bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory of Time – 2024 R (Universal Theory for Everything)
Authors: K Ramkumar
Published: October 2024

“Theory of Time” is a research and analysis report on ‘All kind of Transformation processes’ to find out the reason for changes, this is a Universal Theory & applicable for all natural phenomena. I had found some systematic/ logical/ relational imbalance among the principles of AC Transformer, Ohm’s law, series parallel circuits and law of conservation of energy. I did systematic analysis and research on above said combination principles and identified / formulated/ organized a common transformation mechanism for all and is called ‘Universal Transformation System’(UTS). Here, relative components of all kind of transformation systems are determined, organized systematically for better understanding on relations and also all physical phenomena mechanisms are interpreted through the lens of UTS & found the reformed results are meeting with the general/ natural principles of all kind of transformation systems. I did deeper and wider analysis on electro-magnetic circuits to understand the structure/ mechanism of the transformation system. Law of conservation of energy, AC Transformer’s principles, Newton’s laws and Ohm’s law are base for this theory. By doing relational analysis I could derive Equivalent mechanical transformation principles from Electricity Transformation principles and Mechanical Resistance () to Transformation (RMech.) equation has been successfully formulated. Finally Obtained / reformed results are compared with our practical science and found that the derived principles are meeting with the natural principles of system and its transformation processes. Further, explaining about “how the time is running?”; “what are all the relative components of the time?”; Whether is it possible to stop the time running process? etc. This ©2024 is going to be the final/ completed report on ‘Theory of Time’… in the name of ‘Theory of Nature’. I have finished my research and analysis on all kind of transformation systems. This is updated one, here, I have added some new analysis on secret behind the Black Hole, exact mechanism of Gyroscopic Effects, Donut formation of matter, about human beings, ‘Relation between Centripetal and Centrifugal controls’, importance of Newton’s Absolute time, galactic control on solar system, gravity generator, fusion generator, mechanism of Lagrange Points, there are two differences only in all, review on General Relativity & Special Relativity, constancy of light speed under UTS, optimized free body diagrams, Thermodynamics, ‘𝒎𝒗𝒓’ under UTS, atomic formation structures under gravity & electromagnetism, soul, Law & Justice, tug of war, all mechanisms, you &me
Analysis of the Impact of Superplasticizer on the Compressive Strength of Periwinkle Shell Concrete
Authors: A. O Adeleke , O Alake . , O.O Ekundayo , B.S Ojo , O.O Farayibi .
Published: October 2024

This research project investigates the compressive strength characteristics of superplasticized concrete incorporating periwinkle shell (PS) as partial replacements for granite coarse aggregate. The study aims to assess the influence of superplasticizer content and curing age on the compressive strength development of the novel concrete mixtures. Comparative analysis with plain concrete (control specimen) reveals that superplasticized concrete with periwinkle shell partial replacement exhibits a slower strength development. Results indicate that the compressive strength of superplasticized PS concrete attains its maximum strength (22.07 kN/mm²) at 21 days with a 15% partial replacement and 0.5% superplasticizer content. The findings suggest that optimal strength development for PS partial replacement performs best at higher percentages (15%). Concerning the workability of fresh concrete, PS partial replacement exhibits a consistent increase in slump values with higher percentages of replacement and superplasticizer content, peaking at 55mm at 15% partial replacement and 1.5% superplasticizer content. This study contributes valuable insights into the optimization of compressive strength and workability of superplasticized concrete with PS partial replacements, offering a sustainable and resource-efficient alternative to conventional concrete mixtures
Tracing the Origins of the Wind Catcher: A Comparative Study of Iran, Egypt, and its Influence on Kuwaiti Architecture
Authors: Almekaimi Meshari , Alobaidan Jassim
Published: October 2024

This paper explores the architectural significance and evolution of wind towers and wind catchers, examining their various types and tracing their origins across ancient civilizations. Special emphasis is placed on the dispute between Iran and Egypt regarding the invention of the wind catcher. Furthermore, the study delves into how these architectural elements were introduced to Kuwait and adapted to suit the region’s hot arid climate. By analyzing historical records and architectural adaptations, the research aims to provide insights into the cultural and environmental factors that contributed to the development and diffusion of this sustainable cooling technology in the Gulf region
“A Study To Assess The Attitude Of Parents On Addiction Of Smartphone Among Children InSelected Area Of Makhnumajra Baddi, Distt. Solan, [H.P]”
Authors: Kumari Ms. Deepika , Sharma Ms. Sona
Published: October 2024

