cssi/SciSciGPT-SciSciNet huggingface dataset:
Mammosphere Culture of Established Cell Lines Does Not Enrich for a More Tumorigenic Breast Cancer Stem Cell Population.

Background:The cancer stem cell model suggests that tumors arise from and are maintained by a relatively small proportion of cells, termed cancer stem cells. According to this model, only these cells have the capacity for self-renewal and the ability to repopulate the tumor bulk by giving rise to the phenotypically heterogeneous populations of cells that comprise the primary tumor. Evidence to support the cancer stem cell model has been provided by isolation of subpopulations of cells on the basis of differential expression of cell surface markers, followed by functional transplantation into animal models. These studies reveal that only a small subset of CD44+/CD24-/low cancer cells retain the ability to form new tumors after transplantation in immunodeficient mice, consistent with the cancer stem cell model. These results indicate that it may be necessary to target and eliminate cancer stem cells in order to eradicate tumors.Material and Methods:Previous studies have suggested that only breast stem cells have the capacity to proliferate in suspension as spherical colonies termed mammospheres, and that mammosphere derived breast cancer cells are CD44+/CD24-/low and able to form tumors that reproduce the heterogeneity of the original primary tumor when injected into the mammary fat pad of immunodeficient mice. This indicates that mammospheres are comprised of breast cancer stem cells. To identify and characterize breast cancer stem cells more completely, the mammosphere culture system was used to isolate and propagate breast cancer stem cells from three basal breast cancer cell lines (BT549, MDA231, MDA436) and three luminal breast cancer cell lines (MCF7, SKBR3, T47D). The tumorigenicity of the cultured mammospheres and parental cell lines was examined using dilution studies in immunodeficient mice and gene expression profiles were studied by microarray analysis.Results and Discussion:No significant differences in tumorigenicity were observed between breast cancer cells cultured as mammospheres versus standard culture conditions. Furthermore, no consistent differences in gene expression profiles were observed between mammosphere and parental cells across the panel of cancer cell lines. These results suggest that mammosphere culture is not capable of significantly enriching for a more tumorigenic breast cancer stem cell population from established breast cancer cell lines. This may indicate that cancer subpopulations that exist in primary tumors are lost during the long term culture of breast cancer cell lines and that these systems may not be a suitable model for breast cancer stem cell studies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 502.
Ternary Hybrid Nanoparticle Isomers: Directing the Nucleation of Ag on Pt–Fe3O4 Using a Solid-State Protecting Group

Colloidal hybrid nanoparticles are an important class of materials that incorporate multiple nanoparticles into a single system through solid-state interfaces, which can result in multifunctionality and the emergence of synergistic properties not found in the individual components. These hybrid structures are typically produced using seeded-growth methods, where preformed nanoparticles serve as seeds onto which additional domains are added through subsequent reactions. For hybrid nanoparticles that contain more than two domains, multiple configurations with distinct connectivities and functionalities are possible, and these can be considered as nanoparticle analogues of molecular isomers. However, accessing one isomer relative to others in the same hybrid nanoparticle system is challenging, particularly when the formation of a target isomer is disfavored relative to more stable or synthetically accessible configurations. Here, we show that an iron oxide shell installed onto the Pt domain of Pt–Fe3O4 hybri...
Accurate Analytical Self-Consistent-Field Wave Functions for Nd 3 +

The need for an accurate description of the electronic structure of the important laseractive ion ${\mathrm{Nd}}^{3+}$ stimulated this work. We calculated self-consistent-field wave functions by the analytical-expansion method for the ground state of the laser-active ion ${\mathrm{Nd}}^{3+}(Z=60)$, $4{f}^{3}$, $^{4}I$. The results represent the most accurate wave functions for ${\mathrm{Nd}}^{3+}$ published. All the exponents of the basis functions in the analytical expansion were exhaustively optimized. The virial theorem was satisfied to seven significant figures. Values of $〈{\mathcal{r}}^{n}〉$ for the $4f$ orbital are included.
Genetic Diversity and Differentiation in Northern Populations of the Tree-Hole Mosquito Aedes hendersoni (Diptera: Culicidae)

Natural populations of Aedes hendersoni Cockerell in Indiana and Michigan were analyzed for electrophoretic variation at 23 structural loci. These populations were polymorphic at 45% of their loci and exhibited a mean heterozygosity of 13.4%. Nei's intraspecific genetic distance (D) was 0.008. Interspecific comparisons with a sympatric sibling species, A. triseriatus Say, produced a D value of 0.48. Five enzymes, all non-regulatory, were found to distinguish unambiguously between the two species. A. triseriatus was the more variable species, but A. hendersoni populations were more heterogeneous. No evidence of introgression was detected between the two species.
Major issues in threat analysis and resolving such problems: an addendum to the GAP analysis

