bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 1-Carboxamide-1,4-dihydropyridazines via Recycli­zation of Hydroxypyrrolines with Semicarbazides
Authors: Trofimov Boris , Shabalin Dmitrii , Ivanova Evgeniya , Kuzmin Anton , Dvorko Marina , Schmidt Elena
Published: August 2018

Recyclization of available 5-hydroxypyrrolines with semicarbazide and its analogues has been studied. As a result, rare 1,4-dihydropyridazines with carboxamide function at the N-1 atom have been synthesized in up to 88% isolated yields.
Knee Imaging Following Anterior Cruciate Ligament Reconstruction: The Surgeon's and Radiologist's Perspectives
Authors: Wan Jennifer , Allen Christina , Steinbach Lynne , Srinivasan Ramya
Published: August 2018

Anterior cruciate ligament (ACL) tears are common injuries that if left untreated can result in chronic instability, cartilage damage, meniscal tears, and ligamentous injuries, eventually leading to early osteoarthritis. ACL reconstruction surgeries are therefore increasingly being performed. Despite the fact that most patients achieve excellent postoperative results, patients can present with recurrent instability and pain. These patients often undergo imaging with radiographs, magnetic resonance imaging, and/or computed tomography. An understanding of the imaging appearance of the normal ACL reconstruction and common causes of failure is therefore essential for the interpreting radiologist. This article reviews surgical techniques for ACL reconstruction, highlighting recent technical advances, the normal imaging appearance after ACL reconstruction, etiologies for reconstruction failure, and the diagnosis of these with the aid of imaging.
Imaging of the Knee Following Repair of Focal Articular Cartilage Lesions
Authors: Rehnitz Christoph , Weber Marc-André , Wuennemann Felix
Published: August 2018

Focal chondral or osteochondral lesions of the knee are common lesions involving either the cartilage layers or the cartilage layers and the subchondral bone. Despite their heterogeneous clinical presentation, they are important risk factors for the premature development of osteoarthritis. Therefore, early detection of osteochondral lesions and focal cartilage defects is crucial. In symptomatic (osteo-)chondral lesions, numerous therapeutic strategies, ranging from conservative treatment to surgical procedures such as marrow stimulation, osteochondral autograft transplantation, or autologous chondrocyte implantation are available. Musculoskeletal radiologists should be familiar with these surgical procedures, the evaluation of the postoperative findings as well as the possible complications when interpreting postoperative imaging studies. This review article describes the different surgical approaches to focal osteochondral lesions of the knee with emphasis on postoperative imaging findings and the pitfalls possibly encountered by the radiologist.
Congenital Diaphragmatic Hernia Presenting with Tension Pneumothorax in a 3-Year-Old Boy
Authors: Balks Maren , Gosemann Jan-Hendrik , Sorge Ina , Lacher Martin , Hirsch Franz
Published: August 2018

We report the case of a 3-year-old boy who presented with an upper respiratory tract infection and severe dyspnea. A chest X-ray revealed a left-sided tension pneumothorax with mediastinal shift and suspected enterothorax. After thoracic computed tomography (CT) scan, a chest tube was inserted, which drained fluid which had the same consistency and color as the one derived from the nasogastric (NG) tube. The boy underwent diagnostic laparoscopy for suspected bowel perforation, which confirmed a left-sided Bochdalek hernia with herniation of the viscera into the chest. After repositioning of the herniated organs into the abdomen, a gastric perforation was identified and repaired. This case demonstrates that the cause of a tension pneumothorax in an infant may be a rare combination of congenital diaphragmatic hernia (CDH) and perforation of a visceral hollow organ.
Feasibility of Electronic Health Record–Based Triggers in Detecting Dental Adverse Events
Authors: Kalenderian Elsbeth , Obadan-Udoh Enihomo , Yansane Alfa , Kent Karla , Hebballi Nutan , Delattre Veronique , Kookal Krisna , Tokede Oluwabunmi , White Joel , Walji Muhammad
Published: August 2018

Background We can now quantify and characterize the harm patients suffer in the dental chair by mining data from electronic health records (EHRs). Most dental institutions currently deploy a random audit of charts using locally developed definitions to identify such patient safety incidents. Instead, selection of patient charts using triggers and assessment through calibrated reviewers may more efficiently identify dental adverse events (AEs).

Objective Our goal was to develop and test EHR-based triggers at four academic institutions and find dental AEs, defined as moderate or severe physical harm due to dental treatment.

Methods We used an iterative and consensus-based process to develop 11 EHR-based triggers to identify dental AEs. Two dental experts at each institution independently reviewed a sample of triggered charts using a common AE definition and classification system. An expert panel provided a second level of review to confirm AEs identified by sites reviewers. We calculated the performance of each trigger and identified strategies for improvement.

Results A total of 100 AEs were identified by 10 of the 11 triggers. In 57% of the cases, pain was the most common AE identified, followed by infection and hard tissue damage. Positive predictive value (PPV) for the triggers ranged from 0 to 0.29. The best performing triggers were those developed to identify infections (PPV = 0.29), allergies (PPV = 0.23), failed implants (PPV = 0.21), and nerve injuries (PPV = 0.19). Most AEs (90%) were categorized as temporary moderate-to-severe harm (E2) and the remainder as permanent moderate-to-severe harm (G2).

