cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism

Unlike glycolytic enzymes that directly catabolize glucose to pyruvate, the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFBs) control the conversion of fructose-6-phosphate to and from fructose-2,6-bisphosphate, a key regulator of the glycolytic enzyme phosphofructokinase-1 (PFK-1). One family member, PFKFB3, has been shown to be highly expressed and activated in human cancer cells, and derivatives of a PFKFB3 inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), are currently being developed in clinical trials. However, the effectiveness of drugs such as 3PO that target energetic pathways is limited by survival pathways that can be activated by reduced ATP and nutrient uptake. One such pathway is the process of cellular self-catabolism termed autophagy. We hypothesized that the functional glucose starvation induced by inhibition of PFKFB3 in tumor cells would induce autophagy as a pro-survival mechanism and that inhibitors of autophagy could increase the anti-tumor effects of PFKFB3 inhibitors. We found that selective inhibition of PFKFB3 with either siRNA transfection or 3PO in HCT-116 colon adenocarcinoma cells caused a marked decrease in glucose uptake simultaneously with an increase in autophagy based on LC3-II and p62 protein expression, acridine orange fluorescence of acidic vacuoles and electron microscopic detection of autophagosomes. The induction of autophagy caused by PFKFB3 inhibition required an increase in reactive oxygen species since N-acetyl-cysteine blocked both the conversion of LC3-I to LC3-II and the increase in acridine orange fluorescence in acidic vesicles after exposure of HCT-116 cells to 3PO. We speculated that the induction of autophagy might protect cells from the pro-apoptotic effects of 3PO and found that agents that disrupt autophagy, including chloroquine, increased 3PO-induced apoptosis as measured by double staining with Annexin V and propidium iodide in both HCT-116 cells and Lewis lung carcinoma (LLC) cells. Chloroquine also increased the anti-growth effect of 3PO against LLCs in vivo and resulted in an increase in apoptotic cells within the tumors. We conclude that PFKFB3 inhibitors suppress glucose uptake, which in turn causes an increase in autophagy. The addition of selective inhibitors of autophagy to 3PO and its more potent derivatives may prove useful as rational combinations for the treatment of cancer.
A quantitative methodology to evaluate motion-based animation techniques

We present a novel methodology to quantitatively evaluate the synthesized motion generated by a motion-based animation technique. Our quantitative evaluation methodology provides a measure of how well each algorithm synthesizes motion based on their rotational and translational similarities to the ground truth in a motion database. To demonstrate the effectiveness of our methodology, we focus on techniques that combine different motions into a single spliced action where individual motions are performed simultaneously. We implement three splicing algorithms to perform a comparison study based on our quantitative evaluation methodology. The splicing algorithms considered are spatial body alignment, segmentation-based, and naive DOF replacement. The spatial body alignment adapts the spliced motion according to this joint correlation and, consequently, performs best under our evaluation methodology.
Actin-based motor properties of native myosin VIIa.

Myosin VIIa has critical roles in the inner ear and the retina. To help understand how this protein functions, native myosin VIIa was tested for mechanoenzymatic properties. Myosin VIIa was immunoprecipitated from retinal tissue and found to be associated with calmodulin in a Ca2+-sensitive manner. Myosin VIIa Mg-ATPase activity was detected; in the absence of Ca2+ (i.e. with bound calmodulin), it was stimulated by f-actin with a Kcat of 4.3 s–1 and with 7 μM actin required for half-maximal activity. In a sliding filament motility assay, myosin VIIa moved actin filaments with a velocity of 190 nm s–1. These results demonstrate that myosin VIIa is a calmodulin-binding protein and a bona fide actin-based motor.
Planetary adventures: my life as a NASA software engineer: banquet address

There are a number of stories from experiences working at NASA that make good classroom anecdotes. These come from working in different roles on a variety of missions and pre-missions. The Telerobot Project was prototype work for a remote controlled robot, which led to applications for the robot arm on the space shuttle and the rovers on Mars. During the Voyager Neptune Encounter, a natural language processor was coupled with a database which was constantly being updated with information, such as the number of known moons of Neptune. This system was available in the press room during the encounter. The Sequence Automation Research Group applied state-of-the-art technologies to automating the sequence planning process for missions, including the Galileo Mission to Jupiter. On its way to study the polar regions of the sun, the Ulysses mission flew close to Jupiter for a gravity assist. Some of these experiences refer to planning the science activities on the Ulysses spacecraft during the Jupiter fly-by and to negotiating for Deep Space Network time for the mission. The SIR-C shuttle-based Earth imaging RADAR mission had software system engineering challenges for the mission operations system. This system involved four internal software systems and four external systems, including the flight software and the RADAR system equations software. For the Cassini mission to Saturn, these experiences include testing the flight software for the RADAR instrument, developing the instrument operations system, and completing the preliminary planning for the operations of the RADAR instrument.
Investigation of the Impact of Surface Blending and Ultraviolet Radiation Exposure on Elastomer Seal Leak Rate Performance for Space Seal Applications

