cssi/SciSciGPT-SciSciNet huggingface dataset:
Transient Absorption Dynamics of Sterically Congested Cu(I) MLCT Excited States

Subpicosecond through supra-nanosecond transient absorption dynamics of the homoleptic Cu(I) metal-to-ligand charge transfer (MLCT) photosensitizers including the benchmark [Cu(dmp)2](+) (dmp =2,9-dimethyl-1,10-phenanthroline) chromophore, as well as [Cu(dsbp)2](+) (dsbp =2,9-di(sec-butyl)-1,10-phenanthroline and [Cu(dsbtmp)2](+) (dsbtmp =2,9-di(sec-butyl)-3,4,7,8-tetramethyl-1,10-phenanthroline) were investigated in dichloromethane and tetrahydrofuran solutions. Visible and near-IR spectroelectrochemical measurements of the singly reduced [Cu(dsbp)2](+) and [Cu(dsbtmp)2](+) species were determined in tetrahydrofuran, allowing for the identification of redox-specific phenanthroline-based radical anion spectroscopic signatures prevalent in the respective transient absorption experiments. This study utilized four different excitation wavelengths (418, 470, 500, and 530 nm) to elucidate dynamics on ultrafast times scales spanning probe wavelengths ranging from the UV to the near-IR (350 to 1450 nm). With the current time resolution of ∼150 fs, initial excited state decay in all three compounds was found to be independent of excitation wavelength. Not surprisingly, there was little to no observed influence of solvent in the initial stages of excited state decay in any of these molecules including [Cu(dmp)2](+), consistent with results from previous investigators. The combined experimental data revealed two ranges of time constants observed on short time scales in all three MLCT chromophores and both components lengthen as a function of structure in the following manner: [Cu(dsbtmp)2](+) < [Cu(dsbp)2](+) < [Cu(dmp)2](+). The molecule with the most inhibited potential for distortion, [Cu(dsbtmp)2](+), possessed the fastest ultrafast dynamics as well as the longest excited state lifetimes in both solvents. These results are consistent with a small degree of excited state distortion, rapid intersystem crossing, and weak vibronic coupling to the ground state. The concomitant systematic variation in both initial time constants, assigned to pseudo-Jahn-Teller distortion and intersystem crossing, suggest that both processes are intimately coupled in all molecules in the series. The variability in these time scales illustrate that strongly impeded structural distortion in Cu(I) MLCT excited state enables more rapid surface crossings in the initial deactivation dynamics.
PI 3-kinases and Src kinases regulate spreading and migration of cultured VSMCs.

Pulmonary artery smooth muscle cell (PASMC) adhesion, spreading, and migration depend on matrix-stimulated reorganization of focal adhesions. Platelet-derived growth factor (PDGF) activates intrace...
87 IMMUNOHISTOCHEMICAL DETERMINATION OF ESTROGEN RECEPTORS IN THE TREATMENT AND PATHOGENESIS OF MELASMA

Background Melasma is a commonly acquired hypermelanosis of the skin due to various etiological factors. These include sun exposure, oral contraceptives, certain medications, and other factors. Observations Melasma poses a therapeutic challenge to clinicians and current treatments are inconsistent. Melasma is especially troublesome during cosmetic procedures such as chemical peels and laser resurfacing in which severe rebound pigmentation can occur. Methods 3-mm biopsies were taken from two female patients (ages 39, 45) with recalcitrant melasma from the forehead region. Frozen sections of the tissues were taken and mouse monoclonal antibody against human estrogen receptors was tested at various dilutions to determine the optimum concentrations required for reproducible immunostaining with minimal background staining. Results The immunohistochemical staining showed the presence of estrogen receptors on lesional (pigmented) skin and the absence of these receptors on non-lesional (non-pigmented) skin. From a qualitative standpoint, the estrogen receptors seem to be localized only to the melasma affected skin. Conclusion Our study demonstrates the role of estrogen receptors in melasma and suggests the direct role of estrogen in the pathogenesis of melasma. Therefore, patients with melasma would benefit from the competitive blockade of these estrogen receptors. The use of topical tamoxifen for blocking active estrogen receptors offers an additional therapeutic tool in treating melasma refractory to conventional therapy. Initial experience with topical tamoxifen has demonstrated clinical improvement in a number of melasma cases, although further work is required to demonstrate its efficacy. Additionally, these findings can be used to predict the likelihood of hyperpigmentation after laser resurfacing, chemical peels, and other cosmetic procedures.
Awareness of Behavioral Tracking and Information Privacy Concern in Facebook and Google

Internet companies record data about users as they surf the web, such as the links they have clicked on, search terms they have used, and how often they read all the way to the end of an online news article. This evidence of past behavior is aggregated both across websites and across individuals, allowing algorithms to make inferences about users’ habits and personal characteristics. Do users recognize when their behaviors provision information that may be used in this way, and is this knowledge associated with concern about unwanted access to information about themselves they would prefer not to reveal? In this online experiment, the majority of a sample of web-savvy users was aware that Internet companies like Facebook and Google can collect data about their actions on these websites, such as what links they click on. However, this awareness was associated with lower likelihood of concern about unwanted access. Awareness of the potential consequences of data aggregation, such as Facebook or Google knowing what other websites one visits or one’s political party affiliation, was associated with greater likelihood of reporting concern about unwanted access. This suggests that greater transparency about inferences enabled by data aggregation might help users associate seemingly innocuous actions like clicking on a link with what these actions say about them.
Value of positron emission tomography in staging ocular adnexal lymphomas and evaluating their response to therapy.

