bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of a dynamic molecular switch
Authors: Taylor Susan S. , Meharena Hiruy S. , Kornev Alexandr P.
Published: May 2019

Eukaryotic protein kinases (EPKs) regulate almost every biological process and have evolved to be dynamic molecular switches; this is in stark contrast to metabolic enzymes, which have evolved to be efficient catalysts. In particular, the highly conserved active site of every EPK is dynamically and transiently assembled by a process that is highly regulated and unique for every protein kinase. We review here the essential features of the kinase core, focusing on the conserved motifs and residues that are embedded in every kinase. We explore, in particular, how the hydrophobic core architecture specifically drives the dynamic assembly of the regulatory spine and consequently the organization of the active site where the γ‐phosphate of ATP is positioned by a convergence of conserved motifs including a conserved regulatory triad for transfer to a protein substrate. In conclusion, we show how the flanking N‐ and C‐terminal tails often classified as intrinsically disordered regions, as well as flanking domains, contribute in a highly kinase‐specific manner to the regulation of the conserved kinase core. Understanding this process as well as how one kinase activates another remains as two of the big challenges for the kinase signaling community. © 2019 IUBMB Life, 71(6):672–684, 2019
Competing endogenous RNA network of endometrial carcinoma: A comprehensive analysis
Authors: Liu Jinhui , Nie Sipei , Liang Junya , Jiang Yi , Wan Yicong , Zhou Shulin , Cheng Wenjun
Published: May 2019

Competing endogenous RNA (ceRNA) network is dysregulated in the initiation and progression of tumors. In the present study, we explored the regulatory mechanism of ceRNA in endometrial carcinoma (EC) and the potential key molecules with potential value in the diagnosis, treatment, and prognosis of EC. The long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles (552 EC tissues and 35 nontumor tissues) and microRNAs (miRNAs) expression profiles (546 EC tissues and 33 nontumor tissues) were downloaded from The Cancer Genome Atlas database to identify differentially expressed RNAs (DERNAs) in EC. An integrated bioinformatics analysis was used to construct an EC‐specific ceRNA network and select key molecules. As a result, 96 differentially expressed lncRNAs (DElncRNAs), 29 differentially expressed miRNAs (DEmiRNAs), and 77 differentially expressed mRNAs (DEmRNAs) were identified. An EC‐specific ceRNA network was built based on nine DElncRNAs significantly associated with overall survival. CCNB1 was found as a key gene in EC through the weighted gene coexpression network analysis and protein‐protein interaction network analysis. Our ceRNA network showed C2orf48 and LINC00483 might upregulate CCNB1 via competing with miR‐183. In addition, we found a subnetwork which contained survival‐associated DERNAs (AC110491.1, LINC00483‐miR‐192‐GRHL1). The results of reverse transcription quantitative polymerase chain reaction supported the relative expressions of C2orf48, LINC00483 were upregulated and that of AC110491.1 was downregulated in EC. We further found C2orf48 was upregulated in serous EC, endometrioid EC, and mixed serous and endometrioid EC. LINC00483 was upregulated in mixed serous and endometrioid EC compared with that in the normal tissues according to UALCAN database. In addition, candidate small molecular drugs were screened out by ConnectivityMap based on the 77 DEmRNAs in the ceRNA network. Eventually, C2orf48, LINC00483, and AC110491.1 were identified as three key lncRNAs in EC.
Affective forecasting and accuracy in social anhedonia: Predicted and experienced emotion for a social interaction
Authors: Moore Melody M. , Chan Raymond C. K. , Huang Jia , Martin Elizabeth A.
Published: May 2019

Objective

Previous research suggests people with social anhedonia (SocAnh) exhibit deficits in anticipated pleasure for social stimuli relative to controls. However, previous research has relied on hypothetical social stimuli and has focused on anticipated pleasure without examining negative affect.

Method

Participants were informed that they would complete an “enjoyable” sharing task with a peer and were asked to forecast positive and negative affect during the interaction. After the interaction, participants reported their experienced emotions.

Results

We found SocAnh and controls anticipated and experienced similar levels of positive affect and that both groups underpredicted positive affect. The SocAnh group anticipated and experienced more negative affect than controls and was more accurate in forecasting negative affect.

Conclusion

This is the first study to show that SocAnh is associated with the heightened anticipation of negative affect and that experiencing heightened negative affect during social interactions could drive reduced motivation and desire to engage in future social interaction.
NOD2 agonist murabutide alleviates radiation‐induced injury through DNA damage response pathway mediated by ATR
Authors: Liu Lei , Qu Hongjin , Qin Hongran , Yang Yanyong , Liao Zebin , Cui Jianguo , Gao Fu , Cai Jianming
Published: May 2019

Injury‐induced by ionizing radiation (IR) severely reduces the quality of life of victims. The development of radiation protectors is regarded as one of the most resultful strategies to alleviate damages caused by IR exposure. In the present study, we investigated the radioprotective effects of the agonist of nucleotide‐binding‐oligomerization‐domain‐containing proteins 2 called murabutide (MBD) and clarified the potential mechanisms. Our results showed that the pretreatment with MBD effectively protected cultured cells and mice against IR‐induced toxicity and the pretreatment with MBD in vitro and in vitro also inhibited apoptosis caused by IR exposure. The downregulation of γ‐H2AX and the upregulation of ATR signaling pathways by MBD treatment indicated that the radioprotective effects of MBD were due to the stimulation of DNA damage response (DDR) pathway to repair DNA double‐strand breaks caused by IR exposure. As the radioprotective effects of MBD were diminished by the ATR selective inhibitor rather than the ATM inhibitor, ATR pathway was confirmed to be a more crucial checkpoint pathway in mediating the stimulation of DDR pathway by MBD. Taken together, our data provide a novel and effective protector to relieve the injury induced by IR exposure.
PARTICLE − The RNA podium for genomic silencers
Authors: O'Leary Valerie B. , Ovsepian Saak V. , Smida Jan , Atkinson Michael J.
Published: May 2019

