Forcing function control of Faraday wave instabilities in viscous shallow fluids

We investigate the relationship between the linear surface wave instabilities of a shallow viscous fluid layer and the shape of the periodic, parametric-forcing function (describing the vertical acceleration of the fluid container) that excites them. We find numerically that the envelope of the resonance tongues can only develop multiple minima when the forcing function has more than two local extrema per cycle. With this insight, we construct a multi-frequency forcing function that generates at onset a non-trivial harmonic instability which is distinct from a subharmonic response to any of its frequency components. We measure the corresponding surface patterns experimentally and verify that small changes in the forcing waveform cause a transition, through a bicritical point, from the predicted harmonic short-wavelength pattern to a much larger standard subharmonic pattern. Using a formulation valid in the lubrication regime (thin viscous fluid layer) and a WKB method to find its analytic solutions, we explore the origin of the observed relation between the forcing function shape and the resonance tongue structure. In particular, we show that for square and triangular forcing functions the envelope of these tongues has only one minimum, as in the usual sinusoidal case.Comment: 12 pages, 10 figure

Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion

Recent descriptions of significant heterogeneity in normal stem cells and cancers have altered our understanding of tumorigenesis, emphasizing the need to understand how single stem cells are subverted to cause tumors. Human myeloproliferative neoplasms (MPNs) are thought to reflect transformation of a hematopoietic stem cell (HSC) and the majority harbor an acquired V617F mutation in the JAK2 tyrosine kinase, making them a paradigm for studying the early stages of tumor establishment and progression. The consequences of activating tyrosine kinase mutations for stem and progenitor cell behavior are unclear. In this article, we identify a distinct cellular mechanism operative in stem cells. By using conditional knock-in mice, we show that the HSC defect resulting from expression of heterozygous human JAK2V617F is both quantitative (reduced HSC numbers) and qualitative (lineage biases and reduced self-renewal per HSC). The defect is intrinsic to individual HSCs and their progeny are skewed toward proliferation and differentiation as evidenced by single cell and transplantation assays. Aged JAK2V617F show a more pronounced defect as assessed by transplantation, but mice that transform reacquire competitive self-renewal ability. Quantitative analysis of HSC-derived clones was used to model the fate choices of normal and JAK2-mutant HSCs and indicates that JAK2V617F reduces self-renewal of individual HSCs but leaves progenitor expansion intact. This conclusion is supported by paired daughter cell analyses, which indicate that JAK2-mutant HSCs more often give rise to two differentiated daughter cells. Together these data suggest that acquisition of JAK2V617F alone is insufficient for clonal expansion and disease progression and causes eventual HSC exhaustion. Moreover, our results show that clonal expansion of progenitor cells provides a window in which collaborating mutations can accumulate to drive disease progression. Characterizing the mechanism(s) of JAK2V617F subclinical clonal expansions and the transition to overt MPNs will illuminate the earliest stages of tumor establishment and subclone competition, fundamentally shifting the way we treat and manage cancers

Pattern formation in 2-frequency forced parametric waves

We present an experimental investigation of superlattice patterns generated on the surface of a fluid via parametric forcing with 2 commensurate frequencies. The spatio-temporal behavior of 4 qualitatively different types of superlattice patterns is described in detail. These states are generated via a number of different 3--wave resonant interactions. They occur either as symmetry--breaking bifurcations of hexagonal patterns composed of a single unstable mode or via nonlinear interactions between the two primary unstable modes generated by the two forcing frequencies. A coherent picture of these states together with the phase space in which they appear is presented. In addition, we describe a number of new superlattice states generated by 4--wave interactions that arise when symmetry constraints rule out 3--wave resonances.Comment: The paper contains 34 pages and 53 figures and provides an extensive review of both the theoretical and experimental work peformed in this syste

"It All Ended in an Unsporting Way": Serbian Football and the Disintegration of Yugoslavia, 1989-2006

Part of a wider examination into football during the collapse of Eastern European Communism between 1989 and 1991, this article studies the interplay between Serbian football and politics during the period of Yugoslavia's demise. Research utilizing interviews with individuals directly involved in the Serbian game, in conjunction with contemporary Yugoslav media sources, indicates that football played an important proactive role in the revival of Serbian nationalism. At the same time the Yugoslav conflict, twinned with a complex transition to a market economy, had disastrous consequences for football throughout the territories of the former Yugoslavia. In the years following the hostilities the Serbian game has suffered decline, major financial hardship and continuing terrace violence, resulting in widespread nostalgia for the pre-conflict era

ProtoDESI: First On-Sky Technology Demonstration for the Dark Energy Spectroscopic Instrument