Conclusion EHR-based triggers are a promising approach to unearth AEs among dental patients compared with a manual audit of random charts. Data in dental EHRs appear to be sufficiently structured to allow the use of triggers. Pain was the most common AE type followed by infection and hard tissue damage.
Husten – Differenzialdiagnosen
Authors: Koch Andrea , Behr Jürgen
Published: August 2018

A thorough anamnesis and the physical examination of a patient with cough mostly lead the way to the further diagnostic and therapeutic procedure. As far as there are no obvious reasons for the cough symptoms, any case of persisting chronic cough needs a diagnostic clarification – including computed tomography of the thorax and bronchoscopy as the final step. If clinical findings make them necessary, also invasive diagnostic procedures – such as bronchoscopy, thoracoscopy and surgical biopsy of the lung – must not be avoided. According to the clinical presentation appropriate medical disciplines have to be consulted for the diagnostic clarification of chronic cough. Besides pulmonology und allergology these are ENT medicine, gastroenterology, cardiology, infectiology, neurology and possibly psychiatry. The therapy of chronic and acute cough should be aimed at a causal treatment approach.
Diagnostik und Therapie der Nebenniereninsuffizienz
Authors: Harbeck Birgit , Lehnert Hendrik
Published: August 2018

Adrenal insufficiency is a potentially life-threatening endocrine disorder. Therefor it is very important to detect the symptoms in sufficient time and treat effectively to avoyed acute renal insufficiency. This article provides an insight into diagnostically procedures and therapeutically specific aspects of this rare endocrine disease.
Investigation on the optimized algorithm for electrostatic tomography
Authors: Gao H. M. , Fan B. Y. , Min Y. X. , Chang Qi
Published: August 2018

Particle charging in gas-solid two-phase flow is an important concern in many industrial processes. The technique of electrostatic tomography (EST) based on particle charging can achieve flow regime identification and infer concentration and flow rate by detecting the charged particles. Successful application of EST depends on the sensitivity map and the image reconstruction algorithm. In this paper, the effects of the sensitivity map on EST were demonstrated and a novel sensitivity map was presented. Then, optimized Tikhonov iterative algorithm (ITIK) was proposed to improve the quality of EST. The simulated results illustrate that the novel sensitivity map improves the quality of the reconstructed image of EST and the optimized ITIK has better performance in reconstructing the image of EST when compared with linearized back-projection algorithm, iterative linearized back-projection algorithm, and ITIK. Finally, the experimental studies were conducted and the simulated results were validated. The results indicate that the novel sensitivity map and the optimized algorithm can enable good applications of EST in gas-solid two-phase flow measurement.
Application of loofah sponge three-dimensional cage-shape activated carbon fiber with high strength in an air-cathode microbial fuel cell
Authors: Zhang Shici , Bao Xizhong , Wan Fang , Xie Yu , Liu Qi , Zhou Boxun , Xia Shibin
Published: August 2018

Microbial fuel cells (MFCs) could achieve both sewage treatment and power generation, and an appropriate cathode material with a suitable structure could improve the MFC performance. The three-dimensional (3D) cage-shape materials derived from loofah sponge, as activated carbon fibers with high strength, were first utilized in the single-chamber air-cathode MFC (loofah sponge activated carbon fibers (LSACF)-MFC). In this study, the maximum compressive strength of LSACF as high as 202.4 kPa was achieved when the activated temperature and time were 750 °C and 60 min, respectively. Under such conditions, the 3D morphological characteristic and relatively large Brunauer-Emmett-Teller (BET) specific surface area (422.5 m2/g) were indicated to facilitate the attachment of exoelectrogenic bacteria and decrease the internal resistance of the MFC system. According to the polarization and power density curve, the internal resistance was 420 Ω, and meanwhile, the maximum power density of 4083 mW/m3 was achieved. These results suggest that this LSACF with high strength has great potential for the MFC application.
Development and characterization of a helicon plasma source
Authors: Sharma N. , Chakraborty M. , Neog N. K. , Bandyopadhyay M.
Published: August 2018

The Helicon Plasma Source (HeliPS) designed and developed at the Centre of Plasma Physics—Institute for Plasma Research is a versatile helicon plasma device, which operates in a wide range of magnetic field configurations from 50 G to 500 G. This device is dedicated to perform a broad range of research activities. The main objective for development of the HeliPS is to carry out studies on ion-ion plasmas in electronegative gases. In the near future, ion-ion plasmas will be formed in electronegative gases in the downstream of the plasma production region. Although the system is primarily designed to carry out ion-ion plasma experiments, the same system can also be used for experimental studies on some basic helicon plasma properties such as wave propagation, wave coupling, and plasma instability. At present, argon plasma is produced with a RF power supply of 13.56 MHz frequency. External circuit parameters, such as antenna current, plasma resistance (Rp), and internal parameters, such as electron density and temperature, are measured. The details of the experimental setup development, device characteristic, as well as preliminary plasma production and characterization to confirm occurrence of the helicon plasma in the system are presented in this article.
First-principle electronic properties of dilute-P AlNP deep ultraviolet semiconductor
Authors: Borovac Damir , Tan Chee-Keong , Tansu Nelson
Published: August 2018

