bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthogonal time-of-flight mass spectrometry of an ion beam with a broad kinetic energy profile
Authors: Miller S. W. , Prince B. D. , Bemish R. J.
Published: October 2017

A combined experimental and modeling effort is undertaken to assess a detection system composed of an orthogonal extraction time-of-flight (TOF) mass spectrometer coupled to a continuous ion source emitting an ion beam with kinetic energy of several hundred eV. The continuous ion source comprises an electrospray capillary system employing an undiluted ionic liquid emitting directly into vacuum. The resulting ion beam consists of ions with kinetic energy distributions of width greater than a hundred of eV and mass-to-charge (m/q) ratios ranging from 111 to 500 000 amu/q. In particular, the investigation aims to demonstrate the kinetic energy resolution along the ion beam axis (axial) of orthogonally extracted ions in measurements of the axial kinetic energy-specific mass spectrum, mass flow rate, and total ion current. The described instrument is capable of simultaneous measurement of a broad m/q range in a single acquisition cycle with approximately 25 eV/q axial kinetic energy resolution. Mass resolutions of ∼340 (M/ΔM, FWHM) were obtained for ions at m/q = 1974. Comparison of the orthogonally extracted TOF mass spectrum to mass flow and ion current measurements obtained with a quartz-crystal microbalance and Faraday cup, respectively, shows reasonable numeric agreement and qualitative agreement in the trend as a function of energy defect.
Some remarks concerning the centrifugal term approximation
Authors: Ferreira F. J. S. , Bezerra V. B.
Published: October 2017

We generalize the Pekeris approximation for the centrifugal term potential, l(l+1)r2, and use this to obtain the solutions of the radial Schrödinger equation for the arbitrary angular quantum number, l, of the Hulthén potential. We also obtain the expressions for the bound state energies corresponding to this potential and calculate their values for different states and compare with other results presented in the literature. We also consider some models of physical potentials, namely, the Eckart potential, the Poschl-Teller potentials, the Rosen-Morse potential, the Woods-Saxon potential, and the Manning-Rosen potential. Thus, following straightforward the example corresponding to the Hulthén potential, we show what the radial solutions and the energy spectra for these potentials are.
Z-scan confocal method for indirect focus location
Authors: Castro-Marín Pablo , Castro-Olvera Gustavo , Ruíz Camilo , Garduño-Mejía Jesús , Rosete-Aguilar Martha , Bruce Neil C.
Published: October 2017

We present a new technique that we have defined as the z-scan confocal method to determine the location and size of the focal spot in a tightly focused ultrashort laser pulse. The method permits accurate positioning of a target in the focal spot with a fast response. The technique is designed to help to automatize the location of an overdense target in focus in a laser plasma experiment and suitable to be implemented in a closed loop configuration setup. The method allows for a fast localization of the focal position and the relative motion of the target with respect to it. As an example of the potential of the technique we have measured the defocusing of a fast rotating disc in several radii to reconstruct the motion of the disc at focus.
Operating silicon-based lasers with high quantum efficiency above room temperature
Authors: Cockbill Louisa
Published: October 2017

PbSrS cladding with a PbS active layer grown directly on silicon was found to have a high operating temperature of up to 313K.
Researchers report simple, nondestructive method to extract minority carrier diffusion lengths
Authors: Kim Meeri
Published: October 2017

A purely electrical technique can be used to optimize the design of optoelectronic devices by better understanding material properties.
Role of environmental and spatial processes structuring fish assemblages in streams of the eastern Amazon
Authors: Benone N. L. , Ligeiro R. , Juen L. , Montag L. F. A.
Published: October 2017

Considering the increasing importance of analysing spatial structure in ecological studies, the aims of the present study were to test whether fluvial distances and environmental factors are important drivers of the β-diversity of stream fish assemblages, and whether β-diversity is different in distinct hydrological periods. Specimens were sampled at 33 stream sites in the eastern Amazon. Eight environmental variables were measured at each site and fluvial distances between pairs of stream sites were determined. Environmental variables were the main factors structuring fish assemblages in both periods. However, fluvial distances were important only during the flood period. This can be related to the formation of extensive flood plains in this period, which increases connectivity between streams, breaking habitat isolation and increasing the regional signal for fish species. The higher correlation of β-diversity with environmental variables during the flood period may be related to decreased dispersal limitations and intermediate dispersal. Finally, β-diversity was higher during the flood period, highlighting the importance of the heterogeneity of the flood plain to stream biota. The results of the present study indicate that spatial and environmental factors play complementary roles in structuring fish assemblages in Amazon streams, and that β-diversity was affected by changes in the habitat connectivity experienced in different hydrological periods.
Tracking anguillid eels: five decades of telemetry-based research
Authors: Béguer-Pon Mélanie , Dodson Julian J. , Castonguay Martin , Jellyman Don , Aarestrup Kim , Tsukamoto Katsumi
Published: October 2017