Radiation exposure can evoke cellular stress responses. Emerging recognition that long non‐coding RNAs (lncRNAs) act as regulators of gene expression has broadened the spectra of molecules controlling the genomic landscape upon alterations in environmental conditions. Knowledge of the mechanisms responding to low dose irradiation (LDR) exposure is very limited yet most likely involve subtle ancillary molecular pathways other than those protecting the cell from direct cellular damage. The discovery that transcription of the lncRNA PARTICLE (promoter of MAT2A‐ antisense radiation‐induced circulating lncRNA; PARTICL) becomes dramatically instigated within a day after LDR exposure introduced a new gene regulator onto the biological landscape. PARTICLE affords an RNA binding platform for genomic silencers such as DNA methyltransferase 1 and histone tri‐methyltransferases to reign in the expression of tumor suppressors such as its neighboring MAT2A in cis as well as WWOX in trans. In silico evidence offers scope to speculate that PARTICLE exploits the abundance of Hoogsten bonds that exist throughout mammalian genomes for triplex formation, presumably a vital feature within this RNA silencer. PARTICLE may provide a buffering riboswitch platform for S‐adenosylmethionine. The correlation of PARTICLE triplex formation sites within tumor suppressor genes and their abundance throughout the genome at cancer‐related hotspots offers an insight into potential avenues worth exploring in future therapeutic endeavors.
Long noncoding RNA FOXD3‐AS1 promotes colon adenocarcinoma progression and functions as a competing endogenous RNA to regulate SIRT1 by sponging miR‐135a‐5p
Authors: Wu Qiong , Shi Min , Meng Wenying , Wang Yugang , Hui Pingping , Ma Jiali
Published: May 2019

More and more documents have proved that the abnormal expression of long noncoding RNAs (lncRNAs) are correlated with the initiation and progression of colorectal cancer (CRC). lncRNA FOXD3‐AS1 has been reported in glioma for its oncogenic property. According to the survival analysis of The Cancer Genome Atlas database, FOXD3‐AS1 upregulation implied lower survival rate of patients with CRC. Quantitative real‐time polymerase chain reaction showed the overexpression of FOXD3‐AS1 in both CRC tissues and cells. The Kaplan–Meier method demonstrated the prognostic value of FOXD3‐AS1 for patients with CRC. To explore the effect of FOXD3‐AS1 on CRC progression, loss‐of‐function experiments were carried out, whose results indicated that knockdown of FOXD3‐AS1 suppressed cell proliferation, migration, and invasion, inhibited cell cycle and promoted cell apoptosis in vitro. In vivo experiments affirmed that FOXD3‐AS1 affected tumor growth. FOXD3‐AS1 expression was enriched in the cytoplasm of CRC cells. Mechanism experiments revealed that FOXD3‐AS1 served as a competing endogenous RNA to upregulate SIRT1 by sponging miR‐135a‐5p. In addition, SIRT1 silencing also restrained cell proliferation and motility. Rescue assays revealed the biological function of FOXD3‐AS1/miR‐135a‐5p/SIRT1 axis in CRC progression. In conclusion, FOXD3‐AS1 promotes CRC progression by regulating miR‐135a‐5p/SIRT1 axis, shedding lights on the way to CRC treatments.
Restoration of p53 acetylation by HDAC inhibition permits the necrosis/apoptosis switch of pancreatic ainar cell during experimental pancreatitis in mice
Authors: Hu Yangyang , Dai Juanjuan , Zong Guanzhao , Xiao Jingbo , Guo Xingya , Dai Yiqi , Lu Zhanjun , Wan Rong
Published: May 2019

The severity of acute pancreatitis (AP) is greatly attributed to the pancreatic acinar cell (PAC) death response. It has been established that the apoptosis‐inducing therapy can protect against experimental pancreatitis and have great clinical therapeutic potential. However, current pharmacologic agents that target apoptosis during AP largely lack specificity. Thus, it remains imperative to reveal the specific mechanisms governing acinar cell death. Death responses of PAC are manifested by the progressive necrosis accompanied by apoptosis silencing during AP in mice. In this study, we found that the transcriptional activity of p53 was impaired and the expressions of its proapoptotic targets Puma and CD95 were significantly decreased, which explains the apoptosis silencing during AP. Furthermore, we found that the functional depression of p53 was resulted from histone deacetylase (HDAC)‐mediated deacetylation of p53 C‐terminal in PAC during AP. Treatment of the HDAC inhibitor trichostatin‐A restored p53 apoptosis pathway, resulted in a necrosis/apoptosis switch and protected mice from cerulein‐ or l‐Arg‐induced AP. Our research identified the HDAC‐dependent regulation of p53 activity as a critical mechanism underlying acinar cell death response, which represents a specific target for the treatment of AP.
microRNA‐25 promotes cardiomyocytes proliferation and migration via targeting Bim
Authors: Qin Xiaofeng , Gao Shufang , Yang Yadong , Wu Leilei , Wang Liming
Published: May 2019

