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Background Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status. Methods A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS. Results 97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection. Discussion In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.

Wnt/β-catenin signaling is one of the key cascades regulating embryogenesis and tissue homeostasis; it has also been intimately associated with carcinogenesis. This pathway is deregulated in several tumors, including colorectal cancer, breast cancer, and desmoid tumors. It has been shown that CTNNB1 exon 3 mutations are associated with an aggressive phenotype in several of these tumor types and may be associated with therapeutic tolerance. Desmoid tumors typically have a stable genome with β-catenin mutations as a main feature, making these tumors an ideal model to study the changes associated with different types of β-catenin mutations. Here, we show that the apoptosis mechanism is deregulated in β-catenin S45F mutants, resulting in decreased induction of apoptosis in these cells. Our findings also demonstrate that RUNX3 plays a pivotal role in the inhibition of apoptosis found in the β-catenin S45F mutants. Restoration of RUNX3 overcomes this inhibition in the S45F mutants, highlighting it as a potential therapeutic target for malignancies harboring this specific CTNNB1 mutation. While the regulatory effect of RUNX3 in β-catenin is already known, our results suggest the possibility of a feedback loop involving these two genes, with the CTNNB1 S45F mutation downregulating expression of RUNX3, thus providing additional possible novel therapeutic targets for tumors having deregulated Wnt/β-catenin signaling induced by this mutation.

BACKGROUND AND OBJECTIVES Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas. MATERIALS AND METHODS A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed. RESULTS A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P

In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers.The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS.949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P 0.001), younger age (53.3 versus 63.7 years, P 0.001), and receipt of adjuvant radiation (P 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23).Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data.

We have investigated the electronic structure and optical properties of CdSe doped with molecular oxygen by using first-principle local density-functional theory (DFT) based on a hybrid functional. We find that interstitial oxygen molecule introduces two kinds of states in CdSe: filled states which are degenerate and strongly hybridized with the top of the valence bands and one empty state lying in the middle of the gap. The origin of these states can be traced to the 1πg molecular orbitals of O2. We compared the optical absorption spectra of CdSe with and without molecular oxygen. States introduced by oxygen molecules lower the absorption onset of CdSe to ∼1.0eV while hybridization causes redistribution of the oscillator strengths of CdSe transitions from the ultraviolet to the infrared. Our results demonstrate that doping small molecules into semiconductors can alter the electronic and optical properties of the host in ways different from atomic dopants.

The Cherenkov Telescope Array (CTA) is the next-generation ground-based observatory for very-high-energy gamma rays. One candidate design for CTA's medium-sized telescopes consists of the Schwarzschild-Couder Telescope (SCT), featuring innovative dual-mirror optics. The SCT project has built and is currently operating a 9.7-m prototype SCT (pSCT) at the Fred Lawrence Whipple Observatory (FLWO); such optical design enables the use of a compact camera with state-of-the art silicon photomultiplier detectors. A partially-equipped camera has recently successfully detected the Crab Nebula with a statistical significance of 8.6 standard deviations. A funded upgrade of the pSCT focal plane sensors and electronics is currently ongoing, which will bring the total number of channels from 1600 to 11328 and the telescope field of view from about 2.7° to 8° . In this work, we will describe the technical and scientific performance of the pSCT.

A prototype Schwarzschild-Couder Telescope (pSCT) has been constructed at the Fred Lawrence Whipple Observatory as a candidate for the medium-sized telescopes of the Cherenkov Telescope Array Observatory (CTAO). CTAO is currently entering early construction phase of the project and once completed it will vastly improve very high energy gamma-ray detection component in multi-wavelength and multi-messenger observations due to significantly improved sensitivity, angular resolution and field of view comparing to the current generation of the ground-based gamma-ray observatories H.E.S.S., MAGIC and VERITAS. The pSCT uses a dual aspheric mirror design with a $9.7$ m primary mirror and $5.4$ m secondary mirror, both of which are segmented. The Schwarzschild-Couder (SC) optical system (OS) selected for the prototype telescope achieves wide field of view of $8$ degrees and simultaneously reduces the focal plane plate scale allowing an unprecedented compact ($0.78$m diameter) implementation of the high-resolution camera ($6$mm/ $0.067$deg per imaging pixel with $11,328$ pixels) based on the silicon photo-multipliers (SiPMs). The OS of the telescope is designed to eliminate spherical and comatic aberrations and minimize astigmatism to radically improve off-axis imaging and consequently angular resolution across all the field of view with respect to the conventional single-mirror telescopes. Fast and high imaging resolution OS of the pSCT comes with the challenging submillimeter-precision custom alignment system, which was successfully demonstrated with an on-axis point spread function (PSF) of $2.9$ arcmin prior to the first-light detection of the Crab Nebula in 2020. Ongoing and future commissioning activities are reported.