Aim of study to assess the level of attitude of parents on addiction of smartphone among children in selected area of Makhnumajra, Baddi, Distt. Solan. Material And Methods: A quantitative research approach, non-experimental, descriptive research design was used in this study. The sample was selected by random sampling technique. Sample size was 120. A Likert scale was used to assess the level of attitude of parents regarding addiction of smartphone among children in selected area of Makhnumajra Baddi. The tool was validated by the experts and found to be valid for this study. The results show that out of 120 parents, 3.33% were disagree, 33.33% were strongly disagree, 10.00% were agree and 53.33% were strongly agree regarding addiction of smartphone among children. The study participants showed strongly agree regarding addiction of smartphone and significant association was found among socio demographic variables as education of mother. Study Findings Regarding level of attitude of parents among addiction of smartphone of childrenwere found to be like this: The level of attitude of parents regarding addiction of smartphone among children revealed that out of 120 parents 4(3.33) parents were disagree, 40(33.33) parent were strongly disagree, 12(10.00) parents were agree and 64(53.33) parents were strongly agree regarding addiction of smartphone of children. With regard to the association between the attitude regarding addiction of smartphone by children among parents and selected socio- demographic variables in the present study findings revealed that there was a significantly associated with mother’s education. Conclusion: The study shows that parents of Makhnumajra Baddi were strongly agree related to addiction of smart phone among children
Addressing the rising threat of antibiotic resistance by optimizing phage therapy to combat antibiotic resistant bacteria
Authors: Kachhala Vaidehi
Published: October 2024

Antibiotics have long been a cornerstone in the fight against virulent microbial infections, significantly improving public health outcomes. However, their widespread and persistent use has led to a serious threat: antimicrobial resistance (AMR). This growing issue thus raises a consequential threat to public health and the environment. Consequently, necessitating the search for an efficacious substitute is the need of the hour. The resurgence of interest in phage therapy, one of the old remedies, is due to its preciseness in targeting the bacterial cells and causing lysis of the bacterial cell without causing harm to human or animal cells. Researchers worldwide are exploring the viability and efficiency of phage therapy as a means to address the challenge raised by the growing antibiotic resistance. This review paper discusses the current progress on bacteriophages as a promising alternative to antibiotics in response to the growing issue of antibiotic resistance. It covers various aspects, including the history and structure of bacteriophages, methods of preparation, their current status in research and therapy, and their potential future applications
Retrospective Study Of The Clinical Characteristics Of Cases With Covid-19
Authors: Mohamed Eman Samy , Shama Dr. Mohamed Abd Elhady , Ali Zeinab Hussein
Published: October 2024

background: COVID-19 pandemic placed immense pressure on health systems. The disease is transmitted by inhalation or contact with infected droplets. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue and malaise. The aim of this study was to determine the clinical characteristics of cases with covid-19. Design: Observational retrospective study was followed in this study. Study setting: This study was conducted at Tanta main university hospital and Itay El-baroud general hospital. Subjects: A purposeful sample of 100 adult isolated patients from the previosly mentioned settings was included in the study. Collection tools: one tool was used to collect data in this study "Covid-19 clinical characteristics assessment sheet" this tool consists of 2 parts: Part (1): Demograhic data of the studied cases with covid-19 Part (2): clinical characteristics of studied cases with covid-19. The results were as follow: the results indicated that around one third of the participants were dead and there was highly significant relationship between hypertension, diabetes mellitus, serum Ferritin level and blood group A and death (p<0.001). ICU admission rate was 71% and 35% of covid-19 cases needed invasive mechanical ventilation. Conclusion: it was concluded that the majority of confirmed covid-19 patients were old males. The highly reported signs and symptoms were fatigue, weakness, anorexia, tachypnea and fever. Hypertension and diabetes mellitus were the most reported comorbid diseases of confirmed covid-19 patients. Recommendations: Generalize the awareness of the most reported clinical characteristics of covid-19 to help health care providers to make the correct initial suspected diagnosis of COVID-19
The Effect Of Implementing A Bundle Of Evidence-Based Pain Management On Patient's Perception Of Pain And Clinical Outcomes
Authors: Elabdein Zeinab A. , El-Aziz Amany L. Abdel , Elshiek Abdel F. Tawfik , Ali Zeinab H.
Published: October 2024

Background: Evidence-based practice in pain management has been shown to provide improvements in patient outcomes. Aim: this study aimed to determine the effect of implementing a bundle of evidence-based pain management to improve patients' perception of pain and clinical outcomes. Research design: A quasi-experimental research design was used. Setting: the study was conducted on 3 surgical units (general, orthopedics and oncology surgery in Sayed Galal Hospital Sampling: a purposive sample of 70 adult patients was included in the study. Tools of data collection: four tools were used, first tool: a structured interviewing questionnaire. Second tool: Physiological parameters data. Third tool: Pain assessment by using The McGill Pain Questionnaire. Fourth tool: Groningen Sleep quality Scale. Result: the main results revealed that there was a statistically significant improvement in BP, HR, RR and Pso2 in the study group after intervention. There was statistically significant reducing total pain severity in the study group as well compared to control group with p-value = (0.01*). There was a highly statistically significant improvement of sleep quality at 3rd day postoperatively, with a p-value of 0.001* among study group. Conclusion: the implementation of a bundle of evidence-based pain management had a positive effect on reducing pain intensity, improvement of physiological parameters and sleep quality among the study group compared to control group. Recommendations: this study recommended that, reduplication this study in a large probability sample, using a bundle of evidence-based pain management in a different-surgical-wards. Set pain assessment scale as a part of a routine measurement like a vital-signs in surgical units
Equations for hydraulic conductivity estimation from particle size distribution: A dimensional analysis
Authors: Wang Ji‐Peng , François Bertrand , Lambert Pierre
Published: September 2017