microRNAs (miRNAs) are pleiotropic players in cardiac development. Recent evidence have suggested miRNAs as promisingly therapeutic targets for cardiac regeneration. This study aimed to reveal the potential effects of miR‐25 on cardiomyocytes proliferation and migration. Sprague‐Dawley rats received left coronary occlusion surgery to induce an in vivo model of myocardial ischemia/reperfusion (I/R) injury. Expression changes of miR‐25 and Bim were tested by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blot. Besides, primary neonatal and adult cardiomyocytes were transfected by the antisense oligonucleotides or mimic specific for miR‐25, and then 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT), 5‐ethynyl‐2’‐deoxyuridine (EdU), Boyden chamber, and terminal‐deoxynucleotidyl transferase‐mediated nick end labeling (TUNEL) assay were respectively used to determine cardiomyocytes growth and migration. Binding effects of miR‐25 on the 3'‐untranslated region (3’‐UTR) of Bim was assessed by dual‐luciferase reporter assay. We found that miR‐25 was low expressed, whereas Bim was highly expressed in I/R injury model and hypoxia‐stimulated cardiomyocytes. Downregulation of miR‐25 in neonatal and adult cardiomyocytes markedly reduced cell proliferation and migration, but promoted apoptosis. Consistently, downregulation of miR‐25 decreased the expression of cyclin E2, cyclin D1, and CDK4, and increased the expression of p57 (KIP2) in cardiomyocytes. We additionally found that Bim was a target of miR‐25. The inhibitory effects of miR‐25 downregulation on cardiomyocytes survival and migration were all significantly attenuated when Bim was silenced. To sum up, our study demonstrates that miR‐25 downregulation inhibits cardiomyocytes proliferation and migration, but promotes apoptosis. The role of miR‐25 in cardiomyocytes was by targeting Bim.
Three‐dimensional space variable–separated PGD in electrostatic field problems: A comparison between two implementations
Authors: Yan Shuai , Zong Wei , Xu Xiaoyu , Li Yalan , Ren Zhuoxiang
Published: May 2019

Proper generalized decomposition (PGD) is a promising model order reduction (MOR) technique to solve partial differential equations (PDEs). It usually bases on an explicit variable‐separated formulation of the problems to be solved. However, it can be expensive to derive the separated formulations. Also, the PGD process can become inefficient because of the massive separated terms. Another way of implementing PGD is based on direct integration. In this work, we illustrate this kind of implementation algebraically by introducing tensors to represent the operator and right‐hand side of the problem. The separated formulation–based PGD and tensor‐based PGD are compared in computational complexity and accuracy. The pros and cons of both approaches are discussed. The methods are applied in three‐dimensional (3D) electrostatic field problems.
Simulation of temperature series and small networks from data
Authors: Washington Benjamin , Seymour Lynne , Lund Robert , Willett Kate
Published: May 2019

It is often desirable to simulate a single temperature series or a collection (network) of temperature series. Accurate simulations can enhance our understanding of temperature trends and variabilities. Simulation can also be used to generate data with known specifications, which are useful in assessing climate data processing routines such as quality control and homogenization algorithms. Possessing multiple realistic temperature series is often beneficial as only one natural record of our climate is available. The current popularity of general circulation models (GCMs) demonstrates how important simulation techniques are. However, even with sophisticated downscaling, it is difficult to replicate station temperature data that have realistic seasonal cycles as well as realistic temporal and spatial correlations. This paper reviews and studies statistical time series methods that can replicate a single series or a network of series from data. The methods are purely statistical—no atmospheric dynamics are involved—and attempt to produce replicates of the records under study. The work here develops (a) methods that simulate temperatures from a fixed season (say a particular day or month of the year) that match the distributional characteristics of the observed data; (b) methods for simulating an entire series that matches the series' temporal autocorrelations and seasonal cycle; and (c) methods for simulating a network of series that reproduce the data's observed seasonal cycles and spatial and temporal autocorrelations. Applications are given throughout, including one where a GCM series and local station data are used in tandem to describe long‐term trends and inject realistic station‐level short‐term fluctuations. This paper can be used as a tutorial for the simulation of a single climate observation, an entire climate series, or a network of multiple climate series simultaneously. Extensions of the ideas that involve GCMs are also examined.
Endoscopic palliation of biliary obstruction
Authors: Aadam A. Aziz , Liu Kevin
Published: May 2019

Advanced pancreaticobiliary malignancy tends to be uncurable at presentation and causes significant morbidity for patients. Palliation for malignant biliary obstruction should be minimally invasive, cost‐effective, and aim to improve quality of life of patients. Strategies of endoscopic palliation of malignant biliary obstruction can differ based on sites and degree of biliary obstruction with complex decisions of optimal stent type and placement that involve conscientious planning by a multidisciplinary team.
The Debate About Bait: A Red Herring in Wildlife Research
Authors: Stewart Frances E. C. , Volpe John P. , Fisher Jason T.
Published: May 2019

