bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Interfacial Solar Steam Generator with Controlled Macromorphology Derived from Flour via “Dough Figurine” Technology
Authors: Li Zhengtong , Wang Chengbing , Li Zeyu , Deng Lin , Su Jinbu , Shi Jing , An Meng
Published: May 2019

A solar‐driven interface steam generator (SISG) has potential applications in saline water desalination and polluted water purification. A shape‐ and size‐controlled, low‐cost, eco‐friendly solar‐absorber material is urgently desired for practical applications of SISGs. Herein, a facile, sustainable, and scalable approach is proposed to produce tailored SISGs with controlled macromorphology derived from flour via “dough figurine” technology originating from the China Han Dynasty. Three kinds of self‐floated flour‐based absorbers, i.e., near‐cylindrical (integrated), near‐spherical (loose packing), and powdery (dense packing) absorber used as SISGs, are discussed. More importantly, it is found that the macromorphology significantly influences water transport and interfacial thermal management of SISGs; thus the integrated absorber has an obvious advantage over the other two absorbers, which possesses a high evaporation efficiency of 71.9% at normal solar illumination. The proposed “dough figurine” technology breaks the limitations of the inherent geometry of reported biomass‐based SISGs, which provides an important guidance for SISG use in remote and impoverished areas.
Pharmacologic Inhibition of Epidermal Growth Factor Receptor Suppresses Nonalcoholic Fatty Liver Disease in a Murine Fast‐Food Diet Model
Authors: Bhushan Bharat , Banerjee Swati , Paranjpe Shirish , Koral Kelly , Mars Wendy M. , Stoops John W. , Orr Anne , Bowen William C. , Locker Joseph , Michalopoulos George K.
Published: May 2019

Epidermal growth factor receptor (EGFR) is a critical regulator of hepatocyte proliferation and liver regeneration. Our recent work indicated that EGFR can also regulate lipid metabolism during liver regeneration after partial hepatectomy. Based on these findings, we investigated the role of EGFR in a mouse model of nonalcoholic fatty liver disease (NAFLD) using a pharmacological inhibition strategy. C57BL6/J mice were fed a chow diet or a fast‐food diet (FFD) with or without EGFR inhibitor (canertinib) for 2 months. EGFR inhibition completely prevented development of steatosis and liver injury in this model. In order to study if EGFR inhibition can reverse NAFLD progression, mice were fed the FFD for 5 months, with or without canertinib treatment for the last 5 weeks of the study. EGFR inhibition remarkably decreased steatosis, liver injury, and fibrosis and improved glucose tolerance. Microarray analysis revealed that ~40% of genes altered by the FFD were differentially expressed after EGFR inhibition and, thus, are potentially regulated by EGFR. Several genes and enzymes related to lipid metabolism (particularly fatty acid synthesis and lipolysis), which were disrupted by the FFD, were found to be modulated by EGFR. Several crucial transcription factors that play a central role in regulating these lipid metabolism genes during NAFLD, including peroxisome proliferator–activated receptor gamma (PPARγ), sterol regulatory element‐binding transcription factor 1 (SREBF1), carbohydrate‐responsive element‐binding protein, and hepatocyte nuclear factor 4 alpha, were also found to be modulated by EGFR. In fact, chromatin immunoprecipitation analysis revealed that PPARγ binding to several crucial lipid metabolism genes (fatty acid synthase, stearoyl‐coenzyme A desaturase 1, and perilipin 2) was drastically reduced by EGFR inhibition. Further upstream, EGFR inhibition suppressed AKT signaling, which is known to control these transcription factors, including PPARγ and SREBF1, in NAFLD models. Lastly, the effect of EGFR in FFD‐induced fatty‐liver phenotype was not shared by receptor tyrosine kinase MET, investigated using MET knockout mice. Conclusion: Our study revealed a role of EGFR in NAFLD and the potential of EGFR inhibition as a treatment strategy for NAFLD.
Interferon‐Induced Transmembrane Proteins Mediate Viral Evasion in Acute and Chronic Hepatitis C Virus Infection
Authors: Wrensch Florian , Ligat Gaëtan , Heydmann Laura , Schuster Catherine , Zeisel Mirjam B. , Pessaux Patrick , Habersetzer François , King Barnabas J. , Tarr Alexander W. , Ball Jonathan K. , Winkler Michael , Pöhlmann Stefan , Keck Zhen‐yong , Foung Steven K.H. , Baumert Thomas F.
Published: May 2019

Although adaptive immune responses against hepatitis C virus (HCV) infection have been studied in great detail, the role of innate immunity in protection against HCV infection and immune evasion is only partially understood. Interferon‐induced transmembrane proteins (IFITMs) are innate effector proteins restricting host cell entry of many enveloped viruses, including HCV. However, the clinical impact of IFITMs on HCV immune escape remains to be determined. Here, we show that IFITMs promote viral escape from the neutralizing antibody (nAb) response in clinical cohorts of HCV‐infected patients. Using pseudoparticles bearing HCV envelope proteins from acutely infected patients, we show that HCV variants isolated preseroconversion are more sensitive to the antiviral activity of IFITMs than variants from patients isolated during chronic infection postseroconversion. Furthermore, HCV variants escaping nAb responses during liver transplantation exhibited a significantly higher resistance to IFITMs than variants that were eliminated posttransplantation. Gain‐of‐function and mechanistic studies revealed that IFITMs markedly enhance the antiviral activity of nAbs and suggest a cooperative effect of human monoclonal antibodies and IFITMs for antibody‐mediated neutralization driving the selection pressure in viral evasion. Perturbation studies with the IFITM antagonist amphotericin B revealed that modulation of membrane properties by IFITM proteins is responsible for the IFITM‐mediated blockade of viral entry and enhancement of antibody‐mediated neutralization. Conclusion: Our results indicate IFITM proteins as drivers of viral immune escape and antibody‐mediated HCV neutralization in acute and chronic HCV infection. These findings are of clinical relevance for the design of urgently needed HCV B‐cell vaccines and might help to increase the efficacy of future vaccine candidates.
Development of electrically conductive hybrid nanofibers based on CNT‐polyurethane nanocomposite for cardiac tissue engineering
Authors: Shokraei Nasim , Asadpour Shiva , Shokraei Shabnam , Nasrollahzadeh Sabet Mehrdad , Faridi‐Majidi Reza , Ghanbari Hossein
Published: May 2019

