bluuebunny/crossref_metadata_2025 huggingface dataset:
The Traveling Salesman Problem in the Natural Environment
Authors: Phillips Flip , O'Connell Thomas , Layton Oliver
Published: July 2019

Is it possible for humans to navigate in the natural environment wherein the path taken between various destinations is 'optimal' in some way? In the domain of optimization this challenge is traditionally framed as the "Traveling Salesman Problem" (TSP). What strategies and ecological considerations are plausible for human navigation? When given a two-dimensional map-like presentation of the destinations, participants solve this optimization exceptionally well (only 2-3% longer than optimum)^1, 2^. In the following experiments we investigate the effect of effort and its environmental affordance on navigation decisions when humans solve the TSP in the natural environment. Fifteen locations were marked on two outdoor landscapes with flat and varied terrains respectively. Performance in the flat-field condition was excellent (&8764;6% error) and was worse but still quite good in the variable-terrain condition (&8764;20% error), suggesting participants do not globally pre-plan routes but rather develop them on the fly. We suggest that perceived effort guides participant solutions due to the dynamic constraints of effortful locomotion and obstacle avoidance.
Evaluation of HIV infected Cells
Authors: Nallasamy Kumaresan
Published: July 2019

In this paper, Human Immunodeficiency Virus (HIV) infected cells is found out using a Simulink model. The Simulink solution is equivalent or very close to the exact solution of the problem. Accuracy of the Simulink solution to this problem is better than the existing numerical methods. The main advantage of Simulink model is that solution of any dynamicalproblem can be obtained by anybody without writing any codes. Anillustrative numerical example is presented for the proposed method.
Hierarchical nanomechanics of collagen microfibrils
Authors: Gautieri Alfonso , Vesentini Simone , Redaelli Alberto , Buehler Markus J.
Published: July 2019

Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to organisms and is thus the prime construction materials in biology. Collagen is also the dominating material in the extracellular matrix and its stiffness controls cell differentiation, growth and pathology. However, the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility and nonlinear mechanical response remains unknown. By using x-ray diffraction data of a collagen fibril (Orgel et al., PNAS, 2006) here we present an experimentally validated model of the nanomechanics of a collagen microfibril that incorporates the full biochemical details of the amino acid sequence of constituting molecules. We demonstrate that mechanical testing of hydrated (wet) collagen microfibrils yields a Young’s modulus of ≈300 MPa at small and ≈1.2 GPa at larger deformation in excess of 10% strain, in excellent agreement with experimental data. Dehydrated (dry) collagen microfibrils show a significantly increased Young’s modulus of ≈1.8-2.25 GPa owing to a much tighter molecular packing, in agreement with experimental measurements. Our results demonstrate that the unique mechanical properties of collagen microfibrils arise due to their hierarchical structure, where key deformation mechanisms are straightening of twisted molecules at small strains, followed by axial stretching and eventual molecular uncoiling. These mechanisms explain the striking difference of the modulus of collagen fibrils compared with single molecules, which is found in the range of 4.8±2 GPa or ≈10-20 times greater. The atomistic model of collagen microfibril mechanics enables the bottom-up elucidation of structure-property relationships in a broader class of collagen materials (e.g. tendon, bone, cornea), including studies of genetic disease where the incorporation of biochemical details is essential.
The True Colours of Carbon
Authors: Thomas Sebastian , Hoegh-Guldberg Ove , Griffiths Andrew , Dargusch Paul , Bruno John
Published: July 2019

Carbon offset projects in developing countries are one of the principal mechanisms designed to reduce greenhouse gas emissions and promote sustainable development yet have critical limitations in both areas. Here we present a framework for categorizing carbon offset projects according to four general approaches to the reduction of greenhouse gas emissions: (1) efficiency ('Brown'); innovation ('Red'), terrestrial sequestration ('Green') or sequestration in aquatic environments ('Blue'). Analysis of the 6109 CDM projects currently in the CDM "pipeline" reveals that 99% are Brown or Red, and only 1% are Green or Blue, yet Green and Blue projects typically offer a far greater range of benefits for ecosystems and society. The analysis concludes that the designers of emissions trading schemes should endorse Green and Blue offset projects as preferred forms of emissions offsetting, and that firms using offsets for compliance purposes be required to declare in public reports the colours of their offset acquisitions. Such reform will help redirect demand in carbon markets toward blue and green offset projects, increasing the sustainability outcomes of carbon offset developments.
Self-organization of intrinsically disordered proteins with folded N-termini
Authors: Simister Philip , Schaper Fred , O'Reilly Nicola , McGowan Simon , Feller Stephan
Published: July 2019

Thousands of human proteins lack recognizable tertiary structure in most of their chains. Here we hypothesize that some use their structured N-terminal domains (SNTDs) to organise the remaining protein chain via intramolecular interactions, generating partially structured proteins. This model has several attractive features: as protein chains emerge, SNTDs form spontaneously and serve as nucleation points, creating more compact shapes. This reduces the risk of protein degradation or aggregation. Moreover, an interspersed pattern of SNTD-docked regions and free loops can coordinate assembly of sub-complexes in defined loop-sections and enables novel regulatory mechanisms, for example through posttranslational modifications of docked regions.
On the dimensionality of the Avogadro constant and the definition of the mole
Authors: Wheatley Nigel
Published: July 2019

