cssi/SciSciGPT-SciSciNet huggingface dataset:
Adiponectin attenuates abdominal aortic aneurysm formation in hyperlipidemic mice

Abstract Objective Abdominal aortic aneurysms (AAA) are age-associated, life-threatening inflammatory dilations of the abdominal aorta. Human population studies have shown an association between obesity and AAA formation, but the molecular mechanisms underlying this connection remain largely unexplored. Adiponectin is an anti-inflammatory adipokine that is downregulated in obesity. In this study we evaluated the role of adiponectin in a model of AAA using apolipoprotein E/adiponectin double-knockout ( Apoe −/− Apn −/− ) mice. Approach and results Angiotensin II (Ang II)-infusion in male Apoe −/− Apn −/− mice led to a higher incidence of AAA and a significant increase of maximal aortic diameter compared with that of Apoe −/− mice (2.12 ± 0.07 mm vs. 1.67 ± 0.09 mm, respectively at 28 days). Adiponectin deficiency augmented the early infiltration of macrophages and increased the expression of pro-inflammatory factors in the dilated aortic wall. MMP-2 and MMP-9 activation was also augmented in the aorta of Apoe −/− Apn −/− mice compared to Apoe −/− mice. These data suggest that the downregulation of adiponectin could directly contribute to the elevated incidence of AAA observed in obese individuals. Conclusions Adiponectin attenuates Ang II-induced vascular inflammation and AAA formation in mice.
Age-related changes in the spontaneous motor rhythms of the senescence-accelerated mouse (SAMP8).

The present study examined the effect of age on the spontaneous motor rhythms of mice during wheel running. The spontaneous motor tempo (SMT) of wheel running was measured for the P8 strain of the senescence-accelerated mouse (SAMP8) by recording the sequence of time intervals (measured in milliseconds) for successive revolutions of a run-wheel over the course of 16 days. Analyses of the distribution of interrevolution intervals of 2-, 7-, and 12-month-old SAMP8 revealed an age-related slowing of wheel running and a corresponding increase in variability consistent with Weber's law. All three age groups also demonstrated a practice effect over the course of testing best described by a power law. These findings provide evidence of age-related changes in the spontaneous motor rhythms of the SAMP8 that occur as early as 7 months of age. The results are consistent with age-related changes in human subjects and suggest that spontaneous wheel-running behavior in rodents may be a good model for studying SMT.
AGI Book Review

Muscovite and rare metal-muscovite pegmatites Shmakin, B. M., 1976, PEGMATITES CONTAINING MUSCOVITE AND RARE METALS (MINERALOGICAL, GEOCHEMICAL AND GENETIC CHARACTERISTICS OF PEGMATITES FROM EAST SIBERIA AND INDIA) (Muskovitovyye i redkometal'nomuskovitovyye pegmatity (mineralogo-geokhimicheskaya i geneticheskaya kharakteristika pegmatitov Vostochnoy Sibiri i Indii): AN SSSR SO Inst. Geochim., Izd-vo Nauka, Siberian Div., Novosibirsk, 367 pp., illus. (incl. tables, geol. sketch maps). Reviewed by A.A. Beus Mineralogy of the Donets basin Lazarenko, Ye. K., Panov, B. S., Gruba, V. I., 1975, MINERALOGY OF THE DONETS BASINS (Mineralogiya Donetskogo Basseyna), Izd-vo Naukova Dumka, Kiev, v. I, 252 pp., 159 figs., price - Rubles 1.95; v. II, 502 pp., 315 figs., price - Rubles 3.44. Reviewed by Eugene A. Alexandrov
Designing energy-efficient optical line terminal for TDM passive optical networks

This paper proposes a novel scheme which can efficiently reduce the energy consumption of Optical Line Terminals (OLTs) in Time Division Multiplexing (TDM) Passive Optical Networks (PONs) such as EPON and GPON. Currently, OLTs consume a significant amount of energy in PON, which is one of the major FTTx technologies. To be environmental friendly, it is desirable to reduce energy consumption of OLT as much as possible; such requirement becomes even more urgent as OLT keeps increasing its provisioning data rate, and higher data rate provisioning usually implies larger energy consumption. In this paper, we propose a novel energy-efficient OLT structure which guarantees services of end users with the smallest number of power-on OLT line cards. More specifically, we adapt the number of power-on OLT line cards to the real-time incoming traffic. Also, in order to avoid service disruption resulted by powering off OLT line cards, proper optical switches are equipped in OLT to dynamically configure the communications between OLT line cards and ONUs.
What can we learn from neutrinoless double beta decay experiments

We assess how well next generation neutrinoless double beta decay and normal neutrino beta decay experiments can answer four fundamental questions. 1) If neutrinoless double beta decay searches do not detect a signal, and if the spectrum is known to be inverted hierarchy, can we conclude that neutrinos are Dirac particles? 2) If neutrinoless double beta decay searches are negative and a next generation ordinary beta decay experiment detects the neutrino mass scale, can we conclude that neutrinos are Dirac particles? 3) If neutrinoless double beta decay is observed with a large neutrino mass element, what is the total mass in neutrinos? 4) If neutrinoless double beta decay is observed but next generation beta decay searches for a neutrino mass only set a mass upper limit, can we establish whether the mass hierarchy is normal or inverted? We base our answers on the expected performance of next generation neutrinoless double beta decay experiments and on simulations of the accuracy of calculations of nuclear matrix elements.
Brief Note: Effects of Prostaglandins, Epinephrine and NaF on Human Leukocyte, Platelet and Liver Adenyl Cyclase

