cssi/SciSciGPT-SciSciNet huggingface dataset:
Cardiorenal metabolic syndrome and diabetic cognopathy.

The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer’s disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term ‘diabetic cognopathy’ (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial bloodbrain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions.
Structure characterization of films from drying oils cured under infrared light

Drying oils have been considered as water resistant coatings for bio-based packaging materials; however, their curing rates are slow for industrial applications. Infrared radiation was investigated in this study as a means to increase the curing rate of linseed and tung oils. The effect of oil pretreatment with gamma radiation was also investigated. FTIR spectroscopy was used to monitor chemical changes during oil oxidation. Results indicated that infrared radiation increased the curing rate of linseed and tung oils. The oxidation rate of both oils, as monitored by the decrease of the 3010 cm−1 FTIR peak, followed an exponential decay. The structure of cured films was examined by SEM. Images of films cross section were used to develop a qualitative model of the curing process. Linseed and tung oil showed differences in structural development during drying. In the case of linseed oil, the formation of a tough skin layer slowed down oxygen diffusion to the oil underneath, resulting in slow curing. For the case of tung oil, the skin layer shrank as it formed allowing oxygen diffusion and fast curing of tung oil. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Biologic agents in the treatment of colorectal cancer: an update

SUMMARY Biologic agents are drugs that are made by living organisms. A number of these agents are now routinely used in the treatment of metastatic colorectal cancer. These biologic agents block aspects of specific signaling pathways. They are commonly presumed to have a more selective and targeted action in comparison to cytotoxic chemotherapy, although this assumption is not always borne out by data. These agents were developed with the goal of reducing the use of cytotoxic chemotherapy and thereby reducing the associated toxicities, however they are most commonly used concurrently with cytotoxics, and so the older toxicities often remain. This paper will provide a critical overview of the biologic agents that are currently used in the management of metastatic colorectal cancer, focusing on VEGF and the EGF receptor inhibitors. The rationale behind the use of these biologic agents, including the clinical trials incorporating these agents, will be discussed, and the toxicities associated with these agen...
The burden of Duchenne muscular dystrophy: An international, cross-sectional study

Objective: The objective of this study was to estimate the total cost of illness and economic burden of Duchenne muscular dystrophy (DMD). Methods: Patients with DMD from Germany, Italy, United Kingdom, and United States were identified through Translational Research in Europe–Assessment & Treatment of Neuromuscular Diseases registries and invited to complete a questionnaire online together with a caregiver. Data on health care use, quality of life, work status, informal care, and household expenses were collected to estimate costs of DMD from the perspective of society and caregiver households. Results: A total of 770 patients (173 German, 122 Italian, 191 from the United Kingdom, and 284 from the United States) completed the questionnaire. Mean per-patient annual direct cost of illness was estimated at between $23,920 and $54,270 (2012 international dollars), 7 to 16 times higher than the mean per-capita health expenditure in these countries. Indirect and informal care costs were substantial, each constituting between 18% and 43% of total costs. The total societal burden was estimated at between $80,120 and $120,910 per patient and annum, and increased markedly with disease progression. The corresponding household burden was estimated at between $58,440 and $71,900. Conclusions: We show that DMD is associated with a substantial economic burden. Our results underscore the many different costs accompanying a rare condition such as DMD and the considerable economic burden carried by affected families. Our description of the previously unknown economic context of a rare disease serves as important intelligence input to health policy evaluations of intervention programs and novel therapies, financial support schemes for patients and their families, and the design of future cost studies. Neurology® 2014;83:529–536
A change in the climate: Online social capital and the spiral of silence

This study explores the connection between online social capital and the Spiral of Silence. Online social capital is an individual’s network of social connections, a network that enables and encourages social cooperation. The Spiral of Silence theory suggests that an opinion can become dominant if those who perceive their opinion to be in the minority do not speak up because society threatens them with isolation. A study of 550 individuals explored their willingness to speak up on an issue, and assessed whether they thought they held a majority of a minority opinion. This study compared both their bonding social capital (via homogeneous networks) and bridging social capital (via heterogeneous networks) to their willingness to speak up and their perceptions of whether others held their opinions. Regression analyses shows that bridging social capital is a key influencer in people’s willingness to speak up in social media and other online venues.
Lack of Genetic Differentiation in Aggressive and Secondary Bark Beetles (Coleoptera: Curculionidae, Scolytinae) from Arizona