BACKGROUND AND OBJECTIVE: An observational case series to assess the value of positron emission tomography (PET) in staging ocular adnexal lymphomas and evaluating their response to therapy. PATIENTS AND METHODS: The clinical records of 16 consecutive patients with ocular adnexal lymphoma for whom pretreatment and posttreatment PET scans and corresponding computed tomography (CT) and magnetic resonance imaging (MRI) scans were available were compared. RESULTS: Pretreatment PET scans demonstrated fluorine 18-fluorodeoxyglucose (FDG) positive lesions in 15 orbits of 12 patients. In 1 patient with low-grade follicular lymphoma of the orbit, PET revealed an additional focus of lymphoma in the deltoid muscle that was missed on clinical examination and conventional radiography. All of the posttreatment PET scans showed complete resolution of FDG uptake, suggesting good response to therapy. However, posttreatment CT and MRI scans demonstrated residual masses in 3 patients. CONCLUSIONS: PET is valuable for initial staging of ocular adnexal lymphomas and may be a good adjunct to conventional imaging in evaluation of response to therapy.
Three Voices of Socio-Legal Studies

The connection between law and contemporary social science emerged as a consequence of the quest for social reform. As law became more instrumental, it also became more empirical, more concerned with policy. For this process, it turned to social science. Social science complied and has become an adjunct to law in the quest for solving social problems. As this partnership has developed, the relationship between law and social science has matured. Not only has social science sought to educate and influence law, it has also incorporated law into its own disciplinary concerns. Furthermore, the field of socio-legal studies may be on the verge of establishing itself as a separate and distinct discipline, independent of the practical concerns of law.The scholarly intersection of law and social science — or socio-legal studies, as I shall call it — now speaks with at least three voices addressed to at least three audiences. It speaks as policy analysis, a handmaiden to law. It also speaks in the traditional language of the social sciences. Thirdly, it may be gaining a voice of its own, reflecting a belief that law is a distinct form of ordering that merits its own position among the scholarly disciplines, separate from both scholarly fields and the professional concerns of law. At their core, each of these enterprises entails a distinct voice, a distinct audience, and a distinct agenda.
Interpreting traffic dynamics using ubiquitous urban data

Given a large collection of urban datasets, how can we find their hidden correlations? For example, New York City (NYC) provides open access to taxi data from year 2012 to 2015 with about half million taxi trips generated per day. In the meantime, we have a rich set of urban data in NYC including points-of-interest (POIs), geo-tagged tweets, weather, vehicle collisions, etc. Is it possible that these ubiquitous datasets can be used to explain the city traffic? Understanding the hidden correlation between external data and traffic data would allow us to answer many important questions in urban computing such as: If we observe a high traffic volume at Madison Square Garden (MSG) in NYC, is it because of the regular peak hour or a big event being held at MSG? If a disaster weather such as a hurricane or a snow storm hits the city, how would the traffic be affected?Most of existing studies on traffic dynamics focus only on traffic data itself and do not seek for external datasets to explain traffic. In this paper, we present our results in attempts to understand taxi traffic dynamics in NYC from multiple external data sources. We use four real-world ubiquitous urban datasets, including POIs, weather, geo-tagged tweets, and collision records. To address the heterogeneity of ubiquitous urban data, we present carefully-designed feature representations for these datasets. Our analysis suggests that POIs can well describe the regular traffic patterns. In addition, geo-tagged tweets can be used to explain irregular traffic caused by big events, and weather may account for abnormal traffic drops.
242. Genetically Engineered Mesenchymal Stem Cell Spheroids for Brain Tumor Therapy

