pandole Satish P. , Chugh Jeetender , Chikkali Samir H.
Published: May 2020

Insertion or coordination copolymerization of ethylene with di‐substituted olefins is challenging and the choice of di‐substituted mono‐functional olefin versus di‐substituted di‐functional olefin (DDO) appears to be decisive. Here we show that DDO‐inserted species are amenable to ethylene insertion and polymerization. DDOs such as 2‐acetamidoacrylic acid (AAA), methyl 2‐acetamidoacrylate (MAAA), and ethyl 2‐cyanoacrylate (ECA) were treated with palladium complex [{P∧O}PdMe(L)] (P∧O=κ2‐P,O−Ar2PC6H4SO2O with Ar=2‐MeOC6H4; L=C2H6OS) and the existence of respective insertion intermediates in moderate yield (up to 37 %) was established. These intermediates were exposed to ethylene and corresponding ethylene‐inserted products were isolated and characterized. A careful comparison with three model compounds confirmed ethylene insertion and polymerization. Thus, the combined experimental and computational investigations show that DDO‐inserted species can undergo ethylene insertion and polymerization.
Single nucleotide polymorphisms facilitate distinctness‐uniformity‐stability testing of soybean cultivars for plant variety protection
Authors: Achard F. , Butruille M. , Madjarac S. , Nelson P.T. , Duesing J. , Laffont J‐L. , Nelson B. , Xiong J. , Mikel Mark A. , Smith J.S.C.
Published: May 2020

Plant variety protection (PVP), or plant breeders’ rights, provides intellectual property protection (IPP) for cultivars. Technical requirements are distinctness, uniformity, and stable (DUS) reproduction. However, field trials are increasingly resource demanding and potentially inconclusive for soybean (Glycine max[L.] Merr.). Our objective was to establish methodologies using molecular markers to facilitate DUS testing while maintaining current IPP levels. We determined that DNA from 10–15 bulked plants represented cultivar genotype. Single nucleotide polymorphism (SNP) data were highly robust in the face of missing and mistyped data; concordances among five laboratories were >.9888. We used SNP, morphological, physiological, and pedigree information to examine 322 publicly available cultivars including 187 with PVPs. Associations among cultivars following multivariate analyses of genetic distances from SNP data and from pedigree kinship data were very similar. A SNP similarity of 98.6% was the maximum at which cultivars also differed for morphological characteristics. Many (38%) cultivar pairs with members >90% SNP similarity expressed different morphologies with SNP similarities ranging 96–98.6%. Of cultivars <96% SNP similar, only a single pair differed by a single morphological difference; all others differed by more than two morphological characteristics. A SNP similarity of 96% between soybean cultivars represents an initial and conservative point of demarcation between cultivars that have morphological differences and those that do not. Chronological monitoring of pedigree–kinship and SNP similarities showed little evidence that a lack of genetic diversity in F2breeding populations contributed to challenges in DUS among U.S. soybean cultivars.
HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion
Authors: Hiroshima Kenzo , Wu Di , Hamakawa Shinji , Tsuruoka Shingo , Ozaki Daisuke , Orikasa Hideki , Hasegawa Mizue , Koh Eitetsu , Sekine Yasuo , Yonemori Yoko , Nabeshima Kazuki , Tsuji Shoutaro , Miyagi Yohei , Imai Kohzoh
Published: May 2020

Background

The specificity and sensitivity of HEG1 for malignant mesothelioma (MM) is high. The use of BAP1/MTAP immunohistochemistry (IHC) is recommended to separate benign and malignant mesothelial proliferations. We determined how ancillary techniques can be used for the cytological diagnosis of MM with effusion.

Methods

Cell blocks from effusions from cases with MM, reactive mesothelial cells (RMCs), and carcinomas were analyzed by IHC with HEG1, BAP1, and MTAP and with homozygous deletion (HD) of CDKN2A by fluorescence in situ hybridization. Staining scores were calculated for IHC by adding the number of categories for the staining intensity and the staining extension.

Results

HEG1 was positive in all (41/41) MMs, but negative in carcinomas, except for ovarian carcinomas. Overall 76.9% (20/26) of RMCs and 28.6% (6/21) of ovarian carcinomas expressed HEG1. BAP1 loss was found in 71.1% of MMs, but none was found in RMCs. MTAP loss was found in 76.2% of MMs, but none was found in RMCs. 73.9% of MMs harbored HD of CDKN2A. There was concordance between loss of MTAP and HD of CDKN2A in 95% of MMs.

Conclusion

HEG1 is a good marker for mesothelial differentiation in effusion cytology. HD of CDKN2A is frequently observed in cell blocks from effusions of MMs, and MTAP IHC may act as a surrogate for HD of CDKN2A. Cell block analysis is recommended for effusions of unknown origins with the following methods: IHC with HEG1 and claudin 4 to validate the mesothelial origin, followed by BAP1 and MTAP IHC to confirm malignancy.
Benefit of buspirone on chemoreflex and central apnoeas in heart failure: a randomized controlled crossover trial
Authors: Giannoni Alberto , Borrelli Chiara , Mirizzi Gianluca , Richerson George B. , Emdin Michele , Passino Claudio
Published: May 2020

Aims

Increased chemosensitivity to carbon dioxide (CO2) is an important trigger of central apnoeas (CA) in heart failure (HF), with negative impact on outcome. We hypothesized that buspirone, a 5HT1A receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO2 chemosensitivity and CA in
HF.