The novel 9.7m Schwarzschild-Couder Telescope (SCT), utilizing aspheric dual-mirror optical system, has been constructed as a prototype medium size x-ray telescope for the Cherenkov Telescope Array (CTA) observatory. The prototype SCT (pSCT) is designed to achieve simultaneously the wide (>= 8°) field of view and the superior imaging resolution (0.067 per pixel) to significantly improve scientific capabilities of the observatory in conducting the sky surveys, the follow-up observations of multi-messenger transients with poorly known initial localization and the morphology studies of x-ray sources with angular extent. In this submission, we describe the hardware and software implementations of the telescope optical system as well as the methods specifically developed to align its complex optical system, in which both primary and secondary mirrors are segmented. The pSCT has detected Crab Nebula in June 2020 during ongoing commissioning, which was delayed due to worldwide pandemic and is not yet completed. Verification of pSCT performance is continuing and further improvement of optical alignment is anticipated.

For the first time in the history of ground-based $\gamma$-ray astronomy, the on-axis performance of the dual mirror, aspheric, aplanatic Schwarzschild-Couder optical system has been demonstrated in a $9.7$-m aperture imaging atmospheric Cherenkov telescope. The novel design of the prototype Schwarzschild-Couder Telescope (pSCT) is motivated by the need of the next-generation Cherenkov Telescope Array (CTA) observatory to have the ability to perform wide ($\geq 8^{\circ}$) field-of-view observations simultaneously with superior imaging of atmospheric cascades (resolution of $0.067^{\circ}$ per pixel or better). The pSCT design, if implemented in the CTA installation, has the potential to improve significantly both the $\gamma$-ray angular resolution and the off-axis sensitivity of the observatory, reaching nearly the theoretical limit of the technique and thereby making a major impact on the CTA observatory sky survey programs, follow-up observations of multi-messenger transients with poorly known initial localization, as well as on the spatially resolved spectroscopic studies of extended $\gamma$-ray sources. This contribution reports on the initial alignment procedures and point-spread-function results for the challenging segmented aspheric primary and secondary mirrors of the pSCT., Comment: 19 pages, 11 figures, proceedings for SPIE Optical Engineering + Applications, 2020, Online Only

Background Sarcomas are malignant heterogeneous tumors of mesenchymal derivation. Dedifferentiated liposarcoma (DDLPS) is aggressive with recurrence in 80% and metastasis in 20% of patients. We previously found that miR-133a was significantly underexpressed in liposarcoma tissues. As this miRNA has recently been shown to be a tumor suppressor in many cancers, the objective of this study was to characterize the biological and molecular consequences of miR-133a underexpression in DDLPS. Methods Real-time PCR was used to evaluate expression levels of miR-133a in human DDLPS tissue, normal fat tissue, and human DDLPS cell lines. DDLPS cells were stably transduced with miR-133a vector to assess the effects in vitro on proliferation, cell cycle, cell death, migration, and metabolism. A Seahorse Bioanalyzer system was also used to assess metabolism in vivo by measuring glycolysis and oxidative phosphorylation (OXPHOS) in subcutaneous xenograft tumors from immunocompromised mice. Results miR-133a expression was significantly decreased in human DDLPS tissue and cell lines. Enforced expression of miR-133a decreased cell proliferation, impacted cell cycle progression kinetics, decreased glycolysis, and increased OXPHOS. There was no significant effect on cell death or migration. Using an in vivo xenograft mouse study, we showed that tumors with increased miR-133a expression had no difference in tumor growth compared to control, but did exhibit an increase in OXPHOS metabolic respiration. Conclusions Based on our collective findings, we propose that in DDPLS, loss of miR-133a induces a metabolic shift due to a reduction in oxidative metabolism favoring a Warburg effect in DDLPS tumors, but this regulation on metabolism was not sufficient to affect DDPLS. Electronic supplementary material The online version of this article (10.1186/s12935-018-0583-2) contains supplementary material, which is available to authorized users.

