MicroRNAs as Potential Biomarkers in the Differential Diagnosis of Lipomatous Tumors and Their Mimics

Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests. Recognizing the important role that microRNAs (miRNAs) play in tumorigenesis and their potential utility in tumor classification, we analyzed routine clinical tissue samples of benign and malignant lipomatous tumors, as well as other sarcoma mimics, to identify distinguishing miRNA-based signatures that can aid in the differential diagnosis of these entities. We discovered a 6-miRNA signature that separated lipomas from WDLPS with high confidence (AUC of 0.963), as well as a separate 6-miRNA signature that distinguished DDLPS from their more aggressive histologic mimics (AUC of 0.740). Functional enrichment analysis unveiled possible mechanistic involvement of these predictive miRNAs in adipocytic cancer-related biological processes and pathways such as PI3K/AKT/mTOR and MAPK signaling, further supporting the relevance of these miRNAs as biomarkers for adipocytic tumors. Our results demonstrate that miRNA expression profiling may potentially be used as an adjunctive tool for the diagnosis of benign and malignant adipocytic tumors. Further validation studies are warranted.     

Alchemical Design of Pharmacological Chaperones with Higher Affinity for Phenylalanine Hydroxylase

Phenylketonuria (PKU) is a rare metabolic disease caused by variations in a human gene, PAH, encoding phenylalanine hydroxylase (PAH), and the enzyme converting the essential amino acid phenylalanine into tyrosine. Many PKU-causing variations compromise the conformational stability of the encoded enzyme, decreasing or abolishing its catalytic activity, and leading to an elevated concentration of phenylalanine in the blood, which is neurotoxic. Several therapeutic approaches have been developed to treat the more severe manifestations of the disorder, but they are either not entirely effective or difficult to adhere to throughout life. In a search for novel pharmacological chaperones to treat PKU, a lead compound was discovered (compound IV) that exhibited promising in vitro and in vivo chaperoning activity on PAH. The structure of the PAH-IV complex has been reported. Here, using alchemical free energy calculations (AFEC) on the structure of the PAH-IV complex, we design a new generation of compound IV-analogues with a higher affinity for the enzyme. Seventeen novel analogues were synthesized, and thermal shift and isothermal titration calorimetry (ITC) assays were performed to experimentally evaluate their stabilizing effect and their affinity for the enzyme. Most of the new derivatives bind to PAH tighter than lead compound IV and induce a greater thermostabilization of the enzyme upon binding. Importantly, the correspondence between the calculated alchemical binding free energies and the experimentally determined ΔΔG_b values is excellent, which supports the use of AFEC to design pharmacological chaperones to treat PKU using the X-ray structure of their complexes with the target PAH enzyme.     

5G Based on Cognitive Radio

Both the cognitive radio (CR) and the fifth generation of cellular wireless standards (5G) are considered to be the future technologies: on one hand, CR offers the possibility to significantly increase the spectrum efficiency, by smart secondary users (CR users) using the free licensed users spectrum holes; on the other hand, the 5G implies the whole wireless world interconnection (WISDOM—Wireless Innovative System for Dynamic Operating Megacommunications concept), together with very high data rates Quality of Service (QoS) service applications. In this paper, they are combined together into a “CR based 5G”. With this aim, two novel ideas are advanced: the 5G terminal is a CR terminal and the CR technology is chosen for WISDOM concept. Thus, the 5G takes CR flexibility and adaptability and makes the first step through a commercial and tangible form.     

Strategic justification of advanced manufacturing technology using an extended AHP model

Layered manufacturing has emerged as a highly versatile process to produce complex parts compared with conventional manufacturing processes, which are either too costly to implement or just downright not possible. However, this relatively new manufacturing process is characterized by a few outstanding issues that have kept the process from being widely applied. One such issue is the reduced part accuracy caused by the primitive method of generating the layer contours. Current practice generates the layer contours by simply intersecting a set of parallel planes through the computer model of the design part. The volumetric geometry of each layer is then constructed by extruding the layer contour by the layer thickness in the part building direction. This practice often leads to distorted part geometry due to the unidirectional bias of the extruded layers. This paper proposes a novel scheme to correct the systematic part distortion of layered manufactured parts resulting from the improperly generated layer contours. A new layer contour generation method utilizing the sectional projected data of a point cloud representation of the part surface is introduced. The systematic part distortion is reduced by extruding the outer boundary of the projected point data into the layer volumetric geometry. The boundary contour construction algorithm is able to adapt to changing density of the point set in order to keep the captured level of detail consistent. Specifically devised case studies were carried out to validate the proposed method.     

Modeling of Particle Emission During Dry Orthogonal Cutting

Because of the risks associated with exposure to metallic particles, efforts are being put into controlling and reducing them during the metal working process. Recent studies by the authors involved in this project have presented the effects of cutting speeds, workpiece material, and tool geometry on particle emission during dry machining; the authors have also proposed a new parameter, named the dust unit (D _u), for use in evaluating the quantity of particle emissions relative to the quantity of chips produced during a machining operation. In this study, a model for predicting the particle emission (dust unit) during orthogonal turning is proposed. This model, which is based on the energy approach combined with the microfriction and the plastic deformation of the material, takes into account the tool geometry, the properties of the worked material, the cutting conditions, and the chip segmentation. The model is validated using experimental results obtained during the orthogonal turning of 6061-T6 aluminum alloy, AISI 1018, AISI 4140 steels, and grey cast iron. A good agreement was found with experimental results. This model can help in designing strategies for reducing particle emission during machining processes, at the source.     

An Algorithm to Detect the Presence of 3D Target Motion from ISAR Data

We present an algorithm to detect the presence of 3D target motion from ISAR data. Based on the 3D point scatterer model, we first examine the effect of 3D motion on ISAR imaging. It is shown that existing motion compensation algorithms cannot properly focus targets exhibiting 3D motion during the imaging interval. An algorithm is then derived to blindly detect the degree of 3D target motion from raw radar data. It is based on measuring the linearity of phases between two or more point scatterers on the target. The phase estimation is implemented using the adaptive joint time-frequency technique. Examples are provided to demonstrate the effectiveness of the 3D motion detection algorithm with both simulation and real ISAR data. The detection results are corroborated with the truth motion data from on-board motion sensors and correlated with the resulting ISAR images.     

Indoor Ad Hoc Proximity-Location Sensing for Service Provider Selection

There are protocols that can be used by mobile clients to discover service providers in foreign networks to which they get attached, e.g., SDP of Bluetooth and SLP of IETF. These protocols do address service discovery, but do not address the selection of a service provider among a set of candidates according to a physical proximity of the client and service provider. The goal of the research described in this paper is to integrate proximity-based selection mechanisms to service discovery protocols. We present in this paper protocols that allow nomadic clients to discover and select service providers according to physical proximity.