Methods and results

The BREATH study was a randomized, double‐blind, placebo‐controlled, crossover study (EudraCT‐code 2015‐005383‐42). Outpatients with systolic HF (left ventricular ejection fraction <50%) and moderate‐severe CA [nocturnal apnoea‐hypopnoea index (AHI) ≥15 events/h] were randomly assigned to either oral buspirone (15 mg thrice daily) or placebo for 1 week, with a crossover design (1 week of wash‐out). The primary effectiveness endpoint was a decrease in CO2 chemosensitivity >0.5 L/min/mmHg. The primary safety endpoint was freedom from serious adverse events. Sixteen patients (age 71.3 ± 5.8 years, all males, left ventricular ejection fraction 29.8 ± 7.8%) were enrolled. In the intention‐to‐treat analysis, more patients treated with buspirone (8/16, 50%) had a CO2 chemosensitivity reduction >0.5 L/min/mmHg from baseline than those treated with placebo (1/16, 6.7%) (difference between groups 43%, 95% confidence interval 14–73%, P = 0.016). Buspirone compared to baseline led to a 41% reduction in CO2 chemosensitivity (P = 0.001) and to a reduction in the AHI, central apnoea index and oxygen desaturation index of 42%, 79%, 77% at nighttime and 50%, 78%, 86% at daytime (all P < 0.01); no difference was observed after placebo administration (all P > 0.05). No patient reported buspirone‐related serious adverse events.

Conclusions

Buspirone reduces CO2 chemosensitivity and improves CA and oxygen saturation across the 24 h in patients with
HF.
Characterization of the inflammatory‐metabolic phenotype of heart failure with a preserved ejection fraction: a hypothesis to explain influence of sex on the evolution and potential treatment of the disease
Authors: Packer Milton , Lam Carolyn S.P. , Lund Lars H. , Maurer Mathew S. , Borlaug Barry A.
Published: May 2020

Accumulating evidence points to the existence of an inflammatory‐metabolic phenotype of heart failure with a preserved ejection fraction (HFpEF), which is characterized by biomarkers of inflammation, an expanded epicardial adipose tissue mass, microvascular endothelial dysfunction, normal‐to‐mildly increased left ventricular volumes and systolic blood pressures, and possibly, altered activity of adipocyte‐associated inflammatory mediators. A broad range of adipogenic metabolic and systemic inflammatory disorders – e.g. obesity, diabetes and metabolic syndrome as well as rheumatoid arthritis and psoriasis – can cause this phenotype, independent of the presence of large vessel coronary artery disease. Interestingly, when compared with men, women are both at greater risk of and may suffer greater cardiac consequences from these systemic inflammatory and metabolic disorders. Women show disproportionate increases in left ventricular filling pressures following increases in central blood volume and have greater arterial stiffness than men. Additionally, they are particularly predisposed to epicardial and intramyocardial fat expansion and imbalances in adipocyte‐associated proinflammatory mediators. The hormonal interrelationships seen in inflammatory‐metabolic phenotype may explain why mineralocorticoid receptor antagonists and neprilysin inhibitors may be more effective in women than in men with HFpEF. Recognition of the inflammatory‐metabolic phenotype may improve an understanding of the pathogenesis of HFpEF and enhance the ability to design clinical trials of interventions in this heterogeneous syndrome.
Relationship between T cell receptor clonotype and PD‐1 expression of tumor‐infiltrating lymphocytes in colorectal cancer
Authors: Sukegawa Kenta , Shitaoka Kiyomi , Hamana Hiroshi , Kobayashi Eiji , Miyahara Yoshihiro , Fujii Keisuke , Tsuda Kei , Saeki Shiori , Nagata Takuya , Ozawa Tatsuhiko , Saito Shigeru , Fujii Tsutomu , Muraguchi Atsushi , Shiku Hiroshi , Kishi Hiroyuki
Published: May 2020

Adoptive T cell therapy using tumor‐specific T cells or TCR‐modified T cells is a promising next‐generation immunotherapy. The major source of tumor‐reactive T cells is PD‐1+ tumor‐infiltrating lymphocytes (TILs). In contrast, PD‐1− TILs have received little attention. Here, we analyzed the TCR‐β repertoires of PD‐1− and PD‐1+ CD8+ TILs derived from colorectal cancer and breast cancer. Approximately 40–60% of the PD‐1+ population consisted of oligoclonal populations in both colorectal cancer and breast cancer. In contrast, approximately 37% of the PD‐1− population consisted of an oligoclonal population in colorectal cancer, whereas 14% of them were oligoclonal in breast cancer. In colorectal cancer, the TCR repertoires of PD‐1−CD8+ TILs and PD‐1+CD8+ TILs hardly overlapped. Interestingly, clonally expanded CD8+ TILs in primary tumors and the metastases expressing the same clonotypic TCR showed the same phenotype regarding the PD‐1‐expression. These results suggest that the intrinsic properties of TCRs determine the fate of TILs in terms of whether they become PD‐1+ or PD‐1− in the tumor microenvironment. Further functional analysis of TCRs in TILs will allow us to better understand the regulatory mechanisms for PD‐1 expression on TILs and may contribute to tumor immunotherapy.
Preparation of methylammonium lead iodide (CH3NH3PbI3) thin film perovskite solar cells by chemical vapor deposition using methylamine gas (CH3NH2) and hydrogen iodide gas
Authors: Mortan Claudiu , Hellmann Tim , Buchhorn Moritz , d'Eril Melzi Marco , Clemens Oliver , Mayer Thomas , Jaegermann Wolfram
Published: May 2020

