124 research outputs found
Silicon Mie Resonators for Highly Directional Light Emission from monolayer MoS2
Controlling light emission from quantum emitters has important applications
ranging from solid-state lighting and displays to nanoscale single-photon
sources. Optical antennas have emerged as promising tools to achieve such
control right at the location of the emitter, without the need for bulky,
external optics. Semiconductor nanoantennas are particularly practical for this
purpose because simple geometries, such as wires and spheres, support multiple,
degenerate optical resonances. Here, we start by modifying Mie scattering
theory developed for plane wave illumination to describe scattering of dipole
emission. We then use this theory and experiments to demonstrate several
pathways to achieve control over the directionality, polarization state, and
spectral emission that rely on a coherent coupling of an emitting dipole to
optical resonances of a Si nanowire. A forward-to-backward ratio of 20 was
demonstrated for the electric dipole emission at 680 nm from a monolayer MoS2
by optically coupling it to a Si nanowire
Genomic profiling reveals the potential role of TCL1A and MDR1 Deficiency in chemotherapy-induced cardiotoxicity
Background: Anthracyclines, such as doxorubicin (Adriamycin), are highly effective chemotherapeutic agents, but are well known to cause myocardial dysfunction and life-threatening congestive heart failure (CHF) in some patients.
Methods: To generate new hypotheses about its etiology, genome-wide transcript analysis was performed on whole blood RNA from women that received doxorubicin-based chemotherapy and either did, or did not develop CHF, as defined by ejection fractions (EF)≤40%. Women with non-ischemic cardiomyopathy unrelated to chemotherapy were compared to breast cancer patients prior to chemo with normal EF to identify heart failure-related transcripts in women not receiving chemotherapy. Byproducts of oxidative stress in plasma were measured in a subset of patients.
Results: The results indicate that patients treated with doxorubicin showed sustained elevations in oxidative byproducts in plasma. At the RNA level, women who exhibited low EFs after chemotherapy had 260 transcripts that differed \u3e2-fold (pIn vitro studies confirmed that inhibition of MDR1 by verapamil in rat H9C2 cardiomyocytes increased their susceptibility to doxorubicin-induced toxicity.
Conclusions: It is proposed that chemo-induced cardiomyopathy may be due to a reduction in TCL1A levels, thereby causing increased apoptotic sensitivity, and leading to reduced cardiac MDR1 levels, causing higher cardiac levels of doxorubicin and intracellular free radicals. If so, screening for TCL1A and MDR1 SNPs or expression level in blood, might identify women at greatest risk of chemo-induced heart failure
Electron quantum metamaterials in van der Waals heterostructures
In recent decades, scientists have developed the means to engineer synthetic
periodic arrays with feature sizes below the wavelength of light. When such
features are appropriately structured, electromagnetic radiation can be
manipulated in unusual ways, resulting in optical metamaterials whose function
is directly controlled through nanoscale structure. Nature, too, has adopted
such techniques -- for example in the unique coloring of butterfly wings -- to
manipulate photons as they propagate through nanoscale periodic assemblies. In
this Perspective, we highlight the intriguing potential of designer
sub-electron wavelength (as well as wavelength-scale) structuring of electronic
matter, which affords a new range of synthetic quantum metamaterials with
unconventional responses. Driven by experimental developments in stacking
atomically layered heterostructures -- e.g., mechanical pick-up/transfer
assembly -- atomic scale registrations and structures can be readily tuned over
distances smaller than characteristic electronic length-scales (such as
electron wavelength, screening length, and electron mean free path). Yet
electronic metamaterials promise far richer categories of behavior than those
found in conventional optical metamaterial technologies. This is because unlike
photons that scarcely interact with each other, electrons in subwavelength
structured metamaterials are charged, and strongly interact. As a result, an
enormous variety of emergent phenomena can be expected, and radically new
classes of interacting quantum metamaterials designed
Photodynamic therapy in the therapy for recurrent/persistent nasopharyngeal cancer
To determine the efficacy of Photodynamic therapy of patients with recurrent Nasopharyngeal Carcinoma we reviewed all available literature
The Liberation of Embryonic Stem Cells
Mouse embryonic stem (ES) cells are defined by their capacity to self-renew and their ability to differentiate into all adult tissues including the germ line. Along with efficient clonal propagation, these properties have made them an unparalleled tool for manipulation of the mouse genome. Traditionally, mouse ES (mES) cells have been isolated and cultured in complex, poorly defined conditions that only permit efficient derivation from the 129 mouse strain; genuine ES cells have not been isolated from another species in these conditions. Recently, use of small molecule inhibitors of glycogen synthase kinase 3 (Gsk3) and the Fgf-MAPK signaling cascade has permitted efficient derivation of ES cells from all tested mouse strains. Subsequently, the first verified ES cells were established from a non-mouse species, Rattus norvegicus. Here, we summarize the advances in our understanding of the signaling pathways regulating mES cell self-renewal that led to the first derivation of rat ES cells and highlight the new opportunities presented for transgenic modeling on diverse genetic backgrounds. We also comment on the implications of this work for our understanding of pluripotent stem cells across mammalian species
Histone Demethylase JMJD2B Functions as a Co-Factor of Estrogen Receptor in Breast Cancer Proliferation and Mammary Gland Development
Estrogen is a key regulator of normal function of female reproductive system and plays a pivotal role in the development and progression of breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B) constitutes a key component of the estrogen signaling pathway. JMJD2B is expressed in a high proportion of human breast tumors, and that expression levels significantly correlate with estrogen receptor (ER) positivity. In addition, 17-beta-estradiol (E2) induces JMJD2B expression in an ERα dependent manner. JMJD2B interacts with ERα and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ERα target sites, demethylates H3K9me3 and facilitates transcription of ER responsive genes including MYB, MYC and CCND1. As a consequence, knockdown of JMJD2B severely impairs estrogen-induced cell proliferation and the tumor formation capacity of breast cancer cells. Furthermore, Jmjd2b-deletion in mammary epithelial cells exhibits delayed mammary gland development in female mice. Taken together, these findings suggest an essential role for JMJD2B in the estrogen signaling, and identify JMJD2B as a potential therapeutic target in breast cancer
Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity
The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/ or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and Cterminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) inconjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons inV1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu593, Trp596 and Lys601. The 136 and/or 142glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection
Topological mosaics in moiré superlattices of van der Waals heterobilayers
Van der Waals (vdW) heterostructures formed by 2D atomic crystals provide a
powerful approach towards designer condensed matter systems. Incommensurate
heterobilayers with small twisting and/or lattice mismatch lead to the
interesting concept of Moir\'e superlattice, where the atomic registry is
locally indistinguishable from commensurate bilayers but has local-to-local
variation over long range. Here we show that such Moir\'e superlattice can lead
to periodic modulation of local topological order in vdW heterobilayers formed
by two massive Dirac materials. By tuning the vdW heterojunction from normal to
the inverted type-II regime via an interlayer bias, the commensurate
heterobilayer can become a topological insulator (TI), depending on the
interlayer hybridization controlled by the atomic registry between the vdW
layers. This results in mosaic pattern of TI regions and normal insulator (NI)
regions in Moir\'e superlattices, where topologically protected helical modes
exist at the TI/NI phase boundaries. By using symmetry based k.p and
tight-binding models, we predict that this topological phenomenon can be
present in inverted transition metal dichalcogenides heterobilayers. Our work
points to a new means of realizing programmable and electrically switchable
topological superstructures from 2D arrays of TI nano-dots to 1D arrays of TI
nano-stripes.Comment: 17 pages,5 figure
Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study
Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised
- …