Surface blending is a typical step in the manufacturing process of molded elastomer seals used to remove surface imperfections. Using O-rings molded from S0383-70 silicone elastomer oriented in a face seal configuration, this study screened for negative effects of docking seal surface blending. The study was separated into two distinct phases. Phase I used twenty-seven different surface treatments applied to a sample set of 130 O-ring specimens to examine the individual and combined effects of surface blending and ultraviolet radiation exposure on air leak rate. Combinations of blend surface area, blend location, and ultraviolet radiation exposure level were screened to determine the most influential factors and to narrow the variables investigated in Phase II. The second phase employed an enhanced leak rate test system and a test sample set comprised of both Phase I specimens and supplementary O-rings to quantitatively examine the impact of blending and ultraviolet radiation exposure on measured leak rate. Statistical analysis of leak rate test data indicated that blending alone did not significantly affect the leak rate of specimens not exposed to ultraviolet radiation. In the absence of surface blending, ultraviolet radiation exposure was shown to increase sample leak rate at statistically significant levels. The largest leak rate increases, however, occurred when O-ring sealing surface blending was coupled with subsequent ultraviolet radiation exposure. In those instances, the ability of the O-rings to create an effective seal was significantly compromised.
V-localizations andV-Kleisli algebras

We prove a pushout theorem for localizations and Kleisli categories over a symmetric monoidal closed categoryV. That is, suppose ∑ is aV-localizable subcategory of aV-categoryA and thatT=(T,η,μ) is aV-monad onA. Then under suitable relations betweenT and ∑ we show that there is aV-monadT′ induced onA[∑-1] such that the Kleisli category ofT′ is the pushout of the localization functor Φ:A→A[∑-1] and the free functor F:A→K(T). Consequently,K(T′)≈K(T) [S-1] for some S ⊑K(T). We give several examples of this situation.
Differential effects of Ras signaling through NFκB on skeletal myogenesis

Oncogenic Ras (H-Ras G12V) inhibits skeletal myogenesis through multiple signaling pathways. Previously, we demonstrated that the major downstream effectors of Ras (i.e., MEK/MAPK, RalGDS and Rac/Rho) play a minor, if any, role in the differentiation-defective phenotype of Ras myoblasts. Recently, NFkappaB, another Ras signaling target, has been shown to inhibit myogenesis presumably by stimulating cyclin D1 accumulation and cell cycle progression. In this study, we address the involvement of NFkappaB activation in the Ras-induced inhibition of myogenesis. Using H-Ras G12V and three G12V effector-loop variants, we detect high levels of NFkappaB transcriptional activity in C3H10T1/2-MyoD cells treated with differentiation medium. Myogenesis is blocked by all Ras proteins tested, yet only in the case of H-Ras G12V are cyclin D1 levels increased and cell cycle progression maintained. Expression of IkappaBalpha SR, an inhibitor of NFkappaB, does not reverse the differentiation-defective phenotype of Ras expressing cultures, but does induce differentiation in cultures treated with tumor necrosis factor (TNFalpha) or in cultures expressing the RelA/p65 subunit of NFkappaB. These data confirm that NFkappaB is a target of Ras and suggest that the cellular actions of NFkappaB require additional signals that are discriminated by the Ras effector-loop variants. Results with IkappaBalpha SR convincingly demonstrate that H-Ras G12V does not rely on NFkappaB activity to block myogenesis, an observation that continues to implicate another unidentified signaling pathway(s) in the inhibition of skeletal myogenesis by Ras.
Preliminary Evaluation of 15-[18F]Fluoro-3-oxa-pentadecanoate as a PET Tracer of Hepatic Fatty Acid Oxidation

The liver is an important site of fat oxidation. Abnormalities of hepatic mitochondrial fatty acid oxidation (HMFAO) are associated with obesity, type II diabetes, alcoholic hepatitis, and nonalcoholic steatohepatitis. Noninvasive assessment of HMFAO by PET has been impeded by the lack of a specific radiotracer. Methods: No-carrier-added 15-[18F]fluoro-3-oxa-pentadecanoate (FOP) was synthesized and evaluated in living rats and isolated rat livers. Results: FOP showed high uptake and slow clearance of radioactivity from livers in living rats. Inhibition of HMFAO by pretreatment of fasting rats with the carnitine palmitoyltransferase-I (CPT-I) inhibitor reduced the liver-to-blood ratio by 64%. In isolated rat livers, perfused in normoxic (95% O2) and hypoxic (15% O2) conditions with glucose (5 mmol/L) and palmitate (0.15 mmol/L), the externally measured kinetics of FOP showed reversible binding in tissue. The kinetics were adequately fit by a catenary 2-compartment model for estimation of tracer distribution volumes (DVs). The DVs of both compartments were found to correlate with fractional palmitate oxidation rate (FPOR) in experiments in normoxic and hypoxic conditions. The correlation was particularly strong for the slower second compartment (DV2 [mL/g dry weight] = 34.1 FPOR [mL/min/g dry weight] − 0.7, r = 0.89). Relatively small levels of diffusible metabolites of FOP were formed in vivo and in isolated rat liver. Conclusion: The selective uptake of FOP by liver and the high sensitivity of hepatic FOP DV to changes of HMFAO with CPT-I inhibition and hypoxia suggests potential usefulness for the 3-oxa fatty acid analog in assessments of hepatic mitochondrial oxidation of exogenous fatty acids with PET. These data emphasize that further studies are required to clarify the intracellular disposition of FOP in the liver and test its validity as a tracer of HMFAO over a broad range of conditions.
L- and T-type voltage-gated Ca2+ currents in adrenal medulla endothelial cells.