The electronic properties of dilute-P AlN1-xPx alloys are investigated by means of First-Principle Density Functional Theory (DFT) calculations, where the phosphorus (P) content is varied from 0% up to 6.25%. Band structure calculations indicate significant modifications of the electronic properties with the introduction of P-atoms, with the possibility of tuning the energy band gap from 6.19eV down to 4.32eV by inserting 6.25% P-content in the AlN-based system. The carrier effective masses and lattice parameters (a and c) were analyzed, and a large bowing parameter of b = 28.3 ± 0.5 eV was found. Moreover, our findings suggest a potential pathway to engineer the valence band crossover between the crystal-field split-off (CH) band and the heavy hole (HH) band by inserting low amounts of P-content (∼1-2%) into the AlN1-xPx alloy. Thus, the dilute-P AlN1-xPx alloys may serve as potential candidates for implementation as the active region material for dominant transverse electric (TE) polarization for deep-UV emitting devices.
A source drain symmetric and interchangeable bidirectional tunneling field effect transistor
Authors: Jin Xiaoshi , Gao Yunxiang , Liu Xi , Lee Jong-Ho
Published: August 2018

A novel bidirectional tunneling field effect transistor with source drain symmetric and interchangeable functions (SDSI BT FET) is proposed in this work. Different from the conventional tunneling field effect transistors (TFET), once the absolute value of drain-to-source bias voltage is determined, no matter which of the source drain interchangeable electrode is set to be drain, the proposed SDSI BT FET brings stable and unified transfer characteristics, thereafter, shows the source drain symmetric and interchangeable functions, which makes it more compatible with CMOS circuit compared to conventional TFET. It also has inherited the advantages of conventional TFET including lower subthreshold swing, lower static power dissipation, etc. Furthermore, through design optimization, a lower reverse biased leakage current and higher Ion-Ioff ratio can be observed.
Mid-infrared quantum cascade laser arrays with electrical switching of emission frequencies
Authors: Jiang Aiting , Jung Seungyong , Jiang Yifan , Vijayraghavan Karun , Kim Jae Hyun , Belkin Mikhail A.
Published: August 2018

We present a design of quantum cascade laser arrays made of ridge-waveguide devices in which the emission frequency can be electrically switched between several specified values. Our approach relies on fabricating multiple independently-biased distributed feedback grating sections along the laser ridge waveguides. Switchable single-mode lasing from the laser facet is achieved by balancing the injection pumping of the different grating sections. Our method provides a robust solution that can increase the tuning bandwidth of the quantum cascade laser arrays without increasing the size of the array emission aperture.
Cross-sectional survey of Chinese-speaking and Thai-speaking female sex workers in Sydney, Australia: factors associated with consistent condom use
Authors: Foster Rosalind , McCormack Lynne , Thng Caroline , Wand Handan , McNulty Anna
Published: August 2018

Background Previous studies have described inconsistent condom use in Chinese- and Thai-speaking female sex workers in Sydney, Australia. In the present study, we describe the demographics and safe sexual practices in the Chinese- and Thai-speaking female sex workers attending the Sydney Sexual Health Centre (SSHC) in 2014–15. Methods: A self-completed 60-item anonymous questionnaire, adapted from previous surveys conducted in 1993 and 2003, was translated into Chinese and Thai and administered to female sex workers attending the SSHC or seen on outreach. Results: In all, 488 surveys were distributed, of which 435 were returned; 43% in Chinese and 57% in Thai. Most women did not plan on sex work before their arrival in Australia. Compared with Chinese-speaking women, Thai-speaking women rated themselves higher on English language literacy, had better knowledge of the transmission of HIV and sexually transmissible infections (STIs) and were more likely to practice 100% condom use. Overall, 72% of the sex workers surveyed reported consistent condom use for vaginal sex at work. Conclusions: Consistent condom use for vaginal sex at work among Chinese- and Thai-speaking female sex workers has decreased slightly from that reported in a similar survey conducted by the SSHC in 2003, when 85% of sex workers reported consistent condom use. There are significant differences between Chinese- and Thai-speaking sex workers in terms of both knowledge and safer sex practices. Ongoing health promotion efforts should focus on providing culturally appropriate education around STIs and safe sex practices not only to workers, but also to parlour owners, managers and consumers.
Inferential seemings and the problem of reflective awareness
Authors: Moretti Luca
Published: August 2018

Phenomenal conservatism (PC) is the internalist view that non-inferential justification rests on appearances. PC’s advocates have recently argued that seemings are also required to explain inferential justification. The most developed view to this effect is Michael Huemer ’s theory of inferential seemings (ToIS). Luca Moretti has recently shown that PC is affected by the problem of reflective awareness, which makes PC open to sceptical challenges. In this paper I argue that ToIS is afflicted by a version of the same problem and it is thus hostage to inferential scepticism. I also suggest a possible response on behalf of ToIS’s advocates.
The influence of temperature on deformation-induced martensitic transformation in 301 stainless steel
Authors: Das Yadunandan B. , Forsey Alexander N. , Kelleher Joe , Kabra Saurabh , Fitzpatrick Michael E. , Simm Thomas H. , Gungor Salih , Moat Richard J.
Published: August 2018

