cssi/SciSciGPT-SciSciNet huggingface dataset:
Method development for detecting the novel cyanide antidote dimethyl trisulfide from blood and brain, and its interaction with blood

The antidotal potency of dimethyl trisulfide (DMTS) against cyanide poisoning was discovered and investigated in our previous studies. Based on our results it has better efficacy than the Cyanokit and the Nithiodote therapies that are presently used against cyanide intoxication in the US. Because of their absence in the literature, the goal of this work was to develop analytical methods for determining DMTS from blood and brain that could be employed in future pharmacokinetic studies. An HPLC-UV method for detection of DMTS from blood, a GC-MS method for detection of DMTS from brain, and associated validation experiments are described here. These analytical methods were developed using in vitro spiking of brain and blood, and are suitable for determining the in vivo DMTS concentrations in blood and brain in future pharmacokinetic and distribution studies. An important phenomenon was observed in the process of developing these methods. Specifically, recoveries from fresh blood spiked with DMTS were found to be significantly lower than recoveries from aged blood spiked in the same manner with DMTS. This decreased DMTS recovery from fresh blood is important, both because of the role it may play in the antidotal action of DMTS in the presence of cyanide, and because it adds the requirement of sample stabilization to the method development process. Mitigation procedures for stabilizing DMTS samples in blood are reported.
Improving Software Development for Embedded Systems

Software development for embedded systems can be challenging. One reason for this is that computing engineers may not have sufficient preparation in a well-defined software development process and computer scientists do not often have sufficient knowledge of low-level architecture of controller devices. The actual implementation of software for embedded subsystems is usually carried out with the C programming language and might also require assembly language routines called from the C program. Several existing micro-controller development boards include software support for developing C and assembly programs. Examples of these types of boards are: Arduino boards and Silicon Labs Development kits. The software support provided mainly includes software tools such as: C compiler, editor, debugger, utilities for transferring the compiled program to the actual micro-controller board. This paper presents the first version of the high-level systems programming language Systems Computing Language (SCL). This is part of larger ongoing project that has as its goal the investigation of newer approaches, methods, techniques, and tools for improving the software development of embedded systems. The language syntax is defined at a higher level of abstraction than C, C++, and Java. Its compiler is implemented as a pre-processor that generates C code, that will subsequently be compiled and linked with standard tools. This paper provides an overview of systems programming languages, a description of the main features of the SCL language, then presents an example of an SCL program implemented for an Arduino program.
Decoupling Economic Growth and Carbon Emissions

John Deutch is an emeritus Institute Professor at the Massachusetts Institute of Technology where he has been a member of the faculty since 1970. He has served as Chairman of the Department of Chemistry, Dean of Science, and Provost. In the Carter Administration, he served as Director of Energy Research (1977–1979), Acting Assistant Secretary for Energy Technology (1979), and Undersecretary (1979–1980) in the US Department of Energy. He has been a member of the President's Nuclear Safety Oversight Committee (1980–1981); the White House Science Council (1985–1989); the President's Committee of Advisors on Science and Technology (1997–2001), and the Secretary of Energy Advisory Board (2008–2016). John Deutch has published widely on technical and policy aspects of energy and the environment and has been a member of the board of directors or of the technical advisory committees of several energy companies.
Selection Bias in Mutual Fund Flow-Induced Fire Sales: Causes and Consequences

Trading pressure following mutual fund outflows generates a potentially powerful quasi-experimental setting in which stock price variation is orthogonal to firm characteristics. To exclude information-based trading, strategies using this variation incorporate an assumption that managers sell firms in proportion to portfolio weights. I show that this assumption drives selection bias in price fluctuations. It inflates price impacts for poorly performing, illiquid firms with lower growth – firms that managers systematically avoid selling. Results drawn using these prices are twice the magnitude of unbiased results. Extensive selection bias precludes potential fixes. Numerous recent studies exploiting this variation should be re-evaluated.
Incidence of hidradenitis suppurativa among tobacco smokers: a population-based retrospective analysis in the U.S.A.

SummaryBackground The relationship between tobacco use and hidradenitis suppurativa (HS) is controversial. Objectives To determine the incidence of HS among tobacco smokers. Methods Retrospective cohort analysis identifying incident HS cases among adult tobacco smokers and nonsmokers sampled from a demographically heterogeneous population-based sample of over 50 million unique patients across all census regions in the U.S.A. Results We identified 3 924 310 tobacco smokers, which included 7860 patients newly diagnosed with HS. Tobacco smokers diagnosed with HS were most commonly aged 18–39 years (3795 of 7860; 48·3%), women (5640 of 7860; 71·8%), white (5200 of 7860; 66·2%) and those with body mass index (BMI) ≥ 30 (5690 of 7860; 72·4%). Overall incidence of HS was 0·20% (7860 of 3 924 310) among tobacco smokers and 0·11% (8430 of 8 027 790) among nonsmokers (P < 0·001). Incidence was greatest among tobacco smokers who were aged 30–39 years (0·35%), women (0·28%), African Americans (0·46%) and those with BMI ≥ 30 (0·33%). The overall adjusted odds of developing HS was 1·90 (95% confidence interval 1·84–1·96) among tobacco smokers, compared with nonsmokers (P < 0·001). HS incidence among tobacco smokers remained increased within each demographic subgroup. Conclusions Incidence of HS appears to be doubled among tobacco smokers. These findings may support evidence-based counselling efforts for the cessation of smoking in populations at risk for HS.
The Impact of Attitudes and Experience on Small Business Computer Use