Estimating hydraulic conductivity from particle size distribution (PSD) is an important issue for various engineering problems. Classical models such as Hazen model, Beyer model, and Kozeny‐Carman model usually regard the grain diameter at 10% passing (
) as an effective grain size and the effects of particle size uniformity (in Beyer model) or porosity (in Kozeny‐Carman model) are sometimes embedded. This technical note applies the dimensional analysis (Buckingham's
theorem) to analyze the relationship between hydraulic conductivity and particle size distribution (PSD). The porosity is regarded as a dependent variable on the grain size distribution in unconsolidated conditions. It indicates that the coefficient of grain size uniformity and a dimensionless group representing the gravity effect, which is proportional to the mean grain volume, are the main two determinative parameters for estimating hydraulic conductivity. Regression analysis is then carried out on a database comprising 431 samples collected from different depositional environments and new equations are developed for hydraulic conductivity estimation. The new equation, validated in specimens beyond the database, shows an improved prediction comparing to using the classic models.
Incorporation of a Redox‐Active Bis(guanidine) in Low‐Dimensional Tin and Lead Iodide Structures
Authors: Herrmann Hendrik , Walter Petra , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: September 2017

Redox‐active, protonated guanidines are incorporated in tin and lead iodide structures to protect the metal atoms from being oxidized and to thereby increase the stability of these materials. They could serve as preferred place of attack for incoming dioxygen, reducing it to redox‐inactive water, while being themselves oxidized to a stable dication without significant structural changes. This work focuses on the synthesis and bulk characterization of two first examples for tin and lead iodide materials with redox‐active guanidines.
Assessments for bone regeneration using the polycaprolactone SLUP (salt‐leaching using powder) scaffold
Authors: Cho Yong Sang , Hong Myoung Wha , Quan Meiling , Kim So‐Youn , Lee Se‐Hwan , Lee Seung‐Jae , Kim Young Yul , Cho Young‐Sam
Published: September 2017

Salt‐leaching using powder (SLUP) scaffolds are novel salt‐leaching scaffolds with well‐interconnected pores that do not require an organic solvent or high pressure. In this study, in vitro and in vivo cell behaviors were assessed using a PCL (polycaprolactone) SLUP scaffold. Moreover, using PCL, conventional salt‐leaching and 3D‐plotted scaffolds were fabricated as control scaffolds. Morphology, mechanical property, water absorption, and in vitro/in vivo cell response assessments were performed to clarify the characteristics of the SLUP scaffold compared with control scaffolds. Consequently, we verified that the interconnectivity between the pores of the SLUP scaffold was enhanced compared with conventional salt‐leaching scaffolds. Moreover, in vitro cell attachment and proliferation of the SLUP scaffold were higher than those of the 3D‐plotted scaffold because of their morphological characteristic. Furthermore, we revealed that new bone formation and bone ingrowth of the SLUP scaffold was superior to those of the calvarial defect model and 3D‐plotted scaffold because of the high porosity and improved interconnectivity of pores by the SLUP technique without high pressure using powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3432–3444, 2017.
Decision 22/2016. (XII. 5.) AB on the Interpretation of Article E)(2) of the Fundamental Law
Authors: Mohay Ágoston , Tóth Norbert
Published: September 2017

In a case of first impression, the Constitutional Court of Hungary (CCH or Court) ruled on November 30, 2016 that, in exceptional cases, it is competent to consider whether Hungary's obligations to the European Union (EU) violate fundamental individual rights (including human dignity) or Hungarian sovereignty as protected by the Hungarian Constitution. The decision places Hungary squarely within the growing group of EU member states whose constitutional courts have decided that, despite the decisions of the European Court of Justice regarding the primacy of EU law, EU member states are not compelled to violate their domestic constitutional obligations in carrying out their shared EU commitments.
Notes on the multiplicative ergodic theorem
Authors: FILIP SIMION
Published: September 2017

The Oseledets multiplicative ergodic theorem is a basic result with numerous applications throughout dynamical systems. These notes provide an introduction to this theorem, as well as subsequent generalizations. They are based on lectures at summer schools in Brazil, France, and Russia.
DIVERSITY IN SMALLHOLDER CITRUS ORCHARDS AND CULTIVATION BOTTLENECKS: RESEARCH AVENUES FOR IMPROVED PRODUCTION IN BENIN, WEST AFRICA
Authors: AKOHOUE FÉLICIEN , SEGNON ALCADE C. , ACHIGAN-DAKO ENOCH G.
Published: September 2017

Despite tremendous efforts made in agricultural sectors in sub-Saharan Africa in the last two decades, fruits production and consumption to reduce malnutrition and chronic diseases remain low and have received less attention. Moreover, our knowledge of the current production situation and options for improvement are still limited. In this study, we investigated citrus farming systems and production bottlenecks to identify leverage points for intensification of smallholder citrus farming systems in Benin. We provided a typology of citrus orchards based on 17 quantitative and qualitative variables using Factor Analysis of Mixed Data combined with Hierarchical Cluster Analysis. The typology revealed four categories of citrus farms based on biophysical resources, socioeconomic resources and system management practices. Categories 1 and 2 included farms characterised by less diversified cropping systems with non-recommended management practices. Orchard categories 3 and 4 included farms with high varietal diversity and improved management practices. However, farmers of category 4 neglected staking and digging practices. The inadequate farming practices explained some of the production bottlenecks, which were orchard-type dependent. We discussed the implications of our findings and suggested a number of policy and strategic decisions as well as research and development actions for improving citrus production in Benin.
Sexual-size dimorphism modulates the trade-off between exploiting food and wind resources in a large avian scavenger
Authors: Alarcón Pablo A. E. , Morales Juan M. , Donázar José A. , Sánchez-Zapata José A. , Hiraldo Fernando , Lambertucci Sergio A.
Published: September 2017