An upscalable chemical vapor deposition setup has been built‐up and employed in producing methylammonium lead iodide (MAPI) thin film perovskite solar cells, leading to a maximum efficiency of 12.9%. The method makes use of methylamine gas and hydrogen iodide gas to transform a predeposited layer of lead(II)iodide (PbI2) into MAPI. Although the reaction mechanism includes the intermediate phases lead oxide (PbO) and lead hydroxide (Pb(OH)2), indicated at least on the surface of the samples by XPS, neither species could be observed in XRD measurements of the stepwise reaction, which show a mixture of highly oriented cubic and tetragonal MAPI perovskite lattice systems.
Experimental assessment on LPG fire extinguishing properties of three chemical powders before and after milling action
Authors: Ibrahim Haidar , Patruni Jagannadha R.
Published: May 2020

The extinguishing performance of three dry chemical powders (DCPs) was investigated through a lab‐scale suppression system for liquefied petroleum gas (LPG) fire. The magnesium hydroxide (Mg(OH)2), sodium bicarbonate (NaHCO3), and commercial ABC − MAP powders are used to prepare two groups of samples: raw samples and milled samples. The effect of milling action on the properties of DCPs, such as the bulk density, microstructure, particle size, thermal decomposition, and the extinguishing performance, is analyzed. The density test revealed that the bulk density increased after milling, and the Mg(OH)2 had a lower density than the other powders. The microstructure analysis showed that the milled powders had a smaller particle size and more regular shapes than raw powders. The thermal analysis demonstrated that the powder decomposition process was somewhat similar with a slight difference in initial decomposition temperature and degradation rate. The fire tests proved that the extinguishing efficacy greatly improved after the samples were milled. Moreover, the experiments indicated that the milled Mg(OH)2 was superior in fire extinguishing to the other samples with shorter extinction time and less agent quantity consumed. Based on the results, it can be inferred that the milling action has a significant influence in enhancing the extinguishing mechanisms' efficiency of DCPs.
Nonserologic test for COVID‐19: How to manage?
Authors: Torretta Sara , Zuccotti Gianvincenzo , Cristofaro Valentina , Ettori Jacopo , Solimeno Lorenzo , Battilocchi Ludovica , D'Onghia Alessandra , Pignataro Lorenzo , Capaccio Pasquale
Published: May 2020

Background

Diagnosis of Severe Acute Respiratory Coranavirus‐2 (SARS‐CoV‐2) infection is currently based on real‐time PCR (RT‐PCR) performed on either nasopharyngeal (NPS) or oropharyngeal (OPS) swabs; saliva specimen collection can be used, too. Diagnostic accuracy of these procedures is suboptimal, and some procedural mistakes may account for it.

Methods and results

The video shows how to properly collect secretions from the upper airways for nonserologic diagnosis of COVID‐19 by nasopharyngeal swab (NPS), oropharyngeal swab (OPS), and deep saliva collection after throat‐cleaning maneuver, all performed under videoendoscopic view by a trained ENT examiner.

Conclusions

We recommend to perform NPS after elevation of the tip of the nose in order to reduce the risk of contamination from the nasal vestible, and to let it flow over the floor of the nasal cavity in parallel to the hard palate in order to reach the nasopharynx. Then the tip of the swab should be left in place for few seconds, and then rotated in order to achieve the largest absorption of nasopharyngeal secretions. Regards OPS, gentle anterior tongue depression should be used to avoid swab contamination from the oral cavity during collection of secretions from the posterior pharyngeal wall. These procedural tricks would enhance diagnostic reliability.
Geostatistical features of streambed vertical hydraulic conductivities in Frenchman Creek Watershed in Western Nebraska
Authors: Abimbola Olufemi P. , Mittelstet Aaron R. , Gilmore Troy E.
Published: May 2020

This study evaluated the spatial variability of streambed vertical hydraulic conductivity (Kv) in different stream morphologies in the Frenchman Creek Watershed, Western Nebraska, using different variogram models. Streambed Kv values were determined in situ using permeameter tests at 10 sites in Frenchman, Stinking Water and Spring Creeks during the dry season at baseflow conditions. Measurements were taken both in straight and meandering stream channels during a 5 day period at similar flow conditions. Each test site comprised of at least three transects and each transect comprised of at least three Kv measurements. Linear, Gaussian, exponential and spherical variogram models were used with Kriging gridding method for the 10 sites. As a goodness‐of‐fit statistic for the variogram models, cross‐validation results showed differences in the median absolute deviation and the standard deviation of the cross‐validation residuals. Results show that using the geometric means of the 10 sites for gridding performs better than using either all the Kv values from the 93 permeameter tests or 10 Kv values from the middle transects and centre permeameters. Incorporating both the spatial variability and the uncertainty involved in the measurement at a reach segment can yield more accurate grid results that can be useful in calibrating Kv at watershed or sub‐watershed scales in distributed hydrological models.
Sediment Transport Assessment for Rio Gualaxo Do Norte After the Fundão Dam Failure
Authors: Estigoni Marcus V , Nelson Andrew D , Dufficy Annie , Torrealba Sebastian Fernando , de Lima Guilherme
Published: May 2020

