cssi/SciSciGPT-SciSciNet huggingface dataset:
Performance-based controller for civil engineering structures

The authors present two control strategies for applications to civil engineering structures, referred to as the generalized H/sub 2/ based control and peak-to-peak based control, respectively. Both control strategies are capable of addressing the performance-based design of structures, in the sense that the design requirements for the peak response quantities, such as peak interstory drifts, peak shear forces, peak floor accelerations, etc., can be satisfied. Likewise, these two controllers minimize an upper bound of the peak response components of a controlled output vector. The design procedures for these two controllers are formulated in the framework of linear matrix inequalities (LMIs) so that the LMI toolbox in MATLAB can be used effectively and conveniently for the controller design. These control strategies are applied to a seismically excited 20-story benchmark building to demonstrate their applicability to practical problems as well as their control performances. Simulation results illustrate that the performances of both the generalized H/sub 2/ based controller and the peak-to-peak based controller are very plausible in comparison with the LQG control method.
Pharmacogenetics of neural injury recovery

Relatively few pharmacological agents are part of routine care for neural injury, although several are used or under consideration in acute stroke, chronic stroke, traumatic brain injury and secondary stroke prevention. Tissue plasminogen activator is approved for the treatment of acute ischemic stroke, and genetic variants may impact the efficacy and safety of this drug. In the chronic phase of stroke, several drugs such as L-dopa, fluoxetine and donepezil are under investigation for enhancing rehabilitation therapy, with varying levels of evidence. One potential reason for the mixed efficacy displayed by these drugs may be the influence of genetic factors that were not considered in prior studies. An understanding of the genetics impacting the efficacy of dopaminergic, serotonergic and cholinergic drugs may allow clinicians to target these potential therapies to those patients most likely to benefit. In the setting of stroke prevention, which is directly linked to neural injury recovery, the most highly...
Matrix metalloproteinases in development and disease

Matrix metalloproteinases (MMPs) are key modulators of many biological processes during pathophysiological events, such as skeletal formation, angiogenesis, cellular migration, inflammation, wound healing, coagulation, lung and cardiovascular diseases, arthritis, and cancer. Twenty-four members of the MMP family have been identified in humans, degrading many components of the extracellular matrix, cellular receptors, and cytokines. This review describes the molecular structure, activation and inhibition, and substrate specificity of MMPs, and their biological function in development and disease.
High Thermoelectric Efficiency of n-type PbS

PbS shares several features with the other lead chalcogenides PbX (X: Te, Se), which are good thermoelectric materials. PbS has a potential advantage in that it is quite earth abundant and inexpensive. In this work we tune the transport properties in n-type, single-phase polycrystalline PbS_(1-x)Cl_x (x ≤ 0.008) with different carrier densities. Lead chloride provides a nearly 100% efficient doping control up to 1.2 × 10^(20) cm^(−3). The maximum zT achieved at 850 K is 0.7 with a predicted zT ∼ 1 at 1000 K. This is about twice as high as what was previously reported (∼0.4) for binary PbS. Compared with the other lead chalcogenides the higher effective mass and higher lattice thermal conductivity makes binary PbS an inferior thermoelectric material. However this study also predicts greater potential of zT improvement in PbS by material engineering such as alloying or nanostructuring compared to PbSe or PbTe. Considering their abundance and low cost, PbS based materials are quite competitive among the lead chalcogenides for thermoelectric applications.
Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences

Protein–protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs,technical limitations precludecertain PPIsfrom detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using reoccurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of ~99.95% and executes 16000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29589 high confidence interactions of ~210 7 possible pairs. Of these, 14438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.
Calibration Weighting When Model and Calibration Variables Can Differ

Calibration weighting is an easy-to-implement yet powerful tool for reducing the standard errors of many population estimates derived from a sample survey by forcing the weighted sums of certain “calibration” variables to equal their known (or better-estimated) population totals. Although originally developed to reduce standard errors, calibration weighting can also be used to reduce or remove selection biases resulting from unit nonresponse. To this end, nonrespondents are usually assumed to be “missing at random,” that is, the response mechanism is assumed to be a function of calibration variables with either known values in the entire sample or known population totals. It is possible, however, to use calibration-weighting to compensate for unit nonresponse when response is a function of model variables that need not be calibration variables; in fact, some model variables can have values known only for respondents. We will explore some recent findings connected with this methodology.
Theory: Interrupting the Feedback Loop, and the Role of Expectancy

The model of behavioral self-regulation that has been presented thus far describes the various processes that are presumed to occur when the self-regulation system is operating efficiently and smoothly, when there are no obstacles to self-regulation. To recapitulate, the model holds people to be active (though not necessarily unbiased) information processors, who go about recognizing and categorizing aspects of themselves and the various behavioral contexts in which they find themselves. Sometimes these categorizations imply or have associated with them information that is used as a standard for subsequent behavior. If attention is self-directed at that point, it evokes a matching-to-standard sequence, whereby ongoing behavior is adjusted so that it more closely approximates the standard. Such, we believe, are the mechanisms by which behavioral self-regulation occurs.
Position Paper: The Case for JavaScript Transactions

