bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Single‐Domain Function in a Modular Assembly Line Alters the Size and Shape of a Complex Polyketide
Authors: Peng Huiyun , Ishida Keishi , Hertweck Christian
Published: October 2019

The structural wealth of complex polyketide metabolites produced by bacteria results from intricate, highly evolved biosynthetic programs of modular assembly lines, in which the number of modules defines the size of the backbone, and the domain composition controls the degree of functionalization. We report a remarkable case where polyketide chain length and scaffold depend on the function of a single β‐keto processing domain: A ketoreductase domain represents a switch between diverging biosynthetic pathways leading either to the antifungal aureothin or to the nematicidal luteoreticulin. By a combination of heterologous expression, mutagenesis, metabolite analyses, and in vitro biotransformation we elucidate the factors governing non‐colinear polyketide assembly involving module skipping and demonstrate that a simple point mutation in type I polyketide synthase (PKS) can have a dramatic effect on the metabolic profile. This finding sheds new light on possible evolutionary scenarios and may inspire future synthetic biology approaches.
Bioactive Peptide Brush Polymers via Photoinduced Reversible‐Deactivation Radical Polymerization
Authors: Sun Hao , Choi Wonmin , Zang Nanzhi , Battistella Claudia , Thompson Matthew P. , Cao Wei , Zhou Xuhao , Forman Christopher , Gianneschi Nathan C.
Published: October 2019

Harnessing metal‐free photoinduced reversible‐deactivation radical polymerization (photo‐RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme‐responsive and pro‐apoptotic peptide brush polymers. Thermolysin‐responsive peptide‐based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo a morphology transition to worm‐like micelles upon enzyme‐triggered cleavage of coronal peptide sidechains. Moreover, pro‐apoptotic polypeptide brushes show enhanced cell uptake over individual peptide chains of the same sequence, resulting in a significant increase in cytotoxicity to cancer cells. Critically, increased grafting density of pro‐apoptotic peptides on brush polymers correlates with increased uptake efficiency and concurrently, cytotoxicity. The mild synthetic conditions afforded by photo‐RDRP, make it possible to access well‐defined peptide‐based polymer bioconjugate structures with tunable bioactivity.
Convergent Total Syntheses of (−)‐Rubriflordilactone B and (−)‐pseudo‐Rubriflordilactone B
Authors: Mohammad Mujahid , Chintalapudi Venkaiah , Carney Jeffrey M. , Mansfield Steven J. , Sanderson Pollyanna , Christensen Kirsten E. , Anderson Edward A.
Published: October 2019

A highly convergent strategy for the synthesis of the natural product (−)‐rubriflordilactone B, and the proposed structure of (−)‐pseudo‐rubriflordilactone B, is described. Late stage coupling of diynes containing the respective natural product FG rings with a common AB ring aldehyde precedes rhodium‐catalyzed [2+2+2] alkyne cyclotrimerization to form the natural product skeleton, with the syntheses completed in just one further operation. This work resolves the uncertainty surrounding the identity of pseudo‐rubriflordilactone B and provides a robust platform for further synthetic and biological investigations.
Umpolung Strategy for α‐Functionalization of Aldehydes for the Addition of Thiols and other Nucleophiles
Authors: Blom Jakob , Reyes‐Rodríguez Gabriel J. , Tobiesen Henriette N. , Lamhauge Johannes N. , Iversen Marc V. , Barløse Casper L. , Hammer Niels , Rusbjerg Matilde , Jørgensen Karl Anker
Published: October 2019

Nucleophile–nucleophile coupling is a challenging transformation in organic chemistry. Herein we present a novel umpolung strategy for α‐functionalization of aldehydes with nucleophiles. The strategy uses organocatalytic enamine activation and quinone‐promoted oxidation to access O‐bound quinol‐intermediates that undergo nucleophilic substitution reactions. These quinol‐intermediates react with different classes of nucleophiles. The focus is on an unprecedented organocatalytic oxidative α‐thiolation of aldehydes. The reaction scope is demonstrated for a broad range of thiols and extended to chemoselective bioconjugation, and applicable to a large variety of aldehydes. This strategy can also encompass organocatalytic enantioselective coupling of α‐branched aldehydes with thiols forming quaternary thioethers. Studies indicate a stereoselective formation of the intermediate followed by a stereospecific nucleophilic substitution reaction at a quaternary stereocenter, with inversion of configuration.
The Development of Epoxidized Hemp Oil Prepolymers for the Preparation of Thermoset Networks
Authors: Omonov Tolibjon S. , Patel Vinay , Curtis Jonathan M.
Published: October 2019

