cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification and characterization of high affinity antisense PNAs for the human unr (upstream of N-ras) mRNA which is uniquely overexpressed in MCF-7 breast cancer cells

We have recently shown that an MCF-7 tumor can be imaged in a mouse by PET with 64Cu-labeled Peptide nucleic acids (PNAs) tethered to the permeation peptide Lys4 that recognize the uniquely overexpressed and very abundant upstream of N-ras or N-ras related gene (unr mRNA) expressed in these cells. Herein we describe how the high affinity antisense PNAs to the unr mRNA were identified and characterized. First, antisense binding sites on the unr mRNA were mapped by an reverse transcriptase random oligonucleotide library (RT-ROL) method that we have improved, and by a serial analysis of antisense binding sites (SAABS) method that we have developed which is similar to another recently described method. The relative binding affinities of oligodeoxynucleotides (ODNs) complementary to the antisense binding sites were then qualitatively ranked by a new Dynabead-based dot blot assay. Dissociation constants for a subset of the ODNs were determined by a new Dynabead-based solution assay and were found to be 300 pM for the best binders in 1 M salt. PNAs corresponding to the ODNs with the highest affinities were synthesized with an N-terminal CysTyr and C-terminal Lys4 sequence. Dissociation constants of these hybrid PNAs were determined by the Dynabead-based solution assay to be about 10 pM for the highest affinity binders.
Pleistocene Extinction of Genyornis newtoni: Human Impact on Australian Megafauna

More than 85 percent of Australian terrestrial genera with a body mass exceeding 44 kilograms became extinct in the Late Pleistocene. Although most were marsupials, the list includes the large, flightless mihirung Genyornis newtoni. More than 700 dates onGenyornis eggshells from three different climate regions document the continuous presence of Genyornis from more than 100,000 years ago until their sudden disappearance 50,000 years ago, about the same time that humans arrived in Australia. Simultaneous extinction of Genyornis at all sites during an interval of modest climate change implies that human impact, not climate, was responsible.
Attendees' needs and service priorities in a large convention center: application of the importance-performance theory.

Abstract The study identified attendees’ needs and service priorities when attending an exhibition at a large convention center. Data was collected using self-administered questionnaires from 566 subjects attending five different exhibitions. The results indicated that overall cleanliness of the convention center, a well-maintained facility, and helpfulness of guest services personnel were top priorities for attendees regarding the convention center's facility services. Attendees also attributed high importance to the following features of the convention facility: directional signage within the convention center, availability of high quality lodging near the convention center, sufficient restrooms throughout the facility, and ability to get cell phone signal. Furthermore, statistically significant differences were found between the level of importance and performance of the majority of the facility services and features of the convention center. Implications for decision makers regarding these importance–performance gaps are discussed.
Titanium diffusion in gold thin films

Abstract In the present study, diffusion phenomena in titanium/gold (Ti/Au) thin films occurring at temperatures ranging between 200 and 400 °C are investigated. The motivation is twofold: the first objective is to characterize Ti diffusion into Au layer as an effect of different heat-treatments. The second goal is to prove that the implementation of a thin titanium nitride (TiN) layer between Ti and Au can remarkably reduce Ti diffusion. It is observed that Ti atoms can fully diffuse through polycrystalline Au thin films (260 nm thick) already at temperatures as a low as 250 °C. Starting from secondary ion mass spectroscopy data, the overall diffusion activation energy ΔE = 0.66 eV and the corresponding pre-exponential factor D0 = 5 × 10− 11 cm2/s are determined. As for the grain boundary diffusivity, both the activation energy range 0.54
Bioenergy crop greenhouse gas mitigation potential under a range of management practices

Perennial grasses have been proposed as viable bioenergy crops because of their potential to yield harvestable biomass on marginal lands annually without displacing food and to contribute to greenhouse gas (GHG) reduction by storing carbon in soil. Switchgrass, miscanthus, and restored native prairie are among the crops being considered in the corn and agricultural regions of the Midwest and eastern United States. In this study, we used an extensive dataset of site observations for each of these crops to evaluate and improve the DayCent biogeochemical model and make predictions about how both yield and GHG fluxes would respond to different management practices compared to a traditional corn-soy rotation. Using this model-data integration approach, we found 30–75% improvement in our predictions over previous studies and a subsequent evaluation with a synthesis of sites across the region revealed good model-data agreement of harvested yields (r 2 > 0.62 for all crops). We found that replacement of corn-soy rotations would result in a net GHG reduction of 0.5, 1.0, and 2.0 Mg C ha 1 yr 1 with average annual yields of 3.6, 9.2, and 17.2 Mg of dry biomass per year for native prairie, switchgrass, and miscanthus respectively. Both the yield and GHG balance of switchgrass and miscanthus were affected by harvest date with highest yields occurring near onset of senescence and highest GHG reductions occurring in early spring before the new crops emergence. Addition of a moderate length rotation (10–15 years) caused less than a 15% change to yield and GHG balance. For policy incentives aimed at GHG reduction through onsite management practices and improvement of soil quality, post-senescence harvests are a more effective means than maximizing yield potential.
Hrs Interacts with Sorting Nexin 1 and Regulates Degradation of Epidermal Growth Factor Receptor

Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a mammalian homologue of yeast vacuolar protein sorting (Vps) protein Vps27p; however, the role of Hrs in lysosomal trafficking is unclear. Here, we report that Hrs interacts with sorting nexin 1 (SNX1), a recently identified mammalian homologue of yeast Vps5p that recognizes the lysosomal targeting code of epidermal growth factor receptor (EGFR) and participates in lysosomal trafficking of the receptor. Biochemical analyses demonstrate that Hrs and SNX1 are ubiquitous proteins that exist in both cytosolic and membrane-associated pools, and that the association of Hrs and SNX occurs on cellular membranes but not in the cytosol. Furthermore, endogenous SNX1 and Hrs form a ∼550-kDa complex that excludes EGFR. Immunofluorescence and subcellular fractionation studies show that Hrs and SNX1 colocalize on early endosomes. By using deletion analysis, we have mapped the binding domains of Hrs and SNX1 that mediate their association. Overexpression of Hrs or its SNX1-binding domain inhibits ligand-induced degradation of EGFR, but does not affect either constitutive or ligand-induced receptor-mediated endocytosis. These results suggest that Hrs may regulate lysosomal trafficking through its interaction with SNX1.
Seasonality of trichomycetes in larval black flies from South Carolina, USA

Trichomycete fungi are common endobionts of aquatic insect larvae, but little is known of their ecology. In this study, the seasonality of trichomycete colonization of larval black flies (Diptera: Simuliidae) was investigated in three streams in northwestern South Carolina. At least eight species of trichomycetes were found in two species of black flies, and 93.8% of 1819 larval black flies examined contained trichomycetes. Significant differences were found in the seasonal prevalence of Harpella melusinae, Simuliomyces microsporus, and Paramoebidium spp. at one of three sites. At this site, the lowest mean prevalence for H. melusinae occurred in winter (67%) versus the other seasons (96-100%), whereas mean prevalence was lowest in summer for Simuliomyces microsporus (1%) versus the other seasons (2-21%) and lowest in summer for P. spp. (9%) versus the other seasons (45-67%). Significant differences in levels of colonization among seasons were not detected. Conjugations of H. melusinae (representing early stages of sexual reproduction) occurred most frequently in the spring and winter (up to 14% of larvae). Sexual reproduction (represented by zygospores) of Legeriomycetaceae occurred most frequently in the spring and fall (up to 17% of larvae).
Designing simulation experiments

Much effort goes into building and validating simulation models. Similar care is necessary in the use of the model to support decision making. Good simulation experiment design is important to get useful and valid insights for specific management questions. This introductory tutorial gives an overview of experiment design techniques for justifying and planning a series of simulation runs to uncover the impact of system design parameters on simulation output performance. Graphical methods are emphasized.
Floating-point division and square root implementation using a Taylor-series expansion algorithm

Hardware support for floating-point (FP) arithmetic is an essential feature of modern microprocessor design. Although division and square root are relatively infrequent operations in traditional general-purpose applications, they are indispensable and becoming increasingly important in many modern applications. In this paper, a fused floating-point multiply/divide/square root unit based on Taylor-series expansion algorithm is presented. The implementation results of the proposed fused unit based on standard cell methodology in IBM 90 nm technology exhibits that the incorporation of square root function to an existing multiply/divide unit requires only a modest 23% area increase and the same low latency for divide and square root operation can be achieved (12 cycles). The proposed arithmetic unit also exhibits a reasonably good area-performance balance.
Clinical Manifestations of α-Thalassemia

α-Thalassemia mutations affect up to 5% of the world’s population. The clinical spectrum ranges from an asymptomatic condition to a fatal in utero disease. Hemoglobin H disease results from mutations of three α-globin genes. Deletional forms result in a relatively mild anemia, whereas nondeletional mutations result in a moderate to severe disease characterized by ineffective erythropoiesis, recurrent transfusions, and growth delay. Hemosiderosis develops secondary to increased iron absorption, as well as transfusion burden. Hemoglobin Bart’s hydrops fetalis is usually a fatal in utero disease caused by the absence of α genes. Population screening to identify at-risk couples is essential. Affected pregnancies result in severe fetal and maternal complications. Doppler ultrasonography with intrauterine transfusion therapy may improve the fetal prognosis but creates ethical challenges for the family and health providers.
Gemifloxacin-Associated Neurotoxicity Presenting as Encephalopathy