The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the universe using the baryon acoustic oscillations technique. The spectra of 35 million galaxies and quasars over 14,000 square degrees will be measured during a 5-year survey. A new prime focus corrector for the Mayall telescope at Kitt Peak National Observatory will deliver light to 5,000 individually targeted fiber-fed robotic positioners. The fibers in turn feed ten broadband multi-object spectrographs. We describe the ProtoDESI experiment, that was installed and commissioned on the 4-m Mayall telescope from August 14 to September 30, 2016. ProtoDESI was an on-sky technology demonstration with the goal to reduce technical risks associated with aligning optical fibers with targets using robotic fiber positioners and maintaining the stability required to operate DESI. The ProtoDESI prime focus instrument, consisting of three fiber positioners, illuminated fiducials, and a guide camera, was installed behind the existing Mosaic corrector on the Mayall telescope. A Fiber View Camera was mounted in the Cassegrain cage of the telescope and provided feedback metrology for positioning the fibers. ProtoDESI also provided a platform for early integration of hardware with the DESI Instrument Control System that controls the subsystems, provides communication with the Telescope Control System, and collects instrument telemetry data. Lacking a spectrograph, ProtoDESI monitored the output of the fibers using a Fiber Photometry Camera mounted on the prime focus instrument. ProtoDESI was successful in acquiring targets with the robotically positioned fibers and demonstrated that the DESI guiding requirements can be met.Comment: Accepted versio

Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes

Massive palindromes in the human Y chromosome harbor mirror-image gene pairs essential for spermatogenesis. During evolution, these gene pairs have been maintained by intrapalindrome, arm-to-arm recombination. The mechanism of intrapalindrome recombination and risk of harmful effects are unknown. We report 51 patients with isodicentric Y (idicY) chromosomes formed by homologous crossing over between opposing arms of palindromes on sister chromatids. These ectopic recombination events occur at nearly all Y-linked palindromes. Based on our findings, we propose that intrapalindrome sequence identity is maintained via noncrossover pathways of homologous recombination. DNA double-strand breaks that initiate these pathways can be alternatively resolved by crossing over between sister chromatids to form idicY chromosomes, with clinical consequences ranging from spermatogenic failure to sex reversal and Turner syndrome. Our observations imply that crossover and noncrossover pathways are active in nearly all Y-linked palindromes, exposing an Achilles' heel in the mechanism that preserves palindrome-borne genes.National Institutes of Health (U.S.)Howard Hughes Medical InstituteNetherlands Organization for Scientific ResearchUniversity of Amsterdam. Academic Medical CenterBoehringer Ingelheim (Fellowship

D4+˙T2D_4\dot{+} T^2 Mode Interactions and Hidden Rotational Symmetry

Bifurcation problems in which periodic boundary conditions or Neumann boundary conditions are imposed often involve partial differential equations that have Euclidean symmetry. As a result the normal form equations for the bifurcation may be constrained by the ``hidden'' Euclidean symmetry of the equations, even though this symmetry is broken by the boundary conditions. The effects of such hidden rotation symmetry on $D_4\dot{+} T^2$ mode interactions are studied by analyzing when a $D_4\dot{+} T^2$ symmetric normal form $\tilde{F}$ can be extended to a vector field ${\rm \cal F}$ with Euclidean symmetry. The fundamental case of binary mode interactions between two irreducible representations of $D_4\dot{+} T^2$ is treated in detail. Necessary and sufficient conditions are given that permit $\tilde{F}$ to be extended when the Euclidean group ${\rm \cal E}(2)$ acts irreducibly. When the Euclidean action is reducible, the rotations do not impose any constraints on the normal form of the binary mode interaction. In applications, this dependence on the representation of ${\rm \cal E}(2)$ implies that the effects of hidden rotations are not present if the critical eigenvalues are imaginary. Generalization of these results to more complicated mode interactions is discussed.Comment: 77 pages (Latex), 3 figures available in hard copy from the author ([email protected]); paper accepted for publication in Nonlinearit

Comparison of the Value of Nursing Work Environments in Hospitals Across Different Levels of Patient Risk