Gliobastoma is one of the most aggressive forms of brain cancer. Each year 18,000 people are diagnosed with glioblastomas with an average survival of 10 to 12 months. MSC are an attractive candidate for cell based therapy since they can be easily isolated, manipulated and have no immune rejection. MSC transduced with TRAIL are capable of migrating towards the tumor cells and kill the tumor cells due to bystander effect1xAssessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Sasportas, L.S. et al. Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 4822–4827Crossref | PubMed | Scopus (252)See all References. However, for cell based therapy migration, survival and retention are the major factors. MSC in spheoridal form has shown to have increased expression of CXCR4 which is critical for migration towards tumor cells2xAggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Bartosh, T.J. et al. Proc. Natl. Acad. Sci. U. S. A. 2010; 107: 13724–13729Crossref | PubMed | Scopus (287)See all References. The spheroidal form also might help the cells to survive for longer and prevent it from getting washed out due to the extracellular matrix surrounding the cells and larger size respectively. Hence MSC in spheroidal created using a microfluidic platform was used for cell based therapy to treat glioma. The MSC self assembled to form spheroids within the double emulsion in 150 mins. Live/dead staining demonstrated high viability of the cells in the spheroid. Semi-quantitative RT-PCR demonstrated enhanced expression of CXCR4 in the MSC spheroids. This translated to higher migration of the MSC spheroids compared to MSC as seen by increased directionality, velocity, euclidian distance and displacement of the center of mass. MSC was shown to produce TRAIL constantly for 6 days. Condition media collected from MSC-sTRAIL single and spheroids were collected and showed higher caspase 3/7 activation and effectively killed the cancer cells. Hence MSCs in spheroidal form are an excellent candidate for treating glioblastomas. In the future the spheroidal retention and survival will be tested in vivo. This will be followed by survival analysis to ascertain the therapeutic efficacy of MSC-TRAIL.View Large Image | Download PowerPoint Slide
Experimental Investigation of Blast Mitigation for Target Protection

An explosion yielding a blast wave can cause catastrophic damage to a building and its personnel. This threat defines an immediate importance for understanding blast mitigation techniques via readily available materials. An unconfined mass of water in the form of a free flowing sheet is one possible readily available mitigant. This chapter focuses narrowly on the protection of high-valued structures and other large targets where removal from the threat zone is often impossible. In these situations, methods are needed to dissipate and reflect incoming blast waves and mitigate damage potential. Any proposed mitigation method must be evaluated for effectiveness, and while steady advances in computational physics have been made in this area, experimentation remains crucial. Therefore, this chapter emphasizes experimental methods for evaluation of blast mitigation, both from a practical and fundamental standpoint. In addition, some of the capabilities of current computational methods are highlighted. The chapter begins with a review of the underlying physics. This is followed by a brief overview of experimental methods. Finally, the remainder of the chapter is dedicated to recent experimental and computational results for a potential configuration involving protective water sheets.
Videoexoscopic real-time intraoperative navigation for spinal neurosurgery: a novel co-adaptation of two existing technology platforms, technical note

Image-guided approaches to spinal instrumentation and interbody fusion have been widely popularized in the last decade [1-5]. Navigated pedicle screws are significantly less likely to breach [2, 3, 5, 6]. Navigation otherwise remains a point reference tool because the projection is off-axis to the surgeon's inline loupe or microscope view. The Synaptive robotic brightmatter drive videoexoscope monitor system represents a new paradigm for off-axis high-definition (HD) surgical visualization. It has many advantages over the traditional microscope and loupes, which have already been demonstrated in a cadaveric study [7]. An auxiliary, but powerful capability of this system is projection of a second, modifiable image in a split-screen configuration. We hypothesized that integration of both Medtronic and Synaptive platforms could permit the visualization of reconstructed navigation and surgical field images simultaneously. By utilizing navigated instruments, this configuration has the ability to support live image-guided surgery or real-time navigation (RTN). Medtronic O-arm/Stealth S7 navigation, MetRx, NavLock, and SureTrak spinal systems were implemented on a prone cadaveric specimen with a stream output to the Synaptive Display. Surgical visualization was provided using a Storz Image S1 platform and camera mounted to the Synaptive robotic brightmatter drive. We were able to successfully technically co-adapt both platforms. A minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) and an open pedicle subtraction osteotomy (PSO) were performed using a navigated high-speed drill under RTN. Disc Shaver and Trials under RTN were implemented on the MIS TLIF. The synergy of Synaptive HD videoexoscope robotic drive and Medtronic Stealth platforms allow for live image-guided surgery or real-time navigation (RTN). Off-axis projection also allows upright neutral cervical spine operative ergonomics for the surgeons and improved surgical team visualization and education compared to traditional means. This technique has the potential to augment existing minimally invasive and open approaches, but will require long-term outcome measurements for efficacy.
Analytic Energy Gradients for Variational Two-Electron Reduced-Density-Matrix-Driven Complete Active Space Self-Consistent Field Theory

Analytic energy gradients are presented for a variational two-electron reduced-density-matrix (2-RDM)-driven complete active space self-consistent field (CASSCF) method. The active-space 2-RDM is determined using a semidefinite programing (SDP) algorithm built upon an augmented Lagrangian formalism. Expressions for analytic gradients are simplified by the fact that the Lagrangian is stationary with respect to variations in both the primal and the dual solutions to the SDP problem. Orbital response contributions to the gradient are identical to those that arise in conventional CASSCF methods in which the electronic structure of the active space is described by a full configuration interaction (CI) wave function. We explore the relative performance of variational 2-RDM (v2RDM)- and CI-driven CASSCF for the equilibrium geometries of 20 small molecules. When enforcing two-particle N-representability conditions, full-valence v2RDM-CASSCF-optimized bond lengths display a mean unsigned error of 0.0060 A and a ma...
Human interaction with robotic systems: performance and workload evaluations.