Objective:To report a case of acute encephalopathy associated with ingestion of gemifloxacin, a fluoroquinolone.Case Summary:A 67-year-old woman presented to the emergency department with an acute alteration in mental status. Twenty-four hours earlier she had taken one 320-mg tablet of her husband's gemifloxacirt prescription to treat symptoms of a mild upper respiratory infection. During her initial evaluation at our institution, the woman was dysphasia, unable to follow commands, and agitated, suggesting encephalopathy. A thorough diagnostic investigation did not reveal any structural, metabolic, or infectious etiology. Her mental status returned to normal within 2 days without any definitive treatment.Discussion:Fluoroquinolone-associated neurotoxicity may manifest as encephalopathy, seizures, confusion, or toxic psychosis. To date, none of these adverse effects, specifically encephalopathy, has been reported with gemifloxacin. An objective causality assessment revealed that encephalopathy was probably...
Engagement and institutional advancement

The Carnegie data offer important information about how institutions allocate funding for engagement and develop marketing and fundraising campaigns to support engagement activities.
Adaptive IIR filtering

An overview is presented of several methods, filter structures, and recursive algorithms used in adaptive infinite-impulse response (IIR) filtering. Both the equation-error and output-error formulations are described, although the focus is on the adaptive algorithms and properties of the output-error configuration. These parameter-update algorithms have the same generic form, and they are based on a prediction-error performance criterion. A direct-form implementation of the adaptive filters is emphasized, but alternative realizations such as the parallel and lattice forms are briefly discussed. Several important issues associated with adaptive IIR filtering, including stability monitoring, the SPR condition, and convergence, are addressed. >
Clocked molecular quantum-dot cellular automata

Quantum-dot cellular automata (QCA) is an approach to computing that eliminates the need for current switches by representing binary information as the configuration of charge among quantum dots. For molecular QCA, redox sites of molecules serve as the quantum dots. The Coulomb interaction between neighboring molecules provides device-device coupling. By introducing clocked control of the QCA cell, power gain, reduced power dissipation, and computational pipelining can be achieved. We present an ab initio analysis of a simple molecular system, which acts as a clocked molecular QCA cell. The intrinsic bistability of the molecular charge configuration results in dipole or quadrupole fields that couple strongly to the state of neighboring molecules. We show how clocked control of the molecular QCA can be accomplished with a local electric field.
First Class Patterns

Pattern matching is a great convenience in programming. However, pattern matching has its problems: it conflicts with data abstraction; it is complex (at least in Haskell, which has pattern guards, irrefutable patterns, n+k patterns, as patterns, etc.); it is a source of runtime errors; and lastly, one cannot abstract over patterns as they are not a first class language construct. This paper proposes a simplification of pattern matching that makes patterns first class. The key idea is to treat patterns as functions of type "a→ Maybe b"--i.e., "a→ (Nothing|Just b)"; thus, patterns and pattern combinators can be written as functions in the language.
Acetyl-CoA Synthetase from the Amitochondriate EukaryoteGiardia lamblia Belongs to the Newly Recognized Superfamily of Acyl-CoA Synthetases (Nucleoside Diphosphate-forming)

The gene coding for the acetyl-CoA synthetase (ADP-forming) from the amitochondriate eukaryote Giardia lamblia has been expressed in Escherichia coli. The recombinant enzyme exhibited the same substrate specificity as the native enzyme, utilizing acetyl-CoA and adenine nucleotides as preferred substrates and less efficiently, propionyl- and succinyl-CoA. N- and C-terminal parts of the G. lamblia acetyl-CoA synthetase sequence were found to be homologous to the α- and β-subunits, respectively, of succinyl-CoA synthetase. Sequence analysis of homologous enzymes from various bacteria, archaea, and the eukaryote, Plasmodium falciparum, identified conserved features in their organization, which allowed us to delineate a new superfamily of acyl-CoA synthetases (nucleoside diphosphate-forming) and its signature motifs. The representatives of this new superfamily of thiokinases vary in their domain arrangement, some consisting of separate α- and β-subunits and others comprising fusion proteins in α-β or β-α orientation. The presence of homologs of acetyl-CoA synthetase (ADP-forming) in such human pathogens as G. lamblia, Yersinia pestis, Bordetella pertussis,Pseudomonas aeruginosa, Vibrio cholerae,Salmonella typhi, Porphyromonas gingivalis, and the malaria agent P. falciparum suggests that they might be used as potential drug targets.
Ecological Speciation: Crossing the Divide

The magnitude of niche shifts associated with ecological speciation and the factors that regulate the process are poorly understood. I propose that ecological transitions most often involve the invasion of habitats most accessible through seed dispersion and by relatively small genetic changes. A significant seed rain is required for the recruitment of chance variants that are somewhat adapted to the novel conditions, as well as for the expansion of the genetic repertoire necessary for the evolution of a well-adapted entity. The probability of exploiting a new niche is an inverse function of the amount of genetic change that is required. Genes with large effect facilitate the change. There is considerable evidence that substantial habitat and pollinator niche shifts may occur with relatively few gene changes. There is speculation that populations may establish in new habitats through adaptive developmental and physiological changes induced by the environment, and then undergo genetic changes that stabilize the new phenotypes. Hybridization provides an unusual opportunity for major ecological change over a relatively short time span.
A new species of Passadenoides Neunzig from Wyoming and New Mexico (Lepidoptera: Pyralidae: Phycitinae)

A new phycitine species, Passadenoides montanus, is described from specimens collected in Albany Co., Wyoming and Grant Co., New Mexico. The adults and male and female genitalia are illustrated.
Positive and negative mood effects on solving a resource dilemma

A resource dilemma is a situation in which maximizing individual profits contradicts the conservation of a resource. How do people solve a resource dilemma if they are in positive or negative mood? There are some models which offer different explanations and predict different outcomes: (1) the cognitive capacity explanation expects that people in negative mood are hampered in performing a cognitive task because their cognitive capacity is reduced by thinking about their emotional state; (2) the mood repair explanation assumes that people in negative mood overexploit the resource to improve their mood; (3) the motivational explanation claims two different strategies depending on mood state. The hypotheses derived from the three models were tested in two experiments. The results lend some support to the motivational explanation.
Relationship between Native-State Solubility and Non-Native Aggregation of Recombinant Human Granulocyte Colony Stimulating Factor: Practical Implications for Protein Therapeutic Development

Prescreening methods are needed in the biotechnology industry for rapid selection of protein therapeutic candidates and formulations of low aggregation propensity. In recent reports solubility measurements have shown promise as one such method, although the connection between protein solubility and non-native aggregation is not well understood. In the present investigation, recombinant human granulocyte colony stimulating factor (rhGCSF) was used to explore this relationship since it was previously shown to rapidly undergo non-native aggregation/precipitation under physiological conditions in a reaction attenuated by the addition of sucrose [Krishnan, S.; et al. Biochemistry 2002, 41, 6422–6431]. Strong correlations were found between rhGCSF non-native aggregation and both solubility and thermal stability as a function of sucrose concentration. We believe these results make sense in the context of an rhGCSF aggregation mechanism where loss of monomer to insoluble aggregate is limited by association to an ...
Ion-Surface Interactions During Epitaxy

Recent work on low-energy ion-assisted deposition of epitaxial films is reviewed. Much of the interest in this area has centered on the use of very low ion energies (≈ 25 eV) and high fluxes (> 1 ion per deposited atom) obtained using novel ion-assisted deposition techniques. These methods have been applied in ultra-high vacuum, allowing the preparation of high-purity semiconductor materials. The following ion-surface interaction effects during epitaxy are discussed: improvements in crystalline perfection during low temperature epitaxy, ion damage effects, improved homogeneity and properties in III-V alloys grown within miscibility gaps, and changes in nucleation mechanism from Stranski-Krastanov to layer-by-layer.
A global perspective on the topographic response to fault growth

Precise factors controlling the coevolution of deformation and topography in tectonically active landscapes remain poorly understood due to complex feedbacks between numerous possible variables. Here we examine the links between fault kinematics, emergent topography, and environmental factors on a global data set of active fault-driven mountain ranges (n = 41). Using simple regressions between tectonic, climatic, and topographic variables, we explore the controls on fault-driven landscape development at the range scale. For each fault in our Google Earth accessible database, we compiled (1) topographic metrics from a 30-m digital elevation model including along-strike changes in elevation and relief, fault length, and tip zone length (the along-strike distance from fault tip to where the associated relief stops increasing) and gradient; (2) long-term (10 4–6 yr) tectonic variables including fault slip rate, displacement rate, displacement, and age; (3) climatic variables including annual precipitation; and (4) rock type from geologic maps. Our results show that all mountain ranges reach a uniform value of relief within some distance from their tips and the length scale of this relief growth correlates with long-term vertical displacement rate (R = 0.55) and slip rate (R = 0.51). We apply a well-established framework for fault growth as the tectonic boundary condition to estimate the time required to achieve this uniform relief (∼10 4–6 yr) and suggest that this threshold time indicates regional tectonomorphic equilibrium. Strong correlations between annual precipitation and deformation rates (R > 0.60), and between lithologic strength and mountain relief (R > 0.70), allude to other principal forces affecting emergent landscape form that are often ignored. Our findings demonstrate that fault-driven topography always saturates in relief, suggest there are quantifiable fault-kinematic controls on landscape form, and hint that landscape relief patterns may, in turn, be used to estimate rates of faulting.
Magnitude and duration of cue-induced craving for marijuana in volunteers with cannabis use disorder.

Abstract Aims Evaluate magnitude and duration of subjective and physiologic responses to neutral and marijuana (MJ)–related cues in cannabis dependent volunteers. Methods 33 volunteers (17 male) who met DSM-IV criteria for Cannabis Abuse or Dependence were exposed to neutral (first) then MJ-related visual, auditory, olfactory and tactile cues. Mood, drug craving and physiology were assessed at baseline, post-neutral, post-MJ and 15-min post MJ cue exposure to determine magnitude of cue- responses. For a subset of participants (n = 15; 9 male), measures of craving and physiology were collected also at 30-, 90-, and 150-min post-MJ cue to examine duration of cue-effects. Results In cue-response magnitude analyses, visual analog scale (VAS) items craving for, urge to use, and desire to smoke MJ, Total and Compulsivity subscale scores of the Marijuana Craving Questionnaire, anxiety ratings, and diastolic blood pressure (BP) were significantly elevated following MJ vs. neutral cue exposure. In cue-response duration analyses, desire and urge to use MJ remained significantly elevated at 30-, 90- and 150-min post MJ-cue exposure, relative to baseline and neutral cues. Conclusions Presentation of polysensory MJ cues increased MJ craving, anxiety and diastolic BP relative to baseline and neutral cues. MJ craving remained elevated up to 150-min after MJ cue presentation. This finding confirms that carry-over effects from drug cue presentation must be considered in cue reactivity studies.
Factors affecting the development of speech recognition in steady and modulated noise.

This study used a checkerboard-masking paradigm to investigate the development of the speech reception threshold (SRT) for monosyllabic words in synchronously and asynchronously modulated noise. In asynchronous modulation, masker frequencies below 1300 Hz were gated off when frequencies above 1300 Hz were gated on, and vice versa. The goals of the study were to examine development of the ability to use asynchronous spectro-temporal cues for speech recognition and to assess factors related to speech frequency region and audible speech bandwidth. A speech-shaped noise masker was steady or was modulated synchronously or asynchronously across frequency. Target words were presented to 5–7 year old children or to adults. Overall, children showed higher SRTs and smaller masking release than adults. Consideration of the present results along with previous findings supports the idea that children can have particularly poor masked SRTs when the speech and masker spectra differ substantially, and that this may arise...
Predictors of independence in instrumental activities of daily living: Amnestic versus nonamnestic MCI

ABSTRACTIntroduction: Individuals with mild cognitive impairment (MCI) demonstrate deficits in instrumental activities of daily living (IADL) that place them at high risk for progression to dementia. The cognitive profiles, IADL deficits, and risk of progression differ between MCI subgroups of amnestic (aMCI) and nonamnestic MCI (naMCI), though many studies of functional impairment have not examined these subgroups separately. This study aims to determine whether common neuropsychological measures, as well as the related concept of patient anosognosia, are associated with IADL functioning differently in aMCI compared to naMCI. Method: Seventy-one individuals were identified as naMCI, and 99 individuals were identified as aMCI based on neuropsychological evaluation. Controlling for age, gender, and education, we examined whether performance on neuropsychological tests predicted informant-rated IADL dysfunction. We also investigated the ability of patient awareness, as rated by clinicians and informants, to...
Water Resources Management in the Lerma-Chapala Basin, Mexico : A Case Study

Water resources have become an increasingly important topic of discussion in natural resources and environmental management courses. To address the need for more critical thinking in the classroom and to provide an active learning experience for undergraduate students, we present a case study based on water competition and manage- ment in the Lerma-Chapala basin of Mexico. This case was designed to promote critical thinking and enhance learning in undergraduate students through their engagement in a relevant contemporary management issue. We discuss the value of a case-study approach for natural resource and environmental courses, as well as approaches to using this case study in the classroom. The case study contains background information and stakeholder profiles relevant to the issue of water management in the Lerma-Chapala basin. It also provides sample discussion questions to help inspire higher-level think- ing among students.
Turbulence model verification and validation in an open source environment

In this paper, the verification of two low-Reynolds-number turbulence models in an open source environment is reported. The two models are the Spalart-Allmaras model without the ft2 term and the k – ω SST model using vorticity in production estimation. Grid convergence is achieved in all verification cases, while reasonable agreements with other codes are found. The two turbulence models are also validated through comparison with some well-known validation cases, the results of which show good agreement with experimental data. The differences between the results obtained from incompressible and compressible codes are also discussed. The impact of wall distance estimation on the performance of turbulence modelling is also evaluated through grid convergence studies. Within the realm of search algorithms for wall distance estimation, a three-level search approach is found to be necessary in order to achieve correct and converged results, especially for skewed meshes. It is shown, through a 2D bump flow grid convergence study, that the use of a one-level search approach can not only lead to a maximum friction coefficient deviation of 3.8%, but also cause an inconsistent convergence behaviour.
The influence of interpregnancy interval on infant mortality.

Background In Ohio, the infant mortality rate is above the national average and the black infant mortality rate is more than twice the white infant mortality rate. Having a short interpregnancy interval has been shown to correlate with preterm birth and low birthweight, but the effect of short interpregnancy interval on infant mortality is less well established. Objective We sought to quantify the population impact of interpregnancy interval on the risk of infant mortality. Study Design This was a statewide population-based retrospective cohort study of all births (n = 1,131,070) and infant mortalities (n = 8152) using linked Ohio birth and infant death records from January 2007 through September 2014. For this study we analyzed 5 interpregnancy interval categories: 0- Results Short interpregnancy intervals were common in Ohio during the study period. Of all multiparous births, 20.5% followed an interval of P Conclusion An interpregnancy interval of 12-60 months (1-5 years) between birth and conception of next pregnancy is associated with lowest risk of infant mortality. Public health initiatives and provider counseling to optimize birth spacing has the potential to significantly reduce infant mortality for both white and black mothers.
A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling

The development of small-molecule fluorescent probes through addition of a lipidated cysteine residue next to a caged fluorophore enables detection of endogenous cysteine depalmitoylation by acyl–protein thioesterases in vitro and in live cells.
Endoplasmic Reticulum Stress Modulation as a Target for Ameliorating Effects of Blast Induced Traumatic Brain Injury

Blast traumatic brain injury (bTBI) has been shown to contribute to progressive neurodegenerative disease. Recent evidence suggests that endoplasmic reticulum (ER) stress is a mechanistic link between acute neurotrauma and progressive tauopathy. We propose that ER stress contributes to extensive behavioral changes associated with a chronic traumatic encephalopathy (CTE)-like phenotype. Targeting ER stress is a promising option for the treatment of neurotrauma-related neurodegeneration, which warrants investigation. Utilizing our validated and clinically relevant Sprague-Dawley blast model, we investigated a time course of mechanistic changes that occur following bTBI (50 psi) including: ER stress activation, iron-mediated toxicity, and tauopathy via Western blot and immunohistochemistry. These changes were associated with behavioral alterations measured by the Elevated Plus Maze (EPM), Forced Swim Test (FST), and Morris Water Maze (MWM). Following characterization, salubrinal, an ER stress modulator, was given at a concentration of 1 mg/kg post-blast, and its mechanism of action was determined in vitro. bTBI significantly increased markers of injury in the cortex of the left hemisphere: p-PERK and p-eIF2α at 30 min, p-T205 tau at 6 h, and iron at 24 h. bTBI animals spent more time immobile on the FST at 72 h and more time in the open arm of the EPM at 7 days. Further, bTBI caused a significant learning disruption measured with MWM at 21 days post-blast, with persistent tau changes. Salubrinal successfully reduced ER stress markers in vivo and in vitro while significantly improving performance on the EPM. bTBI causes robust biochemical changes that contribute to neurodegeneration, but these changes may be targeted with ER stress modulators.
A Review of the Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitors: A Focus on Diabetic Ketoacidosis.

Diabetes is a complex, chronic medical condition affecting 29.1 million people in the United States (9.3% of the population) and is projected to affect one in three Americans by 2050 if the current trend continues (1). Diabetes management can be challenging, often requiring multiple therapeutic agents as the disease progresses. Current guidelines recommend metformin as first-line pharmacological therapy for the treatment of type 2 diabetes. Multiple second-line options are available for patients whose A1C goal is not achieved with monotherapy, and selection should be based on patient- and drug-specific factors. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, the newest U.S. Food and Drug Administration (FDA)–approved oral antidiabetic agents, are among these options for patients with type 2 diabetes. Canagliflozin, dapagliflozin, and empagliflozin are the currently available SGLT2 inhibitors in the United States (2,3). Sodium–glucose cotransporter 1 (SGLT1) is predominantly located in the small intestine, but is also expressed in the kidneys, trachea, heart, and colon (4,5). In the kidneys, SGLT1 is primarily located in the S3 segment of the proximal convoluted tubule (PCT) (4). SGLT2 is expressed in the kidneys and primarily located in the S1 and S2 segments of the PCT (4,5). In normoglycemic adults, about 180 g of glucose (Figure 1) is filtered per day in the glomerulus, and most is reabsorbed (4,6). In people with diabetes, reabsorption of glucose is increased compared to people without diabetes (7,8). SGLT1 and SGLT2 are located in the apical membrane and facilitate the transport of glucose with sodium from the renal tubular lumen into the cells (Figure 2) (4). FIGURE 1. Structures of glucose, phlorizin, canagliflozin, dapagliflozin, and empagliflozin. FIGURE 2. Cotransport of glucose and sodium by SGLT1 and SGLT2 in the PCT. Phlorizin (Figure 1), an O -glucose derivative/ O -glycoside, was discovered in …
Co-Ranking Authors in Heterogeneous News Networks

Expert Finding has been a widely studied area of research. However, most of the work in this area has focused solely on analyzing networks representing people in academia. In this work, we will present an approach for two types of heterogeneous news sources (i.e., Traditional Network Sources (TNS) and Policy Network Sources (PNS)) for experts on a set of topics. Our overall objective is to discover who are the expert journalists and policy analysts on specific topics. This work is based on our intuition that the PNS and TNS could complement each other, thus leveraging information for the learning task. We propose a probabilistic generative model named Context-based Latent Dirichlet Allocation (CBLDA) that performs the task of co-ranking authors in the heterogeneous networks of TNS and PNS. We will demonstrate that our proposed approach outperforms baselines in terms of precision, mean average precision, and discounted cumulative gain.
The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA expressions, which could target the 3'-UTR of Ccr6 mRNA for decay. Accordingly, knock-out of HuR reduced CCR6 expression on Th17 cells and impaired their migration to CNS compared with the response of WT Th17 cells and thereby ameliorated EAE. Together, these findings highlight how HuR contributes to Th17 cell-mediated autoimmune neuroinflammation and support the notion that targeting HuR might be a potential therapeutic intervention for managing autoimmune disorders of the CNS.
Lacrimal Gland Repair after Short-term Obstruction of Excretory Duct in Rabbits

Aqueous tear-deficient dry eye is a multifactorial chronic disorder in which the lacrimal glands fail to produce enough tears to maintain a healthy ocular surface. The existence of lacrimal gland stem/progenitor cells was proposed in several species, yet their origin and characteristics are not very clear. Here, we investigated the presence of resident progenitor cells and their regenerative potential in a rabbit model with lacrimal gland main excretory duct ligation-induced injury. The ligation-injured lacrimal glands temporarily decreased in weight and had impaired tear secretion. Protein expression profiles and transcriptional profiles were obtained from injured tissue. Isolated lacrimal gland progenitor cells were tested and characterized by stem cell-related marker evaluation, single cell clonal assay and three-dimensional (3-D) culture. The results of our study indicate that lacrimal glands are capable of tissue repair after duct ligation-induced injury, likely involving resident stem/progenitor cells and epithelial-mesenchymal transitions. Lacrimal gland progenitor cells isolated from ligated tissue can differentiate in 3-D culture. The results provide further insights into lacrimal gland stem/progenitor cell physiology and their potential for treating severe cases of tear deficiency.
A brief intervention for preparing ICU families to be proxies: A phase I study.

Background Family members of critically ill patients report high levels of conflict with clinicians, have poor understanding of prognosis, struggle to make decisions, and experience substantial symptoms of anxiety, depression, and post-traumatic stress regardless of patient survival status. Efficient interventions are needed to prepare these families to act as patient proxies. Objectives To assess a brief "patient activation" intervention designed to set expectations and prepare families of adult intensive care unit (ICU) patients to communicate effectively with the clinical team. Design Phase I study of acceptability and immediate side effects. Setting and participants 122 healthcare proxies of 111 consecutive patients with a stay of ≥24 hours in the Johns Hopkins Hospital Medical ICU (MICU), in Baltimore, Maryland. Intervention Reading aloud to proxies from a booklet (Flesch-Kincard reading grade level 3.8) designed with multidisciplinary input including from former MICU proxies. Results Enrolled proxies had a median age of 51 years old with 83 (68%) female, and 55 (45%) African-American. MICU mortality was 18%, and 37 patients (33%) died in hospital or were discharged to hospice. Among proxies 98% (95% CI: 94% - 100%) agreed or strongly agreed that the intervention was appropriate, 98% (95% CI: 92% - 99%) agreed or strongly agreed that it is important for families to know the information in the booklet, and 54 (44%, 95% CI 35%- 54%) agreed or strongly agreed that parts of the booklet are upsetting. Upset vs. non-upset proxies were not statistically or substantially different in terms of age, sex, education level, race, relation to the patient, or perceived decision-making authority. Conclusions This patient activation intervention was acceptable and important to nearly all proxies. Frequently, the intervention was simultaneously rated as both acceptable/important and upsetting. Proxies who rated the intervention as upsetting were not identifiable based on readily available proxy or patient characteristics.
Age-dependent expression pattern in the mammalian brain of a novel, small peptide encoded in the 22q11.2 deletion syndrome region.

Abstract 22q11.2 deletion syndrome (22q11.2DS) carries increased risk for both physical and psychiatric symptoms, including a high risk for schizophrenia. Understanding the genetic elements within the deletion region therefore has the potential to unlock the mysteries of both diseases. While most of the protein-coding genes in this region have been characterized, novel elements, such as non-coding RNAs and small Open Reading Frames (sORFs) remain unstudied. We have identified a novel, highly-conserved mouse sORF in a region of the mouse genome that is orthologous to a portion of the 22q11.2 deletion. This region was previously associated with age-dependent synaptic plasticity abnormalities. We refer to it as the P lasticity A ssociated N eural T ranscript S hort, or Pants. In developing and aging mouse brain, Pants expression is strongest in hippocampus, especially in areas CA3 and CA2, throughout the dorsoventral axis. The Pants peptide is expressed throughout the hippocampus, with an age-dependent increase in stratum lucidum at 16 weeks of age. This expression pattern suggests a potential role for Pants in many hippocampal behaviors, as well as a potential role in the age-dependent neurologic deficits displayed by 22q11.2DS model mice and patients.
Using conceptual matrices, knowledge maps, and scripted cooperation to improve personal management strategies.

