bluuebunny/crossref_metadata_2025 huggingface dataset:
Endosomal-lysosomal organellar assembly (ELYSA) structures coordinate lysosomal degradation systems through mammalian oocyte-to-embryo transition
Authors: Satouh Yuhkoh , Tatebe Takaki , Tanida Isei , Yamaguchi Junji , Uchiyama Yasuo , Sato Ken
Published: July 2024

Mouse oocytes undergo drastic changes in organellar composition and their activities during maturation from the germinal vesicle (GV) to meiosis II (MII) stage. After fertilization, the embryo degrades parts of the maternal components via lysosomal degradation systems, including autophagy and endocytosis, as zygotic gene expression begins during embryogenesis. Here, we demonstrate that endosomal-lysosomal organelles form large spherical assembly structures, termed ELYSAs, in mouse oocytes. ELYSAs are observed in GV oocytes, attaining sizes up to 7–8 μm in diameter in MII oocytes. ELYSAs comprise tubular-vesicular structures containing endosomes, lysosomes, autophagosome-like membranes in the outer layer, with cytosolic components contained within. The V1-subunit of vacuolar ATPase tends to localize to the periphery of ELYSAs in MII oocytes. After fertilization, the V1-subunit is recruited to immature endosomes and lysosomes as ELYSAs are gradually disassembled at the 2-cell stage, which leads to further acidification of endosomal-lysosomal organelles. These findings suggest that the ELYSAs maintain endosomal-lysosomal activity in a static state in oocytes for timely activation during early development.
Effect of Mulligan Calcaneal Taping on Dynamic Balance and Functional Performance in Subjects with Plantar Fasciitis: A Prospective Cohort Study
Authors: Jakhotiya Chetna , Shroff Riddhi Ashish , Ganjave Pranita
Published: July 2024

Introduction: Plantar fasciitis is the most common cause of heel and foot pain, leading individuals to use compensatory techniques to alleviate their pain, resulting in an antalgic gait. These compensations alter the feeling of joint position and muscle activation, making it challenging to maintain an upright posture within the base of support. According to Mulligan's concept, rigid tape allows painful or restricted movements with quick pain relief and increased range of motion while correcting positional faults and reducing tensile tension on the fascia, thereby decreasing inflammation and microscopic tears. Currently, there is a scarcity of data studying the effect of Mulligan’s calcaneal taping on dynamic balance. Aim: To evaluate the effect of Mulligan’s calcaneal taping on dynamic balance and functional performance in subjects with plantar fasciitis. Materials and Methods: The study was a prospective cohort study conducted at D.Y. Patil Hospital and Research Centre, Navi Mumbai, Maharashtra, India. It began in March 2023 and concluded in March 2024, spanning one year. Thirty-six subjects were randomly divided into group A (n=18) and group B (n=18). Subjects experiencing pain for more than six weeks, aged between 18-60 years, with a positive Windlass test, plantar medial heel pain, and abnormal foot posture index (between +6 to +9) were included in the study. The experimental group received Mulligan’s calcaneal taping along with conventional physiotherapy exercises, while the control group received only conventional physiotherapy exercises. Pre-post assessments were conducted using the star excursion balance test for dynamic balance assessment and the Foot Function Index (FFI) for functional performance. Results: Statistically significant differences were found among the medial (p-value=0.0212), posteromedial (p-value=0.0199), and posterior (p-value=0.0091) directions of the star excursion balance test. Both groups did not show statistically significant differences in the FFI score. However, with effect size, there was good clinical significance for the FFI score and all directions of the star excursion balance test except the posterolateral direction. Conclusion: Mulligan calcaneal taping has been shown to be more effective in improving dynamic balance in subjects with plantar fasciitis
STEM Exposure and STEM Career Aspirations to Senior High School Students in Davao Doctors College, Inc.
Authors: Provendido Lourence Anthony L. , Rosal Princess Ira P. , Patosa Casey Fiona B. , Panayas Sunshine C. , Velasquez Arman Jay C.
Published: July 2024

This study aimed to determine STEM exposure and STEM career aspirations to senior high school student in Davao Doctors College, Inc. It specifically looked into the level of STEM exposure in terms of personal, environmental, and behavioral. It also aimed to determine the level of STEM career aspiration of SHS student. Furthermore, this study aimed to find if there is a significant relationship between STEM exposure and STEM career aspirations. This study employed a quantitative research design specifically a descriptive-correlational method. This was conducted, in November 2023. The respondents of this study were 266 of grade 12 senior high school STEM students. The research instruments used were an adapted survey questionnaire. The results showed that the overall mean score of the STEM exposure to senior high school students was described as high (3.85) and STEM career aspirations was described as high (4.15). The relationship between the two variables was significant (R= .7596). This suggest that exposure to STEM influence students’ aspirations toward STEM careers.
Antifungal Activity of Jatropha curcas Seed Extracts Analysed by GC-MS against Two Cowpea (Vigna unguiculata L.) Pathogenic Fungi
Authors: Nadège Tchasep Wandji , Patrice Ngatsi Zemko , William Kuate Tueguem Nobert , Tize Tize , Thierry Atindo Songwe , Eric Ndongo Biyo’o , Laurence Ngata Ngadjui , Christian Gbaporo Gbaporo Fabrice , Bekolo Ndongo
Published: July 2024