Deformation-induced martensitic transformations are increasingly being used to create desirable mechanical properties in steels. Here, the kinetics of the deformation-induced martensitic transformation is investigated at 300, 263, 223, 173 and 100 K using in situ neutron diffraction during tensile loading. The results from these experiments show a distinct change in the transformation behaviour between 300 K and the tests conducted at 263 K and below, causing a difference in martensite structure. The difference in transformation kinetics is correlated to the suppression of slip at low temperatures, as evidenced using diffraction peak intensity analysis for different grain families and corroborated using transmission electron microscopy. A direct correlation between the deformation-induced martensite fraction and the work-hardening rate is shown.
Sino-Angolan agricultural cooperation: still not reaping rewards for the Angolan agricultural sector
Authors: Parker Leon , Fourie Elsje
Published: August 2018

This briefing examines the recent creation and downfall of seven Chinese-funded agro-industrial farms in Angola, and sees in the outcome of this initiative the latest demonstration of the difficulties in converting China’s and Angola’s resource-based relationship into a more economically sustainable and developmental partnership.
The wretched of the earth and strategy: Fanon’s ‘Leninist’ moment?
Authors: Newlove Chris James
Published: August 2018

This paper argues that Fanon puts forward the importance of a strategic approach to winning the goals of national independence from colonialism as part of the wider fight for a different social and economic system. In The wretched of the earth Fanon supports a strategic focus along similar lines to Lenin. The interpretation of the national bourgeoisie and the native working class within the colony put forward by Fanon is directly influenced by his readings of Lenin. Alongside his diverse lessons and influences, this paper will argue that Fanon’s ‘Leninist’ moment should be acknowledged.
Plasma irisin is increased following 12 weeks of Nordic walking and associates with glucose homoeostasis in overweight/obese men with impaired glucose regulation
Authors: Korkmaz Ayhan , Venojärvi Mika , Wasenius Niko , Manderoos Sirpa , Deruisseau Keith C. , Gidlund Eva‐Karin , Heinonen Olli J. , Lindholm Harri , Aunola Sirkka , Eriksson Johan G. , Atalay Mustafa
Published: August 2018

Irisin is a myokine that is thought to be secreted in response to exercise that may help to prevent obesity and maintain normal glucose metabolism. In this study we investigated the associations between irisin and glucose homeostasis in middle‐aged, overweight and obese men (n = 144) with impaired glucose regulation, and the impact of exercise training on these relationships. The participants underwent 12 weeks of resistance or aerobic (Nordic walking) exercise training three times per week, 60 minutes per session. Venous blood (n = 105) and skeletal muscle samples (n = 45) were obtained at baseline and post‐intervention. Compared to controls, Nordic walking, but not resistance training, increased irisin levels in plasma (9.6 ± 4.2%, P = 0.014; 8.7 ± 4.9%, P = 0.087; respectively) compared to controls. When considering all subjects, baseline irisin correlated positively with atherogenic index of plasma (r = 0.244, P = 0.013) and 2‐hour insulin levels (r = 0.214, P = 0.028), and negatively with age (r = −0.262, P = 0.007), adiponectin (r = −0.240, P = 0.014) and McAuley index (r = −0.259, P = 0.008). Training‐induced FNDC5 mRNA changes were negatively correlated with HbA1c (r = −0.527, P = 0.030) in the resistance training group and with chemerin in the Nordic walking group (r = −0.615, P = 0.033). In conclusion, 12‐weeks of Nordic walking was more effective than resistance training in elevating plasma irisin, in middle‐aged men with impaired glucose tolerance. Thus, the change in irisin in response to exercise training varied by the type of exercise but showed limited association with improvements in glucose homeostasis.
Caspase-11 auto-proteolysis is crucial for noncanonical inflammasome activation
Authors: Lee Bettina L. , Stowe Irma B. , Gupta Aaron , Kornfeld Opher S. , Roose-Girma Merone , Anderson Keith , Warming Søren , Zhang Juan , Lee Wyne P. , Kayagaki Nobuhiko
Published: August 2018

Intracellular LPS sensing by caspase-4/5/11 triggers proteolytic activation of pore-forming gasdermin D (GSDMD), leading to pyroptotic cell death in Gram-negative bacteria-infected cells. Involvement of caspase-4/5/11 and GSDMD in inflammatory responses, such as lethal sepsis, makes them highly desirable drug targets. Using knock-in (KI) mouse strains, we herein provide genetic evidence to show that caspase-11 auto-cleavage at the inter-subunit linker is essential for optimal catalytic activity and subsequent proteolytic cleavage of GSDMD. Macrophages from caspase-11–processing dead KI mice (Casp11Prc D285A/D285A) exhibit defective caspase-11 auto-processing and phenocopy Casp11−/− and caspase-11 enzymatically dead KI (Casp11Enz C254A/C254A) macrophages in attenuating responses to cytoplasmic LPS or Gram-negative bacteria infection. GsdmdD276A/D276A KI macrophages also fail to cleave GSDMD and are hypo-responsive to inflammasome stimuli, confirming that the GSDMD Asp276 residue is a nonredundant and indispensable site for proteolytic activation of GSDMD. Our data highlight the role of caspase-11 self-cleavage as a critical regulatory step for GSDMD processing and response against Gram-negative bacteria.
Determinants of selective ion permeation in the epithelial Na+ channel
Authors: Yang Lei , Palmer Lawrence G.
Published: August 2018