The use of bait (or attractants) to lure animals to a sampling site is common in wildlife research and important for optimizing species detection rates. The effect of bait on animal movement and space‐use, however, is contested, fueled by concerns bait may affect animal movement and increase residency time. If founded, bait may bias parameter estimates from density, species distribution, resource selection, or behavioral models, produce spurious ecological inferences, and skew resulting management recommendations. To test whether animal movement varies with proximity to bait, we used high‐resolution global positioning system telemetry data of 10 fishers (Pekania pennanti), temporally paired with 64 baited wildlife camera traps, to quantify the effect of bait on individual and population movement metrics. Although bait appeared to have a significant correlative effect on 1‐hour movement segments, landscape characteristics had an effect 1.7 times greater, where the proportion of mixed forest and cultivation explained the majority of variability in animal movements. We contend that maximizing probability of detection and controlling or modeling local‐scale landscape variability that could affect the probability of detection is a more important consideration in wildlife research than the effect of bait, which is eclipsed by differences incurred by natural habitat heterogeneity. Failing to maximize the probability of detection may obscure the modest bias potentially presented by the use of bait, or attractants, on ecological inference. © 2019 The Wildlife Society
Identifying gene mutations of Chinese patients with polycystic kidney disease through targeted next‐generation sequencing technology
Authors: Wang Tao , Li Qinggang , Shang Shunlai , Geng Guangrui , Xie Yuansheng , Cai Guangyan , Chen Xiangmei
Published: May 2019

Background

Polycystic kidney disease (PKD) is the most common hereditary kidney disease. The main mutational genes causing autosomal dominant polycystic kidney disease (ADPKD) are PKD1 and PKD2 as well as some rare pathogenic genes. Unilateral PKD is rare in clinics, and its association with gene mutations is unclear.

Methods

Targeted next‐generation sequencing (NGS) was performed to detect the renal ciliopathy‐associated genes (targeted NGS panel including 63 genes) in PKD patients.

Results

Forty‐eight PKD1 and PKD2 mutation sites were detected in 44 bilateral PKD patients, of which 48 were PKD1 mutation sites (87.5%) and six were PKD2 mutation sites (12.5%). All of which exhibited typical ADPKD. Furthermore, we detected HNF1B heterozygous mutations in three families. Although these three patients showed HNF1B heterozygous mutations, their clinical characteristics differed and showed phenotypic heterogeneity.

Conclusions

Targeted NGS panel was helpful in detecting typical ADPKD patients and even in non‐typical PKD patients. Macromutation in HNF1B may lead to bilateral PKD. The 16 novel PKD gene mutation sites and two novel PKD2 gene mutation sites discovered in this study have some significance in genetic counseling for ADPKD patients, and increase the number of studied families and expand the mutation database of ADPKD.
PMS2 germline mutation c.943C>T (p.Arg315*)‐induced Lynch syndrome‐associated ovarian cancer
Authors: Guo Xiaoqing , Wu Weimin , Gao Hao , Li Xiaofeng , He Qizhi , Zhu Yong , Liu Na
Published: May 2019

Background

Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation‐induced LS‐associated ovarian cancer (LSAOC) has rarely been reported.

Methods

Next‐generation sequencing (NGS) or Sanger sequencing was used to detect the genetic status of one family including four generations with 16 members. Then, quantitative real‐time PCR (qPCR), western blotting, immunohistochemistry (IHC) staining, and Swiss‐Model software were used to identify the function of the PMS2 mutation.

Results

Five individuals [I‐1, II‐1, II‐2, II‐4, and III‐2 (proband)] suffered from LS‐associated cancers, for example, colon cancer, gastric cancer, and ovarian cancer, with the age of onset ranging from 39 to 70 years old. A PMS2 germline heterozygous mutation (c.943C>T) was confirmed in three members [II‐9, III‐2, and IV‐1] by gene sequencing. In addition, this PMS2 mutation was verified by qPCR, western blotting, and IHC, and a dramatic change with partial loss of the C‐terminal domain in an α‐helix might be exhibited.

Conclusion

Carrying PMS2 germline mutations (c.943C>T) confers an extremely high susceptibility of suffering from LS‐associated cancers. Thus, close clinical monitoring and prophylactic surgery is highly recommended to help reduce the morbidity and mortality of LS‐associated cancers.
The Enamel Phenotype in Homozygous Fam83h Truncation Mice
Authors: Wang Shih‐Kai , Hu Yuanyuan , Smith Charles E. , Yang Jie , Zeng Chunhua , Kim Jung‐Wook , Hu Jan C‐C. , Simmer James P.
Published: May 2019

Background

Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human mutations.

Methods

We generated and characterized a mouse model (Fam83hTr/Tr) expressing a truncated FAM83H protein (amino acids 1–296), which recapitulated the ADHCAI‐causing human FAM83H p.Tyr297* mutation.

Results

Day 14 and 7‐week Fam83hTr/Tr molars exhibited rough enamel surfaces and slender cusps resulting from hypoplastic enamel defects. The lateral third of the Fam83hTr/Tr incisor enamel layer was thinner, with surface roughness and altered enamel rod orientation, suggesting disturbed enamel matrix secretion. Regular electron density in mandibular incisor enamel indicated normal enamel maturation. Only mildly increased posteruption attrition of Fam83hTr/Tr molar enamel was observed at 7‐weeks. Histologically, the Fam83hTr/Tr enamel organ, including ameloblasts, and enamel matrices at sequential stages of amelogenesis exhibited comparable morphology without overt abnormalities, except irregular and less evident ameloblast Tomes' processes in specific areas.