Conductive nanofibers have been considered as one of the most interesting and promising candidate scaffolds for cardiac patch applications with capability to improve cell–cell communication. Here, we successfully fabricated electroconductive nanofibrous patches by simultaneous electrospray of multiwalled carbon nanotubes (MWCNTs) on polyurethane nanofibers. A series of CNT/PU nanocomposites with different weight ratios (2:10, 3:10, and 6:10wt%) were obtained. Scanning electron microscopy, conductivity analysis, water contact angle measurements, and tensile tests were used to characterize the scaffolds. FESEM showed that CNTs were adhered on PU nanofibers and created an interconnected web‐like structures. The SEM images also revealed that the diameters of nanofibers were decreased by increasing CNTs. The electrical conductivity, tensile strength, Young's modulus, and hydrophilicity of CNT/PU nanocomposites also enhanced after adding CNTs. The scaffolds revealed suitable cytocompatibility for H9c2 cells and human umbilical vein endothelial cells (HUVECs). This study indicated that simultaneous electrospinning and electrospray can be used to fabricate conductive CNT/PUnanofibers, resulting in better cytocompatibility and improved interactions between the scaffold and cardiomyoblasts.
A comparison of diverticulitis in Crohn's disease versus ulcerative colitis
Authors: Persaud Alana , Ahmed Ahmed , Kakked Gaurav , Shulik Oleg , Ahlawat Sushil
Published: May 2019

Background and Aim

Inflammatory bowel disease (IBD) and diverticulitis both increase morbidity, especially when associated with in‐patient hospitalization. This study aimed to evaluate whether hospitalization burden differs for diverticulitis in patients with a history of Crohn's disease (CD) compared to ulcerative colitis (UC).

Method

All patients hospitalized for acute diverticulitis with pre‐existing UC or CD in 2014 were selected using the national in‐patient sample. Cases were identified using the International Classification of Diseases, Ninth Edition codes. Primary outcomes were mortality, cost of admission, length of stay (LOS), and colectomy.

Results

A total of 1815 patients were admitted with diverticulitis, and those with CD had a hospitalization associated with decreased cost (aOR −14 537, 95% CI −27 316 to −1758; P = 0.026) and LOS (aOR −1.31, 95% CI −2.41 to −0.208; P = 0.02) compared to UC. A second analysis comparing diverticulitis hospitalization between those with CD and those with the absence of IBD showed no significant difference in mortality (aOR 2.47, 95% CI 0.59 to 10.36; P = 0.22), LOS (aOR 0.03, 95% CI −0.47 to 0.54; P = 0.92), or cost of admission (aOR −2196, 95% CI −6933 to 2539; P = 0.36) between the cohorts.

Conclusion

Patients with UC have worsened hospitalization outcomes when being treated for diverticulitis compared to CD. While the findings may be a result of a difference in colectomy rates, the etiology may also be multifactorial. These conclusions have not been previously described, and further investigations would better characterize these associations.
Macrophage priming is dispensable for NLRP3 inflammasome activation and restriction of Leishmania amazonensis replication
Authors: de Carvalho Renan V H , Silva Alexandre L N , Santos Leonardo L , Andrade Warrison A , de Sá Keyla S G , Zamboni Dario S
Published: May 2019

The NLRP3 inflammasome is activated in response to multiple stimuli and triggers activation of caspase-1 (CASP1), IL-1β production, and inflammation. NLRP3 activation requires two signals. The first leads to transcriptional regulation of specific genes related to inflammation, and the second is triggered when pathogens, toxins, or specific compounds damage cellular membranes and/or trigger the production of reactive oxygen species (ROS). Here, we assess the requirement of the first signal (priming) for the activation of the NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) infected with Leishmania amazonensis. We found that BMDMs express the inflammasome components NLRP3, ASC, and CASP1 at sufficient levels to enable the assembly and activation of NLRP3 inflammasome in response to infection. Therefore, priming was not required for the formation of ASC specks, CASP1 activation (measured by fluorescent dye FAM-YVAD), and restriction of L. amazonensis replication via the NLRP3 inflammasome. By contrast, BMDM priming was required for CASP1 cleavage (p20) and IL-1β secretion, because priming triggers robust up-regulation of pro-IL-1β and CASP11 that are important for efficient processing of CASP1 and IL-1β. Taken together, our data shed light into the cellular and molecular processes involved in activation of the NLRP3 in macrophages by Leishmania, a process that is important for the outcome of Leishmaniasis.
Leadership in Postmodernity: A Dystopia of Crumbling Façades and Apathy
Authors: Jackson Ross , Reboulet Amanda , Bode Tim
Published: May 2019

