• An Analysis of a Signature-based Approach for an Intrusion Detection System in a Wireless Body Area Network (WBAN) using Data Mining Techniques

      Kholidy, Hisham A.; Medina, Serene Elisabeth; Kholidy, Hisham A.; Advisor (SUNY Polytechnic Institute, 2020)
      Wireless Body Area Networks (WBANs) use biosensors worn on, or in the human body, which collect and monitor a patient’s medical condition. WBANs have become increasingly more beneficial in the medical field by lowering healthcare cost and providing more useful information that medical professionals can use for a more accurate, and faster diagnosis. Due to the fact that the data collected from a WBAN is transmitted over a wireless network, there are several security concerns involved. This research looks at the various attacks, and concerns involved with WBANs. A real physiological dataset, consisting of ECG signals obtained from a 25-year-old male, was used in this research to test accuracy of various decision tree classifiers. The Weka software was used to analysis the accuracy and detection rate results of this dataset in its original form, versus a reduced dataset consisting of less, more important attributes. The results concluded that the use of decision tree classifiers using data mining, is an efficient way to test the increased accuracy on a real dataset obtained from a WBAN once it has been altered. The original dataset produced results where the ROC curve ranged from 0.313 (31%) to 0.68 (68%), meaning their accuracy is not very high and the detection rate is low. Once an attribute selection feature was used on the dataset, the newly reduced set showed ROC curves ranging from 0.68 (68%) to 0.969 (97%) amongst the three classes. As a result, decision tree models were much more accurate with a higher detection rate when used on a real dataset that was reduced to function better as a detector for a WBAN.
    • Analysis of cdGAP in Extracellular Matrix Rigidity Sensing and Cell Migration

      Turner, Chris; Wormer, Duncan (2014)
      CdGAP is a Rac1/Cdc42 specific GTPase activating protein that localizes to cell–matrix adhesions through an interaction with the adhesion scaffold α-parvin/actopaxin to regulate lamellipodia formation and cell spreading. In chapter 2 of this thesis, using a combination of siRNA-mediated silencing and over expression, I show that cdGAP negatively regulates directed and random migration by controlling adhesion maturation and dynamics through the regulation of both adhesion assembly and disassembly. Interestingly, cdGAP was also localized to adhesions formed in three-dimensional matrix environments and cdGAP depletion promoted cancer cell migration and invasion through 3D matrices. Cell migration in 3D CDMs more closely approximates the topography of in vitroconnective tissues, suggesting that cdGAP likely plays an important regulatory role in cell migration in vivo. Other aspects of the extracellular matrix also influence cell migration. Specifically, motile cells are capable of sensing the stiffness of the surrounding extracellular matrix through integrin-mediated focal adhesions and migrate towards regions of higher rigidity in a process known as durotaxis. Durotaxis plays an important role in normal development and disease progression, including tumor invasion and metastasis. However, the signaling mechanisms underlying focal adhesion-mediated rigidity sensing and durotaxis are poorly understood. In chapter three of this thesis, I utilizefibronectin-coated polydimethoxysiloxane gelsto manipulate substrate compliance, and show that cdGAP is necessary for U2OS osteosarcoma cells to coordinate cell shape changes and migration as a function of extracellular matrix stiffness. CdGAP regulated rigidity-dependent motility by controlling membrane protrusion and adhesion dynamics, as well as by modulating Rac1 activity. I also found that CdGAP was necessary for U2OS cell durotaxis. Taken together, these data identify cdGAP as an important component of an integrin-mediated signaling pathway that senses and responds to mechanical cues in the extracellular matrix in order to coordinate directed cell motility.These findings highlight the importance of GAP proteins in the regulation of Rho family GTPases andprovide insight into how GAPs co-ordinate the cell migration machinery.
    • ANALYSIS OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR-ERLIN1/2 COMPLEX-RNF170 AXIS MUTATIONS THAT RESULT IN NEURODEGENERATIVE DISEASE