This study investigates the attitudes of small business owners/managers toward computers and how computers are used in small businesses. A survey of 236 firms revealed that a majority of the respon...
Parental Self-efficacy and Adolescent Risky and Antisocial Behavior:The Mediating Role of Parental Punishment and School Engagement

The aim of this study was to examine direct effects of parental self-efficacy on adolescents’ risky and antisocial behaviour as well as serial indirect effects through parental punishment and adolescents’ school engagement. Data used in the paper were collected in a two-wave longitudinal study conducted within the research project “Parents’ work, family economic hardship, and well-being of parents and children”. In this paper, data collected from 193 adolescents (120 girls) and their parents were used. Adolescents completed the Self-Reported Risky and Antisocial Behaviour Scale (Vrselja et al., 2009), the School Engagement Measure (Fredricks et al., 2005), and the Punishment Subscale of the Parenting Behaviour Questionnaire (Kerestes et al., 2012). Mothers and fathers completed the Parental Self-Efficacy Subscale of the Parental Competence Scale (Kerestes et al., 2011). Process macro (Hayes, 2013) for SPSS was used to test the proposed direct and indirect effects. The results showed that paternal, unlike maternal, self-efficacy had a direct effect on adolescents’ risky and antisocial behaviour. Lower self-efficacy in fathers contributed positively to more pronounced risky and antisocial behaviour in adolescents. Further, maternal self-efficacy had an indirect effect on adolescents’ risky and antisocial behaviour through the maternal use of harsh punishment and lower adolescents’ behavioural school engagement. There were no significant indirect effects of maternal or paternal self- efficacy on adolescents’ risky and antisocial behaviour in models with emotional and cognitive school engagement as mediators. The findings of the study point to different mechanisms by which maternal and paternal self- efficacy and adolescents’ school engagement contribute to adolescents’ risky and antisocial behaviour.
Modeling Microenvironmental Regulation of Glioblastoma Stem Cells: A Biomaterials Perspective

Following diagnosis of a glioblastoma (GBM) brain tumor, surgical resection, chemotherapy and radiation together yield a median patient survival of only 15 months. Importantly, standard treatments fail to address the dynamic regulation of the brain tumor microenvironment that actively supports tumor progression and treatment resistance. It is becoming increasingly recognized that specialized niches within the tumor microenvironment maintain a population of highly malignant glioblastoma stem-like cells (GSCs). GSCs are resistant to traditional chemotherapy and radiation therapy, suggesting that they may be responsible for the near universal rates of tumor recurrence and associated morbidity in GBM. Thus, disrupting microenvironmental support for GSCs could be critical to developing more effective GBM therapies. Three-dimensional (3D) culture models of the tumor microenvironment are powerful tools for identifying key biochemical and biophysical inputs that impact malignant behaviors. Such systems have been used effectively to identify conditions that regulate GSC proliferation, invasion, stem-specific phenotypes, and treatment resistance. Considering the significant role that GSC microenvironments play in regulating this tumorigenic sub-population, these models may be essential for uncovering mechanisms that limit GSCs malignancy.
The Microscopy Society Of America's Project MICRO: The Vermont Experience

Project MICRO (Microscopy in Curriculum - Research Outreach) is an initiative by the Microscopy Society of America (MSA) to connect scientists with middle school teachers in an effort to introduce young students to the scientific method. Through a collaboration with the Lawrence Hall of Science (LHS) at the University of California, Berkeley, a teacher's manual was produced as part of the LHS GEMS (Great Explorations in Math and Science) series. This manual, entitled “Microscopic Explorations”, can be used by scientists and middle school teachers alike to prepare a Project MICRO “Festival” to be presented in the classroom. Detailed information concerning Project MICRO in general, and the Microscopic Explorations manual can be obtained from the Project MICRO web page from MSA (http://www.msa.microscopy.com/ProjectMicro/PMHomePage.html).
TG-51 reference dosimetry for the Halcyon™: A clinical experience