AbstractWe first tested the effect of differing tactile informational forms (i.e. directional cues vs. static cues vs. dynamic cues) on objective performance and perceived workload in a collaborative human–robot task. A second experiment evaluated the influence of task load and informational message type (i.e. single words vs. grouped phrases) on that same collaborative task. In both experiments, the relationship of personal characteristics (attentional control and spatial ability) to performance and workload was also measured. In addition to objective performance and self-report of cognitive load, we evaluated different physiological responses in each experiment. Results showed a performance–workload association for directional cues, message type and task load. EEG measures however, proved generally insensitive to such task load manipulations. Where significant EEG effects were observed, right hemisphere amplitude differences predominated, although unexpectedly these latter relationships were negative. A...
Fatigue crack growth rates of X100 steel welds in high pressure hydrogen gas considering residual stress effects

Abstract Fatigue crack growth rate (FCGR) data were measured in high pressure hydrogen gas versus stress intensity factor range (ΔK) in specimens removed from a X100 welded steel pipe. Three distinct regions of the pipe weld were examined: base metal, weld fusion zone, and heat affected zone. Tests were performed at a load ratio (R) of 0.5, frequency of 1 Hz, and at a hydrogen gas pressure of 21 MPa. Tests were also performed in air at 10 Hz as a reference. Fatigue crack growth rates were observed to be over an order of magnitude higher for tests performed in hydrogen compared to the rates from tests in air. Residual stress measurements were collected on identical specimens cut from the base metal, weld, and heat affected zone to account for their influence on measured FCGR data. The slitting method provided residual stress and residual stress intensity factor (Kres), the effect of which was removed from the FCGR data using Knorm in order to provide a more direct comparison of crack growth resistance of the base metal, weld and heat affected zone. Prior to accounting for residual stress, FCGR in hydrogen gas appeared to be highest in the weld fusion zone. After accounting for residual stress effects, the weld fusion zone FCGR data converged to the base metal FCGR data, which underscores the importance of accounting for residual stress effects when assessing fatigue performance.
Measurement of Skin Dose in Primary Irradiation of Maxillary Sinus Carcinoma

Abstract Subcutaneous involvement frequently occurs in maxillary sinus carcinoma. Radical resection does not include removal of the skin at risk. In standard postoperative wedge-pair treatment plans, the surface dose is dependent upon beam weighting, beam energy, and patient contour. Thermoluminescent dosimetry (TLD) measurements were performed to evaluate the surface dose of patients undergoing postoperative irradiation of maxillary sinus carcinoma following primary resection. When 60 Gy was delivered to isocenter with a 45° wedge pair and 6 MV photons with 1 cm bolus, the subcutaneous tissues at risk received approximately 30 Gy. Based upon presented TLD measurements, supplemental electron beam therapy to the subcutaneous tissues if primarily involved should be considered.
Small mammal habitat associations at patch and landscape scales in Oregon.

To investigate multiscale habitat associations, we examined patterns of capture rates of small mammals in thirty 250-300 ha landscapes in the central Oregon Coast Range. We compared capture rates of 14 species within >7 patch types to expected capture rates based on sampling effort. We used landscape level capture rates to test for associations with percent area (composition) and 8 pattern indices at the landscape scale. Capture rates of 10 of 14 small mammal species were higher in conifer and/or mixed large sawtimber patch types. At the landscape scale, capture rates of 6 of 14 species of small mammals were positively associated with the area of patch types. The pattern of patches on the landscape may influence the distribution of 5 small mammal species in this region. We conclude that some small mammals may respond to landscape pattern and/or composition, while other small mammals may not respond to either landscape pattern or composition. Our results suggest that mature forest habitat, patch richness, pattern, and composition are key landscape features that should be considered in management plans, particularly when biodiversity of forest floor mammals is a management objective.
SAES ST 909 Pilot Scale Methane Cracking Tests

AbstractPilot scale (0.5 kg) SAES St 909 methane cracking tests were conducted for potential tritium process applications. Up to 1400 hours tests were done at 700°C, 202.7 kPa (1520 torr) with a 0.03 sLPM feed of methane plus impurities, in a 20 vol% hydrogen, balance helium, stream. Carbon dioxide gettered by St 909 can be equated to an equivalent amount of methane gettered, but equating nitrogen to an equivalent amount of methane was nitrogen feed composition dependent. A decreased hydrogen feed increased methane getter rates while a 30°C drop in one furnace zone increased methane emissions by over a factor of 30. The impact of gettered nitrogen can be somewhat minimized if nitrogen feed to the bed has been stopped and sufficient time given to recover the methane cracking rate.
On the Anatomical Substrate for Flavor