Conclusions

Considering Fam83h−/− mice showed no enamel phenotype, while Fam83hTr/Tr (p.Tyr297*) mice displayed obvious enamel malformations, we conclude that FAM83H truncation mutations causing ADHCAI in humans disturb amelogenesis through a neomorphic mechanism, rather than haploinsufficiency.
National initiative brings health systems together to transform BH care
Authors: Canady Valerie A.
Published: May 2019

Addressing the challenges associated with vulnerable populations and improving behavioral health access and outcomes, while managing the financial impact, are the goals associated with the coming together of more than two dozen health systems last month in a new effort to transform this country's behavioral health resources, particularly in underserved communities.
A low‐cost variable polarization reflectarray based on controllable wave‐path difference
Authors: Wang Quan , Shao Zhen Hai , Jin Mou Ping , Zhang Xiao Lin , Fang Jia , Chen Qian , Zou Wen Man
Published: May 2019

A variable polarization reflectarray antenna is investigated in this communication. It consists of the dual‐layer three parallel dipole loops (TPDLs) to independently control the reflected spatial compensative phase and the phase difference of two orthogonal LP components. In this case, the proposed variable polarization reflectarray can transform a linear polarization (LP) mode into an arbitrary polarization mode by simply rotating the feeder and adjusting the wave‐path difference between the dual‐layer TPDL. A detailed operating mechanism of the variable polarization is introduced in this work. As an example, a 13 × 13‐element offset reflectarray is designed, fabricated, and measured. Four different polarization states of right‐hand circularly polarized (RHCP), 45°LP, left‐hand CP (LHCP), and 135°LP are measured and validated with a specific incident LP wave. The measured gains of 22 dB and 1.5‐dB gain bandwidths of 11% are achieved for all the states. This new reflectarray antenna is especially useful for low‐cost variable polarization applications.
Technical Note: Sensitive volume effects on ion chamber responses in longitudinal magnetic fields
Authors: Reynolds Michael , Rathee Satyapal , Fallone B. Gino
Published: May 2019

Purpose

It has been shown that ion chamber dose response Monte Carlo simulations, in transverse magnetic fields, are susceptible to small changes in the scored sensitive volume. Changes in sensitive volumes have been investigated as a surrogate for modeling the true collection volume governed by the electric field. This work has not been fully extended to longitudinal fields. This study investigates the effect of the sensitive volume of ion chambers on magnetic field dose response within longitudinal magnetic fields.

Methods

The egs_chamber application within EGSnrc was used to model the Exradin A19, A28, and A1SL ion chambers within a uniform longitudinal magnetic field. The sensitive volume of the ion chambers was varied by removing portions of the air volume (from 0.2 to 3 mm) closest to the chamber stem from the dose scoring region; the dose to the scoring volume as a function of magnetic fields strength was normalized to 0 T in all cases.

Results

With the chamber long axis oriented parallel to the radiation and magnetic fields, for every magnetic field strength, all investigated chambers' dose response remained inside statistical variations for all investigated chamber sensitive volumes. When the chamber long axis is oriented perpendicular to the radiation and magnetic fields, the A28 and A1SL show negligible sensitive volume effects, while the A19 under responded by 0.5% for the largest removed volume of 3 mm.

Conclusions

When the ion chambers' long axis is parallel to the radiation and magnetic fields, the magnetic field dose response is unaffected by small changes in sensitive volume. When oriented perpendicularly, only the A19 exhibits sensitive volume based magnetic field dose response changes, and only with ≥ 1 mm of assumed insensitive volume. We can therefore safely assume complete charge collection in Monte Carlo calculated correction factors involving similar chambers in similar conditions.
Testicular somatic cells in the stony coral Euphyllia ancora express an endogenous green fluorescent protein
Authors: Chiu Yi‐Ling , Shikina Shinya , Chang Ching‐Fong
Published: May 2019

In a variety of organisms, adult gonads contain several specialized somatic cells that regulate and support the development of germline cells. In stony corals, the characteristics and functions of gonadal somatic cells remain largely unknown. No molecular markers are currently available that allow for the identification and enrichment of gonadal somatic cells in corals. Here, we showed that the testicular somatic cells of a stony coral, Euphyllia ancora, express an endogenous green fluorescent protein (GFP). Fluorescence microscopy showed that, in contrast to the endogenous expression of the red fluorescent protein of E. ancora ovaries that we have previously reported, the testes displayed a distinct green fluorescence. Molecular identification and spectrum characterization demonstrated that E. ancora testes expressed a GFP (named EaGFP) that is a homolog of the GFP from the jellyfish Aequorea victoria and that possesses an excitation maximum of 506 nm and an emission maximum of 514 nm. Immunohistochemical analyses revealed that the testicular somatic cells, but not the germ cells, expressed EaGFP. EaGFP was enclosed within one or a few granules in the cytoplasm of testicular somatic cells, and the granule number decreased as spermatogenesis proceeded. We also showed that testicular somatic cells could be enriched by using endogenous GFP as an indicator. The present study not only revealed one of the unique cellular characteristics of coral testicular cells but also established a technical basis for more in‐depth investigations of the function of testicular somatic cells in spermatogenesis in future studies.
Anxiety severity does not influence treatment outcomes in patients with interstitial cystitis/bladder pain syndrome
Authors: Yu Wan Ru , Peng Tai Chu , Yeh Hui Ling , Kuo Hann‐Chorng
Published: May 2019

Aims

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) typically experience anxiety mood status, which is closely connected with physical and psychological status and treatment outcome. This study aimed to evaluate the impact of anxiety severity on therapeutic results in IC/BPS patients.