      Wojcikiewicz, Richard; WRIGHT, FORREST (2017)
      Inositol 1,4,5-trisphosphate receptors (IP3Rs) are endoplasmic reticulum (ER) proteins that assemble into tetrameric IP3- and Ca2+-gated Ca2+ channels. Activation of IP3Rs begins with stimulation of cell surface receptors that elevate cytosolic IP3 levels. IP3, with its co-agonist Ca2+, binds to IP3Rs and causes a conformational change that results in the opening of the channel aperture, allowing for Ca2+ ions to flow from stores within the ER lumen to the cytosol and thereby promoting a number of Ca2+-dependent cellular events, including secretion, neurotransmitter release and cell division. Intriguingly, it appears that the same conformational change that IP3Rs undergo during activation makes them a target for degradation by the ubiquitin-proteasome pathway. This processing allows the cell to fine-tune its internal Ca2+ responses to extracellular stimuli. In the Wojcikiewicz lab, it was discovered that processing of activated IP3Rs is mediated by the Erlin1/2 complex, a large (~2MDa) complex composed of the proteins Erlin1 and Erlin2. Constitutively-associated with the Erlin1/2 complex is the E3 ubiquitin ligase RNF170. Thus, we employed TALEN and CRISPR/Cas9-mediated gene editing technologies to abrogate expression of these three proteins to define their roles in this process. Remarkably, analysis of cells lacking RNF170 showed that it is required for all ubiquitination of activated IP3Rs. Investigation into the roles of Erlin1 and Erlin2 uncovered that Erlin2 is the “dominant partner” in the Erlin1/2 complex, mediating complex interaction with activated IP3Rs and bringing RNF170 into place to allow for ubiquitination to proceed. Mutations to RNF170 (R199C) and Erlin2 (T65I) have been identified as causative for progressive neurodegenerative diseases. Investigation of the R199C mutation on IP3R processing by RNF170 uncovered that while the mutation did not affect normal RNF170 function, it destabilized the RNF170 protein, resulting in a significantly reduced cellular complement of RNF170 and inhibition of IP3R degradation. Analysis of the Erlin2 T65I mutation showed that the effect of the mutation on Erlin1/2 complex function was two-fold. First, Erlin2 T65I interaction with activated IP3Rs was completely blocked, thereby inhibiting recruitment of RNF170 and subsequent ubiquitination and processing. Second, normal binding of the Erlin1/2 complex to phosphoinositol-3-phosphate (PI(3)P) – the significance and function of which remains undefined – was drastically inhibited. Examination of complex assembly and stability by SDS-PAGE and Native PAGE showed no destabilization of individual Erlin2 proteins nor of overall Erlin1/2 complex assembly. These data demonstrate that proper and tight control of IP3R levels in the cell are critical to overall cellular homeostasis, as disruptive mutations to requisite mediators of IP3R processing - the Erlin1/2 complex and RNF170 – result in the development of progressive neurodegenerative disease.
    • ANALYSIS OF TEMPERATURE SENSITIVE CYK-1 MUTATIONS EFFECT ON MUSCLE DEVELOPMENT ON CAENORHABDITIS ELEGAN SLARVAE