Despite the limited scope of this study, the data show that homogenates of human leukocytes, platelets and liver are capable of synthesizing cyclic AMP, and that such preparations are responsive to hormonal stimulation. Epinephrine stimulates cyclic AMP production in liver and leukocyte homogenates, and NaF shows a stimulatory effect in each tissue. 1,8 The data confirm the previous reports 10,11 that prostaglandin E 1 stimulates platelet adenyl cyclase, but further shows a lack of stimulation by prostaglandin F/ 1β . Incubation of leukocytes with the prostaglandins showed a similar effect. It is suggested that further study may establish a relationship between adenyl cyclase stimulation and chemotaxis or phagocytic activity of circulating leukocytes as has been reported in amebae. 12 Since systemic enzyme deficiencies such as phosphorylase in Hers’ Disease 13 and amylo-1.4→1.6-transglucosidase in Andersens’ Disease 14 are evident in leukocytes, it is suggested that further study of circulating leukocytes may also detect an abnormal responsiveness or a deficiency of adenyl cyclase.
Overview of contraception.

The United States has the highest rates of adolescent pregnancy and birth of any country in the industrialized Western world; adolescent pregnancy rates in the United States are more than two to three times the rates of Canada or Europe and eight times higher than rates in the Netherlands and Japan. It has been estimated that approximately one third of American girls will experience at least one pregnancy before the age of 20 even taking into account declining adolescent pregnancy rates from the early 1990s to 2002. Approximately 820000 adolescent pregnancies occurred in the United States in 2003. The rate of adolescent births in the United States has fallen since its high in the early 1950s and since a recent peak in the 1990s to a new low of 41.7 births per 1000 adolescents aged 15 to 19 years; this represents a 33% drop since 1991. The rate for 10- to 14-year-olds has declined by 57%. Depending on how the question is phrased and when it is asked 70% to 90% of adolescent pregnancies are unplanned. (excerpt)
Nitrogen isotope exchange between NO and NO2 and its implications for δ15N variations in tropospheric NOx and atmospheric nitrate

The nitrogen (N) isotope exchange between nitric oxide (NO) and nitrogen dioxide (NO2) has been previously suggested to influence N stable isotope compositions (δ15N) of these molecules. However, there is disagreement in the magnitude of the N isotopic fractionation ( αNO2/NO) resulting from this exchange process between previous experimental and theoretical studies. To this end, we measured αNO2/NO associated with this exchange reaction at various temperatures. Our results indicate αNO2/NO to be 1.0403 ± 0.0015, 1.0356 ± 0.0015, and 1.0336 ± 0.0014 at 278 K, 297 K, and 310 K, respectively. These measured values are within experimental error of the values we calculated using a modified version of the Bigeleisen-Mayer equation corrected for accurate zero-point energies, indicating an agreement between experiment and theory. Modeling of this exchange reaction demonstrates that δ15N-NO2 may exhibit a diurnal and seasonal profile if N isotopic equilibrium is achieved.
Political Legitimacy and Economic Growth

Studies that examine the sources of growth in developing economies including Africa have moved away from the traditional "proximate" determinants that focused on capital accumulation and factor productivity to "deeper" determinants of growth mainly institutions. Traditional sources such as capital accumulation (physical or human) and technology are not causes of growth; they are growth (North and Thomas, 1973). Though vaguely defined, it is widely acknowledged that political institutions underpin much of the difference in growth performance of economies. However, we remain remarkably ignorant about how and which political institutions influence economic growth. Existing literature provides a dichotomous characterization of political institutions into democratic Vs. autocratic to characterize the relationship to economic growth. But this distinction does not seem to capture the relevant differences in growth performance. The existence of both democratic and autocratic states that registered both poor and fast growth has put into question the basic thesis. This study attempts to address this challenge. It provides a theoretical framework and empirical evidence to show that differences in growth performance between countries are explained by differences in the degree of state legitimacy. The basic argument that political legitimacy of the state is fundamental to growth, in this study, rests on three fundamental mechanisms: 'the policy effectiveness hypothesis, 'the fiscal capacity hypothesis' and 'the political-loser hypothesis'.
Off-Year Apple Bearing and Apple Spur Growth.

(1920). Off-Year Apple Bearing and Apple Spur Growth. Journal of Pomology and Horticultural Science: Vol. 2, No. 1, pp. 16-37.
Isolation of an L type culture from a Gram positive spore-bearing bacillus.

SummaryColonies similar in appearance and properties to the L type colonies of Gram negative bacilli were isolated from cultures of several large Gram positive bacilli. The L type colonies obtained from a spore-producing strain grew equally well from cultures obtained from heated spores as from the original culture, indicating that the L type colonies grew from the bacilli and were not an accidental contamination of the culture.
The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis.

