Deformation behavior of flexible pavements by finite element simulation

Flexible pavement is usually designed based on certain axle load limits and climatic conditions. The Iraqi code has specified certain load limits per each axle type that should not be exceeded. However, many trucks violate these limits by carrying additional weights to decrease the transportation cost. These overweight trucks cause severe deterioration to the pavement and thus reduce its life. The Iraqi authorities generally charges the violating trucks a penalty based on their weights. This penalty could be very small compared to the damage occurring to the pavement based on these over weights. Also, some trucks may carry huge weights that the pavement may not support, so unloading such trucks could be a suitable solution rather than paying few amounts of money and deteriorating the pavement. The study aims at studying the effect of axle load increase, and the variation in pavement moduli, on the overall pavement life. It also aims to estimate the overweight truck limits that could be penalized or unloaded. The research uses the ABAQUS software conditions to estimate the tensile strains occurring under the asphalt concrete (AC) layer and the compressive strains above the subgrade surface. These computed strains are incorporated in the fatigue cracking and rutting models to estimate the pavement life for different axle weights. Results showed that violating trucks should be unloaded when their weights exceed certain limits

Redesain Museum Airlangga Dengan Pendekatan Simbolik Kerajaan Kediri

Museum Airlangga merupakan museum yang mengelola benda peninggalan masa lalu di Kota Kediri. Museum ini mengelola benda peninggalan dari Kerajaan Kediri mulai awal masa berdiri hingga berakhir pemerintahan Kerajaan Kediri. Museum Airlangga termasuk jenis museum arkeologi karena jenis peninggalan yang termasuk peninggalan sejarah masa lampau. Museum Airlangga yang sekarang dijadikan satu-satunya fasilitas pemerintah kota untuk menampung, memelihara dan menjaga barang arkeologi peninggalan Kerajaan Kediri. Museum Airlangga keadaannya memprihatikan. Kondisi Museum Airlangga memprihatinkan, sebab bagian bangunan di museum tersebut roboh dan tidak kunjung diperbaiki. Museum Airlangga kurang mencerminkan museum kekinian jika ditinjau dari teori seven trend museum. Menjawab permasalahan tersebut, perancangan ulang merupakan salah satu pemecahan yang solutif untuk memecahkan masalah dalam museum. Pengkajian yang mendalam dan hasil evaluasi yang selektif mampu memberikan jawaban sesuai dengan kebutuhan dan ketentuan museum zaman sekarang. Museum Airlangga yang akan dirancang ulang merupakan salah satu ikon Kota Kediri karena merupakan salah satu museum arkeologi terbesar kedua di Jawa Timur. Peninggalan Kerajaan Kediri yang kental di dalam museum membawa filosofi yang kuat sehingga mampu menjadi materi yang kuat dalam merancang ulang museum. Sejarah Kerajaan Kediri merupakan interpretasi dari keberadaaan Kerajaan Kediri sehingga mampu dijadikan simbol yang tepat dalam merancang ulang dengan pendekatan simbolik

The alternate GNB3 splice variant, Gβ3s, exhibits an altered signalling response to EGF stimulation, which leads to enhanced cell migration

It has recently been reported that the duplication of the GNB3 gene has been shown to be directly linked to an obesity phenotype, both in humans and also in a humanised mouse model. Moreover, the common human GNB3 c.825C>T polymorphism (rs5443) causes this ubiquitously expressed gene to be aberrantly spliced approximately 50% of the time leading to the production of both a normal Gβ3 protein and a truncated, possibly less stable subunit, known as Gβ3s. The presence of the GNB3 825T allele has previously been shown to be associated with predisposition to hypertension, obesity, various cancers, Alzheimers, age related cognitive function, erectile dysfunction as well as a marker for pharmacogenetic drug action. Great controversy, however, currently exists as to whether these phenotypes associated with the 825T allele are a) mainly due to the presence of the smaller, possibly more active, Gβ3s subunit or b) merely down to the haploinsufficiency of the normal GNB3 transcript, due to its frequent aberrant splicing. In order to try and address these two conflicting hypothesis, we report on the identification and characterisation of signalling alterations unique to the presence of Gβ3s protein subunit. Moreover we also show the physiological consequences associated with altered signalling, directly induced by the Gβ3s subunit. For this, we used both an EBV transformed lymphoblast cell line homozygote for GNB3 825T/825T (TT) and a stable Gβ3s expressing recombinant COS-7 clone. In both of these cell lines that express the Gβ3s subunit, we found enhanced cytosolic calcium influx upon stimulation with EGF, TGFα and VEGF ligands, as compared to “normal” GNB3 controls with the 825C/825C (CC) genotype. This aberrant calcium influx also led to an increase in ERK, but not AKT1, phosphorylation. Despite the lack of AKT1 activation, we paradoxically observed a significant increase in phosphorylation of its downstream substrates, namely mTOR and p70S6k (KS6B2). Moreover we observed a decrease in phospho FoxO3a only in Gβ3s expressing cells, but not in the “normal” GNB3 (CC) control cell line. The presence of the Gβ3s subunit also appeared to alter the distinct localisation patterns of both Foxo3a and AKT1, while also increasing the colocalisation of mTOR and p70S6K. Subsequent growth factor stimulation studies revealed that EGF treatment, of Gβ3s expressing cells, appeared to cause a significant decrease in cAMP levels, which, in turn resulted in both enhanced caveolin-1a phosphorylation, and an increase in actin stress fibre formation. The identification of these distinct Gβ3s specific signalling alterations were indicative of a more aggressive migratory phenotype. This led us to further investigate and confirm that the presence of the Gβ3s subunit also appears to cause significantly enhanced migration and robust scratch wound healing kinetics, as compared to cells harbouring only the normal copy of the gene. These data therefore present convincing evidence that the Gβ3s subunit is stable, functional and its presence can significantly alter signalling pathways, in different cell types