Identification of regions that warrant conservation attention is a top priority among global environmental concerns. Conventionally, this objective was achieved via recognizing natural landscapes based on the number of IUCN Red Listed species, percentage of endemism and species diversity. A recent innovation in conservation biology is the use of GIS-based threat analysis models to identify key areas of conservation importance. Compared with GAP Analysis, which only identifies biodiversity-rich unprotected lands, threat analysis serves as a rigorous tool in conservation planning which specifically recognizes threats and habitat suitability to different taxa based on a spatially-explicit analysis. Threat analysis is a highly flexible process which involves building up a model with multiple independent (without autocorrelations) variables that both positively and negatively affect distribution and population persistence of a concerned species. Parameters include rate of land-use change, population density, population growth rate, land management regimes, protection status, habitat suitability and land stewardship. Threat analysis models can be used to understand the current status of a particular species (or a community) and can be used to project future trends about the species under consideration. This publication provides an overview of uses of GIS-based threat analyses in conservation biology and provides insights on the limitations of these models and the directions that should be taken in future.
Application of Non-Contrast Enhanced Magnetic Resonance Angiography in Hand Artery Imaging in Patients with Rheumatoid Arthritis

Objective To investigate the effectiveness of application of non-contrast enhanced magnetic resonance angiography(NCE-MRA) in hand artery imaging in patients with rheumatoid arthritis(RA). Methods Altogether 32 RA patients who had been treated in the hospital from January 2013 to December 2014 were selected as the research object. All patients were scanned by hand artery NCEMRA and contrast-enhanced magnetic resonance angiography(CE-MRA). And then the signal-to-noise ratio(SNR), signal-to-noise ratio(CNR) and vascular edge sharpness of the NCE-MRA and CE-MRA imaging results were compared. Additionally, image quality was evaluated and statistically compared. Results The vascular edge sharpness, SNA and CNR in NCE-MRA Group were higher than that in CEMRA Group with statistically significant differences(P0.05). The image quality in NCE-MRA Group were obviously better than that in CE-MRA Group with statistically significant differences(P0.05). Conclusion Application of non-contrast enhanced magnetic resonance angiography in patients with rheumatoid arthritis could improve the imaging quality of the hand artery segments. And SNR, CNR as well as the vascular edge sharpness of NCE-MRA at each artery location were higher than those of CEMRA, which showed its higher diagnostic effectiveness and deserved promotion.
Effect of endotoxin on systemic and skeletal muscle O2 extraction.

Patients with the adult respiratory distress syndrome (ARDS) show a pathological dependence of O2 consumption (VO2) on O2 delivery (QO2, blood flow X arterial O2 content). In these patients, a defe...
The Laminated Medium

An important motivation for a detailed study of the propagation of harmonic waves in laminated media and fiber reinforced composites is that effective elastic constants can conveniently be measured by ultrasonic testing techniques. These techniques have the advantage that small specimens can be used, and that good control and reproducibility can be achieved. Typically one measures phase velocity or group velocity for a number of frequencies. The extrapolation to zero frequency then provides the velocity for very long waves, from which an effective elastic constant can be determined.
Auswertung von Ausdrücken

„Ein Programm ist eine Menge von Bearbeitungsregeln. Eine Bearbeitungsregel besteht aus zwei Teilen: dem Muster auf der linken Seite und dem Ersetzungstext auf der rechten Seite. Die Berechnung besteht darin, nacheinander Ausdrucke auszuwerten. Ein Ausdruck wiederum wird ausgewertet, indem Bearbeitungsregeln gesucht werden, deren Muster einem Teil des Ausdrucks entsprechen. Solch ein Teil wird dann durch den Ersetzungstext der entsprechenden Regel ersetzt, und der Prozes wird solange wiederholt, bis sich keine passenden Ersetzungsregeln mehr finden lassen.“
Coping with Problematic Events in Dating Relationships: The Influence of Dependence Power on Severity Appraisals and Decisions to Communicate.

Inevitably, individuals in dating relationships will at some time behave in a manner that violates mutually understood standards for appropriate behavior. Prior research suggested that when a partner's behavior is problematic, that partner's dependence power exerts a chilling effect on both appraisals of event severity and decisions to communicate with the partner about those actions (Cloven & Roloff, 1993; Roloff & Cloven, 1990; Solomon & Samp, 1998). This investigation examined the influence of dependence power on appraisals and communicative decisions related to an individual's own problematic behavior. Sixty‐five individuals reported their commitment to their dating relationship, their partner's commitment, and their dating alternatives. Next, respondents were presented with a set of hypothetical problematic events, from which the most realistic event was selected. We asked participants to rate the severity of the selected event and report the degree to which they would communicate with their partner ...
"I Am out of My Comfort Zone": Self-Study of the Struggle of Adapting to the Professional Identity of a Teacher Educator.