Cowpea (Vigna unguiculata L. Walp.), native to Africa, is one of the most popular and widely grown seed legumes in arid and semi-arid areas. In these areas, fusarium wilt and white rots caused by Fusarium oxysporum Schl. f.sp. tracheiphilum and Sclerotinia sclerotiorum are the most devastating pathogens of cowpea crops, causing losses of 50-100 %, respectively. This study aims to evaluate the antifungal potential of biochemical compounds in Jatropha curcas L. seed extracts identified by GC-MS analysis against F. oxysporum and S. sclerotiorum. In vitro tests were carried out using aqueous, acetone and hexane extracts of J. curcas seeds at concentrations of 15, 30, 60 and 120 μL/mL and a synthetic fungicide (3.33 g/L). Mycelial growth and Minimal Inhibitory Concentrations (MIC50) were assessed. As a result, J. curcas seed extracts are rich in phytochemical molecules such as 9,12-octadecadienoic acid (Z,Z) ; n-Hexadecanoic acid ; Squalene ; D-Limonene ; 9,15-octadecadienoic acid, methy and 1,3-Dioxane, 5-ethyl-2,2-dimethyl, with antifungal activity. Total inhibition (100%) of mycelial growth of F. oxysporum and S. sclerotiorum was obtained in Petri dishes contaminated with the aqueous and acetone extracts at concentrations C3=60 µL/mL and C4=120 µL/mL, as well as with the synthetic fungicide. The MIC50 obtained with isolates of S. sclerotiorum and F. oxysporum were 9.2 and 9.96 µL/mL with the aqueous extract, respectively followed by the acetone extract (12.96 and 14.97 µL/mL). All Jatropha curcas lethal extracts tested were fungistatic, but the synthetic fungicide was fungicidal. Bioformulation based on J. curcas and characterization of pathogen are needed.
Innovations in Thermal Management Techniques for Enhanced Performance and Reliability in Engineering Applications
Authors: Zhoghuo Yuhan , Alex Kian Hua
Published: July 2024

Thermal management is a critical aspect of engineering applications, playing a pivotal role in enhancing performance and ensuring the reliability of various systems. This paper presents an overview of recent innovations and advancements in thermal management techniques aimed at addressing challenges associated with heat dissipation, thermal regulation, and temperature control in engineering applications. The importance of effective thermal management is highlighted in the context of emerging technologies such as electric vehicles, renewable energy systems, data centers, and electronic devices, where excessive heat generation can lead to performance degradation, component failure, and reduced operational lifespan. The abstract begins by emphasizing the significance of thermal management in engineering applications, emphasizing its role in improving performance and reliability. It discusses the challenges posed by heat generation and the need for innovative solutions to address thermal issues effectively.  It hints at the diverse range of techniques to be covered, including passive and active cooling methods, phase change materials, thermal interface materials, and advanced heat exchangers. Furthermore, it suggests that the paper will explore how these techniques contribute to enhanced performance and reliability in engineering applications. In summary, this paper offers insights into the latest developments in thermal management, providing valuable information for researchers, engineers, and industry professionals seeking to optimize thermal performance and ensure the reliability of their systems in diverse engineering applications.
Investigating the IMF cone angle control of Pc3‐4 pulsations observed on the ground
Authors: Bier Elianna A. , Owusu Nana , Engebretson Mark J. , Posch Jennifer L. , Lessard Marc R. , Pilipenko Viacheslav A.
Published: February 2014

Many studies have shown that Pc3‐4 pulsations (~0.014–0.1 Hz) observed in Earth's magnetosphere during daytime hours originate in the ion foreshock region of the solar wind, just upstream from Earth's bow shock. They occur when the interplanetary magnetic field (IMF) is primarily radial—when the IMF cone angle θxB ≤ 45°. However, our knowledge of ion foreshock conditions is often incomplete because of the very limited number of spacecraft providing upstream data. In this study we compared 13 months of wave observations at two widely separated ground stations (Hornsund, Svalbard and Halley, Antarctica) to IMF values in the OMNI database in order to test this relation. Values of θxB and the empirically predicted wave frequency (fcalc = 0.06 BIMF) were compared to daily Fourier spectrograms displaying pulsation power and frequency. Although there was often good temporal agreement between low θxB and increased Pc3‐4 wave power, numerous counterexamples were also evident. A statistical study of wave activity in quarter hour increments showed that Pc3‐4 pulsations were associated with low θxB values, 81% of the time at Hornsund and 83% at Halley. IMF cone angle data from all available upstream monitors were compared to wave observations for a more limited number of days; many of these showed inconsistent IMF orientations. This study indicates some of the limitations of the existing upstream monitors and provides a quantitative estimate (~80%) of the accuracy of the OMNI data set in characterizing conditions near the nose of Earth's bow shock under predominantly radial IMF conditions.
Measurements of the neutron spectrum on the Martian surface with MSL/RAD
Authors: Köhler J. , Zeitlin C. , Ehresmann B. , Wimmer‐Schweingruber R. F. , Hassler D. M. , Reitz G. , Brinza D. E. , Weigle G. , Appel J. , Böttcher S. , Böhm E. , Burmeister S. , Guo J. , Martin C. , Posner A. , Rafkin S. , Kortmann O.
Published: February 2014