Visions of leadership range from the sublime to the despairing. Between these extremes, future leadership might be defined in ways largely indistinguishable from its past. As those producing leadership literature are incentivized to create more of the same, it is useful to question whether its consumption will follow suit. With its rejection of metanarratives, situating leadership in postmodernity provides space in which to interrogate what is taking place within this field, and to start to sketch its implications for the future. Corpus linguistics approaches were applied to a sample of leadership publications to reveal rhetorical sediments. In particular, the concept of power was analyzed to explore how it is presented in leadership literature situated in postmodernity. Through this process, a dystopian picture potentially emerges in which a façade of leadership crumbles and a form of apathy of those engaged in its propagation is betrayed.
Interaction of aloe active compounds with calf thymus DNA
Authors: Das Abhi , Suresh Kumar Gopinatha , Dutta Sanjay
Published: May 2019

Natural anthraquinone compounds have emerged as potent anticancer chemotherapeutic agents because of their promising DNA‐binding properties. Aloe vera is among one of the very well‐known medicinal plants, and the anthraquinone derivatives like aloe emodin (ALM), aloins (ALN), and aloe emodin‐8‐glucoside (ALMG) are known to have immense biological activities. Here, we have used biophysical methods to elucidate the comparative DNA‐binding abilities of these three molecules. Steady‐state fluorescence study indicated complexation between calf thymus DNA (ctDNA) and both the molecules ALM and ALMG whereas ALN showed very weak interaction with DNA. Displacement assays with ctDNA‐bound intercalator (ethidium bromide) and a groove binder (Hoechst 33258) indicated preferential binding of both ALM and ALMG to minor groove of DNA. Isothermal titration calorimetric (ITC) data suggested spontaneous exothermic single binding mode of both the molecules: ALM and ALMG. Entropy is the most important factor which contributed to the standard molar Gibbs energy associated with relatively small favorable enthalpic contribution. The equilibrium constants of binding to ctDNA were (6.02 ± 0.10) × 104 M−1 and (4.90 ± 0.11) × 104 M−1 at 298.15 K, for ALM and ALMG, respectively. The enthalpy vs temperature plot yielded negative standard molar heat capacity value, and a strong negative correlation between enthalpy and entropy terms was observed which indicates the enthalpy entropy compensation behavior in both systems. All these thermodynamic phenomena indicate that hydrophobic force is the key factor which is involved in the binding process. Moreover, the enhancement of thermal stability of DNA helix by ALM and ALMG fully agreed to the complexation of these molecules with DNA.
Cartilage Wear Particles Induce an Inflammatory Response Similar to Cytokines in Human Fibroblast‐Like Synoviocytes
Authors: Estell Eben G. , Silverstein Amy M. , Stefani Robert M. , Lee Andy J. , Murphy Lance A. , Shah Roshan P. , Ateshian Gerard A. , Hung Clark T.
Published: May 2019

The synovium plays a key role in the development of osteoarthritis, as evidenced by pathological changes to the tissue observed in both early and late stages of the disease. One such change is the attachment of cartilage wear particles to the synovial intima. While this phenomenon has been well observed clinically, little is known of the biological effects that such particles have on resident cells in the synovium. The present work investigates the hypothesis that cartilage wear particles elicit a pro‐inflammatory response in diseased and healthy human fibroblast‐like synoviocytes, like that induced by key cytokines in osteoarthritis. Fibroblast‐like synoviocytes from 15 osteoarthritic human donors and a subset of three non‐osteoarthritic donors were exposed to cartilage wear particles, interleukin‐1α or tumor necrosis factor‐α for 6 days and analyzed for proliferation, matrix production, and release of pro‐inflammatory mediators and degradative enzymes. Wear particles significantly increased proliferation and release of nitric oxide, interleukin‐6 and ‐8, and matrix metalloproteinase‐9, ‐10, and ‐13 in osteoarthritic synoviocytes, mirroring the effects of both cytokines, with similar trends in non‐osteoarthritic cells. These results suggest that cartilage wear particles are a relevant physical factor in the osteoarthritic environment, perpetuating the pro‐inflammatory and pro‐degradative cascade by modulating synoviocyte behavior at early and late stages of the disease. Future work points to therapeutic strategies for slowing disease progression that target cell‐particle interactions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1979–1987, 2019
Detecting Ankle Instability With an Instrumented Ankle Arthrometer: An Experimental Study
Authors: Gehring Dominic , Li Lu , Bonsignore Giuseppe , Dorn‐Lange Nadja , Gollhofer Albert , Lohrer Heinz
Published: May 2019

A new instrumented device was developed to quantify ankle joint stability during an anterior talar drawer test. The aim of the present study was to validate this device comparing bone kinematics with arthrometer measurement outcomes. An anterior talar drawer test was performed with 14 cadaver legs using a custom instrumented ankle arthrometer. Using clusters of bone‐pin markers, the relative three‐dimensional movement of calcaneus, talus, and fibula was simultaneously measured. Anterior drawer test was applied on the intact foot and after sequentially sectioning the anterior talofibular ligament, the calcaneofibular ligament, and the posterior talofibular ligament. Cutting the anterior talofibular ligament caused a significant increase in bone‐pin measured anterior translations of calcaneus and talus as well as in the anterior translation of the arthrometer. Analysis of receiver operating characteristic curves indicates a fair to good ability to discriminate between the intact and the sectioned conditions with the arthrometer. Distal distraction, inversion, and internal rotation movements were observed when two and three ligaments were cut. Results revealed that the ankle arthrometer was sensitive to detect changes in bone‐to‐bone movements during an anterior talar drawer test, when the anterior talofibular ligament was sectioned. Presumably due to movements in additional planes of motion, the arthrometer was not able to differentiate between situations with one or more ligaments cut. In conclusion, the instrumented anterior talar drawer tester may augment current procedures in assessing ankle instability primarily caused by ruptures of the anterior talofibular ligament. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2019–2026, 2019
Use of Allogeneic Hypoxic Mesenchymal Stem Cells For Treating Disc Degeneration in Rabbits
Authors: Chiang En‐Rung , Ma Hsiao‐Li , Wang Jung‐Pan , Chang Ming‐Chau , Liu Chien‐Lin , Chen Tain‐Hsiung , Hung Shih‐Chieh
Published: May 2019