AbstractIt is often assumed that graduate students will develop as teacher educators simply by participating in a doctoral program. However, research has shown that doctoral students find the shift from teaching K-12 to preparing teachers to be a difficult transition. Within the context of a doctoral program community of practice established specifically for the purpose of examining this transition through self-study research, we sought to understand the shift in identity of a novice teacher educator working as an early field experience instructor with elementary science and mathematics preservice teachers. Our findings indicate that the process of self-study research, when supported within a community of practice, offered Jared the opportunity to recognize different aspects of his shifting professional identity, the dominance of particular aspects of his identity in certain situations, and the impact this was having on his students’ development as teachers. Developing this awareness of his adapting profe...
Ethical Issues in Biomaterials Research

Abstract Biomaterials research and science is rapidly evolving with the aim of providing solutions to vexing medical problems. Emerging technologies including nanotechnology, stem cell research, and tissue engineering have led to numerous ethical challenges including safety, long-term viability, and their utility for human implantation. Furthermore, equitable distribution of emerging biomedical technologies among interest groups and nations has not been adequately addressed and warrants further discussion. Currently there are no ethical guidelines to help researchers, biomedical engineers, and scientists to deal with real-world crisis situations associated with biomedical research. This chapter aims to discuss some of these aforementioned issues that are relevant to the topic of ethics related to biomaterials research.
Fractals in Nerve and Muscle

Mechanical vibrations, chemical concentrations, and action potentials are all forms of information that can be transmitted from one point in space to another by means of various mechanisms. We are familiar with the sound waves that enable us to hear the distant roll of thunder and light waves that enable us to see the lightning flash, but we are less familiar with the waves found in excitable media that enable us to transform these sensory inputs into messages usable by the brain. In practice, these latter waves result from the rhythmic timing of spatially distributed pacemakers such as found in the heart, intestine, kidney, uterus, and stomach. These pacemaker cells are nonlinear biological oscillators that are capable of spontaneous excitation, which can also be entrained by external excitation.
Intrinsic properties and strengthening mechanism of monocrystalline Ni-containing ternary concentrated solid solutions

Abstract Ternary single-phase concentrated solid solution alloys (SP-CSAs), so-called "medium entropy alloys", not only possess notable mechanical and physical properties but also form a model system linking the relatively simple binary alloys to the complex high entropy alloys. The knowledge of their intrinsic properties is vital to understand the material behavior and to prompt future applications. To this end, three model alloys NiCoFe, NiCoCr, and NiFe-20Cr have been selected and grown as single crystals. Their elastic constants have been measured using an ultrasonic method, and several key materials properties, such as shear modulus, bulk modulus, elastic anisotropy, and Debye temperatures have been derived. Furthermore, nanoindentation tests have been performed on these three alloys together with Ni, NiCo and NiFe on their (100) surface, to investigate the strengthening mechanisms. NiCoCr has the highest hardness, NiFe, NiCoFe and NiFe-20Cr share a similar hardness that is apparently lower than NiCoCr; NiCo has the lowest hardness in the alloys, which is similar to elemental Ni. The Labusch-type solid solution model has been applied to interpret the nanoindentation data, with two approaches used to calculate the lattice mismatch. By adopting an interatomic spacing matrix method, the Labusch model can reasonably predict the hardening effects for the whole set of materials.
Trabeculectomy with mitomycin-C in the treatment of pediatric glaucomas.

Abstract Purpose To evaluate the effectiveness and safety of trabeculectomy with mitomycin-C (MMC) in the management of childhood glaucomas. Design Retrospective, noncomparative case series. Participants All patients less than 18 years of age who underwent trabeculectomy with MMC from June 1991 through October 1997 were included. Methods The medical records of 29 consecutive patients (29 eyes) were reviewed. Data collected during routine patient follow-up were analyzed. Surgical outcome was evaluated using Kaplan-Meier life-table analysis. Main outcome measures Clinical outcome assessment included intraocular pressure (IOP) control, visual acuity, and identification of complications. Successful IOP control was defined as 5 mmHg ≤ final IOP ≤ 21 mmHg, with or without antiglaucoma medications and without further glaucoma surgery or loss of light perception. Outcomes for the group of patients with primary infantile glaucoma were compared with those for the group with secondary glaucomas. Results Mean patient age was 6.4 ± 4.4 years (range, 0.2–15.3 years). A variety of primary and secondary glaucomas were represented. Mitomycin-C (0.5 mg/ml) on a surgical sponge was applied to the episcleral surface for an average of 3.8 ± 1.0 minutes (range, 1.5–5.0 minutes). Mean follow-up time for patients categorized as successes was 25.1 ± 16.0 months (range, 5.5–59.7 months). The 12-, 24-, and 36-month life-table success rates for IOP control were 82%, 59%, and 59% respectively. There was no difference between the primary infantile glaucoma group and the secondary glaucoma group with respect to length of follow-up, rate of successful IOP control, and incidence of complications. Five patients (17%) experienced late bleb-related infection (BRI) at an average of 27.9 ± 18.1 months (range, 5.4–55.5 months) after surgery. Other complications included hyphema, retinal detachment, late-onset bleb leak, flat anterior chamber, chronic hypotony, decompression retinopathy, suture abscess, and phthisis. Conclusions Trabeculectomy with MMC may be useful in the management of childhood glaucomas in which goniotomy, trabeculotomy, or both have failed. However, the high incidence of BRI in this series over an extended follow-up interval dictates caution in using MMC as an adjunct in pediatric trabeculectomy.
Association between commercial vehicle driver at-fault crashes involving sleepiness/fatigue and proximity to rest areas and truck stops