Importance The literature suggests that hospitals with better nursing work environments provide better quality of care. Less is known about value (cost vs quality). Objectives To test whether hospitals with better nursing work environments displayed better value than those with worse nursing environments and to determine patient risk groups associated with the greatest value. Design, Setting, and Participants A retrospective matched-cohort design, comparing the outcomes and cost of patients at focal hospitals recognized nationally as having good nurse working environments and nurse-to-bed ratios of 1 or greater with patients at control group hospitals without such recognition and with nurse-to-bed ratios less than 1. This study included 25 752 elderly Medicare general surgery patients treated at focal hospitals and 62 882 patients treated at control hospitals during 2004-2006 in Illinois, New York, and Texas. The study was conducted between January 1, 2004, and November 30, 2006; this analysis was conducted from April to August 2015. Exposures Focal vs control hospitals (better vs worse nursing environment). Main Outcomes and Measures Thirty-day mortality and costs reflecting resource utilization. Results This study was conducted at 35 focal hospitals (mean nurse-to-bed ratio, 1.51) and 293 control hospitals (mean nurse-to-bed ratio, 0.69). Focal hospitals were larger and more teaching and technology intensive than control hospitals. Thirty-day mortality in focal hospitals was 4.8% vs 5.8% in control hospitals (P \u3c .001), while the cost per patient was similar: the focal-control was −$163 (95$542 to $215; P = .40), suggesting better value in the focal group. For the focal vs control hospitals, the greatest mortality benefit (17.3$941 per patient ($53 701 vs$52 760; P = .25). The greatest difference in value between focal and control hospitals appeared in patients in the second-highest risk quintile, with mortality of 4.2% vs 5.8% (P \u3c .001), with a nonsignificant cost difference of −$862 ($33 513 vs $34 375; P = .12). Conclusions and Relevance Hospitals with better nursing environments and above-average staffing levels were associated with better value (lower mortality with similar costs) compared with hospitals without nursing environment recognition and with below-average staffing, especially for higher-risk patients. These results do not suggest that improving any specific hospital’s nursing environment will necessarily improve its value, but they do show that patients undergoing general surgery at hospitals with better nursing environments generally receive care of higher value

miR-34a Repression in Proneural Malignant Gliomas Upregulates Expression of Its Target PDGFRA and Promotes Tumorigenesis

Glioblastoma (GBM) and other malignant gliomas are aggressive primary neoplasms of the brain that exhibit notable refractivity to standard treatment regimens. Recent large-scale molecular profiling has revealed distinct disease subclasses within malignant gliomas whose defining genomic features highlight dysregulated molecular networks as potential targets for therapeutic development. The “proneural” designation represents the largest and most heterogeneous of these subclasses, and includes both a large fraction of GBMs along with most of their lower-grade astrocytic and oligodendroglial counterparts. The pathogenesis of proneural gliomas has been repeatedly associated with dysregulated PDGF signaling. Nevertheless, genomic amplification or activating mutations involving the PDGF receptor (PDGFRA) characterize only a subset of proneural GBMs, while the mechanisms driving dysregulated PDGF signaling and downstream oncogenic networks in remaining tumors are unclear. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that regulate gene expression by binding loosely complimentary sequences in target mRNAs. The role of miRNA biology in numerous cancer variants is well established. In an analysis of miRNA involvement in the phenotypic expression and regulation of oncogenic PDGF signaling, we found that miR-34a is downregulated by PDGF pathway activation in vitro. Similarly, analysis of data from the Cancer Genome Atlas (TCGA) revealed that miR-34a expression is significantly lower in proneural gliomas compared to other tumor subtypes. Using primary GBM cells maintained under neurosphere conditions, we then demonstrated that miR-34a specifically affects growth of proneural glioma cells in vitro and in vivo. Further bioinformatic analysis identified PDGFRA as a direct target of miR-34a and this interaction was experimentally validated. Finally, we found that PDGF-driven miR-34a repression is unlikely to operate solely through a p53-dependent mechanism. Taken together, our data support the existence of reciprocal negative feedback regulation involving miR-34 and PDGFRA expression in proneural gliomas and, as such, identify a subtype specific therapeutic potential for miR-34a

Time-Resolved HST Spectroscopy of Four Eclipsing Magnetic Cataclysmic Variables

Time-resolved HST UV eclipse spectrophotometry is presented for the magnetic CVs V1309 Ori, MN Hya, V2301 Oph, and V1432 Aql. Separation of the light curves into wavebands allows the multiple emission components to be distinguished. Photospheric hot spots are detected in V1309 Ori and V2301 Oph. The emission- line spectra of V1309 Ori and MN Hya are unusual, with the strength of N V 1240 and N IV 1718 suggesting an overabundance of nitrogen. Three epochs of observation of the asynchronous V1432 Aql cover ~1/3 of a 50-day lap cycle between the white dwarf spin and binary orbit. The light curves vary from epoch to epoch and as a function of waveband. The dereddened UV spectrum is extremely bright and the spectral energy distribution coupled with the duration of eclipse ingress indicate that the dominant source of energy is a hot (T~35,000K) white dwarf. Undiminished line emission through eclipse indicates that the eclipse is caused by the accretion stream, not the secondary star. The hot white dwarf, combined with its current asynchronous nature and rapid timescale for relocking, suggests that V1432 Aql underwent a nova eruption in the past 75-150 yr. The reversed sense of asynchronism, with the primary star currently spinning up toward synchronism, is not necessarily at odds with this scenario, if the rotation of the magnetic white dwarf can couple to the ejecta during the wind phase of the eruption.Comment: To appear in ApJ Part 1; 25 pages, 12 figure