Bark beetles (Coleoptera: Curculionidae, Scolytinae) play an important role as disturbance agents in ponderosa pine (Pinus ponderosa Douglas ex Lawson) forests of Arizona. However, from 2001 to 2003, elevated bark beetle activity caused unprecedented levels of ponderosa pine mortality. A better understanding of the population structure of these species will facilitate analysis of their dispersal patterns and improve management strategies. Here, we use fluorescently labeled amplified fragment length polymorphism (fAFLP) analysis to resolve genetic variation among and within sampling locations in northcentral Arizona of Ips pini (Say), Dendroctonus brevicomis LeConte, and D. frontalis Zimmermann. We generated genetic fingerprints for >500 beetle specimens and analyzed genetic diversity. For all species, gene flow estimates among sampling locations were high, and significant population subdivision was not discernible across a large portion of ponderosa pine forests in Arizona. However, a weak relationship was detected with I. pini population structure and elevation. Because of the lack of genetic differentiation detected throughout the large study area, our findings suggest these insects are capable of long distance dispersal and exhibit a high degree of gene flow across a broad region. We conclude that our results are consistent with strong dispersal patterns and large population sizes of all three species.
Scalp Defects in Trisomy 13

A chromosomal abnormality should be suspected in every patient with multiple congenital anomalies.It is important to determine the specific type in order to provide the parents with a prognosis and proper genetic counseling.In patients with multiple congenital anomalies who have scalp defects, the most likely diagnosis is Trisomy 13.
Superconductor Bi-oxide films via an electrodeposition process

Non-vacuum electrodeposition and spray deposition process was used to deposit Bi-2212 precursor films. Biaxially textured Bi-2212 superconductor films were prepared from electrodeposited precursor films by melt-quench/melt-growth processing on Ag-coated LAO substrates. Magnetization measurements for the electrodeposited, Bi-2212 superconductor films show critical current density values greater than 5 × 106 A cm−2 at 4 K in zero field. The samples were characterized by x-ray diffraction including θ/2θ, pole figures, omega scans, phi scans, resistance versus temperature (R–T), magnetization measurements, transmission electron microscopy and scanning electron micrographs.
Enterprise resource planning (ERP)—A brief history

Abstract This is a brief history of ERP—enterprise resource planning. Major ERP vendors are discussed as well as the major impact of developments in computer hardware and software on the industry. The industry consolidation that has recently occurred is also discussed. Interviews were conducted with Mr. Ed McVaney, founder of J.D. Edwards, Rick Allen, former VP of Finance and Administration, and Rick Snow, former Chief Legal Counsel of J.D. Edwards. Information was also obtained from Bill Robinson who held the position of “Industry Consultant” with IBM in the mid-1980s.
The role of child maltreatment in early deviations in cognitive and affective processing abilities and later peer relationship problems.

Despite considerable research demonstrating the adverse consequences of child maltreatment, including a heightened risk for adaptational failures and psychopathology, longitudinal evaluations of processes contributing to negative outcomes have been limited. Problems in peer relations constitute a critical developmental risk for future maladaptation among maltreated children, transferring relationship disturbance from the family to new interpersonal contexts. The linkages of a history of child maltreatment to early deviations in cognitive/affective processes, which subsequently lead to difficulties in peer relations were examined. Specifically, in a sample of 46 maltreated and 43 nonmaltreated low-income children, laboratory assessments of affect understanding and cognitive control functioning were conducted, followed by later peer and teacher assessments of peer relations in the school setting. Maltreated children were shown to evidence early deviations in their understanding of negative affect as well as immaturity in their cognitive controls. Maltreated children also were shown to have lower social effectiveness and higher levels of undercontrolled and aggressive behavior in the school setting. Physically abused children were found to be more rejected by their peers. Cognitive control functioning partially mediated the effect of maltreatment on later social effectiveness. Negative affect understanding mediated both the relation of maltreatment on later dysregulated behavior in the peer setting and the effect of physical abuse on later rejection by peers. The results are discussed in terms of their support for organizational/transactional theory and the implications they have for prevention and intervention.
A 40-kilodalton protein binds specifically to an upstream sequence element essential for muscle-specific transcription of the human myoglobin promoter

To define transcriptional control elements responsible for muscle-specific expression of the human myoglobin gene, we performed mutational analysis of upstream sequences (nucleotide positions -373 to +7 relative to the transcriptional start site) linked to a firefly luciferase gene. Transient expression assays in avian and mammalian cells indicated that a CCCACCCCC (CCAC box) sequence (-223 to -204) is necessary for muscle-specific transcription directed either by the native myoglobin promoter or by a heterologous minimal promoter linked to the myoglobin upstream enhancer region. A putative MEF2-like site (-160 to -169) was likewise necessary for full transcriptional activity in myotubes. Mutations within either of two CANNTG (E-box) motifs (-176 to -148) had only minimal effects on promoter function. We identified and partially purified from nuclear extracts a 40-kDa protein (CBF40) that binds specifically to oligonucleotides containing the CCAC box sequence. A mutation of the CCAC box that disrupted promoter function in vivo also impaired binding of CBF40 in vitro. These data suggest that cooperative interactions between CBF40 and other factors including MEF-2 are required for expression of the human myoglobin gene in skeletal muscle.
Further Insights Derived Via Quantal Density Functional Theory

In this chapter we explain insights arrived at via Quantal density functional theory (Q-DFT) of two popular approximation schemes within the framework of local effective potential energy theory. The first of these is the local density approximation (LDA) for ‘exchange’ [1] and ‘exchange-correlation’ [2] as applied within Kohn-Sham (KS) density functional theory [3]. The second is Slater theory [4] for ‘exchange’, the LDA within its context [4], and the Slater Xcti approximation scheme [5] to incorporate Coulomb correlations. The LDA and Slater theory are both ad hoc formulations.
Exceptional multiplicity of cerebral arteriovenous malformations associated with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).