There is a common misconception among educators, and even some metrologists, that the Avogadro constant _N_~A~ is (or should be) a pure number, and not a constant of dimension *N*^–1^ (where *N* is the dimension amount of substance). Amount of substance is measured, and has always been measured, as ratios of other physical quantities, and not in terms of a specified pure number of elementary entities. Hence the Avogadro constant has always been defined in terms of the unit of amount of substance, and not vice versa. The proposed redefinition of the mole in terms of a fixed value of the Avogadro constant would cause additional conceptual complexity for no metrological benefit.
Cholesterol Esterification During Differentiation by Hexamethylene Bisacetamide of Friend Virus-Induced Erythrokeukemia
Authors: Mulas Maria , Mandas Antonella , Abete Claudia , Dessi Sandra , Pani Mario , Manconi Rosa , Mocali Alessandra , Paoletti Francesco
Published: July 2019

Cholesterol is an essential constituent of all mammalian cell membranes, and its availability is therefore a prerequisite for cellular growth and other functions. Several lines of evidence are now indicating an association between alterations of cholesterol homeostasis and cell cycle progression in cancer cells. However, the role of cholesterol in cell differentiation is still largely unknown. To begin to address this issue, in this study we examined changes in cholesterol metabolism and in the mRNA levels of proteins involved in cholesterol import and esterification (multi-drug resistance, MDR-3) and acylCoA:cholesterol acyltransferase (ACAT) and cholesterol export (caveolin-1) in Friend virus-induced erythroleukemia cells (MELC), in the absence or in the presence of the chemical inducer of differentiation, hexamethylene bisacetamide (HMBA). In uninduced MELC, cholesterol synthesis, esterification and MDR-3 and ACAT mRNAs increased as cells progressed from resting to proliferating phase, while caveolin-1 decreased. These results provide evidence that cholesterol esterification “per se” may have a role in cell division. When MELC are treated with HMBA, the reduction of DNA synthesis caused by the inducer is accompanied by an extensive decrease of cholesterol esterification and of ACAT and MDR-3 mRNA levels and by a significant increase in caveolin-1 mRNA. On the other hand, detection of cytoplasmic neutral lipids by staining MELC with oil-ORO, a dye able to evidence CE but not FC, revealed that HMBA-treatment inhibits cholesterol ester accumulation in MELC to approximately the same extent as the ACAT inhibitor, SaH. These results, other than, to add new insights on the possible role of cholesterol metabolism during tumor growth, for the first time indicate a possible involvement of cholesterol esterification pathways in the regulating of differentiation of erythroleukemic cells.
Why do many animals move with a predominance of roughly forward directions?
Authors: Duffy Kevin
Published: July 2019

Animal movements can influence their ecology and demographics. Animal movements are often characterized by path structures with directional persistence. The extent to which directional persistence improves forage success is investigated in this paper using theoretical simulations. It is shown that a movement strategy with directional persistence enables simulated animals to find more forage as compared to a random movement strategy. Situations where resources are chosen with certainty (optimally) are even more successful. Choosing resource with certainty cannot result in directional persistence. However, in cases where animals choose with certainty adjacent cells with resource but continue in their existing direction if none of these have resources then results include directional persistence. It is posited here that this combined strategy is the most effective because if optimal foraging works it is optimally efficient but where foraging is sub-optimal, for a variety of reasons, directional persistence will benefit foraging.
Modeling Animal Movements in Response to Human Disturbances
Authors: Preisler Haiganoush , Ager Alan , Brillinger David , Wisdom Michael
Published: July 2019

Background/Question/Methods

The advent of GPS technology has made it possible to study human - wildlife interactions on large landscapes and quantify behavioral responses to recreation and other anthropogenic disturbances at increasingly fine scales. Of particular interest are the potential impacts on habitat use patterns, energetics, and cascading impacts on fecundity and other life history traits for key wildlife species that are increasingly exposed to human activities. However, the dynamics of free-ranging animal movements are complex, even without disturbances, and quantifying reactions to disturbance on heterogeneous landscapes is difficult. A modeling framework is required that can sort out diel and random movements that mask short and long-term behavioral response to disturbances.In this talk I will discuss how stochastic differential equations (SDE’s) are used to build potential function surfaces for describing movement patterns and responses to disturbances. I will demonstrate the methods using GPS data for free ranging elk within a 1450 ha study area on the Starkey Experimental Forest located in eastern Oregon. The telemetry data were collected as part of a long-term controlled experiment to understand the response of free ranging Rocky Mountain elk (Cervus elaphus) and deer (Odocoileus hemionus) to multiple anthropogenic disturbances including all terrain vehicles, hikers, mountain bikers and equestrians. This work includes the development of statistical procedures to estimate the simultaneous effects of two or more entities (combinations of animals and disturbance agents) on the potential surfaces, to understand the effects of multiple interacting disturbances on observed patterns of movement.2)

Results/Conclusions

We parameterized stochastic differential equations to quantify effects of topography; distance to roads; distance to disturbance, and random movements on elk locations. The GPS technology provided evidence that: 1) elk appear to know the location of roads and the routing of traffic on roads through the forest; 2) hikers and equestrians seem to generate a larger movement response compared to mountain bikers and ATV riders; and, 3) The threshold response distance appears to be well beyond those previously reported in studies that relied on visual methods.The study demonstrated the utility of SDE’s and the motivating concept of potential functions to model animal movements. These methods have also been applied by the authors to study movement patterns in yellow legged frogs (Rana sierrae), elephant seals (Mirounga angustirostris), Monk seals (Monachus schauinslandi) and whale sharks (Rhincodon typus ).
Ultrasonic frogs show extraordinary sex differences in auditory frequency sensitivity
Authors: Shen Jun-Xian , Xu Zhi-Min , Yu Zu-Lin , Wang Shuai , Zheng De-Zhi
Published: July 2019