Advances in telemetry technologies have provided new opportunities to reveal the often-cryptic spatial ecology of anguillid eels. Herein we review 105 studies published between 1972 and 2016 that used a variety of telemetry technologies to study the movements of eels in a variety of habitats. Eight anguillid species have been tracked in three main geographical locations: Western Europe, the north-eastern part of North America and Australasia. Telemetry has proven to be an effective method for determining patterns of yellow eel movements in continental waters. It has also been used extensively to investigate the migratory behaviour of maturing eels as they leave fresh water to reach the sea. Among recent findings is the observation that downstream migration in continental waters is quite discontinuous, characterised by extended stopovers. Reconstructed migration routes in the open ocean obtained from satellite tags have provided indications of spawning areas, extensive vertical migrations and initial clues about the orientation mechanisms at sea. Telemetry studies have also revealed apparent evidence of predation by marine mammals and fish at sea, suggesting a significant natural source of mortality during the eel spawning migration. Finally, we discuss some limitations of telemetry technology and future directions, as well as associated challenges, to the developing field of eel spatial ecology.
Between VP and NN
Authors: Gaeta Livio , Zeldes Amir
Published: October 2017

This paper is concerned with the classification and analysis of different types of German synthetic compounds headed by deverbal agent nouns in -er, such as Romanleser ‘novel-reader’ or Gedankenleser ‘mind-reader’, where the non-head is seen to saturate an argument of the head lexeme while adhering to the semantic interpretation found in corresponding VPs (e.g. the distinct senses of read in the previous examples). In contrast to several previous approaches, which attempt to explain the relationship between VPs and compounds using a unified mechanism of incorporation or derivation, we argue that different compounding patterns require different analyses and that the respective constructions are to some extent independent of each other. While some compounds are modelled after frequent, familiar VPs and take account of the usage profile of syntactic phrases, other productive sets of compounds extend independently lexicalized schemas with fixed compound heads. To support our analysis we undertake the largest empirical survey of these formations to date, using a broad coverage Web corpus. We suggest several categories of verb-object lexeme pairs to account for our data and formulate an analysis of the facts within the framework of Construction Morphology.
Use of agricultural limestone and lime in aquaculture.
Authors: Boyd C. E.
Published: October 2017

Application of agricultural limestone to increase alkalinity to about 50 mg/l improves production in fertilized ponds and enhances water quality in ponds for feed-based aquaculture. Burnt lime and hydrated lime cause an initial high pH, but they can be applied to bottoms of empty ponds for the purpose of neutralizing bottom soil acidity. In addition, even where acidic soil and low alkalinity are not present, burnt or hydrated lime also may be used to raise pH and disinfect pond bottoms. In ponds with low dissolved oxygen and high carbon dioxide (CO
2
) concentrations, burnt lime at 1.28 and hydrated lime at 1.68 times CO
2
concentration will remove CO
2
and prevent it from interfering with oxygen uptake by aquatic animals. Small, frequent applications of lime sometimes are made to ponds to remove CO
2
and phosphate, limit phytoplankton growth, and stabilize pH. The effectiveness of this practice is dubious.
Life History Observations of Adfluvial Chinook Salmon prior to Reintroduction of Anadromous Salmonids
Authors: Brenkman Samuel J. , Sutton Kathryn T. , Marshall Anne R.
Published: October 2017

Pacific salmon Oncorhynchus spp. vary in life history and degree of anadromy, but information on populations inhabiting only freshwater throughout their life cycle is limited. We confirmed the presence of a self-sustaining population of adfluvial Chinook Salmon O. tshawytscha upstream of century-old hydroelectric dams in the Skokomish River system, Washington. Snorkel, redd, and juvenile-trapping surveys revealed their life history attributes prior to planned reintroductions of anadromous salmonids above the dams. Adult Chinook Salmon in Lake Cushman (a reservoir) were large-bodied fish (mean length = 610 mm; mean weight = 5.4 kg), up to 4 years of age, and migrated into the inlet river to spawn in October and November. Annual peak counts of adult spawners were chronically low (35 or less) based on interannual snorkel surveys since 1994. Chinook Salmon parr (n = 780; mean length = 105 mm) of a single cohort were captured (June–August) at the upper dam and had faded parr marks and bright, silvery coloration typical of smolts. Our study confirmed that Chinook Salmon reared and reproduced exclusively in freshwater and suggested a life history pattern most closely resembling anadromous fall-run Chinook Salmon. We reviewed annual hatchery release records from 1926 to 2016 and found no evidence of Chinook Salmon being planted above the dams, in contrast to landlocked Chinook Salmon occurring in Oregon and California reservoirs. These adfluvial Chinook Salmon may be descendants of the native Skokomish River anadromous population, including fish from below the dam, and represent adaptations to the reservoir after dam construction. Lake Cushman Chinook Salmon are federally threatened, the only reported landlocked population in Puget Sound and coastal Washington, and may represent a unique evolutionary legacy worthy of protection.