The Radiation Assessment Detector (RAD), onboard the Mars Science Laboratory (MSL) rover Curiosity, measures the energetic charged and neutral particles and the radiation dose rate on the surface of Mars. An important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, with their deeper penetration depth and ensuing high biological effectiveness. This is very difficult to measure quantitatively, resulting in considerable uncertainties in the total radiation dose. In contrast to charged particles, neutral particles (neutrons and gamma rays) are generally only measured indirectly. Measured spectra are a complex convolution of the incident particle spectrum with the detector response function and must be unfolded. We apply an inversion method (based on a maximum likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. Here we show the first spectra on the surface of Mars and compare them to theoretical predictions. The measured neutron spectrum (ranging from 8 to 740 MeV) translates into a radiation dose rate of 14±4μGy/d and a dose equivalent rate of 61±15μSv/d. This corresponds to 7% of the measured total surface dose rate and 10% of the biologically relevant surface dose equivalent rate on Mars. Measuring the Martian neutron and gamma spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat.
Machine learning and linear regression models to predict catchment‐level base cation weathering rates across the southern Appalachian Mountain region, USA
Authors: Povak Nicholas A. , Hessburg Paul F. , McDonnell Todd C. , Reynolds Keith M. , Sullivan Timothy J. , Salter R. Brion , Cosby Bernard J.
Published: February 2014

Accurate estimates of soil mineral weathering are required for regional critical load (CL) modeling to identify ecosystems at risk of the deleterious effects from acidification. Within a correlative modeling framework, we used modeled catchment‐level base cation weathering (BCw) as the response variable to identify key environmental correlates and predict a continuous map of BCw within the southern Appalachian Mountain region. More than 50 initial candidate predictor variables were submitted to a variety of conventional and machine learning regression models. Predictors included aspects of the underlying geology, soils, geomorphology, climate, topographic context, and acidic deposition rates. Low BCw rates were predicted in catchments with low precipitation, siliceous lithology, low soil clay, nitrogen and organic matter contents, and relatively high levels of canopy cover in mixed deciduous and coniferous forest types. Machine learning approaches, particularly random forest modeling, significantly improved model prediction of catchment‐level BCw rates over traditional linear regression, with higher model accuracy and lower error rates. Our results confirmed findings from other studies, but also identified several influential climatic predictor variables, interactions, and nonlinearities among the predictors. Results reported here will be used to support regional sulfur critical loads modeling to identify areas impacted by industrially derived atmospheric S inputs. These methods are readily adapted to other regions where accurate CL estimates are required over broad spatial extents to inform policy and management decisions.
Increasing Diversity in Geoscience Through Research Internships
Authors: Charlevoix Donna J. , Morris Aisha R.
Published: February 2014

Over the past 9 years, UNAVCO—a university‐governed consortium fostering geoscience research and education focused on geodesy—supported 44 interns through the Research Experiences in Solid Earth Science for Students (RESESS) program. The primary goal of the program is to increase the number of historically underrepresented students entering the geosciences.
Concerns About Extreme Weather Focus on the Need for Better Resilience
Authors: Showstack Randy
Published: February 2014

Weather disasters with damages exceeding $1 billion each have hit the United States 151 times since 1980, and federal disaster declarations have increased from 65 in 2004 to 98 in 2012, according to the U.S. General Accounting Office (GAO). Concern about the number of disasters—including storms, droughts, floods, and wildfires—and their cost to the economy, infrastructure, and human lives was the focus of a 12 February U.S. Senate hearing on extreme weather events and the cost of not being prepared for them. Senators and witnesses spoke about the need for resilience, preparedness, and paying up front for measures that could save money and headaches when disasters occur.
Chain reaction led to breakup of Larsen B Ice Shelf
Authors: Balcerak Ernie
Published: February 2014

In 2002, Antarctica's Larsen B Ice Shelf disintegrated over the course of just a few months. The shelf, which covered more than 3000 square kilometers of ice, had been stable for thousands of years before it broke up, and the processes involved in the sudden breakup were not well understood.
MHD analysis of the velocity oscillations in the outer heliosphere
Authors: Fujiki Ken'ichi , Washimi Haruichi , Hayashi Keiji , Zank Gary P. , Tokumaru Munetoshi , Tanaka Takashi , Florinski Vladimir , Kubo Yuki
Published: February 2014

We carried out a MHD simulation of deep interplanetary space from 2001 to 2009 with a realistic inner boundary condition obtained from a time‐dependent 3‐D ideal MHD model incorporating interplanetary scintillation and synoptic solar magnetic field data. As a result, we found that wavy solar wind structure with amplitudes of 10–50 km/s and a monochromatic wavelength of ~2 AU filled deep interplanetary space beyond ~50 AU from the Sun, which corresponds to a velocity oscillation detected by Voyager 2. The phase of the velocity oscillation is anticorrelated with density fluctuations in our simulation, which suggests that the velocity oscillation should propagate inward toward the Sun in the frame moving with the solar wind but is advected outward by the solar wind in the rest frame of the Sun.
Adsorption‐concentration polarization model for ultrafiltration in mixed matrix membrane
Authors: Mondal Sourav , Mukherjee Raka , Chatterjee Somak , De Sirshendu
Published: February 2014

