bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forsythiae Fructus Inhibits B16 Melanoma Growth Involving MAPKs/Nrf2/HO-1 Mediated Anti-Oxidation and Anti-Inflammation
Authors: Bao Jiaolin , Ding Renbo , Zou Lidi , Zhang Chao , Wang Kai , Liu Fang , Li Peng , Chen Meiwan , Wan Jian-Bo , Su Huanxing , Wang Yitao , He Chengwei 
Published: July 2016

Forsythiae Fructus, the fruits of Forsythia suspensa (Thunb.) Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine (TCM). It is a typical heat-clearing and detoxicating herb, according to TCM theory. In this study, we investigated the antitumor effect of Forsythiae Fructus aqueous extract (FAE) on B16-F10 melanoma cells in vivo. The transplanted B16-F10 melanoma in C57BL/6 mice was established and used for the evaluation of the in vivo antitumor effect of FAE. FAE strongly inhibited the growth of B16-F10 cells in vitro and the tumor in vivo. The survival time of tumor-bearing mice was significantly prolonged by FAE. FAE inhibited cancer cell proliferation and angiogenesis in the tumor, as indicated by the decreased expressions of Ki67 and CD31. The levels of ROS, MDA, TNF-[Formula: see text] and IL-6 decreased, while GSH increased in the FAE treatment group, indicating FAE possesses strong anti-oxidative and anti-inflammatory activity. The expression of anti-oxidant proteins Nrf-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by FAE treatment. These data demonstrated that FAE exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of FAE involved decreases in oxidative stress and inflammation in the tumor, which is closely related to the heat-clearing and detoxicating properties of FAE.
The Effect of Program and Model Structure on the Effectiveness of MC/DC Test Adequacy Coverage
Authors: Gay Gregory , Rajan Ajitha , Staats Matt , Whalen Michael , Heimdahl Mats P. E. 
Published: July 2016

Test adequacy metrics defined over the structure of a program, such as Modified Condition and Decision Coverage (MC/DC), are used to assess testing efforts. However, MC/DC can be “cheated” by restructuring a program to make it easier to achieve the desired coverage. This is concerning, given the importance of MC/DC in assessing the adequacy of test suites for critical systems domains. In this work, we have explored the impact of implementation structure on the efficacy of test suites satisfying the MC/DC criterion using four real-world avionics systems.
Our results demonstrate that test suites achieving MC/DC over implementations with structurally complex Boolean expressions are generally larger and more effective than test suites achieving MC/DC over functionally equivalent, but structurally simpler, implementations. Additionally, we found that test suites generated over simpler implementations achieve significantly lower MC/DC and fault-finding effectiveness when applied to complex implementations, whereas test suites generated over the complex implementation still achieve high MC/DC and attain high fault finding over the simpler implementation. By measuring MC/DC over simple implementations, we can significantly reduce the cost of testing, but in doing so, we also reduce the effectiveness of the testing process. Thus, developers have an economic incentive to “cheat” the MC/DC criterion, but this cheating leads to negative consequences. Accordingly, we recommend that organizations require MC/DC over a structurally complex implementation for testing purposes to avoid these consequences.
How to Train Your Browser
Authors: Mitropoulos Dimitris , Stroggylos Konstantinos , Spinellis Diomidis , Keromytis Angelos D. 
Published: July 2016