Epoxy thermosets comprised of plant oils along with simple curing agents are sustainable and environmentally friendly polymers. The curing agent selected, and its compatibility with epoxy monomers, strongly affects the curing kinetics, the extent of curing, and the final properties of an epoxy polymers. The goal of this work is to expand the application of epoxidized oils in formulating biobased thermoset polymer systems. Epoxidized hemp oil (EHO) was produced with 8% oxirane oxygen content (OOC) after 24 hours using in situ generated performic acid. Two model curing agents—one aromatic (trimellitic anhydride, TMA) and one biobased nonaromatic (citric acid, CA)—with similar molecular weights were selected to study the cure behavior of EHO in acetone. Both curing agents are insoluble in EHO. The prepolymerization curing reaction behavior was monitored via the OOC, attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy, and gel permeation chromatography. It was demonstrated that at 50 °C, the reaction of EHO with TMA was extremely fast to form esters of TMA, while the reaction of EHO with CA was slower and followed different pathways. The cured EHO/TMA epoxy network is rigid and has a high alpha relaxation temperature (T
α) of 89 °C, which is associated with the glass transition temperature (T
g), while the cured EHO/CA network system is semirigid with a T
α of 40 °C. In addition, TGA analysis showed that the EHO/TMA resin system represents a more homogenous structure compared to the EHO/CA system, as indicated by the presence of lower‐temperature decompositions of citric acid derivatives.
Inverse identification of viscosity coefficient for Newtonian and non‐Newtonian slurries during the turbulent pipeline transportation
Authors: Zhang Ji , Yuan Han , Cheng Liang , Mei Ning , Yan Zhe
Published: October 2019

Slurry viscosity is an important parameter that can be used for slurry characterization and pipeline design. This study proposed an inversion method to identify the viscosity coefficient of slurries in turbulent pipeline flow. An inverse heat convection problem with unknown viscosity for Newtonian and non‐Newtonian slurries was solved in a fully developed turbulent pipe flow, and a modified mixing length theory in the turbulent model was applied to improve the estimation accuracy. Through the inversion calculation, the viscosity coefficient was obtained by temperature profile at several measurement positions. An experimental setup was established, and several experiments were conducted to verify the viscosity estimations for slurry flow in this study. The results showed that the method was reliable for identifying the slurry viscosities in the turbulent state and the modified mixing length model can effectively improve the inversion accuracy. This method provided an effective way to detect the rheological properties for determining the operation mode of turbulent slurry pipelines.
Estimating and Controlling the Renewable Microgrid States Using IoT Infrastructure
Authors: Rana Md Masud , Bo Rui , Chen Haotian
Published: October 2019

This paper considers the optimal filter design issue for microgrid state estimation and stabilisation under packet loss conditions. The considered internet of things (IoT) technologies collect system state information from sensors and send control messages to actuators where they are connected over a lossy communication network. From signal processing point of view, this paper develops an optimal state estimation algorithm using the mean squared error principle. Then a feedback controller is designed under the condition of packet dropouts in the communication network. Finally, the convergence of the developed algorithm is numerically shown. The performance of the proposed schemes are demonstrated using the renewable microgrid.
Phase II randomized clinical trial of endosonography and PET/CT versus clinical assessment only for follow-up after surgery for upper gastrointestinal cancer (EUFURO study)
Authors: Bjerring O S , Fristrup C W , Pfeiffer P , Lundell L , Mortensen M B
Published: October 2019

Background

Upper gastrointestinal malignancies have a poor prognosis. There is no consensus on how patients should be followed after surgery. The authors hypothesized that a structured follow-up programme including endoscopic ultrasonography (EUS) and [18F]fluorodeoxyglucose (FDG) PET/CT would detect cancer recurrences, leading to more patients being eligible for therapy.

Methods

After surgery with curative intent for adenocarcinomas in the gastro-oesophageal junction, stomach or pancreas, patients were randomized 1 : 1 to standard clinical assessment in the outpatient clinic at 3, 6, 9, 12, 18 and 24 months after operation, or clinical assessment plus imaging including [18F]FDG PET/CT and EUS. The primary endpoint was number of patients receiving oncological treatment for recurrence. Secondary endpoints were overall and progression-free survival, survival after recurrence detection of isolated locoregional recurrences and risk factors affecting survival.

Results

In total, 183 patients were enrolled, including 93 who underwent standard follow-up and 90 who had follow-up plus imaging. A recurrence was detected in 84 patients within 2 years after surgery (42 in each group), including 33 of 42 patients in the imaging group who were asymptomatic. Some 25 of 42 patients in the imaging group and 14 of 42 in the standard group received chemotherapy (P = 0·028). Although survival after detection of recurrence in asymptomatic patients was significantly longer than that for symptomatic patients (P < 0·001), overall survival from date of surgery in the two treatment groups was comparable.

Conclusion

Follow-up after surgery for upper gastrointestinal cancer with EUS and PET/CT leads to detection of more asymptomatic cancer recurrences and patients referred for treatment without prolonging overall survival. Registration number: NCT02209415 (http://www.clinicaltrials.gov).
Association of statin use with risk of Gleason score‐specific prostate cancer: A hospital‐based cohort study
Authors: Wang Kai , Gerke Travis A. , Chen Xinguang , Prosperi Mattia
Published: October 2019

Background

Conflicting evidence suggests that statins act chemopreventively against prostate cancer (PCa). Whether the association of statin use with PCa risk is Gleason score‐dependent, time‐, dose‐respondent is not well studied.

Methods

We conducted a cohort study at a tertiary hospital in the Southeastern US using longitudinal data of electronic medical records (EMR) from 1994 to 2016. Only cancer‐free men aged >18 years at baseline with follow‐up time of ≥12 months were included. Time‐dependent Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).