Animals are expected to synchronize activity routines with the temporal patterns at which resources appear in nature. Accordingly, species that depend on resources showing temporally mismatched patterns should be expected to schedule routines that balance the chances of exploiting each of them. Large avian scavengers depend on carcasses which are more likely available early in the morning, but they also depend on wind resources (i.e. uplifts) to subside flight which are stronger in afternoon hours. To understand how these birds deal with this potential trade-off, we studied the daily routines of GPS-tagged individuals of the world’s largest terrestrial soaring scavenger, the Andean condor (Vultur gryphus). Andean condors vary largely in weight and show a huge sexual dimorphism that allowed us to evaluate the effect of sex and body size on their daily routines. We found that condors use an intermediate solution strategy between the best times to exploit carcasses and uplifts, with this strategy changing over the year. Bigger males scheduled earlier routines that aligned more closely with uplift availability compared to smaller females, resulting in a partial temporal segregation between sexes. Condors’ routines reflect a sexual-size dependent trade-off that may underpin ecological and sociobiological traits of the studied population.
Development of lithium attachment mass spectrometry – knudsen effusion and chemical ionisation mass spectrometry (KEMS, CIMS)
Authors: Booth A. Murray , Bannan Thomas J. , Benyezzar Med , Bacak Asan , Alfarra M. Rami , Topping David , Percival Carl J.
Published: September 2017

Development of lithium ion attachment for the measurement of atmospherically relevant species in Chemical Ionisation and Knudsen Effusion Mass Spectrometry.
Bis-tris propane in DMSO as a wet scrubbing agent: carbamic acid as a sequestered CO2 species
Authors: Eftaiha Ala'a F. , Qaroush Abdussalam K. , Assaf Khaleel I. , Alsoubani Fatima , Markus Pehl Thomas , Troll Carsten , El-Barghouthi Musa I.
Published: September 2017

We report the chemisorption of CO2 by bis-tris propane dissolved in DMSO via carbamic acid formation.
Synthesized polyvidone-stabilized Rh(0) nanoparticles catalyzed the hydrolytic dehydrogenation of methylamine-borane in ambient conditions
Authors: Gulcan M. , Karataş Y.
Published: September 2017

Polyvidone (PVP40)-stabilized Rh nanoparticles (Rh@PVP40) were synthesized via a classical alcohol reduction technique and were characterized by carrying out TEM, HR-TEM, TEM/EDX, P-XRD analysis, UV/Vis and XPS spectroscopy investigations.
Energy storage applications of biomass-derived carbon materials: batteries and supercapacitors
Authors: Gao Yong-Ping , Zhai Zi-Bo , Huang Ke-Jing , Zhang Ying-Ying
Published: September 2017

Recent advances in the application of biomass-derived carbon materials in batteries and supercapacitors.
Engineering metamaterial absorbers from dense gold nanoparticle stacks
Authors: Hewlett Sheldon , Mock Adam
Published: September 2017

Both ordered and disordered electromagnetic metamaterials have been shown to exhibit interesting and technologically relevant properties that would not be present in the constituent materials in their bulk form. Disordered metamaterials can be fabricated using low-cost and scalable fabrication approaches which are particularly advantageous at the nanoscale. This work shows how a solution-based deposition process can be leveraged to introduce quasi-ordering in disordered gold metamaterials to achieve 94% absorption over the visible spectrum. Full-wave electrodynamic simulations suggest that more advanced structures consistent with this fabrication approach could exhibit 98% average absorption over the entire solar spectrum. We envision this simple and cost-effective fabrication of highly absorbing disordered metamaterials to be of use for thermovoltaics and solar cells.
Efficient molecular density functional theory using generalized spherical harmonics expansions
Authors: Ding Lu , Levesque Maximilien , Borgis Daniel , Belloni Luc
Published: September 2017

We show that generalized spherical harmonics are well suited for representing the space and orientation molecular density in the resolution of the molecular density functional theory. We consider the common system made of a rigid solute of arbitrary complexity immersed in a molecular solvent, both represented by molecules with interacting atomic sites and classical force fields. The molecular solvent density ρ(r,Ω) around the solute is a function of the position r≡(x,y,z) and of the three Euler angles Ω≡(θ,ϕ,ψ) describing the solvent orientation. The standard density functional, equivalent to the hypernetted-chain closure for the solute-solvent correlations in the liquid theory, is minimized with respect to ρ(r,Ω). The up-to-now very expensive angular convolution products are advantageously replaced by simple products between projections onto generalized spherical harmonics. The dramatic gain in speed of resolution enables to explore in a systematic way molecular solutes of up to nanometric sizes in arbitrary solvents and to calculate their solvation free energy and associated microscopic solvent structure in at most a few minutes. We finally illustrate the formalism by tackling the solvation of molecules of various complexities in water.
Synthesis of non-uniformly correlated partially coherent sources using a deformable mirror
Authors: Hyde M. W. , Bose-Pillai S. R. , Wood R. A.
Published: September 2017