On Energy, Laplacian Energy and PP-fold Graphs

For a graph $G$ having adjacency spectrum ($A$-spectrum) $\lambda_n\leq\lambda_{n-1}\leq\cdots\leq\lambda_1$ and Laplacian spectrum ($L$-spectrum) $0=\mu_n\leq\mu_{n-1}\leq\cdots\leq\mu_1$, the energy is defined as $E(G)=\sum_{i=1}^{n}|\lambda_i|$ and the Laplacian energy is defined as $LE(G)=\sum_{i=1}^{n}|\mu_i-\frac{2m}{n}|$. In this paper, we give upper and lower bounds for the energy of $KK_n^j,~1\leq j \leq n$ and as a consequence we generalize a result of Stevanovic et al. [More on the relation between Energy and Laplacian energy of graphs, MATCH Commun. Math. Comput. Chem. {\bf 61} (2009) 395-401]. We also consider strong double graph and strong $p$-fold graph to construct some new families of graphs $G$ for which E(G)> LE(G)

Development of a convolutional neural network joint detector for non-orthogonal multiple access uplink receivers

We present a novel approach to signal detection for Non-Orthogonal Multiple Access (NOMA) uplink receivers using Convolutional Neural Networks (CNNs) in a single-shot fashion. The defacto NOMA detection method is the so-called Successive Interference Cancellation which requires precise channel estimation and accurate successive detection of the user equipment with the higher powers. It is proposed converting incoming packets into 2D image-like streams. These images are fed to a CNN-based deep learning network commonly used in the image processing literature for image classification. The classification label for each packet converted to an image is the transmitted symbols by all user equipment joined together. CNN network is trained using uniformly distributed samples of incoming packets at different signals to noise ratios. Furthermore, let’s performed hyperparameter optimization using the exhaustive search method. Our approach is tested using a modeled system of two user equipment systems in a 64-subcarrier Orthogonal Frequency Division Multiplexing (OFDM) and Rayleigh channel. It is found that a three-layer CNN with 32 filters of size 7×7 has registered the highest training and testing accuracy of about 81. In addition, our result showed significant improvement in Symbol Error Rate (SER) vs. Signal to Noise Ratio (SNR) compared to other state-of-the-art approaches such as least square, minimum mean square error, and maximum likelihood under various channel conditions. When the channel length is fixed at 20, our approach is at least one significant Figure better than the maximum likelihood method at (SNR) of 2 dB. Finally, the channel length to 12 is varied and it is registered about the same performance. Hence, our approach is more robust to joint detection in NOMA receivers, particularly in low signal-to-noise environment

NRF2 regulates HER2 and HER3 signaling pathway to modulate sensitivity to targeted immunotherapies

NF-E2 related factor-2 (NRF2) is an essential transcription factor for multiple genes encoding antioxidants and detoxification enzymes. NRF2 is implicated in promoting cancer therapeutic resistance by its detoxification function and crosstalk with proproliferative pathways. However, the exact mechanism of this intricate connectivity between NRF2 and growth factor induced proliferative pathway remains elusive. Here, we have demonstrated that pharmacological activation of NRF2 by tert-butylhydroquinone (tBHQ) upregulates the HER family receptors, HER2 and HER3 expression, elevates pAKT levels, and enhances the proliferation of ovarian cancer cells. Preactivation of NRF2 also attenuates the combined growth inhibitory effects of HER2 targeting monoclonal antibodies, Pertuzumab and Trastuzumab. Further, tBHQ caused transcriptional induction of HER2 and HER3, while SiRNA-mediated knockdown of NRF2 prevented this and further caused transcriptional repression and enhanced cytotoxicity of the HER2 inhibitors. Hence, NRF2 regulates both HER2 and HER3 receptors to influence cellular responses to HER2 targeting monoclonal antibodies. This deciphered crosstalk mechanism reinforces the role of NRF2 in drug resistance and as a relevant anticancer target

Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes

<p>Abstract</p> <p>Background</p> <p>Infection with high-risk type human papilloma viruses (HPVs) is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features.</p> <p>Results</p> <p>Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE). The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23%) of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2%) were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16^INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1); and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27).</p> <p>Conclusion</p> <p>This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.</p

Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of cognitively impaired patients with concomitant cerebral small vessel disease

Introduction: Plasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non-dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (Aβ) burden on plasma NfL are lacking. Methods: Associations were tested between plasma NfL and brain Aβ, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds. Results: We found that participants with either MTA (defined as MTA score ≥2; neurodegeneration [N]+WMH−) or WMH (cut-off for log-transformed WMH volume at 50th percentile; N−WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH−, N−WMH+, and N−WMH− individuals. Discussion: Plasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment

Computation of Space Heating Energy Requirements and Comparative Analysis of Three Cold Desert Region of Jammu and Kashmir (India) -A Case Study for Solar System Designs

Abstract: The aim of this study is to determine and present heating degree days for three locations in Jammu and Kashmir province of India for solar system designs. The heating energy requirement of a typical residential building of floor area ~100 m 2 in Jammu and Kashmir, has been determined and the heating degree days have been calculated for various base temperatures and are presented in tabular form. The numerical results show that the heat loss from a typical structure in the state is in huge quantity and that can be a significantly reduced in the heating load using well fitted doors and windows