Defect and Hodge numbers of hypersurfaces

We define defect for hypersurfaces with A-D-E singularities in complex projective normal Cohen-Macaulay fourfolds having some vanishing properties of Bott-type and prove formulae for Hodge numbers of big resolutions of such hypersurfaces. We compute Hodge numbers of Calabi-Yau manifolds obtained as small resolutions of cuspidal triple sextics and double octics with higher A_j singularities.Comment: 25 page

Decomposition of semigroup algebras

Let A \subseteq B be cancellative abelian semigroups, and let R be an integral domain. We show that the semigroup ring R[B] can be decomposed, as an R[A]-module, into a direct sum of R[A]-submodules of the quotient ring of R[A]. In the case of a finite extension of positive affine semigroup rings we obtain an algorithm computing the decomposition. When R[A] is a polynomial ring over a field we explain how to compute many ring-theoretic properties of R[B] in terms of this decomposition. In particular we obtain a fast algorithm to compute the Castelnuovo-Mumford regularity of homogeneous semigroup rings. As an application we confirm the Eisenbud-Goto conjecture in a range of new cases. Our algorithms are implemented in the Macaulay2 package MonomialAlgebras.Comment: 12 pages, 2 figures, minor revisions. Package may be downloaded at http://www.math.uni-sb.de/ag/schreyer/jb/Macaulay2/MonomialAlgebras/html

Somatic TP53 Mutations Are Detectable in Circulating Tumor DNA from Children with Anaplastic Wilms Tumors.

BACKGROUND: Diffuse anaplastic Wilms tumor (DAWT) is a rare, high-risk subtype that is often missed on diagnostic needle biopsy. Somatic mutations in TP53 are associated with the development of anaplasia and with poorer survival, particularly in advanced-stage disease. Early identification of DAWT harboring TP53 abnormalities could improve risk stratification of initial therapy and monitoring for recurrence. METHODS: Droplet digital polymerase chain reaction (ddPCR) was used to evaluate 21 samples from 4 patients with DAWT. For each patient, we assessed TP53 status in frozen tumor, matched germline DNA, and circulating tumor DNA (ctDNA) from plasma, serum, and urine collected throughout treatment. RESULTS: Mutant TP53 was detectable in ctDNA from plasma and serum in all patients. We did not detect variant TP53 in the same volume (200 μl) of urine. One patient displayed heterogeneity of TP53 in the tumor despite both histological sections displaying anaplasia. Concentration of ctDNA from plasma/serum taken prenephrectomy varied significantly between patients, ranging from 0.44 (0.05-0.90) to 125.25 (109.75-140.25) copies/μl. We observed variation in ctDNA throughout treatment, and in all but one patient, ctDNA levels fell significantly following nephrectomy. CONCLUSION: We demonstrate for the first time that ddPCR is an effective method for detection of mutant TP53 in ctDNA from children with DAWT even when there is intratumoral somatic heterogeneity. This should be further explored in a larger cohort of patients, as early detection of circulating variant TP53 may have significant clinical impact on future risk stratification and surveillance

Development of high refractive index UiO-66 framework derivatives via ligand halogenation

UiO-66 is a Zr-based metal-organic framework (MOF) with exceptional chemical and thermal stability. The modular design of a MOF allows the tuning of its electronic and optical properties to obtain tailored materials for optical applications. Making use of the halogenation of the 1,4-benzenedicarboxylate (bdc) linker, the well-known monohalogenated UiO-66 derivatives were examined. In addition, a novel diiodo bdc based UiO-66 analogue is introduced. The novel UiO-66-I2 MOF is fully characterized experimentally. By applying density functional theory (DFT), fully relaxed periodic structures of the halogenated UiO-66 derivatives are generated. Subsequently, the HSE06 hybrid DFT functional is used to calculate the electronic structures and optical properties. The obtained band gap energies are validated with UV-Vis measurements to assure a precise description of the optical properties. Finally, the calculated refractive index dispersion curves are evaluated underlining the capabilities to tailor the optical properties of MOFs by linker functionalization

Fragment-based approach for the efficient calculation of the refractive index of metal-organic frameworks

Increasing demands on materials in the field of optical applications require novel materials. Metal-organic frameworks (MOFs) are a prominent class of hybrid inorganic-organic materials with a modular layout. This allows the fine-tuning of their optical properties and the tailored design of optical systems. In the present theoretical study, an efficient method to calculate the refractive index (RI) of MOFs is introduced. For this purpose, the MOF is split into disjoint fragments, the linkers and the inorganic building units. The latter are disassembled until metal ions are obtained. The static polarizabilities are calculated individually using molecular density functional theory (DFT). From these, the MOF's RI is calculated. To obtain suitable polarizabilities, an exchange-correlation functional benchmark was performed first. Subsequently, this fragment-based approach was applied to a set of 24 MOFs including Zr-based MOFs and ZIFs. The calculated RI values were compared to the experimental values and validated using HSE06 hybrid functional DFT calculations with periodic boundary conditions. The examination of the MOF set revealed a speed up of the RI calculations by the fragment-based approach of up to 600 times with an estimated maximal deviation from the periodic DFT results below 4%