The near real-time synthesis of a non-uniformly correlated partially coherent source using a low-actuator-count deformable mirror is demonstrated. The statistical optics theory underpinning the synthesis method is reviewed. The experimental results of a non-uniformly correlated source are presented and compared to theoretical predictions. A discussion on how deformable mirror characteristics such as actuator count and pitch affect source generation is also included.
The optical properties of regenerated silk fibroin films obtained from different sources
Authors: Perotto Giovanni , Zhang Yuji , Naskar Deboki , Patel Nereus , Kaplan David L. , Kundu Subhas C. , Omenetto Fiorenzo G.
Published: September 2017

Silk fibroin possesses unique properties for bio-functional optical interfaces and has been attracting increasing interest as an optical material. Here, we report on the refractive index and absorption coefficient of silk fibroin extracted from Bombyx mori, Antheraea mylitta, Samia ricini, and Antheraea assamensis. The influence of protein molecular weight, residual water content, and crystallinity on refractive index was investigated. The parameters for the Cauchy dispersion law and Urbach absorption were determined for each of the silk fibroins. By exploiting the differences in refractive index between the different fibroins, an all-protein slab waveguide was fabricated.
Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis
Authors: Sarashina-Kida Hana , Negishi Hideo , Nishio Junko , Suda Wataru , Nakajima Yuki , Yasui-Kato Mika , Iwaisako Keiko , Kang Sujin , Endo Nobuyasu , Yanai Hideyuki , Asagiri Masataka , Kida Hiroshi , Hattori Masahira , Kumanogoh Atsushi , Taniguchi Tadatsugu
Published: September 2017

Significance

The imbalance in the intestinal microbiota repertoire, called dysbiosis, underlies the development of inflammatory diseases in the intestine and distant organ systems. Whether and how distant organs regulate the commensal gut bacteria and intestinal homeostasis via microbe-targeted molecules has remained poorly explored. In this study, we show that the gallbladder regulates intestinal immune homeostasis through the production of surfactant protein D (SP-D) that is delivered to the intestine via bile. The importance of the gallbladder-derived SP-D was underscored by an intestinal dysbiosis in SP-D–deficient mice and susceptibility of these mice to dextran sodium sulfate sodium-induced colitis. Our study thus revealed a unique interorgan regulation of intestinal homeostasis by SP-D with potential clinical implications such as cholecystectomy.
Disease-associated mutations in human BICD2 hyperactivate motility of dynein–dynactin
Authors: Huynh Walter , Vale Ronald D.
Published: September 2017

Bicaudal D2 (BICD2) joins dynein with dynactin into a ternary complex (termed DDB) capable of processive movement. Point mutations in the BICD2 gene have been identified in patients with a dominant form of spinal muscular atrophy, but how these mutations cause disease is unknown. To investigate this question, we have developed in vitro motility assays with purified DDB and BICD2’s membrane vesicle partner, the GTPase Rab6a. Rab6a–GTP, either in solution or bound to artificial liposomes, released BICD2 from an autoinhibited state and promoted robust dynein–dynactin transport. In these assays, BICD2 mutants showed an enhanced ability to form motile DDB complexes. Increased retrograde transport by BICD2 mutants also was observed in cells using an inducible organelle transport assay. When overexpressed in rat hippocampal neurons, the hyperactive BICD2 mutants decreased neurite growth. Our results reveal that dominant mutations in BICD2 hyperactivate DDB motility and suggest that an imbalance of minus versus plus end–directed microtubule motility in neurons may underlie spinal muscular atrophy.
Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking
Authors: Selyunin Andrey S. , Iles Lakesla R. , Bartholomeusz Geoffrey , Mukhopadhyay Somshuvra
Published: September 2017

Shiga toxins 1 and 2 (STx1 and STx2) undergo retrograde trafficking to reach the cytosol. Early endosome-to-Golgi transport allows the toxins to evade degradation in lysosomes. Targeting this trafficking step has therapeutic promise, but the mechanism of trafficking for the more potent toxin STx2 is unclear. To identify host factors required for early endosome-to-Golgi trafficking of STx2, we performed a viability-based genome-wide siRNA screen in HeLa cells. 564, 535, and 196 genes were found to be required for toxicity induced by STx1 only, STx2 only, and both toxins, respectively. We focused on validating endosome/Golgi-localized hits specific for STx2 and found that depletion of UNC50 blocked early endosome-to-Golgi trafficking and induced lysosomal degradation of STx2. UNC50 acted by recruiting GBF1, an ADP ribosylation factor–guanine nucleotide exchange factor (ARF-GEF), to the Golgi. These results provide new information about STx2 trafficking mechanisms and may advance efforts to generate therapeutically viable toxin-trafficking inhibitors.
Slow fusion pore expansion creates a unique reaction chamber for co-packaged cargo
Authors: Bohannon Kevin P. , Bittner Mary A. , Lawrence Daniel A. , Axelrod Daniel , Holz Ronald W.
Published: September 2017