Halcyon™ is a single-energy (6 MV-FFF), bore-enclosed linear accelerator. Patient setup is performed by first aligning to external lasers mounted to the front of the bore, and then loading to isocenter through pre-defined couch shifts. There is no light field, optical distance indicator or front pointer mechanism, so positioning is verified through MV imaging with kV imaging scheduled to become available in the future. TG-51 reference dosimetry was successfully performed for Halcyon™ in this imaging-based setup paradigm. The beam quality conversion factor, kQ , was determined by measuring %dd(10)x three ways: (a) using a Farmer chamber with lead filtering, (b) using a Farmer chamber without lead filtering, and (c) using a PinPoint chamber without lead filtering. Values of kQ were determined to be 0.995, 0.996, and 0.996 by each measurement technique, respectively. Halcyon™'s 6 MV-FFF beam was found to be broader than other FFF beams produced by Varian accelerators, and profile measurements at dmax showed the beam to vary less than 0.5% over the dimensions of our Farmer chamber's active volume. Reference dosimetry can be performed for the Halcyon™ accelerator simply, without specialized equipment or lead filtering with minimal dosimetric impact. This simplicity will prove advantageous in clinics with limited resources or physics support.
Characterizing Software Self-healing Systems

The introduction of self-healing capabilities to software systems could offer a way to alter the current, unfavorable imbalance in the software security arms race. Consequently, self-healing software systems have emerged as a research area of particular interest in recent years. Motivated by the inability of traditional techniques to guarantee software integrity and availability, especially against motivated human adversaries, self-healing approaches are meant to complement existing approaches to security.
Regulation of the human cellular glutathione peroxidase gene during in vitro myeloid and monocytic differentiation.

We have used the HL-60 and PLB-985 myeloid leukemia cell lines to examine the regulation of expression of the important intracellular antioxidant enzyme, glutathione peroxidase (GSH-Px), during phagocytic cell differentiation in vitro. Induction of differentiation along the monocytic pathway by phorbol ester results in an approximately twofold rise in enzyme activity and a parallel increase in the rate of 75Se incorporation into immunoprecipitable GSH-Px protein. Induction along the granulocytic pathway by dimethyl formamide (DMF) results in similar changes in steady-state enzyme levels and rates of GSH-Px protein synthesis. Steady-state levels of GSH-Px gene transcripts also increase more than twofold, approximately in parallel with the enzyme levels. Nuclear run-on transcription assays of GSH-Px mRNA synthesis show ratios of induced to uninduced transcript levels of 2.24 and 1.59 with phorbol myristate acetate (PMA) induction and DMF, respectively, in HL- 60 cells, and ratios of 1.34 and 3.46 with PMA and DMF, respectively, in PLB-985 cells. Half lives of GSH-Px mRNA are unchanged or slightly shorter after differentiation of HL-60 cells, and slightly longer after induction of PLB-985. Overall, the present studies show that GSH-Px activity rises during in vitro-induced monocytic or granulocytic differentiation of myeloid cell lines and that the increased expression of the cellular GSH-Px gene occurs through complex mechanisms that include transcriptional up-regulation. This pattern contrasts with the nearly complete cotranslational regulation of GSH-Px expression by exogenous selenium.
Clinical Diagnosis of Hyperlipoproteinemia

Specific physical findings are associated with the different phenotypes of hyperlipoproteinemia and may point up the need for further medical work-up to determine whether hyperlipoproteinemia is primary or secondary. The clinical manifestations of severe elevations in plasma lipid levels include xanthomas, which may be tendinous, tuberous, or eruptive. Xanthelasma is a common type of xanthoma that is seen in the creases of the eyelids. Other clinical manifestations of hyperlipoproteinemia include corneal arcus, lipemia retinalis, abdominal pain and pancreatitis. In patients with certain types of xanthoma whose serum cholesterol and triglyceride levels are normal, hyperlipoproteinemia has been diagnosed on the basis of abnormalities in plasma apoproteins and their subfractions.
When it comes to people, one size doesn’t fit all: A comment on Wayne

Dr. Wayne proposes that an autonomy-based approach to the treatment and care of older patients with dementia be replaced with an agency-based approach. In this commentary, I suggest that such a shi...
The role of adipose stroma in prostate cancer aggressiveness.

Resistance of prostate cancer to treatment remains a challenge. Surgery, chemotherapy, and androgen deprivation therapy cure most patients with early-stage disease. However, metabolic reprogramming, androgen receptor bypass, and sustained immunotolerance results in treatment-refractory prostate cancer that progresses to metastatic and lethal stages.
Transmission spectrum of an optical cavity containing N atoms

The transmission spectrum of a high-finesse optical cavity containing an arbitrary number of trapped atoms is presented in the zero-temperature, low saturation limit. We take spatial and motional effects into account and show that in the limit of strong coupling, the important spectral features can be determined for an arbitrary number of atoms, N. We also show that these results have important ramifications in limiting our ability to determine the number of atoms in the cavity.
Utilizing multiplex fluor LAMPs to illuminate multiple gene expressions in situ

