Abstract Background: Prostate cancer (PCa) poses unique challenges for Non-Hispanic Black Americans (BA), who often face poorer outcomes than Non-Hispanic White Americans (WA). Even after adjusting for socioeconomic factors, BAs are diagnosed younger and experience more severe clinical effects, potentially due to the tumor microenvironment. Within PCa, Endogenous Retroviruses (ERVs) have been shown to regulate immune response genes and have prognostic value in PCa. Despite constituting 8% of the human, ERVs' role in the tumor microenvironment remains incompletely understood. These findings highlight the need to target microenvironment dysregulation in solid tumor therapies, especially for ERV expression in prostate cancer. Methods: Using RNA-sequencing, we investigated the expression of ERVs in BA (n=18) and WA (n=14) tumor adjacent stroma (TAS) samples. We analyzed reads by mapping them to the human genome (hg38). We then used bedtools and data from the Human Endogenous Retrovirus database (HERVd) to calculate the number of reads at each ERV locus (n=519,060). Differentially expressed ERV elements were then identified in an Audic Claverie Test (fold- change cutoff of 2 and padj < 0.05). The expression of protein-coding genes in the same BA (n=18) and WA (n=14) TAS samples was investigated using RNA-sequencing. Regulation of significant ERV elements were compared to the regulation of nearby immune response genes between the two races. We developed primary stroma (carcinoma associated fibroblast, CAFs) culture of different races with PCa using fresh prostatectomy tissues. To investigate the biological functions of ERVs in CAFs, we developed FANA oligonucleotides (synthetic single- stranded nucleic acid analogs that can modulate gene expression by enzymatic degradation of a target RNA) and corresponding primers to knock down specific ERV sequences near key immune response genes in prostate cancer. Results: We examined 32 prostatectomy specimens of BA (n=18) and WA (n=14) PCa. Of the 5,786 statistically significant differentially expressed ERV elements between BA and WA TAS that were identified, 3,274 elements had an increase in ERV expression for BA TAS, and 2,512 elements had a decrease in ERV expression for BA TAS. 61 MER41 elements were found to be differentially expressed between the two races. The MER family sequences contain binding sites for transcription factors that are crucial in cancer, such as STAT1. This transcription factor can regulate genes involved in cell proliferation, apoptosis, and DNA repair. MER41 is in close proximity (within 5000 base pairs) to IFNA6, an immune response gene. We found both MER41 and IFNA6 to be downregulated in BA TAS, as compared to their WA counterparts. We developed FANA oligonucleotides to knockdown MER41E, MER61-Int, HERVL-Int, MLT1A, and LTR61E1 to investigate their effect on nearby gene expression. Conclusion: The CAF models from PCa patients of different races can be used to explore the biological function of ERV inactivation on anti-tumor immune response genes within the tumor microenvironment. Citation Format: Tara S. K. Jennings, Vinay Kumar, Anton N. Nguyen, Michael M. Ittmann, Patricia Castro, Farah Rahmatpanah. Transcriptome analysis of human endogenous retroviral elements in tumor microenvironment of prostate cancer patients of different ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C092.