Acoustic communication plays an important role in the reproductive behavior of anurans. Males of concave-eared torrent frog (_Odorrana tormota_) have ultrasonic communication capacity 1, 2, but it is unknown whether females communicate with ultrasound. Here we show that O. tormota exhibits great sex differences in the auditory frequency sensitivity. Acoustic playback experiments demonstrated that the male's advertisement calls evoke gravid females' positive phonotaxis and vocal responses, whereas ultrasonic components of the male's calls (frequencies above 20 kHz) do not elicit female phonotaxis or vocalization. The behavioral study was complemented by electrophysiological recordings from the auditory midbrain and by laser Doppler vibrometer measurements of the tympanic membrane's response to acoustic stimuli. These measurements revealed that females have an upper frequency limit up to 16 kHz (threshold 107 dB SPL) and no ultrasound sensitivity, unlike males which have an upper frequency limit of up to 35 kHz (87 dB SPL). Single units in the female auditory midbrain have the best excitatory frequencies (BEFs) peaked around 5 kHz, corresponding to the fundamental frequency (F0) of male's most calls, whereas the male auditory midbrain units have BEFs mostly above 8 kHz, largely consistent with the F0 of female courtship calls. Females have a frequency sensitive bandwidth (10 dB above threshold) ranged from 2 to 6 kHz, narrower than that males have (5-20 kHz). The velocity amplitude of the tympanic membranes peaked around 5 kHz in females, whereas 7 kHz in males. The results suggest that the frog species O. tormota is an example of a vertebrate, which demonstrates well phonotaxis and extraordinary sex differences in hearing.
Where is the ‘Jennifer Aniston neuron’?
Authors: Aur Dorian , Steinmetz Peter
Published: July 2019

It is generally believed that spike timing features (firing rate, ISI) are the main characteristics that can be related to neural code. Contrary to this common belief, spike directivity, a new measure that quantifies transient charge density dynamics within action potentials (APs) provides better results in discriminating different categories of visual object recognition. Specifically, intracranial recordings from medial temporal lobe (MTL) of epileptic patients have been analyzed using firing rate, interspike intervals and spike directivity. A comparative statistical analysis of the same spikes from four selected neurons shows that electrical micro-mapped features in neurons display higher separability to input images compared to spike timing features. If the observation vector include data from all 4 neurons then the comparative analysis shows a highly significant separation between categories for spike directivity (p=0.0023) and does not display separability for ISI (p=0.3768) and firing rate (p=0.5492). The presence of electrical micro-maps within APs suggests the existence of an intrinsic “neural code" where information regarding input images is electrically written/coded and read/decoded during AP propagation in the neuron. The occurrence of electrical micro-maps within APs reflects information communication and computation in analyzed neuron within a millisecond-level time domain of AP occurrence. This existence of a “lower level” of coding where information is processed within neurons raises questions regarding the richness and reliability of models that constrain neural code to spike timing features. Additionally, this phenomenon that occurs within APs may provide a step forward in understanding the fundamental gap between molecular description, information processing and neuronal function. Importantly, this paper confirms a new paradigm regarding neural code where information processing, computation and memory formation in the brain can be explained in terms of dynamics and interaction of electric charges.
A logistic regression model for microalbuminuria prediction in overweight male population
Authors: Chen BaoDe , Xu WeiYi , Yu Chen , Ni ZhenYun , Li XueFen , Cui DaWei
Published: July 2019

Background:

Obesity promotes progression to microalbuminuria and increases the risk of chronic kidney disease. Current protocols of screening microalbuminuria are not recommended for the overweight or obese.Design and Methods: A cross-sectional study was conducted. The relationship between metabolic risk factors and microalbuminuria was investigated. A regression model based on metabolic risk factors was developed and evaluated for predicting microalbuminuria in the overweight or obese.

Results:

The prevalence of MA reached up to 17.6% in Chinese overweight men. Obesity, hypertension, hyperglycemia and hyperuricemia were the important risk factors for microalbuminuria in the overweight. The area under ROC curves of the regression model based on the risk factors was 0.82 in predicting microalbuminuria, meanwhile, a decision threshold of 0.2 was found for predicting microalbuminuria with a sensitivity of 67.4% and specificity of 79.0%, and a global predictive value of 75.7%. A decision threshold of 0.1 was chosen for screening microalbuminuria with a sensitivity of 90.0% and specificity of 56.5%, and a global predictive value of 61.7%.

