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A Distinct Pattern Of Growth And Rac1 Signaling In Melanoma Brain Metastasis Cells, Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski, Sinem M Sertel, Silvio O Rizzoli, Bradley Garman, Katherine L Nathanson, Xiaowei Xu, Qing Chen, Jack H Oswald, Michal Lotem, Gordon B Mills, Michael A Davies, Michael P Schön, Ivan Bogeski, Meenhard Herlyn, Adina Vultur

Faculty, Staff and Student Publications

Background: Melanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

Methods: We examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

Results: Brain-specific genetic alterations were not detected; however, MBM cells in vitro …

Mitochondrial Complex Iii Bypass Complex I To Induce Ros In Gpr17 Signaling Activation In Gbm, Sana Kari, Jeyalakshmi Kandhavelu, Akshaya Murugesan, Ramesh Thiyagarajan, Srivatsan Kidambi, Meenakshisundaram Kandhavelu

Department of Chemical and Biomolecular Engineering: Faculty Publications

Guanine nucleotide binding protein (G protein) coupled receptor 17 (GPR17) plays crucial role in Glioblastoma multiforme (GBM) cell signaling and is primarily associated with reactive oxidative species (ROS) production and cell death. However, the underlying mechanisms by which GPR17 regulates ROS level and mitochondrial electron transport chain (ETC) complexes are still unknown. Here, we investigate the novel link between the GPR17 receptor and ETC complex I and III in regulating level of intracellular ROS (ROSi) in GBM using pharmacological inhibitors and gene expression profiling. Incubation of 1321N1 GBM cells with ETC I inhibitor and GPR17 agonist decreased the ROS level, …

Role Of Microorganisms In Communication Between Soil And Plants, Domenico Prisa

Karbala International Journal of Modern Science

Microbial population in the rhizosphere establishes a number of important interactions with plants, whose study is crucial in perspective of sustainable agricultural production. Studies on various plant crops have revealed that, despite the complex microbial biodiversity of the soil, the bacterial microbiome is characterised by multiple functionalities. A better understanding of the molecular mechanisms, underlying the interactions between plants and the microbiome, could enable better development of plants, related to the beneficial action of microorganisms. Therefore, this review aims to describe the characteristics of the rhizosphere microbiome with the interactions that occur between soil and roots, as well as the …

Engineering The Emergent Properties Of Complex Communities, Chang-Yu Chang

Yale Graduate School of Arts and Sciences Dissertations

Microorganisms perform critical functions throughout the biosphere and in biotechnology: from the biogeochemical cycle to the production of sourdough. The overwhelming majority of these functions are usually emergent from the collective outcomes of a large number of microorganisms living in a diverse community. Controlling and manipulating the functions of complex microbial communities is a major aspiration in modern biology. However, we lack a quantitative understanding of how often these functions are emergent, and when it occurs, how we can engineer the emergent properties of microbial communities. In this dissertation, I combine computational approaches with experiments using microbial communities to explore …

Uncovering The Function And Molecular Mechanism Of Mili In Mouse Germline Stem Cells, Yuqi Wang

Yale Graduate School of Arts and Sciences Dissertations

Mouse germline stem cells (GSCs) play critical roles in spermatogenesis by self-renewal and differentiation into daughter spermatogonia. Like other stem cells, the proper functions of mouse GSCs are governed by a delicate regulatory network. PIWI proteins belong to the Argonaute protein family, and they act with piRNAs to control gene expression through transcriptional and post-transcriptional regulation. Extensive research has demonstrated the vital functions of PIWI proteins in germline development, stem cell maintenance, and transposon control. Despite this, the role of PIWI in mammalian GSCs remains largely unknown. MILI is one of three murine PIWI proteins. Recent study has discovered that …

Internal And External State-Dependent Modulation Of Visual Perception And Cortical Processing, Mitchell Paul Morton

Yale Graduate School of Arts and Sciences Dissertations

The ability of humans and other animals to perceive and understand stimuli in the visual world is substantially modulated by internal and external states. Internal states, such as arousal and attention, influence how we can perceive stimuli even when the physical characteristics of that stimulus are constant. Additionally, external configuration of objects in the visual world can influence our perceptual abilities, even when other characteristics remain unchanged. We first studied internal state-dependent modulation of perception by examining what states were associated with accurate perception at threshold, a condition in which the physical properties of a stimulus remain constant, and a …

The Replication Crisis And Ip Law: A Novel Policy Tool For Open Science, Or Cohen Sasson, Ofer Tur‐Sinai