Intervertebral discs (IVDs) are important biomechanical components of the spine. Once degenerated, mesenchymal stem cell (MSC)‐based therapies may aid in the repair of these discs. Although hypoxic preconditioning enhances the chondrogenic potential of MSCs, it is unknown whether bone marrow MSCs expanded under hypoxic conditions (1% O2, here referred to as hypoxic MSCs) are better than bone marrow MSCs expanded under normoxic conditions (air, here referred to as normoxic MSCs) with regards to disc regeneration capacity. The purpose of this study was to compare the therapeutic effects of hypoxic and normoxic MSCs in a rabbit needle puncture degenerated disc model after intra‐disc injection. Six weeks after needle puncture, MSCs were injected into the IVD. A vehicle‐treated group and an un‐punctured sham‐control group were included as controls. The tissues were analyzed by histological and immunohistochemical methods 6 and 12 weeks post‐injection. At 6 and 12 weeks, less disc space narrowing was evident in the hypoxic MSC‐treated group compared to the normoxic MSC‐treated group. Significantly better histological scores were observed in the hypoxic MSC group. Discs treated with hypoxic MSCs also demonstrated significantly better extracellular matrix deposition in type II and XI collagen. Increased CD105 and BMP‐7 expression were also observed upon injection of hypoxic MSCs. In conclusion, hypoxic MSC injection was more effective than normoxic MSC injection for reducing IVD degeneration progression in vivo. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1440–1450, 2019.
Ultrasound Evaluation of Dermal Sinuses/Fistulas in Pediatric Patients
Authors: Hosokawa Takahiro , Takahashi Hiroaki , Miyasaka Yusuke , Ohira Kenji , Tanami Yutaka , Sato Yumiko , Ishimaru Tetsuya , Kawashima Hiroshi , Hosokawa Mayumi , Oguma Eiji , Yamada Yoshitake
Published: May 2019

A dermal sinus/fistula is a common condition; the relevant department should be consulted for appropriate treatment. It is important for radiologists to have adequate knowledge of these conditions to provide the correct diagnosis and recommend subsequent management. This review describes the following lesions: preauricular sinus, midline sinus of the upper lip, nasal dermoid sinus cyst, cheek fistula, first branchial cleft anomaly/sublingual branchial cleft anomaly, thyroglossal duct cyst/fistula, lateral cervical sinus/fistula, congenital dermal sinus/fistula of the anterior chest region, congenital skin sinus/fistula with a sternal cleft, and congenital prepubic sinus. On the basis of the skin orifice location and ultrasound images, radiologists can provide useful information to physicians.
Kinetics of epoxidation by a Musa paradisiaca chloroperoxidase
Authors: Yadav Pratibha , Khare Sunil K. , Sharma Satyawati
Published: May 2019

Epoxidations of indene, styrene, 2‐chlorostyrene, 3‐chlorostyrene, 4‐chlorostyrene, 4‐bromostyrene, and naphthalene using Musa paradisiaca plant juice chloroperoxidase in the presence of H2O2 and t‐butyl peroxide as oxidants have been studied. The steady‐state kinetic parameters, Km and kcat of the enzyme for the above substrates have been determined. The temperature and pH optima of the epoxidation are 25°C and 6.2, respectively. The yield of styrene oxide in the presence of H2O2 was 44%. The results show that M. paradisiaca plant juice chloroperoxidase is a potential biocatalyst for organic epoxidation reactions.
Objective measures and the standardized letter of recommendation in the otolaryngology residency match
Authors: Hu Allison C. , Gu Jeffrey T. , Wong Brian J. F.
Published: May 2019

Objectives/Hypothesis

The objective of this study were to determine if any of the 10 attributes of the standardized letter of recommendation (SLOR) correlate significantly with objective measures of each applicant and to determine whether professor characteristics were associated with reported SLOR attributes.

Study Design

Retrospective cohort study.

Methods

We reviewed 339 SLORs from 187 otolaryngology residency applicants. The 10 SLOR attributes were converted into a percentile score and statistically analyzed.

Results

All 10 SLOR attributes had a mean ± standard deviation above the 80th percentile (0.82‐0.93 ± 0.08‐0.52) and negative skewness. United States Medical Licensing Examination step 1 and 2 scores correlated most strongly with match potential (B = 93.1,P < .001 and B = 96.3, P = .002, respectively). Students from top 40 National Institutes of Health–funded institutions had a significant difference in length of relationship with their letter writer (B = −0.51, P = .02) and interpersonal communication skills (B = −12.9, P = .011). Alpha Omega Alpha (AOA) and non‐AOA members differed in medical knowledge (B = 21.0, P = .007), research (B = −8.80, P = .036), and commitment to otolaryngology (B = −25.89, P = .020). Total number of research experiences correlated most strongly with medical knowledge (B = −16.55, P = .011). There was a significant difference in means between length of relationship and professorial rank (F[4, 339] = 3.61, P = .023), administrative position (F[5, 339] = 5.43, P = .002), and institution of the letter writer (P < .001).