Modern Web applications combine and use JavaScript-based content from multiple untrusted sources. Without proper isolation, such content can compromise the security and privacy of these Web applications. Prior techniques for isolating untrusted JavaScript code do so by restricting dangerous constructs and inlining security checks into third-party code. This paper presents a new approach that extends the JavaScript language to make isolation a language-level primitive. We propose to extend the language using a new transaction construct that allows a Web application to speculatively execute untrusted code and isolate its changes. The Web application can then inspect these speculative actions and commit them only if they comply with the application’s security policies. We discuss use-cases that can benefit from JavaScript support for transactions, present a formalization of JavaScript transactions and conclude with implementation considerations.
Waste Glass Leaching: Chemistry and Kinetics

Nuclear waste glass leaching has been studied extensively during the past ten years. Although much has been learned concerning the kinetics and mechanisms of glass dissolution, it does not appear that accurate predictions can yet be made concerning the release kinetics for specific elements from a given glass as a function of environmental conditions. In order to reliably predict elemental release rates, one needs to know: 1) how a given element is incorporated into the glass structure, 2) how specific sites in the glass react with water, 3) how the composition and reactivity of the leachate influence glass reactivity, 4) how the structure and reactivity of the glass changes in surface alteration layers, and 5) how glass dissolution modifies the chemistry of the leachate. At our current level of understanding, we are only able to make qualitative predictions concerning each of the above factors which allow us to make “order of magnitude” or “upper limit” predictions for radionuclide release rates.
Revision of Diodontus (Hymenoptera: Sphecidae) in America North of Mexico

Twenty-three species of Diodontus are recognized in North America. Keys are provided for identification of males and females. Seven species are placed in synonymy: Xylocelia maestus Mickel, Diodontus nigritus W. Fox, X. ater Mickel, and X. beulahensis Rohwer are synonymized with D. flavitarsis Fox; X. franclemonti Krombein with D. minutus (F.); X. antennatus Mickel with D. metathoracicus (Mickel); and D. florissantensis Rohwer with D. rugosus Fox. One North American species, D. minutus (F.), is shown to be holarctic. One new species, D. retiolus Eighme, is described.
Cardiovascular Effects of Longer-Term, High-Dose OROS Methylphenidate in Adolescents with ADHD

The short-term and longer-term cardiovascular safety of high daily doses of OROS methylphenidate (MPH) of up to 1.5 mg/kg in 114 adolescents with ADHD is reported from Massachusetts General Hospital, Boston, MA.
Short-term mortality in older patients treated with adjuvant chemotherapy for early-stage breast cancer

Chemotherapy for early-stage breast cancer has lowered cancer recurrence and deaths. However, short-term mortality rates due to cancer or treatment in the general population remain largely unknown. In this study, we evaluate the short-term mortality rate and the determinants of such outcome among a cohort of older breast cancer patients treated with adjuvant chemotherapy. This is a population-based study based on the Surveillance, Epidemiology, and End Results Program (SEER)–Medicare and the Texas Cancer Registry (TCR)–Medicare databases. Patients diagnosed with early-stage breast cancer between 2003 and 2011 who were 66 years or older and were treated with adjuvant chemotherapy within 6 months of diagnosis were included. Short-term mortality was defined as death from any cause within one year of breast cancer diagnosis. Descriptive statistics and multivariable logistic regression modeling were used for the analysis. Of the 21,536 patients included, a total of 625 (2.9 %) died within one year of breast cancer diagnosis. In multivariate analysis, older age (using 66–70 as reference category; 71–75 years OR 1.31, 95 % CI 1.05–1.62; 76–80 years OR 1.73, 95 % CI 1.36–2.19; >80 years OR 3.48, 95 % CI 2.7–4.48) and higher comorbidity index (using Charlson score of 0 as a reference, those with score of 1 or >2 had higher risk OR 1.46, 95 % CI 1.19–1.8 and OR 2.98, 95 % CI 2.42–3.67, respectively) were associated with the increased risk of short-term mortality. Other factors significantly associated with the outcome were higher grade and stage, ER-negative status, poor census tract area, and mastectomy. The findings of this study revealed that, in this large cohort of older breast cancer patients treated with adjuvant chemotherapy, 2.9 % of the population died within one year of breast cancer diagnosis. Finally, it was concluded that tumor- and patient-related characteristics were associated with short-term death. Our findings add relevant information that can be used by clinicians when balancing the risk.
Summation by Parts Finite Difference Approximations for Seismic and Seismo-Acoustic Computations