The epithelial Na+ channel (ENaC) is a key transporter mediating and controlling Na+ reabsorption in many tight epithelia. A very high selectivity for Na+ over other cations, including K+, is a hallmark of this channel. This selectivity greatly exceeds that of the closely related acid-sensing channels (ASICs). Here, we assess the roles of two regions of the ENaC transmembrane pore in the determination of cation selectivity. Mutations of conserved amino acids with acidic side chains near the cytoplasmic end of the pore diminish macroscopic currents but do not decrease the selectivity of the channel for Na+ versus K+. In the WT channel, voltage-dependent block of Na+ currents by K+ or guanidinium+, neither of which have detectable conductance, suggests that these ions permeate only ∼20% of the transmembrane electric field. According to markers of the electric field determined by Zn2+ block of cysteine residues, the site of K+ block appears to be nearer to the extracellular end of the pore, close to a putative selectivity filter identified using site-directed mutations. To test whether differences in this part of the channel account for selectivity differences between ENaC and ASIC, we substitute amino acids in the three ENaC subunits with those present in the ASIC homotrimer. In this construct, Li:Na selectivity is altered from that of WT ENaC, but the high Na:K selectivity is maintained. We conclude that a different part of the pore may constitute the selectivity filter in the highly selective ENaC than in the less-selective ASIC channel.
Rapid deformation of IPMC under a high electrical pulse stimulus inspired by action potential
Authors: Zhu Zicai , Bian Changsheng , Ru Jie , Bai Wanfa , Chen Hualing
Published: August 2018

Slow deformation seriously restrains application development of IPMC actuator, especially for thick and ionic liquid-based IPMC. Inspired by the action potential of muscle cell, this letter proposes a concept of high electrical pulse stimulus to accelerate IPMC deformation. By analyzing the dynamic process of voltage drop at the electrode-polymer interface, high voltage pulse is proved theoretically to be safe for IPMC in a short time. After charging the electrical double layer at the interface, the voltage pulse should be reduced to a safe level before electrochemical reactions. In our experiments, applying various high voltage pulses to a thick IPMC, the deformation can be sped up a few hundred times at most without any electrolysis damage. The results strongly support the practicability of the impulsive driving method.
Most boson quantum states are almost maximally entangled
Authors: Friedland Shmuel , Kemp Todd
Published: August 2018

The geometric measure of entanglement

E
E

of an

m
m

qubit quantum state has maximum value bounded above by

m
m

. In previous work of Gross, Flammia, and Eisert, it was shown that

E
≥
m
−
O
(
log
⁡
m
)

E \ge m-O(\log m)

with high probability as

m
→
∞

m\to \infty

. They showed, as a consequence, that the vast majority of states are too entangled to be computationally useful. In this paper, we show that for

m
m

qubit Boson quantum states, the maximal possible geometric measure of entanglement is bounded above by

log
2

m

\log _2\! m

, opening the door to many computationally universal states. We further show the corresponding concentration result that

E
≥

log
2

m
−
O
(
log
⁡
log
⁡
m
)

E \ge \log _2\! m - O(\log \log m)

with high probability as

m
→
∞

m\to \infty

. We extend these results also to

m
m

-mode

n
n

-bit Boson quantum states.
Activation of the apoptotic pathway during prolonged prometaphase blocks daughter cell proliferation
Authors: Uetake Yumi , Sluder Greenfield
Published: August 2018

When untransformed human cells spend >1.5 h in prometaphase under standard culture conditions, all daughters arrest in G1 despite normal division of their mothers. We investigate what happens during prolonged prometaphase that leads to daughter cell arrest in the absence of DNA damage. We find that progressive loss of anti-apoptotic MCL-1 activity and oxidative stress act in concert to partially activate the apoptosis pathway, resulting in the delayed death of some daughters and senescence for the rest. At physiological oxygen levels, longer prometaphase durations are needed for all daughters to arrest. Partial activation of apoptosis during prolonged prometaphase leads to persistent caspase activity, which activates the kinase cascade mediating the post–mitotic activation of p38. This in turn activates p53, and the consequent expression of p21stops the cell cycle. This mechanism can prevent cells suffering intractable mitotic defects, which modestly prolong mitosis but allow its completion without DNA damage, from producing future cell generations that are susceptible to the evolution of a transformed phenotype.
In vivo analysis of outer arm dynein transport reveals cargo-specific intraflagellar transport properties
Authors: Dai Jin , Barbieri Francesco , Mitchell David R. , Lechtreck Karl F.
Published: August 2018