Cross-Site Scripting (XSS) is one of the most common web application vulnerabilities. It is therefore sometimes referred to as the “buffer overflow of the web.” Drawing a parallel from the current state of practice in preventing unauthorized native code execution (the typical goal in a code injection), we propose a script whitelisting approach to tame JavaScript-driven XSS attacks. Our scheme involves a transparent script interception layer placed in the browser’s JavaScript engine. This layer is designed to detect every script that reaches the browser, from every possible route, and compare it to a list of valid scripts for the site or page being accessed; scripts not on the list are prevented from executing. To avoid the false positives caused by minor syntactic changes (e.g., due to dynamic code generation), our layer uses the concept of contextual fingerprints when comparing scripts.
Contextual fingerprints are identifiers that represent specific elements of a script and its execution context. Fingerprints can be easily enriched with new elements, if needed, to enhance the proposed method’s robustness. The list can be populated by the website’s administrators or a trusted third party. To verify our approach, we have developed a prototype and tested it successfully against an extensive array of attacks that were performed on more than 50 real-world vulnerable web applications. We measured the browsing performance overhead of the proposed solution on eight websites that make heavy use of JavaScript. Our mechanism imposed an average overhead of 11.1% on the execution time of the JavaScript engine. When measured as part of a full browsing session, and for all tested websites, the overhead introduced by our layer was less than 0.05%. When script elements are altered or new scripts are added on the server side, a new fingerprint generation phase is required. To examine the temporal aspect of contextual fingerprints, we performed a short-term and a long-term experiment based on the same websites. The former, showed that in a short period of time (10 days), for seven of eight websites, the majority of valid fingerprints stay the same (more than 92% on average). The latter, though, indicated that, in the long run, the number of fingerprints that do not change is reduced. Both experiments can be seen as one of the first attempts to study the feasibility of a whitelisting approach for the web.
Meeting Report: The Role of the Mobilome in Cancer
Authors: Ardeljan Daniel , Taylor Martin S. , Burns Kathleen H. , Boeke Jef D. , Espey Michael Graham , Woodhouse Elisa C. , Howcroft Thomas Kevin 
Published: July 2016

Abstract
Approximately half of the human genome consists of repetitive sequence attributed to the activities of mobile DNAs, including DNA transposons, RNA transposons, and endogenous retroviruses. Of these, only long interspersed elements (LINE-1 or L1) and sequences copied by LINE-1 remain mobile in our species today. Although cells restrict L1 activity by both transcriptional and posttranscriptional mechanisms, L1 derepression occurs in developmental and pathologic contexts, including many types of cancers. However, we have limited knowledge of the extent and consequences of L1 expression in premalignancies and cancer. Participants in this NIH strategic workshop considered key questions to enhance our understanding of mechanisms and roles the mobilome may play in cancer biology. Cancer Res; 76(15); 4316–9. ©2016 AACR.
The WASF3–NCKAP1–CYFIP1 Complex Is Essential for Breast Cancer Metastasis
Authors: Teng Yong , Qin Haiyan , Bahassan Abdulaziz , Bendzunas N. George , Kennedy Eileen J. , Cowell John K. 
Published: July 2016

Abstract
Inactivation of the WASF3 gene suppresses invasion and metastasis of breast cancer cells. WASF3 function is regulated through a protein complex that includes the NCKAP1 and CYFIP1 proteins. Here, we report that silencing NCKAP1 destabilizes the WASF3 complex, resulting in a suppression of the invasive capacity of breast, prostate, and colon cancer cells. In an in vivo model of spontaneous metastasis in immunocompromized mice, loss of NCKAP1 also suppresses metastasis. Activation of the WASF protein complex occurs through interaction with RAC1, and inactivation of NCKAP1 prevents the association of RAC1 with the WASF3 complex. Thus, WASF3 depends on NCKAP1 to promote invasion and metastasis. Here, we show that stapled peptides targeting the interface between NCKAP1 and CYFIP1 destabilize the WASF3 complex and suppress RAC1 binding, thereby suppressing invasion. Using a complex-disrupting compound identified in this study termed WANT3, our results offer a mechanistic proof of concept to target this interaction as a novel approach to inhibit breast cancer metastasis. Cancer Res; 76(17); 5133–42. ©2016 AACR.
Genetic Abrogation of Adenosine A
3
Receptor Prevents Uninephrectomy and High Salt–Induced Hypertension
Authors: Yang Ting , Zollbrecht Christa , Winerdal Malin E. , Zhuge Zhengbing , Zhang Xing‐Mei , Terrando Niccolo , Checa Antonio , Sällström Johan , Wheelock Craig E. , Winqvist Ola , Harris Robert A. , Larsson Erik , Persson A. Erik G. , Fredholm Bertil B. , Carlström Mattias 
Published: July 2016

Background

Early‐life reduction in nephron number (uninephrectomy [
UNX]
) and chronic high salt (
HS
) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating renal, cardiovascular, and metabolic functions as well as inflammatory processes; however, the specific role of the A
3
receptor in cardiovascular diseases is not clear. In this study, gene‐modified mice were used to investigate the hypothesis that lack of A
3
signaling prevents the development of hypertension and attenuates renal and cardiovascular injuries following UNX in combination with HS (
UNX
‐
HS
) in mice.