Abstract Introduction There is ongoing concern at the national level about the availability of adequate commercial vehicle rest areas and truck stops for commercial vehicle drivers to rest or to wait for a delivery window. Methods A retrospective case-control study was conducted to determine the association between the occurrence of sleepiness/fatigue-related (cases) vs. all other human factor-related commercial vehicle driver at-fault crashes (controls) and proximity to rest areas, weigh stations with rest havens, and truck stops. Results Commercial vehicle driver at-fault crashes involving sleepiness/fatigue were more likely to occur on roadways where the nearest rest areas/weigh stations with rest havens/truck stops were located 20 miles or more from the commercial vehicle crash site (Odds Ratio [OR] = 2.32; Confidence Interval [CI] 1.615, 3.335] for 20–39.9 miles vs. Conclusions The use of statewide crash data analysis coupled with ArcGIS mapping capabilities provided the opportunity to both statistically determine and to visualize the association between rest area/weigh station with rest haven/truck stop distance and the occurrence of commercial vehicle driver at-fault crashes involving sleepiness/fatigue. Implementation and evaluation of commercial vehicle employer policies and interventions such as the use of commercial vehicle driver fatigue alert systems may help to reduce fatigue and sleepiness in commercial vehicle drivers. These results can be used by state and local highway transportation officials to inform and increase truck parking availability, especially on parkways.
Recent progress in systemic treatment for lung cancer.

Purpose of review We intend to highlight progress made in 2017 to lung cancer molecular nosology and application of new knowledge to treatment. Recent findings Studies have shown that agents targeting specific molecular defects in lung cancers such as epidermal growth factor receptor(egfr) mutations, alk or ros1 gene rearrangements, are more effective than conventional combination chemotherapy as primary treatment for various lung cancer subgroups. Identification of mechanisms of drug resistance has guided development of improved agents and effective salvage regimens. Progress in reversing tumor-induced immunosuppression has led to further improvements in response rates (RR) including some patients with prolonged durable remissions. Summary State-of-the-art management of patients with lung cancer requires information derived from tumor molecular analysis, obtained either directly from the tumor or from tumor-derived circulating DNA. Empiric combination chemotherapy is no longer uniformly the best available treatment for all patients. Therapeutic decisions should be guided by an understanding of molecular features of an individual patient's tumor. The future gains will likely emerge from finding optimal ways of combining targeted therapy, immunotherapy, and chemotherapy.
Erythrocyte Membrane Elasticity, Fragmentation and Lysis

The intrinsic material behavior of the normal human erythrocyte membrane may be characterized in terms of its deformation and rate of deformation response as result of forces applied to the membrane. The intrinsic properties are defined by μ, the elastic shear modulus reflecting recoverable hyperelastic response; η, shear viscosity defining viscoelastic behavior with internal viscosity energy dissipation; T0, a yield shear indicating the elastic limit of the membrane material; and η p, shear viscosity in the plastic domain, i.e., irrecoverable extension after the elastic limit of the membrane has been exceeded. Experimental values for these constants for normal membranes are: μ = 10-2 dyn/cm; η = 10-4 dyn · s/cm; T0 = 2 × 10-2 dyn/cm; and η p = 10-2 dyn s/cm. The area compressibility modulus, the constant reflecting resistance to compression or dilation of this two-dimensional membrane is high, 300 dyn/cm, and the maximum fractional area expansion which produced lysis is 2 to 4%. Removal of spectrin from the membrane decreases the elastic constant and tension for lysis, whereas modification of glycophorin and other intrinsic membrane proteins does not affect the solid material behavior. Cross-linking agents such as glutaraldehyde (0.008%) increases the elastic constant; this parallels relative inelasticity of the senescent human erythrocyte membrane and suggests a model for membrane senescence.
Ethics of Clinical Trials

The ethical framework for clinical research is built upon guidelines and regulations that emerged as a result of numerous historical atrocities toward human subjects in the name of science such as the Nuremberg Trial, the Jewish Chronic Disease Hospital, the Willowbrook study, and the Tuskegee syphilis study. The fundamental pillars of research ethics are informed consent, beneficence, and justice, which are based on the Belmont Report. Clinical investigators have a responsibility to protect human subjects by upholding collaborative partnership, social value, scientific validity, fair participant selection, favorable risk-benefit ratio, independent review, informed consent, and respect for participants. In partnership with the subjects and their communities, through disclosure of conflicts of interest, and utilizing valid scientific methods, trust in and among the medical community can be strengthened and science can continue to advance.
Toxic Chemicals as Probes of Nerve Membrane Function