Abstract Background: Non-Hispanic Black American patients (BA) with prostate cancer (PCa) tend to fare worse than their Non-Hispanic White American counterparts (WA), even with consideration of socioeconomic disparities. Clinically, BA face diagnosis at younger age with worse clinical outcomes. Stromal cells adjacent to the tumor, including carcinoma-associated fibroblasts (CAFs), play a critical role in tumorigenesis of PCa. Dysfunction in the tumor microenvironment play a crucial role in mediating prostate cancer tumorigenesis and is emerging as a key target for cancer therapy in solid tumors. Methods: To investigate whether DNA methylation varies in tumor adjacent stroma (TAS) among PCa patients with different geographical ancestries, areas immediate adjacent to tumor (i.e., less than 1mm) removed for methylation analysis. A complete genome-wide DNA methylation of PCa stroma using 17 BA and 15 WA patients who had radical prostatectomy was carried out. Methyl-Captured (mCap) sequencing data was generated for TAS of prostate cancer FFPE tissues. Methylated sites were identified with the MACS2 callpeak function using a band width of 300 bp and a false discovery rate of q < 0.05. A consensus peak set was derived from the aligned reads of BA and WA prostate cancer stroma samples that were sequenced. Pathway analysis was performed using Ingenuity Pathway Analysis (IPA) tools. CAFs from primary tumors of BA and WA was prepared by tissue culture and treated with demethylating agent (i.e., 5-Azacytidine) for 24 hours followed by maintenance of the cells in drug-free medium for 7-10 days and subjected to mCap sequencing. Results: We found racial disparities in genome-wide DNA methylation in TAS between the two populations in which BA PCa patients had significantly increased in global DNA methylation as compared to their WA counterpart (p value < 0.001). Hypomethylation occurred in CAFs from BA patients treated with 5-Azacytidine. We identified 1041 methylated sites corresponding to 409 unique genes that were differentially methylated in BA vs WA (p value < 0.05). Pathway analysis identified significant association between methylated genes in BA TAS and immune response pathways including IL-13, JACK/STAT, T cell receptors, NF-KB, and PD-1, PDL1 cancer immunotherapy. Evaluation of the methylome profile between patients based on the post-prostatectomy resection margins, negative (R0) vs positive (R1), showed that R0 resections had significantly greater (p value < 0.001) methylation than R1 resections. Further analysis identified 984 sites corresponding to 373 differentially methylated, unique genes (p value < 0.05). Conclusion: Tumor-adjacent stroma of BA prostate cancer patients has a distinct methylome as compared to WA patients. Differences in immune response pathways suggests a distinct immune response in TAS in men of different races. Citation Format: Santosh Sankaran, James Nguyen, Tara Jennings, Vinay Kumar, Michael B. Lilly, Michael M. Ittmann, Patricia Castro, Liankun Song, Thomas Keane, Weiping Chu, Xiaolin Zi, Omid Yazdanpanah, Arash Rezazadeh Kalebasty, Farah Rahmatpanah. Tumor-microenvironment from African-American prostate cancer exhibit methylation of multiple immune modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2148.

Abstract Introduction. Prostate cancer (PCa) of American men of African ancestry (AA) is diagnosed at an earlier median age and more advanced stage with a poorer prognosis and significantly higher mortality than in Americans of primarily Northern European ancestry (EA). The mechanism of how ancestry contributes to aggressive PCa in AA patients is not well understood. Given the inherent heterogeneity and multifocality of prostate cancer, Spatial transcriptomics is of particular interest because it allows distinct cell populations within the tumor microenvironment to be characterized, and their possible effects on local tumors to be identified. Here we compare transcription between four AA and four EA patients in regions of peritumoral stroma, inflammation, Benign Prostatic Hyperplasia (BPH), and Gleason score patterns 3 (G3) and 4 (G4). Methods: Formalin fixed, paraffin embedded (FFPE) prostatectomy tissue blocks were obtained from 8 patients (4 AA and 4 EA) prior to treatment of the patients and matched for clinical variables (i.e., biochemical relapse, age, Gleason score, and tumor stage). 10um tissue sections were mounted onto Visium Spatial Gene Expression Slides and processed following 10x Genomics protocol. Sample counts were processed through Space Ranger. 18000 unique genes, spatial barcodes, and clinician guided annotations were imported to the R program Seurat. Data was processed using SCTransform. Significance of each transcript differences between each tissue were calculated. Results: Digital histologic slides of prostate cancer specimens from AA (n=4) and EA (n=4) patients were annotated by a urologic pathologist to identify regions of peritumoral stroma, inflammation, BPH, G3, and G4. Each spot was interrogated for the expression of 18000 transcripts, with an average of 17796 being detected per spot. Among the largest differences observed between AA and EA, G3 and G4 had distinct transcriptome profiles in the four AA as compared to G3 and G4 in four EA. Also, when differential expression (padj < 0.05) in peritumoral stroma was compared to G4 in AA, we identified 290 differentially expressed genes, whereas the same comparison in EA cohorts identified 600 differentially expressed genes. Conclusion: Spatial transcriptomic analysis revealed differences in gene expression across multiple tissue types in prostate cancer patients of different ancestries. Citation Format: Vinay Kumar, Dominic Castaneda, James A. Nguyen, Giovanna A. Giannico, Michael M. Ittmann, Patricia Castro, Omid Yazdanpanah, Arash Rezazadeh, Tara S. Jennings, Michael Mcclelland, Farah Rahmatpanah. Spatial transcriptomic analysis of histologically matched regions adjacent to and within prostate cancer reveals RNA expression differences between African Americans and European Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2150.

Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have integrated into the human genome. Using publicly available RNA-seq data from 63 cervical cancer patients, we investigated the expression of ERVs in cervical cancers. Four aspects of cervical cancer were investigated: patient ancestral background, tumor HPV type, tumor stage and patient survival. Between the racial subgroups, 74 ERVs were significantly differentially expressed, with Black Americans having 30 upregulated and 44 downregulated (including MER21C, HERV9-int, and HERVH-int) ERVs when compared to White Americans. We found that 3313 ERVs were differentially expressed between HPV subgroups, including MER41A, HERVH-int and HERVK9. There were 28 downregulated (including MLT1D and HERVH-int) and 61 upregulated (including MER41A) ERVs in locally advanced-stage compared to early-stage samples. Tissue microarrays of cervical cancer patients were used to investigate the protein expression of ERVs with protein coding potential (i.e., HERVK and ERV3). Significant differences in protein expression of ERV3 (p = 0.000905) were observed between early-stage and locally advanced-stage tumors. No significant differential expression at the protein level was found for HERVK7 (p = 0.243). We also investigated a prognostic model, supplementing a baseline prediction model using FIGO stage, age and HPV positivity with ERVs data. The expression levels of all ERVs in the HERVd were input into a Lasso-Cox proportional hazards model, developing a predictive 67-ERV panel. When ERVs expression levels were supplemented with the clinical data, a significant increase in prognostic power (p = 9.433 × 10−15) relative to that obtained with the clinical parameters alone (p = 0.06027) was observed. In summary, ERV RNA expression in cervical cancer tumors is significantly different among racial cohorts, HPV subgroups and disease stages. The combination of the expression of certain ERVs in cervical cancers with clinical factors significantly improved prognostication compared to clinical factors alone; therefore, ERVs may serve as future prognostic biomarkers and therapeutic targets. Novelty and Impact: When endogenous retroviral (ERV) expression signatures were combined with currently employed clinical prognosticators of relapse of cervical cancer, the combination outperformed prediction models based on clinical prognosticators alone. ERV expression signatures in tumor biopsies may therefore be useful to help identify patients at greater risk of recurrence. The novel ERV expression signatures or adjacent genes possibly impacted by ERV expression described here may also be targets for the development of future therapeutic interventions.

