Pharmacological reprogramming of macrophages through aptamiRs

Nucleic acid-based molecules have certain advantages over conventional drugs or protein-based target approaches. Chemically synthetized nucleic acids-based molecules are known as aptamers. They are selected from a combinatorial oligonucleotide library in a unique way called "SELEX" (systematic evolution of ligands by exponential enrichment). These are single-stranded oligonucleotides with specific three-dimensional configuration. They can be bound to their specific target with high affinity and specificity. Recently, aptamers targeting mammalian cells have emerged as potential candidates for use as delivery vehicles. Numerous therapeutic agents including miRNA, siRNA, peptides, proteins, nanoparticles, and chemotherapeutics can be delivered into the cells via cell-targeting aptamers. Macrophages and dendritic cells (DCs) play a vital role in the immune response. These cells are involved in physiological and pathological processes in the body. DCs are considered to be one of the most potent ―professional‖ antigen presenting cells (APCs) and have the properties to present endogenous or foreign antigens on their surfaces for the activation of T cells. Therefore, DC-based vaccines designed for activation and proliferation of T cells have significant immunotherapy-related importance. On the other side, macrophages play a key role in different diseases including chronic inflammation. miRNA 125a-5p is highly upregulated in chronic inflammatory macrophages and may have an impact on the polarization of macrophages or on the condition of the disease. In the current study, it was explored that an aptamer targeting immune cells could be used as a delivery vehicle. Herein, Next generation sequencing (NGS) data of murine bone marrow-derived DCs cell-SELEX was used to identify a promising aptamer targeting macrophages and DCs. DC 12 aptamer has been identified and characterized as a promising and suitable delivery vehicle. It has been shown that DC 12 aptamer is non-immunogenic and internalizes into the cells. The study found that DC 12 aptamer guided uptake of antagomir 125a-5p may end up in the endosomal compartment of macrophages, thereby limiting its inhibitory effect. However, DC 12 has the potential to deliver OT-I peptide into the desired processing compartment of BM-DCs for the targeted activation of CD8 T cells. In summary, aptamers have the potential to replace other carrier molecules, but further investigation will be needed as regards the delivery of the cargo into the cell cytoplasm

Exploring Computational Complexity Of Ride-Pooling Problems

Ride-pooling is computationally challenging. The number of feasible rides grows with the number of travelers and the degree (capacity of the vehicle to perform a pooled ride) and quickly explodes to the sizes making the problem not solvable analytically. In practice, heuristics are applied to limit the number of searches, e.g., maximal detour and delay, or (like we use in this study) attractive rides (for which detour and delay are at least compensated with the discount). Nevertheless, the challenge to solve the ride-pooling remains strongly sensitive to the problem settings. Here, we explore it in more detail and provide an experimental underpinning to this open research problem. We trace how the size of the search space and computation time needed to solve the ride-pooling problem grows with the increasing demand and greater discounts offered for pooling. We run over 100 practical experiments in Amsterdam with 10-minute batches of trip requests up to 3600 trips per hour and trace how challenging it is to propose the solution to the pooling problem with our ExMAS algorithm. We observed strong, non-linear trends and identified the limits beyond which the problem exploded and our algorithm failed to compute. Notably, we found that the demand level (number of trip requests) is less critical than the discount. The search space grows exponentially and quickly reaches huge levels. However, beyond some level, the greater size of the ride-pooling problem does not translate into greater efficiency of pooling. Which opens the opportunity for further search space reductions.Comment: 13 pages, 7 figures, Submitted to The Transportation Research Board (TRB), Annual Meeting (102nd

RADIOLOGICAL AND PATHOLOGICAL CORRELATION OF LUNG NODULES IN A BACKGROUND OF METASTATIC DISEASE

Background: Computed tomography (CT) imaging has improved the chances of detecting small indeterminate (<1 cm) lung nodules. The determination of the underlying malignant or benign nature of a lung nodule poses a great diagnostic challenge and depends on a number of factors, including the radiographic appearance of nodule, the presence of non-pulmonary metastases, characteristics of growth and histological criteria. Methods: The medical records of 89 patients admitted to our specialist cancer centre between 2008 and 2013 were reviewed. Patients of all age groups and tumour category were included in the study. Clinical data of these patients were collected and the following parameters were analysed: Radiographic diagnosis, location, size, laterality and number of nodules and histological impression. The radiological findings were then correlated with histopathological findings. The nodules were sub-classified into groups on the basis of size (A = 0–0.5 cm; B = 0.5–0.9 cm; C = 1.0–1.5 cm and D = >1.5 cm). Results: CT scan reports of 89 patients with lung nodules were reviewed. On radiology, 73/89 (82%) were reported to be malignant nodule. Histopathological review of the biopsies of these 89 nodules confirmed malignancy in 50/89 (56.2%) patients. CT scan was found to be highly sensitive (94%, 95% confidence interval [CI]: 83.43–98.68%) but with a very low specificity (33.3%, 95% CI: 19.10–50.22%). CT scan was found to have a higher negative predictive value (81.2%, 95% CI: 54.34–95.73%) and a lower positive predictive value 64.4% (95% CI: 52.31–75.25%) when correlated with histopathological findings. Pathology of these nodules included metastatic sarcoma (27/89; 30.3%) and carcinoma (18/89; 20.2%). The frequency of the biopsy-proven malignant nodules on the right side was 26/45 (57.8%) and on the left side was 24/44 (54.5%) (P = 0.832). Malignant nodules were more frequent in lower lobes (28/43, 65.1%) than in upper lobes (14/32, 43.8%). These two sites combined accounted for 84% of all malignant nodules. There was a significant correlation between nodule size and likelihood of underlying malignancy. The overall prevalence of malignancy in the larger nodules (C and D) was much higher (23/30 and 76.7%) compared to the smaller sized (A and B) nodules (27/58 and 46.8%), P < 0.05.Conclusion: CT scan is a useful tool in the initial clinical assessment of indeterminate lung nodules with high sensitivity (94%) and a high negative predictive value (81.2%).Key words: Computed tomography, fibrosis, indeterminate lung nodule, infection, lung nodule, malignancy, metastase