Received March 7, 2017; accepted July 5, 2017 Published online October 20, 2017
Effects of different heat–moisture treatments on the physicochemical properties of brown rice flour
Authors: Nakamura Sumiko , Okumura Hisako , Sugawara Masayoshi , Noro Wataru , Homma Noriyuki , Ohtsubo Ken’ichi
Published: October 2017

We evaluated the effect of heat–moisture treatment (HMT) on the main chemical components, physical properties, and enzyme activities of two types of brown rice flour: high-amylose Koshinokaori and normal-quality Koshiibuki. Five different HMTs using brown rice (moisture content was 12.0%) were assessed: 0.1 MPa/120 °C for 5 or 10 min, 0.2 MPa/134 °C for 5 or 10 min and 0.3 MPa/144 °C for 10 min. HMT, decreased the α-amylase and lipase activities, and fat acidity, and slightly increased the dietary fiber and resistant starch levels. After 2 months’ storage at 35 °C, rice samples that were treated with 0.2 MPa/134 °C or 0.3 MPa/144 °C for 10 min had a lower fat acidity than untreated samples, which would be useful for long-term storage and export of rice flour. And HMT exhibited inhibition of retrogradation in the pasting and physical properties, which is profitable to promote the qualities of the rice products.
Microstructure evolution and fracture behaviour of friction stir welded 6061-T6 thin plate joints under high rotational speed
Authors: Liu F. J. , Fu L. , Chen H. Y.
Published: October 2017

6061-T6 sheets with 0.8 mm thickness were successfully welded using high-speed friction stir welding (FSW) technology. The microstructural evolution and fracture behaviour of the joints were studied. The results show that sound joints could be obtained at the investigated high rotational speed of 8000 rev min−1 and welding speeds of 300–1200 mm min−1. Compared with conventional rotational speed, the grain size in the nugget zone (NZ) is obviously refined under high rotational speed. The Mg2Si, Al8Fe2Si and Al2CuMg precipitates reprecipitated adequately in the NZ during high-speed FSW, resulting in the number of the precipitates increased significantly, and further alleviating the weld softening. The difference in weld softening leads to different fracture characteristics during the tensile process. After artificial aging, the maximum welding softening in all joints is located in the heat affected zone, and the fracture is characterised by brittle fracture.
An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns
Authors: Graessl Melanie , Koch Johannes , Calderon Abram , Kamps Dominic , Banerjee Soumya , Mazel Tomáš , Schulze Nina , Jungkurth Jana Kathrin , Patwardhan Rutuja , Solouk Djamschid , Hampe Nico , Hoffmann Bernd , Dehmelt Leif , Nalbant Perihan
Published: October 2017

Rho GTPase-based signaling networks control cellular dynamics by coordinating protrusions and retractions in space and time. Here, we reveal a signaling network that generates pulses and propagating waves of cell contractions. These dynamic patterns emerge via self-organization from an activator–inhibitor network, in which the small GTPase Rho amplifies its activity by recruiting its activator, the guanine nucleotide exchange factor GEF-H1. Rho also inhibits itself by local recruitment of actomyosin and the associated RhoGAP Myo9b. This network structure enables spontaneous, self-limiting patterns of subcellular contractility that can explore mechanical cues in the extracellular environment. Indeed, actomyosin pulse frequency in cells is altered by matrix elasticity, showing that coupling of contractility pulses to environmental deformations modulates network dynamics. Thus, our study reveals a mechanism that integrates intracellular biochemical and extracellular mechanical signals into subcellular activity patterns to control cellular contractility dynamics.
What Can Elder Mistreatment Researchers Learn About Primary Prevention From Family Violence Intervention Models?
Authors: Meyer Kylie , Yonashiro-Cho Jeanine , Gassoumis Zachary D , Mosqueda Laura , Han S Duke , Wilber Kathleen H
Published: October 2017

Elder mistreatment (EM) is a public health problem that harms millions of older Americans each year. Despite growing recognition of its occurrence, there are no evidence-based primary prevention programs. Although EM is distinct from other areas of family violence, including child maltreatment and intimate partner violence, common risk factors and theoretical underpinnings point to opportunities for prevention strategies. Drawing on evidence-based best practices found in other fields of family violence, we identify approaches that could be tested to prevent EM at the hands of family caregivers, who are among the most likely to commit mistreatment. Specifically, we examine home visiting approaches primarily used in the child maltreatment field and identify components that have potential to inform EM interventions, including prevention. We conclude that there is enough information to begin testing a prevention intervention for EM that targets caregivers.
Schur $P$-positivity and Involution Stanley Symmetric Functions
Authors: Hamaker Zachary , Marberg Eric , Pawlowski Brendan
Published: October 2017

The involution Stanley symmetric functions$\hat{F}_y$ are the stable limits of the analogs of Schubert polynomials for the orbits of the orthogonal group in the flag variety. These symmetric functions are also generating functions for involution words and are indexed by the involutions in the symmetric group. By construction, each $\hat{F}_y$ is a sum of Stanley symmetric functions and therefore Schur positive. We prove the stronger fact that these power series are Schur $P$-positive. We give an algorithm to efficiently compute the decomposition of $\hat{F}_y$ into Schur $P$-summands and prove that this decomposition is triangular with respect to the dominance order on partitions. As an application, we derive pattern avoidance conditions which characterize the involution Stanley symmetric functions which are equal to Schur $P$-functions. We deduce as a corollary that the involution Stanley symmetric function of the reverse permutation is a Schur $P$-function indexed by a shifted staircase shape. These results lead to alternate proofs of theorems of Ardila–Serrano and DeWitt on skew Schur functions which are Schur $P$-functions. We also prove new Pfaffian formulas for certain related involution Schubert polynomials.
Orphans in the Market: The History of Orphan Drug Policy
Authors: Mikami Koichi
Published: October 2017

