The Fourth-Century AD Expansion of the Graeco-Roman Settlement of Karanis (Kom Aushim) in the Northern Fayum*

The Graeco-Roman town of Karanis, founded during the Ptolemaic Period in the north-eastern Fayum in the third century bc and long thought to have been abandoned in the third century ad actually saw a substantial expansion during the fourth century AD. With the creation of an 3 extension towards the west and the expansion of the eastern part, the town grew in both directions. We argue that this expansion may be related to a sudden rise of the water level in Lake Moeris (Lake Qarun), perhaps linked to a catastrophic dam breach in the eastern part of the Fayum, and the subsequent relocation of the inhabitants of the low-lying settlements north and east of the lake

Reliability Analysis of an Axial Compressor Based on One-Dimensional Flow Modeling and Survival Signature

This paper presents a procedure for the reliability analysis of a multistage axial compressor regarding blade-specific roughness effects, based on the survival signature approach. As a result, a time-dependent evolution of the system reliability is obtained along with a prioritization technique for monitoring and regeneration of the rough blade rows by capturing the most critical system components. For this purpose, a one-dimensional flow model is developed and utilized to evaluate the aerodynamic influences of the blade-specific roughness on the system performance parameters, namely the overall pressure ratio and the isentropic efficiency. In order to achieve transparency and high numerical efficiency for time-dependent analyses in practice, the physics-based compressor model is translated into an illustrative, function-based system model. This system model is established by conducting a Monte Carlo simulation along with a variance-based global sensitivity analysis, with the input variables being the row-specific blade roughness. Based on the system model, the roughness impact in different blade-rows is ranked by the relative importance (RI) index, and the corresponding time-dependent reliability of the compressor system in terms of pressure ratio and efficiency is estimated through its survival function. Furthermore, uncertainties in the roughness-induced failure rates of the components are modeled using imprecise probabilities. Consequently, bounds on the reliability function and the importance indices for the blade-surface roughness in each blade row are captured, which enhances the decision-making process for maintenance activities under uncertainty.</jats:p

Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease

<p>Abstract</p> <p>Background</p> <p>Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.</p> <p>Results</p> <p>Before aggregation, up-regulation of gene expression predominated, while after aggregates became visible, down-regulation and up-regulation occurred to the same extent. After aggregates became visible there was a down-regulation of dopamine biosynthesis genes accompanied by down-regulation of dopamine levels in culture, indicating the utility of this model to identify functionally relevant pathways. Furthermore, genes of the anti-oxidant Nrf2-ARE pathway were up-regulated, possibly as a protective mechanism. In parallel, we discovered alterations in genes which may result in increased oxidative stress and damage.</p> <p>Conclusion</p> <p>Up-regulation of gene expression may be more important in HD pathology than previously appreciated. In addition, given the pathogenic impact of oxidative stress and neuroinflammation, the Nrf2-ARE signaling pathway constitutes a new attractive therapeutic target for HD.</p

Machine learning in Huntington’s disease:exploring the Enroll-HD dataset for prognosis and driving capability prediction

Background: In biomedicine, machine learning (ML) has proven beneficial for the prognosis and diagnosis of different diseases, including cancer and neurodegenerative disorders. For rare diseases, however, the requirement for large datasets often prevents this approach. Huntington’s disease (HD) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the coding region of the huntingtin gene. The world’s largest observational study for HD, Enroll-HD, describes over 21,000 participants. As such, Enroll-HD is amenable to ML methods. In this study, we pre-processed and imputed Enroll-HD with ML methods to maximise the inclusion of participants and variables. With this dataset we developed models to improve the prediction of the age at onset (AAO) and compared it to the well-established Langbehn formula. In addition, we used recurrent neural networks (RNNs) to demonstrate the utility of ML methods for longitudinal datasets, assessing driving capabilities by learning from previous participant assessments. Results: Simple pre-processing imputed around 42% of missing values in Enroll-HD. Also, 167 variables were retained as a result of imputing with ML. We found that multiple ML models were able to outperform the Langbehn formula. The best ML model (light gradient boosting machine) improved the prognosis of AAO compared to the Langbehn formula by 9.2%, based on root mean squared error in the test set. In addition, our ML model provides more accurate prognosis for a wider CAG repeat range compared to the Langbehn formula. Driving capability was predicted with an accuracy of 85.2%. The resulting pre-processing workflow and code to train the ML models are available to be used for related HD predictions at: https://github.com/JasperO98/hdml/tree/main . Conclusions: Our pre-processing workflow made it possible to resolve the missing values and include most participants and variables in Enroll-HD. We show the added value of a ML approach, which improved AAO predictions and allowed for the development of an advisory model that can assist clinicians and participants in estimating future driving capability.</p

Pioglitazone Decreases Plasma Cholesteryl Ester Transfer Protein Mass, Associated With a Decrease in Hepatic Triglyceride Content, in Patients With Type 2 Diabetes