Flavor contributes significantly to the control of feeding behavior and the pleasure associated with eating. It has long been recognized that flavor consists of far more than simple gustatory sensibility. Odor, texture, temperature, consistency and taste each contribute in varying degrees. The neural mechanisms underlying this amalgam of sensations, much less its influence over ingestion, have yet to be specified. Recent investigations of both the gustatory and olfactory systems, however, provide an anatomical basis for interaction between these two chemical senses. Additional evidence indicates that other, non-chemical, oral sensibilities (thermal and tactile) may converge on the same areas.
Gastric Motility Disturbances by Drugs

A major consequence of drug-induced changes in gastric motility is the effect on the rate of gastric emptying (GE). Drugs are one of many factors affecting GE. The characteristics of the gastric contents are a major factor, including its volume, size, density, temperature, viscosity, osmolality, and caloric value. Splanchnic blood flow, body position, and electrolyte balance also affect GE. Even gravity (or its absence) plays a role in the rate of GE [2]. The presence of food generally delays GE.
Strategies for Ensuring Use of Needs Assessment Findings: Experiences of a Community Substance Abuse Prevention Program

This article offers specific strategies for ensuring utilization of needs assessment findings. It is designed to help prevention specialists, community planners, program evaluators, and involved citizens maximize their efforts in developing community services by tying those services closely to community needs. Program evaluators who completed a broad-based community needs assessment commissioned by their organization, found that the organization had gone ahead in developing programs and saw the needs assessment findings as unrelated to their ongoing activities. Far from being unique, this situation is common in organizations where participants feel an urgency to get programs under way to address widespread community problems.
Seeds as sources of preformed water for desert-dwelling granivores

Measurements were made on the moisture contents of naturally occurring seeds from the Mojave Desert and of the moisture uptake of such seeds when placed in conditions of differing humidities. Seeds in the field sometimes contained high proportions of water (> 20 per cent), but were often dry (
Is There a Prescription to Treat Pediatric Obesity

Pediatric obesity is complex-in every way. The pathogenesis, which is a result of a multitude of factors combined with social and environmental factors makes it a crisis with overwhelming challenges. It is difficult to treat pediatric obesity; however, guidelines attempt to clarify how to approach treatment. These strategies are mostly interventions in lifestyle because only 1 medication is approved for treating obesity in children. The approach to the treatment of pediatric obesity will need to be a one that relies on the available data, a continued drive for additional research and publication, sharing of practice experience, and continued efforts at prevention.
Obstructive sleep apnea risk and subclinical atherosclerosis in South Asians living in the United States.

Abstract Objectives The objective of this study was to examine the association between high risk of obstructive sleep apnea (OSA) and subclinical atherosclerosis among South Asians in the United States. Design A secondary analysis of cross-sectional data. Setting/Participants A community-based cohort of 906 men and women participating in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Measurements The Berlin Questionnaire was used to screen for OSA risk. Coronary artery calcium (CAC), common carotid artery intima-media thickness (IMT), and internal carotid artery IMT were used as measures of subclinical atherosclerosis. Results The majority of participants (59%) with high OSA risk had CAC scores >0 compared with only 41% of participants with low OSA risk (P Conclusions High OSA risk, which includes overlapping comorbidities of HTN and obesity, was not associated with the time living in the US but was associated with subclinical atherosclerosis markers. These cardiovascular disease risk factors should include evaluation of the spectrum of SDB among all adults, including South Asian men and women.
Nanoimpacts at Active and Partially Active Electrodes: Insights and Limitations.

While the electrochemical nanoimpact technique has recently emerged as a method of studying single entities, its scope is limited by its typical requirement of a catalytically active particle impacting an inert electrode. We show that an active particle-active electrode type scheme can provide valuable mechanistic insight into electrochemical reactions. When an individual Pt electrocatalyst adsorbs to the surface of a partially active electrode, further reduction of electrode-produced species can proceed on the nanocatalyst. Furthermore, current transients obtained during hydrogen evolution allow simultaneous measurement of the Pt catalyst over different length scales, the size dependency suggesting H atom intercalation as a plausible catalytic deactivation mechanism. Although experimental and computational results show that outer-sphere redox probes are unproductive for particle characterization, the breadth of inner-sphere electrochemical reactions makes this a promising method for understanding the properties of catalytic nanomaterials, one at a time.
Iterative Thematic Inquiry: A New Method for Analyzing Qualitative Data:

Because themes play such a central role in the presentation of qualitative research results, we propose a new method, Iterative Thematic Inquiry (ITI), that is guided by the development of themes. ...
Google Fiber Community Connections: Promises, pitfalls, and outcomes in Austin, Texas

Community Connections is a program tied to Google Fiber that provides free gigabit fiber connections to public or nonprofit facilities such as schools, libraries, community centers, and municipal b...
Case Report: Two Cases of Chemotherapy Refractory Metastatic Penile Squamous Cell Carcinoma With Extreme Durable Response to Pembrolizumab.

Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy, and those patients with metastatic disease have limited treatment options. Treatment is largely comprised of platinum-based chemotherapy, however patients progressing after initial chemotherapy have a median overall survival (OS) of less than six months. Based on a high percentage of PD-L1 expression in patients with PSCC, and its biological similarities to other squamous cell carcinomas, we present two patient cases treated with pembrolizumab with extraordinary durable treatment response far beyond treatment with standard therapy. Main Body: The first patient is a 64 year old male with PSCC who was treated with neoadjuvant chemotherapy, partial penectomy, and adjuvant radiation prior to developing metastatic disease. He had a high TMB (14 mutations/Mb) and was started on pembrolizumab with a complete response, which has been maintained for 38 months. The second patient is an 85 year old male with PSCC who was treated with partial penectomy and adjuvant chemotherapy and radiation prior to developing metastatic disease. He had positive PD-L1 expression CPS 130) and was started on pembrolizumab with a partial response, which has been maintained for 18 months after starting treatment. Conclusions: These two cases of extreme durable response with pembrolizumab (with molecular data including TMB and PD-L1 status) represent a significant clinical benefit in this patient population. With limited treatment options that result in a median OS of less than six months, along with the toxicity profile of chemotherapy which may not be tolerated in elderly patients with comorbidities, this survival benefit with pembrolizumab, along with advances in tumor sequencing and clinical trials shows that there is a potentially significant benefit with novel therapies in this patient population.
Bliss is Ignorance: The Interpersonal Costs of Being Very Happy

Across three studies, we demonstrate that the magnitude of emotion matters. The same emotion (e.g., happiness) can have very different effects at high levels than it does at moderate levels. In our...
Development and Validation of the Oral Health Values Scale.

Objectives Oral health values, the degree to which one places importance on or demonstrates investment in improving or maintaining one's dental status, are believed to vary across individuals. Research on this construct is in its infancy, so a new Oral Health Values Scale (OHVS) was developed and validated. The aim was to create a multidimensional measure of oral health values that could be used in future epidemiological or behavioural investigations involving determinants of dental treatment-seeking behaviour and/or oral health. Methods The OHVS was developed in three cross-sectional phases. A 45-item pool was developed, and 12 expert raters from various oral health professions rated the items for their representativeness and relevance, as well as specificity and clarity. Based on the expert feedback, an initial 30-item scale was subsequently established and administered to a developmental sample (N = 306) using Amazon's Mechanical Turk (MTurk). The scale was further refined to be 12 items and its structure was confirmed in a validation sample (N = 308), also using MTurk. Correlations among OHVS scores and other oral health-related constructs were examined in the developmental and validation samples. Results Expert review of items for the oral health values construct and the OHVS provided initial evidence of content validity. The final 12-item scale exhibited a four-factor structure with good internal consistency, α = 0.84. The psychometric properties of the final scale were confirmed in a second sample using confirmatory factor analysis, although evidence for the OHVS's four-factor structure was mixed. Overall, OHVS scores were consistently related to other oral health constructs in anticipated ways, providing evidence of construct validity. Conclusions The OHVS demonstrated content validity, internal consistency, and construct validity. Results suggest that the OHVS is a psychometrically sound instrument.
Immune System and Methamphetamine: Molecular Basis of a Relationship.

Use of methamphetamine (Meth) as a drug of abuse is on the rise worldwide. Besides its effect on the function of the brain, Meth has detrimental effects on how the immune system functions. As documented in the literature, various experimental models (cellular, animal, mice, and non-human primates) have been used that have contributed to the overall knowledge about immune system impairments from Meth exposure. It has to be noted that while Meth is used in very few treatments, it affects a broad range of biological mechanisms, not only immune regulation, in a negative manner. Undoubtfully, the effect of Meth is highly complex; moreover, the initial molecular triggers remain unknown. Analyses of available literature suggests that the effect of Meth is not prompted by one underlying mechanism. Whether the effect of Meth is acute or long-lasting, the overall effect is negative. Further advancement of our knowledge on Meth's specific actions will require systematic experimental approaches using all available models. In addition, bioinformatic analyses are necessary to build a comprehensive model as a needed tool to fill the gap in knowledge.
Application of saturation absorption spectroscopy to study the hyperfine structure of 235U and accurate 235U/238U isotope ratio determinations at 861.031 nm

The uranium transition 5f36d7s2 (5L6) → 5f37s27p (5K5) at 861.031 nm was studied using saturation absorption spectroscopy. The hyperfine structure of the 235U isotope was determined by measuring the Doppler-suppressed absorption spectrum, and the hyperfine structure constants were obtained by employing transition-specific line strength theory and spectral fitting. The magnetic-dipole and electric-quadrupole constants were determined to be A = −3.2887 ± 0.1957 mK and B = 31.8712 ± 8.0789 mK for the upper state 5f37s27p (5K5). A theoretical calculation for the hyperfine structure constants of the 235U isotope was also carried out by the relativistic configuration-interaction (RCI) method, and the obtained values were found to be in agreement with the measured values. In addition, the line profile of 238U was experimentally investigated for different excitation intensities and modeled using the RCI method for estimating the transition probability and oscillator strength, with various residual broadening mechanisms considered beyond the radiative decay. We show that these results allow us to make improvements on the precision of spectral measurements using our previously developed technique for isotope ratio determinations in atomic beams.
Neoliberal rules: A critical multimodal analysis of metonymy on high school webpages