We develop stable finite difference approximations for a multi-physics problem that couples elastic wave propagation in one domain to acoustic wave propagation in another domain. The approximation consists of one finite difference scheme in each domain together with discrete interface conditions that couple the two schemes. The finite difference approximations use summation-by-parts (SBP) operators, which lead to stability of the coupled problem. Furthermore, we develop a new way to enforce boundary conditions for SBP discretizations of first order problems. The new method, which uses ghost points to enforce the boundary conditions, is a flexible alternative to the more established projection and SAT methods.
Analysis on epidemiological characteristic of varicella among kindergartens and schools in Daxing district of Beijing, 2011-2013

Objective To understand the epidemiological characteristics of varicella in Daxing District in Beijing, and provide the basis for further prevention and control of varicella in kindergartens and schools. Methods We collected the data of varicella cases and outbreaks in Daxing District from 2011 to 2013, and the data was analyzed by the descriptive statistics. Results 3168 varicella cases were reported during 2011-2013, and the average incidence was 75.06/100,000. There were 1763 cases among kindergartens and schools, accounting for 55.65%. Most of cases occurred in spring and winter, and the ratio of male-female was 1.49:1. There was a high incidence in the primary school students, accounting for 47.87%. With the rise of semester from primary section, the incidence of varicella showed a downward trend. The fever and rash degree of students who got the varicella vaccine was lighter than that of unvaccinated, and 80.52% of them got the varicella after vaccination over three years. Most of outbreaks occurred in the primary school. Conclusion Surveillance should be strengthened in spring and winter, especially for the elementary school students,and we need improve the vaccination rates of varicella vaccine to reduce the incidence of varicella and outbreaks.
Highly Stable, Amide-Bridged Autoinducing Peptide Analogues that Strongly Inhibit the AgrC Quorum Sensing Receptor in Staphylococcus aureus.

Blocking quorum sensing (QS) pathways has attracted considerable interest as an approach to suppress virulence in bacterial pathogens. Toward this goal, we recently developed analogues of a native autoinducing peptide (AIP-III) signal that can inhibit AgrC-type QS receptors and attenuate virulence phenotypes in Staphylococcus aureus. Application of these compounds is limited, however, as they contain hydrolytically unstable thioester linkages and have only low aqueous solubilities. Herein, we report amide-linked AIP analogues with greatly enhanced hydrolytic stabilities and solubilities relative to our prior analogues, whilst maintaining strong potencies as AgrC receptor inhibitors in S. aureus. These compounds represent powerful tools for the study of QS.
ISP Liability for Third-Party Defamation

Abstract By definition, libel is any written, printed, or pictorial statement that damages a person by defaming his character or reputation, damaging him in his occupation, or exposing him to public ridicule. Responsible book, newspaper, and magazine publishers take great care to avoid publishing articles that could expose them to a libel suit. A publisher's legal department reviews text, often word by word, to ensure that they will not be subject to an expensive and embarrassing judgment.
The Palliative Performance Scale Predicts Three- and Six-Month Survival in Older Adult Patients Admitted to the Hospital through the Emergency Department.

Background There is often little information on long-term prognosis available for Emergency Medicine physicians when decisions on admission, treatment, or consultations are being made for patients. There is a new focus to understand if palliative support should be offered in the emergency department (ED) and the Palliative Performance Scale (PPS), a screening tool used in other settings in palliative care, has been little used in the ED. Objective The goal of this study was to assess the prognostic value of the PPS in predicting three- and six-month survival in patients admitted through the ED. Design A prospective cohort study. Setting/subjects We evaluated 123 patients over the age of 55 years admitted through the ED of a tertiary care hospital in New England in November and December of 2013. Measurements Each patient's PPS score was evaluated initially in the ED, with follow-up assessments of PPS and survival at three and six months. Results Baseline PPS for the 123 patients was 72 ± 22. Information on 72 subjects (58.5%) at three months was 60 assessed and 12 deaths. Information on 47 subjects (38.2%) at six months was 26 assessed and 21 deaths (nine further deaths from three months). There were no significant differences in the demographics or PPS score in those evaluated and those lost to follow-up at three or six months. Patients with an initial PPS score of 30 or less had 14% survival at six months. Conclusion In this small preliminary study, The PPS score may predict survival in patients admitted to the hospital through the ED. The ease of use holds promise that use of the PPS in the ED may help ED physicians predict survival and plan for better disposition, advocate for patient wishes, and initiate palliative care consultation.
Morphological identification of the Soprano Pipistrelle ( Pipistrellus pygmaeus Leach, 1825) in Croatia.