Expression of viral proteins may result in susceptibility of cells to the cytotoxic effect of Tumor Necrosis Factor Alpha (TNF). While murine C127 cells containing the bovine papillomavirus type 1 (BPV-1) genome were reported to exhibit increased TNF sensitivity, the gene(s) responsible was not identified. The BPV-1 E6 oncoprotein induces tumorigenic transformation of murine C127 cells and stimulates transcription when targeted to a promoter. BPV-1 E6 was introduced into C127 cells (PBE6) by retroviral infection and stable clones were isolated. These cells showed increased apoptosis in response to TNF, as measured by several criteria. TNF-induced apoptosis in PBE6 cells was accompanied by increased release of arachidonic acid, indicating that phospholipase A2 was activated. We also provide evidence that BPV-1 E6 mediated-sensitization of cells to TNF-induced apoptosis can ocur in the absence of p53.
We Need Professional Help: Advocating for a Consistent Standard of Review When Regulations of Professional Speech Implicate the First Amendment

The Circuits are split as to what level of scrutiny should be applied to challenged regulations of professional speech. In the past two years, the Third and Fourth Circuits have chosen to apply intermediate scrutiny to regulations of professional speech whereas the Ninth and Eleventh Circuits have chosen to apply rational basis review. This Note argues for the adoption of intermediate scrutiny as the appropriate standard with which to analyze regulations of professional speech, which are inherently content-based. In doing so, this Note explores the genesis of the professional speech doctrine as well as the implications of withholding First Amendment protections from professional speech.
FeAl/Al_2O_3 Nano-composite Obtained by Mechanically Activated Spark Plasma Synthesis

Method of mechanically activated spark plasma sintering (MASPS) was used. First, the powders of Fe, Al and Al2O3 were activated by high energy ball-milling. Then the powders were synthesized and Consolidated by spark plasma sintering machine. The activation function of Al2O3, the influence of the sintering process on microstructure and properties of the composite were discussed. The results indicated that FeAl/Al2O3 nano-composites with fine grains and high density could be obtained by MASPS, and the highest density was 96. 4%.
Type 2 Diabetes Prediction

In this chapter, we review prediction models for type 2 diabetes, starting with models without genetic information and moving on to models with increasing complexity in terms of incorporating genetic information. We discuss the strength of current prediction models and indicate how we might be able to improve diabetes prediction in the future. For a complementary discussion of prediction models in the context of obesity, please see Chap. 23.
Nokia Drops the Torch

When Stephen Elop joined Nokia as President and CEO in September 2010, he faced a daunting turnaround challenge. Nokia’s mobile device market share, which had peaked in 2007 at around 40 % worldwide, had fallen to under 30 %. The decline coincided with the launch of Apple’s wildly popular iPhone line and Google’s release of its open and free Android mobile operating system. This new competition triggered a tectonic shift in consumer demand, wireless carrier and app developer interest away from Nokia’s classic hardware-centric phone designs to Internet-connected smartphones with an abundance of applications. But that long-term shift and Nokia’s inability to keep pace are only obvious in retrospect. Elop joined Nokia amid expressions of optimism from the company’s directors that “The core strategy is solid and Nokia will continue to power through what is a substantial transformation (from a hardware company to a software company). Elop will help to accelerate that” (Nokia 2010).
Risk Factors for Early Death After Rituximab-Based Immunochemotherapy in Older Patients With Diffuse Large B-Cell Lymphoma

Background Older patients with diffuse large B-cell lymphoma (DLBCL) are at risk of severe chemotherapy-related morbidity and mortality. Our objective was to quantify the risk and identify factors associated with death during the first cycle of immunochemotherapy in this population. Patients and methods Using Medicare claims linked to the population-based SEER registry (SEER-Medicare), we studied patients with DLBCL aged 65 years and older who received immunochemotherapy containing rituximab, cyclophosphamide, and vincristine, in combination with doxorubicin, mitoxantrone, or etoposide in 2003-2012. Risk factors for death and hospitalization within the first 30 days of treatment were studied in multivariable logistic regression models. Results We identified 5,530 patients with a median age of 76 years, of whom 94% received doxorubicin-containing immunochemotherapy. Granulocyte colony-stimulating factor (G-CSF) was administered to 66% of patients during the first treatment cycle. Cumulative incidence of death at day 30 was 2.2%. The risk was significantly higher in patients aged 75 years and older and those who had B symptoms, chronic kidney disease, poor functional status, use of walking aids or wheelchairs, and prior hospitalization or upper endoscopy. The group with 0 to 1 risk factors (56% of patients) had a very low (0.6%) risk of early death, whereas the group with 4 or more risk factors (6% of patients) had a risk of 8.3%. Receipt of G-CSF was associated with a lower probability of early death in the high-risk group. The incidence of hospitalization within the first 30 days was 23.5%, peaking at day 8 of the cycle. Conclusions Among older patients with DLBCL who receive contemporary immunochemotherapy, 1 in 45 die during the first month of treatment, and 1 in 4 are hospitalized. Factors identifiable from administrative/electronic records can stratify this risk and could be incorporated into decision support tools. Prophylactic G-CSF is not administered to more than one-third of patients, indicating an opportunity for improved preventive interventions.
Second Order-Based Real-Time Anomaly Detection for Application Maintenance Services