      Pruyne, David; Laszlo, Arianna (2017)
      Sarcomeres are the most basic unit of muscle cells. Formins are actin regulatory proteins that are important for actin filament polymerization and nucleation, and might be responsible for the actin filamentassembly in sarcomeres. In Caenorhabditis elegans, two formins (CYK-1 and FHOD-1) were found in the body wall muscle (BWM), specifically in the Z-line of sarcomeres. Previously, BWM were analyzed in null cyk-1(ok2300) mutant worms, derived from heterozygous parents, and fhod-1(tm2363) mutantworms, andwere found to have smaller muscles than wild-type worms. Yet, there was still functional CYK-1 present in the worms due to inherited maternal CYK-1. To eliminate this potential source of CYK-1, cyk-1(or596ts) temperature sensitive mutant worms were used to allow for all CYK-1 to be non-functional at 26°C. The focus of this study was to understand the importance of cyk-1on muscle development in C. eleganslarvae. Wild-type, fhod-1(tm2363), cyk-1(or596ts), and fhod-1(tm2363);cyk-1(or596ts) double mutant wormsat L1 larval stage were observed for worm shape and muscle abnormalities. Abnormal worm shapes were observed in fhod-1, cyk-1, and more commonly in fhod-1;cyk-1mutant worms at permissive and restrictive temperatures. Abnormal muscle was observed in both permissive and restrictive temperatures forfhod-1, cyk-1, and fhod-1;cyk-1mutant worms that had abnormal worm shapes, while all worms that had normal body shape usually had normal muscle at both temperatures. Worms were alsotested to determine long-termeffects of cyk-1and fhod-1mutations on muscle development. Worms were held at permissive or restrictive temperatures for various times. Fhod-1and cyk-1mutant worms showed reduced muscle size compared to wild-type, while fhod-1;cyk-1mutant worms displayed a more severelyreduced muscle size. Next, cyk-1orfhod-1were tested to see whether they can rescue muscle cell size after mosaic expressionin a cyk-1(-) or fhod-1(-) mutant worm background. Fhod-1(+) muscle cells showeda significant increase in muscle cell size compared to fhod-1(-) cells, while cyk-1(+) muscle cells showeda non-significant increase in muscle size compared to cyk-1(+/-) cells. This shows cell-autonomousexpressionoffhod-1influencesmuscle growth, while cyk-1expression in another organ might influence muscle development.
    • ANTIVIRAL ACTIVITY AND MECHANISM OF ACTION OF A NOVEL URACIL ANALOG FOR VARICELLA-ZOSTER VIRUS

      Moffat, Jennifer; DE, CHANDRAV (2015)
      The alphaherpesvirus varicella-zoster virus (VZV) is widespread in humans. VZV causes primary and recurrent diseases that are preventable with live vaccines and are treatable with antiviral drugs. New antiviral drugs for varicella-zoster virus (VZV) with increased potency are needed, especially to prevent post-herpetic neuralgia. The purpose of this project was to evaluate β-L-1-[5-(E-2-Bromovinyl)-2-(hydroxymethyl)-1,3-dioxolan-4- yl)] uracil (L-BHDU) and 5′-O-valyl-L-BHDU for efficacy, safety, resistance, and mechanism of action in three models of VZV replication: primary human foreskin fibroblasts (HFFs), skin organ culture (SOC) and in SCID-Hu mice with skin xenografts. We found that L-BHDU and valyl-L-BHDU were safe and effective against VZV in culture and in a mouse model. Herpes simplex virus Type 1 was also sensitive to LBHDU in cultured cells. The mechanism of action of L-BHDU and its effect on drugdrug interactions were not known. Given its similar structure to brivudine (BVdU), we addressed whether L-BHDU, like BVdU, inhibits 5-fluorouracil (5-FU) metabolism. LBHDU did not interfere with 5FU metabolism, indicating that L-BHDU is a safer drug than BVdU. However, L-BHDU antagonized the activity of acyclovir (ACV), BVdU and foscarnet (PFA) in cultured cells, which was due to competition for phosphorylation by VZV thymidine kinase (TK). The mechanism of action of L-BHDU was studied by evaluating its activity against related α-herpesviruses and by analyzing resistant VZV viii strains. VZV strains resistant to L-BHDU (L-BHDUR ) were cross-resistant to ACV and BVdU but not to PFA and cidofovir (CDV). Whole genome sequencing of L-BHDUR strains identified mutations in ATP-binding (G22R) and nucleoside binding (R130Q) domains of VZV TK. The purified L-BHDUR TKs were enzymatically inactive and failed to phosphorylate the drug. In wild type VZV- infected cells, L-BHDU was converted to L-BHDU mono- and diphosphate forms; cells infected with L-BHDUR virus did not phosphorylate the drug. We also investigated whether addition of nucleosides reversed LBHDU inhibition of VZV in dividing and quiescent HFFs. Excess thymidine and uridine, but not purines, in proportion to L-BHDU restored VZV replication only in dividing cells, suggesting that the active form of L-BHDU interfered with pyrimidine biosynthesis. Like other herpesviruses, VZV infection induced thymidine triphosphate (dTTP) in confluent cells while L-BHDU treatment decreased the dTTP pool. Some herpesviruses raise dNTP pools by inducing cellular enzymes. However, VZV infection did not increase cellular thymidylate synthase (TS) expression to facilitate viral replication. Furthermore, the active form of L-BHDU did not interfere with cellular metabolism, suggesting a viral target. Further studies are required to identify the target(s) of L-BHDU active form(s).
    • AOSOS Master Hyperguide: A Hypertextual Guide to Using America's One Stop Operating System