Sarcomas are malignant heterogenous tumors of mesenchymal derivation. Emerging data suggest that miRNA might have a causal role in sarcomagenesis. Herein, we used a selective miRNA screening platform to study the comparative global miRNA expression signatures in a cohort of human sarcomas with the caveat that comparisons between tumor and non-tumor cells were performed from the same patients using formalin-fixed paraffin-embedded tissue. Five histologic types were examined that included: myxoid liposarcoma, well-differentiated liposarcoma, dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, and synovial sarcoma. In addition, soft-tissue lipomas and normal fat were included as a separate set of controls for the lipogenic tumors. Clustering analysis showed a distinct global difference in expression patterns between the normal and sarcoma tissues. Expression signatures in an unsupervised hierarchical clustering analysis revealed tight clustering in synovial and myxoid liposarcomas, and the least clustering was observed in the pleomorphic rhabdomyosarcoma subtype. MiR-145 showed underexpression in pleomorphic rhabdomyosarcoma, well-differentiated liposarcoma, and synovial sarcoma. Unexpectedly, we found that a set of muscle-specific microRNAs (miRNAs; myomiRs): miR-133, miR-1, and miR-206 was significantly underexpressed in well-differentiated liposarcoma and synovial sarcoma, suggesting that they may function as tumor suppressors as described in muscle-relevant rhabdomyosarcomas. In addition, a tight linear progression of miRNA expression was identified from normal fat to dedifferentiated liposarcoma. These results suggest that miRNA expression profiles could elucidate classes of miRNAs that may elicit tumor-relevant activities in specific sarcoma subtypes.

Rhabdomyosarcoma is a mesenchymal malignancy associated with the skeletal muscle lineage and is also the most common pediatric soft tissue cancer. Between the two pediatric subtypes, embryonal and alveolar rhabdomyosarcoma, the alveolar subtype is generally more aggressive and high-risk. Despite intensive multimodal therapy, patients with high-risk rhabdomyosarcoma continue to have poor prognosis. In this chapter we address the mechanisms underlying the dysregulation of myogenesis in rhabdomyosarcoma. We specifically focus on recently identified signaling pathways that function to inhibit myogenesis and how similar functions have been shown to overlap in rhabdomyosarcoma, potentially contributing to the disease.

Rhabdomyosarcoma is a mesenchymal malignancy associated with the skeletal muscle lineage and is also the most common pediatric soft tissue cancer. Between the two pediatric subtypes, embryonal and alveolar rhabdomyosarcoma, the alveolar subtype is generally more aggressive and high-risk. Despite intensive multimodal therapy, patients with high-risk rhabdomyosarcoma continue to have poor prognosis. In this chapter we address the mechanisms underlying the dysregulation of myogenesis in rhabdomyosarcoma. We specifically focus on recently identified signaling pathways that function to inhibit myogenesis and how similar functions have been shown to overlap in rhabdomyosarcoma, potentially contributing to the disease.

Background Osteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease. Methodology and principal findings RT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes. Conclusions These data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

Leiomyosarcoma (LMS) is a malignant soft tissue sarcoma (STS) with a dismal prognosis following metastatic disease. Chemotherapeutic intervention has demonstrated to have modest clinical efficacy with no curative potential in LMS patients. Previously, we demonstrated pan-HDAC inhibition to have a superior effect in various complex karyotypic sarcomas. In this study, our goal is to evaluate the therapeutic efficacy of mocetinostat alone and in combination with gemcitabine in LMS. Human leiomyosarcoma (LMS) cell lines were used for in vitro and in vivo studies. Compounds tested included the class I HDAC inhibitor, mocetinostat, and nucleoside analog, gemcitabine. MTS and clonogenic assays were used to evaluate the effect of mocetinostat on LMS cell growth. Cleaved caspase 3/7 analysis was used to determine the effects of mocetinostat on apoptosis. Compusyn software was used to determine in vitro synergy studies for the combination of mocetinostat plus gemcitabine. A LMS xenograft model in SCID mice was used to test the impact of mocetinostat alone, gemcitabine alone and the combination of mocetinostat plus gemcitabine. Mocetinostat abrogated LMS cell growth and clonogenic potential, and enhanced apoptosis in LMS cell lines. The combination of mocetinostat plus gemcitabine exhibited a synergistic effect in LMS cells in vitro. Similarly, mocetinostat combined with gemcitabine resulted in superior anti-LMS effects in vivo. Mocetinostat reduced the expression of gemcitabine-resistance markers RRM1, RRM2, and increased the expression of gemcitabine-sensitivity marker, hENT1, in LMS cells. LMS are aggressive, metastatic tumors with poor prognosis where effective therapeutic interventions are wanting. Our studies demonstrate the potential utility of mocetinostat combined with gemcitabine for the treatment of LMS.

Background STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5. Methods and findings An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization. LY5 was evaluated in vitro demonstrating good biologic activity against rhabdomyosarcoma, osteosarcoma and Ewing’s sarcoma cell lines at high nanomolar/low micromolar concentrations, as well as specific inhibition of STAT3 phosphorylation without effects on other STAT3 family members. LY5 exhibited excellent oral bioavailability in both mice and healthy dogs, and drug absorption was enhanced in the fasted state with tolerable dosing in mice at 40 mg/kg BID. However, RNAi-mediated knockdown of STAT3 did not phenocopy the biologic effects of LY5 in sarcoma cell lines. Moreover, concentrations needed to inhibit ex vivo metastasis growth using the PuMA assay were significantly higher than those needed to inhibit STAT3 phosphorylation in vitro. Lastly, LY5 treatment did not inhibit the growth of sarcoma xenografts or prevent pulmonary metastasis in mice. Conclusions LY5 is a novel small molecule inhibitor that effectively inhibits STAT3 phosphorylation and cell proliferation at nanomolar concentrations. LY5 demonstrates good oral bioavailability in mice and dogs. However LY5 did not decrease tumor growth in xenograft mouse models and STAT3 knockdown did not induce concordant biologic effects. These data suggest that the anti-cancer effects of LY5 identified in vitro were not mediated through STAT3 inhibition.