Adsorption has been found to be significant in ultrafiltration by mixed matrix membrane. Removal of very low molecular weight solutes compared to the molecular weight cut off of the membrane is facilitated by adsorption. The modeling of the adsorption coupled with concentration polarization is presented based on the mathematical approach developed by Gekas et al. (Gekas et al. Chem Eng Sci. 1993;48:2753–2765), from the first principles. However, extensive modifications were included in theoretical development including those suggested by Ruiz‐Bevia et al. (Ruiz‐Bevia et al. Chem Eng Sci. 1997;52:2343–2352). The developed model captured the rejection dynamics with the help of retention factor. The model equations were solved under the framework of boundary layer analysis, using the integral approach. Effects of the adsorption isotherm and the different parameters affecting the system performance were also investigated. Further, experimental validation of the model results with two different mixed matrix ultrafiltration studies was also elucidated. © 2014 American Institute of Chemical Engineers AIChE J, 60: 2354–2364, 2014
Inventory pinch based, multiscale models for integrated planning and scheduling‐part I: Gasoline blend planning
Authors: Castillo Pedro A. Castillo , Mahalec Vladimir
Published: February 2014

A two‐level algorithm to compute blend plans that have much smaller number of different recipes, much shorter execution times, and the same cost as the corresponding multiperiod mixed‐integer nonlinear programming is introduced. These plans become a starting point for computation of approximate schedules, which minimize total number of switches in blenders and swing tanks. The algorithm uses inventory pinch points to delineate time periods where optimal blend recipes are likely constant. At the first level, nonlinear blend models are optimized via nonlinear programming. The second level uses fixed recipes (from the first level) in a multiperiod mixed‐integer linear programming to determine optimal production plan followed by an approximate schedule. Approximate schedules computed by the multiperiod inventory pinch algorithm in most of the case studies are slightly better than those computed by global optimizers (ANTIGONE, GloMIQO) while requiring significantly shorter execution times. Such schedules provide constraints for subsequent detailed scheduling in Part II. © 2014 American Institute of Chemical Engineers AIChE J, 60: 2158–2178, 2014
Seasonal variation of peripheral blood leukocyte telomere length in Costa Rica: A population‐based observational study
Authors: Rehkopf David H. , Dow William H. , Rosero‐Bixby Luis , Lin Jue , Epel Elissa S. , Blackburn Elizabeth H.
Published: February 2014

Objectives

Peripheral blood leukocyte telomere length (LTL) is increasingly being used as a biomarker of aging, but its natural variation in human populations is not well understood. Several other biomarkers show seasonal variation, as do several determinants of LTL. We examined whether there was monthly variation in LTL in Costa Rica, a country with strong seasonal differences in precipitation and infection.

Methods

We examined a longitudinal population‐based cohort of 581 Costa Rican adults age 60 and above, from which blood samples were drawn between October 2006 and July 2008. LTL was assayed from these samples using the quantitative PCR method. Multivariate regression models were used to examine correlations between month of blood draw and LTL.

Results

Telomere length from peripheral blood leukocytes varied by as much as 200 base pairs depending on month of blood draw, and this difference is not likely to be due to random variation. A moderate proportion of this association is statistically accounted for by month and region specific average rainfall. We found shorter telomere length associated with greater rainfall.

Conclusions

There are two possible explanations of our findings. First, there could be relatively rapid month‐to‐month changes in LTL. This conclusion would have implications for understanding the natural population dynamics of telomere length. Second, there could be seasonal differences in constituent cell populations. This conclusion would suggest that future studies of LTL use methods to account for the potential impact of constituent cell type. Am. J. Hum. Biol. 26:367–375, 2014. © 2014 Wiley Periodicals, Inc.
A novel prodrug‐based strategy to increase effects of bumetanide in epilepsy
Authors: Töllner Kathrin , Brandt Claudia , Töpfer Manuel , Brunhofer Gerda , Erker Thomas , Gabriel Mario , Feit Peter W. , Lindfors Jenna , Kaila Kai , Löscher Wolfgang
Published: February 2014

Objective

There is considerable interest in using bumetanide, a chloride importer Na‐K‐Cl cotransporter antagonist, for treatment of neurological diseases, such as epilepsy or ischemic and traumatic brain injury, that may involve deranged cellular chloride homeostasis. However, bumetanide is heavily bound to plasma proteins (∼98%) and highly ionized at physiological pH, so that it only poorly penetrates into the brain, and chronic treatment with bumetanide is compromised by its potent diuretic effect.

Methods

To overcome these problems, we designed lipophilic and uncharged prodrugs of bumetanide that should penetrate the blood–brain barrier more easily than the parent drug and are converted into bumetanide in the brain. The feasibility of this strategy was evaluated in mice and rats.

Results

Analysis of bumetanide levels in plasma and brain showed that administration of 2 ester prodrugs of bumetanide, the pivaloyloxymethyl (BUM1) and N,N‐dimethylaminoethylester (BUM5), resulted in significantly higher brain levels of bumetanide than administration of the parent drug. BUM5, but not BUM1, was less diuretic than bumetanide, so that BUM5 was further evaluated in chronic models of epilepsy in mice and rats. In the pilocarpine model in mice, BUM5, but not bumetanide, counteracted the alteration in seizure threshold during the latent period. In the kindling model in rats, BUM5 was more efficacious than bumetanide in potentiating the anticonvulsant effect of phenobarbital.

