Grants

DECD

Continuation and completion of streetscape improvements along West Main Street from Deepwood Drive to Grove/Warren Streets

Woodbury

Continuation of MS4 permitting process

DECD

Continuation of streetscape and other improvements in the Village Center

The ARTS Council of the Southern Finger Lakes

Continuation of support in Chemung, Schuyler, Steuben and Cortland

DECD

Continuation of the design and construction of the Silas Deane Highway Revitalization program

DECD

Continuation of the façade improvement program, traffic calming and installation of tourism signs

DECD

Continuation of the Historic downtown Revitalization Project

DECD

Continuation of the Main Street Commercial Revitalization plan

DECD

Continuation of the Main Street corridor improvements including façade improvements, sidewalk installation, tree installation, community event sign and pedestrian cross walk signal

DECD

Continuation of the Main Street streetscape program

DECD

Continuation of the sidewalk replacement program

DECD

Continuation of the Silas Deane Highway revitalization project

DECD

Continuation of the Village Center Sidewalks and Lighting project

National Institutes of Health

Continuation or Revision of NIDCR Clinical Trial Planning and Implementation Cooperative Agreement (UH3 Clinical Trial Required)

DSS

Continued renovation of the West Hartland Community Center

Air Force -- Research Lab

Continuing Human Enabling Enhancing Restoring and Sustaining

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Applicant: Ahmad Haidar Project Summary: Abstract Diabetic ketoacidosis (DKA) is still a life-threatening risk in type 1 diabetes (T1D) that can occur with acute illness or insulin interruption. Currently, the only means to monitor this risk are capillary or urine testing, which provide few measurements only prompted by symptoms of the patient, or by monitoring for high glucose levels with continuous glucose monitoring, which do not always correlate with ketosis. Sodium-glucose-linked cotransporter 2 (SGLT2) inhibitors are a group of anti-hyperglycemic medications that have been shown to have cardiovascular and renal benefits, and reduce all- cause mortality in those with and without diabetes. These medications, when studied in T1D, increased risk of euglycemic DKA except with empagliflozin 2.5 mg, which had no renal benefit in post-hoc analyses. Despite the risk, their off-label use in T1D remains common worldwide. A continuous ketone monitor (CKM) has the potential to revolutionize the safety around ketosis management. A sensor that alarms at increasing levels of beta-hydroxybutyrate can allow for immediate action to prevent DKA from occurring. It can also provide useful information on normal biochemistry with SGLT2 inhibitor use in T1D. We aim to conduct a 2-part outpatient study, assessing the use of CKM to reduce ketosis and DKA while using SGLT2 inhibitors. In Part 1A, 24 participants with T1D will use a CKM and be given empagliflozin 2.5 mg for four weeks then empagliflozin 10 mg for five weeks. Participants will perform an exercise challenge during the fourth week of empagliflozin 10 mg use and be on a low-carb diet during the last week of empagliflozin 10 mg use. From this study, CKM data and participant characteristics will be collected to better understand how changes in ketone levels are affected by varying doses of empagliflozin, and which metrics help predict ketosis and DKA. Using this data, we will refine our CKM algorithm that aims to (1) prevent DKA in people with T1D on empagliflozin, and (2) identify which individuals can continue safely on higher doses of empagliflozin. Moreover, we aim to develop educational guidelines pertaining to the general use of the CKM system, and its use in managing DKA risk, exercise, and low-carb diets. Part 2 will be a 6-month study where 72 participants with T1D will use a CKM and be given empagliflozin at escalating doses until they reach their maximum tolerated dose, as determined by our refined algorithm. Education will be provided using the educational guidelines developed in Part 1, and the efficacy of our refined algorithm will be assessed. The goal of our work is to provide a safe way for people with T1D to use SGLT2 inhibitors. Page 1 of 1

NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases

Project Summary Psoriasis is a debilitating autoimmune skin disease that affects more than 125 million adults globally. While prototypically associated with immune cell infiltration in the skin, psoriasis preferentially affects the extensor surfaces of the joints such as the outside of the elbows and knees. Current treatments for psoriasis include topical steroids, which have poor side-effect profiles with long-term use, and systemic immunomodulatory agents, which, although promising, have notable off-target immune effects. Better understanding of the nature of inflammation in the skin may help to develop more precisely targeted therapeutics for psoriasis and associated disorders. The epidermis of the skin, chiefly composed of keratinocytes, provides an essential barrier between the organism and the environment. Mechanical disruption of the barrier is associated with development of lesions in psoriasis and associated disorders; however, it isn’t understood how barrier disruption vs. mechanical sensation of strain by keratinocytes contributes to their development of psoriatic phenotype. While canonical inflammatory cells are the drivers of acute inflammation in psoriasis, their action depends on a receptive environment built up by keratinocyte signaling and behavior. In addition, there is evidence that keratinocyte autoregulatory loops may establish that autoimmune-prone environment prior to stimulation by canonical immune cells. As mechanosensing cells at the skin barrier, keratinocytes are uniquely privileged in the information available to them—unlike canonical immune cells, they have access to both mechanical stimuli and direct exposure to the status of the epidermal barrier. In this way, keratinocytes are critical messengers of mechanical and physical barrier status. However, it is difficult to tease apart contributions to inflammation, as there is currently no method for continuously monitoring inflammatory markers at minute resolution. Furthermore, there is currently no system for applying physiologic strain to 3D models of psoriasis in vitro. The technology development portion of this proposal is to design such a continuous monitoring device and develop a system for applying strain to 3D models of keratinocytes. This proposal will build the tools necessary to test the hypothesis that keratinocyte mechanosensing modulates their inflammatory behavior in psoriasis. In Aim 1, I will optimize and validate reagentless sensing devices for continuous monitoring of immunoregulatory cytokines released by keratinocytes. This aim will seek to understand what events happen on the minute-to- minute scale as keratinocytes experience mechanical strain. In Aim 2, I will build a novel tissue culture system for applying controlled strains and measuring mechanical properties of 3D human skin models. In this aim I will visualize the effect of strain on cytoskeletal and extracellular matrix mechanics, and determine how applied strains change the threshold for autoimmune activation of keratinocytes.