Abstract After the discovery of two different phonic types within the common pipistrelle ( Pipistrellus pipistrellus ), mtDNA analysis confirmed the existence of two separate species named as common pipistrelle ( P. pipistrellus ) and soprano pipistrelle ( P. pygmaeus ). The discrimination of these two cryptic species using external characters and measures has proved to be somewhat problematic. We examined two colonies of soprano pipistrelle from Donji Miholjac, Croatia. As a result, only two characters proved to be of help for field identification: wing venation (89% of cases) and penis morphology and colour for males. The difference in length between the 2 nd and 3 rd phalanxes of the 3 rd finger should be discarded as diagnostic trait between P. pipistrellus and P. pygmaeus in Croatia. Riassunto Identificazione su basi morfologiche del pipistrello pigmeo ( Pipistrellus pygmeaus , Leach, 1825) in Croazia. A seguito della descrizione di due differenti "tipi fonici" nel pipistrello nano ( Pipistrellus pipistrellus ) e della successiva conferma su basi genetiche dell'esistenza di due specie distinte, designate come pipistrello nano ( P. pipistrellus ) e pipistrello pigmeo ( P. pygmaeus ), la distinzione delle due specie in base a caratteristiche morfologiche esterne si e dimostrata un problema di difficile soluzione. Sulla base delle caratteristiche distintive e delle differenze biometriche proposte da altri Autori, sono state esaminate due colonie di pipistrello pigmeo a Donji Miholjac, in Croazia. I risultati ottenuti evidenziano che, tra tutti i potenziali caratteri sinora proposti, solo due risultano utili per un'identificazione diretta sul campo: la venatura delle ali, risultata utile alla discriminazione nell'89% degli esemplari analizzati, e la colorazione e morfologia del pene nei maschi. La presunta diversa lunghezza della seconda e terza falange del terzo dito e invece risultata inefficace per una corretta discriminazione tra P. pipistrellus e P. pygmaeus in Croazia.
Student Performance in Curricula Centered on Simulation-Based Inference: A Preliminary Report

ABSTRACT“Simulation-based inference” (e.g., bootstrapping and randomization tests) has been advocated recently with the goal of improving student understanding of statistical inference, as well as the statistical investigative process as a whole. Preliminary assessment data have been largely positive. This article describes the analysis of the first year of data from a multi-institution assessment effort by instructors using such an approach in a college-level introductory statistics course, some for the first time. We examine several pre-/post-measures of student attitudes and conceptual understanding of several topics in the introductory course. We highlight some patterns in the data, focusing on student level and instructor level variables and the application of hierarchical modeling to these data. One observation of interest is that the newer instructors see very similar gains to more experienced instructors, but we also look to how the data collection and analysis can be improved for future years, es...
A win-win for women's reproductive health: A nonsteroidal contraceptive and fertoprotective neoadjuvant.

Women are born with a complete complement of ovarian follicles for their reproductive lifetime. Each ovarian follicle contains a single oocyte, packaged in a region of the ovary that is as close to a metabolic desert as a functioning tissue can be and still survive. Little vasculature intercalates this outer cortex region, where a tough extracellular matrix holds the germ cell-somatic cell unit, the follicle, in its long-term suspended animation. The biological isolation of this million-follicle ovarian reserve is changed when individual follicles are activated through signaling mechanisms that are now known, but by factor(s) that have remained elusive. One of the key paracrine-acting factors that controls early follicle activity is Mullerian inhibiting substance/anti-Mullerian hormone (MIS/AMH), and its profound role on the entire ovarian reserve is elegantly described by Kano et al. (1) in PNAS. MIS/AMH is a TGF-β superfamily member, first identified as a factor produced by male embryos, that blocks the development of female Mullerian ducts from the bipotential reproductive tract (2). Mutations in MIS/AMH in males can result in both male and female urogenital tracts that must be surgically resected. This powerful reproductive tract-regulating hormone has no known effect on adult male fertility; however, in the female, it takes on a completely different role that is necessary for follicle activation. The paper by Kano et al. (1) details this function using a gene therapy approach … [↵][1]1Email: tkw{at}northwestern.edu. [1]: #xref-corresp-1-1
Suppression of homogeneous crystal nucleation of the NiAl intermetallic by a composition gradient: A molecular dynamics study

Molecular dynamics simulations of homogeneous nucleation of the NiAl intermetallic phase from a liquid solution on cooling indicate that this phase transformation is suppressed in the presence of a composition gradient. A simulation method is designed to generate a sustaining composition gradient at the interface between two materials. As the composition gradient increases, the nucleation energy barrier rises, the critical nucleus size increases, and the nucleus shape develops an increasing asymmetry. A polymorphic nucleation model for a disk-shaped nucleus that incorporates the composition dependence of interfacial free energies was observed to describe the atomic-scale details of the simulation well. Critical nuclei shapes and volumes predicted by the model match with those appearing in the molecular dynamics simulations.
Transforming undergraduate biology learning with inquiry-based instruction