Objectives: Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that gained access to germline cells allowing integration into the human genome. Emerging data suggest that some ERVs may become activated allowing epigenetic alterations through DNA methylation or histone modification, which can further alter gene regulation. This may serve as a targeted therapeutic opportunity in modulating oncogenesis, through aberrant oncogene activation or tumor suppressor gene inactivation. This is an emerging area of exploration in ovarian cancer. Methods: We applied our ERV mapping tools (1) to RNA-seq data from 24 female patients with ovarian, fallopian tube, or primary peritoneal cancers to investigate expression of ~550,000 ERV elements from the Human Endogenous Retrovirus database (HERVd) (2, 3). Univariate Cox regression models were constructed with normalized ERV expression data and the most significantly differentially expressed ERVs were then filtered using a penalized Lasso-Cox proportional-hazards model. ERV expression, alongside the available clinical data (including age, histotypes, and tumor stage) were provided as inputs and linear predictors generated by the model separated samples into either high or low risk categories. We identified a panel of 15 predictive ERVs and these risk evaluations allowed for Kaplan-Meier analyses of survival by clinical parameters alone versus combined with ERV signature. We also performed a secondary analysis of platinum resistant ovarian cancers using RNA-seq data (GSE102118) to investigate the effect of demethylating agent guadecitabine on ERV expression (n=9) (4). Results: Exploratory analyses of ERVs demonstrated significantly different expression between histologies (clear cell, mucinous, endometrioid, high grade serous) and FIGO disease stage. In our prognostic model, Kaplan-Meier survival analysis using only clinical parameters resulted in a significance level of 0.0013, however the supplemented model combining the 15-ERV panel and the clinical data discriminated the two risk groups for time to recurrence at a much higher significance level of p = 7.076 × 10−8. Included in the 15 ERV panel are HERVK, HERV3, and several putative ERV promoters including LTR12, LTR7, LTR3 and LTR4 (5). In our secondary analysis of platinum-resistant patients, the ERV transcripts were compared for each patient pre- and post-guadecitabine treatment and there were several ERVs with risk-predictive values induced in patients receiving guadecitabine including LTR7, LTR12 and HERVK. Conclusions: In summary, ERV RNA expression in ovarian cancer is significantly different between histologies and disease stages. The ability to successfully classify patients as either high-risk or low-risk for disease progression is of considerable value for patient management and ERVs may improve prognostication and guide future therapeutic targeting. Citation Format: Jill Alldredge, Vinay Kumar, Brook Sanders, Farahnaz Rahmatpanah. Endogenous human retroviruses in epithelial ovarian cancers: An exploratory analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6219.

The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue. Differential expression of an immunology/oncology protein panel (n = 58) was measured. OX40L and CTLA4 were expressed at higher levels while 22 other proteins, including CD11c, were expressed at lower levels (FDR < 0.2 and p-value < 0.05) in TAS as compared to tumor epithelia. A tissue microarray analysis of 97 patients with 1547 cores found positive correlations between high expression of CD11c and increased time to recurrence in tumor and TAS, and inverse relationships for CTLA4 and OX40L, where higher expression in tumor correlated with lower time to recurrence, but higher time to recurrence in TAS. Spatial transcriptomic analysis using a Cancer Transcriptome Atlas panel (n = 1825 genes) identified 162 genes downregulated and 69 upregulated in TAS versus tumor, 26 downregulated and 6 upregulated in CD45+ TAS versus CD45+ tumor. We utilized CIBERSORTx to estimate the relative immune cell fractions using CD45+ gene expression and found higher average fractions for memory B, naïve B, and T cells in TAS. In summary, the combination of protein expression differences, immune cell fractions, and correlations of protein expression with time to recurrence suggest that closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.

Naso-endoscopy, inspect the entire nasal cavity (NC) to objectively identify a clearer NC, however, being invasive it is uncomfortable to patients. Hence, a non-invasive alternative is required, which objectively identifies clearer NC. Nasal MRI is a non-invasive alternative technique that precisely and objectively recognizes a clearer NC. Hence, this study was planned to find the utility and reliability of MRI for the identification of clearer NC. In this prospective observational study, Cohen's kappa interrater agreement with linear weights test was used to assess the reliability of MRI assessment in assigning clearer NC by finding the agreement between MRI and naso-endoscopy for the identification of clearer NC. As smooth negotiation through the assigned clearer NC, predicts the actual success of an assessment technique perfectly. So, the agreement between MRI assigned clearer NC with ultimate NC of tube negotiation was evaluated. We found an excellent agreement between the MRI and naso-endoscopy for the identification of clearer NC (ĸ = 0.91, 95%CI 0.83–0.97). Similarly, excellent agreement was found for MRI classified clearer NC and the NC through which tube was ultimately negotiated (k = 0.97, 95%CI 0.93–1.00). We found nasal MRI as a useful assessment technique that objectively identifies a clearer NC and eases out tube negotiation. NCT03675698 and 09/17/2018.