Results

Among 13 065 men, 2976 were diagnosed with PCa over median follow‐up of 6.6 years. Statin use was associated with lower risk of both Gleason low‐ (score <7: aHR, 0.85; 95% CI, 0.74‐0.96) and high‐grade PCa (score ≥7: aHR, 0.54; 95% CI, 0.42‐0.69). The protective association was observed only when statins had been used for a relatively longer duration (≥11 months) or higher dose (≥121 defined daily doses), and were more pronounced for PCa of higher Gleason score (<7: aHR, 0.85, 95% CI, 0.74‐0.96; 7 [3 + 4]: aHR, 0.62, 95% CI, 0.43‐0.90; 7 [4 + 3]: aHR, 0.49, 95% CI, 0.29‐0.82; 8: aHR, 0.60, 95% CI, 0.37‐0.96; 9‐10: aHR, 0.24, 95% CI, 0.11‐0.54). Lipophilic statins (aHR, 0.83; 95% CI, 0.72‐0.95) might be more protective than hydrophilic statins (aHR, 0.91, 95% CI, 0.63‐1.33) against PCa.

Conclusion

Statin use might be associated with reduced PCa risk only when used for a relatively longer duration, and the risk reduction was higher for PCa of higher Gleason score.
A prospective clinical trial of the second‐look procedure for transoral surgery in patients with T1 and T2 laryngeal, oropharyngeal, and hypopharyngeal cancer
Authors: Nishimura Goshi , Sano Daisuke , Arai Yasuhiro , Hatano Takashi , Takahashi Hideaki , Tanabe Teruhiko , Wada Takashi , Morishita Daiki , Oridate Nobuhiko
Published: October 2019

Background

Transoral surgery (TOS) has been widely applied for early T‐stage head and neck cancer (HNC). The resection is performed with a minimum safety margin for function preservation under a limited surgical field; therefore, it is difficult to have a strong conviction about the complete resection. This study aims to evaluate the completeness of the initial TOS procedure; possibility of primary control by TOS alone; and predictive factors in patients with early T‐stage laryngeal, oropharyngeal, and hypopharyngeal cancer.

Methods

Patients were treated by TOS at the primary site with or without neck dissection. The patients were divided into two groups based on the pathological evaluation of their surgical specimens: the control (observation) group, in that the resection was considered complete and the intervention (second‐look procedure) group, in that incomplete tumor resection was suspected. The predictive factors for the possibility and/or limitations of complete resection by TOS were then analyzed.

Results

The study enrolled 26 and 25 patients in the control and intervention group, respectively. The success rate for single resection was 66% and the predictive factor was tumor depth obtained by enhanced computed tomography (CT) examination (odds ratio, 7.870, P = .0243). The success rate for definitive therapy by TOS alone was 83% and the predictive factor was poor differentiation observed on pathological examination (odds ratio, 6.800, P = .0248).

Conclusions

TOS has the potential for both definitive resection and function preservation with minimal invasiveness. Identification of the risk factors for TOS is advantageous for accurate treatment selection in patients with early T‐stage HNC.
OIG: Inadequate mental health services hurting detained children
Authors: Knopf Alison
Published: October 2019

Children crossing the southern border are traumatized and in need of mental health services under conditions that were only exacerbated by Department of Homeland Security (DHS) policy last year, according to an Office of Inspector General (OIG) report evaluating the performance of the Department of Health and Human Services (HHS) in caring for these children.
‘Don't look away’: Help your child learn empathy from news of separated children
Authors: Knopf Alison
Published: October 2019

The tragedy of the immigrant children who have been separated from their parents is too intense to “teach” to young children. “Don't look away” was a frequent theme when the stories, pictures, and videos started coming out showing children who were separated from their parents. Even adults couldn't take it.
Nachweis des Feuerwiderstands von Ziegelmauerwerk – Tipps für eine effiziente Bemessung
Authors: Graubner Carl‐Alexander , Purkert Benjamin
Published: October 2019

In Germany, structural fire design of masonry is carried out in a simplified way using tabulated minimum wall thicknesses depending on the loading level in fire. Against this background the procedure of structural fire design is shown briefly before two approaches for a more efficient verification of the fire resistance are explained. The first possibility is to determine the reduction factor for the design value of the actions in fire more precisely and thereby reduce the loading level. Secondly, a design methodology is presented which can be applied in case of masonry walls with low vertical load but a large load eccentricity at mid‐height of the wall. Finally, the verification of the fire resistance of masonry according to national technical approval is discussed with an explanation how to obtain the same loading level in fire if the design is based on DIN EN 1996‐3/NA as when it is based on DIN EN 1996‐1‐1/NA.
Experimentelle Traglastermittlung einer teilweise bewehrten Lochfassade aus Ziegelmauerwerk
Authors: Förster Valentin , Graubner Carl‐Alexander , Proske Tilo
Published: October 2019

For a new multi‐storey car park over the Central Bus Station (ZOB) in Kiel, a perforated clinker brick veneer facade not conforming to standards was planned. The design and technical characteristics of the facade have already been described in the article by Medzech and Schrade in this issue [1]. This article deals with the experimental investigations carried out to obtain a project‐related one‐off approval (ZiE). These experiments contain in particular large tests on storey‐height wall sections, which were subjected to eccentric compressive loading and partly to horizontal loads representing wind action. Supplementary small tests on unreinforced and reinforced masonry served to determine the bending capacity, the anchoring capacity of the reinforcement and the load‐bearing capacity of the wall anchors in the masonry. Due to the special facade construction with special bricks for the project, wall anchors, reinforcement bar couplers and unique test set‐ups had to be developed for the specific project.
Parkhaus ZOB Kiel: Eine gelochte Mauerwerksfassade für den Zentralen Omnibusbahnhof
Authors: Medzech Jürgen , Schrade Holger
Published: October 2019

On the occasion of the Olympic sailing competitions in Kiel, the ZOB and the multi‐storey car park above it were built in 1972.

