Haplodeficiency of the 9p21 tumor suppressor locus causes myeloid disorders driven by the bone marrow microenvironment.

The chromosome 9p21 locus comprises several tumor suppressor genes including MTAP, CDKN2A, and CDKN2B, and its homo- or heterozygous deletion is associated with reduced survival in multiple cancer types. We report that mice with germ line monoallelic deletion or induced biallelic deletion of the 9p21-syntenic locus (9p21s) developed a fatal myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)-like disease associated with aberrant trabecular bone formation and/or fibrosis in the bone marrow (BM). Reciprocal BM transfers and conditional targeting of 9p21s suggested that the disease originates in the BM stroma. Single-cell analysis of 9p21s-deficient BM stroma revealed the expansion of chondrocyte and osteogenic precursors, reflected in increased osteogenic differentiation in vitro. It also showed reduced expression of factors maintaining hematopoietic stem/progenitor cells, including Cxcl12. Accordingly, 9p21s-deficient mice showed reduced levels of circulating Cxcl12 and concomitant upregulation of the profibrotic chemokine Cxcl13 and the osteogenesis- and fibrosis-related multifunctional glycoprotein osteopontin/Spp1. Our study highlights the potential of mutations in the BM microenvironment to drive MDS/MPN-like disease.

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation.

The development of dendritic cells (DCs), including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs), is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected Flt3L-driven DC differentiation using CRISPR-Cas9-based screening. Genome-wide screening identified multiple regulators of DC differentiation including subunits of TSC and GATOR1 complexes, which restricted progenitor growth but enabled DC differentiation by inhibiting mTOR signaling. An orthogonal screen identified the transcriptional repressor Trim33 (TIF-1γ) as a regulator of DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, deletion of Trim33 caused rapid loss of DC progenitors, pDCs, and the cross-presenting cDC1 subset. Trim33-deficient Flt3+ progenitors up-regulated pro-inflammatory and macrophage-specific genes but failed to induce the DC differentiation program. Collectively, these data elucidate mechanisms that control Flt3L-driven differentiation of the entire DC lineage and identify Trim33 as its essential regulator.

Cryptographic scheme using genetic algorithm and optical responses of periodic structures.

This study employed the optical responses of periodic structures, multiple-variable functions with sufficient complexity, to develop a cryptographic scheme. The characteristics of structures could be delivered easily with the ciphertext, a series of numbers containing plaintext messages. Two optimization methods utilizing a genetic algorithm were adopted to generate the periodic structure profile as a critical encryption/decryption key. The robustness of methods was further confirmed under various limits. The ciphertext could only be decrypted by referring to the codebook after acquiring the pre-determined optical response. The confidentiality and large capacity of the scheme revealed the enhanced coding strategies here while the success of the scheme was demonstrated with the delivery of an example message.

Impacts of geometric modifications on infrared optical responses of metallic slit arrays.

This work numerically investigates optical responses (absorptance, reflectance, and transmittance) of deep slits with five nanoscale slit profile variations at the transverse magnetic wave incidence by employing the rigorous coupled-wave analysis. For slits with attached features, their optical responses can be much different due to the modified cavity geometry and dangled structures, even at wavelengths between 3 and 15 microm. The shifts of cavity resonance excitation result in higher transmittance through narrower slits at specific wavelengths and resonance modes are confirmed with the electromagnetic fields. Opposite roles possibly played by features in increasing or decreasing absorptance are determined by the feature position and demonstrated by Poynting vectors. Correlations among all responses of a representative slit array, the angle of incidence, and the slit density are also comprehensively studied. When multiple slit types coexist in an array (complex slits), a wide-band transmittance or absorptance enhancement is feasible by merging spectral peaks contributed from each type of slits distinctively. Discrepancy among infrared optical responses of four selected slit combinations is explained while effects of slit density are also discussed.

Mueller Matrix of Specular Reflection Using an Aluminum Grating Surface with Oxide Nanofilm.

The accurate nondestructive and real-time determination of the critical dimensions of oxide nanofilms on periodic nanostructures has potential applications in nanofabrication techniques. Mueller ellipsometry is fast, accurate, nondestructive, and can be used in the ambient air. This study used the elements of a Mueller matrix of specular reflection, which is based on a Mueller ellipsometry method, to evaluate the thickness of an oxide nanofilm on an aluminum grating surface. By using non-traditional rigorous coupled-wave analysis (RCWA), we decomposed the Mueller matrix to obtain the relationship between the evaluated polarization properties of reflected light and the dimensions of oxide nanofilms on aluminum grating surfaces. We also quantitatively analyzed the Mueller matrix elements' variation due to the thicknesses of top, sidewall, and bottom oxides. We consider these oxide films are naturally formed and of nonuniform thickness on grating structures. The results show that the elements of Mueller matrix shift with the increasing of the uniform thickness of oxide at a fixed wavelength. Moreover, as oxide nanofilms on grating structures are nonuniform, the impact of the thickness of side wall oxide on the Mueller matrix elements is more obvious than that of top and bottom oxides at the relative larger incidence wavelength range. The finding of this work may facilitate the nondestructive and real-time measurement of the thickness of oxide nanofilms on metal gratings where the metal is easily oxidized.

UNIFIED analytical formulation of thin-film radiative properties including partial coherence.

Radiative properties of thin films are derived based on the concept of optical coherence theory. Instead of the previous approach of deriving the property formulas based on the degree of coherence, a direct integration approach to obtain the averaged properties over a finite spectral resolution is developed. The analytical results are in excellent agreement with the measured spectra. The formulas are compact in form and easy to use to invert optical properties or film thicknesses with measured reflectance or transmittance. Rigorous criteria for incoherent and coherent limits can be easily reduced from the general formulas and the resulting equations corresponding to those of geometric and wave optics, respectively. These criteria are very useful in determining under what situations simpler wave optics and geometric optics formulas can be applied.