250 research outputs found
An Analysis of Anonymity in the Zcash Cryptocurrency
Cryptocurrencies such as Bitcoin have shown that a game theory approach to decentralized consensus can create value. In Bitcoinâs game theory, as long as an adversary does not acquire a majority of computational power it is more profitable for them to obey by the rules of the network. Moreover, Bitcoinâs transparent, immutable, publicly auditable ledger allows any party to trivially verify the correctness of transactions. This transparency means that an adversary may, while obeying the rules of the network, trace the flow of transactions. By corresponding a transaction to an individual, the adversary may determine the source and destination of that userâs funds, resulting in a serious loss of privacy. Several alternative cryptocurrencies ("altcoins") have endeavored to create systems that preserve privacy. The chief difficulty in creating such a system is devising a way that the correctness of transactions can be easily verified while obscuring the underlying details of the transactions. Such systems are akin to homomorphic encryption, where operations carried out on ciphertext correspond to the same operation on the cleartext. In this thesis, we review a cryptographic method known as zk-SNARKs for anonymizing transactions in cryptocurrencies. We summarize the mathematical foundations of this construction, tracing the development of its underlying principles through the literature. We also analyze Zcash, a publicly traded cryptocurrency that uses zk-SNARKs. Using blockchain analysis along with certain heurestics, we are able to potentially deanonymize transactions that account for 31.5% of Zcashâs private transaction volume.Master of ScienceComputer and Information Science, College of Engineering & Computer ScienceUniversity of Michigan-Dearbornhttps://deepblue.lib.umich.edu/bitstream/2027.42/143130/1/quesnelle-thesis.pdfDescription of quesnelle-thesis.pdf : Thesi
Michigan Statewide Nonprofit Leadership Census 2022
The Michigan Statewide Nonprofit Leadership Census identifies the percentage of BIPOC (Black, Indigenous, and People of Color) nonprofit leaders statewide to provide a clear understanding of the racial and ethnic composition of staff members and boards at nonprofits. The report, which identifies equity issues facing different communities across the state, focused on six regions: Lakeshore/West Michigan, Metro Detroit, Mid-State/Central Michigan, Southern Central Michigan, Tip of the Mitt, and the Upper Peninsula.Key findings include:Metro Detroit reported the highest percentage of BIPOC-led organizations (38%), while Tip of the Mitt reported the lowest (1%).The budget range reported for most responding nonprofit organizations was concentrated in two groups: more than 250,000 or 5 million.At the state level, the majority of nonprofits (93%) reported only one executive director who is more likely to be at least one of the following characteristics: White, female, aged 45â64 years old, and one who has served in the leadership role for no more than five years.Reporting at least one BIPOC executive director was associated with more organizations reporting multiple executive directors, younger directors, as well as a higher percentage of BIPOC members on its board and staff.Housing was determined to be a pressing equity issue in Michigan. Notably, BIPOC-led organizations are much more likely to choose race and ethnicity as one of their community's most pressing equity issues
YaRN: Efficient Context Window Extension of Large Language Models
Rotary Position Embeddings (RoPE) have been shown to effectively encode
positional information in transformer-based language models. However, these
models fail to generalize past the sequence length they were trained on. We
present YaRN (Yet another RoPE extensioN method), a compute-efficient method to
extend the context window of such models, requiring 10x less tokens and 2.5x
less training steps than previous methods. Using YaRN, we show that LLaMA
models can effectively utilize and extrapolate to context lengths much longer
than their original pre-training would allow, while also surpassing previous
the state-of-the-art at context window extension. In addition, we demonstrate
that YaRN exhibits the capability to extrapolate beyond the limited context of
a fine-tuning dataset. We publish the checkpoints of Llama 2 7B/13B fine-tuned
using YaRN with 64k and 128k context windows at
https://github.com/jquesnelle/yar
Intracellular Signaling Mechanisms of Resistance to EGFR-Targeting Agents
The epidermal growth factor receptor (EGFR) is widely expressed in head and neck squamous cell carcinomas (HNSCC) and activates many growth and survival pathways within tumor cells. EGFR-targeting agents are only modestly effective in treating HNSCC, however, and a consistent mechanism of resistance has not been identified, in part, due to the paucity of preclinical models. This dissertation focuses on generating EGFR-inhibitor resistant preclinical models in order to identify biomarkers that may be predictive of response to these agents.
We have assessed the response of a panel of HNSCC cell lines to the EGFR inhibitors erlotinib and cetuximab to determine their relevance as models of resistance to these agents. We defined a narrow range of response to erlotinib in HNSCC cells in vitro. We attempted to generate models of cetuximab resistance in cell line-derived xenografts and heterotopic tumorgrafts directly from primary HNSCC patient tumors. Our studies in HNSCC suggest that heterotopic xenografts are more representative of patient response to cetuximab than cell-line derived xenografts, although we did establish a model of cetuximab resistance from bladder cancer cell line-derived xenografts.