The debris flood created by the 5 November 2015 failure of the Fundão dam in Brazil injected a large amount of fine sediment in the Gualaxo do Norte River system. Although coarse and sand-sized sediment injections in rivers have been studied in relative detail, little is known about river response to overloading of mud-sized sediments (consisting of clay and silt). This paper presents an assessment of suspended sediment transport occurring in and along the Gualaxo do Norte River after the Fundão dam failure to contribute to the general understanding of how rivers recover following large inputs of mud-sized sediments (consisting of clay and silt). The average total sediment removal estimated based on the last 2 rainy periods is 54 466 tonnes, ranging from 37 385 to 71 546 tonnes according to the uncertainty analysis. The sediment transport analysis suggests that the Gualaxo do Norte River is returning to its pre-event morphological character in terms of sediment transport. However, the morphologic recovery of the system has been constrained in recent years by decreased stream power, the result of moderate wet seasons and limited large flood events. We anticipate that future larger flood events will transport most of the remaining available in-channel tailings, speeding up the physical morphologic recovery of the Gualaxo do Norte River, which is a key component of improving water quality and eventually the river ecology. Although the proposed approach for the sediment budget is simplified and has limitations and uncertainties, it provides a scientific basis to explain the natural fluvial processes that have been occurring in the river system. The approach used for the sediment budget presented in this paper could be applied to similar cases with limited data. Integr Environ Assess Manag 2020;16:572–582. © 2020 SETAC
Pericyte dysfunction due to Shb gene deficiency increases B16F10 melanoma lung metastasis
Authors: He Qi , Li Xiujuan , He Liqun , Li Yousheng , Betsholtz Christer , Welsh Michael
Published: May 2020

Intravasation, vascular dissemination and metastasis of malignant tumor cells require their passage through the vascular wall which is commonly composed of pericytes and endothelial cells. We currently decided to investigate the relative contribution of these cell types to B16F10 melanoma metastasis in mice using an experimental model of host Shb gene (Src homology 2 domain‐containing protein B) inactivation. Conditional inactivation of Shb in endothelial cells using Cdh5‐CreERt2 resulted in decreased tumor growth, reduced vascular leakage, increased hypoxia and no effect on pericyte coverage and lung metastasis. RNAseq of tumor endothelial cells from these mice revealed changes in cellular components such as adherens junctions and focal adhesions by gene ontology analysis that were in line with the observed effects on leakage and junction morphology. Conditional inactivation of Shb in pericytes using Pdgfrb‐CreERt2 resulted in decreased pericyte coverage of small tumor vessels with lumen, increased leakage, aberrant platelet‐derived growth factor receptor B (PDGFRB) signaling and a higher frequency of lung metastasis without concomitant effects on tumor growth or oxygenation. Flow cytometry failed to reveal immune cell alterations that could explain the metastatic phenotype in this genetic model of Shb deficiency. It is concluded that proper pericyte function plays a significant role in suppressing B16F10 lung metastasis.
Association between meat and saturated fatty acid intake and lung cancer risk: The Japan Public Health Center‐based prospective study
Authors: Cai Honglin , Sobue Tomotaka , Kitamura Tetsuhisa , Ishihara Junko , Sawada Norie , Iwasaki Motoki , Shimazu Taichi , Tsugane Shoichiro
Published: May 2020

Red meat or saturated fatty acid (SFA) intake has been reported to increase lung cancer (LC) risk in several western countries. However, in Asia, studies on the relationship between meat and SFA intake with LC incidence are still relatively insufficient, and their conclusions are inconsistent. We investigated the association of meat and SFA intake with LC incidence in a population‐based prospective cohort study in Japan. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for LC risk according to meat intake and SFA intake. A total of 73 187 participants (32 934 men and 40 253 women) aged 45 to 74 years participated in our study. During the follow‐up period of 1 151 839 person‐years (median, 16.0 year) from 1995 to 2013 for Cohort I and from 1998 to 2013 for Cohort II, 1315 (901 men and 414 women) newly diagnosed cases of LC were identified. In men, we found an adverse association between total red meat intake (HR and 95% CI: 1.25 [1.02‐1.53]; Ptrend = .008) and LC risk. Additionally, borderline statistically significant elevated risks of LC were seen with high intake of unprocessed red meat and processed red meat. However, no positive association between total red meat intake and LC risk was observed in women. In contrast, poultry and fish intake were not associated with LC risk in either men or women. We concluded that a high total intake of total red meat was associated with moderately elevated LC risk in men.
IUBMB focused meeting: 10thconference Inhibitors of Protein Kinases. Kinase inhibitors in target biology and disease (IPK2019)
Authors: Poznanski Jaroslaw , Fabbro Doriano
Published: May 2020

The 10th jubilee conference (IPK2019) took place on September 15–19, 2019 in Warsaw, on the Ochota campus as the IUBMB Focused Meeting entitled “Inhibitors of Protein Kinases. Kinase inhibitors in target biology and disease”.
Epigenetic changes of osteoblasts in response to titanium surface characteristics
Authors: Ichioka Yuki , Asa'ad Farah , Malekzadeh Behnosh Öhrnell , Westerlund Anna , Larsson Lena
Published: May 2020