In situ gene expression detection is the best way to determine temporal and spatial differences in gene expression. However, in situ hybridization procedures are inherently difficult to execute and typically suffer from degradation of sample tissues, limited sensitivity to genes with low expression, high background, and limitation to single gene detections. We propose to utilize an isothermal gene amplification technique, LAMP (Loop-Mediated Isothermal Amplification), to solve these problems in a novel way. LAMP greatly amplifies the signal of expressed genes and can use multiple sets of primers and different fluorescent-labeled probes to produce multiplex gene detection. LAMP is a rapid, isothermal reaction that reduces the handling and degradation of tissue by cutting down on the washing steps required by other methods. Using this technique, we have successfully amplified 3 target genes, have produced positive fluorescent in situ results simultaneously for two genes. We have also demonstrated that LAMP can be used to exploit standard NBT/BCIP (nitro-blue tetrazolium chloride/5-bromo-4-chloro-3'-indolyphosphate p-toluidine salt) detection of single expression. In situ LAMP is a robust and applicable method that can be exploited for detection of gene expression in plant species, as well as in animals and bacteria.
Smart Agriculture in Uganda

Smart agriculture for subsistence farming is addressed in theory, laboratory and field. A non-profit, nongovernmental organization and two Ugandan women's cooperatives in the target area, the Wakiso District of Uganda, are partners with the IEEE Special Interest Group for Humanitarian Technology (SIGHT) at the University of Colorado in this effort to demonstrate cost effective, small scale, smart agriculture. The target area has abundant ground water but presently irregular rainfall. Manual watering is manpower intensive in an occupation already has poor return on investment. Solar pumps and gravity feeds are low priced, low maintenance ad consume no fuel. Inexpensive systems for solar pumping of ground water from a shallow (15 m) tube well to an elevated water storage tank for gravity feed are designed and demonstrated. A system with a 400 W pump and 5000 l tank is shown to be sufficient for a one hectare maize field. Inclusion of a 300 W surface pump with atomizer sprayers is used for a vertical mushroom farm at a second cooperative. A sensor and communication system that informs farmers to the state of dampness in their field has been characterized. The system allows farmers to decide when to activate drip/atomizer irrigation. Scaling of this irrigation approach is discussed.
β-Catenin and TCFs/LEF signaling discordantly regulate IL-6 expression in astrocytes.

The Wnt/β-catenin signaling pathway is a prolific regulator of cell-to-cell communication and gene expression. Canonical Wnt/β-catenin signaling involves partnering of β-catenin with members of the TCF/LEF family of transcription factors (TCF1, TCF3, TCF4, LEF1) to regulate gene expression. IL-6 is a key cytokine involved in inflammation and is particularly a hallmark of inflammation in the brain. Astrocytes, specialized glial cells in the brain, secrete IL-6. How astrocytes regulate IL-6 expression is not entirely clear, although in other cells NFκB and C/EBP pathways play a role. We evaluated here the interface between β-catenin, TCFs/LEF and C/EBP and NF-κB in relation to IL-6 gene regulation in astrocytes. We performed molecular loss and/or gain of function studies of β-catenin, TCF/LEF, NFκB, and C/EBP to assess IL-6 regulation in human astrocytes. Specifically, siRNA mediated target gene knockdown, cDNA over expression of target gene, and pharmacological agents for regulation of target proteins were used. IL-6 levels was evaluated by real time quantitative PCR and ELISA. We also cloned the IL-6 promoter under a firefly luciferase reporter and used bioinformatics, site directed mutagenesis, and chromatin immunoprecipitation to probe the interaction between β-catenin/TCFs/LEFs and IL-6 promoter activity. β-catenin binds to TCF/LEF to inhibits IL-6 while TCFs/LEF induce IL-6 transcription through interaction with ATF-2/SMADs. β-catenin independent of TCFs/LEF positively regulates C/EBP and NF-κB, which in turn activate IL-6 expression. The IL-6 promoter has two putative regions for TCFs/LEF binding, a proximal site located at -91 nt and a distal site at -948 nt from the transcription start site, both required for TCF/LEF induction of IL-6 independent of β-catenin. IL-6 regulation in human astrocytes engages a discordant interaction between β-catenin and TCF/LEF. These findings are intriguing given that no role for β-catenin nor TCFs/LEF to date is associated with IL-6 regulation and suggest that β-catenin expression in astrocytes is a critical regulator of anti-inflammatory responses and its disruption can potentially mediate persistent neuroinflammation.
Housestaff perceptions on training and discussing the Maryland Orders for Life Sustaining Treatment Form (MOLST).