We developed an inquiry-driven course to enable students to develop skills they need to effectively use large amounts of information available on the Internet (including evaluating information, synthesizing, and collaborating) and engage more deeply with science content. Student teams collaborated to construct a scientific question, research what was known at the time about the answer to their question, and generate a final product to communicate their findings using multimedia on a web-based platform. Course iterations consistently yielded at least one group of students who transformed from struggling to successful, which led us to use content and narrative analysis of case studies to distinguish group types. We found three group types: High Engaging (HE), Transformed (T), and Low Engaging (LE). Each group type succeeded in creating a final web-based project. However, the projects created varied in level of cognitive depth between groups and indicated traits common to each group type. We outline similarities and differences among group types, use differences in groups to identify mechanisms that could facilitate deeper levels of cognitive engagement, and make recommendations about how educators can enable an increase in the number of highly engaged students in this type of inquiry-based course.
Some Demonstration Programs for Use in Teaching Elementary Probability and Statistics: Parts 3 and 4

In this second paper of a series, two programs for EGA-equipped IBM-PC compatible machines are included with indications of their pedagogical uses in the teaching of elementary probability and stat...
Systematic analysis of ribophagy in human cells reveals bystander flux during selective autophagy.

Ribosomes are abundant cellular machines 1,2 that are regulated by assembly, supernumerary subunit turnover and nascent chain quality control mechanisms 1–5 . Moreover, nitrogen starvation in yeast has been reported to promote selective ribosome delivery to the vacuole in an autophagy conjugation system dependent manner, a process called ‘ribophagy’ 6,7 . However, whether ribophagy in mammals is selective or regulated is unclear. Using Ribo–Keima flux reporters, we find that starvation or mTOR inhibition promotes VPS34-dependent ribophagic flux, which, unlike yeast, is largely independent of ATG8 conjugation and occurs concomitantly with other cytosolic protein autophagic flux reporters 8,9 . Ribophagic flux was not induced upon inhibition of translational elongation or nascent chain uncoupling, but was induced in a comparatively selective manner under proteotoxic stress induced by arsenite 10 or chromosome mis-segregation 11 , dependent upon VPS34 and ATG8 conjugation. Unexpectedly, agents typically used to induce selective autophagy also promoted increased ribosome and cytosolic protein reporter flux, suggesting significant bulk or ‘bystander’ autophagy during what is often considered selective autophagy 12,13 . These results emphasize the importance of monitoring non-specific cargo flux when assessing selective autophagy pathways.
Do magnetic resonance imaging and computed tomography provide equivalent measures of rotator cuff muscle size in glenohumeral osteoarthritis

Background Rotator cuff muscle volume is associated with outcomes after cuff repair and total shoulder arthroplasty. Muscle area on select magnetic resonance imaging (MRI) slices has been shown to be a surrogate for muscle volume. The purpose of this study was to determine whether computed tomography (CT) provides an equivalent measurement of cuff muscle area to a previously validated MRI measurement. Methods We included 30 patients before they were undergoing total shoulder arthroplasty with both preoperative CT and MRI scans performed within 30 days of one another at 1 institution using a consistent protocol. We reoriented CT sagittal and MRI sagittal T1 series orthogonal to the scapular plane. On both CT and MRI scans, we measured the area of the supraspinatus, infraspinatus–teres minor, and subscapularis on 2 standardized slices as previously described. We calculated intraclass correlation coefficients and mean differences. Results For the 30 subjects included, when MRI and CT were compared, the mean intraclass correlation coefficients were 0.989 (95% confidence interval [CI], 0.976-0.995) for the supraspinatus, 0.978 (95% CI, 0.954-0.989) for the infraspinatus–teres minor, and 0.977 (95% CI, 0.952-0.989) for the subscapularis. The mean differences were 0.2 cm2 (95% CI, 0.0-0.4 cm2) for the supraspinatus (P = .052), 0.8 cm2 (95% CI, 0.1-1.4 cm2) for the infraspinatus–teres minor (P = .029), and –0.3 cm2 (95% CI, –1.2 to 0.5 cm2) for the subscapularis (P = .407). Conclusion CT provides nearly equivalent measures of cuff muscle area to an MRI technique with previously validated reliability and accuracy. While CT underestimates the infraspinatus area as compared with MRI, the difference is less than 1 cm2 and thus likely clinically insignificant.
Phosphodiesterase type 5 in men with vasculogenic and post‐radical prostatectomy erectile dysfunction: is there a molecular difference?

