cssi/SciSciGPT-SciSciNet huggingface dataset:
cAMP‐independent signal pathways stimulate hyphal morphogenesis in Candida albicans

Summary The fungal pathogen Candida albicans can transition from budding to hyphal growth, which promotes biofilm formation and invasive growth into tissues. Stimulation of adenylyl cyclase to form cAMP induces hyphal morphogenesis. The failure of cells lacking adenylyl cyclase (cyr1Δ) to form hyphae has suggested that cAMP signaling is essential for hyphal growth. However, cyr1Δ mutants also grow slowly and have defects in morphogenesis, making it unclear whether hyphal inducers must stimulate cAMP, or if normal basal levels of cAMP are required to maintain cellular health needed for hyphal growth. Interestingly, supplementation of cyr1Δ cells with low levels of cAMP enabled them to form hyphae in response to the inducer N-acetylglucosamine (GlcNAc), suggesting that a basal level of cAMP is sufficient for stimulation. Furthermore, we isolated faster-growing cyr1Δ pseudorevertant strains that can be induced to form hyphae even though they lack cAMP. The pseudorevertant strains were not induced by CO2, consistent with reports that CO2 directly stimulates adenylyl cyclase. Mutational analysis showed that induction of hyphae in a pseudorevertant strain was independent of RAS1, but was dependent on the EFG1 transcription factor that acts downstream of protein kinase A. Thus, cAMP-independent signals contribute to the induction of hyphal responses.
Fallacies in our understanding of mycotoxins

It is arguable that mycotoxins offer a new challenge to the logical framework on which microbiology is erected. The time honored concepts of cause and effect are not as clear and simple with mycotoxins as we would wish and frequently assume. We have nondescript diseases with multiple nondescript causes. It is a rare field outbreak in which everything equals what is seen in the laboratory. A microbiologist working with mycotoxins is like a microbiologist working with mixed cultures, he not only feels lost but to a certain extent he is lost with the customary road signs vague and obscured or even misleading. Nevertheless, mycotoxicology reflects reality with all its excitement and complexity as do few other areas of science. Mycotoxins are a real and present hazard as they have been for ages. It is up to us to question, acknowledge, and correct the fallacies hindering our goal of relieving mankind of the affliction of mycotoxins.
Shape memory polymers with enhanced visibility for magnetic resonance- and X-ray imaging modalities

Abstract Currently, monitoring of minimally invasive medical devices is performed using fluoroscopy. The risks associated with fluoroscopy, including increased risk of cancer, make this method especially unsuitable for pediatric device delivery and follow-up procedures. A more suitable method is magnetic resonance (MR) imaging, which makes use of harmless magnetic fields rather than ionizing radiation when imaging the patient; this method is safer for both the patient and the performing technicians. Unfortunately, there is a lack of research available on bulk polymeric materials to enhance MR-visibility for use in medical devices. Here we show the incorporation of both physical and chemical modifying agents for the enhancement of both MR and X-ray visibility. Through the incorporation of these additives, we are able to control shape recovery of the polymer without sacrificing the thermal transition temperatures or the mechanical properties. For long-term implantation, these MR-visible materials do not have altered degradation profiles, and the release of additives is well below significant thresholds for daily dosages of MR-visible compounds. We anticipate our materials to be a starting point for safer, MR-visible medical devices incorporating polymeric components. Statement of Significance Shape memory polymers (SMPs) are polymeric materials with unique shape recovery abilities that are being considered for use in biomedical and medical device applications. This paper presents a methodology for the development of MR and X-ray visible SMPs using either a chemically loaded or physical loaded method during polymer synthesis. Such knowledge is imperative for the development and clinical application of SMPs for biomedical devices, specifically for minimally-invasive vascular occlusion treatments, and while there are studies pertaining to the visibility of polymeric particles, little work has been performed on the utility of biomaterials intended for medical devices and the impact of how adding multiple functionalities, such as imaging, may impact material safety and degradation.
Synthesis of α-l-Threofuranosyl Nucleoside 3'-Monophosphates, 3'-Phosphoro(2-Methyl)imidazolides, and 3'-Triphosphates.

α-l-Threofuranosyl nucleic acid (TNA) is an artificial genetic polymer composed of vicinal 2′,3′-phosphodiester bonds linking adjacent threofuranosyl nucleosides. TNA is one of a small number of genetic polymers that are both highly resistant to nuclease digestion and capable of cross-pairing with DNA and RNA. Although an efficient method for synthesizing TNA nucleosides has been reported, very few advances have been made in the synthesis of phosphorylated TNA compounds. Here, we describe a highly efficient method for synthesizing α-l-threofuranosyl nucleoside 3′-monophosphates (tNMPs), 3′-phosphoro(2-methyl)imidazolides (2-MeImptNs), and 3′-triphosphates (tNTPs) bearing the four genetic bases of adenine (A), cytosine (C), thymine (T), and guanine (G). We suggest that this strategy, which provides access to grams of tNMPs, hundreds of milligrams of 2-MeImptNs, and tens of milligrams of tNTPs, will help advance the use of TNA monomers in exobiology and biotechnology applications.
Corneal sensitivity and tear production in 108 horses with ocular disease