We investigated voltage-dependent Ca2+ channels of bovine adrenal medulla endothelial cells with the whole cell version of the patch-clamp technique. Depolarization elicited an inward current that ...
Androgen receptor activity modulates responses to cisplatin treatment in bladder cancer

Cisplatin (CDDP)-based combination chemotherapy remains the mainstream treatment for advanced bladder cancer. However, its efficacy is often limited due to the development of resistance for which underlying mechanisms are poorly understood. Meanwhile, emerging evidence has indicated the involvement of androgen-mediated androgen receptor (AR) signals in bladder cancer progression. In this study, we aimed to investigate whether AR signals have an impact on sensitivity to CDDP in bladder cancer cells. UMUC3-control-short hairpin RNA (shRNA) cells with endogenous AR and AR-negative 647V/5637 cells stably expressing AR were significantly more resistant to CDDP treatment at its pharmacological concentrations, compared with UMUC3-AR-shRNA and 647V-vector/5637-vector control cells, respectively. A synthetic androgen R1881 significantly reduced CDDP sensitivity in UMUC3, 647V-AR, or 5637-AR cells, and the addition of an anti-androgen hydroxyflutamide inhibited the effect of R1881. In these AR-positive cells, R1881 treatment also induced the expression levels of NF-κB, which is known to involve CDDP resistance, and its phosphorylated form, as well as nuclear translocation of NF-κB. In CDDP-resistant bladder cancer sublines established following long-term culture with CDDP, the expression levels of AR as well as NF-κB and phospho-NF-κB were considerably elevated, compared with respective control sublines. In bladder cancer specimens, there was a strong trend to correlate between AR positivity and chemoresistance. These results suggest that AR activation correlates with CDDP resistance presumably via modulating NF-κB activity in bladder cancer cells. Targeting AR during chemotherapy may thus be a useful strategy to overcome CDDP resistance in patients with AR-positive bladder cancer.
Long-term clinical assessment of the efficacy of adjunctive coronary endarterectomy

The risk and putative efficacy of coronary thromboendarterectomy (TEA) as an adjunct to coronary artery-bypass graft (CABG) operations remain incompletely defined. To address this question, we assessed the long-term results attained in two concurrent cohorts of consecutive patients undergoing myocardial revascularization during a remote period (1971 to 1975). Eighty patients underwent distal right coronary artery (RCA) TEA plus RCA CABG plus one or more other CABGs (Group A) and 592 patients underwent RCA CABG plus one or more other CABGs (Group B). Cumulative follow-up totaled 2,969 patient-years; follow-up (98% complete) averaged 5.7 years for Group A and 4.7 years for Group B. Average number of vessels diseased and of CABG/patient were 3.0 and 2.7 for Group A and 2.9 and 2.8 for Group B. For Group A and Group B, respectively, operative mortality rates were 3.8% versus 2.9% (p = NS) and perioperative myocardial infarction (MI) rates were 16% versus 8% (p
Hydrologic response and recovery to prescribed fire and vegetation removal in a small rangeland catchment

Prescribed fire can be used to return wild lands to their natural fire cycle, control invasive weeds, and reduce fuel loads, but there are gaps in the understanding of post-disturbance responses of vegetation and hydrology. The impact of a prescribed fire and subsequent aspen cutting on evapotranspiration (ET) and streamflow was assessed for the Upper Sheep Creek catchment, a 26-ha headwater catchment dominated by low sagebrush, mountain big sagebrush, and aspen within the Reynolds Creek Experimental Watershed. The 2007 prescribed fire consumed 100% of the mountain big sagebrush and approximately 21% of the low sagebrush. The aspen, which were mostly untouched by the fire, were cut in the fall of 2008. Post-disturbance ET and vegetation recovery were related to the loss of rooting depth. ET recovered within 2 years on the low sagebrush area with limited rooting depth, while that on the deeper-rooted mountain big sagebrush area took 4 years to recover. ET from the aspen trees, which can sprout from existing roots, recovered within 2 years. The influence of vegetation disturbance on streamflow was assessed using both empirical time trend analysis and process-based modelling. Although both approaches suggested approximately a 20% increase in streamflow during the 6 years post-disturbance, results from the empirical time trend analysis were marginally significant (p = 0·055), while those from the process-based modelling were not statistically significant. Marginal streamflow response can be attributed to rapid post-disturbance recovery of the aspen where most of the streamflow originates. Published 2016. This article is a U.S. Government work and is in the public domain in the USA
Cultural Involvement, Indigenous Identity, and Language: An Exploratory Study of Zapotec Adolescents and Their Parents

This exploratory study analyzed the influence of Zapotec parental socialization practices on the cultural awareness and involvement, ethnic identity, and Zapotec language use of their adolescent ch...
Genome-Wide Epigenetics in Myeloid Leukemias.