Background On-line tutorials are being increasingly used in medical education, including in teaching housestaff skills regarding end of life care. Recently an on-line tutorial incorporating interactive clinical vignettes and communication skills was used to prepare housestaff at Johns Hopkins Hospital to use the Maryland Orders for Life Sustaining Treatment (MOLST) form, which documents patient preferences regarding end of life care. 40% of housestaff who viewed the module felt less than comfortable discussing choices on the MOLST with patients. We sought to understand factors beyond knowledge that contributed to housestaff discomfort in MOLST discussions despite successfully completing an on-line tutorial. Methods We conducted semi-structured telephone interviews with 18 housestaff who completed the on-line MOLST training module. Housestaff participants demonstrated good knowledge of legal and regulatory issues related to the MOLST compared to their peers, but reported feeling less than comfortable discussing the MOLST with patients. Transcripts of interviews were coded using thematic analysis to describe barriers to using the MOLST and suggestions for improving housestaff education about end of life care discussions. Results Qualitative analysis showed three major factors contributing to lack of housestaff comfort completing the MOLST form: [1] physician barriers to completion of the MOLST, [2] perceived patient barriers to completion of the MOLST, and [3] design characteristics of the MOLST form. Housestaff recommended a number of adaptations for improvement, including in-person training to improve their skills conducting conversations regarding end of life preferences with patients. Conclusions Some housestaff who scored highly on knowledge tests after completing a formal on-line curriculum on the MOLST form reported barriers to using a mandated form despite receiving training. On-line modules may be insufficient for teaching communication skills to housestaff. Additional training opportunities including in-person training mechanisms should be incorporated into housestaff communication skills training related to end of life care.
Faculty Perceptions of Research Assessment at Virginia Tech

In the spring of 2019, survey research was conducted at Virginia Polytechnic Institute and State University (Virginia Tech), a large, public, Carnegie-classified R1 institution in southwest Virginia, to determine faculty perceptions of research assessment as well as how and why they use researcher profiles and research impact indicators. The Faculty Senate Research Assessment Committee (FSRAC) reported the quantitative and qualitative results to the Virginia Tech Board of Visitors to demonstrate the need for systemic, political, and cultural change regarding how faculty are evaluated and rewarded at the university for their research and creative projects. The survey research and subsequent report started a gradual process to move the university to a more responsible, holistic, and inclusive research assessment environment. Key results from the survey, completed by close to 500 faculty from across the university, include: a.) the most frequently used researcher profile systems and the primary ways they are used (e.g., profiles are used most frequently for showcasing work, with results indicating that faculty prefer to use a combination of systems for this purpose); b.) the primary reasons faculty use certain research impact indicators (e.g., number of publications is frequently used but much more likely to be used for institutional reasons than personal or professional reasons); c.) faculty feel that research assessment is most fair at the department level and least fair at the university level; and d.) faculty do not feel positively towards their research being assessed for the allocation of university funding.
Security assurance of MongoDB in singularity LXCs: an elastic and convenient testbed using Linux containers to explore vulnerabilities

It is essential to ensure the data security of data analytical frameworks as any security vulnerability existing in the system can lead to a data loss or data breach. This vulnerability may occur due to attacks from live attackers as well as automated bots. However inside attacks are also becoming more frequent because of incorrectly implemented security requirements and access control policies. Thus, it is important to understand security goals and formulate security requirements and access control policies accordingly. Therefore, it is equally important to identify the existing security vulnerabilities of a given software system. To find the available vulnerabilities against any system, it is mandatory to conduct vulnerability assessments as scheduled tasks in a regular manner. Thus, an easily deployable, easily maintainable, accurate vulnerability assessment testbed or a model is helpful as facilitated by Linux containers. Nowadays Linux containers (LXCs) which have operating system level virtualization, are very popular over virtual machines (VMs) which have hypervisor or kernel level virtualization in high performance computing (HPC) due to reasons, such as high portability, high performance, efficiency and high security (Chae et al in Clust Comput 22:1765-1775, 2019. https://doi.org/10.1007/s10586-017-1511-2 ). Hence, LXCs can make an efficient and scalable vulnerability assessment testbed or a model by using already developed analyzing tools such as OpenVas, Dagda, PortSpider, MongoAudit, NMap, Metasploit Framework, Nessus, OWASP Zed Attack Proxy, and OpenSCAP, to assure the required security level of a given system very easily. To verify the overall security of any given software system, this paper first introduces a virtual, portable and easily deployable vulnerability assessment general testbed within the Linux container network. Next, the paper presents, how to conduct experiments using this testbed on a MongoDB database implemented in Singularity Linux containers to find the available vulnerabilities in 1. MongoDB application itself, 2. Images accompanied by containers, 3. Host, and 4. Network by integrating seven tools: OpenVas, Dagda, PortSpider, MongoAudit, NMap, Metasploit Framework, and Nessus to the container-based testbed. Finally, it discusses how to use generated results to improve the security level of the given system.
A Dilemma for Driver on Virtues of Ignorance

For Julia Driver, some virtues involve ignorance. Modesty, for example, is a disposition to underestimate self-worth, and blind charity is a disposition not to see others’ defects. Such “virtues of ignorance,” she argues, serve as counterexamples to the Aristotelian view that virtue requires intellectual excellence. But Driver seems to face a dilemma: if virtues of ignorance involve ignorance of valuable knowledge, then they do not merit virtue status; but if they involve ignorance of trivial knowledge, then they do not preclude intellectual excellence. So, either there are no virtues of ignorance, or there are no virtues of ignorance – at least not the sort of ignorance that precludes intellectual excellence. Virtues of ignorance therefore fail as counterexamples to Aristotelian virtue theory.
Four Challenges Associated with Current Mathematical Modeling Paradigm of Infectious Diseases and Call for a Shift