      Baertschi, Adam (2016-12-01)
      In today's business world, it is common for guidance to be disseminated by a training authority or central, decision-making body to the people that make up the organization's staff. This guidance can be anything from fire drill procedures to instructions on how to use software vital to the organization's operations. Many private and governmental agencies still rely on sending out standardized textual documents that contain the intended instruction. Using a governmental department of New York State as an example, we can quickly identify the problems with this method of guidance and look to Information Design for a solution.
    • Applicability of the Julia Programming Language to Forward Error-Correction Coding in Digital Communications Systems

      Quinn, Ryan; Andriamanalimanana, Bruno R.; Advisor; Sengupta, Saumendra; Reviewer; Spetka, Scott; Reviewer (2018-05)
      Traditionally SDR has been implemented in C and C++ for execution speed and processor efficiency. Interpreted and high-level languages were considered too slow to handle the challenges of digital signal processing (DSP). The Julia programming language is a new language developed for scientific and mathematical purposes that is supposed to write like Python or MATLAB and execute like C or FORTRAN. Given the touted strengths of the Julia language, it bore investigating as to whether it was suitable for DSP. This project specifically addresses the applicability of Julia to forward error correction (FEC), a highly mathematical topic to which Julia should be well suited. It has been found that Julia offers many advantages to faithful implementations of FEC specifications over C/C++, but the optimizations necessary to use FEC in real systems are likely to blunt this advantage during normal use. The Julia implementations generally effected a 33% or higher reduction in source lines of code (SLOC) required to implement. Julia implementations of FEC algorithms were generally not more than 1/3 the speed of mature C/C++ implementations.While Julia has the potential to achieve the required performance for FEC, the optimizations required to do so will generally obscure the closeness of the implementation and specification. At the current time it seems unlikely that Julia will pose a serious challenge to the dominance of C/C++ in the field of DSP.
    • The Application of Social Networks to the Marketing of Industrial Products

      Perlstein, Roger (2010-12-01)
      Social networking changes the way people share ideas and communicate. Advantages in portability, reach, and access contribute to acceptance of social networks and the likelihood that they will continue to grow. While these systems were initially used by individuals, they were not as widely employed by businesses. Some firms however are leveraging these tools and integrating social networking into their marketing. Where social networks are used by businesses, they are primarily focused on consumer goods, home and family, electronics and entertainment. Business-to-business applications are not as widely used and some question whether such tools offer significant benefits in such settings. This thesis studies social network marketing for a vehicle lift manufacturer. It addresses viability, strategy and practices for a vehicle maintenance equipment manufacturer. It analyzes data collected from other similar companies to identify best practices for the use of such tools and details the current state of the industry for this market.
    • Applied Hypertext Theory in a Demonstration of a Non-Sequential Audio Narrative

      Fitzpatrick, Philip J (2016-05)
      A Non-sequential, narrative can present objects, actual or imaginary, which depict connected events, presented in a medium that affords opportunities to determine the sequence of the presentation. Non-sequential, narratives can have multiple beginnings but no end although they do offer levels of saturation. Hypertext techniques can be used as a platform for the creation of a non-sequential narrative through links to text and multimedia as hypermedia. This paper reviews Non-sequential narrative and hypertext techniques and their affordances to a reader/listener for novel exploration and new narrative creation from an existing audio narrative. A demonstration project for applying hypertext techniques to audio based on the Serial, Undisclosed and Serial Dynasty related podcasts to allow reader/listener narrative exploration and creation are also examined. The function of a future application to allow for a listener to segue directly between audio segments.
    • Applying Game Learning Principles to Analyze and Identify Improvements for Scuba Training Simulations