While the role of genetic alterations in cancer is well-recognized, epigenetic deregulation has only recently been identified as a hallmark of malignant transformation. The term “epigenetic” refers to a heritable regulation of gene expression that is not dependent on changes in the DNA sequence. These epigenetic modifications – including but not limited to DNA methylation and covalent modifications of histone tails – play a crucial role in determining chromatin structure and gene expression. Abnormal epigenetic regulation can lead to aberrant chromatin structure and deregulation of transcriptional activity. Epigenetic lesions can affect cancer-related genes, such as CDKN2B, CDKN2A, RB, and BRCA1, and it is not rare for epigenetic lesions to accompany genetic mutations of these and other genes, suggesting that epigenetic deregulation can form a part of the multi-step process of oncogenesis. An alteration in the distribution of DNA methylation has been demonstrated in AML as well as in other malignancies. Generally, intergenic DNA methylation is reported to decrease and promoter methylation to increase. Hypomethylation of DNA can lead to genomic instability and further increase the number of genetic lesions, while promoter hypermethylation has been associated with aberrant silencing of tumor suppressor genes. Altered levels of acetylation at specific histone residues were also shown to be associated with aberrant chromatin structure and gene deregulation in AML. Several oncogenic transcription factors and fusion proteins, such as PML-RARalpha, and AML1-ETO, can introduce aberrant epigenetic programming in myeloid cells through recruitment of epigenetic modifying enzymes to their target genes. However, the emerging field of epigenomic profiling has yielded evidence that epigenetic deregulation in AML is more profound and cannot always be linked to the presence of a given fusion protein. The mechanisms leading to genome-wide epigenetic deregulation still remain largely unidentified, although environmental factors and aging can contribute to this process. Current epigenetic profiling studies have revealed that DNA methylation or histone modification patterns can identify biologically distinct forms of AML that may not be readily identified through other methods. New data suggest that specific DNA methylation profiles may be associated with response to therapeutic agents, including epigenetic-targeted drugs. Numerous epigenetic candidate biomarkers have been recently described in both myeloid and lymphoid malignancies. Integrative analysis of DNA methylation, histone modifications, and gene expression may synergize to identify in far greater depth than single platform studies differences in gene regulation among leukemias. Overall, the emerging field of epigenomics provide a new opportunity to more accurately identify biological variation and therapeutically target acute myeloid leukemias.
Acceptable regret model in the end-of-life setting: Patients require high level of certainty before forgoing management recommendations.

Abstract Background The acceptable regret model postulates that under some circumstances decision-makers may tolerate wrong decisions. The purpose of this work is to empirically evaluate the acceptable regret model of decision-making in the end-of-life care setting, where terminally ill patients consider seeking curative treatment versus accepting hospice/palliative care. Methods We conducted interviews with 48 terminally ill patients to assess their preferences about end-of-life treatment choices. We first elicited the patient's regret of potentially wrong choices with regards to the recommended management and provided information on life expectancy estimated by two prognostication models. We then elicited the patients' level of acceptable regret by assessing their tolerance for potentially wrongly accepting hospice care versus continuing unnecessary treatment. Using the levels of acceptable regret, we computed: (1) the probability of death above which a patient would tolerate wrongly accepting hospice care and (2) the probability of death below which the patient would tolerate unnecessary treatment. We also assessed patients' understanding of the interview questions using a 7-point Likert scale. Results We found that the median probability of death above which a patient would tolerate wrongly accepting hospice care was 96% (95% CI 94–98%), whereas the median probability of death below which a patient would tolerate unnecessary treatment was 2.5% (95% CI 0.3–5%). We also found that the levels of acceptable regret measured for wrong hospice referral (mean = 1.52; SD = 2.26; min = 0; max = 7.72) were similar to the levels of acceptable regret measured for unnecessary treatment (mean = 2.10; SD = 4.33; min = 0; max = 23) (KW test; p = 0.68) indicating that acceptable regret levels for either of the wrong decisions is felt similarly. The results were independent of the estimated probability of death communicated to patients before the acceptable regret interview. Conclusions We have elicited empirical data that corroborated the acceptable regret hypothesis. The requirement for high level of certainty before accepting recommended management may explain the difficulties related to decision-making in the end-of-life setting.
“Nuestra captividad”: Captivity and religious difference in an early seventeenth-century translation of the Epistola Rabbi Samuelis (1339)

ABSTRACTThis study concerns a manuscript authored by Diego de la Torre (Lilly Sp. Hist. 1628), an Andalusian Carmelite who was taken captive in the 1620s and brought to Tunis. The manuscript begins with a prologue to his Spanish translation of the Epistola Rabbi Samuelis, a fourteenth-century Latin polemic concerning the captivity of the Jews. The prologue is dedicated to a French nobleman and fellow captive, Thomas d'Arcos, who infamously converted to Islam and whose name has been consequently blotted out in the manuscript. A close reading of the text that follows sheds further light on the translator's perspective as a “captivo” in the preliminaries of the epistle. It shows how Diego de la Torre's version of the Epistola—as an example of what Clem Robyns has theorized as a “defensive translation”—associates Christian enslavement with notions of Jewish captivity, and also expresses anxieties over maintaining religious difference and the threat of apostasy in Muslim North Africa during the early seventeen...
How Can Community Organizations Support Urban Transformative Teacher Leadership? Lessons From Three Successful Alliances

AbstractTeachers who organize for educational equity and social justice generally do so through teacher-led professional networks. Community organizations (COs) that seek to support such teacher leaders can face challenges in working with their organic and often horizontally organized networks. This article examines three case studies of COs that developed successful alliances with urban teacher leaders in teacher-led networks and identifies specific strategies COs used to support the teachers.
Gamma irradiation of fine-emulsion sausage containing sodium diacetate.