Application Maintenance Services (AMS) is essential for applications executed on servers to function properly. Its objective is to reduce the application incidents happened and quickly recover services from application failures/issues. The application incidents defined as events when there are some application failures/issues happened are major concerns of AMS, therefore we propose a second order-based anomaly detection method to describe and predict application incidents based on analysis of monitored server traffic metrics. The proposed method first detects anomalies for each metric, second builds the linkage between detected anomalies for all metrics of the server and application incidents, and then predicts potential application incidents. Through the experiments, we find that the presented method provides satisfactory results for identify application incident, which gives more than 90 percentage recall rate while about 65 percentage precision rate.
Explicit estimates for the distribution of numbers free of large prime factors

Abstract There is a large literature on the asymptotic distribution of numbers free of large prime factors, so-called smooth or friable numbers. But there is very little known about this distribution that is numerically explicit. In this paper we follow the general plan for the saddle point argument of Hildebrand and Tenenbaum, giving explicit and fairly tight intervals in which the true count lies. We give two numerical examples of our method, and with the larger one, our interval is so tight we can exclude the famous Dickman–de Bruijn asymptotic estimate as too small and the Hildebrand–Tenenbaum main term as too large.
Structural Basis for Substrate Recognition by the Ankyrin Repeat Domain of Human DHHC17 Palmitoyltransferase

DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates is still poorly understood. There is currently no structural information about the interaction between any DHHC enzyme and protein substrates. In this study we have investigated the structural and thermodynamic bases of interaction between the ankyrin repeat domain of human DHHC17 (ANK17) and Snap25b. We solved a high-resolution crystal structure of the complex between ANK17 and a peptide fragment of Snap25b. Through structure-guided mutagenesis, we discovered key residues in DHHC17 that are critically important for interaction with Snap25b. We further extended our finding by showing that the same residues are also crucial for the interaction of DHHC17 with Huntingtin, one of its most physiologically relevant substrates.
Achieving urinary continence in cloacal exstrophy: The surgical cost

Abstract Introduction Cloacal exstrophy (CE) is a severe midline congenital abnormality that requires numerous surgical corrections to achieve an acceptable quality of life. Candidates for urinary continence undergo multiple procedures, most often continent bladder diversions, to become socially dry. Here, the authors investigate the number of genitourinary interventions that patients with CE undergo to attain urinary continence. Materials and methods A retrospective review of a prospectively maintained database of 1311 exstrophy epispadias complex patients was performed. Patients with CE who have had at least one continence procedure were included. A continence procedure was defined as bladder neck reconstruction with or without augmentation, bladder neck transection with continent urinary diversion, augmentation cystoplasty, or use of injectable bulking agents. Continence was defined as a dry interval greater than 3 hours without leakage at night. Results In total, 140 CE and CE variant patients have been managed at the authors' institution. Of the 116 CE patients, 59 received at least one continence procedure, 14 were excluded for incontinent diversion or cystectomy, and the remaining 43 patients are awaiting a continence procedure. At the time of analysis, 42 (71%) patients who underwent a continence procedure were dry. The median number of total urologic procedures to reach urinary continence was 4 (range 2–10). This included 1 bladder closure (range 1–3), 2 urinary continence procedures (range 1–4), and 1 (range 0–4) "other" genitourinary procedures. The median time to urinary continence was 11.0 years (95% CI [9.2–14.2]). Conclusions A majority of CE patients who undergo a diversion procedure can achieve urinary continence. However multiple continence procedures are likely necessary. Of patients who are candidates for a continence procedure, half will be continent by the age of 11. Level of Evidence Level IV, Case series with no comparison group.
A 6.75–8.25-GHz −250-dB FoM Rapid ON/OFF Fractional-N Injection-Locked Clock Multiplier

A rapid ON/OFF LC-based fractional-N injection-locked clock multiplier (ILCM) is presented. The proposed architecture extends the merits of ILCMs to fractional-N operation. It employs a high-resolution digital-to-time converter to align the injected pulses to the oscillator’s zero crossings. An all-digital frequency-tracking loop continuously tunes the oscillator free-running frequency toward the target output frequency. The proposed clock multiplier can be powered ON from a completely OFF state almost instantaneously. Background calibration techniques ensure that robust operation across process, voltage, and temperature. Fabricated in 65-nm CMOS process with an active area of 0.27 mm2, the prototype ILCM generates output clock in the range of 6.75–8.25 GHz using a 115-MHz reference clock. It achieves integrated jitter performance of 109 fsrms (integer-N) and 177 fsrms (fractional-N), while consuming only 2.65 (integer-N) and 3.25 mW (fractional-N). This translates to the best-reported FoMJ of −255 (integer-N) and −250 dB (fractional-N). The turn-on time is less than 4 ns in both the integer- and fractional-N modes, illustrating almost instantaneous settling.
Lattice-valued spaces: ⊤-Completions

Abstract The concept of a ⊤-Convergence space has recently been introduced and studied. These spaces are related to the top level space of a lattice-valued convergence space. In order to consider completions, ⊤-Cauchy spaces are defined and investigated in the present work. Each ⊤-Cauchy space possesses a completion and, moreover, each topological ⊤-Cauchy space has a topological completion. Completions of ⊤-uniform limit spaces are also introduced.
Patients With Infected Total Hip Arthroplasty Undergoing 2-Stage Exchange Arthroplasty Experience Massive Blood Loss.