Conclusions:

The prediction model was an effective tool for screening microalbuminuria by using routine data among overweight populations.
Origin of biological information: Inherent occurrence of intron-rich split genes, coding for complex extant proteins, within pre-biotic random genetic sequences
Authors: Senapathy Periannan , Kumar Brajendra , Singh Chandan , Senapathy Sudar , Balan Bipin , Kuppuswami Raj
Published: July 2019

The origin of biological information is an unexplained phenomenon. Prior research in resolving the origin of proteins, based on the assumption that the first genes were contiguous prokaryotic sequences has not succeeded. Rather, it has been established that contiguous protein-coding genes do not exist in practically any amount of random genetic sequences. We found that complex eukaryotic proteins could be inherently encoded in split genes that could exist by chance within mere micrograms to milligrams of random DNA. Using protein amino acid sequence variability, codon degeneracy, and stringent exon-length restriction, we demonstrate that split genes for proteins of extant eukaryotes occur extensively in random genetic sequences. The results provide evidence that an abundance of split genes encoding advanced proteins in a small amount of prebiotic genetic material could have ignited the evolution of the eukaryotic genome.
Methanogen consortium metabolism characteristic analysis of Illinois basin by real time monitor method
Authors: Xiao Dong , Wang Enyuan
Published: July 2019

Microbially Enhance Coalbed Methane technology is used to improve methane content in coalbeds. The methanogen consortium metabolism process is the basic avenue for MECoM to yield methane with some organic compounds in coal. Detailed information about the metabolism process is needed in studying the microbial consortium mechanism. Traditional gas analysis is limited by gas source and test complexity. The real time monitor with Infrared gas sensor breaks the gas analysis limitation. It shows much more detailed information than the traditional analysis method including information about microbial growth factor changes, reaction speeds for environmental changes, the detailed relationship between CH4 and CO2, methane yield and the consumption factor by real time. With these factors, MECoM can be much better evaluated and controlled. Experiments show that inhibitory and incentive effects will influence the whole organic material conversion to methane period. Not until a microbial community achieves a balanced condition, can methane generation reach a stable condition.
Co-transformation of Oil Palm Using Agrobacterium-Mediated Transformation
Authors: Le Vu
Published: July 2019

Agrobacterium-mediated transformation is being used as an alternative method for improving the conventional breeding. In this study, immature embryos (IEs) of oil palm are chosen as explants for transformation. &x03B2;-glucuronidase (gus) and green fluorescence protein (GFP) were harbored by the two plasmids pCAMBIA 1304 and pCAMBIA 1302 respectively. The results were obtained at least four days after transformation. The IEs placing in the N6O medium for 7 days were then co-cultivated with A.tumefaciens suspension within 30 mins and then incubated in the dark for 1 day. In single transformation, GUS assay revealed that about 64% transient transformation frequency was obtained for IEs two weeks after co-cultivation, GFP activity was recorded as 41.67% transformation frequency for IEs 4 days after co-cultivation. In co-transformation, the transformation frequency was lower than single transformation and there was no GFP activity recorded in co-transformation.
Grb2 binds to PTEN and regulates its nuclear translocation to maintain the genomic stability in DNA damage response
Authors: Hou Bolin , Xu Shanshan , Xu Yang , Gao Quan , Zhang Caining , Liu Ling , Yang Huaiyi , Jiang Xuejun , Che Yongsheng
Published: July 2019

Growth factor receptor bound protein 2 (Grb2) is an adaptor protein critical for signal transduction and endocytosis, but its role in DNA damage response (DDR) remains unknown. Here, we report that either knockdown of Grb2 or overexpression of the mutated Grb2 promotes micronuclei formation in response to oxidative stress. Furthermore, Grb2 was demonstrated to interact with phosphatase and tensin homologue (PTEN; a tumor suppressor essential for nuclear stability), and the loss of Grb2 reduced the nuclear-localized PTEN, which was further decreased upon stimulation with hydrogen peroxide (H2O2). Overexpression of the T398A-mutated, nuclear-localized PTEN reduced micronuclei frequency in the cells deficient of functional Grb2 via rescuing the H2O2-dependent expression of Rad51, a protein essential for the homologous recombination (HR) repair process. Moreover, depletion of Grb2 markedly decreased the expression of Rad51 and its interaction with PTEN. Notably, Rad51 showed a preference to immunoprecipation with the T398A-PTEN mutant, and silencing of Rad51 alone accumulated micronuclei concurring with decreased expression of both Grb2 and PTEN. Our findings indicate that Grb2 interacts with PTEN and Rad51 to regulate genomic stability in DDR by mediating the nuclear translocation of PTEN to affect the expression of Rad51.
Increase in HDAC9 suppresses myoblast differentiation via epigenetic regulation of autophagy in hypoxia
Authors: Zhang Zhang , Zhang Liqiang , Zhou You , Li Liya , Zhao Jiangdong , Qin Wen , Jin Zuolin , Liu Wenjia
Published: July 2019

Extremely reduced oxygen (O2) levels are detrimental to myogenic differentiation and multinucleated myotube formation, and chronic exposure to high-altitude hypoxia has been reported to be an important factor in skeletal muscle atrophy. However, how chronic hypoxia causes muscle dysfunction remains unknown. In the present study, we found that severe hypoxia (1% O2) significantly inhibited the function of C2C12 cells (from a myoblast cell line). Importantly, the impairment was continuously manifested even during culture under normoxic conditions for several passages. Mechanistically, we revealed that histone deacetylases 9 (HDAC9), a member of the histone deacetylase family, was significantly increased in C2C12 cells under hypoxic conditions, thereby inhibiting intracellular autophagy levels by directly binding to the promoter regions of Atg7, Beclin1, and LC3. This phenomenon resulted in the sequential dephosphorylation of GSK3β and inactivation of the canonical Wnt pathway, impairing the function of the C2C12 cells. Taken together, our results suggest that hypoxia-induced myoblast dysfunction is due to aberrant epigenetic regulation of autophagy, and our experimental evidence reveals the possible molecular pathogenesis responsible for some muscle diseases caused by chronic hypoxia and suggests a potential therapeutic option.
PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination
Authors: Kim Ji-Eun , Lee Duk-Shin , Kim Min Ju , Kang Tae-Cheon
Published: July 2019