Conclusions

Overall, the lack of correlation between SLOR attributes and objective measures suggests that the SLOR adds little to the residency application. Professor characteristics were similarly not associated with any of the 10 SLOR attributes; however, there were significant differences in the length of relationship between the professor and students with respect to professor rank, administrative rank, and institution of the letter writer.

Level of Evidence

NA

Laryngoscope, 130:603–608, 2020
Head‐Up Sleep May Cure Patients With Intractable Benign Paroxysmal Positional Vertigo: A six‐Month Randomized Trial
Authors: Horinaka Akira , Kitahara Tadashi , Shiozaki Tomoyuki , Ito Taeko , Wada Yoshiro , Yamanaka Toshiaki , Nario Kazuhiko
Published: May 2019

Objectives

The aim of the present study was to assess head‐position management for intractable idiopathic benign paroxysmal positional vertigo (BPPV) when lying down. We hypothesized that head‐up sleep (HUS) could prevent free‐floating otoliths from entering the semicircular canals.

Study Design

A prospective two‐arm multicenter randomized controlled trial.

Methods

BPPV was diagnosed in 611 patients (611/1,520; 40.2%) according to the 2015 diagnostic guidelines issued by the International Classification of Vestibular Disorders. Among them, 201 patients were intractable (201/611; 32.9%), 88 of whom were idiopathic and subsequently enrolled in the study. Patients randomly received intervention with HUS at greater than 45° (n = 44) or head‐down sleep (HDS; n = 44) when lying down. Before treatment, they completed several examinations, including subjective visual vertical (SVV). The specific diagnoses for the 88 patients with BPPV included horizontal type cupula (n = 40), horizontal type canal (n = 13), posterior type (n = 26), and probable and/or atypical BPPV (n = 9).

Results

Patient backgrounds did not differ significantly between the HUS and HDS groups. Visual analog scale (VAS) scores of vertiginous sensation were significantly lower in the HUS group than in the HDS group at both the third month and sixth month post‐treatment. Positional/positioning nystagmus observed just before treatment disappeared significantly more often in the HUS group than in the HDS group until the sixth post‐treatment month. Further, especially in HUS group, VAS scores in SVV− group (n = 24) were significantly lower than those in the SVV+ group (n = 20) sixth month post‐treatment.

Conclusions

Controlling free‐floating otoliths is not easy due to aging of the otolith organs. Repeatedly returning the endless free‐floating debris from the canals to the utricle through physical means is not a good strategy. Therefore, HUS when lying down at home could be recommended as an initial treatment for patients with intractable idiopathic BPPV.

Level of Evidence

1b
In perspective: An update on telomere targeting in cancer
Authors: Sugarman Eric T. , Zhang Gao , Shay Jerry W.
Published: May 2019

Engaging a telomere maintenance mechanism during DNA replication is essential for almost all advanced cancers. The conversion from normal and premalignant somatic cells to advanced malignant cells often results (85%‐90%) from the reactivation of the functional ribonucleoprotein holoenzyme complex, referred to as telomerase. Modulation of the human telomerase reverse transcriptase (hTERT) appears to be rate limiting to produce functional telomerase and engage a telomere maintenance mechanism. The remaining 10% to 15% of cancers overcome progressively shortened telomeres by activating an alternative lengthening of telomeres (ALT) maintenance mechanism, through a DNA recombination pathway. Exploration into the specific mechanisms of telomere maintenance in cancer have led to the development of drugs such as Imetelstat (GRN163L), BIBR1532, 6‐thio‐dG, VE‐822, and NVP‐BEZ235 being investigated as therapeutic approaches for treating telomerase and ALT tumors. The successful use of 6‐thio‐dG (a nucleoside preferentially recognized by telomerase) that targets and uncaps telomeres in telomerase positive but not normal telomerase silent cells has recently shown impressive effects on multiple types of cancer. For example, 6‐thio‐dG overcomes therapy‐resistant cancers in a fast‐acting mechanism potentially providing an alternative or additional route of treatment for patients with cancer. In this perspective, we provide a synopsis of the current landscape of telomeres and telomerase processing in cancer development and how this new knowledge may improve outcomes for patients with cancer.
Oxygen‐sensitive MRI assessment of tumor response to hypoxic gas breathing challenge
Authors: Yang Donghan M. , Arai Tatsuya J. , Campbell James W. , Gerberich Jenifer L. , Zhou Heling , Mason Ralph P.
Published: May 2019

Oxygen‐sensitive MRI has been extensively used to investigate tumor oxygenation based on the response (R2* and/or R1) to a gas breathing challenge. Most studies have reported response to hyperoxic gas indicating potential biomarkers of hypoxia. Few studies have examined hypoxic gas breathing and we have now evaluated acute dynamic changes in rat breast tumors.