Interpretation

Our data demonstrate that the goal of designing bumetanide prodrugs that specifically target the brain is feasible and that such drugs may resolve the problems associated with using bumetanide for treatment of neurological disorders. ANN NEUROL 2014;75:550–562
Encapsulation with the Protrusion of Cruciform 9,10‐Bis(arylethynyl)anthracene Derivatives in a Self‐Assembled Boronic Ester Cavitand Capsule: Photochemical and Photophysical Properties
Authors: Hirumi Yohei , Tamaki Kento , Namikawa Tomotaka , Kamada Kenji , Mitsui Masaaki , Suzuki Kengo , Kobayashi Kenji
Published: February 2014

The self‐assembled boronic ester cavitand capsule 3 quantitatively and tightly encapsulates 2,6‐diacetoxy‐9,10‐bis(arylethynyl)anthracene derivatives 4 a–4 c as highly fluorescent cruciform guests to form complexes 4 a@3, 4 b@3, and 4 c@(3)2. The structural features of capsule 3, which possesses two polar bowl‐shaped aromatic cavity ends and four large equatorial windows connected by dynamic boronic ester bonds, made it possible to encapsulate cruciform 4 with protection of the reactive anthracene core inside the capsule and with two protruding arylethynyl groups, the π‐conjugated arms of compound 4, through two of the equatorial windows of the capsule. Thus, complexes 4 a@3, 4 b@3, and 4 c@(3)2 show greater resistance to photochemical reactions in solution and fluorescence quenching in the powder state compared to free guests 4. In addition to the improved photostability, restriction of the free rotation of the arylethynyl groups of guests 4 upon encapsulation results in sharpening of the UV/Vis absorption peaks with a red‐shift and a significant increase in some of the two‐photon‐absorption peaks of complexes 4 a@3, 4 b@3, and 4 c@(3)2 compared with free guests 4.
Design of a Maximally Permissive Liveness‐enforcing Supervisor with Reduced Complexity for Automated Manufacturing Systems
Authors: Wang ShouGuang , Zhou MengChu , Wu WenHui
Published: February 2014

This paper deals with the problems of computational and structural complexity in designing maximally permissive liveness‐enforcing supervisors for a class of Petri nets called Systems of Simple Sequential Processes with Resources (S3PR) without ξ‐resources. The supervisor consists of two parts: the first part proposes an algorithm to extract a desired emptied strict minimal siphon (SMS) from a given emptied siphon based on loop resource subsets. This is faster than the existing ones. The second part proposes a siphon‐based deadlock prevention policy, which can obtain a maximally permissive liveness‐enforcing supervisor with reduced structural complexity and no weighted monitors, owing to the contribution of the first part, which can compute a desired SMS such that one with the smallest number of resource places is selected first for control. Several flexible manufacturing systems are used to show the proposed method and its superior performance over the previous ones.
Investigation of Maternal Genotype Effects in Autism by Genome‐Wide Association
Authors: Yuan Han , Dougherty Joseph D.
Published: February 2014

Like most psychiatric disorders, autism spectrum disorders have both a genetic and an environmental component. While previous studies have clearly demonstrated the contribution of in utero (prenatal) environment on autism risk, most of them focused on transient environmental factors. Based on a recent sibling study, we hypothesized that environmental factors could also come from the maternal genome, which would result in persistent effects across siblings.

In this study, the possibility of maternal genotype effects was examined by looking for common variants (single‐nucleotide polymorphisms or SNPs) in the maternal genome associated with increased risk of autism in children. A case/control genome‐wide association study was performed using mothers of probands as cases, and either fathers of probands or normal females as controls. Autism Genetic Resource Exchange and Illumina Genotype Control Database were used as our discovery cohort (n = 1616). The same analysis was then replicated on Simon Simplex Collection and Study of Addiction: Genetics and Environment datasets (n = 2732).

We did not identify any SNP that reached genome‐wide significance (P < 10−8), and thus a common variant of large effect is unlikely. However, there was evidence for the possibility of a large number of alleles of effective size marginally below our power to detect. Autism Res 2014, 7: 245–253. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
Diversity through duplication: Whole‐genome sequencing reveals novel gene retrocopies in the human population
Authors: Richardson Sandra R. , Salvador‐Palomeque Carmen , Faulkner Geoffrey J.
Published: February 2014

Gene retrocopies are generated by reverse transcription and genomic integration of mRNA. As such, retrocopies present an important exception to the central dogma of molecular biology, and have substantially impacted the functional landscape of the metazoan genome. While an estimated 8,000–17,000 retrocopies exist in the human genome reference sequence, the extent of variation between individuals in terms of retrocopy content has remained largely unexplored. Three recent studies by Abyzov et al., Ewing et al. and Schrider et al. have exploited 1,000 Genomes Project Consortium data, as well as other sources of whole‐genome sequencing data, to uncover novel gene retrocopies. Here, we compare the methods and results of these three studies, highlight the impact of retrocopies in human diversity and genome evolution, and speculate on the potential for somatic gene retrocopies to impact cancer etiology and genetic diversity among individual neurons in the mammalian brain.
What subject matter questions motivate the use of machine learning approaches compared to statistical models for probability prediction?
Authors: Binder Harald
Published: February 2014