PURPOSE To describe the clinical and imaging features of seven patients with hereditary hemorrhagic telangiectasia and an exceptional number of cerebral arteriovenous malformations (AVMs). METHODS One hundred thirty-six patients from a dedicated hereditary hemorrhagic telangiectasia clinic were screened systematically for cerebral AVMs by means of MR imaging. Thirty-one were found to have abnormalities suggestive of a vascular malformation. Eighteen of these 31 patients subsequently underwent diagnostic cerebral angiography. RESULTS Of the 18 patients who had cerebral angiography, all were found to have at least one AVM and seven were found to have three or more AVMs. The number of cerebral AVMs detected ranged from three to nine. At angiography, the AVMs varied in size from 3 to 25 mm in maximal dimension and consisted of a poorly defined plexiform nidus that typically had a single arterial feeding pedicle and a single draining vein. The two largest AVMs (20- and 25-mm nidus, respectively) contained intranidal aneurysms. Treatment included embolization, surgical excision, or follow-up management. CONCLUSIONS Multiple cerebral AVMs are associated with hereditary hemorrhagic telangiectasia and further highlight the uniqueness of central nervous system involvement by this systemic angiodysplasia. MR imaging can underestimate the number and size of cerebral AVMs; therefore, catheter angiography is necessary to establish the extent of central nervous system involvement in this disorder.
Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53

Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used mouse models that depleted YY1 at two distinct stages of thymocyte development. When YY1 was depleted in CD4(-)CD8(-) double-negative thymocytes, development to the CD4(+)CD8(+) double-positive stage was impaired, due to increased apoptosis that prevented expansion of post-β-selection thymocytes. When YY1 was depleted in double-positive thymocytes, they underwent increased cell-autonomous apoptosis in vitro and displayed a shorter lifespan in vivo, as judged by their ability to undergo secondary Vα-to-Jα recombination. Mechanistically, we found that the increased apoptosis in YY1-deficient thymocytes was attributed to overexpression of p53, because concurrent loss of p53 completely rescued the developmental defects of YY1-deficient thymocytes. These results indicated that YY1 functions as a critical regulator of thymocyte survival and that it does so by suppressing the expression of p53.
Nonischemic ST-Segment Elevation

Scenario: This is a resting 12-lead ECG obtained in a 47-year-old African American male patient presenting to the emergency department with complaints of atypical chest pain. The patient has no prior history of heart disease but is a smoker and has a sedentary lifestyle. ECG PUZZLER A regular feature of the American Journal of Critical Care, the ECG Puzzler addresses ECG interpretation for clinical practice. We welcome letters to the Editors regarding this feature.
Normal Variations in the Susceptibility of Human Fibrin to Streptococcus Fibrinolysin.

There are marked differences in the susceptibilities of different samples of presumably normal human plasma-clot to the thrombolysin formed or secreted by certain strains of S. hemolyticus. While one clot may be completely liquefied within 30 minutes after admixture with a given lytic culture, the clot from a second, presumably normal individual may show no sign of softening even after 24-hours incubation with this culture.1To test the possibility that this difference may be due to quantitative differences in fibrin-content, parallel fibrinolytic titrations were made with different concentrations of the same isolated fibrin. Typical data thus obtained are recorded in Table I.From this table it is seen that the rate and completeness of fibrinolysis with a given lytic filtrate varies inversely with the fibrin-content. Complete insusceptibility to lysis, however, does not result from an increase in fibrin-content even to 4 times that of the average normal human plasma-clot. This result is in line with the st...
Leadership in Libraries: A Focus on Ethnic-Minority Librarians, by Maha Kumaran. Oxford: Chandos Publishing, 2012. 187 p. $80.00. ISBN-13: 978-1843346586

How does librarianship address the need for diverse leadership from a global perspective? In her book, Leadership in Libraries: A Focus on Ethnic-Minority Librarians, Maha Kumaran makes a commendab...
Gap junctions in rabbit corneal epithelium: limited permeability and inhibition by cAMP