Listeria monocytogenes, a psychrotrophic foodborne pathogen, is a frequent postprocess contaminant of ready-to-eat(RTE) meat products, including frankfurters and bologna. Ionizing radiation can eliminate L. monocytogenes from RTE meats. Sodium diacetate (SDA) incorporated into fine-emulsion sausages inhibits the growth of L. monocytogenes. Irradiation of L. monocytogenes suspended in SDA solutions resulted in synergistic reductions of the microorganism. L. monocytogenes populations were reduced by >9 log10 units at a radiation dose of 1.5 kGy when suspended in 0.125% SDA solution. In contrast, the D10-values (the ionizing radiation doses required to reduce the population by 90%) were 0.58, 0.59, 0.57, and 0.53 kGy for L. monocytogenes populations suspended in emulsions containing 0, 0.125, 0.25, and 0.5% SDA, respectively. The D10-values for L. monocytogenes surface inoculated onto frankfurters dipped in 0, 0.125, 0.25, and 0.5% SDA solutions were 0.58, 0.53, 0.54, and 0.52 kGy, respectively. Postirradiat...
Staffing to Stabilize the Tail Probability of Delay in Service Systems with Time-Varying Demand

Analytic formulas are developed to set the time-dependent number of servers to stabilize the tail probability of customer waiting times for the Gt/GI/st + GI queueing model, which has a nonstationary non-Poisson arrival process (the Gt), nonexponential service times (the first GI), and allows customer abandonment according to a nonexponential patience distribution (the +GI). Specifically, for any delay target w > 0 and probability target α ∈ (0, 1), we determine appropriate staffing levels (the st) so that the time-varying probability that the waiting time exceeds a maximum acceptable value w is stabilized at α at all times. In addition, effective approximating formulas are provided for other important performance functions such as the probabilities of delay and abandonment, and the means of delay and queue length. Many-server heavy-traffic limit theorems in the efficiency-driven regime are developed to show that (i) the proposed staffing function achieves the goal asymptotically as the scale increases, a...
Other Extrarenal Manifestations of Autosomal Dominant Polycystic Kidney Disease

ADPKD is a systemic disease with extrarenal as well as renal manifestations. Extrarenal manifestations that will be discussed in this chapter are (1) intracranial aneurysms (ICA), (2) cardiac valve abnormalities, (3) vascular abnormalities, (4) diverticular disease and diverticulitis, (5) abdominal hernias, and (6) bronchiectasis. The prevalence of asymptomatic ICA is about 8%, which is 3–4× higher than the general population. Asymptomatic patients with a family history suggestive of an ICA or subarachnoid hemorrhage (SAH) or ADPKD patients with a previous ruptured ICA should be screened for ICA. Cardiac valve abnormalities, especially mitral valve prolapse (MVP), occur in 18–31% of ADPKD patients. The vascular abnormalities in ADPKD are caused by blood vessel alterations linked to Pkd1 or 2 gene mutations. Vascular abnormalities include endothelial dysfunction, increased carotid intimal and medial thickness, biventricular diastolic dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS), and arterial dissections. ADPKD patients with end-stage renal disease (ESRD) have a higher incidence of diverticulitis once on dialysis or after kidney transplant. On CT scan, there is a threefold increased prevalence of bronchiectasis. Evidence is presented that the vascular abnormalities, cardiac valve abnormalities, ICA, and diverticular disease seen in ADPKD represent a systemic defect in basement membrane collagen and other basement membrane proteins. The presence of ICA or MVP in ADPKD patients does not affect the progression of kidney disease or survival after ESRD.
Declining brachytherapy utilization for high-risk prostate cancer—Can clinical pathways reverse the trend?