NHLBI - National Heart Lung and Blood Institute

Blood pressure (BP) is one of the strongest risk factors for cardiovascular disease (CVD) and still cannot be monitored in a continuous and unobtrusive manner due to technological limitations, leaving significant gaps in evaluating CVD risk. Continuous BP monitoring during sleep may be crucial in the discovery of new CVD biomarkers for two primary reasons: 1. sleep is a more controlled-environment than the active periods of daytime and 2. the autonomic nervous system undergoes significant changes during sleep that are essential for restorative processes. Disruptions to the autonomic function, or imbalance between the sympathetic and parasympathetic activity, are prevalent in CVD, leading to higher frequency and magnitude of BP fluctuations and overall increased stress to the cardiovascular (CV) system. Furthermore, because of the strong relationship between sleep disorders and CVD, measuring BP during sleep can identify underlying mechanisms and potential causal relationships. Current methods to measure BP in sleep use intermittent cuff-based monitors, leaving lengthy unmonitored gaps between measurements. However, rapid BP fluctuations occurring in spans of tens of seconds can be significant. Many devices have recently been developed that attempt to measure BP non- invasively and continuously, but no technology has demonstrated the accuracy, responsiveness, usability and cost-effectiveness to fill the unmet need. This proposed project builds upon the company’s core beat-to-beat BP sensing technology to develop VeriSleep, a wearable device that quantifies CV burden, or total work the heart experiences in real-time, in order to provide a stronger and more direct biomarker for CV health. To do so, a robust device will be built that can withstand the rigors of the nighttime environment and measure absolute and relative changes of BP in mmHg. The project also seeks to validate the core technology’s ability to track transient BP surges in healthy individuals undergoing induced hypoxia and breathing maneuvers. Finally, the project will use the core technology to evaluate differences between healthy and non-healthy (apneic) patients based on metrics derived from the continuous BP measurements. The proposed project represents the first of its kind technology to directly measure continuous BP during sleep, enabling classification of CV conditions based on CV burden. This will refine our understanding of CVD, providing deeper insights into this complex condition and potentially enabling more personalized approaches.

NYC Department of Cultural Affairs

Continuum Culture & Arts, Inc.

City of Richmond

Contra Costa Family Justice Center

RaySecur, Inc

Defense and Law Enforcement and Security and Safety Equipment and Supplies

HNTB CORPORATION

Engineering and Research and Technology Based Services-Professional engineering services-Civil engineering-Highway engineering

NINDS - National Institute of Neurological Disorders and Stroke

Resting state functional magnetic resonance imaging (rs-fMRI) contains a wealth of information about the large-scale structure of intrinsic neural activity in the brain and is widely used to study alterations in neurological or psychiatric disorders. Our prior work demonstrates that intrinsic brain activity is dominated by a few whole- brain spatiotemporal patterns that occur repeatedly over time, but little is known about the mechanisms that coordinate these patterns and therefore about how altered patterns in brain disorders should be interpreted. The spatiotemporal patterns exhibit features that are undetectable with time-averaged analysis methods (e.g., functional connectivity) and which may provide important insight into underlying neurophysiology. Three prominent features in need of explanation are sparse instances of strong transient network activity; variability in the amplitude of the rs-fMRI signal across brain areas and over time; and propagation along the cortex that happens concurrently with network interactions. We have developed an innovative method for simultaneous wide-field optical imaging (WOI) and rs-fMRI that will allow us to test potential explanations for these features of intrinsic activity. WOI can detect fluorescence from activity in specific types of cells over the entire cortex, obtaining images of spatial patterns rather than the localized measurements obtained with electrophysiology. Functional connectivity has been observed in WOI of excitatory and inhibitory activity, suggesting that transient network activation patterns of both types of neurons may underlie the strong transient activations observed with rs-fMRI. Aim 1 utilizes simultaneous rs-fMRI and WOI of excitatory and inhibitory neurons to determine if the transient patterns of activity are common and synchronous across modalities. Aim 2 uses the same method to investigate the relationship between the amplitudes of excitatory and inhibitory activity and the amplitudes of the rs-fMRI fluctuations. Finally, we hypothesize that signal propagation is mediated by astrocytes, which have been shown to give rise to traveling waves. Aim 3 applies simultaneous rs-fMRI and WOI to determine the role of astrocytes in the propagation of signal across the cortex. This proposal will make strides toward understanding the coordination of intrinsic brain activity, which is altered in nearly every psychiatric and neurodegenerative disorder. The proposed experiments provide insight into these alterations for the purposes of diagnosing, evaluating, and treating dysfunction in the brain. The knowledge gained about the large-scale organization of brain activity will help to bridge the gap between fundamental studies of activity in local circuits and the whole-brain activity detectable with noninvasive imaging techniques. As experiments proceed, we will further refine the cutting-edge technologies that we have developed for multi-modal WOI and rs-fMRI studies, and we will make the methods and the resulting data freely available.