We aimed to investigate the influence of titanium surface characteristics on epigenetic mechanisms and DNA damage/repair pathways. Osteoblast‐like cells (MG63) were incubated on glass, smooth titanium, and minimally rough titanium discs, respectively, for 0, 1, 6, and 24 hr. The presence of double‐stranded DNA damage (γH2AX), DNA repair (Chk2), and epigenetic markers (AcH3 & DNMT1) were investigated using immunofluorescence. There were no Chk2‐positive cells on the minimally rough titanium surfaces at all‐time points, in comparison to glass and smooth titanium. Total γH2AX‐positive cells on minimally rough titanium gradually decreased as incubation time increased, on the contrary to smooth titanium. Minimally rough titanium surfaces induced cytoplasmic staining of DNMT1 up to 99% at 24 hr. For epigenetic markers related to the DNA damage/repair pathway, minimally rough titanium surfaces showed the lower percentage of AcH3‐positive cells compared to glass and smooth titanium surface. The findings in the current study show that titanium surface characteristics indeed influence DNA damage and the DNA repair pathway, including epigenetic factors.
Enhanced nerve cell proliferation and differentiation on electrically conductive scaffolds embedded with graphene and carbon nanotubes
Authors: Sun Yuan , Liu Xifeng , George Matthew N. , Park Sungjo , Gaihre Bipin , Terzic Andre , Lu Lichun
Published: May 2020

Conduits that promote nerve regeneration are currently of great medical concern, particularly when gaps exist between nerve endings. To address this issue, our laboratory previously developed a nerve conduit from biodegradable poly(caprolactone fumarate) (PCLF) that supports peripheral nerve regeneration. The present study improves upon this work by further developing an electrically conductive, positively charged PCLF scaffold through the incorporation of graphene, carbon nanotubes (CNTs), and [2‐(methacryloyloxy)ethyl]trimethylammonium chloride (MTAC) (PCLF–Graphene–CNT–MTAC) using ultraviolet (UV) induced photocrosslinking. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy were used to assess the incorporation of CNTs and graphene into PCLF–Graphene–CNT–MTAC scaffolds, which displayed enhanced surface roughness and reduced electrochemical impedance when compared to neat PCLF. Scaffolds with these surface modifications also showed improved growth and differentiation of rat pheochromocytoma 12 cells in vitro, with enhanced cell growth, neurite extension, and cellular migration. Furthermore, an increased number of neurite protrusions were observed when the conduit was electrically stimulated. These results show that the electrically conductive PCLF–Graphene–CNT–MTAC nerve scaffolds presented here support the cellular behaviors that are critical for nerve regeneration, ultimately making this material an attractive candidate for regenerative medicine applications.
Layer‐by‐layer self‐assembly polyelectrolytes loaded with cyclic adenosine monophosphate enhances the osteo/odontogenic differentiation of stem cells from apical papilla
Authors: Zhang Jing , Zhao Irene ShuPing , Yu Ollie YiRu , Li QuanLi , Mei May Lei , Zhang ChengFei , Chu Chun Hung
Published: May 2020

Cyclic adenosine monophosphate (cAMP) is a second messenger involved in the dental regeneration. However, efficient long‐lasting delivery of cAMP that is sufficient to mimic the in vivo microenvironment remains a major challenge. Here, cAMP was loaded in stem cells from apical papilla (SCAPs) using layer‐by‐layer self‐assembly with gelatin and alginate polyelectrolytes (LBL‐cAMP‐SCAPs). LBL‐cAMP‐SCAPs expressed cAMP and increased the phosphorylation level of cAMP‐response element‐binding protein (CREB) which were evaluated by immunofluorescence and western blotting (WB). Enzyme‐linked immunosorbent assay (ELISA) demonstrated that a sustained release of cAMP and vascular endothelial growth factor (VEGF) were present up to 14 days. Scanning electron microscopy (SEM) found LBL‐coated SCAPs exhibited a spheroid‐like morphology. CCK8 and live/dead staining showed that LBL treatment had no significant effect on cell proliferation and viability. LBL‐cAMP‐SCAPs enhanced mineralized nodule formation and up‐regulated the mRNA levels of the osteogenesis‐related genes, as well as related transcription factor‐2 protein level which were revealed by Alizarin red staining, RT‐PCR and WB, respectively. In conclusion, LBL self‐assembly loaded with cAMP promoted the osteo/odontogenic differentiation of SCAPs, thereby providing a potential strategy for bioactive molecular delivery in dental regeneration.
Metabolism, Excretion, and Pharmacokinetics of Lorlatinib (PF‐06463922) and Evaluation of the Impact of Radiolabel Position and Other Factors on Comparability of Data Across 2 ADME Studies
Authors: Stypinski Daria , Fostvedt Luke , Lam Justine L. , Vaz Alfin , Johnson Theodore R. , Boerma Jan S. , Pithavala Yazdi K.
Published: May 2020