Purpose To compare corneal sensitivity and tear production in horses with keratitis to horses with other ocular disease. Method Retrospective medical record review was used to identify equine patients presented during a 1-year period for an ocular complaint who had Schirmer Tear Test (STT) or Corneal Touch Threshold (CTT) measured. Variables studied included patient age and sex; affected eye; category of presenting ocular complaint (keratitis vs. other ocular complaint); STT; and CTT. Patients with a complaint of ulcerative keratitis, immune-mediated keratitis, and stromal abscess were categorized in the keratitis group. Patients with a complaint of uveitis, as well as lid, lens, or retinal disease, were categorized in the group having other ocular disease. For patients presenting more than once in 2013, only the first visit at which STT or CTT was measured was included. For patients with bilateral disease, STT and CTT of both eyes were averaged. Results A total of 108 patients were included, 45 with keratitis and 63 with other ocular disease. Average age was 13.65 years, with more males (77) than females (31). Adjusted for age, STT in affected eyes did not differ significantly between the two groups (keratitis = 29.92 mm/min; other ocular disease = 27.96 mm/min), but CTT was significantly lower in patients with keratitis (33.78 mm) than in patients with other ocular disease (40.10 mm). Conclusions Corneal sensitivity may be decreased in patients with keratitis. It is not known whether this is a cause or an effect of corneal disease.
Generating conflict: Gold, water and vulnerable communities in the Colombian Highlands

Foreign direct investment is commonly believed to have a stabilizing effect in countries receiving investments, and is believed to lead to positive development outcomes. This chapter pushes back on these assumptions. Informed by nearly four years of intermittent ethnographic fieldwork in the towns surrounding the Paramo de Santurban in the rural highlands of Colombia, it provides a grounded account of how investments by foreign mining companies may destabilize populations and cause conflict, rather than perpetuate stability. This empirical study lends support to the argument that the design of the FDI project, and the process by which it is established, may determine whether the project will be beneficial or detrimental to common development goals, including whether it will cause conflict or act as a stabilizing force. This chapter is largely informed by the fieldwork that led to the production of the documentary film directed by the author, There is Nothing Else/Otra Cosa No Hay, in which many of the topics discussed herein are explored in further detail.
Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases

The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system. Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities. Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).
Prediction of temperature induced office worker's performance during typing task using EEG

Understanding how indoor environment affects office worker's performance and developing methods to predict human performance in changing indoor environment have become highly important research topic bearing significant economic and sociological impact. While past research groups have attempted to find predictors for performance they do not provide satisfactory predictions. We conduct in this paper a study to predict human performance by developing a regression model using neurophysiological signals collected from electroencephalogram (EEG), during simulated office-work tasks under different indoor room temperatures (22°C and 30°C). We found that using brain power spectral densities (PSD) from EEG as predictors provides the higher R2 than predictors using skin temperature or heart rate by approximately over 3 folds. Finally, we showed that the predictor using EEG is more robust than regression models using skin temperature and heart rate. Our work shows the potential of using brain signals to accurately predict human office work performance.
Coherence analysis of trunk and leg acceleration reveals altered postural sway strategy during standing in persons with multiple sclerosis.

Balance task performance is affected in persons with multiple sclerosis (PwMS), but the control strategies used to perform specific tasks are not well understood. The purpose of this study was to evaluate segmental control during quiet standing in PwMS and controls to understand whether MS alters use of the ankle and hip strategies to manage postural sway. Coherence of acceleration between the trunk and legs was evaluated with accelerometers placed on the sacrum and lower leg. Thirty-six PwMS and 20 healthy control subjects performed quiet standing with eyes open and closed while center of pressure (CoP) and acceleration of postural sway was measured. Acceleration frequencies were divided into lower frequencies (≤1.0 Hz) and higher frequencies (>1.0 Hz) to categorize sway characteristics. With eyes open, coherence was significantly lower in PwMS compared to controls at lower frequencies only. With eyes closed, coherence was significantly lower in PwMS compared to controls, who use an ankle strategy at lower frequencies only, at both lower and higher frequencies. Both groups showed decreased coherence with increasing frequency when eyes were open and closed. Coherence was significantly correlated with CoP sway area in PwMS during the eyes closed condition only. The reduced coherence in PwMS during both lower and higher frequency sway indicates PwMS utilize a mixed ankle-hip sway strategy regardless of sway frequency. This is in contrast to sway in healthy subjects which utilizes an ankle strategy at lower frequencies and a mixed strategy at higher frequencies. Lack of adaptability in segmental control strategy likely contributes to abnormal postural control, as reflected by CoP sway patterns, in PwMS.
Videogame Type Simulation of Mancur Olson's Dictatorship, Democracy and Development: A Randomized Experiment

Evidence from a randomize experiment that computer based videogames improve learners recall of information.
The Trump Effect: “Lights Out” on the Age of Enlightenment

President Trump’s one major 2017 policy victory was a tax cut for the 1%. His Republican Congress cagily balanced it against projected revenue increases that future leaders will be forced to genera...
Hot and bothered: effects of elevated Pco2 and temperature on juvenile freshwater mussels.