Mathematical models are critical tools to characterize COVID-19 dynamics and take action accordingly. We identified 4 major challenges associated with the current modeling paradigm (SEIR) that hinder the efforts to accurately characterize the emerging COVID-19 and future epidemics. These challenges included (1) lack of consistent definition of "case"; (2) discrepancy between patient-level clinical insights and population-level modeling efforts; (3) lack of adequate inclusion of individual behavioral and social influence; and (4) allowing little flexibility of including new evidence and insights when our knowledge evolved rapidly during the pandemic. Therefore, these challenges made the current SEIR modeling paradigm less practical to handle the complex COVID-19 and future pandemics. Novel and more reliable data sources and alternative modeling paradigms are needed to address these issues.
The development of novel Sigma-2 targeted alpha-emitting radioligand astatine-211-MM3 as a potential radiotherapeutic for breast cancer

8 Objectives The Sigma-2 receptor is a unique therapeutic target in cancer due to its preferential expression in rapidly dividing cells, and to a lesser extent in dormant cells, compared to healthy tissue. Targeting the Sigma-2 receptor with an alpha emitting radioconjugate provides a new strategy for delivering high doses of radiation selectively to cancer cells with a potential lethality irrespective of cell cycle status unlike conventional therapies. In this work we report the pre-clinical evaluation of 211At-MM3 in breast cancer models. Methods 211At-MM3 was synthesized from stannylated precursor and was purified by HPLC. The dissociation constant (Kd) of 211At-MM3 was determined using live EMT-6 breast cancer cells. The therapeutic effect of 211At-MM3 was tested on EMT6, MDA-MB-231 and MCF-7 breast cancer cells, assessed by cell viability measured 72 hrs post treatment. In vivo biodistribution in balb/c mice bearing EMT6 xenografts was measured after intravenous administration of 10 microCuries 211At-MM3; animals were sacrificed at 5 minutes, 1 and 2 hours, after radiotracer administration. Results 211At-MM3 was produced in adequate quantities and cell binding assays showed high affinity for the Sigma-2 receptor and cytotoxicity was observed in all breast cancer cell lines tested. In vivo biodistribution resulted in high tumor targeting with an average of 4.93% injected dose/gram in the tumor at 2 hours and a tumor/muscle ratio of 4. Conclusions 211At-MM3 retains high affinity for the Sigma-2 receptor in vitro and in vivo with promising tumor targeting capabilities. In vitro cytotoxicity experiments reveal therapeutic efficacy across multiple breast cancer cell lines and collectively this work establishes the proof of concept for 211At-MM3 as a potential alpha-emitting radiotherapeutic meriting further exploration. Research Support Funding and Support: This research was supported by the Department of Energy DE-FOA-0001075 as part of the multi-disciplinary research and training program in Breast Cancer Molecular Imaging and Targeted Radiochemistry at the University of Pennsylvania.
Implementing two-dimensional autocorrelation in either survival or natural mortality improves a state-space assessment model for Southern New England-Mid Atlantic yellowtail flounder

Abstract Survival is an important population process in fisheries stock assessment models and is typically treated as deterministic. Recently developed state-space assessment models can estimate stochastic deviations in survival, which represent variability in some ambiguous combination of natural mortality (M), fishing mortality (F), and migration. These survival deviations are generally treated as independent by age and year, despite our understanding that many population processes can be autocorrelated and that not accounting for autocorrelation can result in notable bias. We address these concerns, as well as the strong retrospective pattern found in the last assessment of Southern New England yellowtail flounder (Limanda ferruginea), by incorporating two-dimensional (2D, age and year) first-order autocorrelation in survival and M. We found that deviations were autocorrelated among both years (0.53 ± 0.09, 0.63 ± 0.16) and ages (0.33 ± 0.12, 0.40 ± 0.16) when estimated for survival or M, respectively. Models with 2D autocorrelation on survival or M fit the data better and had reduced retrospective pattern than models without autocorrelation. The best fit model included 2D autocorrelated deviations in survival as well as independent deviations in M and altered estimates of spawning stock biomass by 18 % and F by 21 % in model years. In short-term projections with F = 0, including 2D autocorrelation in survival or M reduced spawning stock biomass by 48 %. We conclude that incorporating 2D autocorrelated variation in survival or M could improve the assessment of Southern New England yellowtail flounder in terms of model fit and consistency of biomass projections.
Acute kidney injury and hepatorenal syndrome in cirrhosis