Rabbit corneas were mounted in Ussing chambers, and the apical membrane of the superficial cells (SCs) was permeabilized by exposure to digitonin in a Ca(2+)-free Ringer solution. This treatment resulted in the generation of large (60.7 +/- 13.2 microA/cm2, n = 25) Na(+)-dependent tear (T)-to-stroma (S) short-circuit currents (Isc). The Isc was abolished by ouabain and by 1.4 mM Ca2+ and was inhibited by heptanol, 18 alpha-glycyrrhetinic acid, and dieldrin, effects consistent with the notion that corneal transepithelial fluxes include translocations through gap junctions (GJs) before basolateral membrane transport. T-to-S Isc were also generated when T-side Na+ was replaced by K+, eliciting a T-to-S K+ flux via basolateral K+ channels and when, with either Na+ or K+ on the T side, channels were introduced at the apical membrane with amphotericin B. The Isc in all four conditions exhibited similar sensitivity to GJ inhibitors and were inhibited by adenosine 3',5'-cyclic monophosphate (cAMP) elevation. Fluorophotometry combined with SC permeabilization with digitonin demonstrated that the half-time for the SC to sub-SC movement of 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (mol wt 540) exceeded 3 h. These results indicate that junctional communications along the epithelial stratification axis are highly restricted and modulated by cAMP concentration.
Management of Urinary Calculous Disease in Patients with Renal Cysts: Review of 12 Years of Experience in 18 Patients

During the last 12 years 18 patients with urinary calculi were found to have associated cystic renal disease. We herein describe the difficulties in diagnosing and in treating this group, which included patients with simple single renal cysts, multiple cysts of 1 or both kidneys and polycystic renal disease. Renal calculi may be caused by or perpetuated by renal cystic disease. After spontaneous passage or surgical removal renal calculi may recur as long as renal cysts continue to cause urinary stasis owing to obstruction and distortion of the renal calices. Superimposed renal infection may cause further difficulties in diagnosis and treatment. The timely removal of calculi and the relief of obstruction caused by the cysts and stones are emphasized. We further recommend the judicious use of antibiotics, correction of electrolyte disturbances and prolonged followup in an attempt to prevent future calculous disease.
Metrics on Fully Ranked Data

This chapter reviews, in part, an approach to permutation data presented in Diaconis’ monograph, Group Theory in Statistics [D2].
Evaluation of Fuel Benefits Depending on Continuous Descent Approach Procedures

In this work arrival traffic following a continuous descent approach profile into the Hartsfield-Jackson Atlanta International Airport was simulated based on actual recorded traffic data. The fuel ...
Frequency tolerance of RF micromechanical disk resonators in polysilicon and nanocrystalline diamond structural materials

A statistical evaluation of the absolute and matching tolerances of the resonance frequencies of surface-micromachined micromechanical 1-port disk resonators is conducted by fabricating and measuring a large quantity (>100) of devices in both polysilicon and nanocrystalline diamond structural materials. Through this analysis, respective average resonance frequency absolute and matching tolerances of 450 ppm and 343 ppm for polysilicon, and 756 ppm and 392 ppm for diamond, have been demonstrated on a measured set of 6 dies on 4-inch wafers fabricated using university facilities. The measured matching tolerance is sufficient to allow implementation of RF pre-select or image-reject filters for wireless communications with a confidence interval better than 99.7% over tested dies without the need for frequency trimming
Abstract 4519: Development of a whole body physiologically-based pharmacokinetic (PBPK) model with individualized tumor compartment for topotecan (TPT) in mice bearing neuroblastoma (NB)

Intratumoral pharmacokinetic (PK) and pharmacodynamic (PD) heterogeneity contribute to variability in NB tumor response to chemotherapy and can be responsible for tumor relapse. Herein we propose to develop a whole body PBPK model with an individualized tumor compartment to derive individual tumor specific concentration-time profiles for the NB standard of care drug TPT. This model can then relate intratumoral heterogeneity in tumor blood flow to PD response and antitumor effects. PK studies of TPT (0.6, 1.25, 5, and 20 mg/kg, IV bolus) will be performed in CD1 nude mice (n = 3 mice/time point) bearing orthotopic NB (NB5) xenograft. Blood samples will be collected at predetermined time points using cardiac puncture, and plasma separated and stored until analysis. Animals will be perfused using saline solution to remove residual blood, and tissue samples including tumor, muscle, adipose, bone, liver, gallbladder, kidney, spleen, lungs, brain, heart, duodenum, and large intestine collected. TPT concentrations in plasma and tissue homogenate samples will be quantified using a validated HPLC fluorescence spectrophotometry method. Tumor samples will be divided into two sections each, one for TPT quantification and one for immunohistochemistry of PD markers for DNA damage (γ-H2AX) and apoptosis (CASP3). A cohort of mice will be used to quantify tumor blood flow using contrast-enhanced ultrasound (CEUS) using MicroMarker® microbubbles prior to dosing the mice for the PK study. TPT plasma and tissue concentration-time data will be used to develop the whole-body PBPK model with an individualized tumor compartment using NONMEM. Individual tumor perfusion data obtained using CEUS will be combined with the PBPK model to derive tumor specific concentration-time profiles. A preliminary study conducted in non-tumor bearing mice receiving TPT 5 mg/kg showed that TPT plasma and tissue concentration-time data were reasonably described by our PBPK model. As expected from our previous studies, the brain tissue was found to have the lowest exposure to TPT with a brain to plasma partition coefficient (Kp,brain ∼ 8%). We also observed high permeability of TPT (Kp > 1) into the gallbladder, duodenum, large intestine, spleen, liver and kidney. In future we will study the correlations between individual tumor concentrations based on our comprehensive PBPK model and γ-H2AX and CASP3 activity. Citation Format: Yogesh T. Patel, Megan O. Jacus, Abbas Shirinifard, Abigail D. Davis, Suresh Thiagarajan, Stacy L. Throm, Vinay M. Daryani, Andras Sablauer, Clinton F. Stewart. Development of a whole body physiologically-based pharmacokinetic (PBPK) model with individualized tumor compartment for topotecan (TPT) in mice bearing neuroblastoma (NB). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4519. doi:10.1158/1538-7445.AM2015-4519
Cell biology: Healthy skin rejects cancer