High pressure measurements attracted attention from the Semiconductor Physics community after the discovery of William Paul's Empirical Rule. The technique gained further momentum with the invention of the diamond-anvils high pressure cell. Since diamond is transparent from near IR to near UV many forms of optical spectroscopy (such as photoluminescence, modulation spectroscopy, and Raman scattering) have now been routinely carried out under high pressure. The fact that diamonds are also transparent to X-ray means structural phase transitions induced by pressure can be studied together with optical measurements. Further advances, such as electrical and magnetic measurements under hydrostatic (and sometimes quasi-hydrostatic) high pressure conditions, have established high pressure as a general, powerful, and indis pensable technique in studying semiconductors. From a review of these past achievements I will attempt to "predict" how high pressure techniques will impact semiconductor physics in the future. I will draw examples from areas as diverse as new materials for spintronics and renewable energies, topological insulators to possible multi-ferroic semiconductors.

When used as a photocatalyst, titanium dioxide (TiO(2)) absorbs only ultraviolet light, and several approaches, including the use of dopants such as nitrogen, have been taken to narrow the band gap of TiO(2). We demonstrated a conceptually different approach to enhancing solar absorption by introducing disorder in the surface layers of nanophase TiO(2) through hydrogenation. We showed that disorder-engineered TiO(2) nanocrystals exhibit substantial solar-driven photocatalytic activities, including the photo-oxidation of organic molecules in water and the production of hydrogen with the use of a sacrificial reagent.

In this paper we have applied first-principle density-functional theory to calculate some of the interesting roles played by vacancies in material properties, such as magnetic properties and complex formation. We use as examples our recent results on vacancies in group III-V semiconductors like GaN and II-VI semiconductor like CdTe.

Background: Osteosarcoma (OS) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and play a fundamental role in cancer. Given that canine OS is a well-validated spontaneous large animal model of the human disease, the purpose of this study was to characterize the impact of miR-34a expression in canine OS tumor lines to better understand its potential role in the biology of this disease. Methods: Real-time PCR was used to assess miR-34a expression in primary canine OS tumors, canine OS cell lines, and normal canine osteoblasts. Canine OSA8 and Abrams cell lines were stably transduced with empty vector or pre-miR-34a lentiviral constructs to determine the consequences of miR-34a on cell proliferation, cell cycle distribution, invasion, and migration. Gene expression profiling of canine OSA8 cells with enforced miR-34a expression was performed using RNA sequencing and changes in mRNA expression were validated using real-time PCR. Results: Real-time PCR demonstrated that miR-34a expression levels were significantly decreased in primary canine OS tumors and canine OS cell lines as compared to normal canine osteoblasts. In canine OS cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant downregulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of downregulated miR-34a target genes showed enrichment of several biologic processes related to cell invasion and motility. Lastly, we validated changes in miR-34a target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OS cells overexpressing miR-34a. Concordant with these data, primary canine OS tumor tissues demonstrated increased expression levels of putative miR-34a target genes. Conclusions: Our data demonstrate that miR-34a expression is significantly decreased in primary canine OS tumor tissues and canine OS cell lines compared to normal canine osteoblasts. These results are concordant with data generated in human OS tumors, suggesting that loss of miR-34a may be fundamental to the disease process in both species. Our data demonstrate that miR-34a contributes to invasion and migration in canine OS cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OS. As such, miR-34a may represent a novel target for therapeutic intervention in OS. Citation Format: Cecilia M. Lopez, Peter Y. Yu, Xiaoli Zhang, Ayse Selen Yilmaz, Cheryl A. London, Joelle M. Fenger. MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines: A comparative oncology study [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A14.

Lateral and vertical ordered one-dimensional quantum structures, i.e. InGaAs/GaAs(001) quantum dot chains and quantum wires, have been obtained using molecular beam epitaxy. It was found that the InGaAs wires or dot chains sit on two-dimensional wetting layers and run along the [-110] direction, as the result of anisotropic strain and in-plane adatom diffusion. This anisotropic nature produces a model system for studying the electronic properties of one-, two-, and three-dimensional quantum confinements and related optical responses. The strain anisotropy is of importance in determining the electronic states of the quantum structures and the surrounding strained barrier. The strain-induced effects, such as change of band-gap and splitting of heavy–light hole states, were studied experimentally and theoretically. Optical anisotropy of these quantum structures is also discussed.