Rats bearing syngeneic subcutaneous (n = 15) or orthotopic (n = 7) 13762NF breast tumors were exposed to a 16% O2 gas breathing challenge and monitored using blood oxygen level dependent (BOLD) R2* and tissue oxygen level dependent (TOLD) T1‐weighted measurements at 4.7 T. As a control, we used a traditional hyperoxic gas breathing challenge with 100% O2 on a subset of the subcutaneous tumor bearing rats (n = 6). Tumor subregions identified as responsive on the basis of R2* dynamics coincided with the viable tumor area as judged by subsequent H&E staining. As expected, R2* decreased and T1‐weighted signal increased in response to 100% O2 breathing challenge. Meanwhile, 16% O2 breathing elicited an increase in R2*, but divergent response (increase or decrease) in T1‐weighted signal. The T1‐weighted signal increase may signify a dominating BOLD effect triggered by 16% O2 in the relatively more hypoxic tumors, whereby the influence of increased paramagnetic deoxyhemoglobin outweighs decreased pO2. The results emphasize the importance of combined BOLD and TOLD measurements for the correct interpretation of tumor oxygenation properties.
Synthesis and characterization of PANI/P‐2M conductive composites: Thermal, rheological, mechanical, and electrical properties
Authors: Pati Santwana , Kumar Vipin , Goto Teruya , Takahashi Tatsuhiro , Yokozeki Tomohiro
Published: May 2019

In this article, a new conductive thermosetting resin system was developed using Polyaniline with 2‐Methacryloyloxyethyl acid phosphate (P‐2 M) as a dopant. The resin has shown better steady state viscosity and enhanced mechanical properties as high as 3 ± 0.8 GPa as compared to our previously developed resin system of PANI‐DBSA. A DSC analysis was conducted to estimate the activation energy and the exact amount of energy for doping and curing process of the resin. The resin was synthesized with various wt% of PANI and each combination was characterized in detail. As the amount of PANI was increased, the electrical conductivity significantly enhanced. The maximum electrical conductivity obtained is 0.5 S/m, which is lower than other conductive resins but is many orders higher than epoxy resin. The uncured resin was studied for its viscosity change with shear rate and the constitution of PANI in the resin and we obtained a desirable steady‐state viscosity of the resin. Thus, the newly developed resin with efficient steady state viscosity in the favorable range, optimized electrical conductivity, and superior mechanical properties, can be applied into CFRP fabrication.
Pharmacotherapy of Autism Spectrum Disorder: Results from the Randomized BAART Clinical Trial
Authors: DeVane C. Lindsay , Charles Jane M. , Abramson Ruth K. , Williams John E. , Carpenter Laura A. , Raven Sarah , Gwynette Frampton , Stuck Craig A. , Geesey Mark E. , Bradley Catherine , Donovan Jennifer L. , Hall Alicia G. , Sherk Shelley T. , Powers Nancy R. , Spratt Eve , Kinsman Anne , Kruesi Markus J. , Bragg John E.
Published: May 2019

The objective of this trial, Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART), was to provide support and guidance for an evidence‐based approach for the selection and monitoring of initial pharmacotherapy in patients with autism by assessing predictors of efficacy, tolerability, and safety. This randomized double‐blind parallel‐group study was conducted in three academic medical centers and a single private pediatric practice. Eighty children or adolescents (aged 6–17 yrs) with autistic disorder were enrolled, and 61 patients were randomized to the study drug. Of those patients, 51 completed the 10‐week trial, and 31 completed an optional 12‐week blinded extension phase. All patients were treated with 2 weeks of placebo before random assignment to receive aripiprazole (31 patients) or risperidone (30 patients) for 10 weeks. Sixteen placebo responders (20%) were excluded from further analysis. Drug dosing followed U.S. Food and Drug Administration (FDA) labeling, and weekly dosage adjustments were allowed until week 4; patients were then maintained on a fixed dose for 6 additional weeks. Safety, physical, and psychological assessments were recorded weekly or every 2 weeks. No significant differences in severity of illness between the aripiprazole and risperidone groups were noted at baseline. All patients significantly improved on the Aberrant Behavior Checklist‐Irritability subscale after 1 week and continued for the remaining 9 weeks and the extension phase. Improvement was greatest in the risperidone group at every assessment period and was statistically significantly better than that in the aripiprazole group at weeks 3 and 6 (p<0.05). No dose‐limiting adverse events occurred during the dose‐titration period. Mean weight gain in the aripiprazole group was significantly less than that in the risperidone group at week 4 (0.62 vs 1.38 kg, p=0.033) and week 10 (1.61 vs 3.31 kg, p<0.001), but the difference became nonsignificant for the 31 patients completing the 3‐month extension phase (4.36 vs 5.55 kg, p=0.26). Pharmacotherapy of patients with autism spectrum disorder resulted in behavioral improvement within 1 week and lasted at least 22 weeks. Weight gain occurred to a greater degree with risperidone than aripiprazole initially, but the differences became nonsignificant by the end of the trial. Our trial supports previous results of drug efficacy and safety in patients with autism spectrum disorder from other trials and extends the evidence‐based support for choosing an FDA‐approved drug for initial pharmacotherapy for autism spectrum disorder.
Development of a Combined pH‐ and Redox‐Sensitive Bi‐Electrode Glass Thin‐Film Sensor
Authors: Iken Heiko , Bronder Thomas S. , Goretzki Alexander , Kriesel Jana , Ahlborn Kristina , Gerlach Frank , Vonau Winfried , Zander Willi , Schubert Jürgen , Schöning Michael J.
Published: May 2019