This is a discussion of the following papers: “Probability estimation with machine learning methods for dichotomous and multicategory outcome: Theory” by Jochen Kruppa, Yufeng Liu, Gérard Biau, Michael Kohler, Inke R. König, James D. Malley, and Andreas Ziegler; and “Probability estimation with machine learning methods for dichotomous and multicategory outcome: Applications” by Jochen Kruppa, Yufeng Liu, Hans‐Christian Diener, Theresa Holste, Christian Weimar, Inke R. König, and Andreas Ziegler.
Risk prediction with machine learning and regression methods
Authors: Steyerberg Ewout W. , van der Ploeg Tjeerd , Van Calster Ben
Published: February 2014

This is a discussion of issues in risk prediction based on the following papers: "Probability estimation with machine learning methods for dichotomous and multicategory outcome: Theory" by Jochen Kruppa, Yufeng Liu, Gérard Biau, Michael Kohler, Inke R. König, James D. Malley, and Andreas Ziegler; and "Probability estimation with machine learning methods for dichotomous and multicategory outcome: Applications" by Jochen Kruppa, Yufeng Liu, Hans‐Christian Diener, Theresa Holste, Christian Weimar, Inke R. König, and Andreas Ziegler.
Antibody approaches to prepare clinically transplantable cells from human embryonic stem cells: Identification of human embryonic stem cell surface markers by monoclonal antibodies
Authors: Choi Hong Seo , Kim Won‐Tae , Ryu Chun Jeih
Published: February 2014

Human embryonic stem cells (hESCs) are unique cell populations, possessing both unlimited self‐renewal capacity and pluripotency, i.e. the potential to give rise to all kinds of specialized cells in the human body. Marker molecules expressed on the surface of hESCs are important for the identification, characterization, and clinical application of hESCs. Compared with conventional genomics‐ or proteomics‐based approaches, generating monoclonal antibody (mAb) libraries against hESCs using alternative methodologies expands the repertoire of mAbs raised against non‐protein markers, for example, glycolipid antigens. Additional information about the conformation and post‐translational modification of surface molecules can also be obtained. In this article, we review how mAb libraries against hESC surface markers have been developed using whole‐cell and decoy immunization strategies.
Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production
Authors: George Kevin W. , Chen Amy , Jain Aakriti , Batth Tanveer S. , Baidoo Edward E.K. , Wang George , Adams Paul D. , Petzold Christopher J. , Keasling Jay D. , Lee Taek Soon
Published: February 2014

The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven‐gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high‐throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways. Biotechnol. Bioeng. 2014;111: 1648–1658. © 2014 Wiley Periodicals, Inc.
Agrobacterium tumefaciens mediated transient expression of plant cell wall‐degrading enzymes in detached sunflower leaves
Authors: Jung Sang‐Kyu , Lindenmuth Benjamin E. , McDonald Karen A. , Hwang Min Sook , Bui Mai Q. Nguyen , Falk Bryce W. , Uratsu Sandra L. , Phu My L. , Dandekar Abhaya M.
Published: February 2014

For biofuel applications, synthetic endoglucanase E1 and xylanase (Xyn10A) derived from Acidothermus cellulolyticus were transiently expressed in detached whole sunflower (Helianthus annuus L.) leaves using vacuum infiltration. Three different expression systems were tested, including the constitutive CaMV 35S‐driven, CMVar (Cucumber mosaic virus advanced replicating), and TRBO (Tobacco mosaic virus RNA‐Based Overexpression Vector) systems. For 6‐day leaf incubations, codon‐optimized E1 and xylanase driven by the CaMV 35S promoter were successfully expressed in sunflower leaves. The two viral expression vectors, CMVar and TRBO, were not successful although we found high expression in Nicotiana benthamiana leaves previously for other recombinant proteins. To further enhance transient expression, we demonstrated two novel methods: using the plant hormone methyl jasmonic acid in the agroinfiltration buffer and two‐phase optimization of the leaf incubation temperature. When methyl jasmonic acid was added to Agrobacterium tumefaciens cell suspensions and infiltrated into plant leaves, the functional enzyme production increased 4.6‐fold. Production also increased up to 4.2‐fold when the leaf incubation temperature was elevated above the typical temperature, 20°C, to 30°C in the late incubation phase, presumably due to enhanced rate of protein synthesis in plant cells. Finally, we demonstrated co‐expression of E1 and xylanase in detached sunflower leaves. To our knowledge, this is the first report of (co)expression of heterologous plant cell wall‐degrading enzymes in sunflower. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:905–915, 2014
Methane Activation by Diatomic Molybdenum Carbide Cations
Authors: Li Zi‐Yu , Yuan Zhen , Zhao Yan‐Xia , He Sheng‐Gui
Published: February 2014