Neuronal precursor cell expressed developmentally downregulated 4-2 (NEDD4-2) is an E3 ubiquitin ligase to regulate ion transport by controlling cellular trafficking/endocytosis and lysosomal degradation of ion channels and transporters. Thus, NEDD4-2 is relevant to neuronal excitability and epileptic encephalopathies in human patients. However, the regulatory molecules for NEDD4-2 dephosphorylation have been still elusive. Here, we demonstrate that pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN) specifically dephosphorylated NEDD4-2 serine (S) 448 site. PLPP/CIN deletion inhibited NEDD4-2 ubiquitination, and diminished the responsiveness of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) by facilitating NEDD4-2-mediated ubiquitination of GluA1 subunit under physiological condition. PLPP/CIN overexpression reversed these effects. These PLPP/CIN-mediated processes were required for the increased seizure severity and its progression in response to kainic acid (KA). Therefore, we suggest the novel function of PLPP/CIN as a NEDD4-2 phosphatase, which may be a potential therapeutic target for NEDD4-2-associated diseases as well as various neurological and psychiatric disorders, including epilepsy.
The natural compound neobractatin inhibits tumor metastasis by upregulating the RNA-binding-protein MBNL2
Authors: Zhang Juan , Zheng Zhaoqing , Wu Man , Zhang Li , Wang Jing , Fu Wenwei , Xu Naihan , Zhao Zhili , Lao Yuanzhi , Xu Hongxi
Published: July 2019

Tumor metastasis is the predominant cause of lethality in cancer. We found that Neobractatin (NBT), a natural compound isolated from Garcinia bracteata, could efficiently inhibit breast and lung cancer cells metastasis. However, the mechanisms of NBT inhibiting cancer metastasis remain unclear. Based on the RNA-sequencing result and transcriptome analysis, Muscleblind-like 2 (MBNL2) was found to be significantly upregulated in the cells treated with NBT. The Cancer Genome Atlas (TCGA) database analysis indicated that the expression of MBNL2 in breast and lung carcinoma tumor tissues was significantly lower compared to normal tissues. We thus conducted to investigate the antimetastatic role of MBNL2. MBNL2 overexpression mimicked the effect of NBT on breast cancer and lung cancer cell motility and metastasis, in addition significantly enhanced the inhibition effect of NBT. MBNL2 knockdown furthermore partially eliminated the inhibitory effect of NBT on metastasis. Mechanistically, we demonstrated that NBT- and MBNL2-mediated antimetastasis regulation significantly correlated with the pAKT/epithelial-mesenchymal transition (EMT) pathway. Subsequent in vivo study showed the same metastasis inhibition effect in NBT and MBNL2 in MDA-MB-231 xenografts mouse model. This study suggest that NBT possesses significant antitumor activity in breast and lung cancer cells that is partly mediated through the MBNL2 expression and enhancement in metastasis via the pAKT/EMT signaling pathway.
Free-standing and ultrathin inorganic light-emitting diode array
Authors: Tchoe Youngbin , Chung Kunook , Lee Keundong , Jo Janghyun , Chung Kyungmin , Hyun Jerome K. , Kim Miyoung , Yi Gyu-Chul
Published: July 2019

We report on the fabrication and characteristics of an individually addressable gallium nitride (GaN) microdisk light-emitting diode (LED) array in free-standing and ultrathin form. A high-quality GaN microdisk array with n-GaN, InGaN/GaN quantum wells and p-GaN layers was epitaxially grown on graphene microdots patterned on SiO2/Si substrates. Due to the weak attachment of the graphene microdots to the growth substrate, a microdisk array coated with a polyimide layer was easily separated from the substrate using mechanical or chemical methods to form an ultrathin free-standing film. Individually addressable microdisk LEDs were created by forming thin metal contacts on the p-GaN and n-GaN surfaces in a crossbar configuration. Each microdisk LED that comprised an ultrahigh resolution array of 2500 pixels per inch was found to be uniquely addressable. The devices in free-standing form exhibited stable electrical and optoelectronic characteristics under extreme bending conditions and continuous operation mode despite the absence of a heat dissipating substrate. These results present promising approaches for the fabrication of high-quality inorganic semiconductor devices for ultrahigh resolution and high-performance flexible applications.
PRKCSH contributes to tumorigenesis by selective boosting of IRE1 signaling pathway
Authors: Shin Gu-Choul , Moon Sung Ung , Kang Hong Seok , Choi Hyo-Sun , Han Hee Dong , Kim Kyun-Hwan
Published: July 2019

Unfolded protein response (UPR) is an adaptive mechanism that aims at restoring ER homeostasis under severe environmental stress. Malignant cells are resistant to environmental stress, which is largely due to an activated UPR. However, the molecular mechanisms by which different UPR branches are selectively controlled in tumor cells are not clearly understood. Here, we provide evidence that PRKCSH, previously known as glucosidase II beta subunit, functions as a regulator for selective activation of the IRE1α branch of UPR. PRKCSH boosts ER stress–mediated autophosphorylation and oligomerization of IRE1α through mutual interaction. PRKCSH contributes to the induction of tumor-promoting factors and to tumor resistance to ER stress. Increased levels of PRKCSH in various tumor tissues are positively correlated with the expression of XBP1-target genes. Taken together, our data provide a molecular rationale for selective activation of the IRE1α branch in tumors and adaptation of tumor cells to severe environmental stress.
Dendrite fragmentation induced by massive-like δ–γ transformation in Fe–C alloys
Authors: Yasuda Hideyuki , Morishita Kohei , Nakatsuka Noriaki , Nishimura Tomohiro , Yoshiya Masato , Sugiyama Akira , Uesugi Kentaro , Takeuchi Akihisa
Published: July 2019