Live imaging shows that healthy skin cells surround and expel neighbours that have cancer-promoting mutations, revealing that tissues can recognize and eliminate mutant cells to prevent tumour initiation. See Letter p.334 Cells acquire mutations frequently, but they rarely develop into macroscopic tumours. How the body deals with these defective cells is unclear. Valentina Greco, Slobodan Beronja and colleagues created transgenic mice with skin stem cells carrying genetic mutations known to induce tumour growth. Using intravital imaging, the researchers found that the expression of activated Wnt/β-catenin or oncogenic Hras results in outgrowths, which then regress. The deformation of skin tissue architecture is directly related to the regression of the outgrowths. The dismantling of aberrant structures containing mutant cells requires the activity of neighbouring wild-type cells. The mutant cells are either eliminated or integrated into functional skin appendages. Intriguingly, physical manipulation of the skin tissue architecture using laser tissue ablation is corrected in a similar fashion.
In Search of the “Vulnerable Plaque”: Can it Be Localized and Will Focal Regional Therapy Ever Be an Option for Cardiac Prevention?

The search to find the location of future plaque ruptures or plaque erosions leading to myocardial infarction (so-called “vulnerable plaques”) is an important area of cardiovascular research. Systemic therapy, including use of statins, targets the vulnerable patient. However, adverse events cannot be completely eliminated with the appropriate application of systemic therapies and thus has given rise to the possibility of local or regional therapy of “vulnerable plaques” to prevent future events. Until now, no criteria have been developed for consideration of this therapy. For such a strategy to work, there should be several prerequisites. These involve the identification of susceptible lesions, the number of lesions, their natural history, and proof that an interventional technique is preferable to medical therapy alone. The greatest deficiency relates to the fact that until the natural history of presumed “vulnerable plaques” is known one can never truly identify what constitutes a “vulnerable plaque.” Much work needs to be done in this area, but ongoing and new trials should provide important information that could potentially change drastically how coronary artery disease is diagnosed and treated.
A feasibility study on a low-cost, smartphone-based solution of pulse transit time measurement using cardio-mechanical signals

This paper presents a pilot study on a new method of measuring pulse transit time (PTT) using a commercial smartphone. An application based on an Android smartphone is developed to collect seismocardiogram (SCG) and gyrocardiogram (GCG) signals. The system is designed with a minimized amount of external sensors to reduce the total cost and complexity of the system. PTT measurements are calculated as a time difference between the fiducial points in photoplethysmography (PPG) recordings from a reference sensor module and SCG or GCG signals detected by the internal inertial sensors of a smartphone. A DSP system is designed and experimentally tested on five healthy subjects at rest. Our results suggest that the proposed solution could be a promising method to develop a low-cost, home-based PTT monitor.
Mitochondrial Voltage-Dependent Anion Channel Protein Por1 Positively Regulates the Nuclear Localization of Saccharomyces cerevisiae AMP-Activated Protein Kinase.

ABSTRACT Snf1 protein kinase of the yeast Saccharomyces cerevisiae is a member of the highly conserved eukaryotic AMP-activated protein kinase (AMPK) family, which is involved in regulating responses to energy limitation. Under conditions of carbon/energy stress, such as during glucose depletion, Snf1 is catalytically activated and enriched in the nucleus to regulate transcription. Snf1 catalytic activation requires phosphorylation of its conserved activation loop threonine (Thr210) by upstream kinases. Catalytic activation is also a prerequisite for Snf1’s subsequent nuclear enrichment, a process that is mediated by Gal83, one of three alternate β-subunits of the Snf1 kinase complex. We previously reported that the mitochondrial voltage-dependent anion channel (VDAC) proteins Por1 and Por2 play redundant roles in promoting Snf1 catalytic activation by Thr210 phosphorylation. Here, we show that the por1Δ mutation alone, which by itself does not affect Snf1 Thr210 phosphorylation, causes defects in Snf1 and Gal83 nuclear enrichment and Snf1’s ability to stimulate transcription. We present evidence that Por1 promotes Snf1 nuclear enrichment by promoting the nuclear enrichment of Gal83. Overexpression of Por2, which is not believed to have channel activity, can suppress the localization and transcription activation defects of the por1Δ mutant, suggesting that the regulatory role played by Por1 is separable from its channel function. Thus, our findings expand the positive roles of the yeast VDACs in carbon/energy stress signaling upstream of Snf1. Since AMPK/Snf1 and VDAC proteins are conserved in evolution, our findings in yeast may have implications for AMPK regulation in other eukaryotes, including humans. IMPORTANCE AMP-activated protein kinases (AMPKs) sense energy limitation and regulate transcription and metabolism in eukaryotes from yeast to humans. In mammals, AMPK responds to increased AMP-to-ATP or ADP-to-ATP ratios and is implicated in diabetes, heart disease, and cancer. Mitochondria produce ATP and are generally thought to downregulate AMPK. Indeed, some antidiabetic drugs activate AMPK by affecting mitochondrial respiration. ATP release from mitochondria is mediated by evolutionarily conserved proteins known as voltage-dependent anion channels (VDACs). One would therefore expect VDACs to serve as negative regulators of AMPK. However, our experiments in yeast reveal the existence of an opposite relationship. We previously showed that Saccharomyces cerevisiae VDACs Por1 and Por2 positively regulate AMPK/Snf1 catalytic activation. Here, we show that Por1 also plays an important role in promoting AMPK/Snf1 nuclear localization. Our counterintuitive findings could inform research in areas ranging from diabetes to cancer to fungal pathogenesis.
Low-dose x-ray tomography using photon-counting detector (Conference Presentation)