Methods

We prospectively enrolled IC/BPS patients who had previously undergone any kind of treatment for their disease. The primary endpoint was a change in Beck Anxiety Inventory (BAI) scores at 3 months after treatment. Secondary endpoints included changes in the Global Response Assessment (GRA), O'Leary‐Sant symptom score (OSS), and Numerical Rating Scale (NRS) at 3 months after treatment. Urodynamic studies were also compared with the clinical symptom scores.

Results

Overall, 85 IC/BPS patients (mean age, 53.1 ± 12.4 years) were included in the study. At 3 months, changes in the GRA were not significantly different among the different anxiety severity groups. At baseline, 55 (64.7%) patients had moderate or severe anxiety. We observed a significant positive correlation between the change in BAI and the change in OSS after treatment and a significantly negative correlation with GRA at 3 months. Moreover, improvements in OSS and NRS were associated with the change in GRA. Changes in IC symptoms, but not physiological outcomes, were associated with improved anxiety status after treatment. In addition, the change in BAI was significantly associated with age, baseline BAI, and changes in OSS and GRA after treatment.

Conclusions

Baseline anxiety severity does not influence treatment outcomes of IC/BPS. Patients should receive active treatment regardless of their baseline anxiety status.
Energy Management Program Leads to Operational Improvements
Authors: Sowby Robert B. , Jones Steven C. , Christiansen Sam , Jensen Matt
Published: May 2019

The city of North Salt Lake, Utah, recently reduced its water system's energy use by 25 percent. Distribution system pressures and water quality also improved as the water system staff embraced energy‐efficient operations.
Cost‐Effectiveness of Early Childhood Interventions to Enhance Preschool: Evidence from a Randomized Experiment in Head Start Centers Enrolling Historically Underserved Populations
Authors: Knight David S. , Landry Susan , Zucker Tricia A. , Merz Emily C. , Guttentag Cathy L. , Taylor Heather B.
Published: May 2019

We evaluate the cost‐effectiveness of two early childhood interventions that use instructional coaching and parent coaching as levers for improvement. The study design allows us to compare the individual effects of each intervention as well as their combined effect on student outcomes. We find that teachers receiving instructional coaching improve their use of evidence‐based instructional practices, while families receiving parent coaching show increases in numerous responsive parenting behaviors associated with positive child outcomes. Both interventions demonstrate positive impacts on students, but only parent coaching shows statistically significant effects across a range of student outcomes. Instructional coaching alone is substantially less costly and may therefore be the most cost‐effective of the three treatment conditions; however, small sample sizes limit our ability to reach definitive conclusions. Policy simulations suggest that implementing these interventions could raise the overall cost‐effectiveness of Head Start by at least 16 percent.
Is there a role for chemotherapy after local relapse in high‐grade osteosarcoma?
Authors: Palmerini Emanuela , Torricelli Elisa , Cascinu Stefano , Pierini Michela , De Paolis Massimiliano , Donati Davide , Cesari Marilena , Longhi Alessandra , Abate Massimo , Paioli Anna , Setola Elisabetta , Ferrari Stefano
Published: May 2019

Background

High‐grade bone osteosarcoma has a high relapse rate. The best treatment of local recurrence (LR) is under discussion. The aim of this study is to analyze LR patterns and factors prognostic for survival.

Methods

LR diagnostic modality (clinical or imaging), pattern of recurrence, and post‐LR survival (PLRS) were assessed.

Results

Sixty‐two patients were identified, with median age 21 years (range, 9–75 years), including 11 (18%) ≤15 years, 30 (48%) from 16 to 29 years; 21 (34%) were older. Patterns of relapse were LR only 58%, LR + distant metastases (DM) 42%. Seventy‐nine percent of patients relapsed within 24 months, and diagnosis was clinical in 88%. LR treatment was surgery 85%, chemotherapy 55%, chemotherapy + surgery 45%. Surgical complete remission after LR (CR2) was achieved in 60% (LR 86%; LR + DM 23%). With a median follow‐up of 43 months (range, 5–235 months), the five‐year PLRS was 37%, significantly better for patients with longer LR‐free interval (LRFI; ≤24 months 31% vs > 24 months 61.5%, P = 0.03), absence of DM (no DM 56% vs DM 11.5%, P = 0.0001), and achievement of CR2 (no CR2 0% vs CR2 58.5%, P = 0.0001). No difference was found according to age and chemotherapy (LR only: five‐year PLRS: 53% without chemotherapy vs 58% with chemotherapy, P = 0.9; LR + DM: five‐year PLRS: 25% without chemotherapy vs 9% with chemotherapy, P = 0.7).