Abstract Background Two-stage exchange arthroplasty is the preferred treatment for chronic periprosthetic joint infection following total hip arthroplasty (THA). These patients are at high risk of substantial blood loss and perioperative blood transfusion. Our study aimed at determining risk factors for blood transfusion during a 2-stage exchange for infected THA. Methods Medical records of 297 patients with infected THA who underwent 2-stage exchange arthroplasty from 1997 to 2016 were reviewed. Blood loss was calculated using a validated formula. Transfusion data, clinical information, and operative data were gathered to determine predictors of blood loss and risk factors for perioperative allogeneic blood transfusion. Results Calculated blood loss was significantly higher during reimplantation than resection arthroplasty (5156.0 ± 3402 mL vs 3706.9 ± 2148 mL; P Conclusion Patients with periprosthetic joint infection following THA have significant blood loss during both stages of exchange arthroplasty, especially reimplantation. Hematological optimization should be considered in all patients requiring a transfusion after the first stage, as these patients are at greater risk of requiring transfusion after the second stage. The use of tranexamic acid dramatically decreases the risk of requiring a transfusion in both stages and should be more ubiquitously incorporated into blood management protocols.
Regulation of adenylate cyclase coupled beta-adrenergic receptors.

Publisher Summary The β -adrenergic receptor, of the two major types of adrenergic receptors α and β , is the only adrenergic receptor associated with the stimulation of adenylate cyclase activity. This chapter reviews few recent results derived from binding studies with the radioligand (±)[ 3 H) alprenolol, which is a potent competitive β -adrenergic antagonist. It emphasizes on three areas: (1) how binding of this radioligand to membranes from a variety of tissues meets the essential criteria expected of binding to β -adrenergic receptors; (2) the nature and properties of the β -adrenergic receptors as revealed by these techniques; and (3) studies of physiological, biochemical, and developmental regulation of the β -adrenergic receptors. The use of radioactively labeled β -adrenergic antagonists such as (-)[ 3 H) alprenolol makes it feasible to identify β -adrenergic receptor binding sites in membrane fractions. The binding sites identified with this ligand fulfill all the criteria of kinetics, affinity, specificity, and stereospecificity expected of the physiologically relevant adenylate cyclase-coupled β -adrenergic receptors. These new methods are applicable to a wide variety of mammalian and non mammalian tissues. These techniques provide an important tool for obtaining new insights into the biochemical nature and physiological regulation of the β -adrenergic receptors, apart from providing the assay methods necessary for purification of the β -adrenergic receptors.
Principles of Complementary and Alternative Medicine for Cancer

Complementary and alternative medicine (CAM) is a general term used to describe techniques as diverse as chiropractic and yoga, iridology and meditation, colonic irrigation and spiritual healing. As such, it resists simple definition. Most published definitions describe CAM simply as practices outside of mainstream care. A more fundamental issue concerns the difference between complementary and alternative approaches. Alternative therapies are used in place of mainstream care. Conversely, complementary therapies are used as adjuncts to mainstream care for symptom management and to enhance quality of life. This distinction is especially important in oncology, where treatment choices can be literally a matter of life and death.
Exploring effects of MEK inhibition in tumor microenvironment in non-small cell lung cancer (NSCLC) pre-clinical models.

12060Background: NSCLCs often harbor mutations in the KRAS oncogene and require improved treatment to provide durable disease control. Targeted therapy via MEK inhibition shows promising but tempor...
Harnessing the Materials Project for machine-learning and accelerated discovery

Improvements in computational resources over the last decade are enabling a new era of computational prediction and design of novel materials. The resulting resources are databases such as the Materials Project (www.materialsproject.org), which is harnessing the power of supercomputing together with state-of-the-art quantum mechanical theory to compute the properties of all known inorganic materials, to design novel materials, and to make the data available for free to the community, together with online analysis and design algorithms. The current release contains data derived from quantum mechanical calculations for more than 70,000 materials and millions of associated materials properties. The software infrastructure carries out thousands of calculations per week, enabling screening and predictions for both novel solids as well as molecular species with targeted properties. As the rapid growth of accessible computed materials properties continues, the next frontier is harnessing that information for automated learning and accelerated discovery. In this article, we highlight some of the emerging and exciting efforts, and successes, as well as current challenges using descriptor-based and machine-learning methods for data-accelerated materials design.
2213 Tumor suppressors p53 and ARF control oncogenic potential of triple-negative breast cancer cells by regulating RNA editing enzyme ADAR1