Outer dynein arms (ODAs) are multiprotein complexes that drive flagellar beating. Based on genetic and biochemical analyses, ODAs preassemble in the cell body and then move into the flagellum by intraflagellar transport (IFT). To study ODA transport in vivo, we expressed the essential intermediate chain 2 tagged with mNeonGreen (IC2-NG) to rescue the corresponding Chlamydomonas reinhardtii mutant oda6. IC2-NG moved by IFT; the transport was of low processivity and increased in frequency during flagellar growth. As expected, IFT of IC2-NG was diminished in oda16, lacking an ODA-specific IFT adapter, and in ift46 IFT46ΔN lacking the ODA16-interacting portion of IFT46. IFT loading appears to involve ODA16-dependent recruitment of ODAs to basal bodies followed by handover to IFT. Upon unloading from IFT, ODAs rapidly docked to the axoneme. Transient docking still occurred in the docking complex mutant oda3 indicating that the docking complex stabilizes rather than initiates ODA–microtubule interactions. In full-length flagella, ODAs continued to enter and move inside cilia by short-term bidirectional IFT and diffusion and the newly imported complexes frequently replaced axoneme-bound ODAs. We propose that the low processivity of ODA-IFT contributes to flagellar maintenance by ensuring the availability of replacement ODAs along the length of flagella.
TetrahymenaRIB72A and RIB72B are microtubule inner proteins in the ciliary doublet microtubules
Authors: Stoddard Daniel , Zhao Ying , Bayless Brian A. , Gui Long , Louka Panagiota , Dave Drashti , Suryawanshi Swati , Tomasi Raphaël F.-X. , Dupuis-Williams Pascale , Baroud Charles N. , Gaertig Jacek , Winey Mark , Nicastro Daniela
Published: August 2018

Doublet and triplet microtubules are essential and highly stable core structures of centrioles, basal bodies, cilia, and flagella. In contrast to dynamic cytoplasmic micro­tubules, their luminal surface is coated with regularly arranged microtubule inner proteins (MIPs). However, the protein composition and biological function(s) of MIPs remain poorly understood. Using genetic, biochemical, and imaging techniques, we identified Tetrahymena RIB72A and RIB72B proteins as ciliary MIPs. Fluorescence imaging of tagged RIB72A and RIB72B showed that both proteins colocalize to Tetrahymena cilia and basal bodies but assemble independently. Cryoelectron tomography of RIB72A and/or RIB72B knockout strains revealed major structural defects in the ciliary A-tubule involving MIP1, MIP4, and MIP6 structures. The defects of individual mutants were complementary in the double mutant. All mutants had reduced swimming speed and ciliary beat frequencies, and high-speed video imaging revealed abnormal highly curved cilia during power stroke. Our results show that RIB72A and RIB72B are crucial for the structural assembly of ciliary A-tubule MIPs and are important for proper ciliary motility.
The Securitization of Language Education
Authors: Perera Kaushalya , Makoni Sinfree
Published: August 2018

This Forum article is a contribution to the development of a securitization perspective on language education. We construe securitization of applied linguistics as the tendency to align national goals for language education, including Teaching English as a Second or Other Language (TESOL) and foreign languages, with broader national and security agendas. Keeping in mind the impact of the World Wars I and II on securitizing language education, we illustrate the more recent impact of this due to 9/11 and the subsequent shifts in global geopolitics. Wepoint to the insidious connections that have been growing for decades between the defense sectors in various countries and regions and language education while drawing attention to the increased pace and intensity of it in current times. We conclude this piece by outlining the ethical challenges which the ongoing securitization of applied linguistics poses for applied linguists.
Revealing tumor heterogeneity of breast cancer by utilizing the linkage between somatic and germline mutations
Authors: Zou Meng , Jin Rui , Au Kin Fai
Published: August 2018

The intra-tumor heterogeneity is associated with cancer progression and therapeutic resistance, such as in breast cancer. While the existing methods for studying tumor heterogeneity only analyze variant allele frequency (VAF), the genotype of variant is also informative for inferring subclones, which can be detected by long reads or paired-end reads. We developed GenoClone to integrate VAF with the genotype of variant innovatively, so it showed superior performance of inferring the number of subclones, estimating the fractions of subclones and identifying somatic single-nucleotide variants composition of subclones. When GenoClone was applied to 389 TCGA breast cancer samples, it revealed extensive intra-tumor heterogeneity. We further found that a few somatic mutations were relevant to the late stage of tumor evolution, including the ones at the oncogene PIK3CA and the tumor suppress gene TP53. Moreover, 52 subclones that were identified from 167 samples shared high similarity of somatic mutations, which were clustered into three groups with the sizes of 24, 14 and 14. It is helpful for understanding the development of breast cancer in certain subgroups of people and the drug development for population level. Furthermore, GenoClone also identified the tumor heterogeneity in different aliquots of the same samples. The implementation of GenoClone is available at http://www.healthcare.uiowa.edu/labs/au/GenoClone/.
Large-scale comparative assessment of computational predictors for lysine post-translational modification sites
Authors: Chen Zhen , Liu Xuhan , Li Fuyi , Li Chen , Marquez-Lago Tatiana , Leier André , Akutsu Tatsuya , Webb Geoffrey I , Xu Dakang , Smith Alexander Ian , Li Lei , Chou Kuo-Chen , Song Jiangning
Published: August 2018