Objectives Endogenous human retroviruses (ERVs) are remnants of exogenous retroviruses that have been integrated into the human genome. Some ERVs may become activated allowing epigenetic alterations through DNA methylation or histone modification, which can further translate into altered gene regulation or transcription. This is a novel area of exploration in cervical cancer. Methods We applied ERV mapping tools to RNA-seq data from 63 cervical cancers to investigate expression of ~550,000 ERV elements from the Human Endogenous Retrovirus database (HERVd) to investigate ERV expression among various cohorts. We also investigated a prognostic model, supplementing a baseline prediction model using FIGO stage, age and HPV-positivity with ERVs. Results 98 ERVs were differentially expressed (padj < 0.1), with Black American patients having 40 upregulated and 58 downregulated (including MER21C, HERVH-int) ERVs when compared to white American patients. Of the 138 ERVs differentially expressed between early-stage and locally advanced-stage groups, 38 were upregulated, including ERV3, and 100 were downregulated. 26,916 ERVs were differentially expressed between HPV positive and negative cohorts. There were significant differences in ERV3 protein expression (p = 0.000905). While clinical parameters are predictive of progression free survival at p = 0.06027, our supplemented model combining a 67-ERV panel and the clinical data, discriminated the two risk groups at p = 9.433 x 1015. Conclusions ERV RNA expression differences in cervical cancers is significantly different among racial cohorts, HPV-subgroups and disease stages. The correlation of ERV expression alongside clinical factors significantly improves prognostication when compared to clinical factors alone and may serve as future therapeutic targets.

Endogenous retroviruses (ERVs) are abundant, repetitive elements dispersed across the human genome and are implicated in various diseases. We investigated two potential roles for ERVs in prostate cancer (PCa). First, the PCa of Black Americans (BA) is diagnosed at an earlier median age and at a more advanced stage than the PCa of White Americans (WA). We used publicly available RNA-seq data from tumor-enriched samples of 27 BA and 65 WA PCa patients in order to identify 12 differentially expressed ERVs (padj < 0.1) and used a tissue microarray of the PCa cores from an independent set of BA and WA patients to validate the differential protein expression of one of these ERVs, ERV3-1 (p = 2.829 × 10−7). Second, we used 57 PCa tumors from patients of all ancestries from one hospital as a training set to identify the ERVs associated with time to biochemical relapse. A 29-ERV prognostic panel was then tested and validated on 35 separate PCa tumors from patients obtained in two different hospitals with a dramatic increase in prognostic power relative to clinical parameters alone (p = 7.4 × 10−11). In summary, ERV RNA expression differences in the prostate tumors of patients of different ancestries may be associated with dissimilarities in the mechanism of cancer progression. In addition, the correlation of expression of certain ERVs in prostate tumors with the risk of biochemical relapse indicates a possible role for ERV expression in cancer progression.

Prostate cancer (PCa) in Black Americans (BA) is diagnosed at an earlier median age and a more advanced stage than PCa in White Americans (WA). Tumor-adjacent stroma (TAS) plays a critical role in tumorigenesis of prostate cancer. We examined RNA expression in both tumor and TAS of BA compared to WA. After evaluating the geographical ancestry of each sample, preliminary analysis of our own RNA-seq data of 7 BA and 7 WA TAS revealed 1706 downregulated and 1844 upregulated genes in BA relative to WA PCa patients (p adj < 0.05). An assessment of published RNA-seq data of clinically matched tumor-enriched tissues from 15 BA and 30 WA patients revealed 932 upregulated and 476 downregulated genes in BA relative to WA (p adj < 0.05). When TAS and tumor epithelial cohorts were compared for the top 2500 statistically significant genes, immune responses were downregulated in BA vs WA TAS, while T cell-exhaustion pathways and the immune checkpoint gene CTLA4 were upregulated in BA vs WA tumors. We found fewer activated dendritic cells in tumor and more CD8 T-cells in TAS of BA versus WA PCa patients. Further characterization of these differences in the immune response of PCa patients of distinct geographical ancestry could help to improve diagnostics, prognostics, and therapy.