This paper examines the history of orphan drug policy, from the emergence of ‘orphans’ in the American pharmaceutical market in the 1960s, through the debates and agitations that resulted in the passage of the US Orphan Drug Act of 1983, to attempts in the 1990s to prevent abuse of that Act and restore its original intentions. Although an increased number of drugs for rare diseases have since been developed and marketed, the extremely high price of some such drugs is considered a major public health issue internationally. The present paper traces the origins of this issue to the market-based approach to resolving the problem of orphan drugs embodied in the 1983 Act. The paper also makes visible an alternative trajectory that existed for a while in the United Kingdom but was eventually abandoned in order to help the biotechnology industry grow in the context of an increasingly integrated European drug market.
Induction of Desmoplastic Trichoepithelioma in a Dermatofibroma
Authors: Georgescu Mihaela , Blödorn-Schlicht Norbert , Böer-Auer Almut
Published: October 2017

Induction of follicular germinative structures above a dermatofibroma (DF) is a common finding. Rarely, induction of a trichoblastoma in a DF has been observed. Here, we report the case of a desmoplastic trichoepithelioma induced by a DF. The lesion with clinical and histological appearance of a DF situated on the left dorsal foot showed an associated adnexal proliferation that fulfilled histopathological criteria of desmoplastic trichoepithelioma. Immunohistochemistry (Ber-EP4, Bcl-2, CK17, CK20, CK7, EMA, and Ki67) helped to confirm the diagnosis and to exclude possible differential diagnoses.
Case Series Analysis of Myopic Progression Control With a Unique Extended Depth of Focus Multifocal Contact Lens
Authors: Cooper Jeffrey , O'Connor Brett , Watanabe Ronald , Fuerst Randall , Berger Sharon , Eisenberg Nadine , Dillehay Sally M.
Published: October 2017

Objectives:

To determine the rate of myopia progression in children fit with a commercially available extended depth of focus (center distance) multifocal soft contact lens with attributes theoretically expected to slow the progression of myopia.

Methods:

A retrospective case series analysis of 32 patients (ages 6–19 years, mean 10.98±2.95) from 10 practice locations was performed. At initial presentation, 44% wore spectacles, 37.5% spherical soft contact lenses, 15.6% a different soft multifocal contact lens, and 3% orthokeratology lenses. All participants showed progression of at least −0.50 diopter with current corrections and were fit with an extended depth of focus (center distance) multifocal soft contact lens (NaturalVue Multifocal 1 Day Contact Lenses; Visioneering Technologies, Inc., Alpharetta, GA). Follow-up time was 6 to 25 months (mean: 10.94±4.76).

Results:

Reductions in the annualized rate of myopic progression from −0.85 D per year ±0.43 D to −0.04 D per year ±0.18 D (P<0.00000) OD, −0.90 D per year ±0.57 D to −0.03 D per year ±0.17 D (P<0.00000) OS were observed. These data represent a reduction of 95.4% OD and 96.25% OS. Approximately 98.4% of the children showed reduction of annualized myopic progression; 91% showed a decrease of 70% or greater. Overall, 81.25% showed complete halting of myopic progression, including 6.25% demonstrating myopic regression.

Conclusions:

This unique extended depth of focus (center distance) daily disposable multifocal contact lens was effective in slowing myopic progression in these children. These findings add to the growing evidence that center distance multifocal soft contact lenses may slow the progression of myopia.
In Vivo Confocal Microscopy Reveals Corneal Reinnervation After Treatment of Neurotrophic Keratopathy With Corneal Neurotization
Authors: Fung Simon S. M. , Catapano Joseph , Elbaz Uri , Zuker Ronald M. , Borschel Gregory H. , Ali Asim
Published: October 2017

Purpose:

To document the presence and location of new sensory nerve fibers after corneal neurotization using in vivo confocal microscopy (IVCM) in 2 patients with neurotrophic keratopathy (NK).

Methods:

Two patients with unilateral advanced NK received corneal neurotization to surgically reinnervate the cornea. IVCM was used to identify subbasal nerve fibers and document corneal reinnervation. In 1 patient (case 1), IVCM was performed before and after corneal neurotization; in the second patient (case 2), IVCM was performed after neurotization and corneal transplantation.

Results:

In case 1, who had hand motion visual acuity due to NK-associated corneal perforation that necessitated cyanoacrylate gluing, preoperative IVCM identified no subbasal nerves; however, subbasal nerves were identified 6 months after corneal neurotization, and there were no further episodes of persistent epithelial defects. In case 2, in whom NK with a total absence of corneal sensation was the result of treated basal skull meningioma, corneal sensation, visual acuity, and ocular surface health improved after corneal neurotization. Deep anterior lamellar keratoplasty was performed 2.5 years after corneal sensation was reestablished. IVCM demonstrated corneal reinnervation at the stromal and subbasal level in a pattern different from the normal cornea.