Certain toxins and chemicals have been used as probes to characterize nerve membrane ionic channels. These neuroactive agents exert highly specific actions on sodium or potassium channel. Tetrodotoxin and saxitoxin block the sodium channel at very low concentrations thereby impairing nervous conduction. They are being used to separate the membrane current into a sodium and potassium component, to eliminate the sodium current, to study the mechanism of synaptic and neuromuscular transmission, and to characterize, isolate and identify the sodium channel. A new toxin isolated from Gonyaulax tamarensis exerts a very similar sodium channel blocking action. Tetraethylammoni urn is known to block the potassium channel. Aminopyridines inhibit the potassium current in a manner dependent upon the membrane potential, time and stimulus frequency, and are effective by external application. These potassium blocking agents are useful tools to eliminate the potassium current, to study synaptic transmission, and to characterize the potassium channel. Grayanotoxins selectively increase the resting sodium permeability thereby causing a large depolarization without much effect on the sodium permeability increase responsible for the action potential generation. The resting sodium channel exhibits a very low permselectivity to various organic and inorganic cations, whereas it shows a high selectivity during activity. Grayanotoxins do not affect the selectivity ratio either at rest or during activity. Batrachotoxin and veratridine also increase the resting sodium permeability. These depolarizing agents are useful probes to characterize the resting sodium channel.
Investigating the underlying structure of particulate matter concentrations: a functional exploratory data analysis study using California monitoring data

Functional data analysis continues to attract interest because advances in technology across many fields have increasingly permitted measurements to be made from continuous processes on a discretized scale. Particulate matter is among the most harmful air pollutants affecting public health and the environment, and levels of PM10 (particles less than 10 micrometers in diameter) for regions of California remain among the highest in the United States. The relatively high frequency of particulate matter sampling enables us to regard the data as functional data. In this work, we investigate the dominant modes of variation of PM10 using functional data analysis methodologies. Our analysis provides insight into the underlying data structure of PM10, and it captures the size and temporal variation of this underlying data structure. In addition, our study shows that certain aspects of size and temporal variation of the underlying PM10 structure are associated with changes in large-scale climate indices that quantify variations of sea surface temperature and atmospheric circulation patterns.
Cytomorphology of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features and the Impact of New Nomenclature on Molecular Testing

The re-naming of noninvasive follicular variant papillary thyroid cancer to the apparently non-malignant, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) impacts the prevalence of malignancy rates, thereby affecting mutation frequency in papillary thyroid cancer. Preoperative assessment of such nodules could affect management in the future. The original publications following the designation of the new nomenclature have been extensively reviewed. With the adoption of NIFTP terminology, a reduction in the follicular variant of papillary thyroid cancer (FVPTC) prevalence is anticipated, as is a modest reduction of papillary thyroid cancer (PTC) prevalence that would be distributed mainly across indeterminate thyroid nodules. Identifying NIFTP preoperatively remains challenging. RAS mutations are predominant but the presence of BRAF V600E mutation has been observed and could indicate inclusion of the classical PTC. The histological diagnosis of NIFTP to designate low-risk encapsulated follicular variant papillary thyroid cancers (EFVPTCs) would impact malignancy rates, thereby altering the mutation prevalence. The histopathologic criteria have recently been refined with an exclusion of well-formed papillae. The preoperative identification of NIFTP using cytomorphology and gene testing remains challenging.
An extension of Darcy’s law incorporating dynamic length scales

Abstract We propose a physics-based, macroscale formulation of multiphase porous-media flows that both honors the validity of Darcy’s law in steady or near-steady flows and accommodates the effects of heterogeneities and nonlinearities in unsteady flows. The new formulation recognizes that parameters characterizing the system operate at different length-scales. In particular, the use of Darcy’s law, predicated on the assumption of near-steady flows, requires dynamic length scales, owing to the possibility of rapid fluctuations in rock properties and fluid saturations attributable to heterogeneity and nonlinearity. We accommodate these dynamic length-scales through dynamic spatial averaging. The length and position of the averaging window are characterized by the length of the mixing zone and the direction of propagation of information in the transport process. We validate the proposed formulation by comparing highly accurate, two-dimensional numerical solutions against core-scale displacement experiments. The proposed paradigm is consistent with the classical multiphase Darcy formulation, in the sense that the latter also represents the results of an averaging approach.
Teleproctoring in Surgery Training to Avoid Technical Misadventures and Video Recording: Responsibility and Liability

Sir William Halsted established what is now the basis of modern American surgical training, namely, patient volume and repetition. Due to changes in surgical training, surgeons are now forced to rapidly learn and adapt to new techniques in order to deliver safe care with adequate outcomes.
Juvenile idiopathic arthritis: an update.