Acute kidney injury (AKI) in cirrhosis, including hepatorenal syndrome (HRS), is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. AKI is separated into two categories, non-HRS AKI and HRS-AKI. The most recent definition and diagnostic criteria of AKI in cirrhosis and HRS have helped diagnose and prognosticate the disease. The pathophysiology behind non-HRS-AKI and HRS is more complicated than once theorized and involves more processes than just splanchnic vasodilation. The common biomarkers clinicians use to assess kidney injury have significant limitations in cirrhosis patients; novel biomarkers being studied have shown promise but require further studies in clinical settings and animal models. The overall management of non-HRS AKI and HRS-AKI requires a systematic approach. Although pharmacological treatments have shown mortality benefit, the ideal HRS treatment option is liver transplantation with or without simultaneous kidney transplantation. Further research is required to optimize pharmacologic and nonpharmacologic approaches to treatment. This article reviews the current guidelines and recommendations of AKI in cirrhosis.
Roles of Eukaryotic Initiation Factor 2 and Eukaryotic Initiation Factor 2 Ancillary Protein Factors in Eukaryotic Protein Synthesis Initiation

The available evidence indicates that although the basic steps of peptide chain initiation are similar in all eukaryotic cells, the specific regulatory mechanisms may be different in animal cells and in lower eukaryotic cells. The basic steps are: (1) formation of a ternary complex between eukaryotic peptide chain initiation factor 2 (eIF-2), Met-transfer RNA (tRNA)f, and GTP: Met-tRNAf · elF-2 · GTP; (2) transfer of Met-tRNAf to 40 S ribosomes and formation of the Met-tRNAf · 40 S · messenger RNA (mRNA) complex; and (3) joining of the Met-tRNAf · 40 S · mRNA complex with 60 S ribosomes and the formation of the Met-tRNAf · 80 S · mRNA complex.
Chapter 2 Non-Market Asset Prices: A Comparison of Three Valuation Approaches

Publisher Summary This chapter presents a comparative analysis of various measures of the benefits from water quality improvements. The experiments are applied in a field context developed for the Lake Okoboji region of Iowa. These glacial lakes offer a relatively unique set of characteristics for experimentation because they are connected and have about the same amenities except water quality. Five measures of water quality value are developed and tested including: realtors' best estimate, comparison of imputed lake frontage prices, a pooled regression estimate based on assessed valuation, willingness to pay, and willingness to be compensated; the last two derived utilizing the contingent valuation method on a very limited sample. As might be expected, the values derived from the different approaches are similar in magnitude, except for the compensation measure. Problems with obtaining valid estimates of compensation are encountered. However, the other values might be expected to be similar because an active “implicit” market for water quality through residence site selection has been operating for several years.
Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-α release

Kotanidou, Anastasia, Augustine M. K. Choi, Richard A. Winchurch, Leo Otterbein, and Henry E. Fessler. Urethan anesthesia protects rats against lethal endotoxemia and reduces TNF-α release.J. Appl....
Environmental data assimilation: methods and challenges

This paper provides an overview of environmental data assimilation methods, with an emphasis on implicit assumptions about linearity, dimensionality, and uncertainty. It also indicates how ensemble and reduced rank concepts may be able to make data assimilation algorithms more flexible and efficient, so they can be applied to complex practical problems.
Full Solution of an Endogenous Sorting Model with Contextual and Income Effects

The paper solves themselves into neighborhoods because they value average schooling among adults in the neighborhood. The paper extends results by Nesheim (2002) but with the addition of income effects on neighborhood choice. Individuals value housing, non-housing consumption, and expected schooling of their children. The latter depends on parental schooling, on a child's ability, and on average schooling in the neighborhood. Neighborhood choice trades off non-housing consumption with children's expected schooling. Individuals choose neighborhoods recongnizing that their neighbors' characteristics are correlated with their own. The equilibrium housing price is associated with endogenous sorting and also allows computation of a neighborhood distributions of income, schooling and other variables of interest.
Enhanced time of arrival estimation with successive cancellation

Two methods for accurate estimation of time or angle of arrival that use successive cancellation techniques are presented. The first method performs successive cancellation with a correlation approach used for each iteration. The second method uses the multiple signal identification and classification (MUSIC) approach for each iteration. The first method exhibits enhanced performance as compared to straight-forward correlation techniques and has lower complexity than high resolution techniques such as MUSIC. The method also performs better than Capon's (1969) minimum variance method and MUSIC when the total time duration of the received signal is small or when the signal-to-noise ratio is low. The second method performs better than MUSIC and Capon's minimum variance approach but is more complex than both of them. The methods are explained in the context of time of arrival estimation.
Transition between linear and nonlinear focusing regimes during filamentation

The transition between linear and nonlinear regimes of focusing for laser filamentation is described and shows the balance between plasma physics and nonlinear propagation for the stability of the laser filament and its properties.
Model-based evaluation