The radiation dosage delivered to the sample is a constant challenge facing X-ray imaging systems. In conventional transmission-based computed tomography (CT), a beam penetrating through thick, high-attenuation region in the sample results in low signal on the detector, and therefore a higher power (e.g., tube current modulation) or longer integration time is often required to maintain signal quality. The issue of radiation dose becomes more sever in coherent scattering X-ray tomography, in which the scattering signal is typically orders of magnitude weaker than the transmitted beam. With X-ray photon-counting detectors, transmitted (or scattered) X-ray photons can be acquired at extremely low photon flux, which enables us to greatly reduce the imaging time and dose administrated to the sample. Instead of counting the average the number of photons within a fixed time interval, the arrival times of only a few photons detected in sequence contain sufficient information to estimate the attenuation (or scattering) property, which allows object reconstruction based on our measurement geometry and noise model. We will also discuss compressive or adaptive data acquisition schemes to implement material identification utilizing the energy sensitivity of X-ray photon-counting detector. Our method can be further parallelized with a photon-counting detector array to achieve fast, low-dose X-ray tomographic imaging based on either attenuation or scattering signals, which could find broad applications in medical diagnosis and security screening.
Adequate Rust Resistance in Oats

For the past 60 years, the use of single genes for specific resistance has formed the basis for most conventional breeding programmes for oat stem rust improvement. While somewhat successful in keeping ahead of the rust pathogen the new resistant cultivars eventually had to be replaced after brief stints of production. Oat breeders, too, were plagued by a paucity of specific resistances to Puccinia graminis f.sp. avenae. In 1965 the super-virulent race 94 (NA-30) surfaced which was capable of attacking all the stem rust resistance genes then known in the cultivated oats in North America. Since that period new sources for stem rust resistance have been reported, many of which were transferred from the wild species of Avena to the cultivated species. Their exotic source of origin, however, does not necessarily assure a more prolonged existence in the cultivated oat if the appropriate race should evolve. One choice for the breeders, however, is to combine these new sources of resistance into various combinations.
Identifying clusters in spatial area data

A task peculiar to spatial data is to find spatial clusters. Three alternative tests will be given here for the case that a region is divided into a number of districts and each district is assigned a numerical value, i. e. the value for a variable of interest. A cluster of districts with high (or low) values cannot just be based on the adjacency of districts since then a random assignment would already produce too many and too large clusters. Thus the cluster definition is based on district triplets, essentially three districts meeting at a common corner. Two tests are designed for a division of the area into marked and unmarked districts. The third, more elaborate test uses the given values directly.
The Silence of God: A Literary Study of Voice and Violence in the Book of Revelation

The violence of Revelation remains problematic. This study offers a literary-critical analysis of the text with postcolonial theory and an intertextual foray into 1 Kgs 19. It argues that God does ...
Fucoidans inhibit the formation of post-operative abdominal adhesions in a rat model