Deposition of CuInSe 2 thin film on CuGaSe 2 thin film and vice versa has been studied by a low pressure metal–organic chemical vapor deposition technique with three precursors without additional Se. The properties of the resultant films have been examined by scanning electron microscopy, X-ray diffraction, and micro-Raman scattering. Good quality and well demarcated films are obtained only in the case of CuInSe 2 grown on CuGaSe 2 . When CuGaSe 2 was grown on top of CuInSe 2 diffusion of Ga into CuInSe 2 was found to produce an alloy film instead.

We have investigated theoretically and experimentally the pressure dependent structural and vibrational properties of single-walled carbon nanotubes (SWNT). Bundles of SWNTs are studied inside a diamond anvil high pressure cell with micro-Raman scattering. The tube diameter and size distribution are determined from the radial breathing modes (RBM) of the tubes. The pressure coefficient and linewidth of one of the high frequency C-C bond stretching modes was found to change suddenly at ∼3 GPa which is well below the structural transformation pressure (P c ) for the tubes in our sample. Molecular dynamics simulations were used to calculate the vibrational density of states of SWNTs as a function of pressure. Our simulations suggest that the experimental results can be explained by a softening of a low-frequency optical mode of the SWNTs - the "squashing" mode - and the dynamical effect of this softening on other phonon modes.

The author Robert Fulghum published in 1988 a book with a rather humorous title: “All I really need to know I learned in Kindergarten”. The book became an instant success and was on the New York Times bestsellers list for 2 years.

In this paper we show that, under resonance condition, the pressure coefficient of the n -th order longitudinal optical (LO) phonon determined by Raman scattering at low temperature exhibits a linear dependence on n. This linear dependence arises from a quadratic dependence of the LO phonon pressure coefficient on the phonon wave vector. The results of the theoretical calculation are in qualitative agreement with recently reported experimental results in CdS [I. H. Choi and P. Y. Yu, phys. stat. sol. (b) 242, 2813 (2005)]. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We review the study of nanocrystals or quantum dots using inelastic light scattering spectroscopies. In particular recent calculations of the phonon density of states and low frequency Raman spectra in Ge nanocrystals are presented for comparison with experimental results.

The pressure dependence of the excitonic photoluminescence and Raman scattering in both hexagonal and cubic CdS films grown on GaAs substrates is reported. We found that the pressure coefficients of the cubic CdS films are equal to those of the hexagonal films within experimental uncertainties. The main difference between their optical and vibrational properties seems to lie in their exciton energies, the hexagonal phase having a slightly higher energy than the cubic phase. Strong enhancement in multi-longitudinal optical (LO) phonon scattering has been observed by “pressure-tuning” the exciton energy to resonate with the excitation laser line. As a result we have been able to determine the pressure coefficients of the higher order LO phonons in CdS for modes as high as 5LO. We found that the pressure coefficients of these higher order LO modes when normalized by the phonon frequency exhibit a systematic decrease with the order of the mode. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We have grown single-phase thin films of CdS on GaAs substrates. The structure of the CdS film has been determined by X-ray diffraction to be either zincblende or wurtzite depending on whether the orientation of the substrate is [100] or [111]. The films are found to be strained by 1% or less. The quality of the films have also been characterized by temperature dependent photoluminescence (PL) and multiphonon resonant Raman scattering (RRS). The PL spectra are dominated by excitonic emission. The observed peak energies are equal to those reported in bulk CdS within experimental errors. RRS of as many seven longitudinal optical (LO) phonon have been observed. The overall quality of the thin films are found to be comparable to those of bulk CdS samples. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The Raman spectra of a single crystal of CdGeP 2 have been measured as a function of pressure using a tunable infrared Ti:sapphire laser and a diamond anvil high pressure cell. The pressure coefficients of the zone-center optical phonons have been determined. The results are compared with those of the corresponding zincblende-type (GaP and InP) and I- III-VI 2 chalcopyrite (AgGaS 2 ) compounds.

Phase-pure InSe thin films have been prepared by a low-pressure metalorganic chemical vapor deposition technique using a single-source precursor: [(Me)2In(μ−SeMe)]2. These films have been characterized by x-ray diffraction and scanning electron microscopy and found to be single-phased and polycrystalline with a hexagonal lattice. The optical properties of the films have been studied via absorption, photoluminescence, and Raman spectroscopies.