Dendrite arm fragmentation is considered in solidification structure tailoring. Time-resolved and in situ imaging using synchrotron radiation X-rays allows the observation of dendrite arm fragmentation in Fe–C alloys. Here we report a dendrite arm fragmentation mechanism. A massive-like transformation from ferrite to austenite rather than the peritectic reaction occurs during or after ferrite solidification. The transformation produces refined austenite grains and ferrite–austenite boundaries in dendrite arms. The austenite grains are fragmented by the liquid phase that is produced at the grain boundary. In unidirectional solidification, a slight increase in temperature moves the ferrite–austenite interface backwards and promotes detachment of the primary and secondary arms at the δ–γ interface via a reverse peritectic reaction. The results show a massive-like transformation inducing the dendrite arm fragmentation has a role in formation of the solidification structure and the austenite grain structures in the Fe–C alloys.
Live cell imaging reveals 3′-UTR dependent mRNA sorting to synapses
Authors: Bauer Karl E. , Segura Inmaculada , Gaspar Imre , Scheuss Volker , Illig Christin , Ammer Georg , Hutten Saskia , Basyuk Eugénia , Fernández-Moya Sandra M. , Ehses Janina , Bertrand Edouard , Kiebler Michael A.
Published: July 2019

mRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions. However, the precise process of mRNA sorting to synapses in neurons remains elusive. Here we use Rgs4 mRNA to investigate 3′-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules display 3′-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3′-UTR causes an anterograde transport bias, which requires the Staufen2 protein. Moreover, the 3′-UTR mediates dynamic, sustained mRNA recruitment to synapses. Visualization at high temporal resolution enables us to show mRNA patrolling dendrites, allowing transient interaction with multiple synapses, in agreement with the sushi-belt model. Modulation of neuronal activity by either chemical silencing or local glutamate uncaging regulates both the 3′-UTR-dependent transport bias and synaptic recruitment. This dynamic and reversible mRNA recruitment to active synapses would allow translation and synaptic remodeling in a spatially and temporally adaptive manner.
Phase stabilization by electronic entropy in plutonium
Authors: Harrison N. , Betts J. B. , Wartenbe M. R. , Balakirev F. F. , Richmond S. , Jaime M. , Tobash P. H.
Published: July 2019

Plutonium metal undergoes an anomalously large 25% collapse in volume from its largest volume δ phase (δ-Pu) to its low temperature α phase, yet the underlying thermodynamic mechanism has largely remained a mystery. Here we use magnetostriction measurements to isolate a previously hidden yet substantial electronic contribution to the entropy of δ-Pu, which we show to be crucial for the stabilization of this phase. The entropy originates from two competing instabilities of the 5f-electron shell, which we show to drive the volume of Pu in opposing directions, depending on the temperature and volume. Using calorimetry measurements, we establish a robust thermodynamic connection between the two excitation energies, the atomic volume, and the previously reported excess entropy of δ-Pu at elevated temperatures.
Bypassing pan-enterovirus host factor PLA2G16
Authors: Baggen Jim , Liu Yue , Lyoo Heyrhyoung , van Vliet Arno L. W. , Wahedi Maryam , de Bruin Jost W. , Roberts Richard W. , Overduin Pieter , Meijer Adam , Rossmann Michael G. , Thibaut Hendrik Jan , van Kuppeveld Frank J. M.
Published: July 2019

Enteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we identify a possible mechanism of PLA2G16 evasion by employing a dual glycan receptor-binding enterovirus D68 (EV-D68) strain. We previously showed that this strain does not strictly require the canonical EV-D68 receptor sialic acid. Here, we employ a haploid screen to identify sulfated glycosaminoglycans (sGAGs) as its second glycan receptor. Remarkably, engagement of sGAGs enables this virus to bypass PLA2G16. Using cryo-EM analysis, we reveal that, in contrast to sialic acid, sGAGs stimulate genome release from virions via structural changes that enlarge the putative openings for genome egress. Together, we describe an enterovirus that can bypass PLA2G16 and identify additional virion destabilization as a potential mechanism to circumvent PLA2G16.
Immune adaptor SKAP1 acts a scaffold for Polo-like kinase 1 (PLK1) for the optimal cell cycling of T-cells
Authors: Raab Monika , Strebhardt Klaus , Rudd Christopher E.
Published: July 2019