OBJECTIVES/SPECIFIC AIMS: Triple-negative breast cancer (TNBC) accounts for one-fifth of the breast cancer patient population. The heterogeneous nature of TNBC and lack of options for targeted therapy make its treatment a constant adventure. The deficiency of tumor suppressors p53 and ARF is one of the known genetic signatures enriched in TNBC. Crucial questions remain about how TNBC is regulated by these genetic alterations. METHODS/STUDY POPULATION: In order to address this issue, we established p53/ARF-defective murine embryonic fibroblast and mammary epithelial cell to study the molecular and phenotypic consequences. Moreover, transgenic mice were generated to investigate the effect of p53/ARF deficiency on mammary tumor development in vivo. RESULTS/ANTICIPATED RESULTS: Increased proliferation and transformation capability were observed in p53/ARF-defective cells, and an aggressive form of mammary tumor was also seen in p53−/−ARF−/− mice. Gene expression profiling and knock-down experiments using shRNAs were conducted to identify inflammatory marker ISG15 and RNA-editing enzyme ADAR1 as potential culprits for the elevated oncogenic potential. Interestingly, we found that the overexpression of ISG15 and ADAR1 is also prevalent in human TNBC cell lines. Reducing ADAR1 expression abrogated the oncogenic potential of human TNBC cell lines, while non-TNBC cells are less susceptible. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate critical roles played by the tumor suppressors p53 and ARF in the pathogenesis of TNBC, likely through regulating ADAR1-mediated RNA modifications. Further understanding of this pathway promises to shed light on genetics-driven vulnerabilities of TNBC and inform development of more effective therapeutic strategies.
Preventing a War in Space

A new race involving the commercialization and potential weaponization of space is accelerating. Recent technological advancements and overt testing over the past several years demonstrate increased international competition to achieve dominance in outer space. At the same time, it is renewing concerns that a war could occur in that arena, resulting in widespread devastation. We depend on space systems for navigation, communication, and exploration, as well as a multitude of other functions essential to modern life. The disabling of several key satellites is enough to introduce chaos into basic Earth operations that rely on communication and timing. If aggressive weapons are used, the resulting debris would most likely destroy surrounding spacecraft, creating more damaging debris in a chain reaction. The world economy could be shattered. In fact, the aftermath of space warfare could be equivalent to that of a nuclear war.
Investigation and modeling of optics damage in high-power laser systems caused by light backscattered in plasma at the target

High-power laser facilities may be restricted in operations by the risk of damage to optics due to the backscattering of laser light from the intended target. A portion of this backscattered light can re-enter the beam line and at sufficient fluence may damage (burn) optical apparatus. Here, the observed cumulative burn pattern on mirrors at the National Ignition Facility (NIF) due to stimulated Brillouin scattering (SBS) at the target is explained using detailed simulations. Our methodology involves using a measurement of a phase plate profile installed at the NIF to provide the laser input to a three-dimensional simulation of laser-plasma interaction in a target typical of that fielded at the NIF. Light scattered by SBS at the target is then followed back to the final aperture of the beam line, back through the phase plate, and to a mirror where damage typically occurs. We find that mirror damage patterns are largely dictated by the phase imprint of the phase plate on the returning SBS light. Our simulations show that the instantaneous SBS signal at the mirror varies on a picosecond time scale and is also highly modulated in space. Temporal averaging of the simulated SBS light pattern on the mirror reveals a pattern in close agreement with the experimentally observed damage. Understanding these burn patterns (distribution, modulation depth) may lead to future phase plate designs that limit damage throughout the optics assembly of high-powered laser facilities.High-power laser facilities may be restricted in operations by the risk of damage to optics due to the backscattering of laser light from the intended target. A portion of this backscattered light can re-enter the beam line and at sufficient fluence may damage (burn) optical apparatus. Here, the observed cumulative burn pattern on mirrors at the National Ignition Facility (NIF) due to stimulated Brillouin scattering (SBS) at the target is explained using detailed simulations. Our methodology involves using a measurement of a phase plate profile installed at the NIF to provide the laser input to a three-dimensional simulation of laser-plasma interaction in a target typical of that fielded at the NIF. Light scattered by SBS at the target is then followed back to the final aperture of the beam line, back through the phase plate, and to a mirror where damage typically occurs. We find that mirror damage patterns are largely dictated by the phase imprint of the phase plate on the returning SBS light. Our simula...
Conjugate symmetry

Conjugate symmetry is an entirely new approach to symmetric Boolean functions that can be used to extend existing methods for handling symmetric functions to a much wider class of functions. These are functions that currently appear to have no symmetries of any kind. Conjugate symmetries occur widely in practice. In fact, we show that even the simplest circuits exhibit conjugate symmetry. To demonstrate the effectiveness of conjugate symmetry we modify an existing simulation algorithm, the hyperlinear algorithm, to take advantage of conjugate symmetry. This algorithm can simulate symmetric functions faster than non-symmetric ones, but due to the rarity of symmetric functions, this optimization is of limited benefit. Because the standard benchmark circuits contain many symmetries it is possible to simulate these circuits faster than is possible with the fastest known event-driven algorithm. The detection and exploitation of conjugate symmetries makes use of GF(2) matrices. It is likely that conjugate symmetry and GF(2) matrices will find applications in many other areas of EDA.
Auriculotemporal Nerve Involvement in Parotid Bed Malignancy.