Vehicular Ad-hoc network (VANET) is one of the emerging technologies for research community to get various research challenges to construct secured framework for autonomous vehicular communication. The prime concern of this technology is to provide efficient data communication among registered vehicle nodes. The several research ideas are implemented practically to improve overall communication in VANETs by considering security and privacy as major aspects of VANETs. Several mechanisms have been implemented using cryptography algorithms and methodologies. However, these mechanisms provide a solution only for some restricted environments and to limited security threats. Hence, the proposed novel mechanism has been introduced, implemented and tested using key management technique. It provides secured network environment for VANET and its components. Later, this mechanism provides security for data packets of emergency messages using cryptography mechanism. Hence, the proposed novel mechanism is named Group Key Management & Cryptography Schemes (GKMC). The experimental analysis shows significant improvements in the network performance to provide security and privacy for emergency messages. This GKMC mechanism will help the VANET user’s to perform secured emergency message communication in network environment.

In the present study, the performance of raw sawdust (RSD) as a biosorbent was assessed for the removal of model dyes (MB-Methylene blue and CR-Congo red) in single as well as binary systems under various wastewater conditions. Biosorption studies in single system under simulated wastewater conditions showed highest uptake of MB and CR taking place at pH 6 and 2, respectively. pH and FTIR studies revealed the binding to be electrostatic in nature, while a inter-particle diffusion mechanism was found to be operative. Irrespective of the nature of the dye, equilibrium was found to be achieved within 60 mins. Biosorption studies carried out in binary systems under similar experimental conditions in simulated wastewater showed no significant difference in the removal efficiency. This could be attributed to the fact that there is no competitive relationship between the cationic (MB) and anionic (CR) dyes when present simultaneously in the wastewater. On the other hand, the results as obtained under real wastewater binary system reveal lower removal capacity for the removal of the dyes which could be due to competitive adsorption of organic pollutants as verified by a 50 % reduction in COD in the real wastewater. Irrespective of the wastewater conditions, isotherm studies showed that at lower adsorbate concentrations, the Langmuir model was operative while the Freundlich model showed higher correlation at higher adsorbate concentrations. Experimental results thus verify the usefulness of RSD as an economic, cost effective and potential biosorbent for the removal of dyes from diverse wastewater conditions

VANET is a next generation communication technology where vehicles create an autonomous network with assistance of RSU (Road Side Units). VANET provides legitimate information to the users on the road, in order to increase the road and user's safety. It provides useful information to the vehicles about directions, location mapping, premises, etc. The fast propagation of emergency and local warning messages to the approaching vehicles will be helpful for preventing secondary accidents. If security of the network is not guaranteed, several attacks may occur, thereby alert messages may not reach to the RSUs on time or message may get spoof due to attack on it. Major attacks on emergency messages such as timing attack, spoofing attack, DoS attack, Sybil attack, etc. would be considered to mitigate and make the communication and infrastructure more secure. One of the major emergency message attack is Sybil, which is used by selfish message propagators to claim authenticity of their message by propagating with multiple identities. By deceiving other nodes with their false support using multiple identifies, they can achieve various purpose in network like vehicle rerouting, speed shift etc. This work proposes a RSU cooperative detection mechanism involving triangulation and fake propagation by RSU to identify the Sybil attacks in the VANET. The proposed methodology secures fast communication emergency messages to prevent secondary accidents by validating the message sources, nodes will accept only the messages from RSU which are digitally signed and source validated against Sybil nodes. The performance evaluation is made with existing methodology and effectiveness of the proposed methodology results demonstrated in article. The spatial location and trajectory of attacker is learnt effectively with RSU cooperation in the proposed work.