Conclusions:

Corneal neurotization restores corneal sensation by reinnervating the stromal and subbasal layers of the cornea. In doing so, corneal neurotization may halt the process of NK and prevent further visual loss.
α-Lipoic Acid as Adjunctive Treatment for Schizophrenia
Authors: Sanders Lia Lira Olivier , de Souza Menezes Carlos Eduardo , Chaves Filho Adriano José Maia , de Almeida Viana Glautemberg , Fechine Francisco Vagnaldo , Rodrigues de Queiroz Maria Goretti , Gonçalvez da Cruz Fonseca Said , Mendes Vasconcelos Silvânia Maria , Amaral de Moraes Maria Elisabete , Gama Clarissa S. , Seybolt Sheila , de Moura Campos Eugênio , Macêdo Danielle , Freitas de Lucena David
Published: October 2017

Purpose/Background

Accumulating evidence suggests an involvement of oxidative stress in the pathophysiology of schizophrenia. This offers a hypothesis-derived therapeutic approach to hinder oxidative damage and its clinical sequelae. α-Lipoic acid (ALA) is a powerful natural antioxidant indicated to treat diabetic neuropathy.

Methods/Procedures

In this pilot investigation, we administered ALA (100 mg/d) for 4 months, as an adjunct to antipsychotic medication, to 10 patients with schizophrenia.

Findings/Results

We found robust improvement in measures of psychopathology (63.9% reduction in Brief Psychiatric Rating Scale scores), neurocognitive parameters, extrapyramidal symptoms, and decreased lipid peroxidation.

Implications/Conclusions

If larger, double-blind, placebo-controlled studies confirm these preliminary findings, ALA could prove useful as adjunctive therapy for schizophrenia.
Geometrical frustration as a potential design principle for peptide-based assemblies
Authors: Jiang Tao , Magnotti Elizabeth L. , Conticello Vincent P.
Published: October 2017

Two-dimensional peptide and protein assemblies have been the focus of increased scientific research as they display significant potential for the creation of functional nanomaterials. Soluble subunits derived from a variety of protein motifs have been demonstrated to self-assemble into structurally defined nanosheets under environmentally benign conditions in which the components often retain their native structure and function. These types of two-dimensional assemblies may have an advantage for nanofabrication in that their extended planar shapes can be more straightforwardly incorporated into the current formats of nanoscale devices. However, significant challenges remain in the fabrication of these materials, particularly in devising methods to control the size, shape and internal structure of the resultant materials. Geometrical frustration may be envisioned as a possible mechanism to exert control over these structural parameters through rational design. While this objective has yet to be realized in practice, we discuss in this article the potential role of geometrical frustration as a principle to rationalize unusual self-assembly behaviour in several examples of two-dimensional peptide assemblies.
Discovery and design of self-assembling peptides
Authors: Zhang Shuguang
Published: October 2017

Peptides are ubiquitous in nature and useful in many fields, from agriculture as pesticides, in medicine as antibacterial and antifungal drugs founded in the innate immune systems, to medicinal chemistry as hormones. However, the concept of peptides as materials was not recognized until 1990 when a self-assembling peptide as a repeating segment in a yeast protein was serendipitously discovered. Peptide materials are so called because they have bona fide materials property and are made from simple amino acids with well-ordered nanostructures under physiological conditions. These structures include well-ordered nanofibres, nanotubes and nanovesicles. These peptide materials have been used for: (i) three-dimensional tissue cell cultures of primary cells and stem cells, (ii) three-dimensional tissue printing, (iii) sustained releases of small molecules, growth factors, monoclonal antibody and siRNA, (iv) accelerated wound healing in reparative and regenerative medicine as well as tissue engineering, (v) used to stabilize membrane proteins including difficult G-protein coupled receptors and photosystem I for designing nanobiodevices, (vi) a few self-assembling peptides have been used in human clinical trials for accelerated wound healings in surgical uses and (vii) in human clinical trials for siRNA delivery for treatment of cancers. It is likely that these self-assembling peptides will open doors for more and more diverse uses. The field of self-assembling peptides is growing in a number of directions in areas of materials, synthetic biology, and clinical medicine and beyond.
Lipid-protein interplay in dimerization of the juxtamembrane domains of epidermal growth factor receptor
Authors: Maeda Ryo , Sato Takeshi , Okamoto Kenji , Yanagawa Masataka , Sako Yasushi
Published: October 2017

Transmembrane (TM) helix and juxtamembrane (JM) domains (TM-JM) bridge the extracellular and intracellular domains of single-pass membrane proteins, including epidermal growth factor receptor (EGFR). TM-JM dimerization plays a crucial role in regulation of EGFR kinase activity at the cytoplasmic side. Although the interaction of JM with membrane lipids is thought to be important to turn on EGF signaling and phosphorylation of Thr654 on JM leads to desensitization, the underlying kinetic mechanisms remain unclear. Especially, how Thr654 phosphorylation regulates EGFR activity is largely unknown. Here, combining single-pair FRET imaging and nanodisc techniques, we showed that phosphatidylinositol 4,5-bis phosphate (PIP2) facilitated JM dimerization effectively. We also found that Thr654 phosphorylation dissociated JM dimers in the membranes containing acidic lipids, suggesting that Thr654 phosphorylation electrostatically prevented the interaction with basic residues in JM and acidic lipids. Based on the single-molecule experiment, we clarified the kinetic pathways of monomer (inactive state) - dimer (active state) transition of JM domains and alteration in the pathways depending on the membrane lipid species and Thr654 phosphorylation.
Diabetes mellitus is associated with increased prevalence of latent tuberculosis infection: Results from the National Health and Nutrition Examination Survey
Authors: Barron Marissa M. , Shaw Kate M. , Bullard Kai McKeever , Ali Mohammed K. , Magee Matthew J.
Published: October 2017

Aims

We aimed to determine the association between prediabetes and diabetes with latent TB using National Health and Nutrition Examination Survey data.