Multiple environmental stressors may interact in complex ways to exceed or diminish the impacts of individual stressors. In the present study, the interactive effects of two ecologically relevant s...
Pediatric primary healthcare providers’ preferences, experiences and perceived barriers to discussing electronic cigarettes with adolescent patients

Introduction: Our aim is to investigate pediatric primary healthcare providers' (PPCPs) perceptions about e-cigarettes and current e-cigarette-related clinical practices with adolescents.Methods: I...
Electromechanical devices for microscale fatigue testing

Publisher Summary The knowledge of the evolution of fatigue damage due to cyclic loading in microscopic components is of paramount importance to the durability and performance of MEMS. The development of novel experimental techniques enabling monitoring of the material dynamic response at submicron scales is of great importance to micromachine technology. The majority of previous reliability studies in this emerging field have been mostly based on simple test structures that cannot simulate the cyclic loading conditions encountered in MEMS devices. The objective of this work was to bridge this gap by introducing microdevices fabricated by standard surface micromachining that are suitable for fatigue testing under conditions that are typical of MEMS devices. The microfabrication and basic characteristics of thin-film polysilicon microdevices for fatigue testing under controlled cyclic loading conditions were presented. The microdevices were excited at resonance using on-chip actuation. Cyclic loading was generated by interdigitized comb drives arranged along radial spokes extending from a suspended ring held in place by thin flexure beams (fatigue specimens) attached to an anchor at the center of the device. Preliminary results demonstrated the potential of the developed experimental procedures to provide insight into the evolution of fatigue damage in polysilicon microstructures.
TFCX shielding optimization

Design analyses and tradeoff studies for the bulk shield of the Tokamak Fusion Core Experiment (TFCX) were performed. Several shielding options were considered to lower the capital cost of the shielding system. Optimization analyses were carried out to reduce the nuclear responses in the TF coils and the dose equivalent in the reactor hall one day after shutdown. Two TFCX designs with different toroidal field (TF) coil configurations were considered during this work. The materials for the shield were selected based upon tradeoff studies and the results from the previous design studies. The main shielding materials are water, concrete, and steel balls (Fe1422 or Nitronic 33). Small amounts of boron carbide and lead are employed to reduce activation, nuclear heating in the TF coils, and dose equivalent after shutdown.
Mobile elements in the yeast mitochondrial genome.

The yeast mitochondrial genome is known to contain an assortment of optional DNA sequences composed primarily of introns, short GC-rich regions (GC clusters), and AT-rich stretches. Since these sequences are optional and present no obvious selection pressure to cells, it is easy to follow their genetic behavior in crosses together with other markers on the mitochondrial genome. Leaving aside the question of why the mitochondrial genome has retained these optional sequences, recent studies have led to the interesting result that some of them show unusual properties in genetic recombination (3).
Medical Students’ Self-evaluations of Their Patient-Centered Cultural Sensitivity: Implications for Cultural Sensitivity/Competence Training

The goals of this study were to (1) empirically assess the need for training in patient-centered culturally sensitive health care among medical students and (2) determine if training in such care needs to be customized to some degree based on individual or subgroup differences. Two hundred seventeen advanced (third- and fourth-year) medical students from 4 medical schools participated. Participants self-reported their current levels of engagement in patient-centered culturally sensitive health care using an online version of the Tucker- Culturally Sensitive Health Care Inventory Provider Form. Results indicated that participating advanced medical students gave self-ratings of engagement in patient-centered culturally sensitive health care that indicate high engagement in some but not all of the behaviors and attitudes that indicate this care. Additionally, their self-ratings differed in association with their gender, race/ethnicity, being fluent in a language other than English, and prior experience providing health care to racial/ethnic minority patients. Conclusions include that some medical students need training in patientcentered culturally sensitive health care, and this training ideally should be assessment-based and customized to address areas where there are low self-ratings of engagement in patient-centered culturally sensitive health care.
Operations to Resect, Replace, or Bypass the Esophagus for Cancer

A number of surgeons have asserted that resection of the lower esophagus and proximal stomach for lesions near the gastric cardia, followed by esophagogastric anastomosis, is an operation with a high mortality rate and a high incidence of reflux esophagitis. On the other hand, we have observed that very few patients experience serious symptoms of reflux esophagitis following esophagogastrectomy with an end-to-side anastomosis. No dietary restrictions have been necessary. In 44 consecutive cases, among patients whose average age was over 70, we encountered (and reported) no clinical anastomotic leaks and no deaths.
Synthesis of Fmoc-Protected (S,S)-trans-Cyclopentane Diamine Monomers Enables the Preparation and Study of Conformationally Restricted Peptide Nucleic Acids