Objectives To clarify the molecular basis of penile erection at the human level and distinguish the mechanisms underlying vasculogenic and post-radical prostatectomy (RP) erectile dysfunction (ED) subtypes. Patients and methods Erectile tissue was obtained from men without history of ED who underwent penile surgery for Peyronie's disease (control group, n = 5) and from men with ED who underwent penile prosthesis implantation (n = 17). ED was categorized into vasculogenic (n = 8) and post-RP (n = 9) subtypes. Penile erectile tissue samples were collected for molecular analyses of protein expressions of neuronal and endothelial isoforms of nitric oxide synthase (nNOS and eNOS, respectively), phospho-nNOS (Ser-1412), phospho-eNOS (Ser-1177), phospho-protein kinase B (Ser-473), phosphodiesterase type 5 (PDE5), α-smooth muscle actin, phospho-myosin phosphatase target subunit 1, RhoA/Rho-associated protein kinase (ROCK)-α, ROCK-β, 4-hydroxy-2-nonenal, and nNOS and eNOS uncoupling by Western blot. Results Vasculogenic ED was characterized by decreased eNOS protein expression and eNOS and nNOS phosphorylation on their activatory sites (Ser-1177 and Ser-1412, respectively), uncoupled eNOS, upregulated PDE5 protein expression, increased ROCK activity, and increased oxidative stress in erectile tissue. Post-RP ED was characterized by decreased nNOS protein expression, increased nNOS phosphorylation on its activatory site (Ser-1412), uncoupled nNOS, downregulated PDE5 protein expression, and increased oxidative stress in erectile tissue. Conclusion The mechanisms of vasculogenic and post-RP ED in the human penis involve derangements in constitutive nitric oxide synthase function, PDE5 protein expression and ROCK activity, and increased oxidative stress, which conceivably provide a molecular basis for chronically reduced nitric oxide bioavailability and increased smooth muscle contraction contributing to erectile impairment. Selective differences in PDE5 protein expression suggest distinct molecular mechanisms are in play for these ED subtypes.
The Impact of Product Usage Warnings in Alcoholic Beverage Advertising

Warnings in alcoholic beverage advertising are a subject of increasing policy interest. An experiment uncovers communication capabilities of such warnings in television advertising—the likely futur...
1482-P: Low-Density Lipoprotein Cholesterol (LDL-C) Management in Patients with Atherosclerotic Cardiovascular Diseases (ASCVD) and Preexisting Diabetes in Alberta, Canada

Background: Lipid-lowering therapy (LLT) reduces the risk of CV events, however, limited real-world data exist on the management of LDL-C in patients with ASCVD and pre-existing diabetes in Canada. Our study describes the clinical characteristics and LDL-C management of patients with ASCVD and diabetes using health system data in Alberta. Methods: A retrospective study was conducted linking multiple health system datasets to examine clinical characteristics and LDL-C levels in those receiving LLT (e.g., statins) after the first LDL-C test. Patients with ASCVD were identified using ICD diagnostic codes between 2011-2015. Similarly, diabetes status was assessed in the year prior to ASCVD diagnosis. LDL-C was assessed at the first (index) and second (follow-up) tests during the study period. LDL-C levels were evaluated based on a threshold of 2.0 mmol/L, as per the 2016 Canadian blood cholesterol management guidelines. Results: Among 144,607 patients with ASCVD and a prescription for LLT (mean age=66.3; 66% male), 27,540 (19.0%) patients were identified with diabetes. Patients with diabetes were more likely to have stroke, myocardial infarction, or peripheral arterial disease. Congestive heart failure and hypertension were found in 26.8% and 87.8% of patients with diabetes compared to 12.5% and 71.5% in those without, respectively. Of the patients with diabetes who had an index and follow-up LDL-C test (n=18,214), 35.0% (n=6,380) did not achieve the guideline specified LDL-C threshold at index. At follow-up (mean=238.9 days after index), 49.0% (n=3,129) of those who did not achieve threshold at index failed to meet the threshold. Conclusions: Nearly half of patients above the LDL-C threshold at the index test did not achieve threshold at the follow-up test, despite receiving LLT. Multifaceted interventions may be required to improve cholesterol management of patients with ASCVD and diabetes in Alberta. Disclosure G. Chen: Consultant; Self; Medlior Health Outcomes Research Ltd. M.S. Farris: Employee; Self; Medlior Health Outcomes Research Ltd. T. Cowling: Stock/Shareholder; Self; Medlior Health Outcomes Research Ltd. M. Tai: Employee; Self; Amgen Inc. L. Pinto: Employee; Self; Amgen Inc. S. Colgan: Employee; Self; Amgen Inc. R. Rogoza: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. T.J. Anderson: None.
Forecasting economic activity with mixed frequency BVARs

Abstract Mixed frequency Bayesian vector autoregressions (MF-BVARs) allow forecasters to incorporate large numbers of time series that are observed at different intervals into forecasts of economic activity. This paper benchmarks the performances of MF-BVARs for forecasting U.S. real gross domestic product growth against surveys of professional forecasters and documents the influences of certain specification choices. We find that a medium–large MF-BVAR provides an attractive alternative to surveys at the medium-term forecast horizons that are of interest to central bankers and private sector analysts. Furthermore, we demonstrate that certain specification choices influence its performance strongly, such as model size, prior selection mechanisms, and modeling in levels versus growth rates.
Use of bone-modifying agents and clinical outcomes in older adults with multiple myeloma.