In this work, a combined pH‐ and redox‐sensitive bi‐electrode glass thin‐film sensor is developed for the simultaneous detection of pH and redox potential in aqueous solutions. Therefore, the pH‐ and redox‐sensitive glass bulk materials are prepared first by glass‐pouring processes and tailored regarding the sensing properties as well as the deposition suitability. A layout for the bi‐electrode transducer structure (sensor chip) is developed is been fabricated on a glass substrate via conventional thin‐film techniques. The sensitive glass bulk materials are transferred on the bi‐electrode structures by means of pulsed laser deposition technique (PLD). The fabricated sensors are physically and electrochemically characterized by means of scanning electron microscopy (SEM), Rutherford backscattering spectrometry (RBS), profilometry, impedance‐ and potentiometric measurements. The fabricated sensor structures are successfully tested in the range pH 5–9 and the redox potential in different solutions including also real test samples of soda and pool water.
Energy Transfer Under Electrical Excitation and Enhanced Electroluminescence in the Nanolaminate Yb,Er Co‐Doped Al2O3 Films
Authors: Yang Yang , Ouyang Zhongtao , Liu Jianzhao , Sun Jiaming
Published: May 2019

The energy transfer from Yb3+ to Er3+ ions under electrical excitation which enhances the Er‐related 1531 nm electroluminescence is evidenced, within the nanolaminate Yb,Er co‐doped Al2O3 films fabricated by atomic layer deposition. The light‐emitting devices based on these nanolaminates present an external quantum efficiency up to 24% and the power efficiency of 2.8×10−3, ≈60% higher than the solely Er‐doped Al2O3 device. The decay dynamics also support, with the radiative lifetime of the Yb3+ emission reduced while that of Er3+ emission rises. The Er3+ and Yb3+ ions are impact‐excited by hot electrons, which stem from Poole–Frenkel conduction mechanism in Al2O3 matrix. This work certifies the potential of sensitizing Er3+ ions by the adjacent Yb3+ ions under electrical excitation, and applications of the rare earth‐doped nanolaminates in silicon‐based optoelectronics.
Synthesizing simulation and field data of solar irradiance
Authors: Sun Furong , Gramacy Robert B. , Haaland Benjamin , Lu Siyuan , Hwang Youngdeok
Published: May 2019

Predicting the intensity and amount of sunlight as a function of location and time is an essential component in identifying promising locations for economical solar farming. Although weather models and irradiance data are relatively abundant, these have yet, to our knowledge, been hybridized on a continental scale. Rather, much of the emphasis in the literature has been on short‐term localized forecasting. This is probably because the amount of data involved in a more global analysis is prohibitive with the canonical toolkit, via the Gaussian process (GP). Here we show how GP surrogate and discrepancy models can be combined to tractably and accurately predict solar irradiance on time‐aggregated and daily scales with measurements at thousands of sites across the continental United States. Our results establish short‐term accuracy of bias‐corrected weather‐based simulation of irradiance, when realizations are available in real space‐time (eg, in future days), and provide accurate surrogates for smoothing in the more common situation where reliable weather data is not available (eg, in future years).
Bias induced by ignoring double truncation inherent in autopsy‐confirmed survival studies of neurodegenerative diseases
Authors: Rennert Lior , Xie Sharon X.
Published: May 2019

Neurodegenerative diseases require an autopsy for confirmation of diagnosis. When death is the event of interest, studies based on autopsy‐confirmed diagnoses result in right truncated survival times because individuals who live past the end of study date do not receive a pathological diagnosis and are therefore not included in the sample. Furthermore, many studies of neurodegenerative diseases recruit subjects only after the onset of the disease, which may result in left truncated survival times. Therefore, double truncation, the simultaneous presence of left and right truncation, is inherent in many autopsy‐confirmed survival studies of neurodegenerative diseases. The main focus of this paper is to inform about the inherent double truncation in these studies and demonstrate how to properly estimate and compare survival distribution functions in this setting. We do so by conducting a case study of subjects with autopsy‐confirmed Alzheimer's disease and frontotemporal lobar degeneration. This case study is supported by extensive simulation studies, which provide several new contributions to the literature on survival distribution estimation in the context of double truncation.
Graphene Oxide‐Assisted and DNA‐Modulated SERS of AuCu Alloy for the Fabrication of Apurinic/Apyrimidinic Endonuclease 1 Biosensor
Authors: Li Junyao , Heng Hang , Lv Jianlin , Jiang Tingting , Wang Zhaoyin , Dai Zhihui
Published: May 2019

Fabrication of high‐performance surface‐enhanced Raman scattering (SERS) biosensors relies on the coordination of SERS substrates and sensing strategies. Herein, a SERS active AuCu alloy with a starfish‐like structure is prepared using a surfactant‐free method. By covering the anisotropic AuCu alloy with graphene oxide (GO), enhanced SERS activity is obtained owing to graphene‐enhanced Raman scattering and assembly of Raman reporters. Besides, stability of SERS is promoted based on the protection of GO to the AuCu alloy. Meanwhile, it is found that SERS activity of AuCu/GO can be regulated by DNA. The regulation is sequence and length dual‐dependent, and short polyT reveals the strongest ability of enhancing the SERS activity. Relying on this phenomenon, a SERS biosensor is designed to quantify apurinic/apyrimidinic endonuclease 1 (APE1). Because of the APE1‐induced cycling amplification, the biosensor is able to detect APE1 sensitively and selectively. In addition, APE1 in human serum is analyzed by the SERS biosensor and enzyme‐linked immunosorbent assay (ELISA). The data from the SERS method are superior to that from ELISA, indicating great potential of this biosensor in clinical applications.
Light‐Directed Liquid Manipulation in Flexible Bilayer Microtubes
Authors: Xu Bo , Zhu Chongyu , Qin Lang , Wei Jia , Yu Yanlei
Published: May 2019