While an initial clinical absorption, distribution, metabolism, and excretion (ADME) study (Study 1; N = 6) with 100 mg/100 µCi [14C]lorlatinib, radiolabeled on the carbonyl carbon, confirmed that the primary metabolic pathways for lorlatinib are oxidation (N‐demethylation, N‐oxidation) and N‐glucuronidation, it also revealed an unanticipated, intramolecular cleavage metabolic pathway of lorlatinib, yielding a major circulating benzoic acid metabolite (M8), and an unlabeled pyrido‐pyrazole substructure. Concerns regarding the fate of unknown metabolites associated with this intramolecular cleavage pathway led to conduct of a second ADME study (Study 2; N = 6) of identical design but with the radiolabel positioned on the pyrazole ring. Results were similar with respect to the overall mass balance, lorlatinib plasma exposures, and metabolic profiles in excreta for the metabolites that retained the radiolabel in both studies. Differences were observed in plasma total radioactivity exposures (2‐fold area under the plasma concentration–time curve from time 0 to infinity difference) and relative ratios of the percentage of dose recovered in urine vs feces (48% vs 41% in Study 1; 28% vs 64% in Study 2). In addition, an approximately 3‐fold difference in the mean molar exposure ratio of M8 to lorlatinib was observed for values derived from metabolic profiling data relative to those derived from specific bioanalytical methods (0.5 vs 1.4 for Studies 1 and 2, respectively). These interstudy differences were attributed to a combination of factors, including alteration of radiolabel position, orthogonal analytical methodologies, and intersubject variability, and illustrate that results from clinical ADME studies are not unambiguous and should be interpreted within the context of the specific study design considerations.
Nucleotide sugar profiles throughout development in wildtype and galt knockout zebrafish
Authors: Haskovic Minela , Coelho Ana I. , Lindhout Martijn , Zijlstra Fokje , Veizaj Raisa , Vos Rein , Vanoevelen Jo M. , Bierau Jörgen , Lefeber Dirk J. , Rubio‐Gozalbo M. Estela
Published: May 2020

Nucleotide sugars (NS) are fundamental molecules in life and play a key role in glycosylation reactions and signal conduction. Several pathways are involved in the synthesis of NS. The Leloir pathway, the main pathway for galactose metabolism, is crucial for production of uridine diphosphate (UDP)‐glucose and UDP‐galactose. The most common metabolic disease affecting this pathway is galactose‐1‐phosphate uridylyltransferase (GALT) deficiency, that despite a lifelong galactose‐restricted diet, often results in chronically debilitating complications. Alterations in the levels of UDP‐sugars leading to galactosylation abnormalities have been hypothesized as a key pathogenic factor. However, UDP‐sugar levels measured in patient cell lines have shown contradictory results. Other NS that might be affected, differences throughout development, as well as tissue specific profiles have not been investigated. Using recently established UHPLC‐MS/MS technology, we studied the complete NS profiles in wildtype and galt knockout zebrafish (Danio rerio). Analyses of UDP‐hexoses, UDP‐hexosamines, CMP‐sialic acids, GDP‐fucose, UDP‐glucuronic acid, UDP‐xylose, CDP‐ribitol, and ADP‐ribose profiles at four developmental stages and in tissues (brain and gonads) in wildtype zebrafish revealed variation in NS levels throughout development and differences between examined tissues. More specifically, we found higher levels of CMP‐N‐acetylneuraminic acid, GDP‐fucose, UDP‐glucuronic acid, and UDP‐xylose in brain and of CMP‐N‐glycolylneuraminic acid in gonads. Analysis of the same NS profiles in galt knockout zebrafish revealed no significant differences from wildtype. Our findings in galt knockout zebrafish, even when challenged with galactose, do not support a role for abnormalities in UDP‐glucose or UDP‐galactose as a key pathogenic factor in GALT deficiency, under the tested conditions.
A first Holocene leaf wax isotope‐based paleoclimate record from the semi‐humid to semi‐arid south‐eastern Caucasian lowlands
Authors: Bliedtner Marcel , Zech Roland , Zech Jana , Schäfer Imke , von Suchodoletz Hans
Published: May 2020

The Holocene paleoclimate of the Caucasus region is rather complex and not yet well understood: while existing studies are mainly based on pollen records from high‐altitude and humid lowland regions, no records are available from the semi‐humid to semi‐arid south‐eastern Caucasian lowlands. Therefore, this study investigated compound‐specific δ2H and δ13C isotopes of leaf wax biomarkers from Holocene floodplain soils in eastern Georgia. Our results show that the leaf wax δ2H signal from the paleosols mostly reflects changes in the moisture source and its isotopic composition. Depleted δ2H values before ~8 cal ka bp change towards enriched values after ~5 cal ka bp and become again depleted after ~1.6 cal ka bp. This trend could be caused by Holocene changes of the isotopic compositions of the Black and eastern Mediterranean Sea, and/or by varying contribution of both moisture sources linked with the North Atlantic Oscillation. The leaf wax δ13C signal from the paleosols directly indicates varying local water availability and drought stress. Depleted δ13C values before ~8 and after ~5 cal ka bp indicate wetter local conditions with higher water availability, whereas more enriched values during the middle Holocene (~8 until at least 5 cal ka bp) indicate drier conditions with increased drought stress.
Funding for Maine schools falls victim to provision in medical marijuana law
Authors: Enos Gary
Published: May 2020

Three Maine public school districts' efforts to bolster student mental health support appear to have collided with the Trump administration's distaste for expanded access to medical marijuana.
New MH coalition featuring storytelling platform launches
Authors: Canady Valerie A.
Published: May 2020

Leading mental health organizations, advocates and celebrities have launched a coalition to destigmatize mental health conditions and address the pervasive public health crisis. The new effort was announced in a May 15 news release by the coalition's founder, social activist and iconic fashion designer Kenneth Cole.
Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5
Authors: Kushner Robert F. , Calanna Salvatore , Davies Melanie , Dicker Dror , Garvey W. Timothy , Goldman Bryan , Lingvay Ildiko , Thomsen Mette , Wadden Thomas A. , Wharton Sean , Wilding John P.H. , Rubino Domenica
Published: May 2020

Objective

The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight.

Methods

Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long‐term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight.

Results

Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%‐81.0%), and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm.

Conclusions

The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long‐term follow‐up.