Background Guidelines recommend bone-modifying agents (BMAs) for all patients initiating treatment for myeloma. We examined adherence to this recommendation, and BMA effectiveness in the era of bortezomib/lenalidomide-based therapy among Medicare beneficiaries. Methods From the linked Surveillance, Epidemiology, and End Results-Medicare registry, we selected beneficiaries receiving anti-myeloma chemotherapy in 2007-2013. We matched BMA recipients (within 90 days of first chemotherapy) to nonrecipients using a propensity score, balancing patient-, disease-, and therapy-related confounders. Cumulative incidence of skeletal-related events (SREs) and overall survival (OS) was compared in proportional hazard models accounting for competing risks and immortal-time bias. Results Among 4611 patients with median age of 76 years, 51% received BMA. Bone-modifying agents use remained steady over time (P = .87) and was significantly less frequent for patients who were older, with comorbidities, without prior SRE, and those treated without bortezomib or lenalidomide. In a propensity score-matched cohort, BMA recipients experienced a lower incidence of SRE (11.0% vs 14.6% at 3 years; subhazard ratio, 0.73; 95% CI, 0.60-0.89) and better OS (53.3% vs 47.8% at 3 years; hazard ratio, 0.86; 95% CI, 0.77-0.95). The results were consistent in the subgroup (76%) treated with bortezomib and/or immunomodulatory drugs (IMiDs). The incidence of osteonecrosis of the jaw (ONJ) was 3.2% at 3 years. Conclusions In this observational study, the observed benefits of early BMA administration among patients treated with contemporary anti-myeloma regimens were similar to historical clinical trials. Frequent omission of BMA highlights a remediable deficiency in the quality of supportive care, and suggests that timely administration may be a useful indicator of quality care in myeloma.
Transcriptome analysis reveals autophagy as regulator of TGFβ/Smad-induced fibrogenesis in trabecular meshwork cells.

The trabecular meshwork (TM) is a specialized ocular tissue, which is responsible, together with the Schlemm’s canal (SC), for maintaining appropriate levels of intraocular pressure. Dysfunction of these tissues leads to ocular hypertension and increases the risk for developing glaucoma. Previous work by our laboratory revealed dysregulated autophagy in aging and in glaucomatous TM cells. In order to gain more insight in the role of autophagy in the TM pathophysiology, we have conducted transcriptome and functional network analyses of TM primary cells with silenced expression of the autophagy genes Atg5 and Atg7. Atg5/7-deficient TM cells showed changes in transcript levels of several fibrotic genes, including TGFβ2, BAMBI, and SMA. Furthermore, genetic and pharmacological inhibition of autophagy was associated with a parallel reduction in TGFβ-induced fibrosis, caused by a BAMBI-mediated reduced activation of Smad2/3 signaling in autophagy-deficient cells. At the same time, TGFβ treatment led to Smad2/3-dependent dysregulation of autophagy in TM cells, characterized by increased LC3-II levels and autophagic vacuoles content. Together, our results indicate a cross-talk between autophagy and TGFβ signaling in TM cells.
Aeromedical retrieval of trauma patients: Impact of flight path model on estimates of population coverage.

Abstract Background The aim of this study was to compare the impact of different flight path models on the calculated population coverage of aeromedical retrieval systems, using the state of Alabama as a case study. Methods Geospatial analysis of U.S. Census Bureau population data using helicopter bases and trauma centers as foci of either circular or elliptical coverage areas. Results Circular isochrone models around helicopter bases or trauma centers suggest that the entire population of Alabama could reach a level I or II trauma center within 60 min. Elliptical isochrones, incorporating outbound and inbound flights, suggest that only 78.8% of the population have ready access to level I or II trauma centers. Conclusion While all three flight path models described have some validity and utility, simplistic circular flight time isochrones around trauma centers and helicopter bases provide overly optimistic estimates of population coverage. The elliptical model provides a more realistic evaluation.
Bacterial manganese sensing and homeostasis

Manganese (Mn) plays a complex role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts and is also important for free-living bacteria to thrive in stressful environments. This review summarizes new aspects of regulatory strategies to control intracellular Mn levels and gives an overview of several newly identified families of bacterial Mn transporters. Recent illustrative examples of advances in quantification of intracellular Mn pools and characterization of the effects of Mn perturbations are highlighted. These discoveries help define mechanisms of Mn selectivity and toxicity and could enable new strategies to combat pathogenic bacteria and promote growth of desirable bacteria.
M&A Policies Review Under the Competition and National Security Laws in China

China’s AML mirrors, by many aspects, the EU Competition Laws. According to Paragraph 2 of Article 17 of the Anti-Monopoly Law, dominant market position refers to the undertaking(s) having the ability to control the price, quantity, or other trading conditions of products in a relevant market, or to hinder or affect other undertakings to enter the relevant market. Since 2006, China began to adopt laws and regulations to describe the procedures it uses to review, and potentially block, proposed foreign acquisitions that it deems are not in China’s national interest.
Seven dangers of designer overspecialization