Methods and Results

Wild‐type (A
3
+/+
) mice subjected to
UNX
‐
HS
developed hypertension compared with controls (mean arterial pressure 106±3 versus 82±3 mm Hg;
P
<0.05) and displayed an impaired metabolic phenotype (eg, increased adiposity, reduced glucose tolerance, hyperinsulinemia). These changes were associated with both cardiac hypertrophy and fibrosis together with renal injuries and proteinuria. All of these pathological hallmarks were significantly attenuated in the A
3
−/−
mice. Mechanistically, absence of A
3
receptors protected from
UNX
‐
HS
–associated increase in renal
NADPH
oxidase activity and Nox2 expression. In addition, circulating cytokines including interleukins 1β, 6, 12, and 10 were increased in A
3
+/+
following
UNX
‐
HS
, but these cytokines were already elevated in naïve A
3
−/−
mice and did not change following
UNX
‐
HS
.

Conclusions

Reduction in nephron number combined with chronic
HS
intake is associated with oxidative stress, chronic inflammation, and development of hypertension in mice. Absence of adenosine A
3
receptor signaling was strongly protective in this novel mouse model of renal and cardiovascular disease.
A Situation-Based Analysis of Flash Flood Fatalities in the United States
Authors: Terti Galateia , Ruin Isabelle , Anquetin Sandrine , Gourley Jonathan J. 
Published: July 2016

Abstract
This paper investigates the circumstances of 1,075 fatalities from flash flooding recorded from 1996 to 2014 across the United States. This study provides insights into the situations of the fatality events as determined by the victims’ profile and activity and the spatiotemporal context of the flooding. A reclassification of the individual fatality circumstance (i.e., location and/or activity) is performed to explore statistically the timing, the duration, and location of the flash flood event and the age and gender of the victims. In agreement with other studies, more than 60% of the reported fatalities were related to vehicles involving mainly males. A geospatial analysis indicated these were most common in southern states. Further, 21% of fatalities occurred outdoors, typically in neighborhoods near streams, where the victims were exhibiting high-risk-taking behavior, such as cleaning out drains and even playing in the floodwaters. Human vulnerability varies dynamically on a subdaily basis and depends on social and natural factors of the flash flood. For example, most campsite-related fatalities were associated with very fast-responding flash flood events (less than 5-h duration), occurred more commonly after midnight, and impacted younger females and males alike. On the other hand, fatalities related to inundation of permanent buildings were most commonly associated with longer-duration events and impacted the elderly. Situational rather than generic examination of vulnerability is required to realistically capture risky cases during short-fuse flood events.
The circumstances in which people perished in flash floods suggest that situational rather than generic examination of vulnerability is required to realistically capture risky cases during short-fuse flood events.
The HMT Multi-Radar Multi-Sensor Hydro Experiment
Authors: Martinaitis Steven M. , Gourley Jonathan J. , Flamig Zachary L. , Argyle Elizabeth M. , Clark Robert A. , Arthur Ami , Smith Brandon R. , Erlingis Jessica M. , Perfater Sarah , Albright Benjamin 
Published: July 2016