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Sulfonated poly(ether ether ketone) composite membranes based on amino‐modified halloysite nanotubes that effectively immobilize phosphotungstic acid
Authors: He Shaojian , Dai Wenxu , Zhai Shaoxiong , Song Hao , Lin Jun
Published: May 2020

In this work, we prepared amino‐modified halloysite nanotubes (PEI‐DHNTs) via the co‐deposition of self‐polymerized dopamine and polyethylenimine (PEI) on the surface of nanotubes, which was confirmed by X‐ray photoelectron spectroscopy (XPS) and Thermogravimetric analysis (TGA). A series of composite proton exchange membranes (PEMs) were prepared by incorporating PEI‐DHNTs and phosphotungstic acid (HPW) into sulfonated poly(ether ether ketone) (SPEEK). It was found that both PEI‐DHNTs and HPW were well dispersed in the polymer matrix, exhibiting excellent filler‐matrix compatibility. The composite membranes demonstrated enhanced proton conductivity, reaching as high as 0.078 S cm−1 with 33.3 wt.% HPW loading, which was ~90% higher than that of SPEEK control membrane. Such improvement was mainly attributed to the strong acid–base pairs formed by PEI‐DHNT with both SPEEK and HPW, which shortened proton hopping distance and created more continuous proton conduction pathways. Furthermore, the membrane conductivity remained almost constant after 1 year's immersion in liquid water, indicating the successful immobilization of HPW in the composite membranes.
Maltodextrin as stabilizer for emulsion polymerization: Adsorption and grafting behavior
Authors: Ferrari Raffaele , Storti Giuseppe , Morbidelli Massimo
Published: May 2020

Emulsion polymerization of the three‐monomer system butyl acrylate–styrene–methacrylic acid was performed in batch using a commercial maltodextrin derived from starch degradation as stabilizer. Stable latexes with narrow particle size distributions were obtained in all examined cases. A method was developed to analyze and quantify the partitioning of the maltodextrin between the continuous phase (supernatant) and the particle phase. Significant differences between the polysaccharides adsorbed onto particles with or without emulsion polymerization reaction were observed. The possible reactions of maltodextrin in presence of a radical initiator were studied in aqueous phase, thus confirming maltodextrin degradation. The formation of copolymers involving the original monomers and the stabilizer according to two different reactive pathways was also confirmed. In terms of adsorbed maltodextrin, two different contributions were observed: maltodextrin physically adsorbed and maltodextrin chemically grafted and/or physically incorporated into the polymer.
Process regulation for encapsulating pure polyamine via integrating microfluidic T‐junction and interfacial polymerization
Authors: Cao Xianwu , Peng Junjie , Fang Xinglei , Yang Zhitao , Liao Zicen , Yan Zhibin , Jiang Chuanxia , Liu Bin , Zhang He
Published: May 2020

The quality of microcapsules directly determines the performance of microcapsule‐based functional materials, such as self‐healing materials. How to achieve high‐quality microcapsules depends on not only the selected microencapsulation technique but also the process regulation. Herein, using tetraethylenepentamine (TEPA) as the core target to be encapsulated by a novel microencapsulation technique through integrating microfluidic T‐junction and interfacial polymerization, this investigation studied how the process parameters influence the microencapsulation process and the quality of the synthesized microcapsules regarding the size, morphology, shell structure, and composition. The studied parameters include the solvent type and surfactant concentration in the co‐flow solution, the fed volume of the co‐flow solution, the types of the solvent, catalyst, and shell‐forming monomer in the reaction solution for the shell‐growth stage, and the reaction temperature at the shell‐growth stage. The influence mechanisms were established based on the observations, and the optimized parameter combination for the process was achieved. Through the parametric study for the microencapsulation technique, this study also lays a solid foundation for the technique to fabricate microcapsules containing other functional substances with high quality.
Opportunities for improving conservation early warning and alert systems
Authors: Tabor Karyn M. , Holland Margaret B.
Published: May 2020

Conservation early warning and alert systems (CEAS) provide tremendous opportunities to inform strategic and effective environmental responses. However, these systems are not systematically evaluated based on how they are contributing to conservation outcomes. We survey the current state of systems enabled by satellite monitoring to support tropical forest management and highlight their recent proliferation and the sparse evaluations of these systems in terms of user adoption and application for improving conservation decisions. To guide practitioners, funders and policymakers to choose the appropriate tool for the application, we distinguish two types of CEAS, Rapid Response and Targeted Response, characterized by the user application and the timeframe for decision‐making. These tools are distinct from monitoring tools used for policy and planning which require routine, high‐accuracy and quantifiable estimates of land cover change. We see a need for more systematic evaluations quantifying their environmental and socioeconomic benefits and improved indicators measuring progress toward achieving conservation outcomes. To inform system developers, we summarize best practices for increasing system adoption and use gleaned from seasoned applications of early warning and alert systems for conservation and humanitarian applications. Engaging diverse stakeholders, building permanent capacity, increasing accessibility and interpretability of the information, and communicating the information value to decision‐makers help root these systems into decision‐making processes. Incorporating local knowledge and on‐the‐ground monitoring information from stakeholders can improve alert accuracy while respectfully honoring local knowledge and garnering stakeholder trust in the systems. Strengthening cross‐institutional networks, building political support, and allocating adequate resources empower decision‐makers to act upon the information. Addressing today’s urgent conservation challenges requires linking accessible, trusted and effective CEAS to empowered people taking conservation actions.
Implement success strategies for supervising staff members working remotely
Authors: McCarthy Claudine
Published: May 2020