      Schaller, Shaun; Yucel, Ibrahim; Thesis Advisor; Kahn, Russell; Second Reader (2018-04)
      The purpose of this project was to analyze whether existing simulations for scuba diving are effective training tools, and to further develop prototype mockups that demonstrate how a simulation embedded with important scuba concepts and procedures can create an effective learning environment. Academic literature is reviewed relating to virtual reality experiences, simulations in training applications, motivational factors for the use of simulations in education, and strategies to embed learning into game simulations. This study uses James Paul Gee’s learning principles for good games (2013) to analyze the scuba simulation game, “Infinite Scuba.” Gee’s learning principles are then applied to develop a series of simulation mockups in which players learn important scuba procedures including: planning a dive, underwater navigation, and underwater communication. The question under investigation is: “What features are needed in a game simulation to be an effective teaching tool and learning experience for open water scuba divers.”
    • Applying Malone’s Motivational Theory and Flow to a Study of Whether Playing Educational  Video Games Influences Motivation and Impacts Learning Outcomes in 5th Grade Mathematics

      Goodnough, Eric P (2012-12-01)
      The purpose of this paper is to explore the possibility that using video games as an educational tool will impact student motivation and learning outcomes for mathematics in a 5th grade classroom. It uses relevant literature and qualitative research to investigate if educational video games provide challenge, fantasy, curiosity, and control as a means of influencing intrinsic motivation, using Malone’s Motivational Theory as a theoretical framework. Additionally, it explores similarities between intrinsic motivation and the characteristics suggested for a game to achieve Flow. Flow is a theory based on the balance of player skill and level of challenge, and can be used as a means for measuring how fun a game is. Specifically, this study examines the gaming features available at the learning website Study Island and how they are implemented in a 5th grade elementary school classroom. By conducting semi-structured interviews with teachers who use the website regularly and using existing standardized test scores to evaluate learning outcomes, I compare the emerging themes from these discussions with the suggested results provided by previous literature on the subject. Based on these comparisons, I attempt to answer the following research question: Does playing educational video games influence motivation and impact learning outcomes in 5 th grade mathematics?
    • Artist Exposure Utilizing Multi-Language Communication Tools

      Rabideau-Bruno, Mary Lou (2011-12-01)
      Abstract not present in the thesis
    • Assessing a Multi-Electron Beam Application Approach for Semiconductor Process Metrology

      Mukhtar, Maseeh; Thiel, Bradley; Dissertation Committee Chair; Bello, Abner; Dissertation Committee; Diebold, Alain; Dissertation Committee; Cady, Nathan; Dissertation Committee; Geer, Robert; Dissertation Committee; Sung, Woongje; Dissertation Committee (2018)
      Radical and disruptive technological approaches regularly require experimental prototypes be built, which is difficult to justify considering their oft-prohibitive requirements in terms of financial and/or time commitments. It is also frequently the situation that use cases for new technologies are not entirely worked out precisely which in turn make it even more difficult to build prototypes but the analysis of simulation data sets from virtual samples can be used to predict sensitivity to the devised signal, detection limits, and impact of design rules and material sets. The results can thus be used to guide prototype design. The aim of this work is to develop and demonstrate a predictive approach to technology assessment and prototype design. This work will focus on two such disruptive technology concepts: electron beam defect inspection and critical dimension measurement. These two concepts are based on the transfer from conventional process metrology technologies i.e., brightfield inspection and optical critical dimension scatterometry to multi-electron beam approaches. Here, a multi-scale modeling approach is used to simulate data streams nominally generated by virtual tools inspecting virtual wafers. To this end, Java Monte Carlo Simulator for Secondary Electrons (JMONSEL) simulations are used to generate expected imaging responses of chosen test cases of patterns and defects with ability to vary parameters for beam energy, spot size, pixel size, and/or defect material and form factor. The patterns are representative of the design rules for aggressively-scaled FinFET-type designs. With these simulated images and resulting shot noise, a signal-to-noise framework is developed, which relates to defect detection probabilities. Additionally, with this infrastructure the effect of detection chain noise and frequency dependent system response can be made, allowing for targeting of best recipe parameters for multi-electron beam inspection validation experiments. Ultimately, leading to insights into how such parameters will impact tool design, including necessary doses for defect detection and estimations of scanning speeds for achieving high throughput for high-volume manufacturing. Simulated images are also executed for measurement of critical dimensions of the abovementioned class of FinFETs. Similarly, validation experiments for multi-electron critical dimension measurements may use the information extracted for development of volume manufacturing metrology systems.
    • Assisting Seniors with Technology Challenges: Video Tutorials for Password Development and Management

