The localization transition in SU(3) gauge theory

We study the Anderson-like localization transition in the spectrum of the Dirac operator of quenched QCD. Above the deconfining transition we determine the temperature dependence of the mobility edge separating localized and delocalized eigenmodes in the spectrum. We show that the temperature where the mobility edge vanishes and localized modes disappear from the spectrum, coincides with the critical temperature of the deconfining transition. We also identify topological charge related close to zero modes in the Dirac spectrum and show that they account for only a small fraction of localized modes, a fraction that is rapidly falling as the temperature increases.Comment: 7 pages, 5 figures, v3: additional data on finer lattice; final, published versio

Engineered Exosomes for Delivery of Therapeutic siRNAs to Neurons

Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data. We established that cholesterol-conjugated siRNAs passively associate to EV membrane and can be productively delivered to target neurons. We extensively characterized this loading process and optimized exosome-to-siRNA ratios for loading. We found that chemical stabilization of 5\u27-phosphate with 5\u27-E-vinylphosphonate and chemical stabilization of all nucleotides with 2\u27-O-methyl and 2\u27-fluoro increases the accumulation of siRNA and the level of mRNA silencing in target cells. Therefore, we recommend using fully modified siRNAs for lipid-mediated loading to EVs. Later, we identified that α-tocopherol-succinate (vitamin E) conjugation to siRNA increases productive loading to exosomes compared to originally described cholesterol. Low EV yield has been a rate-limiting factor in preclinical development of the EV technology. We developed a scalable EV manufacturing process based on three-dimensional, xenofree culture of mesenchymal stem cells and concentration of EVs from conditioned media using tangential flow filtration. This process yields exosomes more efficient at siRNA delivery than exosomes isolated via differential ultracentrifugation from two-dimensional cultures of the same cells. In-depth characterization of EV content is required for quality control of EV preparations as well as understanding composition–activity relationship of EVs. We have generated mass-spectrometry data on more than 3000 proteins and more than 2000 lipid species detected in exosomes (small EVs) and microvesicles (large EVs) isolated from five different producer cells: two cell lines (U87 and Huh7) and three mesenchymal stem cell types (derived from bone marrow, adipose tissue and umbilical cord Wharton’s jelly). These data represent an indispensable resource for the community. Furthermore, relating composition change to activity change of EVs isolated from cells upon serum deprivation allowed us to identify essential components of siRNA-delivering exosomes. Based on these data we reverse engineered natural exosomes into artificial exosomes consisting of dioleoyl-phosphatidylcholine, cholesterol, dilysocardiolipin, Rab7, AHSG and Desmoplakin. These artificial exosomes reproduced efficient siRNA delivery of natural exosomes both in vitro and in vivo. Artificial exosomes may facilitate manufacturing, quality control and cargo loading challenge that currently impede the therapeutic EV field