Purpose Fibrin clot is essential for post-operative abdominal adhesion formation. Fucoidans, sulfated polysaccharides, inhibit fibrin clot formation. In addition, they inhibit inflammation and fibrosis, which also play important roles in adhesion formation. The purpose of this study was to evaluate fucoidans’ potential for inhibiting post-operative abdominal adhesions and measure their effects on systemic coagulation parameters when administered intraperitoneally (IP). Methods and materials Female Sprague Dawley rats were studied. A 2.5x2.5cm full thickness segment of abdominal wall was excised. The skin edges were approximated. This model induces extensive adhesions and allows objective quantitation. Three fucoidans were evaluated- Sigma Fucoidan Crude (SFC), Fucus vesiculosis 95% (Sigma) and, Peridan. One protocol involved continuous infusion into the abdomen from a subcutaneous osmotic pump. Alternatively, boluses of the solutions were injected IP at the end of the operation. Rats were sacrificed a week later. Adhesion extent was scored. Systemic coagulation effects of fucoidans were also evaluated. INR and aPTT were measured following IP injection of the fucoidan solutions and after 7 days of continuous infusion. Results Animals given a continuous infusion of either SFC or Peridan yielded adhesion reduction of 80 to 90% from control. Bolus Peridan had no discernable influence on adhesion formation, but a single bolus of SFC caused significant adhesion reductions. Peridan resulted in prompt aPTT elevations which fell to nearly normal by 5 hours. The maximum peak value after SFC injection was seen in 15 hours. The maximal INR elevations were around 2. Measurement of INR and aPTT after a week of continuous infusion of either Peridan or SFC, were always in the normal control range. The third agent, Sigma, frequently yielded intraperitoneal infection found at autopsy. Conclusions These findings indicate that selected fucoidans infused intraperitoneally for a week after abdominal operations reduce adhesion extent by up to 90%.
Intensity of Nosema ceranae infection is associated with specific honey bee gut bacteria and weakly associated with gut microbiome structure

The honey bee, Apis mellifera, pollinates a wide variety of essential crops in numerous ecosystems around the world but faces many modern challenges. Among these, the microsporidian pathogen Nosema ceranae is one of the primary detriments to honey bee health. Nosema infects the honey bee gut, which harbors a highly specific, coevolved microbiota heavily involved in bee immune function and nutrition. Here, we extend previous work investigating interactions between the honey bee gut microbiome and N. ceranae by studying experimentally infected bees that were returned to their colonies and sampled 5, 10, and 21 days post-infection. We measured Nosema load with quantitative PCR and characterized microbiota with 16S rRNA gene amplicon sequencing. We found significant colony level variation in infection levels, and subtle differences between the microbiota of colonies with high infection levels versus those with low infection levels. Two exact sequence variants of Gilliamella, a core gut symbiont that has previously been associated with gut dysbiosis, were significantly more abundant in bees from colonies with high Nosema loads versus those with low Nosema loads. These bacteria deserve further study to determine if they facilitate more intense infection by Nosema ceranae.
Changes in store for early-stage non-small cell lung cancer

The management of advanced non-small cell lung cancer (NSCLC) has been revolutionized in recent years with the introduction of biomarker-targeted molecular therapies and immune checkpoint inhibitors. In contrast, since adjuvant chemotherapy was first established twenty years ago as the standard of care, little has changed for resected early-stage (IB-IIIA) patients for whom the potential for cure is greatest. In this manuscript we will review recently presented data as well as ongoing/planned studies in this arena. So far, investigative efforts have yielded mixed results regarding the use of tyrosine kinase inhibitors (TKIs) in early-stage NSCLC, though a series of now better planned, biomarker-driven ongoing phase III trials may be more informative. Several innovative immunotherapy studies have already shown promising results principally in the neoadjuvant setting with a large number of pivotal neo-adjuvant and adjuvant trials now in progress. Given the more robust design and biomarker-focused approach of the new generation of studies, significant advances in the optimal curative treatment of early stage NSCLC are anticipated.
Unravelling Starlight: William and Margaret Huggins and the Rise of the New Astronomy

1. Introduction 2. '... the astronomer ... must come to the chemist' 3. The young observer 4. 'A sudden impulse ...' 5. The riddle of the nebulae 6. Moving in the inner circle 7. Stellar motion along the line of sight 8. A new telescope 9. Solar observatories 10. An able assistant 11. Photographing the solar corona 12. A scientific lady 13. Foes and allies 14. The new astronomy 15. 'One true mistress' 16. Conclusion Appendix Index.
Next-Generation Sequencing in 305 Consecutive Patients: Clinical Outcomes and Management Changes

PURPOSE:Next-generation sequencing (NGS) is increasingly used to identify actionable mutations for oncology treatment. We examined the results and use of NGS assays at our institution.PATIENTS AND ...
Infrared study of AlN films prepared by ion beam deposition. 1. Effects of film thickness, aging, and moisture

Specular reflectance FT-IR spectroscopy was employed to study the changes in the chemical composition of ion beam deposited AlN thin films as a function of film thickness, aging under air and vacuum, and exposure to liquid water. Aluminum nitride films 10, 20, and 40 nm thick were prepared by utilizing a pure aluminum metal target and both pure and 25% hydrogen enriched nitrogen. All films were deposited on gold substrates. It was found that the concentration of the Al-N{sub 2} species present in the AlN films strongly depends on the film thickness and on the gas mixture used for film fabrication. The authors also observed that the AlN films fabricated with pure N{sub 2} plasma are less prone to hydrolysis (when exposed to room air) than are the films prepared with H{sub 2}-N{sub 2} plasma. Prolonged vacuum environment had no significant effect on the spectra of the differently prepared AlN films. Exposure to liquid water promoted hydrolysis equally well in N{sub 2} and H{sub 2}-N{sub 2} fabricated AlN films.
Magnesium sulfate inhibits inflammation through P2X7 receptors in human umbilical vein endothelial cells