Juvenile idiopathic arthritis (JIA) is the most common chronic arthropathy of childhood. Previous terminology identified this entity as juvenile rheumatoid arthritis. The 7 subsets of JIA identified under the new classification system are discussed, as are current treatments. A differential diagnosis of JIA is included as this condition continues to be diagnosed by exclusion. Recent studies, which discuss the outcome of adults with previous childhood arthritis, are reviewed. INRODUCTION Many different types of arthritis affect children. Some are acute and self-limiting, such as viral arthritis. Other forms of arthritis represent chronic conditions. The purpose of this article is to review and highlight new developments in chronic arthritis of childhood. The new classification system of juvenile idiopathic arthritis (JIA), formerly juvenile rheumatoid arthritis (JRA), will be discussed. Additionally, information on the occurrence, diagnosis, clinical features, management, and outcome of this disorder will be updated and reviewed.
Personalized surveillance and prognostication of patients undergoing kidney cancer surgery: The 15-year UCLA experience

5045 Background: Renal cell carcinoma (RCC) is a heterogeneous disease with varying biology, clinical manifestations, and outcome. An evolving understanding of prognostic factors for patients is le...
The political theology of entropy: A Katechon for the cybernetic age:

The digital revolution invites a reconsideration of the very essence of politics. How can we think about decision, control, and will at a time when technologies of automation are transforming every...
Estimation of bias-corrected intraclass correlation coefficient for unbalanced clustered studies with continuous outcomes

Intraclass correlation coefficient for data in a clustered study is traditionally estimated from a one-way random-effects model. This model assumes normality for the random cluster effect and the r...
A program logic to verify signal temporal logic specifications of hybrid systems

Signal temporal logic (STL) was introduced for monitoring temporal properties of continuous-time signals for continuous and hybrid systems. Differential dynamic logic (dL) was introduced to reason about the end states of a hybrid program. Over the past decade, STL and its variants have significantly gained in popularity in the industry for monitoring purposes, while dL has gained in popularity for verification of hybrid systems. In this paper, we bridge the gap between the two different logics by introducing signal temporal dynamic logic (STdL) - a dynamic logic that reasons about a subset of STL specifications over executions of hybrid systems. Our work demonstrates that STL can be used for deductive verification of hybrid systems. STdL significantly augments the expressiveness of dL by allowing reasoning about temporal properties in given time intervals. We provide a semantics and a proof calculus for STdL, along with a proof of soundness and relative completeness.
Fit-for-purpose quantitative liquid biopsy based droplet digital PCR assay development for detection of programmed cell death ligand-1 (PD-L1) RNA expression in PAXgene blood samples

Development of a clinically applicable liquid biopsy-based test for PD-L1 mRNA expression would be beneficial in providing complementary evidence to current immunohistochemistry assays. Hence, we report the development of a fit-for-purpose assay for detection of blood PD-L1 mRNA expression using droplet digital polymerase chain reaction (ddPCR). TaqMan® assays were selected based on coverage of the PD-L1 gene and were tested for linearity and efficiency using real-time quantitative PCR. Four reference genes were analyzed in positive control cell line (A549 treated with interferon gamma, [IFN γ]) genomic DNA. The PD-L1 primer/probe sets were also evaluated in ddPCR for limit of blank, limit of detection, and precision. Finally, thirty-five healthy volunteer samples were evaluated to establish a baseline level of PD-L1 expression. In ddPCR, the limit of blank was determined to be 0 copies and the limit of detection was determined to be less than or equal to 19 copies of PD-L1. The average intra-run coefficient of variation in the ddPCR assay was 7.44% and average inter-run CV was 7.70%. Treatment of A549 cells with IFN γ resulted in a 6.7-fold increase in PD-L1 expression (21,580 copies in untreated cDNA versus 145,000 copies in treated cDNA). Analysis of healthy human samples yielded a median value of 1659 PD-L1 copies/μL with a range of 768-7510 copies/μL. The assay was transferred to an external service provider and results from our in-house experiments and those conducted externally shows a correlation of 0.994. In conclusion, a fit-for-purpose liquid biopsy-based, purely quantitative ddPCR assay for the detection of PD-L1 mRNA expression was developed and validated using PAXgene RNA blood samples. Linearity, reproducibility, limit of blank and limit of detection were measured and deemed suitable for clinical application. This ultra-sensitive liquid biopsy ddPCR assay has promising clinical potential in screening, longitudinal monitoring and disease progression detection.
Predictors of US states' adoption of naloxone access laws, 2001-2017.

Abstract Background The opioid crisis has put an increasing strain on US states over the last two decades. In response, all states have passed legislation to implement a portfolio of policies to address the crisis. Although effects of some of these policies have been studied, research into factors associated with state policy adoption decisions has largely been lacking. We address this gap by focusing on factors associated with adoption of naloxone access laws (NAL), which aim to increase the accessibility and availability of naloxone in the community as a harm reduction strategy to reduce opioid-related morbidity and mortality. Methods We used event history analysis (EHA) to identify predictors of the diffusion of naloxone access laws (NAL) from 2001, when the first NAL was passed, to 2017, when all states had adopted NAL. A variety of state characteristics were included in the model as potential predictors of adoption. Results We found that state adoption of NAL increased gradually, then more rapidly starting in 2013. Consistent with this S-shaped diffusion process, the strongest predictor of adoption was prior adoption by neighboring states. Having a more conservative political ideology and having a higher percentage of residents who identified as evangelical Protestants were associated with later adoption of NAL. Conclusion States appear to be influenced by their neighbors in deciding whether and when to adopt NAL. Advocacy for harm reduction policies like NAL should take into account the political and religious culture of a state.
Contribution of Z b resonances to ϒ ( 5 S ) → π π π χ b

