18 research outputs found
Evaluating the End-User Experience of Private Browsing Mode
Nowadays, all major web browsers have a private browsing mode. However, the
mode's benefits and limitations are not particularly understood. Through the
use of survey studies, prior work has found that most users are either unaware
of private browsing or do not use it. Further, those who do use private
browsing generally have misconceptions about what protection it provides.
However, prior work has not investigated \emph{why} users misunderstand the
benefits and limitations of private browsing. In this work, we do so by
designing and conducting a three-part study: (1) an analytical approach
combining cognitive walkthrough and heuristic evaluation to inspect the user
interface of private mode in different browsers; (2) a qualitative,
interview-based study to explore users' mental models of private browsing and
its security goals; (3) a participatory design study to investigate why
existing browser disclosures, the in-browser explanations of private browsing
mode, do not communicate the security goals of private browsing to users.
Participants critiqued the browser disclosures of three web browsers: Brave,
Firefox, and Google Chrome, and then designed new ones. We find that the user
interface of private mode in different web browsers violates several
well-established design guidelines and heuristics. Further, most participants
had incorrect mental models of private browsing, influencing their
understanding and usage of private mode. Additionally, we find that existing
browser disclosures are not only vague, but also misleading. None of the three
studied browser disclosures communicates or explains the primary security goal
of private browsing. Drawing from the results of our user study, we extract a
set of design recommendations that we encourage browser designers to validate,
in order to design more effective and informative browser disclosures related
to private mode
ATM Deficiency Confers Specific Therapeutic Vulnerabilities in Bladder Cancer
Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair-targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss alters the immune microenvironment and improves anti-PD1 response in preclinical bladder models but is not associated with improved anti-PD1/PD-L1 response in clinical cohorts. Last, we show that ATM expression by immunohistochemistry is strongly correlated with response to chemoradiotherapy. Together, these data define a potential role for ATM as a predictive biomarker in bladder cancer
Strange Cases of Sex Chromosome Segregation: the Division of Sex Univalents and Sex Trivalents
Aneuploidy is poorly tolerated by cells and can have catastrophic consequences, including infertility and death, for offspring. Normally, chromosomes partner during meiosis in such a way as to guarantee their correct segregation into daughter cells and prevent aneuploidy. If their connections to one another and to the spindle network are improperly regulated, however, cells can have missing or extra chromosomes as a result. In some species, nonhomologous chromosomes that have no pairing partners in meiosis can have coordinated movements and behaviors that result in their correct delivery into daughter cells. We are interested in how chromosome movements are coordinated to ensure correct chromosome segregation into daughter cells during meiosis. To study this, we look at these strange cases of chromosome segregation, as they could reveal a lot about the coordination of chromosome movements in all species
Co-segregation of sex chromosomes in the male black widow spider Latrodectus mactans (Araneae, Theridiidae)
During meiosis I, homologous chromosomes join together to form bivalents. Through trial and error, bivalents achieve stable bipolar orientations (attachments) on the spindle that eventually allow the segregation of homologous chromosomes to opposite poles. Bipolar orientations are stable through tension generated by poleward forces to opposite poles. Unipolar orientations lack tension and are stereotypically not stable. The behavior of sex chromosomes during meiosis I in the male black widow spider Latrodectus mactans (Araneae, Theridiidae) challenges the principles governing such a scenario. We found that male L. mactans has two distinct X chromosomes, X1 and X2. The X chromosomes join together to form a connection that is present in prometaphase I but is lost during metaphase I, before the autosomes disjoin at anaphase I. We found that both X chromosomes form stable unipolar orientations to the same pole that assure their cosegregation at anaphase I. Using micromanipulation, immunofluorescence microscopy, and electron microscopy, we studied this unusual chromosome behavior to explain how it may fit the current dogma of chromosome distribution during cell division
Resource Allocation in Food-Restricted Male Physocyclus mexicanus (Banks 1898) Spiders Does Not Favor Proportionally Larger Testes (Araneae: Pholcidae)
Abstract. The physiological effects of resource allocation due to dietary restriction in spiders are poorly understood; in fact, the system-wide effects of any environmental stresses on spider physiology remain relatively unstudied. The aim of this study was to show the consequences of dietary restriction in the pholcid spider Physocyclus mexicanus Banks, 1898. Male spiders were fed either a high (ad libitum) diet (n ¼ 43) or low (5–8 Drosophila melanogaster/week) diet (n ¼ 32) through their penultimate instar. We found significant differences in testis volume, body mass, and tibia-patella length [TPL] between the two groups. Linear regression analysis reveals that the differences in testis volume between the two groups are not solely due to differences in body mass; for any given body mass, the low diet group has a smaller mean testis size than the high diet group. Our results suggest that P. mexicanus males allocate resources away from testis volume in times of scarcity
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Correction: Comprehensive Immunoprofiling of High-risk Oral Proliferative and Localized Leukoplakia.
[This corrects the article DOI: 10.1158/2767-9764.CRC-21-0060.][This corrects the article DOI: 10.1158/2767-9764.CRC-21-0060.]
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Comprehensive Immunoprofiling of High-Risk Oral Proliferative and Localized LeukoplakiaImmunoprofiling High-Risk Oral Leukoplakia
Oral leukoplakia is common and may, in some cases, progress to carcinoma. Proliferative leukoplakia is a progressive, often multifocal subtype with a high rate of malignant transformation compared with the more common localized leukoplakia. We hypothesized that the immune microenvironment and gene expression patterns would be distinct for proliferative leukoplakia compared with localized leukoplakia. We summarize key clinicopathologic features among proliferative leukoplakia and localized leukoplakia and compare cancer-free survival (CFS) between subgroups. We analyze immunologic gene expression profiling in proliferative leukoplakia and localized leukoplakia tissue samples (NanoString PanCancer Immune Oncology Profiling). We integrate immune cell activation and spatial distribution patterns in tissue samples using multiplexed immunofluorescence and digital image capture to further define proliferative leukoplakia and localized leukoplakia. Among N = 58 patients (proliferative leukoplakia, n = 29; localized leukoplakia, n = 29), only the clinical diagnosis of proliferative leukoplakia was associated with significantly decreased CFS (HR, 11.25; P < 0.01; 5-year CFS 46.8% and 83.6% among patients with proliferative leukoplakia and localized leukoplakia, respectively). CD8+ T cells and T regulatory (Treg) were more abundant among proliferative leukoplakia samples (P < 0.01) regardless of degree of epithelial dysplasia, and often colocalized to the dysplasia-stromal interface. Gene set analysis identified granzyme M as the most differentially expressed gene favoring the proliferative leukoplakia subgroup (log2 fold change, 1.93; P adj < 0.001). Programmed death ligand 1 (PD-L1) was comparatively overexpressed among proliferative leukoplakia samples, with higher (>5) PD-L1 scores predicting worse CFS (P adj < 0.01). Proliferative leukoplakia predicts a high rate of malignant transformation within 5 years of diagnosis. A prominent CD8+ T-cell and Treg signature along with relative PD-L1 overexpression compared with localized leukoplakia provides strong rationale for PD-1/PD-L1 axis blockade using preventative immunotherapy.SignificanceThis is the first in-depth profiling effort to immunologically characterize high-risk proliferative leukoplakia as compared with the more common localized leukoplakia. We observed a notable cytotoxic T-cell and Treg signature with relative overexpression of PD-L1 in high-risk proliferative leukoplakia providing a strong preclinical rationale for investigating PD-1/PD-L1 axis blockade in this disease as preventative immunotherapy