The two‐storey multi‐storey car park, equipped for about 560 parking spaces, was originally connected to the railway station quay, the main railway station and the city centre by three pedestrian bridges. These bridges were demolished over the years. The new construction of the Atlantic Hotel in 2009 made it necessary to partially demolish the multi‐storey car park and the ZOB. At the same time, preparations began for the redesign of the remaining ZOB site.

However, the original idea of renovating the building, which had been reduced in size by the construction of the new hotel, and additionally increasing it by two parking levels, was rejected.

The poor structural condition and the planning of a new attractive bus station ultimately required demolition.

In the new planning of the ZOB, two construction sites were defined. The design for the new multi‐storey car park on construction site 2 took into account the specifications for the number of storeys, the spacing areas, the maximum eaves height and the materials used in the neighbouring buildings as an independent building.

The rounding of the facade at Stresemannplatz gives passers‐by coming from the west a clearer view of the harbour. The spindle, which is raised above the 6th floor, serves as a recognizable point visible from afar.
Microclimate predicts frost hardiness of alpineArabidopsis thalianapopulations better than elevation
Authors: Lampei Christian , Wunder Jörg , Wilhalm Thomas , Schmid Karl J.
Published: October 2019

In mountain regions, topological differences on the microscale can strongly affect microclimate and may counteract the average effects of elevation, such as decreasing temperatures. While these interactions are well understood, their effect on plant adaptation is understudied.

We investigated winter frost hardiness ofArabidopsis thalianaaccessions originating from 13 sites along altitudinal gradients in the Southern Alps during three winters on an experimental field station on the Swabian Jura and compared levels of frost damage with the observed number of frost days and the lowest temperature in eight collection sites.

We found that frost hardiness increased with elevation in a log‐linear fashion. This is consistent with adaptation to a higher frequency of frost conditions, but also indicates a decreasing rate of change in frost hardiness with increasing elevation. Moreover, the number of frost days measured with temperature loggers at the collection sites correlated much better with frost hardiness than the elevation of collection sites, suggesting that populations were adapted to their local microclimate. Notably, the variance in frost days across sites increased exponentially with elevation. Together, our results suggest that strong microclimate heterogeneity of high alpine environments can preserve functional genetic diversity among small populations.

Synthesis: Here, we tested how plant populations differed in their adaptation to frost exposure along an elevation gradient and whether microsite temperatures improve the prediction of frost hardiness. We found that local temperatures, particularly the number of frost days, are a better predictor of the frost hardiness of plants than elevation. This reflects a substantial variance in frost frequency between sites at similar high elevations. We conclude that high mountain regions harbor microsites that differ in their local microclimate and thereby can preserve a high functional genetic diversity among them. Therefore, high mountain regions have the potential to function as a refugium in times of global change.
Glucose Electro‐oxidation on Graphite Electrode Modified with Nickel/Chromium Nanoparticles
Authors: Kiani Azadeh , Ghaffarinejad Ali , Abolfazl Seyedsadjadi Seyed , Mansouri Atiyeh
Published: October 2019

In this study, an available and inexpensive graphite substrate, was easily modified with Ni/Cr nanoparticles via electrodeposition technique in a very short time (3 min) and used as an electrocatalyst for glucose oxidation in alkaline solution. Graphite electrode modified with Ni/Cr nanoparticles demonstrated an outstanding electrocatalytic performance to glucose oxidation in comparison to examined Ni‐based electrodes or even different materials in other reports. It is noteworthy to mention that adding a little Cr led to a synergistic effect with Ni; accordingly, the presence of Cr not only resulted in a greater adsorption of glucose molecules by chromium oxide but also boosted conductivity of the nickel oxide because of the enhancement of Ni(III) amount. The electrochemical studies were performed by cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The morphology and structure of catalyst layer was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD) and energy dispersive x‐ray spectroscopy (EDS). The linear range of the electrode by cyclic voltammetry was between 2–31 mM with a high sensitivity of 2094 μA cm−2 mM−1. The repeatability and reproducibility of the proposed electrode was examined in glucose solution which were 0.3 % and 4.7 %, respectively. According to the low cost, ease and fast preparation, good repeatability and high sensitivity, this electrode can be a good candidate for nonenzymatic glucose oxidation.
Pattern Recognition of Amino Acids in Wines
Authors: Cioates Negut Catalina , Stefan‐van Staden Raluca‐Ioana , Harja Florian , van Staden Jacobus Frederick
Published: October 2019

New synthesized fatty acid amides (N‐(2‐(piperidin‐1‐yl)ethyl)oleamide, and N‐(2‐(pyrrolidin‐1‐yl)ethyl)oleamide) were used for the design of stochastic sensors based on nanographene paste. The stochastic sensors were used for pattern recognition of four amino acids: L‐histidine, L‐tyrosine, L‐ornithine, and L‐lysine in wines. The pattern recognition was performed based on the signatures recorded for each of the amino acids. The limits of determination allow the assay of amino acids in wine at very low concentrations faster, reliable, and more cost effective than other methods proposed to date.
Family history of cancer and subsequent risk of cancer: A large‐scale population‐based prospective study in Japan
Authors: Hidaka Akihisa , Sawada Norie , Svensson Thomas , Goto Atsushi , Yamaji Taiki , Shimazu Taichi , Iwasaki Motoki , Inoue Manami , Tsugane Shoichiro ,   for the JPHC Study Group
Published: October 2019

