1,485 research outputs found
Effective Confinement as Origin of the Equivalence of Kinetic Temperature and Fluctuation-Dissipation Ratio in a Dense Shear Driven Suspension
We study response and velocity autocorrelation functions for a tagged
particle in a shear driven suspension governed by underdamped stochastic
dynamics. We follow the idea of an effective confinement in dense suspensions
and exploit a time-scale separation between particle reorganization and
vibrational motion. This allows us to approximately derive the
fluctuation-dissipation theorem in a "hybrid" form involving the kinetic
temperature as an effective temperature and an additive correction term. We
show numerically that even in a moderately dense suspension the latter is
negligible. We discuss similarities and differences with a simple toy model, a
single trapped particle in shear flow
Role of Hidden Slow Degrees of Freedom in the Fluctuation Theorem
The validity of the fluctuation theorem for entropy production as deduced
from the observation of trajectories implicitly requires that all slow degrees
of freedom are accessible. We experimentally investigate the role of hidden
slow degrees of freedom in a system of two magnetically coupled driven
colloidal particles. The apparent entropy production based on the observation
of just one particle obeys a fluctuation theorem-like symmetry with a slope of
1 in the short time limit. For longer times, we find a constant slope, but
different from 1. We present theoretical arguments for a generic linear
behavior both for small and large apparent entropy production but not
necessarily throughout. By fine-tuning experimental parameters, such an
intermediate nonlinear behavior can indeed be recovered in our system as well
Variational methods for contracting projected entangled-pair states
The norms or expectation values of infinite projected entangled-pair states
(PEPS) cannot be computed exactly, and approximation algorithms have to be
applied. In the last years, many efficient algorithms have been devised -- the
corner transfer matrix renormalization group (CTMRG) and variational uniform
matrix product state (VUMPS) algorithm are the most common -- but it remains
unclear whether they always lead to the same results. In this paper, we
identify a subclass of PEPS for which we can reformulate the contraction as a
variational problem that is algorithm independent. We use this variational
feature to assess and compare the accuracy of CTMRG and VUMPS contractions.
Moreover, we devise a new variational contraction scheme, which we can extend
to compute general N-point correlation functions
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First-in-human study of TK-positive oncolytic vaccinia virus delivered by adipose stromal vascular fraction cells.
BACKGROUND: ACAM2000, a thymidine kinase (TK)-positive strain of vaccinia virus, is the current smallpox vaccine in the US. Preclinical testing demonstrated potent oncolytic activity of ACAM2000 against several tumor types. This Phase I clinical trial of ACAM2000 delivered by autologous adipose stromal vascular fraction (SVF) cells was conducted to determine the safety and feasibility of such a treatment in patients with advanced solid tumors or acute myeloid leukemia (AML).
METHODS: Twenty-four patients with solid tumors and two patients with AML participated in this open-label, non-randomized dose-escalation trial. All patients were treated with SVF derived from autologous fat and incubated for 15 min to 1 h with ACAM2000 before application. Six patients received systemic intravenous application only, one patient received intra-tumoral application only, 15 patients received combination intravenous with intra-tumoral deployment, 3 patients received intravenous and intra-peritoneal injection and 1 patient received intravenous, intra-tumoral and intra-peritoneal injections. Safety at each dose level of ACAM2000 (1.4 × 10
RESULTS: No serious toxicities (\u3e grade 2) were reported. Seven patients reported an adverse event (AE) in this study: self-limiting skin rashes, lasting 7 to 18 days-an expected adverse reaction to ACAM2000. No AEs leading to study discontinuation were reported. Viral DNA was detected in all patients\u27 blood samples immediately following treatment. Interestingly, in 8 patients viral DNA disappeared 1 day and re-appeared 1 week post treatment, suggesting active viral replication at tumor sites, and correlating with longer survival of these patients. No major increase in cytokine levels or correlation between cytokine levels and skin rashes was noted. We were able to assess some initial efficacy signals, especially when the ACAM2000/SVF treatment was combined with checkpoint inhibition.
CONCLUSIONS: Treatment with ACAM2000/SVF in patients with advanced solid tumors or AML is safe and well tolerated, and several patients had signals of an anticancer effect. These promising initial clinical results merit further investigation of therapeutic utility. Trial registration Retrospectively registered (ISRCTN#10201650) on October 22, 2018
Germline MBD4 deficiency causes a multi-tumor predisposition syndrome
We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management
Germline MBD4-deficiency causes a multi-tumor predisposition syndrome
We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management
Integrated Molecular Characterization of Uterine Carcinosarcoma
SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified
Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an
Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis
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