Conclusions

Early relapse is detected by symptoms in 90% of cases and associated with worse outcome. The achievement of CR2, not age, is crucial for survival. For patients with LR only, better survival was demonstrated, as compared with DM, and no improvement with chemotherapy after surgery was found.
Treatment of Idiopathic Posterior Pelvic Girdle Pain Utilizing a Global Movement Assessment
Authors: Geraci Michael C. , Creighton Andrew
Published: May 2019

Treatment of posterior pelvic girdle pain, including pain generated from the sacroiliac joint [SIJ], can be challenging because the pain can become chronic. A treatment plan targeting only the painful area with isolated treatments such as injection, medication, modalities, or therapy is limited. Globally assessing the patient's kinetic chain is imperative. Identifying a patient's movement impairments within the context of the kinetic chain allows target areas leading to pain in the posterior pelvic region, including the SIJs, to be identified. Before starting an exercise program, the Movement Assessment Tests‐7 (MAT‐7) can be used to screen the spine, SIJs, and major joints of the extremities to identify movement impairments. Tests that comprise the MAT‐7 are comprehensive yet efficient, requiring the patient to pass basic movements before progressing to more advanced movements. This allows the MAT‐7 to be tailored to patients of any age or skill level. Using the MAT‐7, the provider can identify the most difficult movement a patient does well, which is the starting point from which to progress a patient's therapeutic exercise program. Based on the MAT‐7 screen, active therapeutic exercises are prescribed, targeting the movement impairments identified. As a patient advances through their exercise program, the MAT‐7 can be applied to reassess a patient's success with the treatment plan and identify any additional target areas. This movement assessment treatment approach is reproducible, teachable, and applicable to not only posterior pelvic and SIJ pain, but also to pain in the spine and other major joints of the extremities.
Micellization behavior of cationic and anionic surfactant mixtures at different temperatures: Effect of sodium carbonate and sodium phosphate salts
Authors: Mahbub Shamim , Rub Malik Abdul , Hoque Md. Anamul , Khan Mohammed Abdullah , Kumar Dileep
Published: May 2019

Herein, we applied the conductivity measurement technique in order to estimate the critical micelle concentration (cmc) of pure sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) as well as their mixed systems in attendance of different salts at five various temperatures. The micellization of SDS + CTAB mixed systems was found to take place at intermediate cmc values of the two pure surfactants. The values of cmc dwindle with the enhancement of the mole fraction of CTAB. The cmc values follow different trend in different salts. The degree of the interaction between SDS and CTAB in occurrence of salt was estimated from the experimentally estimated value of cmc and their ideal values (cmcid). The observed cmc of individual surfactants along with their mixed systems dwindles in the occurrence of the electrolyte. The values of micellar mole fraction, X1, of CTAB at different stoichiometric mole fractions of CTAB was determined on the basis of different proposed models mentioned in the literature. Different thermodynamics parameters were estimated from the magnitudes of the degree of counterion dissociation and cmc at different temperatures. The magnitudes of free energy of micellization (
), interaction parameter (β), and excess free energy (∆Gex) estimated for the studied systems were obtained to be negative in absence/attendance of electrolyte at all temperatures. The values of activity coefficients (f1 and f2) were also determined on the basis of different proposed models. All of the estimated results signify the strong interaction between the studied amphiphiles.
Higher Structures in Algebraic Quantum Field Theory
Authors: Benini Marco , Schenkel Alexander
Published: May 2019

A brief overview of the recent developments of operadic and higher categorical techniques in algebraic quantum field theory is given. The relevance of such mathematical structures for the description of gauge theories is discussed.
The Rational Higher Structure of M‐theory
Authors: Fiorenza Domenico , Sati Hisham , Schreiber Urs
Published: May 2019

We review how core structures of string/M‐theory emerge as higher structures in super homotopy theory; namely from systematic analysis of the brane bouquet of universal invariant higher central extensions growing out of the superpoint. Since super homotopy theory is immensely rich, to start with we consider this in the rational/infinitesimal approximation which ignores torsion‐subgroups in brane charges and focuses on tangent spaces of super space‐time. Already at this level, super homotopy theory discovers all super p‐brane species, their intersection laws, their M/IIA‐, T‐ and S‐duality relations, their black brane avatars at ADE‐singularities, including their instanton contributions, and, last not least, Dirac charge quantization: for the D‐branes it recovers twisted K‐theory, rationally, but for the M‐branes it gives cohomotopy cohomology theory. We close with an outlook on the lift of these results beyond the rational/infinitesimal approximation to a candidate formalization of microscopic M‐theory in super homotopy theory.
NONMEM Tutorial Part I: Description of Commands and Options, With Simple Examples of Population Analysis
Authors: Bauer Robert J.
Published: May 2019

In this tutorial, the various components of NONMEM will be described, and the basic steps of setting up NONMEM control stream files and data files will be demonstrated. Some basic concepts of nonlinear mixed effects modeling will be discussed, along with simple examples demonstrating how to use NONMEM to perform population analysis of clinical data.
A Review of Strategies for Developing Promising Thermoelectric Materials by Controlling Thermal Conduction
Authors: Yin Yinong , Baskaran Karthikeyan , Tiwari Ashutosh
Published: May 2019

Thermoelectric (TE) materials can play an important role in developing next‐generation advanced energy conversion technologies. The underlying principle for thermoelectric power generation is the utilization of Seebeck effect in which temperature differences drive the electrical current. The performance of a TE material is evaluated by a dimensionless figure of merit, ZT, expressed as ZT = S2σT/κ, where S, σ, T, and κ denote the Seebeck coefficient, electrical conductivity, temperature and thermal conductivity, respectively. As seen from this expression, controlling thermal conduction in TE materials is a key toward obtaining high TE response. The thermal conductivity (κ) consists of two components, namely lattice thermal conductivity (κL) and electronic thermal conductivity (κe), of which the latter is linearly proportional to the electrical conductivity of the material following the Wiedemann‐Franz law. Since reducing the value of κe worsens the value of σ, which is not desired, κL has to be reduced to get an overall lower thermal conductivity. Numerous studies focusing on reducing the thermal conductivity of TE materials have been performed recently. In this paper, a comprehensive review of various strategies used for developing efficient thermoelectric systems by controlling thermal conduction in the TE materials has been provided.
Luminescent Palladacycles Containing a Pyrene Chromophor; Synthesis, Biological and Computational Studies of the Interaction with DNA and BSA
Authors: Karami Kazem , Ramezanpour Azar , Zakariazadeh Mostafa , Shahpiri Azar , Kharaziha Mahshid , Kazeminasab Akram
Published: May 2019