An efficient synthesis of Fmoc-protected (S,S)-trans-cyclopentane PNA (tcypPNA) monomers starting from mono-Boc-protected (S,S)-1,2-cyclopentanediamine is reported. A general synthetic strategy was developed so that tcypPNA monomers with each nucleobase can be made in sufficient quantity and purity for use in solid-phase peptide synthesis (SPPS). The newly synthesized monomers were then successfully incorporated into 10-residue PNA oligomers using standard Fmoc chemistry for SPPS. The different tcypPNAs allow different positions in the sequence to be conformationally constrained with (S,S)-trans-cyclopentane to determine the effects on binding to complementary DNA.
International assessment of massive transfusion protocol contents and indications for activation

BACKGROUND Massive transfusion protocols (MTPs) provide blood products rapidly and in fixed amounts. MTPs are commonly used in trauma but may also be used in other clinical settings, although evidence to support fixed-ratio resuscitation in nontraumatic hemorrhage is lacking. The goals of this study were to describe the types and contents of available MTPs and the clinical indications for MTP activation. METHODS A survey was distributed to 353 transfusion medicine specialists to assess the types and contents of available MTPs. Survey participants were invited to provide the clinical indications for consecutive adult and pediatric MTP activations for at least 6 months during 2015 to 2017. RESULTS There were 125 completed surveys (35% response rate) including three from children's specialty hospitals. Most hospitals that treated adult patients (90/122, 74%) utilized only one MTP for all adult bleeding emergencies, while one hospital had no MTP. Of the 31 hospitals that provided more than one adult MTP, 20 provided MTPs specific for obstetric bleeding cases. Of these, 50% (10/20) included at least one pool of cryoprecipitate or fibrinogen concentrate in the first MTP round, compared with 14% (13/90) of the hospitals with one MTP (p = 0.0012). Fifty-seven hospitals provided the clinical indication for 4176 adult and 155 pediatric MTP activations. Although trauma was the single most common indication, the majority of adult (58%) and pediatric (65%) activations were for nontrauma indications. CONCLUSIONS The majority of hospitals use a single MTP to manage massive hemorrhage. The majority of MTP activations were for nontrauma indications.
A Hidden Dimension of Family Development in the Modern Kingdom of Tonga

The significance of geographically dispersed networks of kinsmen as analytical isolates in the conceptualization of the family is illustrated for the modern Kingdom of Tonga. During the phase of di...
SIMPLIFIED TECHNIQUE FOR THE EVALUATION OF MULTIPLE LAYER INSULATION

A simple method is used to evaluate multi - layer radiation screen insulation on the basis of fin techniques. Only a small section of a cylinder is instrumented supplying heat at one end of the insulation package. The data obtained are in good agreement with results obtained by means of conventional techniques.
Basics of microwave network analysis

Solving Maxwell's equations to analyze a given electromagnetic (EM) problem yields an accurate solution with a plethora of spatiotemporal electric and magnetic fields information that may not be needed. It is also evident that quantities resulting from solving Maxwell's equations are interrelated and reconciled to the transmission line (TL) and circuit theory. Practically, port analysis techniques are more prevalent as a simple and effective method in analyzing microwave and mixed radio frequency (RF) digital circuits. Integrating additional components to the original problem has become an easy task by applying port analysis, where network loss, impedance transformation, and other effects are preserved. While most port parameters are valid to represent the device linear behavior due to small signal stimulus, other parameters are also available to cope with the nonlinear characteristics of circuits due to large signal excitation. Some network parameters are convenient to use than others depending on the circuit topology; therefore, conversions between the different port network parameters are also possible. Circuit analysis techniques can be classified into two categories based on their frequency of operation: low frequency based on quasi-static approximations of Maxwell's equations and high frequency (microwave) circuits based on full-wave EM analysis. At low frequencies, circuit physical dimensions are relatively small when compared to the operating wavelength and phase variation at any point in the circuit is considered negligible. There are several techniques used to analyze low-frequency circuits; however, they are not applicable for circuits operating at high (gigahertz) frequencies due to the domination of parasitic effects. Circuit synthesis techniques greatly benefit from applying port analysis methods to simplify the mathematical representation of the network transfer function and thereby the subsequent steps required to realize the circuit parameters.
A simplified derivation of the ordinary differential equations for the free-surface Green functions

Abstract Ordinary differential equations (ODEs) are derived for the free-surface Green functions and their gradients, in a fluid of infinite depth. The cases of harmonic time-dependence in the frequency domain and impulsive motion in the time domain are considered separately. These ODEs were derived originally by Clement, starting with fourth-oder equations in the time domain and using Fourier transforms to derive a second-order ODE in the frequency domain. In the present work a simpler procedure is followed independently in each domain, transforming the governing Laplace equation to an ordinary differential equation. The results are consistent with the ODEs derived using Clement’s method.
Boosting the cost-effectiveness of luminescent solar concentrators through subwavelength sanding treatment