Kinerja Badan Permusyawaratan Desa dalam Penyelenggaraan Pemerintahan Desa

Badan Permusyawaratan Desa merupakan mitra pemerintah desa yang solid dalam membangun dan mensejahterakan rakyat. Pemerintah Desa dan Badan Permusyawaratan Desa diharapkan bisa membawa kemajuan dengan memberikan pengarahan dan masukan dalam membangun pemerintahan desa menjadi baik.. Fungsi BPD sebagai lembaga yang menetapkan Peraturan Desa bersama Kepala Desa, serta menampung dan menyalurkan aspirasi masyarakat. Tujuan penelitian untuk menejelaskan fungsi kinerja BPD dalam penyelenggaraan Pemerintahan Desa, hambatan-hambatan yang dihadapi BPD dalam mengoptimalkan kinerjanya dalam penyelenggaraan pemerintahan desa, dan upaya-upaya yang dilakukan BPD untuk mengatasi hambatan-hambatan yang timbul dalam rangka optimalisasi kinerja BPD dalam penyelenggaraan pemerintahan desa. Metode yang digunakan dalam penelitian ini adalah metode penelitian kualitatif dengan pendekatan diskriptif. Metode pengumpulan data dalam penelitian ini adalah metode observasi, wawancara, dan dokumentasi. Metode analisis data kualitatif dilakukan secara interaktif dan berlansung secara terus-menerus sampai tuntas, sehingga datanya lebih menekankan pada aspek pemahaman secara mendalam terhadap suatu masalah. Hasil penelitian menunjukkan, bahwa BPD telah menjalankan kedua fungsinya dengan baik. Hambatan-hambatan yang dihadapi oleh BPD dalam melaksanakan fungsinya disebabkan oleh hambatan internal dan eksternal, telah disikapi secara positif oleh BPD. Namun secara umum BPD sudah berjalan dengan baik,komunikasi yang baik antara BPD dan Pemerintahan Desa, dan masyarakat yang cukup puas dengan kinerja pemerintahan desa.The Village Consultative Body is a solid village government partner in building and prospering the people. The Village Government and the Village Consultative Body are expected to be able to bring progress by providing direction and input in developing a good village government. The function of the BPD is an institution that establishes Village Regulations with the Village Head, and accommodates and channeles community aspirations. The research objective is to explain the function of BPD performance in the implementation of Village Government, the obstacles faced by the BPD in optimizing its performance in the administration of village governance, and the efforts made by the BPD to overcome the obstacles that arise in order to optimize BPD performance in implementing village governance. The method used in this study is a qualitative research method with a descriptive approach. The method of data collection in this study is the method of observation, interviews, and documentation. The method of qualitative data analysis is carried out interactively and runs continuously until complete, so that the data emphasizes more on aspects of deep understanding of a problem. The results of the study show that the BPD has carried out both functions well. The obstacles faced by the BPD in carrying out its functions caused by internal and external barriers, have been responded positively by the BPD. But in general the BPD has been running well, good communication between the BPD and the Village Government, and the community is quite satisfied with the performance of the village administration

Binary Matrix Factorisation via Column Generation

Identifying discrete patterns in binary data is an important dimensionality reduction tool in machine learning and data mining. In this paper, we consider the problem of low-rank binary matrix factorisation (BMF) under Boolean arithmetic. Due to the NP-hardness of this problem, most previous attempts rely on heuristic techniques. We formulate the problem as a mixed integer linear program and use a large scale optimisation technique of column generation to solve it without the need of heuristic pattern mining. Our approach focuses on accuracy and on the provision of optimality guarantees. Experimental results on real world datasets demonstrate that our proposed method is effective at producing highly accurate factorisations and improves on the previously available best known results for 15 out of 24 problem instances

A new frontier in atherosclerotic coronary imaging

Comment on 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.[Lancet. 2014

The role of reactive astrocitose in the chronological evolution of traumatic brain injury

Introduction and objectives. This study aims to investigate whether the cerebral modifications of posttraumatic reactive astrocitose can be considered an objective criterion for determining the age of traumatic cranio-cerebral lesions. Materials and methods. The present study consists of a series of 23 medico-legal cases that underwent autopsy inTeleormanCounty(Romania) Department of Forensic Medicine during 2007–2016, with full immune-histochemical microscopic examination using GFAP staining. The study consists of two groups, a series of 13 cases with cranio-cerebral trauma with different posttraumatic survival periods and 9 cases as a control group. Results and discussions. We discovered GFAP+ reactive astrocytes even when death occurred immediately after the trauma event and up to 4 months after the traumatic incident. We also discovered an intense positive correlation between the density of the GFAP+ cell from the perilesional area and the posttraumatic survival period. The highest cerebral density of the GFAP+ astrocytes occurred with acute death prior (1 to 24 hours) and the lowest in the chronic period (over 2 weeks). Conclusions. The gradual and differentiated appearance of the reactive astrocytes in close relation with the cerebral posttraumatic interval, with specific lesional and perilesional distribution as well as in surrounding area, clearly demonstrates that the state of the reactive astrocitose may constitute an objective index for evaluation of the elapsed time after the posttraumatic event