While the immune cell adaptor protein SKAP1 mediates LFA-1 activation induced by antigen-receptor (TCR/CD3) ligation on T-cells, it is unclear whether the adaptor interacts with other mediators of T-cell function. In this context, the serine/threonine kinase, polo-like kinase (PLK1) regulates multiple steps in the mitotic and cell cycle progression of mammalian cells. Here, we show that SKAP1 is phosphorylated by and binds to PLK1 for the optimal cycling of T-cells. PLK1 binds to the N-terminal residue serine 31 (S31) of SKAP1 and the interaction is needed for optimal PLK1 kinase activity. Further, siRNA knock-down of SKAP1 reduced the rate of T-cell division concurrent with a delay in the expression of PLK1, Cyclin A and pH3. Reconstitution of these KD cells with WT SKAP1, but not the SKAP1 S31 mutant, restored normal cell division. SKAP1-PLK1 binding is dynamically regulated during the cell cycle of T-cells. Our findings identify a novel role for SKAP1 in the regulation of PLK1 and optimal cell cycling needed for T-cell clonal expansion in response to antigenic activation.
Changes in Alcohol Consumption and Associated Variables among Older Adults in Spain: A population-based cohort study
Authors: Soler-Vila Hosanna , Ortolá Rosario , García-Esquinas Esther , León-Muñoz Luz Mª , Rodríguez-Artalejo Fernando
Published: July 2019

We examined prospective changes in drinking patterns and their associations with socio-behavioral and health status variables in older adults in Spain using data from a prospective cohort of 2,505 individuals (53.3% women) representative of the non-institutionalized population aged >60 years in Spain. Alcohol consumption was assessed at baseline (2008–10) and at follow-up (2012) with a validated diet history. At risk drinking was defined as consuming >14 g of alcohol/day on average or any binge drinking in the last 30 days; lower amounts were considered light drinking. A total of 26.5% of study participants changed their intake during follow-up. Most participants reduced alcohol intake, but 23.3% of men and 8.9% of women went from light to at risk drinking during the study period. Low social connectivity at baseline was linked to at risk drinking for both sexes. However, the observed associations between changes in social connectivity, morbidity, BMI, or dietary habits and changes in drinking patterns differed by sex. We concluded that since about a quarter of older adults in Spain consume more alcohol than recommended, identifying socio-behavioral factors associated with this behavior is key for designing health campaigns targeting excessive alcohol consumption in this vulnerable population.
A whole-body Fast Field-Cycling scanner for clinical molecular imaging studies
Authors: Broche Lionel M. , Ross P. James , Davies Gareth R. , MacLeod Mary-Joan , Lurie David J.
Published: July 2019

Fast Field-Cycling (FFC) is a well-established Nuclear Magnetic Resonance (NMR) technique that exploits varying magnetic fields to quantify molecular motion over a wide range of time scales, providing rich structural information from nanometres to micrometres, non-invasively. Previous work demonstrated great potential for FFC-NMR biomarkers in medical applications; our research group has now ported this technology to medical imaging by designing a whole-body FFC Magnetic Resonance Imaging (FFC-MRI) scanner capable of performing accurate measurements non-invasively over the entire body, using signals from water and fat protons. This is a unique tool to explore new biomarkers related to disease-induced tissue remodelling. Our approach required making radical changes in the design, construction and control of MRI hardware so that the magnetic field is switched within 12.5 ms to reach any field strength from 50 μT to 0.2 T, providing clinically useful images within minutes. Pilot studies demonstrated endogenous field-dependant contrast in biological tissues in good agreement with reference data from other imaging modalities, confirming that our system can perform multiscale structural imaging of biological tissues, from nanometres to micrometres. It is now possible to confirmex vivoresults obtained from previous clinical studies, offering applications in diagnosis, staging and monitoring treatment for cancer, stroke, osteoarthritis and oedema.
Mass screening for colorectal cancer in a population of two million older adults in Guangzhou, China
Authors: Lin Guozhen , Feng Zhiqiang , Liu Huazhang , Li Yan , Nie Yuqiang , Liang Yingru , Li Ke
Published: July 2019

Screening is an effective measure to prevent and control colorectal cancer (CRC). A mass CRC screening programme was conducted in Guangzhou from 2015 to 2017. Public media and reminders from a mobile short message service were used to invite residents aged between 50 and 74 years. A high-risk factor questionnaire (HRFQ) and biennial faecal immunochemical testing (FIT) were chosen as the primary screening methods, and individuals with a positive test result were referred to a defined hospital for an assessment colonoscopy. During the 3 years, 350,581 residents of the total eligible population of 2,283,214 attended the free first stage of screening. In all, 91.0% of the participants finished the HRFQs and FITs. The total uptake rate was 15.4%, which increased with age, female sex, and rural location. There was 15.9% positivity in the first stage of screening, including 8.5% positive HRFQs, 6.2% positive FITs and 1.2% positive HRFQs and FITs. In total, 10,600 individuals with positive HRFQs/FITs completed an assessment colonoscopy. The total uptake rate of colonoscopies was 18.9%, which decreased with age and female sex. Three hundred fifty-one CRCs and 980 advanced adenomas (AAs) were diagnosed with positive predictive values (PPV) of 3.3% and 9.2%, respectively. The PPVs of CRCs in the exclusively FIT-positive population were 4.9%, which was 10 times greater than in the exclusively HRFQ-positive population (0.5%). The PPVs of CRCs and AAs increased with age and male sex. The detection ratio of localized CRCs (including stage I and stage II) increased 68.1% due to screening. Although the compliance rate was low, the PPVs for CRCs and AAs were high. More effective mobilization of the programme’s needs and subsidies for colonoscopies should be taken into account to increase compliance.
Resting-state prefrontal EEG biomarkers in correlation with MMSE scores in elderly individuals
Authors: Choi Jungmi , Ku Boncho , You Young Gooun , Jo Miok , Kwon Minji , Choi Youyoung , Jung Segyeong , Ryu Soyoung , Park Eunjeong , Go Hoyeon , Kim Gahye , Cha Wonseok , Kim Jaeuk U.
Published: July 2019