One of the most active areas within the field of bioorganometallic chemistry, complexes of N‐heterocyclic carbenes (NHCs), have recently gained interest. Herein, we report two luminescent palladium N‐heterocyclic carbene complexes; namely [Pd{(C,N)‐C6H4CH2NH(CH2CH3)}(1)] (2) and [Pd{(C,N)‐C6H4CH2NH2}(1)] (3) (1=1‐methyl‐3‐(2‐oxo‐2‐(pyren‐1‐yl)ethyl)‐2,3‐dihydroimidazol‐2‐ylidene) which were synthesized from the reaction of luminescent imidazolium salt (1(H)Br) and binuclear Palladacycles. The interactions of them with CT‐DNA evaluated via absorption, emission and CD spectral techniques as well as measurements of viscosity and thermal denaturation and the results have been shown that they bounded to CT‐DNA by intercalation and groove binding modes. The in vitro cytotoxicity of compounds 2–3 and 1(H)Br on human breast (MCF‐7) and cervical epithelial carcinoma (HeLa) cancer cells lines, indicated the wide range of anticancer activities of them with low IC50 values. Moreover, based on the protein binding ability studies, the intrinsic fluorescence of BSA could be strongly quenched by compounds via a static quenching mechanism. Competitive binding study using Eosin, Digoxin and Ibuprofen as site markers, indicated that the compounds could bind to sites I and II on BSA structure. Finally, all data obtained from biophysical studies were validated by molecular modeling study. Computational results showed that palladium complexes have the potential for detection of mismatch DNA.
A Circular Economy Approach to Fish Oil Extraction
Authors: Ciriminna Rosaria , Scurria Antonino , Avellone Giuseppe , Pagliaro Mario
Published: May 2019

Fish oil rich in polyunsaturated omega‐3 fatty acids is extracted in high yield from anchovy filleting waste using d‐limonene as green biosolvent in a simple solid‐liquid extraction performed by mechanically stirring and maceration followed by limonene removal via evaporation under reduced pressure. As limonene is renewably obtained from waste orange peel, this method closes the materials cycle and establishes a circular economy process to obtain high quality fish oil from biowaste available worldwide in several million t/year amount. Significant economic, social and environmental benefits are anticipated.
Atom Probe Tomography for 3D Structural and Chemical Analysis of Individual Proteins
Authors: Sundell Gustav , Hulander Mats , Pihl Astrid , Andersson Martin
Published: May 2019

Determination of the 3D structure of proteins and other biomolecules is a major goal in structural biology, to provide insights to their biological function. Such structures are historically unveiled experimentally by X‐ray crystallography or NMR spectroscopy, and in recent years using cryo‐electron microscopy. Here, a method for structural analysis of individual proteins on the sub‐nanometer scale using atom probe tomography is described. This technique offers a combination of high‐resolution analysis of biomolecules in 3D, and the chemical sensitivity of mass spectrometry. As a model protein, the well‐characterized antibody IgG is used. IgG is encapsulated in an amorphous solid silica matrix via a sol–gel process to provide the requisite support for atom probe analysis. The silica synthesis is tuned to resemble physiological conditions. The 3D reconstructions show good agreement with the protein databank IgG crystal structure. This suggests that the silica‐embedding strategy can open the field of atom probe tomography to the analysis of biological molecules. In addition to high‐resolution structural information, the technique may potentially provide chemical information on the atomic scale using isotopic labeling. It is envisaged that this method may constitute a useful complement to existing tools in structural biology, particularly for the examination of proteins with low propensity for crystallization.
Multifarious Transit Gates for Programmable Delivery of Bio‐functionalized Matters
Authors: Hu Xinghao , Torati Sri Ramulu , Kim Hyeonseol , Yoon Jonghwan , Lim Byeonghwa , Kim Kunwoo , Sitti Metin , Kim CheolGi
Published: May 2019

Programmable delivery of biological matter is indispensable for the massive arrays of individual objects in biochemical and biomedical applications. Although a digital manipulation of single cells has been implemented by the integrated circuits of micromagnetophoretic patterns with current wires, the complex fabrication process and multiple current operation steps restrict its practical application for biomolecule arrays. Here, a convenient approach using multifarious transit gates is proposed, for digital manipulation of biofunctionalized microrobotic particles that can pass through the local energy barriers by a time‐dependent pulsed magnetic field instead of multiple current wires. The multifarious transit gates including return, delay, and resistance linear gates, as well as dividing, reversed, and rectifying T‐junction gates, are investigated theoretically and experimentally for the programmable manipulation of microrobotic particles. The results demonstrate that, a suitable angle of the gating field at a suitable time zone is crucial to implement digital operations at integrated multifarious transit gates along bifurcation paths to trap microrobotic particles in specific apartments, paving the way for flexible on‐chip arrays of biomolecules and cells.