Flexible microfluidic systems have potential in wearable and implantable medical applications. Directional liquid transportation in these systems typically requires mechanical pumps, gas tanks, and magnetic actuators. Herein, an alternative strategy is presented for light‐directed liquid manipulation in flexible bilayer microtubes, which are composed of a commercially available supporting layer and the photodeformable layer of a newly designed azobenzene‐containing linear liquid crystal copolymer. Upon moderate visible light irradiation, various liquid slugs confined in the flexible microtubes are driven in the preset direction over a long distance due to photodeformation‐induced asymmetric capillary forces. Several light‐driven prototypes of parallel array, closed‐loop channel, and multiple micropump are established by the flexible bilayer microtubes to achieve liquid manipulation. Furthermore, an example of a wearable device attached to a finger for light‐directed liquid motion is demonstrated in different gestures. These unique photocontrollable flexible microtubes offer a novel concept of wearable microfluidics.
Ursolic acid induces apoptosis and autophagy in oral cancer cells
Authors: Lin Cheng‐Wen , Chin Hsien‐Kuo , Lee Shou‐Lun , Chiu Chang‐Fang , Chung Jing‐Gung , Lin Zi‐Yin , Wu Chia‐Yung , Liu Ying‐Chen , Hsiao Yung‐Ting , Feng Chia‐Hsien , Bai Li‐Yuan , Weng Jing‐Ru
Published: May 2019

Oral squamous cell carcinoma (OSCC) is the fifth common cause of cancer mortality in Taiwan with high incidence and recurrence and needs new therapeutic strategies. In this study, ursolic acid (UA), a triterpenoid, was examined the antitumor potency in OSCC cells. Our results showed that UA inhibited the proliferation of OSCC cells in a dose‐ and time‐dependent manner in both Ca922 and SCC2095 oral cancer cells. UA induced caspase‐dependent apoptosis accompanied with the modulation of various biological biomarkers including downregulating Akt/mTOR/NF‐κB signaling, ERK, and p38. In addition, UA inhibited angiogenesis as evidenced by abrogation of migration/invasion and blocking MMP‐2 secretion in Ca922 cells. Interestingly, UA induced autophagy in OSCC cells, as manifested by LC3B‐II conversion and increased p62 expression and accumulation of autophagosomes. Inhibition by autophagy inhibitor enhanced UA‐mediated apoptosis in Ca922 cells. The experiment provides a rationale for using triterpenoid in the treatment of OSCC.
Carbohydrate‐based nanomaterials for biomedical applications
Authors: Gim Soeun , Zhu Yuntao , Seeberger Peter H. , Delbianco Martina
Published: May 2019

Carbohydrates are abundant biomolecules, with a strong tendency to form supramolecular networks. A host of carbohydrate‐based nanomaterials have been exploited for biomedical applications. These structures are based on simple mono‐ or disaccharides, as well as on complex, polymeric systems. Chemical modifications serve to tune the shapes and properties of these materials. In particular, carbohydrate‐based nanoparticles and nanogels were used for drug delivery, imaging, and tissue engineering applications. Due to the reversible nature of the assembly, often based on a combination of hydrogen bonding and hydrophobic interactions, carbohydrate‐based materials are valuable substrates for the creations of responsive systems. Herein, we review the current research on carbohydrate‐based nanomaterials, with a particular focus on carbohydrate assembly. We will discuss how these systems are formed and how their properties are tuned. Particular emphasis will be placed on the use of carbohydrates for biomedical applications.

This article is categorized under:

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
On semi‐linear elliptic equation arising from Micro‐Electromechanical Systems with contacting elastic membrane
Authors: Chen Huyuan , Wang Ying , Zhou Feng
Published: May 2019

This paper is concerned with the nonlinear elliptic problem in a bounded domain Ω of with Dirichlet boundary conditions. This problem arises from Micro‐Electromechanical Systems devices in the case that the elastic membrane contacts the ground plate on the boundary. We analyze the properties of minimal solutions to this equation when and the function satisfying for some and . Our results show how the boundary decay of the membrane works on the solutions and pull‐in voltage λ.
The Effects of Conflict on Fertility: Evidence From the Genocide in Rwanda
Authors: Kraehnert Kati , Brück Tilman , Di Maio Michele , Nisticò Roberto
Published: May 2019

Our study analyzes the fertility effects of the 1994 genocide in Rwanda. We study the effects of violence on both the duration time to the first birth in the early post-genocide period and on the total number of post-genocide births per woman up to 15 years following the conflict. We use individual-level data from Demographic and Health Surveys, estimating survival and count data models. This article contributes to the literature on the demographic effects of violent conflict by testing two channels through which conflict influences fertility: (1) the type of violence exposure as measured by the death of a child or sibling, and (2) the conflict-induced change in local demographic conditions as captured by the change in the district-level sex ratio. Results indicate the genocide had heterogeneous effects on fertility, depending on the type of violence experienced by the woman, her age cohort, parity, and the time horizon (5, 10, and 15 years after the genocide). There is strong evidence of a child replacement effect. Having experienced the death of a child during the genocide increases both the hazard of having a child in the five years following the genocide and the total number of post-genocide births. Experiencing sibling death during the genocide significantly lowers post-genocide fertility in both the short-run and the long-run. Finally, a reduction in the local sex ratio negatively impacts the hazard of having a child in the five years following the genocide, especially for older women.
Ginzburg–Landau equations on Riemann surfaces of higher genus
Authors: Chouchkov D. , Ercolani N.M. , Rayan S. , Sigal I.M.
Published: May 2019

We study the Ginzburg–Landau equations on Riemann surfaces of arbitrary genus. In particular, we

Nous étudions les équations de Ginzburg–Landau définies sur des surfaces de Riemann de genre arbitraire. En particulier,