SOLITARY FIBROUS TUMOR OF BREAST

Solitary fibrous tumours (SFTs) are fibroblastic mesenchymal tumour primarily identified in the pleura but are now being reported in other anatomic sites as well. SFT is generally characterised as a radiologically confined neoplasm composed of a proliferated spindle cells arranged in patternless manner. Intervening tissue shows prominent haemangiopericytoma-like vessels. Stroma is usually fibrous. Tumour is positive for CD34. SFT has a specific translocation representing fusion NAB2 with STAT6 genes. This translocation can be highlighted with very good specificity and sensitivity using STAT6 immunohistochemical stain. Some cases of SFTs have also been described in the breast. Rarely, SFT can show aggressive behaviour. SFT enters the differential diagnoses of benign and malignant spindle cell tumours of breast and it is, therefore, important that its clinical, radiological and pathological features are known to clinicians and diagnosticians. Key words: CD34, myofibroblastoma, NAB2-STAT6, solitary fibrous tumou

Flow-Aware Elephant Flow Detection for Software-Defined Networks

Software-defined networking (SDN) separates the network control plane from the packet forwarding plane, which provides comprehensive network-state visibility for better network management and resilience. Traffic classification, particularly for elephant flow detection, can lead to improved flow control and resource provisioning in SDN networks. Existing elephant flow detection techniques use pre-set thresholds that cannot scale with the changes in the traffic concept and distribution. This paper proposes a flow-aware elephant flow detection applied to SDN. The proposed technique employs two classifiers, each respectively on SDN switches and controller, to achieve accurate elephant flow detection efficiently. Moreover, this technique allows sharing the elephant flow classification tasks between the controller and switches. Hence, most mice flows can be filtered in the switches, thus avoiding the need to send large numbers of classification requests and signaling messages to the controller. Experimental findings reveal that the proposed technique outperforms contemporary methods in terms of the running time, accuracy, F-measure, and recall

Mass transfer efficiency of a tall and low plate free area liquid pulsed sieve-plate extraction column

Acknowledgements The authors would like to acknowledge Chakwal group of industries for funding the project. Ms. Madiha, Ms. Zona, Mr. Sohaib, Mr. Abdullah, Mr. Mudassar, and Mr. Salahuddin also deserve our acknowledgements for their assistance in different ways.Peer reviewedPublisher PD

Nocardia Brain Abscess In A Patient With Advanced HIV-AIDS: Case Report

Nocardia is a gram-positive bacterium that causes localised and disseminated infections. A rare case of Nocardia infection in an immunocompromised individual is presented. Nocardiosis should be kept in mind as a diagnosis in immunocompromised patients with a solitary space occupying lesion in the brain

Integrability Properties of the Slepyan-Palmov Model Arising in the Slepyan-Palmov Medium

This study investigates the Slepyan-Palmov (SP) model, which describes plane longitudinal waves propagating within a medium comprising a carrier medium and nonlinear oscillators. The primary objective is to analyze the integrability properties of this model. The research entails two key aspects. Firstly, the study explores the group invariant solution by utilizing reductions in symmetry subalgebras based on the optimal system. Secondly, the conservation laws are studied using the homotopy operator, which offers advantages over the conventional multiplier approach, especially when arbitrary functions are absent from both the equation and characteristics. This method proves advantageous in handling complex multipliers and yields significant outcomes

Impact of Firm Size on Earnings Management; A Study of Textile Sector of Pakistan

The study was conducted to evaluate the impact of firm size on earnings management for the textile sector of Pakistan. For this purpose annual ten years data was obtained from 2004 to 2013 for fifty selected firms from the textile sector of Pakistan. Natural logarithm of total assets was used as the proxy of firm size. On the other hand earning management was the dependent variable of this study. Earnings management was measured through discretionary accruals by using modified Jones model. Descriptive statistics, correlation and panel data analysis was used for capturing the impact of firm size on earnings management. The statistical results of this study revealed that there is positive and significant impact of firm size on earnings management. Keywords: Firm Size, Discretionary Accruals, Earnings Management, Karachi Stock Exchang