Abstract This article explores the ways in which neoliberal ideologies are covertly manifested in the discourse of public high schools. Drawing from Critical Discourse Studies (CDS) (Waugh, Catalano, Al Masaeed, Do & Renigar, 2016; Wodak & Meyer, 2016) and conceptual metonymy, (Barcelona, 2003; Benczes & Barcelona, 2011; Charteris-Black, 2004; Panther & Thornburg, 2003) this multimodal study examines the use of metonymy within Tucson Unified School District (TUSD) high school webpage narratives in order to expose the problematic foundation on which public educational systems are constructed. Specifically, this paper investigates how neoliberal principles of competition and individualism, marketization and colorblindness are hidden within the language, photos and, therefore, the structure of public schools. Findings of this study call for commonly used educational language to be problematized for the role it plays in perpetuating racialized systems of inequality , despite purported efforts toward social justice. Finally, this study insists that traditional models of education must be dismantled so that more humanizing possibilities can be imagined and realized.
The adducin saga: Pleiotropic genomic targets for precision medicine in human hypertension; vascular, renal, and cognitive diseases.

Hypertension is a leading risk factor for stroke, heart disease, chronic kidney disease, vascular cognitive impairment, and Alzheimer's disease. Previous genetic studies have nominated hundreds of genes linked to hypertension and renal and cognitive diseases. Some have been advanced as candidate genes by showing that they can alter blood pressure or renal and cerebral vascular function in knockout animals; however, final validation of the causal variants and underlying mechanisms have remained elusive. This review chronicles 40 years of work, from the initial identification of adducin (ADD) as an ACTIN-binding protein suggested to increase blood pressure in Milan hypertensive rats, to the discovery of a mutation in ADD1 as a candidate gene for hypertension in rats that were subsequently linked to hypertension in man. More recently, a recessive K572Q mutation in ADD3 was identified in Fawn-Hooded Hypertensive (FHH) and Milan Normotensive (MNS) rats that develop renal disease, which is absent in resistant strains. ADD3 dimerizes with ADD1 to form functional ADD protein. The mutation in ADD3 disrupts a critical ACTIN-binding site necessary for its interactions with actin and spectrin to regulate the cytoskeleton. Studies using Add3 knockout and transgenic strains, as well as a genetic complementation study in FHH and MNS rats, confirmed that the K572Q mutation in ADD3 plays a causal role in altering the myogenic response and autoregulation of renal and cerebral blood flow, resulting in increased susceptibility to hypertension-induced renal disease and cerebral vascular and cognitive dysfunction.
Induced Pluripotent Stem-Cell-Derived Neural Cell Types in Treatment of Stroke

Stroke is one of the leading causes of death and long-term disability worldwide, yet there are few viable treatment options. One potentially paradigm-changing treatment option on the horizon is induced pluripotent stem-cell-derivedd neural stem cells (iNSCs). Most treatments in clinical and preclinical phases focus on limiting the damage caused by the initial ischemic event and the secondary injury caused by the immune and inflammatory response and similar elements of the cytotoxic environment. However, iNSCs potentially play a dual therapeutic role in stroke by (1) potentially replacing damaged and lost neural cell types and (2) producing regenerative and protective neural signaling factors. In vivo studies in rodent models have demonstrated that these cells have significant promise with treated animals showing a reduction in lesion size, decrease in immune response, and improvements in behavioral and functional outcomes. However, these improvements are not ubiquitous across all studies suggesting additional work must be done to improve outcomes including assessing alternative delivery approaches, vehicles, and windows of therapy and testing in large-animal models more similar to humans.
Estimation of Angular Velocity of a Moving Object Using Line Correspondences

The change in orientation of a moving object is modeled in this paper. The associated angular velocity is determined through an orthonormal interpolation technique in two steps. This involves solving a linear equation and a polynomial equation of order 5. Simulation shows that the method works effectively even when large errors occur in data measurement and processing.
Racah Polynomials and Recoupling Schemes of su(1,1)

The connection between the recoupling scheme of four copies of $\mathfrak{su}(1,1)$, the generic superintegrable system on the 3 sphere, and bivariate Racah polynomials is identified. The Racah polynomials are presented as connection coefficients between eigenfunctions separated in different spherical coordinate systems and equivalently as different irreducible decompositions of the tensor product representations. As a consequence of the model, an extension of the quadratic algebra ${\rm QR}(3)$ is given. It is shown that this algebra closes only with the inclusion of an additional shift operator, beyond the eigenvalue operators for the bivariate Racah polynomials, whose polynomial eigenfunctions are determined. The duality between the variables and the degrees, and hence the bispectrality of the polynomials, is interpreted in terms of expansion coefficients of the separated solutions.
Quantitative market risk disclosure, bond default risk and the cost of debt : why value at risk?