We discuss the recently presented Belle results on the decays $\mathrm{\ensuremath{\Upsilon}}(5S)\ensuremath{\rightarrow}\ensuremath{\pi}\ensuremath{\pi}\ensuremath{\pi}{\ensuremath{\chi}}_{bJ}(1P)$. The data indicate that in addition to the $\ensuremath{\omega}$ emission, $\mathrm{\ensuremath{\Upsilon}}(5S)\ensuremath{\rightarrow}\ensuremath{\omega}{\ensuremath{\chi}}_{bJ}$, there is a significant nonresonant background in the three pion spectrum. We suggest that a sizable fraction of this background may be associated with the cascade process $\mathrm{\ensuremath{\Upsilon}}(5S)\ensuremath{\rightarrow}\ensuremath{\pi}{Z}_{b}\ensuremath{\rightarrow}\ensuremath{\pi}\ensuremath{\rho}{\ensuremath{\chi}}_{b}$ involving the ${Z}_{b}(10610)$ and ${Z}_{b}(10650)$ resonances. If confirmed by the data, this would be the first observation of transition from the ${Z}_{b}$ resonances to lower bottomonium with emission of a light meson state different from a single pion, which may provide a new input in understanding of the internal dynamics of these resonances.
Refereed papers: A Framework for Understanding Vulnerabilities in Firewalls Using a Dataflow Model of Firewall Internals1 1This work was supported by sponsers of the Center for Education and Research in Information Assurance and Security (CERIAS) at Purdue University.

Vulnerabilities in vendor as well as freeware implementations of firewalls continue to emerge at a rapid pace. Each vulnerability superficially appears to be the result of something such as a coding flaw in one case, or a configuration weakness in another. Given the large number of firewall vulnerabilities that have surfaced in recent years, it is important to develop a comprehensive framework for understanding both what firewalls actually do when they receive incoming traffic and what can go wrong when they process this traffic. An intuitive starting point is to create a firewall dataflow model composed of discrete processing stages that reflect the processing characteristics of a given firewall. These stages do not necessarily all occur in all firewalls, nor do they always conform to the sequential order indicated in this paper. This paper also provides a more complete view of what happens inside a firewall, other than handling the filtering and possibly other rules that the administrator may have established. Complex interactions that influence the security that a firewall delivers frequently occur. Firewall administrators too often blindly believe that filtering rules solely decide the fate of any given packet. Distinguishing between the surface functionality (i.e., functionality related to packet filtering) and the deeper, dataflow-related functionality of firewalls provides a framework for understanding vulnerabilities that have surfaced in firewalls.
Desire To Finish College: An Empirical Link between Motivation and Persistence.

A strong desire for achievement may be seen asan important component of student motivation to completecollege. This study examined the structuralrelationships among four constructs: (1) motivational factors, (2) student background factors, (3)academic performance, and (4) persistence. Motivationand background factors were examined to determine theirdirect and indirect effects on academic performance and persistence for minorities andnonminorities. The study supported utilization offactors external to the students' college experienceidentified in the retention literature based on Bean's(1980) Student Attrition Model. While it was found thatmotivation failed to impact academic performance foreither racial subgroup, a significant motivationaleffect on persistence was found for minorities but notfor nonminorities in this study. Minority studentswith high levels of motivation tended to persist totheir second year. Policy implications arediscussed.
Antidepressant mechanism of ketamine: perspective from preclinical studies

A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine's rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine's antidepressant mechanism of action. Recent preclinical studies indicate that ketamine's antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3β) inactivation. Adjunct GSK-3β inhibitors, such as lithium, can enhance ketamine's efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue.
The Political Economy of Equalization Transfers

Normative theories of fiscal federalism postulate that intergovernmental transfers should be determined by equity and efficiency considerations, to support local governments in providing differentiated public goods to heterogeneous populations, while ensuring an even distribution of basic services across all regions (Musgrave, 1959, 1983; Oates, 1972; Gramlich, 1977). However, a recent surge of empirical evidence shows that the distribution of transfers across local jurisdictions, and what local governments do with these transfers is heavily influenced by political incentives facing both national and local policy-makers. Although the notion that intergovernmental transfers, like most other public policy issues, are influenced by and interact with political institutions and processes, is far from earth-shattering, until recently there had been little attempt to internalize the political implications when analyzing the role of transfers in equalizing access to basic services for all citizens. However, the new evidence shows that politics has such substantial impact on both the distribution and use of resources for local service delivery that it cannot be avoided nor side-stepped when developing intergovernmental fiscal policies for equalization.
Picard groups and infinite matrix rings