A candidate-based approach was used to examine the role of HER2, HER3, and c-Met on mediating EGFR inhibitor resistance. We identified increased phosphorylation of a carboxyl-terminal fragment of HER2 (611-CTF) in cetuximab-resistant cells. Afatinib, an irreversible kinase inhibitor targeting EGFR and HER2, successfully restored cetuximab sensitivity in vitro. When afatinib was combined with cetuximab in vivo, we observed an additive growth inhibitory effect in cetuximab-resistant xenografts. We also show that while c-Met activity is not sufficient to alter cellular response to erlotinib, concomitant inhibition of c-Met and EGFR is required for the deactivation of MAPK in the presence of stimulatory ligands. These data support the proposed role for co-targeting c-Met with EGFR in the treatment of HNSCC.
The studies presented here are significant because, in addition to suggesting that 611-CTF may be a novel biomarker for cetuximab resistance, they provide a thorough assessment of modeling EGFR inhibitor resistance in HNSCC and suggest heterotopic tumorgrafts as a plausible new model for examining cetuximab resistance in future studies
Scheduling a conference to minimize RSVP conflicts
Abstract This paper describes a conference scheduling problem where, at the time of registration, participants RSVP to events which they would like to attend. Based upon these preferences, an assignment of events to rooms and time slots should be determined that minimizes the number of RSVP conflicts and satisfies a number of hard constraints. We show that our problem, and several variants of it, are NP-hard. An integer programming model is developed to solve the problem and a computational study of this model is performed on instances generated from real data. Improvements to the model, including a symmetry breaking reformulation and a dualization of some hard constraints, are shown to significantly improve solution times, making the problem tractable for the desired real world application
Ischemic preconditioning modulates ROS to confer protection in liver ischemia and reperfusion
Ischemia reperfusion (IR) injury is a significant cause of morbidity and mortality in liver transplantation. When
oxygen is reintroduced to the liver graft it initiates a cascade of molecular reactions leading to the release of reactive oxygen species (ROS) and pro-inflammatory cytokines. These soluble mediators propagate a sterile immune response to cause significant tissue damage. Ischemic preconditioning (IPC) is one method that reduces hepatocellular injury by altering the immune response and inhibiting the production of ROS. Studies quantifying the effects of IPC in humans have demonstrated an improved liver enzyme panel in patients receiving grafts pretreated with IPC as compared to patients receiving the standard of care. In our review, we explore current literature in the field in order to describe the mechanism through which IPC regulates the production of ROS and improves IR injury
Priapism After Epidural or Spinal Anesthesia
Introduction: Preoperative epidural and spinal anesthesia improves patient outcomes by reducing potential side effects due to prolonged treatment with general anesthesia as well as mitigating postoperative pain. Rarely, patients receiving epidural and spinal anesthesia develop priapism secondary to administration of the anesthetic agent. Little is known about the development of this complication and its management following onset. Rationale: A case of priapism following administration of epidural anesthesia in Kalamazoo, MI, at Bronson Methodist Hospital, prompted a search of the literature into the etiology, pathophysiology, and management of such cases. Review of Literature: A search of two databases was conducted, including keywords âpriapism, anesthesia, epidural, humansâ among others. This search produced 305 unique articles. Priapism cases due to underlying conditions, such as sickle cell anemia, were excluded. All cases of non-spinal and non-epidural anesthesia were excluded. In total, 36 articles from the search were included in this review. Subsequently, a hand review of the selected articles produced an additional 121 new papers which are currently under review and may be included in our final review. Results: Priapism appears to be a rare complication of anesthesia, but cases are often unreported and real incidence is unknown. Overall incidence of priapism in the United States is 0.2-0.3 cases/100,000. Etiology and contribution of medical, genetic, and environmental factors are unclear. Bolus doses of bupivicaine were involved in multiple reported cases. Interestingly, epidural anesthesia can both cause and treat priapism, suggesting that pathophysiology involves an imbalance of the parasympathetic and sympathetic tone of the penile vasculature. Timing of erection onset complicates treatment of this side effect. Preoperatively, the inciting agent is generally withdrawn and the procedure is postponed until other anesthetic options are explored. Postoperatively, another anesthetic is administered for pain relief. Intraoperatively, the appropriate course of action is multifactorial, depending patientâs underlying health status and variables inherent to the procedure. No long-term adverse effects, such as erectile dysfunction or dysuria, were reported. During the episode patients experienced distress at the inability to urinate and acute pain from the prolonged erection. Conclusion: Priapism due to epidural and spinal anesthesia remains a mysterious phenomenon. Bupivicaine has been suggested as a causative agent, perhaps selectively inhibiting sympathetic tone to the penile vasculature. There are many factors to consider when treating this complication, including procedural and patient characteristics
Ten years of global faculty development in educational scholarship through the IAMSE Medical Educator Fellowship:Submitted on behalf of the IAMSE Educational Scholarship Committee
Pan-HER - an antibody mixture targeting EGFR, HER2, and HER3 abrogates preformed and ligand-induced EGFR homo- and heterodimers:Pan-HER abrogates EGFR dimers
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