Objective:To identify and evaluate patients with parotid bed malignancy demonstrating radiographic findings of auriculotemporal (AT) nerve involvement.Methods:A retrospective review of patients wit...
Scaling parameters in anomalous and nonlinear Hall effects depend on temperature

In the study of the anomalous Hall effect, the scaling relations between the anomalous Hall and longitudinal resistivities play the central role. The scaling parameters by definition are fixed as the scaling variable (longitudinal resistivity) changes. Contrary to this paradigm, we unveil that the electron-phonon scattering can result in apparent temperature dependence of scaling parameters when the longitudinal resistivity is tuned through temperature. An experimental approach is proposed to observe this hitherto unexpected temperature dependence. We further show that this phenomenon also exists in the nonlinear Hall effect in nonmagnetic inversion-breaking materials and may help identify experimentally the presence of the side-jump contribution besides the Berry-curvature dipole.
Cattle, progress, and a victimized nation: Exploring metaphors in current and past immigration discourse

Abstract This paper analyzes three sources of discourse on immigration in the United States: congressional debates from the 1920s representing two polarized sides, a speech by President Obama, and a speech by President Trump. The goal of this analysis was to explore how the conceptual metaphors used in discussing immigration may have changed over the past century, in order to gain insight into the current polarization surrounding this topic. Results reveal striking similarities between Trump’s rhetoric and metaphorical framing and the 1920s anti-immigration side’s arguments, in that both situate the United States as a victim of immigration. In contrast, although there are fewer similarities between Obama’s metaphors and metaphorical frames and those used by earlier supporters of immigration, the claim that immigrants are a benefit to the United States remains constant.
Real-Time Model Predictive Control Based on Prediction-Correction Algorithms

In this work, we consider the problem of Model Predictive Control (MPC). This approach to controlling dynamical systems requires the solution of a finite horizon dynamic program. Especially when the horizon is large, a limitation of this approach is its computational burden since the solutions need to be computed in real-time between control actions. This restricts the applicability of MPC to systems that have large time constants and/or high computational power. To overcome these limitations, we propose a prediction-correction approach that exhibits quadratic convergence thus allowing to compute an approximate solution of the MPC problem efficiently. Numerical examples where we consider a highly nonlinear system support the theoretical conclusions.
Cost-effectiveness of prenatal screening methods for congenital heart defects in pregnancies conceived by in-vitro fertilization

Objectives To determine if a policy of universal fetal echocardiography (echo) in pregnancies conceived by in-vitro fertilization (IVF) is cost-effective as a screening strategy for congenital heart defects (CHDs) and to examine the cost-effectiveness of various other CHD screening strategies in IVF pregnancies. Methods A decision-analysis model was designed from a societal perspective with respect to the obstetric patient, to compare the cost-effectiveness of three screening strategies: (1) anatomic ultrasound (US): selective fetal echo following abnormal cardiac findings on detailed anatomic survey; (2) intracytoplasmic sperm injection (ICSI) only: fetal echo for all pregnancies following IVF with ICSI; (3) all IVF: fetal echo for all IVF pregnancies. The model initiated at conception and had a time horizon of 1 year post-delivery. The sensitivities and specificities for each strategy, the probabilities of major and minor CHDs and all other clinical estimates were derived from the literature. Costs, including imaging, consults, surgeries and caregiver productivity losses, were derived from the literature and Medicare databases, and are expressed in USA dollars ($). Effectiveness was quantified as quality-adjusted life years (QALYs), based on how the strategies would affect the quality of life of the obstetric patient. Secondary effectiveness was quantified as number of cases of CHD and, specifically, cases of major CHD, detected. Results The average base-case cost of each strategy was as follows: anatomic US, $8119; ICSI only, $8408; and all IVF, $8560. The effectiveness of each strategy was as follows: anatomic US, 1.74487 QALYs; ICSI only, 1.74497 QALYs; and all IVF, 1.74499 QALYs. The ICSI-only strategy had an incremental cost-effectiveness ratio (ICER) of $2 840 494 per additional QALY gained when compared to the anatomic-US strategy, and the all-IVF strategy had an ICER of $5 692 457 per additional QALY when compared with the ICSI-only strategy. Both ICERs exceeded considerably the standard willingness-to-pay threshold of $50 000-$100 000 per QALY. In a secondary analysis, the ICSI-only strategy had an ICER of $527 562 per additional case of major CHD detected when compared to the anatomic-US strategy. All IVF had an ICER of $790 510 per case of major CHD detected when compared with ICSI only. It was determined that it would cost society five times more to detect one additional major CHD through intensive screening of all IVF pregnancies than it would cost to pay for the neonate's first year of care. Conclusion The most cost-effective method of screening for CHDs in pregnancies following IVF, either with or without ICSI, is to perform a fetal echo only when abnormal cardiac findings are noted on the detailed anatomy scan. Performing routine fetal echo for all IVF pregnancies is not cost-effective. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Lost in Translation: The Jimmo Case as Policy Implementation Failure:

The Jimmo case involved a 2011 lawsuit against the Centers for Medicare and Medicaid Services (CMS) alleging they illegally used an improvement standard instead of a need standard to make coverage ...
Landscape patterns of ocelot–vehicle collision sites