We investigated whether cognitive decline could be explained by resting-state electroencephalography (EEG) biomarkers measured in prefrontal regions that reflect the slowing of intrinsic EEG oscillations. In an aged population dwelling in a rural community (total = 496, males = 165, females = 331), we estimated the global cognitive decline using the Mini-Mental State Examination (MMSE) and measured resting-state EEG parameters at the prefrontal regions of Fp1 and Fp2 in an eyes-closed state. Using a tertile split method, the subjects were classified as T3 (MMSE 28–30, N = 162), T2 (MMSE 25–27, N = 179), or T1 (MMSE ≤ 24, N = 155). The EEG slowing biomarkers of the median frequency, peak frequency and alpha-to-theta ratio decreased as the MMSE scores decreased from T2 to T1 for both sexes (−5.19 ≤ t-value ≤ −3.41 for males and −7.24 ≤ t-value ≤ −4.43 for females) after adjusting for age and education level. Using a double cross-validation procedure, we developed a prediction model for the MMSE scores using the EEG slowing biomarkers and demographic covariates of sex, age and education level. The maximum intraclass correlation coefficient between the MMSE scores and model-predicted values was 0.757 with RMSE = 2.685. The resting-state EEG biomarkers showed significant changes in people with early cognitive decline and correlated well with the MMSE scores. Resting-state EEG slowing measured in the prefrontal regions may be useful for the screening and follow-up of global cognitive decline in elderly individuals.
Enhanced soil fertility, plant growth promotion and microbial enzymatic activities of vermicomposted fly ash
Authors: Usmani Zeba , Kumar Vipin , Gupta Pratishtha , Gupta Gauri , Rani Rupa , Chandra Avantika
Published: July 2019

It is reported that coal consumption in the Asia-Pacific region is going to increase to about 87.2 percent by 2035. Management of coal combustion residues (CCRs) generated by industries is a major bottleneck towards handling the repercussions of coal usage. The present study investigates a management technique for these potentially hazardous wastes by means of vermicomposting. In the present investigation, studies were made on the effects of various concentrations of vermicomposted fly ash (VCF) added to agricultural soil, on the growth and yield of tomato (Lycopersicon esculentum Mill.) and brinjal (Solanum melongena L.) plants. The toxicity of trace elements in VCF were estimated using coefficient of pollution and potential ecological risk index, which revealed no apparent risks to the environment. A gradual increase in VCF concentrations in the agricultural soil improved the physico-chemical properties, enzymatic activities, microbial biomass, carbon and microbial population upto 90 days after sowing of seeds. The VCF amendments significantly (p < 0.05) improved the soil quality (2.86% nitrogen and 1.05% Phosphorous) and germination percentage (82.22%) of seeds in L. esculentum and also in S. melongena. The results of this study reveal that, CCRs can be effectively managed in agriculture specially in developing economies.
MR-guided Focused Ultrasound Facilitates Sonodynamic Therapy with 5-Aminolevulinic Acid in a Rat Glioma Model
Authors: Wu Sheng-Kai , Santos Marc A. , Marcus Stuart L. , Hynynen Kullervo
Published: July 2019

Glioblastoma multiforme (GBM) continues to have a dismal prognosis and significant efforts are being made to develop more effective treatment methods. Sonodynamic therapy (SDT) is an emerging modality for cancer treatment which combines ultrasound with sonosensitizers to produce a localized cytotoxic effect. It has long been known that ultrasound exposure can cause both thermal and non-thermal bioeffects and it remains an open question to what degree does temperature impact the efficacy of SDT. In order to optimize the ultrasound parameters of SDT, transcranial MRI-guided focused ultrasound (MRgFUS) and real-time MRI thermometry were used to monitor the therapy in a rat brain tumor model. Experiments were performed using a C6 intracranial glioma tumor model in 37 male Sprague Dawley rats. Treatments were performed about 7 days following tumor implantation when the tumor reached 1–3 mm in diameter as determined by MRI. 5-aminolevulinic acid (5-ALA) was injected at a dose of 60 mg/kg six hours before sonication. MRgFUS at 1.06 MHz was delivered continuously at an in situ spatial-peak temporal-average intensity of 5.5 W/cm2 for 20 min. MR thermometry was acquired to monitor the temperature change in the brain during sonication. The tumor growth response for animals receiving 5-ALA alone, FUS alone, 5-ALA + FUS and a sham control group were evaluated with MRI every week following treatment. During 20 min of MRgFUS at 5.5 W/cm2, the temperature within the targeted brain tumor was elevated from 32.3 ± 0.5 °C and 37.2 ± 0.7 °C to 33.2 ± 0.9 °C and 38.4 ± 1.1 °C, respectively. Both the tumor growth inhibition and survival were significantly improved in the 5-ALA + FUS group with 32 °C or 37 °C as the starting core body (rectal) temperature. 5-ALA alone and FUS alone did not improve survival. These promising results indicate that relatively low power continuous wave transcranial MRgFUS in conjunction with 5-ALA can produce an inhibitory effect on rat brain tumor growth in the absence of thermal dose. Further investigation of the ultrasound parameters is needed to improve the therapeutic efficacy of MRgFUS and 5-ALA.