Magnesium sulfate (MgSO4) is utilized for fetal neuroprotection in preterm birth but its mechanism of action is still poorly understood. P2X7 receptor (P2X7R) is required for secretion of IL-1β, and can be blocked by divalent cations such as magnesium (Mg) and its own antagonist, Brilliant Blue G (BBG). We sought to determine whether during inflammation MgSO4 can block endothelial IL-1β secretion, using an in-vitro model. Human umbilical vein endothelial cell (HUVEC) cultures were treated with varying doses of LPS, 2′(3)-Ο-(4-Benzoylbenzoyl) adenosine-5′-triphosphate (BzATP), BBG and MgSO4 for 3- or 24 h. We determined cell cytotoxicity, apoptosis, IL-1β mRNA expression, IL-1β production and secretion and P2X7R expression on HUVECs. We demonstrated that MgSO4 is efficacious in blocking IL-1β-mediated-inflammation in HUVECs, at both the initiation and propagation phases of inflammation. MgSO4 exerts these anti-inflammatory effects via downregulation of P2X7Rs on HUVECs. LPS-exposure increases IL-1β production and secretion in HUVECs, which is further intensified by P2X7R agonist, BzATP while MgSO4 inhibits IL-1β in both presence and absence of BzATP. This effect is similar to the results of P2X7R antagonist, BBG, suggesting that the anti-inflammatory effects of MgSO4 is through P2X7R.
Do oncology researchers adhere to reproducible and transparent principles? A cross-sectional survey of published oncology literature

Objectives As much as 50%–90% of research is estimated to be irreproducible, costing upwards of $28 billion in USA alone. Reproducible research practices are essential to improving the reproducibility and transparency of biomedical research, such as including preregistering studies, publishing a protocol, making research data and metadata publicly available, and publishing in open access journals. Here we report an investigation of key reproducible or transparent research practices in the published oncology literature. Design We performed a cross-sectional analysis of a random sample of 300 oncology publications published from 2014 to 2018. We extracted key reproducibility and transparency characteristics in a duplicative fashion by blinded investigators using a pilot tested Google Form. Primary outcome measures The primary outcome of this investigation is the frequency of key reproducible or transparent research practices followed in published biomedical and clinical oncology literature. Results Of the 300 publications randomly sampled, 296 were analysed for reproducibility characteristics. Of these 296 publications, 194 contained empirical data that could be analysed for reproducible and transparent research practices. Raw data were available for nine studies (4.6%). Five publications (2.6%) provided a protocol. Despite our sample including 15 clinical trials and 7 systematic reviews/meta-analyses, only 7 included a preregistration statement. Less than 25% (65/194) of publications provided an author conflict of interest statement. Conclusion We found that key reproducibility and transparency characteristics were absent from a random sample of published oncology publications. We recommend required preregistration for all eligible trials and systematic reviews, published protocols for all manuscripts, and deposition of raw data and metadata in public repositories.
Framework for Measuring the Impact of C4ISR Technologies and Concepts on Warfighter Effectiveness Using High Resolution Simulation

Abstract : A C4ISR architecture for future forces is a major concern to the Army. This report describes progress of an on-going project to develop a framework for assessing individual communication technologies and concepts by accounting for technological and operational detail. Assessments of communication performance (e.g., message delay and message completion rate) factor terrain, mobility, and other scenario specific details via high-resolution simulations. For such measurements, excessive run-times can be a problem. This is usually the case for high-resolution simulation of communication networks. However, in this paper, it is shown that high-resolution communication network simulation runs (using Qualnet(copyrighted), although time consuming, can be used to capture the dynamics of communication performance in closed form expressions or meta-models. The meta-models can then be embedded into force-on-force simulation (JANUS) to get perhaps the most important performance measure, e.g., warfighter effectiveness. This forms a framework that supports detailed, scenario specific examination of the impact of C4ISR on warfighter effectiveness.
Cerebrovascular Complications in Patients with Cancer

The hypercoagulable state associated with cancer, known since the descriptions of Trousseau in the nineteenth century, has become a well-recognized cause of venous thromboembolism. It has only more recently become apparent that cancer increases the risk of arterial thromboembolism as well. In patients with cancer, cerebrovascular disease is the second leading cause of lesions of the central nervous system (CNS), only behind metastases (Graus F, Rogers LR, Posner, JB, Medicine 64:16–35, 1985). The most frequent cause of cerebrovascular disease in this population is stroke, both ischemic and hemorrhagic; this chapter will focus primarily on these entities. While patients with cancer remain at risk for conventional mechanisms of cerebrovascular disease, cancer patients have unique risk factors including complications of coagulation disorders, direct tumor effects, toxicity of cancer treatment, and increased risk of infection in the setting of immunosuppression. These features make this population distinct from the general population and should be considered carefully during their evaluation and care.