Abstract
There are numerous challenges with the forecasting and detection of flash floods, one of the deadliest weather phenomena in the United States. Statistical metrics of flash flood warnings over recent years depict a generally stagnant warning performance, while regional flash flood guidance utilized in warning operations was shown to have low skill scores. The Hydrometeorological Testbed—Hydrology (HMT-Hydro) experiment was created to allow operational forecasters to assess emerging products and techniques designed to improve the prediction and warning of flash flooding. Scientific goals of the HMT-Hydro experiment included the evaluation of gridded products from the Multi-Radar Multi-Sensor (MRMS) and Flooded Locations and Simulated Hydrographs (FLASH) product suites, including the experimental Coupled Routing and Excess Storage (CREST) model, the application of user-defined probabilistic forecasts in experimental flash flood watches and warnings, and the utility of the Hazard Services software interface with flash flood recommenders in real-time experimental warning operations. The HMT-Hydro experiment ran in collaboration with the Flash Flood and Intense Rainfall (FFaIR) experiment at the Weather Prediction Center to simulate the real-time workflow between a national center and a local forecast office, as well as to facilitate discussions on the challenges of short-term flash flood forecasting. Results from the HMT-Hydro experiment highlighted the utility of MRMS and FLASH products in identifying the spatial coverage and magnitude of flash flooding, while evaluating the perception and reliability of probabilistic forecasts in flash flood watches and warnings.
NSSL scientists and NWS forecasters evaluate new tools and techniques through real-time test bed operations for the improvement of flash flood detection and warning operations.
A Numerical Investigation of Cumulus Thermals
Authors: Hernandez-Deckers Daniel , Sherwood Steven C. 
Published: July 2016

Abstract
Although the steady, entraining, updraft plume is widely taken as the foundational concept of cumulus convection, past studies show that convection is typically dominated by thermals that are transient, more isotropic in shape, and possess interior vortical circulations. Here, several thousand such thermals are tracked in cloud-resolving simulations of transient growing convective events. Most tracked thermals are small (with radius R &lt; 300 m), ascend at moderate rates (~ 2–4 m s−1), maintain an approximately constant size as they rise, and have brief (4–5 min) lifetimes, although a few are much larger, faster, and/or longer lived. They show slight vertical elongation, but few, if any, would be described as plumes. As convection deepens, thermals originate higher up, are larger, and rise faster, although radius and ascent rate are only weakly correlated among individual thermals. The main force opposing buoyancy is a nonhydrostatic pressure drag, not mixing of momentum. This drag can be expressed in terms of a drag coefficient cd that decreases as convection intensifies: deep convective thermals are less damped, with cd ~ 0.2, while shallow convective thermals are more damped, with cd ~ 0.6. The expected dependence of cd based on theoretical form and wave drag coefficients for a solid sphere is inconsistent with these results, since it predicts the opposite dependence on the Froude number. Thus, a theory for drag on cumulus thermals is not straightforward. Overall, it is argued that thermals are a more realistic prototype for atmospheric deep convection than plumes, at least for the less organized convection types simulated here.
Seasonal and Interannual Variations of the Energy Flux Equator and ITCZ. Part II: Zonally Varying Shifts of the ITCZ
Authors: Adam Ori , Bischoff Tobias , Schneider Tapio 
Published: July 2016

Abstract
The ITCZ lies at the ascending branch of the tropical meridional overturning circulation, where near-surface meridional mass fluxes vanish. Near the ITCZ, column-integrated energy fluxes vanish, forming an atmospheric energy flux equator (EFE). This paper extends existing approximations relating the ITCZ position and EFE to the atmospheric energy budget by allowing for zonal variations. The resulting relations are tested using reanalysis data for 1979–2014. The zonally varying EFE is found as the latitude where the meridional component of the divergent atmospheric energy transport (AET) vanishes. A Taylor expansion of the AET around the equator relates the ITCZ position to derivatives of the AET. To a first order, the ITCZ position is proportional to the divergent AET across the equator; it is inversely proportional to the local atmospheric net energy input (NEI) that consists of the net energy fluxes at the surface, at the top of the atmosphere, and zonally across longitudes. The first-order approximation captures the seasonal migrations of the ITCZ in the African, Asian, and Atlantic sectors. In the eastern Pacific, a third-order approximation captures the bifurcation from single- to double-ITCZ states that occurs during boreal spring. In contrast to linear EFE theory, during boreal winter in the eastern Pacific, northward cross-equatorial AET goes along with an ITCZ north of the equator. EFE and ITCZ variations driven by ENSO are characterized by an equatorward (poleward) shift in the Pacific during El Niño (La Niña) episodes, which are associated with variations in equatorial ocean energy uptake.
Eddy Trains and Striations in Quasigeostrophic Simulations and the Ocean
Authors: Chen Changheng , Kamenkovich Igor , Berloff Pavel 
Published: July 2016