Chalcopyrite semiconductors are birefringent as a result of their tetragonal crystal lattice structure. The dispersion of this birefringence contains contributions from the near-bandgap transitions and also from higher energy band-to-band transitions. We report the effect of pressure on the dispersion of the natural birefringence in CdGeP 2 . We found that pressure tends to decrease both contributions. The pressure effect on the near-bandgap contribution results mostly from an increase of the bandgap with pressure.

Background: Sarcomas are malignant heterogeneous tumors of mesenchymal derivation. Dedifferentiated liposarcoma (DDLPS) exhibits aggressive biological behavior with an 80% local recurrence rate and the development of metastasis in approximately 20% of patients. To identify and characterize the molecular alterations that contribute to the development and progression of DDLPS, our laboratory characterized a unique miRNA expression signature associated with human DDLPS tissue compared to paired subjacent normal tissue. We found that several muscle-specific miRNAs (myomiRs), miR-1, -133a, and -206, were significantly underexpressed in liposarcoma tissues. Interestingly, these miRNAs have recently been shown to have tumor suppressor functions in many human cancers. The objective of this study is to characterize the biological and molecular consequences of miR-133a in DDLPS. Methods: Taqman real-time PCR was used to evaluate expression levels of myomiRs in human DDLPS tissue, normal fat tissue, and available human DDLPS cell lines. To evaluate the effects of miR-133a expression on DDLPS cell line behavior in vitro, cells were stably transduced with miR-133a vector or empty lentiviral vector and the effects on cell cycle, proliferation, apoptosis, and migration were assessed. Agilent Seahorse Bioanalyzer system was used to assess metabolism. We performed an in silico search for predicted targets of miR-133a using target prediction databases and compared these target genes to known genes that are highly expressed in human DDLPS tissue. Results: The expression levels of myomiRs were significantly decreased in human DDLPS tissue compared to normal human fat as well as in human DDLPS cell lines compared to a human preadipocyte cell lines. Overexpression of miR-133a decreased cell proliferation, decreased glycolysis, and increased spare respiratory capacity. There was no significant effect on cell cycle, apoptosis, or migration. Using in silico target gene analysis, we identified 18 potential targets of miR-133a. These preliminary results suggest that miR-133a regulates metabolism and proliferation, and its dysregulation might contribute to the oncogenic phenotype of DDLPS. Significance: We have demonstrated that enforced expression of miR-133a decreased proliferation and metabolism in human DDLPS cells. We have identified putative gene targets of miR-133a and are currently dissecting the molecular mechanism by which miR-133a may mediate proliferation and metabolism in DDLPS cell lines. Taken together, these data suggest that miR-133a might play a tumor suppressor role in DDLPS, thereby generating new potential targets for therapeutic intervention to alter the course of this disease. Citation Format: Peter Y. Yu, Hans Iwenofu, Raphael E. Pollock, Denis C. Guttridge. miR-133a function in the pathogenesis of dedifferentiated liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3426. doi:10.1158/1538-7445.AM2017-3426

Introduction: Our laboratory previously demonstrated that miR-9 promotes the invasive properties of normal and malignant mast cells and that overexpression of miR-9 is associated with spontaneous metastasis in canine mast cell tumors (MCTs), a well-established large animal model of malignant mast cell disease. The purpose of this study was to further investigate the biologic effect and mechanisms by which mir-9 enhances normal mast cell invasion. Methods: Bone marrow-derived mast cells (BMMCs) were generated from Cpa3-Cre; miR-9Δfl/Δfl, and Cpa3-Cre; miR-9Δfl/Δfl mice and Taqman miRNA assays were used to quantify mature miR-9 expression. BMMCs were evaluated for differences in proliferative capacity, the ability to migrate through Matrigel, sensitivity to degranulation, and the expression and release of growth factor expression and release following chemical stimulation. RNA sequencing was performed by the OSUCCC Genomics Resource and changes in protein and mRNA expression were validated with Western blotting and quantitative PCR. Results and Conclusions: We generated a transgenic mouse carrying a floxed STOP-miR-9 transgene (miR-9Δfl/Δfl) in which expression of miR-9 occurs only after Cre-mediated recombination and crossed these mice with Cpa3-Cre mice which express Cre recombinase under the control of the carboxypeptidase A3 (Cpa3) promoter, restricting expression of miR-9 to mast cells and basophils. Bone marrow-derived mast cells (BMMCs) derived from Cpa3-Cre;miR-9Δfl/Δfl mice significantly enhanced the invasive phenotype of mast cells. Moreover, the enforced expression of miR-9 in BMMCs markedly changed the production and release of cytokine and growth factors in response to chemical stimulation, including substantial up-regulation of IL-4, IL-13, and GM-CSF transcript and enhanced TGF-β1 release. RNA sequencing revealed a unique transcriptional profile associated with miR-9 over-expression in the Cpa3-Cre;miR-9Δfl/Δfl derived BMMCs and identified increased expression of several mast cell-restricted proteases involved in extracellular matrix and tissue remodeling including CMA1 and MCP-6. Furthermore, transduction of Cpa3-Cre;miR-9Δfl/Δfl derived BMMCs with CMA1 shRNA abrogated miR-9-dependent mast cell invasion. Studies are underway to investigate the regulatory pathway mediated by miR-9 that contributes to CMA1 up-regulation and promotes the invasive phenotype. In summary, these data provide evidence supporting a critical role for miR-9 in mast cell invasion and suggest that dysregulation of miR-9 may contribute to pathologic conditions involving mast cell-mediated tissue remodeling. Citation Format: Joelle M. Fenger, Feng Xu, Xaioli Zhang, Peter Y. Yu, Misty D. Bear, Shanice L. Reynolds, Michael L. Pennell, Vincenzo Coppola, William C. Kisseberth, Stephen J. Galli, Cheryl A. London. A novel Cpa3-Cre; miR-9fl/fl mouse reveals a functional role for miR-9 in promoting mast cell invasion via up-regulation of CMA1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3043. doi:10.1158/1538-7445.AM2017-3043