Abstract In this report, we introduced subwavelength sanding treatment to boost the cost-effectiveness of luminescent solar concentrators (LSCs). It was proven the hypothesis that sanding the device surface to roughness (Rq = 22–105-nm) much smaller than the wavelength of sunlight (λ = 280–4000 nm) would improve the device performance due to much higher scattering gain than scattering loss. Experimental results showed that the sanded devices exhibited power conversion efficiency (ηLSC) and power concentration ratio (C) enhanced by at least 44% and could have the doping concentration of the luminophores significantly reduced by 87.5%. Measurement on the waveguide edge emission revealed that the performance enhancement was attributed to the utilization of the long-wavelength (λ > 800 nm) photons. Monte Carlo ray tracing simulation signified that the subwavelength sanding treatment was also applicable to large-area devices with geometric gain (G) up to 120 (9.29 m2) and devices made of other luminophores. Cost-effectiveness analysis indicated a huge reduction by 45% in the price per watt (PPW) for large-area commercial-sized (80 in. by 40 in.) LSCs. This study suggested that subwavelength sanding treatment was promising to bridge the gap between research and commercialization of the LSCs.
Axonal mechanisms mediating GABA-A receptor inhibition of striatal dopamine release

Abstract Axons of midbrain dopaminergic neurons innervate the striatum where they contribute to movement and reinforcement learning. Past work has shown that striatal GABA tonically inhibits dopamine release, but whether GABA-A receptors directly modulate transmission or act indirectly through circuit elements is unresolved. Here, we use whole-cell and perforated-patch recordings to test for GABA-A receptors on the main dopaminergic neuron axons and branching processes within striatum. Application of GABA depolarized axons, but also decreased the amplitude of axonal spikes, limited propagation and reduced striatal dopamine release. The mechanism of inhibition involved sodium channel inactivation and shunting. Lastly, we show that the positive allosteric modulator diazepam enhanced GABA-A currents on dopaminergic neuron axons and directly inhibited release, but also likely acts by reducing excitatory drive from cholinergic interneurons. Thus, we reveal the mechanisms of GABA-A receptor modulation of dopamine release and provide new insight into the actions of benzodiazepines within the striatum.
Diagnostic test accuracy of ADC values for identification of clear cell renal cell carcinoma: systematic review and meta-analysis

To perform a systematic review on apparent diffusion coefficient (ADC) values of renal tumor subtypes and meta-analysis on the diagnostic performance of ADC for differentiation of localized clear cell renal cell carcinoma (ccRCC) from other renal tumor types. Medline, Embase, and the Cochrane Library databases were searched for studies published until May 1, 2019, that reported ADC values of renal tumors. Methodological quality was evaluated. For the meta-analysis on diagnostic test accuracy of ADC for differentiation of ccRCC from other renal lesions, we applied a bivariate random-effects model and compared two subgroups of ADC measurement with vs. without cystic and necrotic areas. We included 48 studies (2588 lesions) in the systematic review and 13 studies (1126 lesions) in the meta-analysis. There was no significant difference in ADC of renal parenchyma using b values of 0–800 vs. 0–1000 (p = 0.08). ADC measured on selected portions (sADC) excluding cystic and necrotic areas differed significantly from whole-lesion ADC (wADC) (p = 0.002). Compared to ccRCC, minimal-fat angiomyolipoma, papillary RCC, and chromophobe RCC showed significantly lower sADC while oncocytoma exhibited higher sADC. Summary estimates of sensitivity and specificity to differentiate ccRCC from other tumors were 80% (95% CI, 0.76–0.88) and 78% (95% CI, 0.64–0.89), respectively, for sADC and 77% (95% CI, 0.59–0.90) and 77% (95% CI, 0.69–0.86) for wADC. sADC offered a higher area under the receiver operating characteristic curve than wADC (0.852 vs. 0.785, p = 0.02). ADC values of kidney tumors that exclude cystic or necrotic areas more accurately differentiate ccRCC from other renal tumor types than whole-lesion ADC values. • Selective ADC of renal tumors, excluding cystic and necrotic areas, provides better discriminatory ability than whole-lesion ADC to differentiate clear cell RCC from other renal lesions, with area under the receiver operating characteristic curve (AUC) of 0.852 vs. 0.785, respectively (p = 0.02). • Selective ADC of renal masses provides moderate sensitivity and specificity of 80% and 78%, respectively, for differentiation of clear cell renal cell carcinoma (RCC) from papillary RCC, chromophobe RCC, oncocytoma, and minimal-fat angiomyolipoma. • Selective ADC excluding cystic and necrotic areas are preferable to whole-lesion ADC as an additional tool to multiphasic MRI to differentiate clear cell RCC from other renal lesions whether the highest b value is 800 or 1000.
COMPARISON OF NON-MAXIMAL TESTS FOR ESTIMATING EXERCISE CAPACITY

Although maximal incremental exercise tests (GXT) are the gold standard for outcome assessment and exercise proscription, they are not widely available in either fitness or clinical exercise programs. This study compared the prediction of VO2max in healthy, sedentary volunteers using a non-exercise prediction (Matthews, Heil, Freedson & Pastides, 1999), RPE extrapolation to 19 & 20 (Eston, Lambrick, Sheppard & Parfitt, 2008) and the Rockport Walking Test (RWT)(Kline et al, 1987) and of VT using the Talk Test (Foster et al., 2018) and RPE @ 13,14,15. Subjects performed treadmill GXT with gas exchange, submaximal treadmill with RPE and Talk Test, the RWT and the Matthews non-exercise estimation. All methods provided reasonable estimates of both VO2max and VT, with correlations >0.75 and SEE ~1 MET. VO2max was best estimated with extrapolation to RPE=19. VT was observed intermediate between the Last Positive & Equivocal stages of the TT and between RPE 13 & 14. Non-maximal evaluation, and even non-exercise equations can be used as a substitude for maximal GXT with gas exchange to make reasonable estimates of both VO2max and VT.
External Merge Sort for Top-K Queries: Eager input filtering guided by histograms

Business intelligence and web log analysis workloads often use queries with top-k clauses to produce the most relevant results. Values ofk range from small to rather large and sometimes the requested output exceeds the capacity of the available main memory. When the requested output fits in the available memory existing top-k algorithms are efficient, as they can eliminate almost all but the topk results before sorting them. When the requested output exceeds the main memory capacity, existing algorithms externally sort the entire input, which can be very expensive. Furthermore, the drastic difference in execution cost when the memory capacity is exceeded results in an unpleasant user experience. Every day, tens of thousands of production top-k queries executed on F1 Query resort to an external sort of the input. To address these challenges, we introduce a new top-k algorithm that is able to eliminate parts of the input before sorting or writing them to secondary storage, regardless of whether the requested output fits in the available memory. To achieve this, at execution time our algorithm creates a concise model of the input using histograms. The proposed algorithm is implemented as part of F1 Query and is used in production, where significantly accelerates top-k queries with outputs larger than the available memory. We evaluate our algorithm against existing top-k algorithms and show that it reduces I/O traffic and can be up to 11 times faster.
How do distal and proximal risk factors combine to predict suicidal ideation and behaviors? A prospective study of the narrative crisis model of suicide.

Abstract Aim : The Narrative Crisis Model of suicide posits that when individuals with trait vulnerabilities for suicide face stressful life events, they may develop distorted perceptions of themselves and society that culminate in a sense of no future. Referred to as the suicide narrative, these perceptions makes them more likely to experience the Suicidal Crisis Syndrome, an acute affective condition that increases the risk of engaging in suicidal ideation behaviors. The goal of this study was to assess the stage components of this model. Methods : The stage components of the NCM were assessed among adult psychiatric inpatients (N = 223; listwise N = 85) aged 18–65 years old and admitted for suicidal ideation or attempts. Suicidal outcomes were assessed at one month follow-up. Structural equation modeling (SEM) was used to assess the model and its prediction of prospective suicidal outcomes. Results : The model was supported by the SEM and proved to be a good fit for the data. Each temporal stage was significantly predicted by the precedent stage in the model and 13% of the variance in suicidal ideation and behaviors (when assessed conjointly) were explained by the model. When suicidal ideation and attempts were assessed separately, the amount of variance explained was 10.8% for suicidal ideation and 40.7% for suicidal attempts. Discussion : The progression from trait vulnerabilities to suicidal outcomes proposed by the NCM was supported by our findings. These findings have clinical implications in the assessment and treatment of suicide risk and will need replication with larger samples.
Parameter identification approach for support structures in laser powder bed fusion and analysis of influencing factors

Abstract Additive manufacturing, especially laser powder bed fusion (LPBF), enables the build-up of complex parts. LPBF is a technology with high geometric degrees of freedom, but there are production restrictions, e.g. with regard to overhangs. One strategy to produce these components despite the restrictions is the use of support structures. Parameter determination for support structures is strongly neglected in contrast to component parameters. In this paper, a methodology for determining parameters for support structures is presented. Test geometries for the determination of mechanical properties (tensile and torsional properties) are developed. Subsequently, the influence of the manufacturing parameters (e.g. laser power) on the properties of the widely used lattice support are determined for the case-hardening steel 16MnCr5. It can be shown that shear and tensile strength of the support structures are influenced by the applied manufacturing parameters. Furthermore, the influence of geometrical parameters such as grid spacing and perforation on the tensile strength is investigated.
Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United States.