Research in the area of substance abuse suggests that ineffective personal management strategies appear to be a major factor in abuse behavior. In this study, fifty-seven students in an intermediate level psychology class were provided with three tools previously found to enhance academic learning strategies—knowledge maps, scripted peer cooperation, and conceptual matrices—as a means of understanding and improving personal management strategies. Student ratings of the value of these activities were significantly higher than an average or moderate response. Individual differences appear to be an important consideration in predicting participants' perceptions of the value of this approach. Those who felt they had control of whatever happens to them, and those who perceived problems as impactful and had strong desires to change recurring problem situations, had the most positive reactions to the types of activities used in this study.
Quantitative Measures vs. Countermeasures

The appeal of quantitative models of security is that, like mathematical models in general, they can be analyzed to yield insights that are not immediately obvious. Below is a simple example that illustrates the reward of setting up and analyzing a quantitative model. However, the conclusion drawn from this particular model is not to be trusted, because the model is not realistic.
Advancing remote attestation via computer-aided formal verification of designs and synthesis of executables: opinion

Remote Attestation (RA) of embedded/smart/IoT devices is a very important issue on today's security landscape. RA enables a verifier to measures the current internal memory state of an untrusted remote device (prover). RA helps the verifier establish a static or dynamic root of trust in prover. Despite much prior work, state-of-the-art RA techniques unfortunately still lack any solid foundation and offer no ironclad security, safety or robustness guarantees. This paper argues that computer-aided formal verification, and synthesis of executables, of RA protocols and hybrid (software-hardware) architectures is required and currently unaddressed. We believe that this is achievable with current (computer-aided) formal methods frameworks and tools, and that this can help advance and mature RA research if used to establish more rigorous and clear security arguments. To support our opinion, we highlight several examples where subtle issues were missed in the design and security analysis of RA techniques. Despite deceptive simplicity of such protocols, manual analyses and ad hoc implementations often lead to over-simplification of (and subsequent glossing over) important details in the underlying processor and system architectures. Computer-aided formal verification forces a more scrupulous and disciplined consideration of such details, since, otherwise, verification simply fails. The key objective of the research direction we propose is to increase confidence in correctness and security guarantees of current and future RA techniques and their implementations.
It's Our Day: America's Love Affair with the White Wedding, 1945-2005

Review of: "It's Our Day: America's Love Affair with the White Wedding, 1945-2005," by Katherine Jellison.
Palynofacies, paleoenvironment and thermal maturity of early Silurian shales in Saudi Arabia (Qusaiba Member of Qalibah Formation)

Abstract The early Silurian Qusaiba Shales are proven source rocks of the many Paleozoic petroleum systems of Saudi Arabia. In this study, a new, simple and cost-effective method for semi-quantitative analysis and graphical representation of palynological assemblage composition (PZC Phytoplankton–Zooplankton–Cryptospore ternary diagram) and a new visual thermal alteration index (IPA–TAI Integrated Palynomorph–Amorphous organic matter Thermal Alteration Index) integrating amorphous organic matter and palynomorph color, were developed based on the palynological/palynofacies analysis of some selected wells penetrating the early Silurian Qusaiba Shales throughout Saudi Arabia. The methods were tested against independent paleoenvironmental and thermal maturity indicators mainly based on geochemical parameters, confirming their validity as effective alternative methods for optical kerogen analysis and interpretation. The thermal maturity values estimated for core samples in the Qusaiba Shales from 13 wells in Saudi Arabia showed a strong correlation with Vitrinite Reflectance Equivalent (VRE%) maturity values determined from graptolite reflectance and pyrolysis Tmax measurements in the entire range of maturities (immature to overmature stages), proving that the present visual thermal alteration index can be successfully employed as a time efficient and reliable method for estimating thermal maturity in the Qusaiba Shales of Saudi Arabia. The present results show that the Qusaiba Shales were deposited in mostly mid- to outer shelf, and occasionally nearshore marine environments under prevailing dysoxic and anoxic water conditions, resulting in accumulation and preservation of organic matter.
Gender differences in diet and social media: An explorative study

This study aimed to investigate the impact of social media on perceptions of food-related content. We asked participants a series of questions about their diet, attitudes, and social media use. We also manipulated food photos posted on Instagram to reveal varying degrees of information from the social media app (no Instagram information, icons visible, number of likes visible, or caption visible). Participants rated the foods in these photos based on how healthy they perceived them to be and how likely they were to eat them. We then used a 2X4 MANOVA to test whether healthy, unhealthy, and neutral foods were perceived differently between genders and conditions. Results showed no effect of condition, but indicated that men rated unhealthy foods as significantly healthier than women did. We also found that women's perceived healthiness ratings of healthy foods were positively correlated with ratings of how likely they were to eat them; in contrast, there were no relationships between perceived health and likelihood of eating any foods for men. Finally, results of our social media use questions indicated that Facebook was the most popular website used for finding recipes. These findings suggest that while we did not see any between-condition differences, social media may be a factor in what people eat. Furthermore, gender may be a key factor in this relationship.