Seven dangers of overspecialization as they apply to the design process are analyzed. They are: missing the real need, formulation of the wrong problem, wrong design concept, wrong hardware, wrong model, over- or underanalysis and poor presentation. As an example, the design of an unmanned Rover for a mission to Mars is studied with the conclusion reached that, specialization, although necessary, should not shut out all other aspects of design or other disciplines.
Building a Functional Salivary Gland for Cell-Based Therapy: More than Secretory Epithelial Acini

A few treatment options exist for patients experiencing xerostomia due to hyposalivation that occurs as a result of disease or injury to the gland. An opportunity for a permanent solution lies in the field of salivary gland replacement through tissue engineering. Recent success emboldens in the vision of producing a tissue-engineered salivary gland composed of differentiated salivary epithelial cells that are able to differentiate to form functional units that produce and deliver saliva to the oral cavity. This vision is augmented by advances in understanding cellular mechanisms that guide branching morphogenesis and salivary epithelial cell polarization in both acinar and ductal structures. Growth factors and other guidance cues introduced into engineered constructs help to develop a more complex glandular structure that seeks to mimic native salivary gland tissue. This review describes the separate epithelial phenotypes that make up the gland, and it describes their relationship with the other cell types such as nerve and vasculature that surround them. The review is organized around the links between the native components that form and contribute to various aspects of salivary gland development, structure, and function and how this information can drive the design of functional tissue-engineered constructs. In addition, we discuss the attributes of various biomaterials commonly used to drive function and form in engineered constructs. The review also contains a current description of the state-of-the-art of the field, including successes and challenges in creating materials for preclinical testing in animal models. The ability to integrate biomolecular cues in combination with a range of materials opens the door to the design of increasingly complex salivary gland structures that, once accomplished, can lead to breakthroughs in other fields of tissue engineering of epithelial-based exocrine glands or oral tissues.
Recursive Proof Composition from Accumulation Schemes

Recursive proof composition has been shown to lead to powerful primitives such as incrementally-verifiable computation (IVC) and proof-carrying data (PCD). All existing approaches to recursive composition take a succinct non-interactive argument of knowledge (SNARK) and use it to prove a statement about its own verifier. This technique requires that the verifier run in time sublinear in the size of the statement it is checking, a strong requirement that restricts the class of SNARKs from which PCD can be built. This in turn restricts the efficiency and security properties of the resulting scheme.
Enhancing Performance, Security, and Management in Network Function Virtualization

In an era of ubiquitous connectivity, various new applications, network protocols, and online services (e.g., cloud services, distributed machine learning, cryptocurrency) have been constantly creating, underpinning many of our daily activities. Emerging demands for networks have led to growing traffic volume and complexity of modern networks, which heavily rely on a wide spectrum of specialized network functions (e.g., Firewall, Load Balancer) for diverse purposes. Although these (virtual) network functions (VNFs) are widely deployed, they are instantiated in an uncoordinated manner failing to meet growing demands of evolving networks. In this dissertation, we argue that networks equipped with VNFs can be designed in a fashion similar to how computer software is programmed today. By following the blueprint of modularization, networks can be made more efficient, secure, and manageable.
Addressing Teacher Shortages in Rural America: What Factors Help New Teachers Apply to Teach in Rural Settings?

Teacher shortages in rural areas has become a public crisis. This shortage of key personnel requires stakeholders (higher education, state departments, local school districts) to examine factors that help teacher education students choose to apply to rural settings. The current study examines new teacher candidates’ background, preparation for teaching, and perceptions of protective factors on their decisions to work in rural areas. Data from teacher education students in their residencies from 14 institutions were analyzed. Results suggest that student background, including race, level of education, parent education, and high school location are important. White students, those pursuing undergraduate degrees, those from rural high schools, and students who feel more confident in teaching 21st-century critical thinking skills (e.g., using a variety of perspectives, engaging in self-assessment, teaching critical thinking) are also more likely to consider teaching in rural areas. Results are discussed as they relate to recruitment in rural areas.
Examining the longitudinal effects and potential mechanisms of hope on COVID-19 stress, anxiety, and well-being.

Hope is a cognitive trait that predicts both resilience to and recovery from anxiety and stress-related disorders. The present study examines the prospective associations of hope with subsequent anxiety, stress, and well-being during the COVID-19 pandemic. Perceived emotional control, a transdiagnostic vulnerability factor, was also examined as a potential mediator of these relationships. American adults (N = 822) were recruited during the COVID-19 pandemic using Amazon mTURK and structural equation modeling was used to examine how trait hope predicted outcomes approximately one month later. Higher hope was associated with greater well-being and perceived emotional control, as well as lower levels of anxiety and COVID-19 perceived stress. Results also indicated an indirect effect of hope with all outcomes via perceived emotional control. These findings suggest that hope may associated with resilience to the chronic stressors associated with the COVID-19 pandemic.