Background and objectives With multiple medications indicated for mineral metabolism, dialysis providers can apply various strategies to achieve target phosphate and parathyroid hormone (PTH) levels. We describe common prescribing patterns and practice variation in mineral metabolism treatment strategies over the last decade. Design, setting, participants, & measurements In a cohort of adults initiating hemodialysis at Dialysis Clinic, Inc. facilities, we assessed prescriptions of vitamin D sterols, phosphate binders, and cinacalcet longitudinally. To identify the influence of secular trends in clinical practice, we stratified the cohort by dialysis initiation year (2006–2008, 2009–2011, and 2012–2015). To measure practice variation, we estimated the median odds ratio for prescribing different mineral metabolism treatment strategies at 12 months post–dialysis initiation across facilities using mixed effects multinomial logistic regression. Sensitivity analyses evaluated strategies used after detection of first elevated PTH. Results Among 23,549 incident patients on hemodialysis, there was a decline in vitamin D sterol–based strategies and a corresponding increase in strategies without PTH-modifying agents (i.e., phosphate binders alone or no mineral metabolism medications) and cinacalcet-containing treatment strategies between 2006 and 2015. The proportion with active vitamin D sterol–based strategies at dialysis initiation decreased across cohorts: 15% (2006–2008) to 5% (2012–2015). The proportion with active vitamin D sterol–based strategies after 18 months of dialysis decreased across cohorts: 52% (2006–2008) to 34% (2012–2015). The odds of using individual strategies compared with reference (active vitamin D sterol with phosphate binder) varied from 1.5- to two-fold across facilities in 2006–2008 and 2009–2011 cohorts, and increased to two- to three-fold in the 2012–2015 cohort. Findings were similar in sensitivity analyses starting from first elevated PTH measurement. Conclusions Over time, mineral metabolism management involved less use of vitamin D sterol–based strategies, greater use of both more conservative and cinacalcet-containing strategies, and increased practice variation, suggesting growing equipoise.
Microdetermination of phosphate with cetylpyridinium chloride by constant-current potentiometry

Eightμg to 8 mg of phosphorus as orthophosphate were determined by titration with cetylpyridinium chloride after conversion to the 12-molybdophosphate. Solutions were acidified with hydrochloric acid to pH 1.1–1.3. A constant current of 1.1μA in the cathodic direction was applied. A log-log relationship exists between the amount of phosphate present and the optimum Mo∶P ratio. The molybdate blanks are relatively small. Silicate can be determined by a similar method.
Transdermal uptake of benzophenone-3 from clothing: comparison of human participant results to model predictions.

Background Models of transdermal uptake of chemicals from clothing have been developed, but not compared with recent human subject experiments. In a well-characterized experiment, participants wore t-shirts pre-dosed with benzophenone-3 (BP-3) and BP-3 and a metabolite were monitored in urine voids. Objective Compare a dynamic model of transdermal uptake from clothing to results of the human subject experiment. Methods The model simulating dynamic transdermal uptake from clothing was coupled with direct measurements of the gas phase concentration of benzophenone-3 (BP-3) near the surface of clothing to simulate the conditions of the human subject experiment. Results The base-case model results were consistent with the those reported for human subjects. The results were moderately sensitive to parameters such as the diffusivity in the stratum corneum (SC), the SC thickness, and SC-air partition coefficient. The model predictions were most sensitive to the clothing fit. Tighter clothing worn during exposure period significantly increased excretion rates but tighter fit "clean" clothing during post-exposure period acts as a sink that reduces transdermal absorption by transferring BP-3 from skin surface lipids to clothing. The shape of the excretion curve was most sensitive to the diffusivity in the SC and clothing fit. Significance This research provides further support for clothing as an important mediator of dermal exposure to environmental chemicals.
Cysteine sulfhydryls in tau display unusual hyperreactivity

Author(s): Lam, Yi-Li | Advisor(s): Lew, John | Abstract: One of the hallmarks of Alzheimer’s disease is pathological tau aggregation. We previously reported that cinnamaldehyde, found in cinnamon, could inhibit tau aggregation in vitro, by reacting with one or both of the two cysteines in tau. In my thesis, I use spectrophotometric methods to show that both cysteines display hyperreactivity over model sulfhydryl compounds by as much as four fold. The hyperreactivity is specific to cysteines in tau as opposed to those in other sulfhydryl-containing cellular proteins. Cinnamaldehyde (CA) displays several characteristics that make it favorable as a possible inhibitor of aggregation in vivo: it is a water-soluble, brain-permeable molecule that is non-toxic and inexpensive. I now show in my thesis that the hyperreactivity of CA toward tau specifically, as described in this thesis, is an additional favorable property towards the goal of being a potential therapeutic.
13109 Phosphorylation state of Myristoylated Alanine-Rich C-Kinase Substrate Effector Domain mimetics determines its cytotoxicity in glioblastoma and macrophage model