A lumenal secretory granule protein, tissue plasminogen activator (tPA), greatly slows fusion pore dilation and thereby slows its own discharge. We investigated another outcome of the long-lived narrow fusion pore: the creation of a nanoscale chemical reaction chamber for granule contents in which the pH is suddenly neutralized upon fusion. Bovine adrenal chromaffin cells endogenously express both tPA and its primary protein inhibitor, plasminogen activator inhibitor 1 (PAI). We found by immunocytochemistry that tPA and PAI are co-packaged in the same secretory granule. It is known that PAI irreversibly and covalently inactivates tPA at neutral pH. We demonstrate with zymography that the acidic granule lumen protects tPA from inactivation by PAI. Immunocytochemistry, total internal reflection fluorescence (TIRF) microscopy, and polarized TIRF microscopy demonstrated that co-packaged PAI and tPA remain together in granules for many seconds in the nanoscale reaction chamber, more than enough time to inhibit tPA and create a new secreted protein species.
The SAMI Galaxy Survey: understanding observations of large-scale outflows at low redshift with EAGLE simulations
Authors: Tescari E. , Cortese L. , Power C. , Wyithe J. S. B. , Ho I.-T. , Crain R. A. , Bland-Hawthorn J. , Croom S. M. , Kewley L. J. , Schaye J. , Bower R. G. , Theuns T. , Schaller M. , Barnes L. , Brough S. , Bryant J. J. , Goodwin M. , Gunawardhana M. L. P. , Lawrence J. S. , Leslie S. K. , López-Sánchez Á. R. , Lorente N. P. F. , Medling A. M. , Richards S. N. , Sweet S. M. , Tonini C.
Published: September 2017

This work presents a study of galactic outflows driven by stellar feedback. We extract main-sequence disc galaxies with stellar mass 109 ≤ M⋆/ M⊙ ≤ 5.7 × 1010 at redshift z = 0 from the highest resolution cosmological simulation of the Evolution and Assembly of GaLaxies and their Environments (EAGLE) set. Synthetic gas rotation velocity and velocity dispersion (σ) maps are created and compared to observations of disc galaxies obtained with the Sydney-AAO (Australian Astronomical Observatory) Multi-object Integral field spectrograph (SAMI), where σ-values greater than 150 km s−1 are most naturally explained by bipolar outflows powered by starburst activity. We find that the extension of the simulated edge-on (pixelated) velocity dispersion probability distribution depends on stellar mass and star formation rate surface density (ΣSFR), with low-M⋆/low-ΣSFR galaxies showing a narrow peak at low σ (∼30 km s−1) and more active, high-M⋆/high-ΣSFR galaxies reaching σ > 150 km s−1. Although supernova-driven galactic winds in the EAGLE simulations may not entrain enough gas with T <105 K compared to observed galaxies, we find that gas temperature is a good proxy for the presence of outflows. There is a direct correlation between the thermal state of the gas and its state of motion as described by the σ-distribution. The following equivalence relations hold in EAGLE: (i) low-σ peak  ⇔ disc of the galaxy  ⇔ gas with T <105 K; (ii) high-σ tail  ⇔ galactic winds  ⇔ gas with T ≥105 K.
Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis
Authors: Philpott Holly T. , O'Brien Melissa , McDougall Jason J.
Published: September 2017

Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.
‘Luck, chance, and happenstance?Perceptions of success and failure amongst fixed‐term academic staff inUKhigher education’
Authors: Loveday Vik
Published: September 2017

What does it mean to attribute success to ‘luck’, but failure to personal deficiency? In 2015/16, more than 34 per cent of academic employees in UK higher education institutions were employed on temporary contracts, and the sector itself has undergone a substantial transformation in recent years in terms of expansion, measurement, and marketization. Based on two waves of interviews conducted with fixed‐term academic employees at different career stages, the article explores the narrativization of success and failure amongst staff working at the ‘sharp end’ of the so‐called neoliberal academy. Arguing that precarious employment situations precipitate the feeling of being ‘out of control’, the majority of the participants’ narratives were characterized by a distinct lack of agency. The paper explores the recourse to notions of chance and the consolidation of ‘luck’ as an explanatory factor in accounting for why good things happen; however, in tandem with this inclination is the tendency to individualize failure when expectations have been thwarted. While accounts of fixed‐term work are suffused with notions of chance and fortune, ‘luck’ remains an under‐researched concept within sociology. The article thus concludes by considering what the analysis of ‘luck’ might offer for a fuller, politicized understanding of processes at work in the contemporary academy.
Role of the glucose‐sensing receptor in insulin secretion
Authors: Kojima Itaru , Medina Johan , Nakagawa Yuko
Published: September 2017