Model-based evaluation is using a model of how a human would use a proposed system to obtain predicted usability measures by calculation or simulation. These predictions can replace or supplement empirical measurements obtained by user testing. In addition, the content of the model itself conveys useful information about the relationship between the user’s task and the system design.
Earthquake Sloshing in Annular and Cylindrical Tanks

The sloshing response of water in annular as well as in cylindrical tanks under horizontal earthquake ground motions is studied. A linear analysis, developed for the general annular tank problem, is based on potential flow theory. The predicted values of natural frequencies, surface displacements, and dynamic pressures are compared with measured data from shaking table tests. Experimental studies were conducted on 1/80th and 1/15th scale models of a 120-ft (36.6m) annular tank, and correlation data are presented for both sinusoidal and simulated earthquake motions. Test results from the sloshing of water in a 12-ft (3.66m) diam cylindrical tank show that the annular tank solution is also applicable in this case. The range of surface displacement within which linear theory gives satisfactory results was established experimentally.
Railroad Revisionists Revisited: Stock Market Evidence from the Progressive Era

From 1910–1917, the Interstate Commerce Commission repeatedly refused to grant requested railroad rate increases despite rising input costs. An event study shows that several Commission decisions resulted in statistically significant and economically meaningful negative excess returns for railroad stocks. The change in regulatory regime signaled by the 1917 Nationalization of the railroads generated large positive excess returns, which strengthens the assessment that the preceding regime was unfavorable to the railroads. These findings challenge the “revisionist” view of regulatory history, and suggest the need for closer study of regulatory implementation and evolution, and not simply regulatory origins.
Semantic Enhancement for Enterprise Data Management

Taking customer data as an example, the paper presents an approach to enhance the management of enterprise data by using Semantic Web technologies. Customer data is the most important kind of core business entity a company uses repeatedly across many business processes and systems, and customer data management (CDM) is becoming critical for enterprises because it keeps a single, complete and accurate record of customers across the enterprise. Existing CDM systems focus on integrating customer data from all customer-facing channels and front and back office systems through multiple interfaces, as well as publishing customer data to different applications. To make the effective use of the CDM system, this paper investigates semantic query and analysis over the integrated and centralized customer data, enabling automatic classification and relationship discovery. We have implemented these features over IBM Websphere Customer Center, and shown the prototype to our clients. We believe that our study and experiences are valuable for both Semantic Web community and data management community.
Metal‐Based Drugs

Metallopharmaceuticals have a long history in the development of chemotherapy. The more recent success of cisplatin and six related Pt-based antitumor drugs, and longer histories of chrysotherapy (gold treatments) for arthritis, bismuth antiulcer agents, and silver-, antimony- and arsenic-based antimicrobial agents demonstrate that the periodic table represents a potential wealth of medicinal agents to be explored and developed in the future. This article reviews the use of twelve elements (Ag, As, Au, Bi, Ga, Li, Pt, Ru, Sb, Sn, Ti, V) for a wide variety of diseases and disorders. The current state of research on particular applications varies widely – from promising treatments that have not yet reached the clinic to those that are well established empirically despite uncertain mechanisms of action. The array of antitumor agents licensed or in clinical trials includes compounds of As, Ga, Ru, and Ti, in addition to platinum. There are also exciting efforts to apply known treatments or biological properties to new diseases by taking advantage of extensive databases, for example, developing antitumor agents from organotin complexes that have long been used as fungicides and antifouling agents, and antimicrobial agents from gold complexes. The ability to modulate the properties of metal complexes by choice of the oxidation state (AuI vs AuIII; PtII vs PtIV; VIII, VIV & VV, etc.) and design of the medical carrier ligands (e.g. 1,2-diaminocyclohexane vs two ammine ligands for Pt antitumor agents) allows targeting of particular tissues or cells and balancing of lipophilicity, solubility, and reactivity to balance therapeutic activity against toxicity. Many, if not most, metallopharmaceuticals are prodrugs that undergo redox changes and/or ligand exchange reactions in vivo to generate the active species. Hence, research on metallodrug metabolism and pharmacology is as important as the initial medicinal screening of the agents. Keywords: metallopharmaceuticals; metallodrugs; chrysotherapy; cisplatin; silver antimicrobials; platinum antitumor agents; bismuth antiulcer agents
Bacteriophage Detection Methodologies

Recovery of Bacteriophages from Groundwater and Drinking Water ISO Method for the Enumeration of Somatic Coliphages ISO Method for the Enumeration of Bacteriophages Infecting B. Fragilis Qualitative Detection of Coliphages in Source Water—U.S. EPA Method 1601 Quantitative Detection of Coliphages in Source Water—U.S. EPA Method 1602 Other Methods Colorimetric Detection of Bacteriophages Recovery of Bacteriophages from Soils and Biosolids Recovery of Coliphages from Shellfish Recovery of Bacteriophages from Aerosol Samples Molecular Detection and Characterization of Bacteriophages Gene Amplification–Based Methods Keywords: bacteriophage, methodology; methodology; indicators of fecal contamination; indicators of water quality; phage