Abstract Purpose Although external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) offers a 20% improvement in biochemical progression-free survival compared with dose-escalated EBRT alone for men with intermediate and high-risk prostate cancer, population studies show a concerning decline in BB utilization. Methods We modified our clinical pathway (CP) in January 2016 to indicate EBRT with BB as first-choice modality for high-risk prostate cancer, based on preliminary findings of Androgen Suppression Combined with Elective Nodal and Dose-Escalated Radiation Therapy. A retrospective review was performed on 659 patients with high-risk prostate cancer treated with definitive intent EBRT ± BB within a network of 19 sites between December 2011 and July 2017. χ2 test was used to determine changes in practice pattern before vs. after CP modification. Results Before CP modification, 25.2% of patients were planned for BB, compared with 45.4% afterward (p Conclusion Based on recent evidence suggesting improved biochemical progression-free survival with use of BB for high-risk prostate cancer, we modified our CP, after which we observed increased use of a BB across a network, especially among physicians who do not perform brachytherapy. However, physician preference remains the most significant factor in the nonutilization of BB. New mechanisms are needed to overcome this barrier.
Semantics of Non-Classical First Order Predicate Logics

To describe semantics of a logical system one should define notions of a model and the truth in a model. A major part of classical first order model theory can be developed within the standard semantics, while alternative types of semantics (such as sheaves, forcing, polyadic algebras) play an auxiliary role.
Polyhydroxy Alcohols, Cyclitols, and Carbonyl Compounds

This chapter is the first of a series with the primary purpose of demonstrating the structure of compounds that possess distinct taste. Most monohydroxy alcohols have feeble tastes, but in certain cases, unsaturated monohydroxy alcohols with the general structure shown below taste sweet.
Flow Induced Ordered State of Helical Poly-Benzyl-L-Glutamate

Dielectric constant of α-helical poly-benzyl-L-glutamate (PBLG) is measured in the presence of a velocity gradient using rotating cylindrical electrodes. The electric field is applied across the annular gap between electrodes and the vectors of the mechanical and the electrical forces are perpendicular to each other. The dielectric constant decreases with the increasing velocity gradient, as long as the frequency is sufficiently low. When the frequency is increased, the dielectric constant increases slightly and moreover, the dielectric constant is no longer affected by the velocity gradient if the frequency is further increased. In the presence of a sufficiently high velocity gradient, PBLG solutions exhibit a considerably different dielectric relaxation from that without the velocity gradient. A semi-empirical explanation is presented to account for the behavior of polar molecules in a mechanical field and an electrical field.
Combining Simulation and Optimization in River Basin Management

Historically, there has existed a dichotomy in relation to the use of descriptive models (i.e. simulation) and prescriptive models (i.e. optimization) in river basin management. This is unfortunate, since there are unique advantages with each modelling approach which can be greatly enhanced through their joint usage. Descriptive models allow accurate modelling of complex flow and storage mechanisms in a river basin, and are conducive to Monte Carlo analysis and assessment of risks. Descriptive models, on the other hand, cannot directly find the “best” solutions, which represents the primary advantage of prescriptive models. The latter, however, often require simplifying assumptions on model structure. A combined simulation-optimization strategy for river system management is presented. The procedure is evaluated and tested using the Nizao River system in the Dominican Republic as a case study.
Cortical projections to the two retinotopic maps of primate pulvinar are distinct

Comprised of at least five distinct nuclei, the pulvinar complex of primates includes two large visually driven nuclei; one in the dorsal (lateral) pulvinar and one in the ventral (inferior) pulvinar, that contain similar retinotopic representations of the contralateral visual hemifield. Both nuclei also appear to have similar connections with areas of visual cortex. Here we determined the cortical connections of these two nuclei in galagos, members of the stepsirrhine primate radiation, to see if the nuclei differed in ways that could support differences in function. Injections of different retrograde tracers in each nucleus produced similar patterns of labeled neurons, predominately in layer 6 of V1, V2, V3, MT, regions of temporal cortex, and other visual areas. More complete labeling of neurons with a modified rabies virus identified these neurons as pyramidal cells with apical dendrites extending into superficial cortical layers. Importantly, the distributions of cortical neurons projecting to each of the two nuclei were highly overlapping, but formed separate populations. Sparse populations of double-labeled neurons were found in both V1 and V2 but were very low in number (<0.1%). Finally, the labeled cortical neurons were predominately in layer 6, and layer 5 neurons were labeled only in extrastriate areas. Terminations of pulvinar projections to area 17 was largely in superficial cortical layers, especially layer 1.
The Potential Role of Fatty Acids in Treating Diabetic Neuropathy

This review will summarize recent findings of the effect of supplemental fatty acids, with an emphasis on omega-3 polyunsaturated fatty acids, as a treatment for diabetic peripheral neuropathy. Pre-clinical studies have provided evidence that treating diabetic rodents with δ linolenic acid (omega-6 18:3) and to a greater extent with eicosapentaenoic and docosahexaenoic acids (omega-3 20:5 and 22:6, respectively) improve and even reverse vascular and neural deficits. Additional studies have shown resolvins, metabolites of eicosapentaenoic and docosahexaenoic acids, can induce neurite outgrowth in neuron cultures and that treating type 1 or type 2 diabetic mice with resolvin D1 or E1 provides benefit for peripheral neuropathy similar to fish oil. Omega-3 polyunsaturated fatty acids derived from fish oil and their derivatives have anti-inflammatory properties and could provide benefit for diabetic peripheral neuropathy. However, clinical trials are needed to determine whether this statement is true.
Managing Periocular Filler-Related Syndrome Prior to Lower Blepharoplasty.

