Heavy flavor jet tagging algorithm developments at CMS for HL-LHC

The rich physics program at the high luminosity LHC (HL-LHC) requires all final state particles to be reconstructed with good accuracy. However, it also poses formidable challenge of dealing with very high pileup. Different identification algorithms need to be upgraded along with the detectors to improve the overall event reconstruction in such a hostile collision environment. The new timing device in the proposed CMS detector at the HL-LHC allows for the construction of timing observables at the track-level as well as at the jet-level. This information when given as inputs to the deep neural networks, have a potential to improve the existing algorithms used for heavy flavor (HF) jet tagging. In this paper, the latest developments on the studies for HF jet tagging performance at the HL-LHC are presented

Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

"If HTTPS Were Secure, I Wouldn't Need 2FA" - End User and Administrator Mental Models of HTTPS

HTTPS is one of the most important protocols used to secure communication and is, fortunately, becoming more pervasive. However, especially the long tail of websites is still not sufficiently secured. HTTPS involves different types of users, e.g., end users who are forced to make security decisions when faced with warnings or administrators who are required to deal with cryptographic fundamentals and complex decisions concerning compatibility. In this work, we present the first qualitative study of both end user and administrator mental models of HTTPS. We interviewed 18 end users and 12 administrators; our findings reveal misconceptions about security benefits and threat models from both groups. We identify protocol components that interfere with secure configurations and usage behavior and reveal differences between administrator and end user mental models. Our results suggest that end user mental models are more conceptual while administrator models are more protocol-based. We also found that end users often confuse encryption with authentication, significantly underestimate the security benefits of HTTPS. They also ignore and distrust security indicators while administrators often do not understand the interplay of functional protocol components. Based on the different mental models, we discuss implications and provide actionable recommendations for future designs of user interfaces and protocols

Typhoon damage on a shallow mesophotic reef in Okinawa, Japan

Little is known about effects of large storm systems on mesophotic reefs. This study reports on how Typhoon 17 (Jelawat) affected Ryugu Reef on Okinawa-jima, Japan in September 2012. Benthic communities were surveyed before and after the typhoon using line intercept transect method. Comparison of the benthic assemblages showed highly significant differences in coral coverage at depths of 25–32 m before and after Typhoon 17. A large deep stand of Pachyseris foliosa was apparently less resistant to the storm than the shallower high diversity area of this reef. Contradictory to common perception, this research shows that large foliose corals at deeper depths are just as susceptible to typhoon damage as shallower branching corals. However, descriptive functional group analyses resulted in only minor changes after the disturbance, suggesting the high likelihood of recovery and the high resilience capacity of this mesophotic reef

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a class of small-molecule-selective AR-irreversible covalent antagonists (SARICA) represented herein by UT-143 that covalently and selectively bind to C406 and C327 in the AF-1 region. Interfering with LLPS formation with UT-143 or mutagenesis resulted in chromatin condensation and dissociation of AR-V7 interactome, all culminating in a transcriptionally incompetent complex. Biochemical studies suggest that C327 and C406 in the AF-1 region are critical for condensate formation, AR-V7 function, and UT-143\u27s irreversible AR inhibition. Therapeutically, UT-143 possesses drug-like pharmacokinetics and metabolism properties and inhibits PCa cell proliferation and tumor growth. Our work provides critical information suggesting that clinically important AR-V7 forms transcriptionally competent molecular condensates and covalently engaging C327 and C406 in AF-1, dissolves the condensates, and inhibits its function. The work also identifies a library of AF-1-binding AR and AR-SV-selective covalent inhibitors for the treatment of PCa

Vertigo's Musical Gaze: Neo-Riemannian Symmetries and Spirals

Laura Mulvey coined the term ‘male gaze’ (1975), using Lacanian theory as a ‘political weapon’ against the standard mode of viewing in which the viewing subject turns onscreen women into fantasy objects. While politically laudable, her article misconstrues Lacan's concept of ‘the gaze’, the power of which emanates from the object itself. We might better serve Lacanian theory by inverting Mulvey's reading of Alfred Hitchcock's Vertigo to suggest that Scottie (James Stewart) is himself objectified by the mystique of the ‘object’ he watches and follows: Madeleine (Kim Novak). The screen's gaze reduces spectators to objects too. From this perspective, rather than watching the film, the film can be said to be watching us. This extends to Bernard Herrmann's soundtrack, famously influenced by the yearning of Wagner's Tristan und Isolde . Developing David Schwarz's (2006) musical gaze (in which repeated pedal points of Schubert songs gaze at us), I analyse Vertigo ’s frequent emphasis on the pitch class D. A pedal D is often repeated in alluring yet sinister bare octaves as Scottie follows Madeleine. But at key moments in the film, the pitch becomes a sophisticated tool that captivates us in unique ways. Around this central pitch third‐relationships circle. These resonate with neo‐Riemannian theory, particularly in their hexatonic ‘poles’, which Cohn shows to be agents of the Freudian ‘uncanny’ (2004) and which here also serve as an alternative gaze to the reiterated D. Other pitch constellations, in symmetries or spirals, form similar obsessional musical ‘gazes’ that, using Lacanian theory, prompt the question about whether we are listening to the music or the music is listening to us

Development of Resistance towards Artesunate in MDA-MB-231 Human Breast Cancer Cells

Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo. Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, artesunate was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induced due to activation of the tumor progression related transcription factors NFκB and AP-1. Thereby transcription, expression and activity of the matrix-degrading enzyme MMP-1, whose function is correlated with increased invasion and metastasis, was up-regulated upon acquisition of resistance. Additionally, activation of the apoptosis-related factor NFκB lead to increased expression of ant-apoptotic bcl2 and reduced expression of pro-apoptotic bax. Application of artesunate in vivo in a model of xenografted breast cancer showed, that tumors growth was not efficiently abolished as compared to the control drug doxorubicin. Taken together our in vitro and in vivo results correlate well showing for the first time that artesunate induces resistance in highly metastatic breast tumors

Doctor can I buy a new kidney? I've heard it isn't forbidden: what is the role of the nephrologist when dealing with a patient who wants to buy a kidney?

Organ trafficking is officially banned in several countries and by the main Nephrology Societies. However, this practice is widespread and is allowed or tolerated in many countries, hence, in the absence of a universal law, the caregiver may be asked for advice, placing him/her in a difficult balance between legal aspects, moral principles and ethical judgments. In spite of the Istanbul declaration, which is a widely shared position statement against organ trafficking, the controversy on mercenary organ donation is still open and some experts argue against taking a negative stance. In the absence of clear evidence showing the clinical disadvantages of mercenary transplantation compared to chronic dialysis, self-determination of the patient (and, with several caveats, of the donor) may conflict with other ethical principles, first of all non-maleficence. The present paper was drawn up with the participation of the students, as part of the ethics course at our medical school. It discusses the situation in which the physician acts as a counselor for the patient in the way of a sort of “reverse” informed consent, in which the patient asks advice regarding a complex personal decision, and includes a peculiar application of the four principles (beneficence, non-maleficence, justice and autonomy) to the donor and recipient parties