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population‐based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self‐administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable‐adjusted Cox proportional hazards regression models. During 1,802,581 person‐years of follow‐up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07–1.15]), esophagus (2.11 [1.00–4.45]), stomach (1.36 [1.19–1.55]), liver (1.69 [1.10–2.61]), pancreas (2.63 [1.45–4.79]), lung (1.51 [1.14–2.00]), uterus (1.93 [1.06–3.51]) and bladder cancers (6.06 [2.49–14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high‐risk of those cancers.
Spatially resolved diffuse imaging for high‐speed depth estimation of jet injection
Authors: Brennan Kieran A. , Ruddy Bryan P. , Nielsen Poul M. F. , Taberner Andrew J.
Published: October 2019

We investigate the use of spatially resolved diffuse imaging to track a fluid jet delivered at high speed into skin tissue. A jet injector with a short needle to deliver drugs beneath the dermis, is modified to incorporate a laser beam into the jet, which is ejected into ex vivo porcine tissue. The diffuse light emitted from the side and top of the tissue sample is recorded using high‐speed videography. Similar experiments, using a depth‐controlled fiber optic source, generate a reference dataset. The side light distribution is related to source depth for the controlled‐source experiments and used to track the effective source depth of the injections. Postinjection X‐ray images show agreement between the jet penetration and ultimate light source depth. The surface light intensity profile is parameterized with a single parameter and an exponential function is used to relate this parameter to source depth for the controlled‐source data. This empirical model is then used to estimate the effective source depth from the surface profile of the injection experiments. The depth estimates for injections into fat remain close to the side depth estimates, with a root‐mean‐square error of 1.1 mm, up to a source depth of 8 mm.
Long noncoding RNA (MEG3) in urinal exosomes functions as a biomarker for the diagnosis of Hunner‐type interstitial cystitis (HIC)
Authors: Liu Fei , Chen Yuedong , Liu Rongfu , Chen Bin , Liu Chunxiao , Xing Jinchun
Published: October 2019

Background

Toll‐like receptor‐7 (TLR7) is functionally involved in the pathogenesis of Hunner‐type interstitial cystitis (HIC). In addition, maternally expressed gene 3 (MEG3) is implicated in many urethral diseases. In this study, we aimed to verify the hypothesis that exosomal MEG3 in urine can be used as a novel diagnostic biomarker for HIC.

Methods

Electron microscopy was utilized to observe the distribution of urinary exosomes between the case group and the control group. Receiver operating characteristic analysis was utilized to compare the diagnostic values of MEG3 and miR‐19a‐3p. Computational analysis and luciferase assay were conducted to identify the correlation between MEG3 and miR‐19a‐3p as well as between TLR7 and miR‐19a‐3p. In addition, real‐time polymerase chain reaction and Western blot were performed to establish the signaling pathways implicated in the pathogenesis of HIC.

Results

When age and gender distributions are excluded, urinary exosomes were equally distributed between case and control groups. The area under the curve of MEG3 was larger than that of miR‐19a‐3p, indicating that MEG3 has a better value in the diagnosis of HIC. In addition, patients with HIC showed elevated MEG3 expression and inhibited miR‐19a‐3p expression, thus establishing a negative correlation between MEG3 and miR‐19a‐3p. MEG3 and TLR7 were both identified as targets of miR‐19a‐3p, establishing a MEG3/miR‐19a‐3p/TLR7 signaling pathway, in which MEG3 enhances the expression of TLR7 via inhibiting the expression of miR‐19a‐3p.

Conclusion

MEG3 level was upregulated in patients with HIC. In addition, MEG3 downregulated miR‐19a‐3p expression while upregulating TLR7 expression. Furthermore, MEG3 contributes to the pathogenesis of HIC. Therefore, exosomal MEG3 in urine can be used as a biomarker for HIC diagnosis.
MiR‐1827 functions as a tumor suppressor in lung adenocarcinoma by targeting MYC and FAM83F
Authors: Fan Gongchun , Xu Peng , Tu Peng
Published: October 2019

