Sinonasal NUT midline carcinoma: A new histological entity.

Nuclear protein in testis (NUT) midline carcinoma is poorly differentiated carcinoma defined by rearrangement of NUT gene on 15 to other genes, usually BRD4 on 19. It is first described in 1991. These tumors are most commonly seen in the mediastinum and 35% occur in head and neck. It is a highly aggressive tumor with a median survival of 7 months because of ineffective chemotherapy and undefined treatment. Hence, we must differentiate these tumors from other poorly differentiated tumors. Here, we present a case of NUT midline carcinoma of 44-year male, who presented with headache and dizziness, confirmed by immunohistochemistry of NUT antibody. The aim of this case report is to increase the awareness about this entity in adults with brief review of relevant literature.

Power Efficient Random Access for Massive NB-IoT Connectivity.

Sensors enabled Internet of things (IoT) has become an integral part of the modern, digital and connected ecosystem. Narrowband IoT (NB-IoT) technology is one of its economical versions preferable when low power and resource limited sensors based applications are considered. One of the major characteristics of NB-IoT technology is its offer of reliable coverage enhancement (CE) which is achieved by repeating the transmission of signals. This repeated transmission of the same signal challenges power saving in low complexity NB-IoT devices. Additionally, the NB-IoT devices are expected to suffer from congestion due to simultaneous random access procedures (RAPs) from an enormous number of devices. Multiple RAP reattempts would further reduce the power saving in NB-IoT devices. We propose a novel power efficient RAP (PE-RAP) for reducing power consumption of NB-IoT devices in a highly congested environment. The existing RAP do not differentiate the failures due to poor channel conditions or due to collision. After the RAP failure either due to collision or poor channel, the devices can apply power ramping or can transit to a higher CE level with higher repetition configuration. In the proposed PE-RAP, the NB-IoT devices can re-ascertain the channel conditions after an RAP attempt failure such that the impediments due to poor channel are reduced. The power increments and repetition enhancements are applied only when necessary. We probabilistically obtain the chances of RAP reattempts. Subsequently, we evaluate the average power consumption by devices in different CE levels for different repetition configurations. We validate our analysis by simulation studies.

Hydralazine modifies Aß fibril formation and prevents modification by lipids in vitro.

Lipid oxidative damage and amyloid ß (Aß) misfolding contribute to Alzheimer's disease (AD) pathology. Thus, the prevention of oxidative damage and Aß misfolding are attractive targets for drug discovery. At present, no AD drugs approved by the Food and Drug Administration (FDA) prevent or halt disease progression. Hydralazine, a smooth muscle relaxant, is a potential drug candidate for AD drug therapy as it reduces Aß production and prevents oxidative damage via its antioxidant hydrazide group. We evaluated the efficacy of hydralazine, and related hydrazides, in reducing (1) Aß misfolding and (2) Aß protein modification by the reactive lipid 4-hydroxy-2-nonenal (HNE) using transmission electron microscopy and Western blotting. While hydralazine did not prevent Aß aggregation as measured using the protease protection assay, there were more oligomeric species observed by electron microscopy. Hydralazine prevented lipid modification of Aß, and Aß was used as a proxy for classes of proteins which either misfold or are modified by HNE. All of the other hydrazides prevented lipid modification of Aß and also did not prevent Aß aggregation. Surprisingly, a few of the compounds, carbazochrome and niclosamide, appeared to augment Aß formation. Thus, hydrazides reduced lipid oxidative damage, and hydralazine additionally reduced Aß misfolding. While hydralazine would require specific chemical modifications for use as an AD therapeutic itself (to improve blood brain barrier permeability, reduce vasoactive side effects, and optimization for amyloid inhibition), this study suggests its potential merit for further AD drug development.

Lipid oxidation and modification of amyloid-ß (Aß) in vitro and in vivo.

Oxidative damage and amyloid-ß (Aß) protein misfolding are prominent features of Alzheimer's disease (AD). In vitro studies indicated a direct linkage between these two features, where lipid oxidation products augmented Aß misfolding. We tested this linkage further, mimicking specific conditions present in amyloid plaques. In vitro lipid oxidation and lipid modification of Aß were thus performed with elevated levels of copper or physiological levels of calcium. These in vitro experiments were then confirmed by in vivo immunohistochemical and chemical tagging of oxidative damage in brains from the PSAPP mouse model of AD. Our in vitro findings indicate that: 1) high levels of copper prevent lipid oxidation; 2) physiological concentrations of calcium reduce 4 hydroxy-2-nonenal (HNE) modification of Aß; and 3) anti-Aß and HNE antibody epitopes are differentially masked. In vivo we demonstrated increased lipid oxidation around plaques but 4) a lack of immunological colocalization of HNE-adducts with Aß. Thus, the lack of colocalization of Aß and HNE-adduct immunostaining is most likely due to a combination of metals inhibiting HNE modification of Aß, quenching lipid oxidation and a masking of HNE-Aß histopathology. However, other forms of oxidative damage colocalize with Aß in plaques, as demonstrated using a chemical method for identifying oxidative damage. Additionally, these findings suggest that HNE modification of Aß may affect therapeutic antibodies targeting the amino terminal of Aß and that metals effect on lipid oxidation and lipid modification of Aß could raise concerns on emerging anti-AD treatments with metal chelators.