Glucose is a primary stimulator of insulin secretion. It has been thought that glucose exerts its effect by a mechanism solely dependent on glucose metabolism. We show here that glucose induces rapid Ca2+ and cyclic AMP signals in β‐cells. These rapid signals are independent of glucose‐metabolism and are reproduced by non‐metabolizable glucose analogues. These results led us to postulate that glucose activates a cell‐surface receptor, namely the glucose‐sensing receptor. Rapid signals induced by glucose are blocked by inhibition of a sweet taste receptor subunit T1R3 and a calcium‐sensing receptor subunit CaSR. In accordance with these observations, T1R3 and CaSR form a heterodimer. In addition, a heterodimer of T1R3 and CaSR is activated by glucose. These results suggest that a heterodimer of T1R3 and CaSR is a major component of the glucose‐sensing receptor. When the glucose‐sensing receptor is blocked, glucose‐induced insulin secretion is inhibited. Also, ATP production is significantly attenuated by the inhibition of the receptor. Conversely, stimulation of the glucose‐sensing receptor by either artificial sweeteners or non‐metabolizable glucose analogue increases ATP. Hence, the glucose‐sensing receptor signals promote glucose metabolism. Collectively, glucose activates the cell‐surface glucose‐sensing receptor and promotes its own metabolism. Glucose then enters the cells and is metabolized through already activated metabolic pathways. The glucose‐sensing receptor is a key molecule regulating the action of glucose in β‐cells.
A 4D view on insulin secretory granule turnover in the β‐cell
Authors: Müller Andreas , Mziaut Hassan , Neukam Martin , Knoch Klaus‐Peter , Solimena Michele
Published: September 2017

Insulin secretory granule (SG) turnover consists of several highly regulated processes allowing for proper β‐cell function and insulin secretion. Besides the spatial distribution of insulin SGs, their age has great impact on the likelihood of their secretion and their behaviour within the β‐cell. While quantitative measurements performed decades ago demonstrated the preferential secretion of young insulin, new experimental approaches aim to investigate insulin ageing at the granular level. Live‐cell imaging, automated image analysis and correlative light and electron microscopy have fostered knowledge of age‐defined insulin SG dynamics, their interaction with the cytoskeleton and ultrastructural features. Here, we review our recent work in regards to the connection between insulin SG age, SG dynamics, intracellular location and interaction with other proteins.
β‐Cells are not uniform after all—Novel insights into molecular heterogeneity of insulin‐secreting cells
Authors: Avrahami Dana , Wang Yue J. , Klochendler Agnes , Dor Yuval , Glaser Benjamin , Kaestner Klaus H.
Published: September 2017

While the β‐cells of the endocrine pancreas are defined as cells with high levels of insulin production and tight stimulus‐secretion coupling, the existence of functional heterogeneity among them has been known for decades. Recent advances in molecular technologies, in particular single‐cell profiling on both the protein and messenger RNA level, have uncovered that β‐cells exist in several antigenically and molecularly definable states. Using antibodies to cell surface markers or multidimensional clustering of β‐cells using more than 20 protein markers by mass cytometry, 4 distinct groups of β‐cells could be differentiated. However, whether these states represent permanent cell lineages or are readily interconvertible from one group to another remains to be determined. Nevertheless, future analysis of the pathogenesis of type 1 and type 2 diabetes will certainly benefit from a growing appreciation of β‐cell heterogeneity. Here, we aim to summarize concisely the recent advances in the field and their possible impact on our understanding of β‐cell physiology and pathophysiology.
Aggregation and fractal dimension of aggregates formed in sand dunes stabilized byPistachioPAMandPistachioPVAc mulches
Authors: Saiedi N. , Besalatpour A. A. , Shirani H. , Abbaszadeh Dehaji P. , Esfandiarpour I. , Faramarzi M.
Published: September 2017

Wind erosion is a serious environmental problem that has received increased attention by attracting the interest of academics, policy makers and the public. In this study, the effects of combined mulches (denoted asPistachioPAMandPistachioPVAc, used for stabilizing the sand dunes in theDavaran plain in southeasternIran) on aggregate formation and stability indices were investigated by the theory of fractal geometry. In addition, the temporal changes in soil organic carbon (SOC) content and microbial respiration rate (MRR) in the soils treated with the mulches were compared with the control samples during a 5‐month experiment. The results showed significant (P < 0.01) increases in theSOCcontent andMRRfollowing the application (1.5 l m−2) ofPistachioPVAcandPistachioPAMmulches. The rate of release ofCO2was measured in the soils treated with the mulches studied. The largest rate ofCO2release from the three samples taken in weeks 2, 5 and 19 from the beginning of the experiment was about 23.0 µg‐CO2day−1 g−1soil. The smallest and largest mean weight diameters (MWD) of the aggregates formed were observed in the control (0.06 mm) and thePistachioPVAc(1.38 mm) treatments, respectively. The use of mulches had significant (P < 0.01) effects on the fractal dimension of aggregates. The more stable and coarser aggregates formed in the presence ofPistachioPVAchad the smallest fractal dimension. The largest negative correlation between the properties investigated and the fractal dimension was forSOCandMWD. Therefore, it appears that the theory of fractal dimensions is useful for explaining the temporal variation of aggregate stability in soil stabilized by combined mulches.

Highlights

Effects of combined mulches on aggregate formation were investigated with fractal geometry theory (FGT).

The more stable and coarser aggregates formed in the presence ofPistachioPVAmulch had the smallest fractal dimension.

Mulches increased soil organic carbon and microbial respiration significantly (P < 0.01).