Methods

We performed a cross-sectional analysis of 2011-2012 National Health and Nutrition Examination Survey data. Participants ≥20 years were eligible. Diabetes was defined by glycated hemoglobin (HbA1c) as no diabetes (≤5.6% [38 mmol/mol]), prediabetes (5.7-6.4% [3946mmol/mol]), and diabetes (≥6.5% [48 mmol/mol]) combined with self-reported diabetes. Latent TB infection was defined by the QuantiFERON®-TB Gold In Tube (QFT-GIT) test. Adjusted odds ratios (aOR) of latent TB infection by diabetes status were calculated using logistic regression and accounted for the stratified probability sample.

Results

Diabetes and QFT-GIT measurements were available for 4,958 (89.2%) included participants. Prevalence of diabetes was 11.4% (95%CI 9.8-13.0%) and 22.1% (95%CI 20.523.8%) had prediabetes. Prevalence of latent TB infection was 5.9% (95%CI 4.9-7.0%). After adjusting for age, sex, smoking status, history of active TB, and foreign born status, the odds of latent TB infection were greater among adults with diabetes (aOR 1.90, 95%CI 1.15-3.14) compared to those without diabetes. The odds of latent TB in adults with prediabetes (aOR 1.15, 95%CI 0.90-1.47) was similar to those without diabetes.

Conclusions

Diabetes is associated with latent TB infection among adults in the United States, even after adjusting for confounding factors. Given diabetes increases the risk of active TB, patients with co-prevalent diabetes and latent TB may be targeted for latent TB treatment.
The response to selection in Glycoside Hydrolase Family 13 structures: A comparative quantitative genetics approach
Authors: Sergio Hleap Jose , Blouin Christian
Published: October 2017

The Glycoside Hydrolase Family 13 (GH13) is both evolutionary diverse and relevant to many industrial applications. Its members perform the hydrolysis of starch into smaller carbohydrates. Members of the family have been bioengineered to improve catalytic function under industrial environments. We introduce a framework to analyze the response to selection of GH13 protein structures given some phylogenetic and simulated dynamic information. We found that the TIM-barrel is not selectable since it is under purifying selection. We also show a method to rank important residues with higher inferred response to selection. These residues can be altered to effect change in properties. In this work, we define fitness as inferred thermodynamic stability. We show that under the developed framework, residues 112Y, 122K, 124D, 125W, and 126P are good candidates to increase the stability of the truncated protein 4E2O. Overall, this paper demonstrate the feasibility of a framework for the analysis of protein structures for any other fitness landscape.
Juicebox.js provides a cloud-based visualization system for Hi-C data
Authors: Robinson James , Turner Douglass , Durand Neva C. , Thorvaldsdottir Helga , Mesirov Jill P. , Aiden Erez Lieberman
Published: October 2017

Contact mapping experiments such as Hi-C explore how genomes fold in 3D. Here, we introduce Juicebox.js, a cloud-based web application for exploring the resulting datasets. Like the original Juicebox application, Juicebox.js allows users to zoom in and out of such datasets using an interface similar to Google Earth. Furthermore, Juicebox.js encodes the exact state of the browser in a shareable URL. Creating a public browser for a new Hi-C dataset does not require coding and can be accomplished in under a minute.
Monovalent ions modulate the flux through multiple folding pathways of an RNA pseudoknot
Authors: Roca Jorjethe , Hori Naoto , Velmurugu Yogambigai , Narayanan Ranjani , Narayanan Prasanth , Thirumalai D. , Ansari Anjum
Published: October 2017

The functions of RNA pseudoknots (PKs), which are minimal tertiary structural motifs and an integral part of several ribozymes and ribonucleoprotein complexes, are determined by their structure, stability and dynamics. Therefore, it is important to elucidate the general principles governing their thermodynamics/folding mechanisms. Here, we combine experiments and simulations to examine the folding/unfolding pathways of the VPK pseudoknot, a variant of the Mouse Mammary Tumor Virus (MMTV) PK involved in ribosomal frameshifting. Fluorescent nucleotide analogs (2-aminopurine and pyrrolocytidine) placed at different stem/loop positions in the PK, and laser temperature-jump approaches serve as local probes allowing us to monitor the order of assembly of VPK with two helices with different intrinsic stabilities. The experiments and molecular simulations show that at 50 mM KCl the dominant folding pathway populates only the more stable partially folded hairpin. As the salt concentration is increased a parallel folding pathway emerges, involving the less stable hairpin structure as an alternate intermediate. Notably, the flux between the pathways is modulated by the ionic strength. The findings support the principle that the order of PK structure formation is determined by the relative stabilities of the hairpins, which can be altered by sequence variations or salt concentrations. Our study not only unambiguously demonstrates that PK folds by parallel pathways, but also establishes that quantitative description of RNA self-assembly requires a synergistic combination of experiments and simulations.