Hyaluronic acid (HA) fillers are extensively used in periocular volume augmentation. Although they have an excellent safety profile, filler-related issues such as visibility/palpability, contour abnormalities, malar edema, and blue-gray dyschromia can occur. Recognition and management of filler-related issues are critical prior to subsequent procedures. The clinical course of patients who had periocular HA filler-related issues and subsequently underwent lower eyelid blepharoplasty is described. HA filler was dissolved with hyaluronidase (15–30 U/cm2) treatment. Visible lower eyelid fat prolapse after filler removal was corrected with transconjunctival blepharoplasty with fat repositioning and skin resurfacing. Complications and outcome were assessed and recorded. Twenty-three patients (46 eyelids) were treated. All presented with contour abnormalities, 19 with contour abnormalities and malar edema, and seven with blue-gray dyschromia. In 15 patients, one session of hyaluronidase completely dissolved the filler, and in eight patients, two sessions were required. Of these eight patients, edema resolved after the second hyaluronidase injection in four; in the remaining four, mild edema persisted despite absence of visible/palpable filler. Postblepharoplasty, 19 patients had an acceptable outcome with no complications (82.6%). Four patients had prolonged edema postoperatively; three had a resolution by 6 months. In 23 patients who had skin resurfacing procedures, there was no incidence of postinflammatory hyperpigmentation. HA filler-related issues need to be identified and managed prior to further intervention. Hyaluronidase treatment effectively dissolves the filler, but mild malar edema can persist. Outcomes are acceptable after subsequent blepharoplasty, but adequate patient counseling is necessary about expectations and limitations. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
A Trial of Real-Time Electrographic Seizure Detection by Neuro-ICU Nurses Using a Panel of Quantitative EEG Trends

Non-convulsive seizures (NCS) are a common occurrence in the neurologic intensive care unit (Neuro-ICU) and are associated with worse outcomes. Continuous electroencephalogram (cEEG) monitoring is necessary for the detection of NCS; however, delays in interpretation are a barrier to early treatment. Quantitative EEG (qEEG) calculates a time-compressed simplified visual display from raw EEG data. This study aims to evaluate the performance of Neuro-ICU nurses utilizing bedside, real-time qEEG interpretation for detecting recurrent NCS. This is a prospective, single-institution study of patients admitted to the Duke Neuro-ICU between 2016 and 2018 who had NCS identified on traditional cEEG review. The accuracy of recurrent seizure detection on hourly qEEG review by bedside Neuro-ICU nurses was compared to the gold standard of cEEG interpretation by two board-certified neurophysiologists. The nurses first received brief qEEG training, individualized for their specific patient. The bedside qEEG display consisted of rhythmicity spectrogram (left and right hemispheres) and amplitude-integrated EEG (left and right hemispheres) in 1-h epochs. Twenty patients were included and 174 1-h qEEG blocks were analyzed. Forty-seven blocks contained seizures (27%). The sensitivity was 85.1% (95% CI 71.1–93.1%), and the specificity was 89.8% (82.8–94.2%) for the detection of seizures for each 1-h block when compared to interpretation of conventional cEEG by two neurophysiologists. The false positive rate was 0.1/h. Hemispheric seizures (> 4 unilateral EEG electrodes) were more likely to be correctly identified by nurses on qEEG than focal seizures (≤ 4 unilateral electrodes) (p = 0.03). After tailored training sessions, Neuro-ICU nurses demonstrated a good sensitivity for the interpretation of bedside real-time qEEG for the detection of recurrent NCS with a low false positive rate. qEEG is a promising tool that may be used by non-neurophysiologists and may lead to earlier detection of NCS.
Spectroscopic Evidence for Exceptional Thermal Contribution to Electron Beam-Induced Fragmentation

While electron beam induced fragmentation (EBIF) has been reported to result in the formation of nanocrystals of various compositions, the physical forces driving this phenomenon are still poorly understood. We report EBIF to be a much more general phenomenon than previously appreciated, operative across a wide variety of metals, semiconductors and insulators. In addition, we leverage the temperature dependent bandgap of several semiconductors to quantify -- using in situ cathodoluminescence spectroscopy -- the thermal contribution to EBIF, and find extreme temperature rises upwards of 1000K.
Challenges in mobile health app research: Strategies for interprofessional researchers

Abstract Aim The purpose of this brief methodological paper is to discuss critical design features and user characteristics that should be considered when scientists from varied health related fields are testing mobile health apps in different patient populations. Background With the growing number of patients using mobile health tracking apps to manage their health and chronic conditions, interprofessional research on these apps is emerging, potentially having a tremendous impact on clinical practice. However, methodological challenges exist when conducting this type of research. Methods Select methodological challenges are illustrated by study examples and supported by various theoretical frameworks. Strategies addressing these challenges are offered to interprofessional researchers who are initiating clinical research in this field of study. Directions for future research are also proposed. Results Customizability, interactivity, usability, and changing health needs are discussed as key design challenges. Age and health literacy are discussed as important user characteristics influencing the adoption of a new technology. Conclusion Mobile health tracking innovations have the potential to benefit patients. Interprofessional teams studying mobile health apps need to understand how apps should be designed for various patient populations, age groups, and literacy abilities to enhance patient engagement with the technology and ultimately support patients’ health needs.
Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside

Organic solute transporter alpha/beta (OSTα/β) is a heteromeric solute carrier protein that transports bile acids, steroid metabolites and drugs into and out of cells. OSTα/β protein is expressed in various tissues, but its expression is highest in the gastrointestinal tract where it facilitates the recirculation of bile acids from the gut to the liver. Previous studies established that OSTα/β is upregulated in liver tissue of patients with extrahepatic cholestasis, obstructive cholestasis, and primary biliary cholangitis (PBC), conditions that are characterized by elevated bile acid concentrations in the liver and/or systemic circulation. The discovery that OSTα/β is highly upregulated in the liver of patients with nonalcoholic steatohepatitis (NASH) further highlights the clinical relevance of this transporter because the incidence of NASH is increasing at an alarming rate with the obesity epidemic. Since OSTα/β is closely linked to the homeostasis of bile acids, and tightly regulated by the nuclear receptor farnesoid X receptor, OSTα/β is a potential drug target for treatment of cholestatic liver disease, and other bile acid-related metabolic disorders such as obesity and diabetes. Obeticholic acid, a semi-synthetic bile acid used to treat PBC, under review for the treatment of NASH, and in development for the treatment of other metabolic disorders, induces OSTα/β. Some drugs associated with hepatotoxicity inhibit OSTα/β, suggesting a possible role for OSTα/β in drug-induced liver injury (DILI). Furthermore, clinical cases of homozygous genetic defects in both OSTα/β subunits resulting in diarrhea and features of cholestasis have been reported. This review article has been compiled to comprehensively summarize the recent data emerging on OSTα/β, recapitulating the available literature on the structure-function and expression-function relationships of OSTα/β, the regulation of this important transporter, the interaction of drugs and other compounds with OSTα/β, and the comparison of OSTα/β with other solute carrier transporters as well as adenosine triphosphate-binding cassette transporters. Findings from basic to more clinically focused research efforts are described and discussed.
Stability of helical vortex structures shed from flexible rotors

Abstract The presented investigation is motivated by the need to uncover connections between underlying rotor fluid–structure interactions and vortex dynamics to fatigue performance and characterization of flexible rotor blades, their hub, and their supporting superstructure. Towards this effort, temporal stability characteristics of tip vortices shed from flexible rotor blades are investigated numerically. An aeroelastic free-vortex wake method is employed to simulate the helical tip vortices and the associated velocity field. A linear eigenvalue stability analysis is employed to quantify stability trends (growth rate v. perturbation wavenumber) and growth-rate temporal evolution of tip vortices. Simulations of a canonical rotor with rigid blades and its generation of tip vortices are first conducted to validate the stability analysis employed herein. Next, a stationary wind turbine is emulated using the National Renewable Energy Laboratory (NREL) 5-MW reference wind turbine base design to investigate the impact rotor aeroelasticity has on tip-vortex stability evolution in time. Blade flexibility is shown to reduce the sensitivity of tip vortex destabilization to low wavenumber perturbations, also blade-pitch reduces growth-rate magnitude and alters the growth-rate peak dependence on perturbation wavenumber, all of which have in the past not been reported in the rotorcraft literature. The presented investigation aims to develop insight into the tip vortex kinematics and stability of the NREL 5-MW reference wind turbine. However, the frameworks presented herein can be applied to generalized rotor designs to work towards identifying the impact tip-vortex kinematics and stability have on fatigue loading and adverse blade–vortex interaction effects, such as excessive noise emission and rotor vibrations.
Central sleep apnea is uncommon after stroke.

Abstract Objective/background Stroke is often considered a risk factor for central sleep apnea (CSA). The goal of this study was to determine the prevalence and clinical correlates of CSA in patients with ischemic stroke. Patients/methods In this analysis, 1346 participants in the Brain Attack Surveillance in Corpus Christi (BASIC) project underwent a home sleep apnea test shortly after ischemic stroke. Respiratory events during sleep were classified as central apneas, obstructive apneas, or hypopneas. Central apnea index (CAI) was defined as number of central apneas divided by recording time. CSA was defined as CAI ≥5/hour with at least 50% of all scored respiratory events classified as central apneas. Demographics and co-morbidities were ascertained from the medical record. Results Median CAI was 0/hour. Nineteen participants (1.4%) met criteria for CSA. Participants with CSA were more likely to be male, and had lower prevalence of obesity than participants without CSA. There was no association between CSA and other co-morbidities. Conclusions CSA was uncommon in this large cohort of patients with recent ischemic stroke.
Encoding Socio-Historical Exegesis as Social Physics Predicates

This paper concerns developments in social physics rule and schema authoring made as part of the ongoing VESPACE project, a multinational research effort in developing a social physics driven virtual reality experience set in eighteenth-century France. Central to the theoretical application of social physics in this socio-historical context is the concept of citation as AI– that is, the historically-grounded reconstruction of human behavior represented by cited schemata, rules, and actions. In order to facilitate the authoring of domain-specific rules for the Ensemble social physics engine by history and cultural studies experts, we endeavored to develop a new collaborative authoring tool, which we tested in a series of workshops. The results of these workshops revealed various domain needs, as well as the shortcomings of representing data structures using one-to-one correspondences in UX/UI design.