We describe a connection between the Picard group of a ring with local units T and the Picard group of the unital overring End(TT). Using this connection, we show that the three groups Pic(R), Pic(FM(R)), and Pic(RFM(R)) are isomorphic for any unital ring R. Furthermore, eaclh ele- ment of Pic(RFM(R)) arises from an automorphism of RFM(R), which yields an isomorphsm between Pic(RFM(R)) and Out(RFM(R)). As one applica- tion we extend a classical result of Rosenberg and Zelinsky by showing that the group OutR(RFM(R)) is abelian for any commutative unital ring R.
Mutant p53 expression in fallopian tube epithelium drives cell migration

Ovarian cancer is the fifth leading cause of cancer death among US women. Evidence supports the hypothesis that high-grade serous ovarian cancers (HGSC) may originate in the distal end of the fallopian tube. Although a heterogeneous disease, 96% of HGSC contain mutations in p53. In addition, the "p53 signature," or overexpression of p53 protein (usually associated with mutation), is a potential precursor lesion of fallopian tube derived HGSC suggesting an essential role for p53 mutation in early serous tumorigenesis. To further clarify p53-mutation dependent effects on cells, murine oviductal epithelial cells (MOE) were stably transfected with a construct encoding for the R273H DNA binding domain mutation in p53, the most common mutation in HGSC. Mutation in p53 was not sufficient to transform MOE cells but did significantly increase cell migration. A similar p53 mutation in murine ovarian surface epithelium (MOSE), another potential progenitor cell for serous cancer, was not sufficient to transform the cells nor change migration suggesting tissue specific effects of p53 mutation. Microarray data confirmed expression changes of pro-migratory genes in p53(R273H) MOE compared to parental cells, which could be reversed by suppressing Slug expression. Combining p53(R273H) with KRAS(G12V) activation caused transformation of MOE into high-grade sarcomatoid carcinoma when xenografted into nude mice. Elucidating the specific role of p53(R273H) in the fallopian tube will improve understanding of changes at the earliest stage of transformation. This information can help develop chemopreventative strategies to prevent the accumulation of additional mutations and reverse progression of the "p53 signature" thereby, improving survival rates.
Differential recruitment and activation of natural killer cell sub‐populations by Mycobacterium bovis‐infected dendritic cells

Through complex interplay with APCs, subsets of NK cells play an important role in shaping adaptive immune responses. Bovine tuberculosis, caused by Mycobacterium bovis, is increasing in incidence and detailed knowledge of host–pathogen interactions in the natural host is essential to facilitate disease control. We investigated the interactions of NK-cell sub-populations and M. bovis-infected DCs to determine early innate mechanisms in the response to infection. A sub-population of NK cells (NKp46+CD2−) selectively expressing lymphoid homing and inflammatory chemokine receptors were induced to migrate towards M. bovis-infected DCs. This migration was associated with increased expression of chemokines CCL3, 4, 5, 20 and CXCL8 by M. bovis-infected DCs. Activation of NKp46+CD2− NK cells and secretion of IFN-γ was observed, a response reliant on localised IL-12 release and direct cellular interaction. In a reciprocal manner, NKp46+CD2− cells induced an increase in the intensity of cell surface MHC class II expression on DCs. In contrast, NKp46+CD2+ NK cells were unable to secrete IFN-γ and did not reciprocally affect DCs. This study provides novel evidence to demonstrate distinct effector responses between bovine NK-cell subsets during mycobacterial infection.
Early experience with object-oriented message driven computing

A model of parallel computation, message-driven computing (MDC), is presented, along with a language OOMDC/C that implements it. OOMDC/C is an object-oriented version of MDC that has been implemented in a sequential version and in two parallel versions on the Encore multiprocessor, one holding the messages in shared memory and the other copying the messages between processes. It is shown that the model facilitates the use of a variety of parallel data and control structures, including Actors, distributed arrays, communicating processes, remote procedure calls, broadcast and accumulation, data flow graphs, l-structures, streams, active messages, and demand-driven dynamic programming. >
HEALTHY LEADERS: MULTILEVEL HEALTH PROMOTION CONSIDERATIONS FOR DIVERSE UNITED METHODIST CHURCH PASTORS

Community psychologists often work with institutions and leaders, such as clergy, to bring about social change. Studies finding high rates of chronic disease among clergy have called for the design of clergy health interventions. However, among clergy there is substantial diversity. We conducted four focus groups with a cross-section of United Methodist clergy and one focus group each with female, local, young, and large-sized church pastors. We compared themes from the specific versus broader focus groups. Findings are as follows: female pastors felt guilty for taking personal time and experienced pressure to prove themselves; local pastors reported financial strain and utilized a variety of interpersonal relationships; young pastors indicated child-related stress but also greater interest in nutrition, exercise, and church-based health promotion; and large-sized church pastors expressed increased confidence in negotiating personal time and reported more sharing of pastoral duties. We organized themes by levels of the socioecological framework to guide intervention design.