Metal carbide species have been proposed as a new type of chemical entity to activate methane in both gas‐phase and condensed‐phase studies. Herein, methane activation by the diatomic cation MoC+ is presented. MoC+ ions have been prepared and mass‐selected by a quadrupole mass filter and then allowed to interact with methane in a hexapole reaction cell. The reactant and product ions have been detected by a reflectron time‐of‐flight mass spectrometer. Bare metal Mo+ and MoC2H2+ ions have been observed as products, suggesting the occurrence of ethylene elimination and dehydrogenation reactions. The branching ratio of the C2H4 elimination channel is much larger than that of the dehydrogenation channel. Density functional theory calculations have been performed to explore in detail the mechanism of the reaction of MoC+ with CH4. The computed results indicate that the ethylene elimination process involves the occurrence of spin conversions in the CC coupling (doublet→quartet) and hydrogen atom transfer (quartet→sextet) steps. The carbon atom in MoC+ plays a key role in methane activation because it becomes sp3 hybridized in the initial stages of the ethylene elimination reaction, which leads to much lower energy barriers and more stable intermediates. This study provides insights into the CH bond activation and CC coupling involved in methane transformation over molybdenum carbide‐based catalysts.
Triggered Liposomal Release through a Synthetic Phosphatidylcholine Analogue Bearing a Photocleavable Moiety Embedded within the sn‐2 Acyl Chain
Authors: Bayer Andrew M. , Alam Shahrina , Mattern‐Schain Samuel I. , Best Michael D.
Published: February 2014

Liposomes represent promising carriers for drug delivery applications. To maximize this potential, there has been significant interest in developing liposomal systems encapsulating molecular cargo that are highly stable until their contents are released remotely in a controlled manner. Herein, we describe the design, synthesis, and analysis of a photocleavable analogue of the ubiquitous lipid phosphoatidylcholine (PC) for the development of highly stable and controllable photodisruptable membranes. Our strategy was to develop a lipid that closely mimics the structure of PC to optimize favorable properties including biocompatibility and stability of subsequent liposomes when mixed with lipids possessing a broad range of physicochemical properties. Thus, NB‐PC was designed, which contains a photocleavable 2‐nitrobenzyl group embedded within the acyl chain at the sn‐2 position. Following the synthesis of NB‐PC, liposome disruption efficacy was evaluated through photolysis studies involving the detection of nile red release. Studies performed using a range of liposomes with different percentages of NB‐PC, PC, phosphatidylethanolamine (PE), cholesterol, and polyethylene glycol‐PE (PEG‐PE) demonstrated minimal background release in controls, release efficacies that correlate directly with the amount of NB‐PC incorporation, and that release is only minimally impacted by the inclusion of the lipids PE and cholesterol that possess disparate properties. These results demonstrate that the NB‐PC system is a highly stable, flexible, and tunable system for photoinitiated release from liposomal systems.
Ru–η6‐Arene Cations [{(Ph2PC6H4)2B(η6‐Ph)}RuX]+ (X=Cl, H) as Lewis Acids
Authors: Boone Michael P. , Stephan Douglas W.
Published: February 2014

The reactivity of [{(Ph2PC6H4)2B(η6‐Ph)}RuCl][B(C6F5)4] (1) as a Lewis acid was investigated. Treatment of 1 with mono and multidentate phosphorus Lewis bases afforded the Lewis acid–base adducts with the ortho‐carbon atom of the coordinated arene ring. Similar reactivity was observed upon treatment with N‐heterocyclic carbenes; however, adduct formation occurred at both ortho‐ and para‐carbon atoms of the bound arene with the para‐position being favoured by increased steric demands. Interestingly treatment with isocyanides resulted in adduct formation with the B‐centre of the ligand framework. The hydride‐cation [{(Ph2PC6H4)2B(η6‐Ph)}RuH] [B(C6F5)4] was prepared via reaction of 1 with silane. This species in the presence of a bulky phosphine behaves as a frustrated Lewis pair (FLP) to activate H2 between the phosphorus centre and the ortho‐carbon atom of the η6‐arene ring.
A Single‐Molecule‐Level Mechanistic Study of Pd‐Catalyzed and Cu‐Catalyzed Homocoupling of Aryl Bromide on an Au(111) Surface
Authors: Adisoejoso Jinne , Lin Tao , Shang Xue Song , Shi Ke Ji , Gupta Aditi , Liu Pei Nian , Lin Nian
Published: February 2014

On‐surface Pd‐ and Cu‐catalyzed CC coupling reactions between phenyl bromide functionalized porphyrin derivatives on an Au(111) surface have been investigated under ultra‐high vacuum conditions by using scanning tunneling microscopy and kinetic Monte Carlo simulations. We monitored the isothermal reaction kinetics by allowing the reaction to proceed at different temperatures. We discovered that the reactions catalyzed by Pd or Cu can be described as a two‐phase process that involves an initial activation followed by CC bond formation. However, the distinctive reaction kinetics and the CC bond‐formation yield associated with the two catalysts account for the different reaction mechanisms: the initial activation phase is the rate‐limiting step for the Cu‐catalyzed reaction at all temperatures tested, whereas the later phase of CC formation is the rate‐limiting step for the Pd‐catalyzed reaction at high temperature. Analysis of rate constants of the Pd‐catalyzed reactions allowed us to determine its activation energy as (0.41±0.03) eV.
Efficient Asymmetric Hydrogenation of α‐Acetamidocinnamates through a Simple, Readily Available Monodentate Chiral H‐Phosphinate
Authors: Wang Xiang‐Bo , Goto Midori , Han Li‐Biao
Published: February 2014