SIGNIFICANCE

The assembly mechanism of RNA, vital to describing their functions, depends on both the sequence and the metal ion concentration. How the latter influences the folding trajectories remains an important unsolved problem. Here, we examine the folding pathways of an RNA pseudoknot (PK) with key functional roles in transcription and translation, using a combination of experiments and simulations. We demonstrate that the PK, consisting of two helices with differing stabilities, folds by parallel pathways. Surprisingly, the flux between them is modulated by monovalent salt concentration. Our work shows that the order of assembly of PKs is determined by the relative stability of the helices, implying that the folding landscape can be controlled by sequence and ion concentration.
Two spatially distinct Kinesin-14 Pkl1 and Klp2 generate collaborative inward forces against Kinesin-5 Cut7 inS. pombe
Authors: Yukawa Masashi , Yamada Yusuke , Yamauchi Tomoaki , Toda Takashi
Published: October 2017

Kinesin motors play central roles in bipolar spindle assembly. In many eukaryotes, spindle pole separation is driven by Kinesin-5 that generates outward force. This outward force is balanced by antagonistic inward force elicited by Kinesin-14 and/or Dynein. In fission yeast, two Kinesin-14s, Pkl1 and Klp2, play an opposing role against Kinesin-5/Cut7. However, how these two Kinesin-14s coordinate individual activities remains elusive. Here we show that while deletion of eitherpkl1orklp2rescues temperature sensitivecut7mutants, onlypkl1deletion can bypass the lethality caused bycut7deletion. Pkl1 is tethered to the spindle pole body, while Klp2 is localized along the spindle microtubule. Forced targeting of Klp2 to the spindle pole body, however, compensates for Pkl1 functions, indicating that cellular localizations, rather than individual motor specificities, differentiate between the two Kinesin-14s. Interestingly, human Kinesin-14/HSET can replace either Pkl1 or Klp2. Moreover, overproducing HSET induces monopolar spindles, reminiscent of the phenotype of Cut7 inactivation. Taken together, this study has uncovered the biological mechanism of how two different Kinesin-14s exert their antagonistic roles against Kinesin-5 in a spatially distinct manner.

SUMMARY STATEMENT

Proper force-balance generated by Kinesin-5 and Kinesin-14 is crucial for spindle bipolarity. Two fission yeast Kinesin-14s localize to different structures, thereby collaboratively producing inward forces against Kinesin-5-mediated outward force.

Abbreviations used

GBP

GFP-binding protein

MWP complex

Msd1-Wdr8-Pkl1 complex

SPB

spindle pole body

ts

temperature sensitive

γ-TuC

the γ-tubulin complex
Massively parallel single cell lineage tracing using CRISPR/Cas9 induced genetic scars
Authors: Spanjaard Bastiaan , Hu Bo , Mitic Nina , Junker Jan Philipp
Published: October 2017

A key goal of developmental biology is to understand how a single cell transforms into a full-grown organism consisting of many different cell types. Single-cell RNA-sequencing (scRNA-seq) has become a widely-used method due to its ability to identify all cell types in a tissue or organ in a systematic manner1–3. However, a major challenge is to organize the resulting taxonomy of cell types into lineage trees revealing the developmental origin of cells. Here, we present a strategy for simultaneous lineage tracing and transcriptome profiling in thousands of single cells. By combining scRNA-seq with computational analysis of lineage barcodes generated by genome editing of transgenic reporter genes, we reconstruct developmental lineage trees in zebrafish larvae and adult fish. In future analyses, LINNAEUS (LINeage tracing by Nuclease-Activated Editing of Ubiquitous Sequences) can be used as a systematic approach for identifying the lineage origin of novel cell types, or of known cell types under different conditions.
Signposts in the fog: objects facilitate scene representations in left scene-selective cortex
Authors: Brandman Talia , Peelen Marius V.
Published: October 2017

We internally represent the structure of our surroundings even when there is little layout information available in the visual image, such as when walking through fog or darkness. One way in which we disambiguate such scenes is through object cues; for example, seeing a boat supports the inference that the foggy scene is a lake. Recent studies have investigated the neural mechanisms by which object and scene processing interact to support object perception. The current study examines the reverse interaction, by which objects facilitate the neural representation of scene layout. Photographs of indoor (closed) and outdoor (open) real-world scenes were blurred such that they were difficult to categorize on their own, but easily disambiguated by the inclusion of an object. fMRI decoding was used to measure scene representations in scene-selective parahippocampal place area (PPA) and occipital place area (OPA). Classifiers were trained to distinguish response patterns to fully visible indoor and outdoor scenes, presented in an independent experiment. Testing these classifiers on blurred scenes revealed a strong improvement in classification in left PPA and OPA when objects were present, despite the reduced low-level visual feature overlap with the training set in this condition. These findings were specific to left PPA/OPA, with no evidence for object-driven facilitation in right PPA/OPA, object-selective areas, and early visual cortex. These findings demonstrate separate roles for left and right scene-selective cortex in scene representation, whereby left PPA/OPA represents inferred scene layout, influenced by contextual object cues, and right PPA/OPA represents a scene’s visual features.
Temporal metacognition as the decoding of self-generated brain dynamics
Authors: Kononowicz Tadeusz W. , Roger Clémence , van Wassenhove Virginie
Published: October 2017