We propose an alternative structure of TiO2 anatase that has a higher energy oxygen p-like valence band maximum than the pristine TiO2 anatase and thus has a much better alignment with the water splitting levels. This alternative structure is unique when considering a large subspace of possible structural distortions of TiO2 anatase. We propose two routes towards this state and argue that one of them might have been realized in the recently discovered so-called black TiO2., Comment: 7 pages, 9 figures

Using polarized neutron reflectometry, we observe an induced magnetization of $75\ifmmode\pm\else\textpm\fi{}25\text{ }\mathrm{kA}/\mathrm{m}$ at 10 K in a ${\mathrm{La}}_{0.7}{\mathrm{Sr}}_{0.3}{\mathrm{MnO}}_{3}$ $(\mathrm{LSMO})/{\mathrm{BiFeO}}_{3}$ superlattice extending from the interface through several atomic layers of the ${\mathrm{BiFeO}}_{3}$ (BFO). The induced magnetization in BFO is explained by density functional theory, where the size of band gap of BFO plays an important role. Considering a classical exchange field between the LSMO and BFO layers, we further show that magnetization is expected to extend throughout the BFO, which provides a theoretical explanation for the results of the neutron scattering experiment.

Photoluminescence upconversion (PLU) is a phenomenon in which a sample emits photons with energy higher than that of the excitation photon. This effect has been observed in many materials including rare earth ions doped in insulating hosts and semiconductor heterostructures without using high power lasers as the excitation source. Recently, this effect has been observed also in partially CuPt-ordered GaInP{sub 2} epilayers grown on GaAs substrates. As a spectroscopic technique photoluminescence upconversion is particularly well suited for studying band alignment at heterojunction interface. The value of band-offset has been determined with meV precision using magneto-photoluminescence. Using the fact that the pressure coefficient of electrons in GaAs is higher than those in GaInP{sub 2} they have been able to manipulate the band-offset at the GaInP/GaAs interface. By converting the band-offset from Type I to Type II they were able to demonstrate that the efficiency of the upconversion process is greatly enhanced by a Type II band-offset.

PRESSURE DEPENDENCE OF DEFECT EMISSIONS AND THE APPEARANCE OF PRESSURE-INDUCED DEEP CENTERS IN CHALCOPYRITE ALLOYS Ag x Cu 1-x GaS 2 In-Hwan Choi Department of Physics, Chung-Ang University, Seoul, Korea and Peter Y. Yu (a) Department of Physics, University of California, Berkeley, and Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720. ABSTRACT We present the pressure dependence of the defect emissions in the chalcopyrite alloy semiconductor Ag x Cu 1-x GaS 2 for values of the alloy concentration x varying between 0 and 1. A large variation in the pressure coefficients of the different defect emissions with x was found. In one alloy concentration x=0.25 deep levels were found to appear under pressure. Plausible explanations of our results have been proposed. PACS:78.20.Hp; 78.30.Hv; 63.20.Kr Substance Classification: S8.11 (a) email: PYYU@LBL.GOV; fax: 510-643-8497.

Ge nanocrystals of diameters ranging from 4 to 10 nm were synthesized by ion implantation of Ge{sup +} ions into SiO{sub 2} films followed by annealing. Confinement of its optical phonon and of the quasi-two-dimensional E{sub 1} exciton have been observed at room temperature by resonant Raman scattering. The observed size-dependent blueshifts of the E{sub 1} excitons energy (which can be larger than 0.7 eV) are found to be in good agreement with a theoretical calculation based on the effective mass approximation. (c) 2000 The American Physical Society.