TheFGTmight be useful for explaining the temporal variation in aggregate stability of stabilized sand dunes.
From large to small: the immunohistochemical panel in the diagnosis of early hepatocellular carcinoma
Authors: Vasuri Francesco , Malvi Deborah , Bonora Sonia , Fittipaldi Silvia , Renzulli Matteo , Tovoli Francesco , Golfieri Rita , Bolondi Luigi , D'Errico Antonia
Published: September 2017

Aims

The aims of this study were to: validate the use of the immunohistochemical (IHC) markers glutamine synthetase (GS), glypican‐3 (GPC3), heat shock protein‐70 (HSP70) and enhancer of zeste homologue 2 (EZH2) in liver biopsies for the differential diagnosis between small hepatocellular carcinoma (HCC) and non‐neoplastic liver nodules, with special attention to <10‐mm nodules; and assess the actual sensitivity and specificity of the single markers, and their combination, in needle biopsies.

Methods and results

One hundred liver nodules, i.e. 66 HCCs and 34 non‐neoplastic nodules, were prospectively collected from 43 consecutive orthotopic liver transplantation patients, and subjected to ‘backtable’ needle biopsies directly on surgical specimens. IHC evaluation was semi‐automatically performed with a Benchmark Ultra immunostainer. The morphological and IHC diagnosis in surgical specimens was considered to be the gold standard. GS, GPC3, HSP70 and EZH2 showed 16.6%, 10.7%, 28.8% and 62.1% decreases in sensitivity, respectively, from surgical specimen to needle biopsy. Higher decreases were observed in <10‐mm nodules. In 18 HCCs with no morphological diagnostic features of malignancy in biopsies, GPC3 or GS were positive in 16; in seven HCCs, neither morphology nor IHC evaluation ruled out the differential diagnosis made on the basis of needle biopsy.

Conclusions

We present for the first time a direct comparison between surgical specimens and needle biopsies to confirm the usefulness and reproducibility of the most widely used antibodies for the diagnosis of small liver nodules. Our results support the use of IHC evaluation in biopsies for the diagnosis of small liver lesions, although the IHC panel could also give negative results in the presence of obvious HCC, and the possibility of false positives should always be considered.
Altered expression of antigen‐specific memory and regulatory T‐cell subsets differentiate latent and active tuberculosis
Authors: Pathakumari Balaji , Devasundaram Santhi , Raja Alamelu
Published: September 2017

Although one‐third of the world population is infected with Mycobacterium tuberculosis, only 5–10% of the infected individuals will develop active tuberculosis (TB) disease and the rest will remain infected with no symptoms, known as latent TB infection (LTBI). Identifying biomarkers that differentiate latent and active TB disease enables effective TB control, as early detection, treatment of active TB and preventive treatment of individuals with LTBI are crucial steps involved in TB control. Here, we have evaluated the frequency of antigen‐specific memory and regulatory T (Treg) cells in 15 healthy household contacts (HHC) and 15 pulmonary TB patients (PTB) to identify biomarkers for differential diagnosis of LTBI and active TB. Among all the antigens tested in the present study, early secretory antigenic target‐6 (ESAT‐6) ‐specific CD4+ and CD8+ central memory (Tcm) cells showed 93% positivity in HHC and 20% positivity in PTB. The novel test antigens Rv0753c and Rv0009 both displayed 80% and 20% positivity in HHC and PTB, respectively. In contrast to Tcm cells, effector memory T (Tem) cells showed a higher response in PTB than HHC; both ESAT‐6 and Rv0009 showed similar positivity of 80% in PTB and 33% in HHC. PTB patients have a higher proportion of circulating antigen‐reactive Treg cells (CD4+ CD25+ FoxP3+) than LTBI. Rv2204c‐specific Treg cells showed maximum positivity of 73% in PTB and 20% in HHC. Collectively, our data conclude that ESAT‐6‐specific Tcm cells and Rv2204c‐specific Treg cells might be useful biomarkers to discriminate LTBI from active TB.
Generation of T follicular helper cells in vitro: requirement for B‐cell receptor cross‐linking and cognate B‐ and T‐cell interaction
Authors: Kolenbrander Anne , Grewe Bastian , Nemazee David , Überla Klaus , Temchura Vladimir
Published: September 2017

The minimum requirements for in vitro modelling of natural CD4+ T‐cell differentiation into T follicular helper (Tfh) cells are still under investigation. We co‐cultured wild‐type and T‐cell receptor (TCR) transgenic CD4+ T cells from naive mice with dendritic cells and B‐cell receptor (BCR) transgenic B cells in the presence of HIV‐derived virus‐like particles containing matched B‐cell and T‐cell epitopes. This co‐culturing induced co‐expression of Tfh‐master regulator transcription factor BCL‐6 and CXCR5 in up to 10% of the wild‐type and up to 40% of the TCR‐transgenic CD4+ T cells. Phenotypic markers, production of interleukin‐21 and isotype switching of the B cells to IgG1 further indicated a helper function of the induced Tfh cells in vitro. Dendritic cells supported the generation of functional Tfh cells, but were unable to induce them without cognate B cells. Hence, our study presents a robust experimental system for efficient generation of functionally active Tfh cells in vitro and confirms the importance of cognate B‐ and T‐cell cross‐talk for the Tfh differentiation process.