AbstractThis study explores the relationship between coherent eddies and zonally elongated striations. The investigation involves an analysis of two baroclinic quasigeostrophic models of a zonal and double-gyre flow and a set of altimetry sea level anomaly data in the North Pacific. Striations are defined by either spatiotemporal filtering or empirical orthogonal functions (EOFs), with both approaches leading to consistent results. Coherent eddies, identified here by the modified Okubo–Weiss parameter, tend to propagate along well-defined paths, thus forming “eddy trains” that coincide with striations. The striations and eddy trains tend to drift away from the intergyre boundary at the same speed in both the model and observations. The EOF analysis further confirms that these striations in model simulations and altimetry are not an artifact of temporal averaging of random, spatially uncorrelated vortices. This study suggests instead that eddies organize into eddy trains, which manifest themselves as striations in low-pass filtered data and EOF modes.
Tsunami Warning Message Interpretation and Sense Making: Focus Group Insights
Authors: Sutton Jeannette , Woods Chelsea 
Published: July 2016

AbstractHazard warning messages are intended to shift people from a sense of safety to a sense of risk, while providing guidance for protective action. Message features, such as the content elements that are included and the style in which a message is written or delivered, can strengthen or weaken a recipient’s ability to make sense of and act on the message. Under conditions of heightened uncertainty or imminent threat the strategies that people apply to interpret warning messages may make a difference in the protective actions that they choose to take. Importantly, when a hazard is unfamiliar and the threat is imminent, adequate mental models and clearly articulated messages become vital to one’s ability to make decisions about life safety. To better understand the message interpretation and the effects of message sense making on individual risk information processing, this article assesses warnings for an infrequently experienced threat: tsunamis. Using data from four focus groups this research finds that individuals engage in interpretive sense making activities by making comparisons to media accounts of tsunamis and drawing from personal experience with waves and with warnings for other hazards, particularly tornadoes. The analysis presents three primary insights: 1) hazard warning messages must be designed for the end user in mind, including those who are unfamiliar with the hazard; 2) clear and specific information helps to personalize the threat and to reduce anxiety; and 3) message receivers draw from personal and vicarious experiences to assist in message sense making, highlighting the need for consistent language across hazard warnings.
The Contribution of Biomechanical-Biological Interactions of the Spine to Low Back Pain
Authors: Marras William S. , Walter Benjamin A. , Purmessur Devina , Mageswaran Prasath , Wiet Matthew G. 
Published: July 2016

Objective: The objective of this mini-review is to examine a subset of literature that demonstrates multiple interactions between mechanics and biology within the spine and propose how incorporation of these mechano-biologic interactions can be applied to improve the conceptual understanding of tissue tolerances. Background: Low back pain represents a major musculoskeletal problem in the workplace. Traditional biomechanical assessments have employed tissue tolerances as an approach for reducing workplace injuries; however, development of more universal biologically sensitive tolerances requires incorporation of mechano-biologic interactions. Methods: A focused literature review addressing the interactions between mechanical loading and biology in the spine. Results: Mechanical loads applied to the body are distributed across all spatial scales from the body to the tissues to the cells. These mechanical loads regulate cellular metabolism and over time can lead to tissue strengthening or weakening. Mechanical loading also interacts with the biologic environment (e.g., tissue inflammation, nerve sensitization) to influence the perception of pain, thereby changing the risk of experiencing pain. Biologic tissues also exhibit time-dependent changes in mechanical behaviors that occur throughout the day and with disease, suggesting tissue tolerances are time dependent. Conclusion: Incorporating mechano-biologic interactions into the traditional tissue tolerance paradigm through describing tissue tolerances as a function of multiple factors (e.g., preexisting risk factors, underlying pathology, and time) may lead to the development of tissue tolerances that are more representative of the in vivo situation. Application: Efforts must work toward incorporating biological concepts into tissue tolerances in order to improve risk assessment tools.