The bioactivity of microRNA‐1827 (miR‐1827) in lung adenocarcinoma cells would be explored. The expression level of gene and miR‐1827 in 76 pairs of lung adenocarcinoma tissues and adjacent counterparts were analyzed by a quantitative real‐time polymerase chain reaction. Primary lung adenocarcinoma cells were derived from patients’ tissues. These cells were treated with miR‐1827 agomir to mimic the upregulation of endogenous miR‐1827. The malignant degree of lung adenocarcinoma cells in vitro was evaluated by cell proliferation, colony formation, transwell invasion, and apoptosis assays. Western blot analysis was used to observe the transition of lung adenocarcinoma cells from epithelial‐to‐mesenchymal. Target genes of miR‐1827 were predicted by bioinformatics analysis. In addition, the interaction between miR‐1827 and candidate messenger RNAs was verified by dual‐luciferase reporter assay and AGO2‐RNA immunoprecipitation. Besides, the effect of miR‐1827 on tumors was verified by in vivo experiments. Transient gene overexpression was achieved by plasmids transfection. In this study, we found that the expression of miR‐1827 was downregulated in lung adenocarcinoma, and its low expression was significantly correlated with the progression of lung adenocarcinoma and poor prognosis of patients. miR‐1827 overexpression remarkably reduced the malignancy of primary lung adenocarcinoma cells in vitro. MYC and FAM83F were identified as two targeted genes of miR‐1827 in lung adenocarcinoma cells. The levels of these two genes were upregulated in lung adenocarcinoma, and their high expression was significantly associated with the progression of lung adenocarcinoma and poor prognosis of patients. Overexpression of MYC or FAM83F attenuated the effects of miR‐1827 on primary lung adenocarcinoma cells in vitro. In addition, in vivo experiments showed that miR‐1827 inhibited tumor growth by reducing the levels of MYC and FAM83F. In conclusion, miR‐1827 might repress the development of lung adenocarcinoma by targeting oncogenic genes MYC and FAM83F.
New cytotoxic bio‐transformed sesquiterpene by Rhizopus oryzae fungus
Authors: El Aty Abeer Abas Abd , Mohamed Naglaa Salah El‐Deen , Saleh Ibrahim Ahmed , El‐Beih Ahmed Atef , Abdelrazik Mohamed Helmy , Hussien Taha Abdelrahim , Moustafa Mahmoud
Published: October 2019

Due to the rapidly increasing number of pathogenic bacteria, viruses, and tumor cells that possess resistance toward established therapies, lead structures for the development of new drugs are in high demand. The plant material of Tanacetum sinaicum is considered a prolific source of the potent biologically active sesquiterpene Tanacetolide A (1). In our research, we focused on the structural transformation of the substrate Tanacetolide A (compound 1) by suspended culture of the novel locally isolated terrestrial fungus Rhizopus oryzae KX685359. The fungal transformation resulted in the formation of 1β,3α‐dihydroxy‐6α‐hydroperoxy‐eudsm‐4(15)‐ene 12‐oic acid (2) with higher antiproliferative activity against colon cancer cell line (Caco‐2) than that of the parent compound (1).
Reflections from novice youth participatory action researchers: Emphasis on critical gender perspectives
Authors: Pech Alexandria S. , Valencia Bryant G. , Romero Andrea J.
Published: October 2019

Rooted in multiracial feminist theory, this research investigated the roles of adults engaged in youth participatory action research (YPAR) projects focused on developing critical perspectives of gender, power, and critical hope with the youth of color. Across 10 weeks, two novice adult facilitators documented ethnographic observations (i.e., voice memos) of their experiences collaborating with youth in YPAR. Voice memos were transcribed and coded for emergent themes. Our findings highlight how we deconstructed adultism, prioritized humanizing youth, and integrated critical gender perspectives to understand gender as a mechanism of systemic oppression. Our purpose was to capture moments of breakthroughs, realizations, and tensions as scholars contending with inexperience in YPAR and share our journey with other researchers interested in YPAR. We provide recommendations for adults to develop pathways towards humanity for the youth of color, collective resistance and take social justice action steps towards a critically hopeful future.
Quality of collaboration within health promotion partnerships: Impact on sense of community, empowerment, and perceived projects' outcomes
Authors: Cicognani Elvira , Albanesi Cinzia , Valletta Luana , Prati Gabriele
Published: October 2019

Community coalitions or intersectoral partnerships have long been advocated for the promotion of population health. In the present study, we assessed the quality of the functioning of health promotion partnerships created within a large community health promotion program implemented by the Emilia‐Romagna region located in the north‐east of Italy (2014–2016). In particular, we aimed to test the effectiveness of partnership working in strengthening participants' empowerment, sense of community and ultimately, the outcomes of a well‐functioning partnership, conceptualized as including perceived effectiveness of health promotion interventions developed by the partnership, trust in their implementation and personal commitment in health promotion in the future. Participants were 238 stakeholders (e.g., health professionals, representatives of local administrations, teachers, representative of community and volunteer organizations, and citizens) formally included in six partnerships lead by six major local health services. Using Bayesian structural equation modeling, we found that a higher perceived quality of collaboration within the partnership enhances the outcomes of a well‐functioning partnership, by strengthening their sense of a health‐promoting community and empowerment. Sense of community responsibility did not predict future commitment in health promotion. The study findings suggest that community members' ownership and feeling of responsibility, as well as empowerment constitute positive partnership processes.
MicroRNAs: Small molecules with a large impact on pre‐eclampsia
Authors: Hemmatzadeh Maryam , Shomali Navid , Yousefzadeh Yousef , Mohammadi Hamed , Ghasemzadeh Aliyeh , Yousefi Mehdi
Published: October 2019