      Stam, Kathryn; Thesis Advisor; Lizardi, Ryan; Second Reader; Hanna, Margie (2021-05)
      Seniors often have difficulties using evolving technology while keeping their valuable personal data safe. This research effort began with assessing how and why seniors use technology and determining the best educational techniques to help them connect with instructional information. Additional research determined how design principles including layering and progressive disclosure could be applied to enhance these techniques. In an effort to maintain a manageable scope, password development and management was selected as an example technology challenge. The current state of training resources related to these topics on Facebook and YouTube was surveyed and analysis performed to determine if the design principles and instructional techniques discovered through the aforementioned research were evident. Good tips and tricks for strong password development were incorporated into the instructional design/development plan. A Facebook group and training videos were developed to facilitate assisting seniors with password creation and management.
    • Association betweenDRD2/DRD4interaction and conduct disorder: A potential developmental pathway to alcohol dependence

      Mota, Nina R.; Bau, Claiton H. D.; Banaschewski, Tobias; Buitelaar, Jan K.; Ebstein, Richard P.; Franke, Barbara; Gill, Michael; Kuntsi, Jonna; Manor, Iris; Miranda, Ana; et al. (Wiley, 2013-07-02)
    • Association of genetic risk severity with ADHD clinical characteristics

      Kotte, Amelia; Faraone, Stephen V.; Biederman, Joseph (Wiley, 2013-10-17)
      This study sought to examine the association between the cumulative risk severity conferred by the total number of attention-deficit/hyperactivity disorder (ADHD) risk alleles of the DAT1 3′UTR variable number tandem repeat (VNTR), DRD4 Exon 3 VNTR, and 5-HTTLPR with ADHD characteristics, clinical correlates, and functional outcomes in a pediatric sample. Participants were derived from case–control family studies of boys and girls diagnosed with ADHD, a genetic linkage study of families with children with ADHD, and a family genetic study of pediatric bipolar disorder. Caucasian children 18 and younger with and without ADHD and with available genetic data were included in this analysis (N = 591). The association of genetic risk severity with sociodemographic, clinical characteristics, neuropsychological, emotional, and behavioral correlates was examined in the entire sample, in the sample with ADHD, and in the sample without ADHD, respectively. Greater genetic risk severity was significantly associated with the presence of disruptive behavior disorders in the entire sample and oppositional defiant disorder in participants with ADHD. Greater genetic risk severity was also associated with the absence of anxiety disorders, specifically with the absence of agoraphobia in the context of ADHD. Additionally, one ADHD symptom was significantly associated with greater genetic risk severity. Genetic risk severity is significantly associated with ADHD clinical characteristics and co-morbid disorders, and the nature of these associations may vary on the type (externalizing vs. internalizing) of the disorder. © 2013 Wiley Periodicals, Inc.
    • Association of Hindu Society Web Presence: Marketing for a Community Project