Vehicular Ad-hoc network (VANET) has gained huge attraction from research community due to their significant nature of providing the autonomous vehicular communication. The efficient communication is considered as prime concern in these networks however, several techniques have been introduced to improve the overall communication of VANETs. Security and privacy are also considered as prime aspects of VANETs. Maintaining data security and privacy is highly dynamic VANETs is a challenging task. Several techniques have been introduced recently which are based on the cryptography and key exchange. However, these techniques provide solution to limited security threats. Hence, this work introduces a novel approach for key management and distribution in VANET to provide the security to the network and its components. This approach is later incorporated with cryptography mechanism to secure data packets. Hence, the proposed approach is named as Secure Group Key Management and Cryptography (SGKC). The experimental study shows significant improvements in the network performance. This SGKC approach will help the VANET user’s fraternity to perform secured data transmission.

Primary cilia loss is a common feature of advanced cancers. While primary cilia are necessary to initiate Hedgehog (HH)-driven cancers, how HH pathway activity is maintained in advanced cancers devoid of primary cilia is unclear. Here, we find that HH-driven basal cell carcinoma (BCC) accumulates mutations in Alström and Usher syndrome genes. Loss of Alström and Usher syndrome gene expression, which are common underlying causes of deafness and blindness, suppresses primary ciliogenesis and HH signaling but enhances expression of atypical protein kinase C iota/lambda (aPKC), a GLI1 kinase necessary for advanced BCC growth. We show that aPKC expression is inversely correlated with primary ciliogenesis and that superficial BCCs display less primary cilia and higher aPKC expression, with the opposite trend in nodular BCC subtypes. Surprisingly, a constitutively active isoform of aPKC but not full-length protein drives HH pathway activity. Overexpression of the constitutively active aPKC variant can maintain HH pathway activity and tumor growth in the absence of primary cilia. Our results suggest tumors enhance isoform-specific expression of aPKC to prevent mutation-induced cessation of tumor growth.

VANET is an application and subclass of MANET’s, in which nodes are mobiles and considered as moving, communicating vehicles in a wireless adhoc network. Vehicles communicate through dedicated short rage communication (DSRC) via IEEE 802.11p protocol. With the progress of wireless technology, vehicular ad hoc network has become emerging technology to support real-time traffic condition, safety, entertainment, enhance driver experience and emergency navigation in intelligent transport system (ITS). Core of VANETs application is the communication between vehicle to vehicle (V2V), vehicle to roadside unit (V2RSU) and securing the data messages from malicious activities and attackers in the network. Securing V2V and V2RSU communication has raised challenging issues in detecting and avoiding malicious attackers for secure communications. VANET’s are exposed to different threats while routing data, wormhole attack is the most threatening routing attack which severely effects VANET routing data and causes incorrect routing by private tunnels and damages to VANET’s communication in terms of data leakage, data dropping, and delayed delivery. However existing attack detection schemes have failed to meet secured VANETs communication leading to packet loss. In this paper we propose an efficient wormhole detection mechanism by creating potential and trusted neighbour nodes discovery (TNND) in VANETs, which can detect malicious nodes through enabling common forwarding neighbour nodes as witness to monitor data packets are forwarded by malicious nodes. Basically this mechanism is based on trust management. This scheme is resilient and resistant against attackers launching malicious nodes to corrupt entire network. Simulation is carried on event driven network simulator and results shows efficient detection of wormhole nodes, increases packet delivery and performs better than existing detection scheme.

Dimensionality Reduction (DR) is an important technique which is used to reduce the dimensionality of features present in the datasets. This technique is used in various fields such as Data Mining, Machine Learning, Pattern Recognition, Image Retrieval, Text mining etc. In the data mining filed, DR is an important preprocessing technique. Linear Discriminant Analysis (LDA) is a popular DR technique. Traditional LDA technique faces a Small Sample Size (SSS) problem. The SSS problem occurs when the number of samples is less than the dimensionality of the samples. A Lot of feature selection algorithms are proposed in the earlier days, but still the problem persists. Hence, a new feature selection algorithm is proposed in this paper to overcome the SSS problem.

Classification is one of the important techniques of data mining. In the classification task, features play a vital role. Therefore, selecting the relevant features becomes an essential task. Though many feature selection algorithms are available many research works are been carried out to improve the classification accuracy. In this paper, a new methodology is proposed with three different feature selection algorithms to improve the classification accuracy by selecting the relevant features.