Lysine post-translational modifications (PTMs) play a crucial role in regulating diverse functions and biological processes of proteins. However, because of the large volumes of sequencing data generated from genome-sequencing projects, systematic identification of different types of lysine PTM substrates and PTM sites in the entire proteome remains a major challenge. In recent years, a number of computational methods for lysine PTM identification have been developed. These methods show high diversity in their core algorithms, features extracted and feature selection techniques and evaluation strategies. There is therefore an urgent need to revisit these methods and summarize their methodologies, to improve and further develop computational techniques to identify and characterize lysine PTMs from the large amounts of sequence data. With this goal in mind, we first provide a comprehensive survey on a large collection of 49 state-of-the-art approaches for lysine PTM prediction. We cover a variety of important aspects that are crucial for the development of successful predictors, including operating algorithms, sequence and structural features, feature selection, model performance evaluation and software utility. We further provide our thoughts on potential strategies to improve the model performance. Second, in order to examine the feasibility of using deep learning for lysine PTM prediction, we propose a novel computational framework, termed MUscADEL (Multiple Scalable Accurate Deep Learner for lysine PTMs), using deep, bidirectional, long short-term memory recurrent neural networks for accurate and systematic mapping of eight major types of lysine PTMs in the human and mouse proteomes. Extensive benchmarking tests show that MUscADEL outperforms current methods for lysine PTM characterization, demonstrating the potential and power of deep learning techniques in protein PTM prediction. The web server of MUscADEL, together with all the data sets assembled in this study, is freely available at http://muscadel.erc.monash.edu/. We anticipate this comprehensive review and the application of deep learning will provide practical guide and useful insights into PTM prediction and inspire future bioinformatics studies in the related fields.
Cooperation Makes a Group be More Creative
Authors: Lu Kelong , Xue Hua , Nozawa Takayuki , Hao Ning
Published: August 2018

This study investigated how cooperative and competitive interaction modes affect the group creative performance. The participants were recruited as dyads to solve 2 problems either demanding divergent thinking (alternative uses task, AUT) or not (object characteristic task, OCT). The dyads solved 1 of the 2 problems in the cooperative mode and the other in the competitive mode. Functional near-infrared spectroscopy (fNIRS)-based hyperscanning was used to record their neural activities in the prefrontal and right temporal–parietal junction (r-TPJ) regions. Results revealed the dyads showed higher AUT fluency, AUT originality, OCT fluency, and cooperation level in the cooperative mode than in the competitive mode. The fNIRS data revealed increased (task-baseline) interpersonal brain synchronization (IBS) in the right dorsolateral prefrontal cortex (r-DLPFC) and r-TPJ, only for dyads in the AUT/cooperation condition. In both r-DLPFC and r-TPJ, the IBS of dyads in the AUT/cooperation condition was stronger than in the AUT/competition and OCT/cooperation. Moreover, a stronger IBS was evoked between the regions in prefrontal and posterior temporal regions in the AUT/cooperation condition, as compared with the competition mode. These findings suggest that enhanced IBS may underlie the positive effects of cooperation as compared with the competition in terms of group creativity.
Tenofovir Diphosphate in Dried Blood Spots Is Strongly Associated With Viral Suppression in Individuals With Human Immunodeficiency Virus Infections
Authors: Castillo-Mancilla Jose R , Morrow Mary , Coyle Ryan P , Coleman Stacey S , Gardner Edward M , Zheng Jia-Hua , Ellison Lucas , Bushman Lane R , Kiser Jennifer J , Mawhinney Samantha , Anderson Peter L
Published: August 2018

Background

Although tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a predictor of adherence and pre-exposure prophylaxis efficacy, its utility in human immunodeficiency virus (HIV) treatment remains unknown.

Methods

DBS for TFV-DP were collected up to 3 times over 48 weeks in persons living with HIV (PLWH) who were receiving TFV disoproxil fumarate (TDF)-based therapy. Log-transformed baseline TFV-DP was compared using t-tests or analyses of variance; generalized estimating equations were used to estimate the adjusted odds ratio (aOR) of viral suppression (<20 copies/mL) based on the TFV-DP concentration at the study visit.

Results

We analyzed 1199 DBS from 532 participants (76 female; 101 Black, 101 Hispanic). Among the virologically-suppressed participants at baseline (n = 347), TFV-DP was lower in Blacks (geometric mean 1453, 95% confidence interval [CI] 1291–1635) vs Whites (1793, 95% CI 1678–1916; P = .002) and Hispanics (1760, 95% CI 1563–1982; P = .025); in non-boosted (1610, 95% CI 1505–1723) vs. boosted (1888, 95% CI 1749–2037; P = .002) regimens; and in non-nucleoside reverse transcription inhibitor–based (1563, 95% CI 1432–1707) vs. boosted protease inhibitor–based (1890, 95% CI 1704–2095; P = .006) and multiclass-based (1927, 95% CI 1650–2252; P = .022) regimens. The aOR of virologic suppression, after adjusting for age, gender, race, body mass index, estimated glomerular filtration rate, CD4+ T-cell count, antiretroviral drug class and duration of therapy, was 73.5 (95% CI 25.7–210.5; P < .0001) for a TFV-DP concentration ≥1850 fmol/punch compared to <350 fmol/punch.

Conclusions

TFV-DP in DBS is strongly associated with virologic suppression in PLWH on TDF-based therapy and is associated with certain participant characteristics. Further research is required to evaluate this drug adherence and exposure measure in clinical practice.