As critical mediators in biological processes, microRNAs (miRNAs) which are small and endogenous noncoding RNAs have been associated with disease progression, cell proliferation, and development. Pre‐eclampsia (PE), a pregnancy‐related disorder with no early markers or symptoms is recognized as the main reason for fetal and maternal mortality and morbidity in the initial steps or even during pregnancy, worldwide. Clinical symptoms usually appear in the third trimester of the pregnancy. Although numerous research have unraveled several aspects of placenta development abnormalities associated with abnormal trophoblastic invasion and angiogenesis modification, many questions about the PE pathogenesis remains unanswered. A large number of studies have shown the important role of miRNAs as potential biomarkers in the PE prognosis and diagnosis. Here, the latest investigations about the PE and placental miRNAs expression, as well as, the crucial role of miRNA molecules including miR‐210 and miR‐155 which are deregulated in patients with PE, will be argued.
HIV testing services in healthcare facilities in South Africa: a missed opportunity
Authors: Mabuto Tonderai , Hansoti Bhakti , Kerrigan Deanna , Mshweshwe‐Pakela Nolundi , Kubeka Griffiths , Charalambous Salome , Hoffmann Christopher
Published: October 2019

Introduction

South Africa (SA) has the world's highest burden of HIV infection (approximately 7.2 million), yet it is estimated that 23.5% women and 31.5% of men are unaware that they are living with HIV. The 2015 national South African HIV testing guidelines mandate the universal offer of HIV testing services (HTS) in all healthcare facilities.

Methods

A multi‐prong approach was used from January 2017 to June 2017 to evaluate the current implementation of HTS in ten facilities in the Ekurhuleni District of SA. First, we conducted patient exit interviews to quantify engagement in HTS services. Second, we systematically mapped the flow of individual patients through the clinic.

Results

We conducted a total of 2989 exit interviews and followed 568 patients for value stream mapping. Overall self‐reported testing acceptance was high at 84.7% (244), but <10% of the patients (288) were offered testing. Female patients were more likely to be offered testing (233/2046, 11.4% vs. 55/943, 5.8% in males; chi‐square p < 0.005), and also more likely to accept testing (203/233, 87.1% vs. 41/55, 74.6% in males; chi‐square p = 0.02). Value stream mapping revealed that patients offered HIV testing had a total visit time of 51 minutes more (95% CI: 30‐72) compared to those not offered testing.

Conclusions

The poor delivery of HTS appears to be due to a failure to recommend HTS and the added time burden placed on those accepting testing. There were significant differences in both the offer and acceptance of testing by gender. Health system issues need to be addressed to improve HTS delivery.
Genomic instability of TnSMU2 contributes to Streptococcus mutans biofilm development and competence in a cidB mutant
Authors: Turner Matthew E. , Huynh Khanh , Carney O’neshia V. , Gross Dennis , Carroll Ronan K. , Ahn Sang‐Joon , Rice Kelly C.
Published: October 2019

Streptococcus mutans is a key pathogenic bacterium in the oral cavity and a primary contributor to dental caries. The S. mutans Cid/Lrg system likely contributes to tolerating stresses encountered in this environment as cid and/or lrg mutants exhibit altered oxidative stress sensitivity, genetic competence, and biofilm phenotypes. It was recently noted that the cidB mutant had two stable colony morphologies: a “rough” phenotype (similar to wild type) and a “smooth” phenotype. In our previously published work, the cidB rough mutant exhibited increased sensitivity to oxidative stress, and RNAseq identified widespread transcriptomic changes in central carbon metabolism and oxidative stress response genes. In this current report, we conducted Illumina‐based genome resequencing of wild type, cidB rough, and cidB smooth mutants and compared their resistance to oxidative and acid stress, biofilm formation, and competence phenotypes. Both cidB mutants exhibited comparable aerobic growth inhibition on agar plates, during planktonic growth, and in the presence of 1 mM hydrogen peroxide. The cidB smooth mutant displayed a significant competence defect in BHI, which was rescuable by synthetic CSP. Both cidB mutants also displayed reduced XIP‐mediated competence, although this reduction was more pronounced in the cidB smooth mutant. Anaerobic biofilms of the cidB smooth mutant displayed increased propidium iodide staining, but corresponding biofilm CFU data suggest this phenotype is due to cell damage and not increased cell death. The cidB rough anaerobic biofilms showed altered structure relative to wild type (reduced biomass and average thickness) which correlated with decreased CFU counts. Sequencing data revealed that the cidB smooth mutant has a unique “loss of read coverage” of ~78 kb of DNA, corresponding to the genomic island TnSMU2 and genes flanking its 3′ end. It is therefore likely that the unique biofilm and competence phenotypes of the cidB smooth mutant are related to its genomic changes in this region.
Discretization Approaches to Model Metal Cutting with Lagrangian, Arbitrary Lagrangian Eulerian and Smooth Particle Hydrodynamics formulations
Authors: Sridhar Praveen , de Payrebrune Kristin M.
Published: October 2019

With significant technological growth and computing power it is possible to simulate metal cutting processes with different discretization techniques. Classically the Lagrangian or Eulerian finite element formulations are used to model metal cutting process. Lagrangian approach is accurate with it's representation of the domain boundary, but requires a re‐meshing procedure to avoid element distortions. Eulerian approach provides a steady state solution of the chip‐workpiece separation, however its limitation lies in the treatment of convective terms during motion. The Arbitrary Lagrangian‐Eulerian method can be used to combine the advantages of both methods and avoid the disadvantages. In the Lagrangian framework, use of a meshless technique– Smooth Particle Hydrodynamics (SPH) has its advantage in large strain deformation problems without the need for re‐meshing algorithms. This work compares the LAG, ALE and SPH approaches by modelling a turning process.
A single‐center experience using alemtuzumab, fludarabine, melphalan, and thiotepa as conditioning for transplantation in pediatric patients with chronic granulomatous disease
Authors: Bhatt Sima T. , Schulz Ginny , Hente Monica , Slater Ashley , Murray Lisa , Shenoy Shalini , Bednarski Jeffrey J.
Published: October 2019