ABSTRACT IMPACT: This study provides insight into how MED2 impacts the immune cells surrounding glioblastoma that help it to grow and spread; having a more complete understanding of how MED2 works will help us better develop therapies that may one day enter the clinic to improve patient outcomes in glioblastoma. OBJECTIVES/GOALS: The purpose of this study was to determine whether the phosphorylation state of the MED2 peptide impacts its biological activity in GBM and macrophages. MED2 variants include the phosphorylatable wild-type (MED2), pseudo-phosphorylated (MED2-PP), non-phosphorylatable (MED2-NP) and control length (CTL2) peptides. METHODS/STUDY POPULATION: MED2, MED2-NP, MED2-PP, and CTL2 were screened against a panel of molecularly characterized glioblastoma patient derived xenografts and IL4/13 stimulated M2-like THP-1 macrophages. The luminescent cell viability assay, CellTiter-Glo, was used to determine viability. RESULTS/ANTICIPATED RESULTS: The proneural lines XD456 and X1441 were highly sensitive to 5 µM MED2 and 5 µM MED2NP compared to 5 µM MED2PP (p<0.001). There was no statistically significant difference between untreated, 5 µM CTL2, and 5 µM MED2PP groups or between the MED2NP and MED2 treated groups. M2-like THP-1 macrophages were highly sensitive to 10 µM MED2NP compared to 10 µM CTL2 (p<0.01) and 10 µM MED2PP (p<0.01) No statistically significant difference was observed between untreated, 10 µM MED2, 10 µM MED2PP, and 10 µM CTL2 groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: The phosphorylation state of MED2 determines its toxicity. When MED2 is phosphorylated, it is nontoxic to GBM or M2-like macrophages. The non-phosphorylatable version is toxic to both GBM and M2-like macrophages. The wild-type peptide is toxic to GBM but not M2-like macrophages, suggesting that MED2 may be phosphorylated in M2-like macrophages.
Collaborative Goal-Setting Beliefs and Practices of Out-Patient Pediatric Physical Therapists Working in Saudi Arabia and the United States.

AIMS (1) identify and compare family-centered care (FCC) and collaborative goal-setting (CGS) beliefs and practices of out-patient pediatric physical therapists (PTs) in Saudi Arabia (SA) and the United States (US); (2) describe CGS approaches; and (3) determine the association between CGS practices and educational level, clinical experience, and FCC beliefs and practices. METHODS 87 PTs completed an online survey. RESULTS Ninety percent of PTs believed in FCC to a great extent. PTs in the US rated their organization's family-centeredness and their own FCC application significantly higher than PTs in SA. PTs believed in CGS with parents (86%) and children (66%) to a great extent while 69% of PTs reported applying CGS with parents to a great extent compared to 39% with children. PTs in SA rated the importance of determining therapy goals by PTs significantly higher than PTs in the US. The most selected CGS strategy was asking about concerns and needs. Low to moderate significant positive associations were found between CGS practices and PTs belief of their organization's family-centeredness and their own FCC application. CONCLUSION Similarities and differences were found between the two countries in FCC and CGS beliefs and practices. Organizational and individual FCC practices influence CGS practices.
Mt10-CVB3 Vaccine Virus Protects against CVB4 Infection by Inducing Cross-Reactive, Antigen-Specific Immune Responses

Group B coxsackieviruses (CVB) containing six serotypes, B1–B6, affect various organs, and multiple serotypes can induce similar diseases such as myocarditis and pancreatitis. Yet, no vaccines are currently available to prevent these infections. Translationally, the derivation of vaccines that offer protection against multiple serotypes is highly desired. In that direction, we recently reported the generation of an attenuated strain of CVB3, termed Mt10, which completely protects against both myocarditis and pancreatitis induced by the homologous wild-type CVB3 strain. Here, we report that the Mt10 vaccine can induce cross-protection against multiple CVB serotypes as demonstrated with CVB4. We note that the Mt10 vaccine could induce cross-reactive neutralizing antibodies (nABs) against both CVB1 and CVB4. In challenge studies with CVB4, the efficacy of the Mt10 vaccine was found to be 92%, as determined by histological evaluation of the heart and pancreas. Antibody responses induced in Mt10/CVB4 challenged animals indicated the persistence of cross-reactive nABs against CVB1, CVB3, and CVB4. Evaluation of antigen-specific immune responses revealed viral protein 1 (VP1)-reactive antibodies, predominantly IgG2a, IgG2b, IgG3, and IgG1. Similarly, by using major histocompatibility complex class II tetramers, we noted induction of VP1-specific CD4 T cells capable of producing multiple T cell cytokines, with interferon-γ being predominant. Finally, none of the vaccine recipients challenged with CVB4 revealed the presence of viral nucleic acid in the heart or pancreas. Taken together, our data suggest that the Mt10 vaccine can prevent infections caused by multiple CVB serotypes, paving the way for the development of monovalent CVB vaccines to prevent heart and pancreatic diseases of enteroviral origin.