Clinical Trials Registration

NCT02012621.
Incidence of Acute Kidney Injury Among Critically Ill Patients With Brief Empiric Use of Antipseudomonal β-Lactams With Vancomycin
Authors: Schreier Diana J , Kashani Kianoush B , Sakhuja Ankit , Mara Kristin C , Tootooni Mohammad S , Personett Heather A , Nelson Sarah , Rule Andrew D , Steckelberg James M , Tande Aaron J , Barreto Erin F
Published: August 2018

Background

Nephrotoxins contribute to 20%–40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal β-lactam/VAN combinations.

Methods

The study included a retrospective cohort of 3299 ICU patients who received ≥24 but ≤72 hours of an antipseudomonal β-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups.

Results

The overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85–1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71–1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09).

Conclusion

Short courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.
Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria
Authors: Kurtis Jonathan D , Raj Dipak K , Michelow Ian C , Park Sangshin , Nixon Christina E , McDonald Emily A , Nixon Christian P , Pond-Tor Sunthorn , Jha Ambrish , Taliano Ross J , Kabyemela Edward R , Friedman Jennifer F , Duffy Patrick E , Fried Michal
Published: August 2018

Background

In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive.

Methods

We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania. We collected cord blood, measured antibodies to Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), and related these antibodies to the risk of severe malaria in the first year of life. In addition, we vaccinated female mice with PbSEA-1, mated them, and challenged their pups with P. berghei ANKA parasites to assess the impact of maternal PbSEA-1 vaccination on newborns’ resistance to malaria.

Results

Children with high cord-blood anti–PfSEA-1 antibody levels had 51.4% fewer cases of SM compared to individuals with lower anti–PfSEA-1 levels over 12 months of follow-up (P = .03). In 3 trials, pups born to PbSEA-1–vaccinated dams had significantly lower parasitemia and longer survival following a P. berghei challenge compared to pups born to control dams.

Conclusions

We demonstrate that maternally-derived, cord-blood anti–PfSEA-1 antibodies predict decreased risk of SM in infants and vaccination of mice with PbSEA-1 prior to pregnancy protects their offspring from lethal P. berghei challenge. These results identify, for the first time, a parasite-specific target of maternal antibodies that protect infants from SM and suggest that vaccination of pregnant women with PfSEA-1 may afford a survival advantage to their offspring.
Health hazards and risks for musculoskeletal problems among child labourers in the brickfield sector of West Bengal, India
Authors: Das Banibrata
Published: August 2018

Aims

The purpose of this study was to describe the health hazards among child labourers in brickfields, and to assess occupational health problems, together with physiological and respiratory stress, compared with child control subjects.

Methods

A cross-sectional study was conducted on 112 child brickfield workers and 120 control subjects, and a modified Nordic Questionnaire was applied to assess the discomfort felt among both groups of workers. Physiological assessment of the workload was carried out by the measurement of heart rate, blood pressure and spirometry of the workers.

Results

Child brickfield workers suffer from pain, especially in the lower back (97%), shoulder (88%), hands (82%), wrist (76%), neck (73%) and ankle (71%). The post-activity heart rate of the child brickfield workers was 166.5 beats/min, whereas the systolic and diastolic blood pressures were 132.2 and 67.2 mm/Hg, respectively. The forced vital capacity value of child brickfield workers was 2.04, and in the case of the controls it was 2.18, which was significantly different. The forced expiratory volumes in 1 s of experimental and control subjects were 1.82 and 1.92, respectively. The peak expiratory flow rate was significantly different between the two groups.

Conclusions

Most of the brick-making activities were strenuous ones that affected the children. The cardiovascular and respiratory health of the child brickfield workers has changed markedly due to strenuous activity. The child brickfield workers also experienced other occupational health problems and severe musculoskeletal pain.
Should parents see their teen’s medical record? Asking about the effect on adolescent–doctor communication changes attitudes
Authors: Ancker Jessica S , Sharko Marianne , Hong Matthew , Mitchell Hannah , Wilcox Lauren
Published: August 2018

Objective

Parents routinely access young children’s medical records, but medical societies strongly recommend confidential care during adolescence, and most medical centers restrict parental records access during the teen years. We sought to assess public opinion about adolescent medical privacy.

Materials and Methods

The Cornell National Social Survey (CNSS) is an annual nationwide public opinion survey. We added questions about a) whether parents should be able to see their 16-year-old child’s medical record, and b) whether teens would avoid discussing sensitive issues (sex, alcohol) with doctors if parents could see the record. Hypothesizing that highlighting the rationale for adolescent privacy would change opinions, we conducted an experiment by randomizing question order.

Results

Most respondents (83.0%) believed that an adolescent would be less likely to discuss sensitive issues with doctors with parental medical record access; responses did not differ by question order (P = .29). Most also believed that parents should have access to teens’ records, but support for parental access fell from 77% to 69% among those asked the teen withholding question first (P = .01).

Conclusions

Although medical societies recommend confidential care for adolescents, public opinion is largely in favor of parental access. A brief “nudge,” asking whether parental access might harm adolescent–doctor communication, increased acceptance of adolescent confidentiality, and could be part of a strategy to prepare parents for electronic patient portal policies that medical centers impose at the beginning of adolescence.