Chronic granulomatous disease (CGD) is an immune deficiency characterized by defective neutrophil function and increased risk of life‐threatening infections. Allogeneic hematopoietic cell transplantation is curative for CGD, and conditioning regimen impacts transplant‐related outcomes. We report a single‐center prospective study (NCT01821781) of four patients with CGD transplanted using a reduced‐intensity conditioning regimen (RIC) containing alemtuzumab, fludarabine, melphalan, and thiotepa. Patients had early immune reconstitution with low incidence of infections. Disease‐free survival was 75% at a median of five years after transplant. This RIC regimen presents an alternative approach for transplant of patients with CGD who may not tolerate busulfan‐based conditioning.
Comparing ground‐based observations and a large‐eddy simulation of shallow cumuli by isolating the main controlling factors of the mass flux distribution
Authors: Sakradzija Mirjana , Klingebiel Marcus
Published: October 2019

The distribution of mass flux at the cloud base has long been thought to be independent of large‐scale forcing. However, recent idealized modelling studies have revealed its dependence on some large‐scale conditions. Such dependence makes it possible to isolate the observed large‐scale conditions, which are similar to those in large‐eddy simulations (LES), in order to compare the observed and modelled mass flux distributions. In this study, we derive for the first time the distribution of the cloud‐base mass flux among individual shallow cumuli from ground‐based observations at the Barbados Cloud Observatory (BCO) and compare it with the Rain In Cumulus over the Ocean (RICO) LES case study. The procedure of cloud sampling in LES mimics the pointwise measurement procedure at the BCO to provide a mass flux metric that is directly comparable with observations. We find a difference between the mass flux distribution observed during the year 2017 at the BCO and the distribution modelled by LES that is comparable to the seasonal changes in the observed distribution. This difference between the observed and modelled distributions is diminished and an extremely good match is found by subsampling the measurements under a similar horizontal wind distribution and area‐averaged surface Bowen ratio to those modelled in LES. This provides confidence in our observational method and shows that LES produces realistic clouds that are comparable to those observed in nature under the same large‐scale conditions. We also confirm that the stronger horizontal winds and higher Bowen ratios in our case study shift the distributions to higher mass flux values, which is coincident with clouds of larger horizontal areas and not with stronger updrafts.
Two‐sample test based on classification probability
Authors: Cai Haiyan , Goggin Bryan , Jiang Qingtang
Published: October 2019

Robust classification algorithms have been developed in recent years with great success. We take advantage of this development and recast the classical two‐sample test problem in the framework of classification. Based on the estimates of classification probabilities from a classifier trained from the samples, a test statistic is proposed. We explain why such a test can be a powerful test and compare its performance in terms of the power and efficiency with those of some other recently proposed tests with simulation and real‐life data. The test proposed is nonparametric and can be applied to complex and high‐dimensional data wherever there is a classifier that provides consistent estimate of the classification probability for such data.
Flammrichten normal‐ und hochfester Baustähle
Authors: Feldmann Markus , Schäfer Dirk
Published: October 2019

Bedingt durch ein großes Parameterfeld und instationäre Temperatur‐ und Dehnungsverteilungen erscheint der Prozess des Flammrichtens relativ komplex. So basiert das Flammrichten bis heute insbesondere hinsichtlich der erzielbaren Verformungen eher auf – wenn auch plausiblen – Erfahrungswerten als auf ingenieurtechnischen Ansätzen. Hinsichtlich der Materialbeeinflussung existieren hingegen technische Regeln, die Festigkeits‐ und Zähigkeitseinbußen ausschließen sollen. Bei Einsatz hochfester Sorten verändern sich jedoch die Verhältnisse im Vergleich zu normalfesten Stählen, denn mit zunehmender Streckgrenze werden die erzielbaren Verformungen kleiner. Zum Ausgleich dieses Effekts werden oft höhere Temperaturen und Haltezeiten gewählt, was jedoch das Risiko einer Materialbeeinflussung erhöht. Für das Flammrichten hoch‐ und höchstfester Stähle sind also solche Konstellationen zu erforschen, die zu einem nach wie vor einfachen und sicheren Ergebnis führen. Dies zeigt der vorliegende Beitrag in zwei Teilen, indem er die werkstofftechnischen Mechanismen für das Flammrichten auch bei hohen Streckgrenzen klärt. Ausgehend davon werden Anwendungskorridore abgeleitet und Vorschläge für die Verbesserung bestehender Regeln gemacht.

In diesem ersten Teil des Beitrags werden das Prinzip des Flammrichtens normal‐ und hochfester Stähle nebst den Zusammenhängen zwischen Thermodynamik, Metallurgie und Mechanik vorgestellt sowie anhand von Versuchen an Kleinproben die experimentelle und numerische Ermittlung des Wärmeeintrags und der Temperaturen gezeigt.

Der zweite Teil widmet sich den Verformungen und Zwangsmomenten aus dem Flammrichtprozess, der Beeinflussung des Materials und zwei Beispielen zur Vorhersage der Ergebnisse aus dem Flammrichten.