As more staff members find themselves having to adapt to working from home, supervisors also need to adjust by tweaking their strategies for keeping staff connected, motivated, and productive while also promoting everyone's overall well‐being.
Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells
Authors: Rajendiran Smrithi , Smith-Berdan Stephanie , Kunz Leo , Risolino Maurizio , Selleri Licia , Schroeder Timm , Forsberg E. Camilla
Published: May 2020

C-X-C motif chemokine ligand 12 (CXCL12; aka SDF1α) is a major regulator of a number of cellular systems, including hematopoiesis, where it influences hematopoietic cell trafficking, proliferation, and survival during homeostasis and upon stress and disease. A variety of constitutive, temporal, ubiquitous, and cell-specific loss-of-function models have documented the functional consequences on hematopoiesis upon deletion of Cxcl12. Here, in contrast to loss-of-function experiments, we implemented a gain-of-function approach by generating a doxycycline-inducible transgenic mouse model that enables spatial and temporal overexpression of Cxcl12. We demonstrated that ubiquitous CXCL12 overexpression led to an increase in multipotent progenitors in the bone marrow and spleen. The CXCL12+ mice displayed reduced reconstitution potential as either donors or recipients in transplantation experiments. Additionally, we discovered that Cxcl12 overexpression improved hematopoietic stem and progenitor cell mobilization into the blood, and conferred radioprotection by promoting quiescence. Thus, this new CXCL12+ mouse model provided new insights into major facets of hematopoiesis and serves as a versatile resource for studying CXCL12 function in a variety of contexts.
Lineage-specific differentiation of osteogenic progenitors from pluripotent stem cells reveals the FGF1-RUNX2 association in neural crest-derived osteoprogenitors
Authors: Kidwai Fahad , Mui Byron W. H. , Arora Deepika , Iqbal Kulsum , Hockaday Madison , Castro Diaz Luis Fernandez , Cherman Natasha , Martin Daniel , Myneni Vamsee D. , Ahmad Moaz , Futrega Katarzyna , Ali Sania , Merling Randall K. , Kaufman Dan S. , Lee Janice , Robey Pamela G.
Published: May 2020

Human pluripotent stem cells (hPSCs) can provide a platform to model bone organogenesis and disease. To reflect the developmental process of the human skeleton, hPSC differentiation methods should include osteogenic progenitors (OPs) arising from three distinct embryonic lineages: the paraxial mesoderm, lateral plate mesoderm, and neural crest. Although OP differentiation protocols have been developed, the lineage from which they are derived, as well as characterization of their genetic and molecular differences, has not been well reported. Therefore, to generate lineage-specific OPs from human embryonic stem cells and human induced pluripotent stem cells, we employed stepwise differentiation of paraxial mesoderm-like cells, lateral plate mesoderm-like cells, and neural crest-like cells toward their respective OP subpopulation. Successful differentiation, confirmed through gene expression and in vivo assays, permitted the identification of transcriptomic signatures of all three cell populations. We also report, for the first time, high FGF1 levels in neural crest-derived OPs—a notable finding given the critical role of fibroblast growth factors (FGFs) in osteogenesis and mineral homeostasis. Our results indicate that FGF1 influences RUNX2 levels, with concomitant changes in ERK1/2 signaling. Overall, our study further validates hPSCs' power to model bone development and disease and reveals new, potentially important pathways influencing these processes.
Linnaean names in Arum (Araceae): Typification of A. arisarum (≡ Arisarum vulgare) and A. tenuifolium (≡ Biarum tenuifolium)
Authors: Iamonico Duilio
Published: May 2020

As part of ongoing studies on the family Araceae, and of the Italian Loci Classici Census project, the typification of the Linnaean names Arum arisarum (≡ Arisarum vulgare) and A. tenuifolium (≡ Biarum tenuifolium s.str.) is discussed. An image of L'Obel's Arisarum latifolium and a BM specimen are designated respectively as the lectotypes. An epitype (deposited at HFLA) is also designated for A. tenuifolium subsp. tenuifolium.
Sensor Technologies for Automobiles and Robots
Authors: Nonomura Yutaka
Published: May 2020

This paper reviews various sensor technologies with application in automobiles and robots. Several automotive sensors have been developed using the micro‐electromechanical systems (MEMS) technology. The technologies related to combustion pressure sensors, yaw rate sensors, acceleration sensors, and optical scanners are described here. The combustion pressure sensors are used for engine control, while the yaw rate sensors of quartz and silicon crystals and the acceleration sensors are applied for vehicle motion control. Optical scanners are developed for autonomous driving. Several automotive sensors have been significantly reduced in size and cost, and their performance has been improved dramatically by MEMS technology. The inertial force‐sensing system with yaw rate and acceleration sensors enabled the assistant and partner robots to stand on two legs, walk, or invert and move on two wheels. Because the robots are required to have a variety of sensors, a nerve‐net sensing system was developed. This sensing system has three layers: the host, relay, and sensor nodes. The sensor node is a special large‐scale integration called a ‘nerve‐net chip.’ A triaxial force tactile sensor integrated with the nerve‐net chip was developed as a 2.8‐mm square surface‐mountable chip. A force and thermal tactile sensor was also developed, which detected heat flows and discriminated the materials of contacted objects. The heat flow sensor was thinned with thin‐film technology. The sensor technologies will be used for eco cars and autonomous vehicles. Next‐generation robots are also supported by several automotive sensor technologies. © 2020 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.