Road networks can negatively impact wildlife populations through habitat fragmentation, decreased landscape connectivity, and wildlife-vehicle collisions, thereby influencing the spatial ecology and population dynamics of imperiled species. The ocelot (Leopardus pardalis) is a federally endangered wild felid in South Texas, with a high mortality rate linked to vehicle collisions. Using a multi-scale approach, we quantified and examined landscape spatial structure at ocelot roadkill locations, and between roadkill locations of male and female ocelots. We quantified the spatial distribution of land cover types at 26 ocelot–vehicle collision sites in South Texas that occurred from 1984–2017. We compared landscape metrics of woody, herbaceous, and bare ground cover types across multiple spatial scales at roadkill locations to those from random road locations, and between male and female ocelots. Roadkill sites consisted of 13–20% more woody cover than random locations. Woody patches at roadkill sites were 7.1–11% larger (2.4 ha) closer to roads and spaced 10–16 m closer together farther away from roads compared to random locations. Percent woody cover was the best indicator of ocelot–vehicle collision sites; there were no differences in woody cover between male and female road mortality locations. These findings suggest that ocelots are likely struck by vehicles while crossing between habitat patches. Roads that bisect areas of woody cover have negative impacts on ocelots by increasing habitat fragmentation and vulnerability to vehicle collisions. Crossing structures should be placed in areas with ≥ 30% woody cover and 3.5 ha woody patches.
Ambient temperature and UV-cured hybrid coatings from acetoacetylated non-isocyanate polyurethanes

Preparation of ambient and UV curing non-isocyanate polyurethane (NIPU) coatings has been reported using a series of acetoacetylated non-isocyanate polyurethane (AA-NI-PUPO) oligomers. Synthesized oligomers were characterized using various techniques such as Fourier transform infrared and nuclear magnetic resonance spectroscopy. AA-NI-PUPOs showed significantly lower viscosity compared to their non-acetoacetylated counterparts. Ambient temperature-cured systems were formulated by mixing AA-NI-PUPOs and different primary amine compounds in stoichiometric proportions. Michael addition reaction of acrylates and AA-NI-PUPOs was initiated by UV curing using a photobase generator as the catalyst. NIPU coatings were studied for various thermo-mechanical properties and corrosion resistance. The selected UV-cured and ambient-cured samples showed instant and 1-h tack-free time, respectively. Results revealed that with proper selection of acetoacetylated resin and crosslinker type, coatings with properties comparable to conventional PU coatings could be formulated. Moreover, UV-curable coatings with up to 90 wt% solid could be formulated using conventional monomeric acrylates as a reactive diluent. The study demonstrates the feasibility of formulating solvent-free rapid ambient curing non-isocyanate polyurethane coatings.
Open-Loop Self-Calibration of Position Sensor Offset in SM-PMSM Drive Systems

Field-oriented control (FOC) or vector control is a formidable control strategy for permanent magnet synchronous machines (PMSMs) due to high dynamic torque response. However, FOC requires rotor flux orientation information, typically obtained using a position sensor mounted on the motor. The relative displacement between the position sensor and the rotor zero location is a key calibration required to properly orient the stator field based on the rotor magnetic field. A method is proposed herewith that enables the calibration of this relative offset between the position sensor and the rotor zero that reduces the overall manufacturing floor space and manufacturing time. The proposed scheme exploits hardware and software components that are readily available on the motor-drive system for FOC control. The self-calibration scheme generates a slowly rotating stator flux vector to rotate the motor rotor under the no-load condition to collect information about the position sensor alignment. Lack of a need for specialized measurement in comparison to conventional methods saves and space while reducing the calibration time. The novelty lies in the ability to self-calibrate and, in doing so, reduces resource utilization. Analysis, simulation, and experimental results are provided to validate the proposed methodology.
Regulation of Neutrophil Function by Marine n-3 Fatty Acids—A Mini Review

While normal functioning neutrophils contribute in various, critical ways to the maintenance of a stable immune system, their hypo- or hyper-activation has been implicated in the onset or exacerbation of multiple inflammatory conditions often affecting the vulnerable, aging population. As such, many would benefit from interventions capable of targeting neutrophils in disease-specific ways without disrupting their primary role in maintaining immune function. After consumption, marine omega-3 fatty acids are rapidly incorporated into the phospholipid bilayer of neutrophils, changing the fatty acid composition and consequently modifying neutrophil function. In addition to eicosanoid synthesis, the mechanisms by which marine n-3 fatty acids and their metabolites alter neutrophil function involve blockage of transcription factors that subsequently reduce pro-inflammatory gene expression by neutrophils and through the disruption of lipid rafts. In the current mini-review, a brief explanation of marine n-3 fatty acid metabolism is provided and the subsequent impact on neutrophil function is discussed. In addition, current evidence of the effects of marine n-3 fatty acid supplementation on neutrophil function from clinical trials conducted in the past 15 years is summarized.
Turbulent Flow past a Flat Plate at Zero Incidence

The dissipation theorem is applied to fully developed turbulent flow past a flat plate. Most of the velocity profile occurs in a thin layer near the surface, but a layer of turbulence (represented by the eddy viscosity) extends substantially farther into the fluid.