Correction: Tuning the optical properties of the metal-organic framework UiO-66 via ligand functionalization

The authors apologise that the comparison of calculated (HSE06) and experimental band gaps shown in Fig. 3 were incorrect, the experimental values did not match the presented UV-Vis spectra and Tauc plots. The figure is corrected as follows: The corrections shown here do not affect the conclusions in the paper. (Figure Presented).The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers

Tuning the optical properties of the metal-organic framework UiO-66 via ligand functionalization

Metal-organic frameworks (MOFs) are a promising class of materials for optical applications, especially due to their modular design which allows fine-tuning of the relevant properties. The present theoretical study examines the Zr-based UiO-66-MOF and derivatives of it with respect to their optical properties. Starting from the well-known monofunctional amino- and nitro-functionalized UiO-66 derivatives, we introduce novel UiO-66-type MOFs containing bifunctional push-pull 1,4-benzenedicarboxylate (bdc) linkers. The successful synthesis of such a novel UiO-66 derivative is also reported. It was carried out using a para-nitroaniline (PNA)-based bdc-analogue linker. Applying density functional theory (DFT), suitable models for all UiO-66-MOF analogues were generated by assessing different exchange-correlation functionals. Afterwards, HSE06 hybrid functional calculations were performed to obtain the electronic structures and optical properties. The detailed HSE06 electronic structure calculations were validated with UV-Vis measurements to ensure reliable results. Finally, the refractive index dispersion of the seven UiO-66-type materials is compared, showing the possibility to tailor the optical properties by the use of functionalized linker molecules. Specifically, the refractive index can be varied over a wide range from 1.37 to 1.78

Returning to work after stroke: perspectives of employer stakeholders, a qualitative study.

Purpose: More than 40 % of working age adults with stroke fail to return to work. The work context is a key factor in return to work, but little is known about the experiences of employers in supporting employees with stroke. The aim of this study was to explore return to work after stroke from the employer perspective, to identify key features associated with success and to seek participants’ views regarding the role of healthcare in return to work. Methods: Data was gathered through 18 semi-structured interviews with employer stakeholders and included small business owners, line managers, human resources and occupational health staff. Data was analysed thematically. Results: The main themes identified were: the impact of stroke on the employer, characteristics of the employee, communication, knowledge and information, experience of other stakeholders, integrating healthcare in return to work. Conclusion: Employers face complex emotional and practical issues when helping an employee return to work after stroke, for which many lack knowledge and experience. The range and quality of support networks that they access is variable and advice and support from clinicians is welcomed. Further research is necessary to investigate how such support could be funded and integrated within existing service provision

Epigenetic Induction of Cancer-Testis Antigens and Endogenous Retroviruses at Single-Cell Level Enhances Immune Recognition and Response in Glioma

Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of cancer-testis antigens (CTA) in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using New York esophageal squamous cell carcinoma 1 (NY-ESO-1) as a representative inducible CTA, we demonstrate in patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres that basal CTA expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing to render NY-ESO-1 and other CTA into inducible tumor antigens at single-cell resolution. Functionally, NY-ESO-1 T-cell receptor-engineered effector cell targeting of DAC-induced antigen in primary glioma cells promotes specific and polyfunctional T-cell cytokine profiles. In addition to induction of CTA, DAC concomitantly reactivates tumor-intrinsic human endogenous retroviruses, interferon response signatures, and MHC-I. Overall, we demonstrate that DAC induces targetable tumor antigen and enhances T-cell functionality against GBM, ultimately contributing to the improvement of targeted immune therapies in glioma.SignificanceThis study dissects the tumor-intrinsic epigenetic and transcriptional mechanisms underlying enhanced T-cell functionality targeting decitabine-induced cancer-testis antigens in glioma. Our findings demonstrate concomitant induction of tumor antigens, reactivation of human endogenous retroviruses, and stimulation of interferon signaling as a mechanistic rationale to epigenetically prime human gliomas to immunotherapeutic targeting

Predicting discharge to institutional long-term care after stroke: a systematic review & meta-analysis

Background/Objectives: Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke. Design: We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed. Setting: Acute and rehabilitation hospitals. Participants: Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge. Measurements: Factors associated with new institutionalization. Results: From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined. Conclusion: Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting