• 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.
    • Autism spectrum disorder traits in SLC9A9 knock-out mice

      Faraone, Stephen; Yang, Lina (2014)
      utism spectrum disorders (ASDs) are a group of neurodevelopmental disorders which begin in childhood and persist into adulthood. They cause lifelong impairments and are associated with substantial burdens to patients, families and society. Genetic studies have implicated the sodium/proton exchanger (NHE) nine gene, SLC9A9, to ASDs and attention-deficit/hyperactivity disorder (ADHD). SLC9A9 encodes, NHE9, a membrane protein of the late recycling endosomes. The recycling endosome plays an important role in synapse development and plasticity by regulating the trafficking of membrane neurotransmitter receptors and transporters. Here we tested the hypothesis thatSLC9A9 knock-out (KO) mice would show ADHD-like and ASD-like traits. Ultrasonic vocalization recording showed that SLC9A9 KO mice emitted fewer calls and had shorter call durations, which suggest communication impairment. SLC9A9 KO mice lacked a preference for social novelty, but did not show deficits in social approach; SLC9A9 KO mice spent more time self-grooming, an indicator for restricted and repetitive behavior. We did not observe hyperactivity or other behavior impairments which are commonly comorbid with ASDs in human, such as anxiety-like behavior. Our study is the first animal behavior study that links SLC9A9 to ASDs. By eliminating NHE9 activity, it provides strong evidence that lack of SLC9A9 leads to ASD-like behaviors in mice and provides the field with a new mouse model of ASDs.
    • Autophagy, apoptosis, and neurodevelopmental genes might underlie selective brain region vulnerability in attention-deficit/hyperactivity disorder

      Hess, Jonathan L.; Radonjić, Nevena V.; Patak, Jameson; Glatt, Stephen J.; Faraone, Stephen V. (Springer Science and Business Media LLC, 2020-12-18)
      Large-scale brain imaging studies by the ENIGMA Consortium identified structural changes associated with attentiondeficit/ hyperactivity disorder (ADHD). It is not clear why some brain regions are impaired and others spared by the etiological risks for ADHD. We hypothesized that spatial variation in brain cell organization and/or pathway expression levels contribute to selective brain region vulnerability (SBRV) in ADHD. In this study, we used the largest available collection of magnetic resonance imaging (MRI) results from the ADHD ENIGMA Consortium (subcortical MRI n = 3242; cortical MRI n = 4180) along with high-resolution postmortem brain microarray data from Allen Brain Atlas (donors n = 6) from 22 brain regions to investigate our SBRV hypothesis. We performed deconvolution of the bulk transcriptomic data to determine abundances of neuronal and nonneuronal cells in the brain. We assessed the relationships between gene-set expression levels, cell abundance, and standardized effect sizes representing regional changes in brain sizes in cases of ADHD. Our analysis yielded significant correlations between apoptosis, autophagy, and neurodevelopment genes with smaller brain sizes in ADHD, along with associations to regional abundances of astrocytes and oligodendrocytes. The lack of enrichment of common genetic risk variants for ADHD within implicated gene sets suggests an environmental etiology to these differences. This work provides novel mechanistic clues about SBRV in ADHD.
    • Best Practices for Embedding Videos on Oral History Websites

      Tucker, Michelle M. (2012-05-01)
      The study investigates current technical practices for viewing video on the internet. The study also investigates common features of oral history websites that contain video for viewing. 50 websites that contain video for viewing were analyzed for various features such as video upload capability, closed captioning or transcript presence, and video format(s) utilized or accepted. Review of the oral history websites revealed that long interviews are best broken into shorter video segments. Also, the presence of transcripts is helpful to viewers. In addition, research was conducted for recommendations for the creation of best quality videos and most common practices. It was found that the MPEG-4 video format produces a reliable, quality image. An oral history website about the Utica Psychiatric Center was created utilizing these recommendations. The website features videos of interviews with former employees. User testing was employed to critique the website.
    • BGP Routing Protocol

      Parasa, Sai Kiran; Hash, Larry; Advisor (2016-08)
      Border Gateway Protocol is the protocol which makes the Internet work. It is used at the Service provider level which is between different Autonomous Systems (AS). An Autonomous System is a single organization which controls the administrative part of a network. Routing with in an Autonomous System is called as Intra-Autonomous routing and routing between different Autonomous Systems is called as Inter-Autonomous System routing. The routing protocols used within an Autonomous System are called Interior Gateway Protocols (IGP) and the protocols used between the Autonomous Systems are called Exterior Gateway Protocols. Routing Information Protocol (RIP), Open Short Path First (OSPF) and Enhanced Interior Gateway Routing Protocol (EIGRP) are the examples for IGP protocols and Border Gateway Protocol (BGP) is the example for EGP protocols. Every routing protocol use some metric to calculate the best path to transfer the routing information. BGP rather than using a particular metric, it uses BGP attributes to select the best path. Once it selects the best path, then it starts sending the updates in the network. Every router implementing BGP in the network, configures this best path in its Routing Information Base. Only one best route is selected and forwarded to the whole network. [17] Due to the tremendous increase in the size of the internet and its users, the convergence time during link failure in the protocol is very high.
    • Bioengineered Platforms for Human Stem Cell-Based Diagnostic and Therapeutic Interventions

      Paluh, Janet L.; Thesis Advisor; Sharfstein, Susan T.; Committee Member; Xie, Yubing; Committee Member; Wang, Jun; Outside Committee Member; Amini, Nooshin (2020-08)
      Human stem cells offer an unprecedented ability to restore function lost through disease or injury by providing options for cell therapies and regenerative medicine. Two hurdles that delay greater clinical use of stem cells are production of differentiated therapeutic cells in large-scale platforms and the challenge of choosing the optimum cell type and delivery method for cell therapy that is optimized for cell-cell signaling in the therapeutic microenvironment. In my thesis work I investigated different bioengineered platforms in combination with human stem cell technology to mass produce functional hiPSC-derived beta islets in a miniature bioreactor and study cytokine release from multipotent and differentiated hiPSC-derived neural stem cells as neural rosettes and their dissociated cells or differentiating inhibitory and excitatory neurons alone and in mixed cultures applying a neural cell-cell interaction microchip (NCCIM) with features developed specifically for these studies. My work has further expanded the application of hiPSC-derived neurons in an in vitro model of traumatic brain injury. In this study a hybrid culture of hiPSC-derived excitatory pyramidal neurons, inhibitory GABAergic interneurons and immortalized human microglia are being evaluated for secreted cytokines under healthy and stretch injured induced conditions. One of the challenges of TBI is the inability to yet effectively and with minimal invasiveness track changes following injury that may indicate healing or deterioration and an in vitro model is one important contribution to identifying biomarkers.

      Xie, Yubing; Advisor; Torrejon, Karen; Thesis committee; Cady, Nate; Thesis committee; Danias, John; Thesis committee; Sharfstein, Susan; Thesis committee; Tian, Yangzi Isabel (2018-10)
      Glaucoma is one of the leading causes of irreversible blindness in the world. Despite decades of research, intraocular pressure (IOP) is the only known treatable risk factor. IOP is affected by the timely removal of aqueous humor through the conventional outflow track, which is made up of the trabecular meshwork and adjacent Schlemm’s canal. Dysfunction in these tissues due to aging, oxidative stress, metabolic or pathological changes lead to increased flow resistance, elevated IOP, and ultimately glaucoma. Recent advances in ocular regenerative therapy have the potential to rescue glaucomatous tissue function and restore its delicate microenvironment. The possibility of using stem cell-derived trabecular meshwork and Schlemm’s canal cells to recreate a functional outflow tissue are explored in this thesis. Previously, our lab developed a well-defined, micro-porous substrate that promotes in vivo-like physiology and outflow function in primary trabecular meshwork and Schlemm’s canal cell cultures. Using these primary cell cultures as controls, we have created 3D stem cell-derived outflow tissues, evaluated and compared their morphology, expression, outflow facility, and drug responsiveness. To explore the importance of the dynamic microenvironment in outflow function, we developed a dual-flow microfluidic chamber that mimics the basal-to-apical and shear flow of aqueous humor through the conventional outflow track. Overall, this dissertation demonstrates the promising application of stem cells in future glaucoma drug screening and treatment.
    • Biological importance of TIMP-2 phosphorylation on MMP-2 activity

      Bourboulia, Dimitra; Bullard, Renee (2016)
      Matrix metalloproteinases (MMPs) are proteolytic enzymes that are secreted from the cell and play an important role in embryonic development and tissue remodeling. In cancer, MMPs are hyperactive, promoting degradation of the ex-tracellular matrix. Enhancement of MMP proteolytic activity allows tumor cells to migrate and invade surrounding tissues, increasing the chance of metastasis. Tissue inhibitor of metalloproteinases (TIMPs) are also known to act extracellu-larly, and are the endogenous inhibitors of MMPs. To inhibit the protease activi-ty of MMPs, the N-terminus of the TIMP protein binds to the catalytic domain of MMP at a ratio of 1:1. Studies from our lab have found that TIMP-2 is phosphor-ylated on three tyrosine residues, and this phosphorylation increases the inter-action with MMP-2. This is the first time that phosphorylation of TIMP-2 has been reported. Fascinatingly, the proto-oncogene tyrosine kinase c-Src was found to phosphorylate TIMP-2. This is significant in that c-Src has not yet been shown to act extracellularly, and there are no details within the current lit-erature describing how this protein may function outside of the cell. In this the-sis, we usedmammalian cells as a model to decipher whether TIMP-2 phosphor-ylation wasable to occur extracellularly,as well as the effect that phosphoryla-tion of TIMP-2 hadon its functionto both inhibit/activate MMP-2. We found that(1) c-Src is able to phosphorylate TIMP-2 extracellularly in conditioned me-vidia; and (2) phosphorylation of TIMP-2 enhances its function of inhibiting MMP-2 proteolytic activity, as well as assisting in the activation of pro-MMP-2. Our results suggest the presence of anovel mechanismin whichphosphoryla-tion of TIMP-2is able to regulate the extracellular environment through en-hanced interaction with MMP-2. The information gained from this research couldlead to development of novel therapies that use phosphorylated TIMP-2 as a means of decreasing cellular migration and invasion with the overall goal of preventing metastasis.
    • Biomimetic Scaffolds Using Natural/Synthetic Polymers for Salivary Gland Regeneration

      Sfakis, Lauren; Castracane, James; Advisor (2017-06-01)
      Salivary glands are essential in maintaining oral cavity homeostasis. This tissue can become impaired by chemotherapy/radiotherapy given to head and neck cancer patients, as well as systemic diseases. Once this gland is damaged, it has limited ability to regenerate, and so the need for potential biodegradable/biocompatible scaffolds to aid in the growth and repair is of great interest. This soft tissue is made up of multiple cell populations that contribute to the function of the gland. Creating an environment that can recapitulate the one seen in vivo will promote the functionality of the engineered tissue. This research aims to investigate: (1) cell-substrate interactions with salivary gland epithelial cells and nanofiber scaffolds, (2) cell-cell interactions via incorporation of a second native cell population to further enhance epithelial differentiation, mimicking the in vivo microenvironment and (3) the development of engineering a three-dimensional scaffold that will better facilitate the two interactions described above. The hypothesis is that sponge scaffolds that mimic the mechanical properties and architecture of the tissue observed in vivo will provide a platform for future implantation and regeneration strategies. Bio-mimetically engineered scaffold systems for the growth of organs, such as the one described here, yield novel tools for studying organ development in applications for regenerative medicine.
    • Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness

      Faraone, Stephen V.; Biederman, Joseph; Mennin, Douglas; Russell, Ronald (Wiley, 1998-02-07)
      Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is highly comorbid with conduct disorder and sometimes co-occurs with bipolar disorder. This pattern of comorbidity is also seen among relatives of ADHD probands. A growing literature suggests that ADHD with antisocial comorbidity may be nosologically distinct from other forms of ADHD. A similar pattern has been observed for ADHD and bipolar disorder. Given these results, along with the observed comorbidity between conduct and bipolar disorders, we used data from our study of 140 ADHD and 120 control families to determine if conduct and bipolar disorders in ADHD boys should be considered alternative manifestations of the same familial disorder. The probands and their relatives were examined with DSM-III-R structured diagnostic interviews and were assessed for cognitive, achievement, social, school, and family functioning. Our results provide fairly consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes are different manifestations of the same familial condition. As predicted by this hypothesis, there was a significant three-way association between variables assessing the family history of each disorder. Moreover, when families were stratified into bipolar, antisocial, and other types, few differences emerged between the bipolar and antisocial families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:108–116, 1998. © 1998 Wiley-Liss, Inc.
    • Blogging as a Tool to Promote Student-Centered Learning

      Besler, Steven Richard (2013-12-01)
      With recent changes in the educational realm there is an inherent push for students to take an active role in creating their own ways to retain information. This can be defined as Student-centered learning instruction. As the teacher, it is necessary to create an environment to facilitate this style of learning. In order to make this style of learning possible, teachers must develop creative ways to present curriculum. A weblog is a tool that can make Student-centered instruction possible within the classroom. The goal of this research project is to prove that there is a correlation between the implementation of a weblog and Student-centered instruction.
    • Blogging September 11; Transforming Personal Expressions Into Data Visualization in Wordle and Tagxedo

      Lata, Andrzej (2012-05-01)
      September 11, 2001 is one of the most recognizable dates in world's modern history. Much has been said, published and reported about the tragic events and more may still be revealed and understood about that unforgettable day. So much information has been collected about September 11th, and many have studied and analyzed this information. Many educational, governmental and other organizations and institutions have worked and contributed toward a better understanding of the events of that tragic day. Under the guidance and leadership of Professor Steven Schneider, teachers and students of SUNY IT had an opportunity to participate in several projects directed towards a deepening understanding and reflection upon 9/11. I had the opportunity to participate in two of these projects during the Spring and Summer of 2011. My participation sparked my choice of a topic for my final project. I investigated content of blog entries posted immediately after the terrorist acts of September 11th, 2001. the research questions I sought to answer were centered on the personal expression of bloggers; What did they write about? How can this data be captured and analyzed? How can the researcher best present this data and findings? Analyzing blog content, identifying key words and transferring text of blogs into images called word clouds. is the solution I have modeled. The project was finalized by creating 42 word clouds, 21 in Wordle and the same number in Tagxedo, both are word cloud generation software. Sifting through the blogs and examining data in different forms enriched my understanding of the variation in the personal expression of the bloggers and helped me to see what they reported and contributed in a totally new light. There are still many questions to be answered about personal expression of people who reported their stories on the Internet in September, 2001 and many more projects and studies that could contribute much more towards understanding of content of 9/11. My hope is that the findings rand methodology reported here will add a small piece in understanding of what happened in September, 2001.
    • Botnet Campaign Detection on Twitter

      Fields, Jeremy; Sengupta, Saumendra; Adviser; White, Joshura; Reviewer; Spetka, Scott; Reviewer (2016-08)
      The goal of this thesis is to investigate and analyze botnet activity on social media networks. We first start by creating an algorithm and scoring method for “likely bots,” and analyze them in conjunction with their neighboring messages to determine whether there is a likely group of bots, or botnet. Chapters 1 & 2 cover the overview of the work, and the previous research done by others. Multiple datasets were collected from Twitter, over different time frames, including random samples, and targeted topics. Chapters 3 & 4 cover the methodology and results of the approach using these datasets. The method is shown to have high accuracy.
    • Brain Correlates of the Interaction Between5-HTTLPRand Psychosocial Stress Mediating Attention Deficit Hyperactivity Disorder Severity

      van der Meer, Dennis; Hoekstra, Pieter J.; Zwiers, Marcel; Mennes, Maarten; Schweren, Lizanne J.; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.; Buitelaar, Jan K.; et al. (American Psychiatric Association Publishing, 2015-08)
      Objective: The serotonin transporter 5-HTTLPR genotype has been found to moderate the effect of stress on severity of attention deficit hyperactivity disorder (ADHD), with stronger effects of stress in carriers of the short allele than in individuals homozygous for the long allele. The underlying neurobiological mechanism of this gene-environment interaction in ADHD is unknown. The authors aimed to determine whether 5-HTTLPR moderates the effect of stress on brain gray matter volume and, if so, which brain regions mediate the effect of this gene-environment interaction on ADHD severity. Method: Structural MRI, 5-HTTLPR genotype, and stress exposure questionnaire data were available for 701 adolescents and young adults participating in the multicenter ADHD cohort NeuroIMAGE study (from 385 families; 291 with ADHD, 78 with subthreshold ADHD, 332 healthy comparison subjects; 55.8% male; average age: 17.0 years). ADHD symptom count was determined through multi-informant questionnaires. For the analysis, a whole-brain voxel-based morphometry approach was combined with mediation analysis. Results: Stress exposure was associated with significantly less gray matter volume in the precentral gyrus, middle and superior frontal gyri, frontal pole, and cingulate gyrus in S-allele carriers compared with participants homozygous for the L-allele. The association of this gene-environment interaction with ADHD symptom count was mediated by gray matter volume in the frontal pole and anterior cingulate gyrus. Conclusions: 5-HTTLPR genotype moderates the effect of stress on brain regions involved in social cognitive processing and cognitive control. Specifically, regions important for cognitive control link this gene-environment interaction to ADHD severity.

      Matthews, Rick; Dwyer, Chrissa (2013)
      The central nervous system (CNS) is extraordinarily complex in both structure and function. The neural extracellular matrix (ECM) is one of the key classes ofmolecules that regulates thedevelopment of the CNS and maintains its structure and function in the adult.Thereby understanding the function of the neural ECMis key to understanding the CNS. The neural ECM is composed of several nervous-system specificproteins, which are hypothesized to uniquely contribute to the defining physiological functions of the CNS. However,work in this area has been hindered by the highly complex molecular properties of the neural ECM, which stem from alterations in expressionand modifications (resulting from glycosylation and proteolytic cleavage) of its constituents. Further defining mechanisms that alter the expression and modifications of neural ECM constituents are critical to fully understanding its complex array of functions. Often in neuropathologies, the neural ECM undergoes dynamic changes providing a valuable tool to further understand its function andthe opportunity to explore its contribution to disease pathology and utility as a therapeutic target. The work presented herein investigates the role of altered expression of the nervous-system specific ECM constituent, Brain Enriched Hyaluronan Binding (BEHAB)/ brevican(B/b), in glioma,and altered glycosylation of the nervous system enriched ECM constituent, RPTPζ/phosphacan, in O-mannosylrelated congenital muscular dystrophies (CMDs). Our work suggests that increased expression of B/b in the glioma tumor microenvironment (TEM) contributes to the pathological progression of these tumors, and reducing its expression is a valuable therapeutic strategy. Additionally, our work evaluates the transcriptional regulatory mechanisms leading to increases inB/b expression in glioma and highlights the potential value of these mechanisms as therapeutic targets. Our work also identifies the absence of O-mannosyl linked carbohydrates on RPTPζ/phosphacan in the brains of CMD models and suggests that altered glycosylation of RPTPζ/phosphacan may have a role in the neuropathologies underlying these disorders. Overall this work provides valuable insight intothe molecular complexities of the neural ECM stemming from changes in the expression and glycosylation of its constituents and furthers our understanding of its function in the normal CNS and in neuropathologies.
    • Bridges: An All-in-One Resource App to Help Narrow the Digital Divide

      Jofre, Ana; Torres, Abigail; Jofre, Ana; First Reader; Lizardi, Ryan; Second Reader (SUNY Polytechnic Institute, 2020-12)
      goal of this project is to design a user-friendly mobile application prototype for people who are disadvantaged by the digital divide. This includes people who are of lower income and those who live in areas where internet isn't accessible or expensive. This application can be accessed through IOS devices as well as a text messaging service system for those without said device. It is an application that will be extremely easy to use and manage, and where users will be able to access multiple resources to gain not only digital literacy but find places that offer computer labs and internet for free, in case neither is available at home. The mobile application's goal is to create resource where the user has everything, they need in a way that is easily accessible; a product that is not currently on the market. In this paper, I will not only explore research on what the digital divide is, but also how it affects those who are disadvantaged by it and ways we can start to help narrow the gap. I will also explore the advantages of mobile applications and how it can be used to narrow the digital divide.
    • Building a University Information Technology Knowledge Base Using TiddlyWiki

      Stam, Kathryn; Thesis Advisor; Lizardi, Ryan; Second Reader; Fischer, Sam (2021-05)
      Keeping a knowledge base up to date can be a difficult and endless task for an Information Technology Services (ITS) department at a university. As technology emerges and is embraced by students and faculty, ITS can become responsible for supporting end users with all sorts of questions and problems. A knowledge base is a website or application used to store helpful information in the form of articles that can be easily shared with end users, giving them a way to support their technology problems without contacting a live person. When managing a large-scale knowledge base, information can be inadvertently replicated in many different areas and contradict other articles, especially when more than one manager can add or edit information. Information modules, or chunks of verified information that can be referenced and inserted into an article, can help eliminate contradictory information and ensure consistency with information that has to be in multiple places through the use of hypertextuality and transclusion. Hypertextuality is a way of organizing information and documents by creating individual bits of information that are assembled together to create a larger document, and transclusion is a way of assembling hypertext documents by simply referencing one into the other. TiddlyWiki is an application that is built around the idea of hypertextuality and transclusion. This project aims to explore the potential for a knowledge base to be built with the TiddlyWiki application.