The absorption, emission and Raman spectra of the quaternary chalcopyrite alloys AgxCu1−xGaS2 have been measured as a function of the Ag concentration. We find strong and highly nonlinear dependence on the alloy concentration in the optical band gap (a large bowing parameter). On the other hand, most of the Raman peaks exhibit either small energy shifts or large broadening with alloying. We conclude that the effect of substitution of the Ag cations by Cu in AgGaS2 on its band structure cannot be predicted by the simple virtual crystal potential approximation as a result of the large difference in electronegativity and bond length between Ag and Cu.

We report the appearance of a deep donor in the photoluminescence spectra of the chalcopyrite semiconductor alloy Ag{sub 0.25}Cu{sub 0.75}GaS{sub 2} under hydrostatic pressures exceeding 5 GPa. The recombination peaks of this deep donor with acceptors exhibit either zero or a small negative pressure coefficient. Our results suggest the existence of a deep donor level which is resonant with the conduction band at ambient pressure. (c) 2000 The American Physical Society.

The yellow luminescence of n-type GaN has been studied with selective excitation using a combination of Ar ion and dye lasers. Narrower structures whose peak energies follow the excitation photon energy over the width of the yellow luminescence have been observed. Unlike the yellow luminescence excited by above band gap excitations, these fine structures exhibits thermal activated quenching behavior. We propose that these fine structures are due to emission occurring at complexes of shallow donors and deep acceptors which can be resonantly excited by photons with energies below the band gap. The activation energy deduced from their intensity is that for delocalization of electrons out of the complexes. Our results therefore suggest that there is more than one recombination channel (usually assumed to be due to distant donor-acceptor pairs) to the yellow luminescence in GaN.

We report the first observation of a low energy phonon mode in the low-temperature and resonantly-enhanced Raman spectra of AgGaS2. This mode appears as sidebands of one-phonon Raman modes at T < 100 K. Its frequency is 8.0 cm—1 at T = 3.4 K and decreases to 5.7 cm—1 at 90 K. The mode becomes overdamped and difficult to resolve as T is increased to 100 K. We tentatively attribute this “soft mode” with a zone-edge phonon which is observable in two-phonon combination Raman scattering. When alloyed with Cu both the soft mode and the anomalous blue-shift of the band gap in AgGaS2 are suppressed. We propose that this soft mode is responsible for the anomalous blue-shift of the band gap in AgGaS2 at low temperature.

Photoluminescence originating from the GaAs/ (ordered) GaInP2 interface has been studied under the simultaneous application of high magnetic field and high pressure. A sharp threshold dependence on magnetic field was observed in the intensity of the spatially indirect transition between electrons in GaInP2 and holes in GaAs. A model involving trapping of electrons from GaAs into quantum boxes formed by type-II ordered GaInP2 domains is proposed. This model reproduces the pressure-induced variations of the quantum box sizes and demonstrates the ability of this technique to study the properties of nanometer size systems.

We have utilized resonant Raman scattering to investigate the phonon modes of self-organized Ge quantum dots grown by molecular-beam epitaxy. Both Ge-Ge and Si-Ge phonon modes are found to exhibit strong enhancements at the E{sub 1} exciton. The strain in the quantum dots deduced from the phonon energies is consistent with the results of high-resolution transmission electron microscopy. An upper bound on the confinement energy of the E{sub 1} exciton in quantum dots was deduced. The enhancement strength in the Si-Ge phonon indicates strong interaction between this mode and the E{sub 1} exciton of the Ge dots. {copyright} {ital 1999} {ital The American Physical Society}

We report the photoluminescence and absorption spectra of a series of quaternary chalcopyrite alloys with the formula: CuIn1-xGaxSe2 where x varies between 0 and 1 in steps of 0.25. Using a diamond anvil cell we have studied their band gaps and impurity emission peak energies as a function of pressure. We found that while the band gap of CuIn1-xGaxSe2 varies nonlinearly with x the pressure coefficient (alpha) varies linearly with x at a rather large rate of d alpha/dx = 18.6 meV/GPa. We interpret our results in terms of recent theoretical calculations which have been proposed to explain the large difference in alpha between CuGaSe2 and CuInSe2.

We report the observation of a folded zone-edge phonon mode, in addition to the folded L point mode reported already in Raman scattering from ${\mathrm{Ga}}_{x}{\mathrm{In}}_{1\ensuremath{-}x}\mathrm{P}$ epitaxial layers grown on GaAs and containing two variants of CuPt ordering. This Raman mode becomes observable as a result of resonant enhancement at an electronic transition at 2.25 eV reported previously in electroreflectance measurements. Our results suggest that a folding of the Brillouin zone along the [001] direction occurs in partially ordered ${\mathrm{Ga}}_{x}{\mathrm{In}}_{1\ensuremath{-}x}\mathrm{P}$ samples due to the existence of antiphase boundaries.