      DelMedico, Julie E. (2013-08-01)
      This paper illustrates how three graduate students created a unified community voice and spread the ideas of a small group of Bhutanese-Nepali refugees in Utica, New York. Not only did the group meet with the client in his environment to attempt to understand the cultural concerns, they developed a user friendly, professional website dedicated to the mission and history of the Association of Hindu Society of Utica, New York. They interviewed members of the congregation to develop content and developed a comprehensive marketing plan in an effort to connect the 150 Hindu members living in the city of Utica as well as to try and encourage new members to practice the faith of this group. As a result the group reached over 150 members through social networking sites and are continuously trying to generate popularity to this cultural group within the community. A comprehensive overview of the project is outlined within this document with specific attention given to the marketing plan. The marketing efforts were specific to the unique needs of the Hindu practicing Bhutanese-Nepali refugees living in Utica, NY and may not be generalizable to the population at large.
    • Associations Between ADHD and Psychoactive Substance use Disorders:Findings from a Longitudinal Study of High-Risk Siblings of ADHD Children

      Milberger, Sharon; Biederman, Joseph; Faraone, Stephen V.; Wilens, Timothy; Chu, Monica P. (Wiley, 1997-01)
      The purpose of this study was to determine whether the single nucleotide polymorphisms (SNPs) within candidate genes for attention deficit hyperactivity disorder (ADHD) are associated with the age at onset for ADHD. One hundred and forty-three SNPs were genotyped across five candidate genes (DRD5, SLC6A3, HTR1B, SNAP25, DRD4) for ADHD in 229 families with at least one affected offspring. SNPs with the highest estimated power to detect an association with age at onset were selected for each candidate gene, using a power-based screening procedure that does not compromise the nominal significance level. A time-to-onset analysis for family-based samples was performed on these SNPs to determine if an association exists with age at onset for ADHD. Seven consecutive SNPs surrounding the D5 dopamine receptor gene (DRD5), were associated with the age at onset for ADHD; FDR adjusted q-values ranged from 0.008 to 0.023. This analysis indicates that individuals with the risk genotype develop ADHD earlier than individuals with any other genotype. A haplotype analysis across the 6 significant SNPs that were in linkage disequilibrium with one another, CTCATA, was also found to be significant (p-value = 0.02). We did not observe significant associations with age at onset for the other candidate loci tested. Although definitive conclusions await independent replication, these results suggest that a variant in DRD5 may affect age at onset for ADHD
    • Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome

      Thompson, Carlie A.; Karelis, Jason; Middleton, Frank A.; Gentile, Karen; Coman, Ioana L.; Radoeva, Petya D.; Mehta, Rashi; Fremont, Wanda P.; Antshel, Kevin M.; Faraone, Stephen V.; et al. (Wiley, 2017-01-31)
      22q11.2 deletion syndrome is a neurogenetic disorder resulting in the deletion of over 40 genes. Up to 40% of individuals with 22q11.2DS develop schizophrenia, though little is known about the underlying mechanisms. We hypothesized that allelic variation in functional polymorphisms in seven genes unique to the deleted region would affect lobar brain volumes, which would predict risk for psychosis in youth with 22q11.2DS. Participants included 56 individuals (30 males) with 22q11.2DS. Anatomic MR images were collected and processed using Freesurfer. Participants were genotyped for 10 SNPs in the COMT, DGCR8, GNB1L, PIK4CA, PRODH, RTN4R, and ZDHHC8 genes. All subjects were assessed for ultra high risk symptoms of psychosis. Allelic variation of the rs701428 SNP of RTN4R was significantly associated with volumetric differences in gray matter of the lingual gyrus and cuneus of the occipital lobe. Moreover, occipital gray matter volumes were robustly associated with ultra high risk symptoms of psychosis in the presence of the G allele of rs701428. Our results suggest that RTN4R, a relatively under-studied gene at the 22q11 locus, constitutes a susceptibility gene for psychosis in individuals with this syndrome through its alteration of the architecture of the brain. © 2017 Wiley Periodicals, Inc.