Thiazolidinediones reduce hepatic steatosis and increase HDL cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3-Leiden.CETP transgenic mice), a decrease in hepatic triglyceride content is associated with a decrease in plasma cholesteryl ester transfer protein (CETP) mass and an increase in HDL levels. Therefore, the aim of the present study was to assess the effects of pioglitazone on CETP mass in patients with type 2 diabetes. We included 78 men with type 2 diabetes (aged 56.5 +/- 0.6 years; HbA1c 7.1 +/- 0.1%) who were randomly assigned to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching placebo, in addition to glimepiride. At baseline and after 24 weeks of treatment plasma HDL cholesterol levels and CETP mass were measured, and hepatic triglyceride content was assessed by proton magnetic resonance spectroscopy. RESULTS Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile range 2.6-17.4] versus 4.1 [1.9-12.3]%, P <0.05), decreased plasma CETP mass (2.33 +/- 0.10 vs. 2.06 +/- 0.10 microg/ml, P <0.05), and increased plasma HDL cholesterol level (1.22 +/- 0.05 vs. 1.34 +/- 0.05 mmol/l, P <0.05). Metformin did not significantly change any of these parameters. A decrease in hepatic triglyceride content by pioglitazone is accompanied by a decrease in plasma CETP mass and associated with an increase in HDL cholesterol levels. These results in patients with type 2 diabetes fully confirm recent findings in mic

Beam Diagnostics Using BPM Signals from Injected and Stored Beams in a Storage Ring

Many modern light sources are operating in top-off injection mode or are being upgraded to top-off injection mode. The storage ring always has the stored beam and injected beam for top-off injection mode. So the BPM data is the mixture of both beam positions and the injected beam position cannot be measured directly. We propose to use dedicated wide band BPM electronics in the NSLS II storage ring to retrieve the injected beam trajectory with the singular value decomposition (SVD) method. The beam position monitor (BPM) has the capability to measure bunch-by-bunch beam position. Similar electronics can be used to measure the bunch-by-bunch beam current which is necessary to get the injection beam position. The measurement precision of current needs to be evaluated since button BPM sum signal has position dependence. The injected beam trajectory can be measured and monitored all the time without dumping the stored beam. We can adjust and optimize the injected beam trajectory to maximize the injection efficiency. We can also measure the storage ring acceptance by mapping the injected beam trajectory

The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice

Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel

Injection Straight Pulsed Magnet Error Tolerance Study for Top-Off Injection

NSLS II is designed to work in top-off injection mode. The injection straight includes a septum and four fast kicker magnets. The pulsed magnet errors will excite a betatron oscillation. This paper gives the formulas of each error contribution to the oscillation amplitude at various source points in the ring. These are compared with simulation results. Based on the simple formulas, we can specify the error tolerances on the pulsed magnets with the goal to minimize the injection transient and scale it to similar machines. The NSLS-II is a 3 GeV third generation synchrotron light source under construction at Brookhaven National Laboratory. Due to its short lifetime, NSLS-II storage ring requires the top-off injection (once per minute) during which the stored beam orbit is highly desired as transparent. But the errors, from the SR pulsed magnets at the injection straight - kickers (non-closed injection bump) and pulsed septum (time-dependent stray field), excite a stored beam betatron oscillation. The magnitude of the perturbation can be large disturning some of the user experiments. In 2010 injection straight review, based on the experts experiences in ALS, DIAMOND, SLS and SPEAR, we came to the conclusion that the acceptable oscillation amplitude at the long straight is set as 100 {micro}m (i.e. 0.7 {sigma}x) in horizontal plane and 12 {micro}m, 2.5 {sigma}y, in vertical plane for NSLS II. This paper gives the analysis estimate of the different error source tolerance from the pulse magnets and scales it to our requirements. The result is compared with simulation

A Storage Ring based Option for the LHeC

The LHeC aims at the generation of hadron-lepton collisions with center of mass energies in the TeV scale and luminosities of the order of $10^{32}-10^{33} cm^{-2} sec^{-1}$ by taking advantage of the existing LHC 7 TeV proton ring and adding a high energy electron accelerator. This paper presents technical considerations and potential parameter choices for such a machine and outlines some of the challenges arising when an electron storage ring based option, constructed within the existing infrastructure of the LHC, is chosen

Abnormalities in reparative function of lung-derived mesenchymal stromal cells in emphysema

Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in COPD. We hypothesized that lung-derived MSCs (LMSCs) from emphysema patients are hampered in their repair capacity, either intrinsically or due to their interaction with the damaged micro-environment. LMSCs were isolated from lung tissue of controls and severe emphysema patients, and characterized at baseline. Additionally, LMSCs were seeded onto control and emphysematous decellularized lung tissue scaffolds and assessed for deposition of extracellular matrix (ECM). We observed no differences in surface markers, differentiation/proliferation potential and expression of ECM genes between control- and COPD-derived LMSCs. Notably, COPD-derived LMSCs displayed lower expression of FGF10 and HGF mRNA, and HGF and decorin protein. When seeded on control decellularized lung tissue scaffolds, control and COPD-derived LMSCs showed no differences in engraftment, proliferation or survival within 2 weeks, with similar ability to deposit new matrix on the scaffolds. Moreover, LMSC numbers and ability to deposit new matrix was not compromised on emphysematous scaffolds. Collectively, our data show that LMSCs from COPD patients compared to controls show less expression of FGF10 mRNA, HGF mRNA and protein and decorin protein, while other features including the mRNA expression of various ECM molecules are unaffected. Furthermore, COPD-derived LMSCs are capable of engraftment, proliferation and functioning on native lung tissue scaffolds. The damaged, emphysematous micro-environment as such does not hamper the potential of LMSCs. Thus, specific intrinsic deficiencies in growth factor production by diseased LMSCs may contribute to impaired alveolar repair in emphysema