The Composite Index of Leading Economic Indicators: How to Make It More Timely

A major shortcoming of the U.S. leading index is that it does not use the most recent information for stock prices and yield spreads. The index methodology ignores these data in favor of a time-consistent set of components (i.e., all of the components must refer to the previous month). An alternative is to bring the series with publication lags up-to-date with forecasts and create an index with a complete set of most recent components. This study uses tests of ex-ante predictive ability of the U.S. leading index to evaluate the gains to this new 'hot box' procedure of statistical imputation. We find that, across a variety of simple forecasting models, the new approach offers substantial improvements.

The integrated stress response remodels the microtubule-organizing center to clear unfolded proteins following proteotoxic stress

Cells encountering stressful situations activate the integrated stress response (ISR) pathway to limit protein synthesis and redirect translation to better cope. The ISR has also been implicated in cancers, but redundancies in the stress-sensing kinases that trigger the ISR have posed hurdles to dissecting physiological relevance. To overcome this challenge, we targeted the regulatory node of these kinases, namely, the S51 phosphorylation site of eukaryotic translation initiation factor eIF2α and genetically replaced eIF2α with eIF2α-S51A in mouse squamous cell carcinoma (SCC) stem cells of skin. While inconsequential under normal growth conditions, the vulnerability of this ISR-null state was unveiled when SCC stem cells experienced proteotoxic stress. Seeking mechanistic insights into the protective roles of the ISR, we combined ribosome profiling and functional approaches to identify and probe the functional importance of translational differences between ISR-competent and ISR-null SCC stem cells when exposed to proteotoxic stress. In doing so, we learned that the ISR redirects translation to centrosomal proteins that orchestrate the microtubule dynamics needed to efficiently concentrate unfolded proteins at the microtubule-organizing center so that they can be cleared by the perinuclear degradation machinery. Thus, rather than merely maintaining survival during proteotoxic stress, the ISR also functions in promoting cellular recovery once the stress has subsided. Remarkably, this molecular program is unique to transformed skin stem cells, hence exposing a vulnerability in cancer that could be exploited therapeutically

Complementarity, quantum erasure and delayed choice with modified Mach-Zehnder interferometers

Often cited dictums in Quantum Mechanics include "observation disturbance causes loss of interference" and "ignorance is interference". In this paper we propose and describe a series of experiments with modified Mach-Zehnder interferometers showing that one has to be careful when applying such dictums. We are able to show that without interacting in any way with the light quantum (or quanta) expected to behave "wave-like", interference fringes can be lost by simply gaining (or having the potential to gain) the which-path knowledge. Erasing this information may revive the interference fringes. Delayed choice can be added, arriving to an experiment in line with Wheeler's original proposal. We also show that ignorance is not always synonym with having the interference fringes. The often-invoked "collapse of the wavefunction" is found to be a non-necessary ingredient to describe our experiments.Comment: 8 pages, 3 figures; to appear in EPJ

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy

Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient. Nowadays, optical modalities, such as optical coherence tomography (OCT) and Raman spectroscopy (RS), have proven to detect cancer in real time and can provide more detailed clinical information of a lesion, e.g. its penetration depth (stage) and the differentiation of the cells (grade). In this paper, we present an ex vivo study performed with a combined piezoelectric tube-based OCT-probe and fiber optic RS-probe imaging system that allows large field-of-view imaging of bladder biopsies, using both modalities and co-registered visualization, detection and grading of cancerous bladder lesions. In the present study, 119 examined biopsies were characterized, showing that fiber-optic based OCT provides a sensitivity of 78% and a specificity of 69% for the detection of non-muscle-invasive bladder cancer, while RS, on the other hand, provides a sensitivity of 81% and a specificity of 61% for the grading of low- and high-grade tissues. Moreover, the study shows that a piezoelectric tube-based OCT probe can have significant endurance, suitable for future long-lasting in vivo applications. These results also indicate that combined OCT and RS fiber probe-based characterization offers an exciting possibility for label-free and morpho-chemical optical biopsies for bladder cancer diagnostics. © 2020 The Royal Society of Chemistry

Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma

Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib- dexamethasone and bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after bortezomib dosing. Median bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with bortezomib-dexamethasone and bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with bortezomib-dexamethasone versus bortezomib, respectively. Rates of anygrade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of bortezomib-dexamethasone compared with single-agent bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506

Aesthetics of self-scaling: parallaxed transregionalism and Kutluğ Ataman's art practice

This article examines relations of ethnography, contemporary art-practice, globalisation and scalar geopolitics with particular reference to Kutluğ Ataman’s artworks. Having been shortlisted for the Turner Prize at the Tate and awarded the prestigious international Carnegie Prize in 2004 with his forty-screen video installation Küba (2004), Ataman became an extremely well-known, globally acclaimed artist and filmmaker. Self-conscious of their global travel and critically attentive to the contemporary ethnographic turn in the visual arts scene, Ataman’s video-works perform a conscientious failure of representing cultural alterity as indigeneity. Concentrating on the artist’s engagement with ethnography, this article contains three main parts. Analyses of the selection of videos in each part will give an account of different scalar aspects of Ataman’s artworks. It will first revisit a previous study (Çakirlar 2011) on the artist’s earlier work of video-portraits including Never My Soul! (2002) and Women Who Wear Wigs (1999). A detailed discussion of Küba follows, which may be taken as the ‘hinge - work’ in Ataman’s oeuvre that marks a scalar transition in his critical focus - from body and identity to community and geopolitics. The discussion will then move to a brief analysis of the series Mesopotamian Dramaturgies, including the screen-based sculptures Dome (2009), Column (2009), Frame (2009), English as a Second Language (2009), and The Complete Works of William Shakespeare (2009). Rather than addressing scale as a differential concept, this article aims to demonstrate the ways in which Ataman’s art-practice produces self-scaling, self-regioning subjects that unsettle the hierarchical constructions of scale and facilitates a critique of the scalar normativity within the global art world’s regionalisms and internationalisms

Surface-Initiated Controlled Radical Polymerization: State-of-the-Art, Opportunities, and Challenges in Surface and Interface Engineering with Polymer Brushes

The generation of polymer brushes by surface-initiated controlled radical polymerization (SI-CRP) techniques has become a powerful approach to tailor the chemical and physical properties of interfaces and has given rise to great advances in surface and interface engineering. Polymer brushes are defined as thin polymer films in which the individual polymer chains are tethered by one chain end to a solid interface. Significant advances have been made over the past years in the field of polymer brushes. This includes novel developments in SI-CRP, as well as the emergence of novel applications such as catalysis, electronics, nanomaterial synthesis and biosensing. Additionally, polymer brushes prepared via SI-CRP have been utilized to modify the surface of novel substrates such as natural fibers, polymer nanofibers, mesoporous materials, graphene, viruses and protein nanoparticles. The last years have also seen exciting advances in the chemical and physical characterization of polymer brushes, as well as an ever increasing set of computational and simulation tools that allow understanding and predictions of these surface grafted polymer architectures. The aim of this contribution is to provide a comprehensive review that critically assesses recent advances in the field and highlights the opportunities and challenges for future work

A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion

10.1371/journal.ppat.1003297PLoS Pathogens94

Mutations in Wnt2 Alter Presynaptic Motor Neuron Morphology and Presynaptic Protein Localization at the Drosophila Neuromuscular Junction

Wnt proteins are secreted proteins involved in a number of developmental processes including neural development and synaptogenesis. We sought to determine the role of the Drosophila Wnt7b ortholog, Wnt2, using the neuromuscular junction (NMJ). Mutations in wnt2 produce an increase in the number of presynaptic branches and a reduction in immunolabeling of the active zone proteins, Bruchpilot and synaptobrevin, at the NMJ. There was no change, however, in immunolabeling for the presynaptic proteins cysteine-string protein (CSP) and synaptotagmin, nor the postsynaptic proteins GluRIIA and DLG at the NMJ. Consistent with the presynaptic defects, wnt2 mutants exhibit approximately a 50% reduction in evoked excitatory junctional currents. Rescue, RNAi, and tissue-specific qRT-PCR experiments indicate that Wnt2 is expressed by the postsynaptic cell where it may serve as a retrograde signal that regulates presynaptic morphology and the localization of presynaptic proteins