Metacognition, the ability to know about one’s thought process, is self-referential. Here, we combined psychophysics and time-resolved neuroimaging to explore metacognitive inference on the accuracy of a self-generated behavior. Human participants generated a time interval and evaluated the signed magnitude of their temporal production. We show that both self-generation and self-evaluation relied on the power of beta oscillations (β; 15−40 Hz) with increases in early β power predictive of increases in duration. We characterized the dynamics of β power in a low dimensional space (β state-space trajectories) as a function of timing and found that the more distinct trajectories, the more accurate metacognitive inferences were. These results suggest that β states instantiates an internal variable determining the fate of the timing network’s trajectory, possibly as release from inhibition. Altogether, our study describes oscillatory mechanisms for timing, suggesting that temporal metacognition relies on inferential processes of self-generated dynamics.
Locus-Specific Enhancer Hubs And Architectural Loop Collisions Uncovered From Single Allele DNA Topologies
Authors: Allahyar Amin , Vermeulen Carlo , Bouwman Britta A.M. , Krijger Peter H.L. , Verstegen Marjon J.A.M. , Geeven Geert , Kranenburg Melissa van , Pieterse Mark , Straver Roy , Haarhuis Judith H.I. , Teunissen Hans , Renkens Ivo J. , Kloosterman Wigard P. , Rowland Benjamin D. , de Wit Elzo , de Ridder Jeroen , de Laat Wouter
Published: October 2017

Chromatin folding is increasingly recognized as a regulator of genomic processes such as gene activity. Chromosome conformation capture (3C) methods have been developed to unravel genome topology through the analysis of pair-wise chromatin contacts and have identified many genes and regulatory sequences that, in populations of cells, are engaged in multiple DNA interactions. However, pair-wise methods cannot discern whether contacts occur simultaneously or in competition on the individual chromosome. We present a novel 3C method, Multi-Contact 4C (MC-4C), that applies Nanopore sequencing to study multi-way DNA conformations of tens of thousands individual alleles for distinction between cooperative, random and competing interactions. MC-4C can uncover previously missed structures in sub-populations of cells. It reveals unanticipated cooperative clustering between regulatory chromatin loops, anchored by enhancers and gene promoters, and CTCF and cohesin-bound architectural loops. For example, we show that the constituents of the active b-globin super-enhancer cooperatively form an enhancer hub that can host two genes at a time. We also find cooperative interactions between further dispersed regulatory sequences of the active proto-cadherin locus. When applied to CTCF-bound domain boundaries, we find evidence that chromatin loops can collide, a process that is negatively regulated by the cohesin release factor WAPL. Loop collision is further pronounced in WAPL knockout cells, suggestive of a “cohesin traffic jam”. In summary, single molecule multi-contact analysis methods can reveal how the myriad of regulatory sequences spatially coordinate their actions on individual chromosomes. Insight into these single allele higher-order topological features will facilitate interpreting the consequences of natural and induced genetic variation and help uncovering the mechanisms shaping our genome.
optSelect: using agent-based modeling and binary PSO techniques for ensemble feature selection and stability assessment
Authors: Uppal Karan , Lee Eva K.
Published: October 2017

Motivation

Recent studies have shown that the ensemble feature selection approaches are essential for generating robust classifiers. Existing methods for aggregating feature lists from different methods require use of arbitrary thresholds for selecting the top ranked features and do not account for classification accuracy while selecting the optimal set. Here we present a two-stage ensemble feature selection framework for finding the optimal set of features without compromising on classification accuracy.

Methods and Results

We present herein optSelect, a multi agent-based stochastic optimization approach for nested ensemble feature selection. Stage one involves function perturbation, where ranked list of features are generated using different methods and stage two involves data perturbation, where feature selection is performed within randomly selected subsets of the training data and the optimal set of features is selected within each set using the optSelect. The agents are assigned to different behavior states and move according to a binary PSO algorithm. A multi-objective fitness function is used to evaluate the classification accuracy of the agents. We evaluate the system performance using the random probe method and using five publicly available microarray datasets. The performance of optSelect is compared with single feature selection techniques and existing aggregation methods. The results show that the optSelect algorithm improves the classification accuracy compared to both individual and existing rank aggregation methods. The algorithm is incorporated into an R package, optSelect.

Contact

kuppal2@emory.edu
Electrostatic Tuning of a Potassium Channel in Electric Fish
Authors: Swapna Immani , Ghezzi Alfredo , Markham Michael R. , Halling D. Brent , Lu Ying , Gallant Jason R. , Zakon Harold H.
Published: October 2017

Molecular and biophysical variation contributes to the evolution of adaptive phenotypes, particularly behavior, though it is often difficult to understandpreciselyhow. The adaptively significant electric organ discharge behavior of weakly electric fish is the direct result of biophysical membrane properties set by ion channels. Here we describe a voltage-gated potassium channel gene in African mormyrid electric fishes, that is under positive selection and highly expressed in the electric organ. The channel produced by this gene shortens electric organ action potentials by activating quickly and at hyperpolarized membrane potentials. Surprisingly, the source of these unique properties is a derived patch of negatively charged amino acids in an extracellular loop near the voltage sensor. Further, we demonstrate that this portion of the channel functions differently in vertebrates than the generally accepted model based on theshakerchannel, and suggest a role for this loop in the evolutionary tuning of voltage-dependent channels.