This paper investigates the association of SEC-mandated quantitative market risk disclosure (SEC, 1997) with bond default risk and firms' costs of issuing new debt. I examine such an association by partitioning the sample firms based on their current hedging performance. The results indicate that the first quantitative market risk disclosure is associated with bond default risk and cost of issuing debt differently, depending on the success in hedging. After controlling for other market risk factors, default risk and cost of debt both increase for speculative and/or ineffective hedging firms, but bond default risk decreases for effective hedging firms. The results are robust to alternative measures of hedging and speculation. These findings highlight the importance of reporting the effectiveness of a firm's hedging strategy, as required under SFAS No. 133. The analyses also show that the reduction in bond default risk and cost of debt is observed more frequently with the value at risk format than with sensitivity analysis.
Organizational climate, work stress, and depressive symptoms among probation and parole officers

While work environment and stress are important factors for mental health, no studies have assessed whether these factors contribute independently to the psychological well-being of probation and parole officers (PPOs). Using statewide survey data from 825 PPOs, we examine the association between depressive symptoms, work stress, and work environment (using the organizational climate measures of role ambiguity, role conflict, role overload and emotional exhaustion/burnout). Findings indicate that organizational climate and work stress are important predictors of emotional exhaustion/burnout, and that these factors have both indirect and independent associations with depressive symptomotology. Together, models including organizational climate and work stress account for two-thirds of the variability in burnout. Moreover, models incorporating exhaustion/burnout, work stress, and organizational climate account for nearly half of the variability in depressive symptoms. Organization climate measures and work s...
Evaluating whether nature's intrinsic value is an axiom of or anathema to conservation

That at least some aspects of nature possess intrinsic value is considered by some an axiom of conservation. Others consider nature's intrinsic value superfluous or anathema. This range of views among mainstream conservation professionals potentially threatens the foundation of conservation. One challenge in resolving this disparity is that disparaging portrayals of nature's intrinsic value appear rooted in misconceptions and unfounded presumptions about what it means to acknowledge nature's intrinsic value. That acknowledgment has been characterized as vacuous, misanthropic, of little practical consequence to conservation, adequately accommodated by economic valuation, and not widely accepted in society. We reviewed the philosophical basis for nature's intrinsic value and the implications for acknowledging that value. Our analysis is rooted to the notion that when something possesses intrinsic value it deserves to be treated with respect for what it is, with concern for its welfare or in a just manner. From this basis, one can only conclude that nature's intrinsic value is not a vacuous concept or adequately accommodated by economic valuation. Acknowledging nature's intrinsic value is not misanthropic because concern for nature's welfare (aside from its influence on human welfare) does not in any way preclude also being concerned for human welfare. The practical import of acknowledging nature's intrinsic value rises from recognizing all the objects of conservation concern (e.g., many endangered species) that offer little benefit to human welfare. Sociological and cultural evidence indicates the belief that at least some elements of nature possess intrinsic value is widespread in society. Our reasoning suggests the appropriateness of rejecting the assertion that nature's intrinsic value is anathema to conservation and accepting its role as an axiom.
Palliative care for patients with locally advanced and metastatic non-small cell lung cancer

Non-small cell lung cancer (NSCLC) often presents at an advanced stage and can result in a significant symptomatic burden. Many patients with advanced NSCLC experience symptoms that include pain, dyspnea, cough, decreased appetite, weight loss, and depression. Early initiation of palliative care for advanced or metastatic NSCLC can reduce symptoms, improve quality of life, and prolong survival. Palliative care interventions by an interdisciplinary team focus on patient and family and address physical symptoms, illness understanding, coping, and psychosocial and spiritual distress. The addition of systemic therapy to best supportive care can further improve quality of life and prolong survival. Thoracic external beam radiation therapy beam radiotherapy is well tolerated and can improve quality of life and relieve symptoms such as hemoptysis, pain, cough, and dyspnea. For central airway obstruction, external beam radiation therapy, endobronchial brachytherapy, Nd:YAG laser therapy, and photodynamic therapy can improve symptoms. Symptomatic lung metastases to the brain, adrenal glands, and liver or compressing or impinging the spinal cord or nerve roots can also result in patient symptoms and can be managed with medical and pharmacologic interventions, radiation therapy, surgery, ablative therapy, and systemic therapy. All healthcare providers treating patients with advanced or metastatic NSCLC should make palliative care a priority by assessing for pain, dyspnea, coping and psychosocial distress, and other symptoms at each patient encounter to reduce patient morbidity, improve quality of life, and potentially prolong survival.