An air‐stable, simple (RP)‐mentylbenzylphosphinate, readily available in large quantities, can efficiently induce the rhodium‐catalyzed asymmetric hydrogenation of α‐acetamidocinnamates with high enantioselectivity (up to 99.6 % ee). Intramolecular hydrogen bonding plays an important role in this asymmetric induction.
Facile Mechanochemical Synthesis of Nano SnO2/Graphene Composite from Coarse Metallic Sn and Graphite Oxide: An Outstanding Anode Material for Lithium‐Ion Batteries
Authors: Ye Fei , Zhao Bote , Ran Ran , Shao Zongping
Published: February 2014

A facile method for the large‐scale synthesis of SnO2 nanocrystal/graphene composites by using coarse metallic Sn particles and cheap graphite oxide (GO) as raw materials is demonstrated. This method uses simple ball milling to realize a mechanochemical reaction between Sn particles and GO. After the reaction, the initial coarse Sn particles with sizes of 3–30 μm are converted to SnO2 nanocrystals (approximately 4 nm) while GO is reduced to graphene. Composite with different grinding times (1 h 20 min, 2 h 20 min or 8 h 20 min, abbreviated to 1, 2 or 8 h below) and raw material ratios (Sn:GO, 1:2, 1:1, 2:1, w/w) are investigated by X‐ray diffraction, X‐ray photoelectron spectroscopy, field‐emission scanning electron microscopy and transmission electron microscopy. The as‐prepared SnO2/graphene composite with a grinding time of 8 h and raw material ratio of 1:1 forms micrometer‐sized architected chips composed of composite sheets, and demonstrates a high tap density of 1.53 g cm−3. By using such composites as anode material for LIBs, a high specific capacity of 891 mA h g−1 is achieved even after 50 cycles at 100 mA g−1.
Computer simulation of flagellar movement X: Doublet pair splitting and bend propagation modeled using stochastic dynein kinetics
Authors: Brokaw Charles J.
Published: February 2014

Experimental observations on cyclic splitting and bending by a flagellar doublet pair are modeled using forces obtained from a model for dynein mechanochemistry, based on ideas introduced by Andrew Huxley and Terrill Hill and extended previously for modeling flagellar movements. The new feature is elastic attachment of dynein to the A doublet, which allows movement perpendicular to the A doublet and provides adhesive force that can strain attached dyneins. This additional strain influences the kinetics of dynein attachment and detachment. Computations using this dynein model demonstrate that very simple and realistic ideas about dynein mechanochemistry are sufficient for explaining the separation and reattachment seen experimentally with flagellar doublet pairs. Additional simulations were performed after adding a “super‐adhesion” elasticity. This elastic component is intended to mimic interdoublet connections, normally present in an intact axoneme, that would prevent visible splitting but allow sufficient separation to cause dynein detachment and cessation of shear force generation. This is the situation envisioned by Lindemann's “geometric clutch” hypothesis for control of dynein function in flagella and cilia. The simulations show abrupt disengagement of the “clutch” at one end of a bend, and abrupt reengagement of the “clutch” at the other end of a bend, ensuring that active sliding is only operating where it will cause bend propagation from base to tip. © 2014 The Authors. Cytoskeleton, Published by Wiley Periodicals, Inc.
From NMR spectra to structure
Authors: Facelli Julio C. , Ferraro Marta B.
Published: February 2014

This article discusses the existing methods to correlate NMR parameters describing the high resolution NMR spectra of liquids and solid systems with their structural parameters. Those methods are divided into direct and indirect ones. This article includes two types of direct methods: those based on the Nuclear Overhauser Effect (NOE) contributions to the NMR relaxation and those based on direct measurements of the dipolar couplings using several experimental approaches. Indirect methods are based on the intrinsic dependence of J couplings and shieldings on the atomic coordinates of the atoms in a molecule and its surroundings, requiring complex quantum mechanical calculations to relate NMR spectral properties to molecular and crystal structure. This article discusses how changes in chemical bonding, conformation, and stereo configurations that cause measurable changes in NMR parameters closely related to molecular and crystal structure. The final section provides information about the software and hardware required to perform calculations needed to solve structural problems using high resolution NMR. This article intends to provide molecular structural researchers new to the field of NMR, with an overall panorama of the potential of using high resolution NMR for structure elucidation, when other more traditional techniques are not feasible. To this end and to emphasize the didactic value of this work, after each section a brief conclusion has been added to recap the critical concepts. © 2014 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 261–289, 2013.
PBlaman: performance blame analysis based on Palladio contracts
Authors: Brüseke Frank , Wachsmuth Henning , Engels Gregor , Becker Steffen
Published: February 2014

In performance‐driven software engineering, the performance of a system is evaluated through models before the system is assembled. After assembly, the performance is then validated using performance tests. When a component‐based system fails certain performance requirements during the tests, it is important to find out whether individual components yield performance errors or whether the composition of components is faulty. This task is called performance blame analysis. Existing performance blame analysis approaches and also alternative error analysis approaches are restricted, because they either do not employ expected values, use expected values from regression testing, or use static developer‐set limits. In contrast, this paper describes the new performance blame analysis approach PBlaman that builds upon our previous work and that employs the context‐portable performance contracts of Palladio. PBlaman decides what components to blame by comparing the observed response time data series of each single component operation in a failed test case to the operation's expected response time data series derived from the contracts. System architects are then assisted by a visual presentation of the obtained analysis results. We exemplify the benefits of PBlaman in two case studies, each of which representing applications that follow a particular architectural style. Copyright © 2014 John Wiley & Sons, Ltd.