Articles

In recent years, the scientific community has faced a considerable problem the replication crisis. Replication is the process of verifying scientific findings by repeating a published study. It is considered a cornerstone of the scientific enterprise, contributing to the credibility of research findings. Over the past two decades, however, replication has become increasingly difficult; in fact, in some disciplines the non-replicability rate is over 50%. A major factor accounting for this is diminished access to research materials required for replication (replication materials). This problem is particularly acute in computational studies, where the code, software documentation, datasets, and other information are …

Coordination Environment And Thermodynamics Of Colloidal Quantum Dots In Polar Solvents, Nuwanthaka Prasad Jayaweera Millaniyage

Theses and Dissertations

Colloidal semiconductor quantum dots (QDs) have been extensively investigated due to their attractive properties such as size-tunable absorption and emission spectra, large molar extinction coefficients, and significant photostability. These properties make them promising candidates for optoelectronic, photocatalytic, and biomedical applications. Common synthetic procedures of QDs produce nanocrystals capped with long-chain fatty acid derivatives which are stabilized in high boiling point solvents. Especially for bioimaging applications, the exchange of these native hydrophobic ligands with hydrophilic ligands should be performed, while preserving the smaller hydrodynamic radius. The coordination environment and thermodynamic parameters of the ligand exchanges should be carefully investigated to engineer …

Molecular Function And Contribution Of Tbx4 In Development And Disease, Justyna A Karolak, Carrie L Welch, Christian Mosimann, Katarzyna Bzdęga, James D West, David Montani, Mélanie Eyries, Mary P Mullen, Steven H Abman, Matina Prapa, Stefan Gräf, Nicholas W Morrell, Anna R Hemnes, Frédéric Perros, Rizwan Hamid, Malcolm P O Logan, Jeffrey Whitsett, Csaba Galambos, Paweł Stankiewicz, Wendy K Chung, Eric D Austin

Faculty, Staff and Students Publications

Over the past decade, recognition of the profound impact of the TBX4 (T-box 4) gene, which encodes a member of the evolutionarily conserved family of T-box–containing transcription factors, on respiratory diseases has emerged. The developmental importance of TBX4 is emphasized by the association of TBX4 variants with congenital disorders involving respiratory and skeletal structures; however, the exact role of TBX4 in human development remains incompletely understood. Here, we discuss the developmental, tissue-specific, and pathological TBX4 functions identified through human and animal studies and review the published TBX4 variants resulting in variable disease phenotypes. We also outline future research …

Catalyzing Next-Generation Artificial Intelligence Through Neuroai, Anthony Zador, Sean Escola, Blake Richards, Bence Ölveczky, Yoshua Bengio, Kwabena Boahen, Matthew Botvinick, Dmitri Chklovskii, Anne Churchland, Claudia Clopath, James Dicarlo, Surya Ganguli, Jeff Hawkins, Konrad Körding, Alexei Koulakov, Yann Lecun, Timothy Lillicrap, Adam Marblestone, Bruno Olshausen, Alexandre Pouget, Cristina Savin, Terrence Sejnowski, Eero Simoncelli, Sara Solla, David Sussillo, Andreas S Tolias, Doris Tsao

Faculty, Staff and Students Publications

Neuroscience has long been an essential driver of progress in artificial intelligence (AI). We propose that to accelerate progress in AI, we must invest in fundamental research in NeuroAI. A core component of this is the embodied Turing test, which challenges AI animal models to interact with the sensorimotor world at skill levels akin to their living counterparts. The embodied Turing test shifts the focus from those capabilities like game playing and language that are especially well-developed or uniquely human to those capabilities - inherited from over 500 million years of evolution - that are shared with all animals. Building …

Pyrrolopyrrole-Based Materials For High-Contrast Electrochromics, Allison Marie Hawks

Master of Science in Chemical Sciences Theses

Understanding structure-property relationships of underutilized p-conjugated chromophores is an important task for the continued discovery of materials that will find utility in organic electronic applications. Dihydropyrrolo[3,2-b]pyrroles (DHPPs) are synthetically simple and highly tailorable chromophores that can be decorated with diverse functionalities that readily manipulate optoelectronic properties useful for a variety of applications. However, a thorough understanding of how these functionalities influence properties of DHPPs that will be useful in applications such as electrochromism is unknown. Motivated to exploit the synthetic simplicity and tailorability of DHPPs, a family of DHPP chromophores was synthesized to probe how functionality and connectivity …

A New Era Of Morphological Investigations: Reviewing Methods For Comparative Anatomical Studies, K. L. Ford, J. S. Albert, A. P. Summers, B. P. Hedrick, E. R. Schachner, A. S. Jones, K. Evans, P. Chakrabarty

School of Medicine Faculty Publications

The increased use of imaging technology in biological research has drastically altered morphological studies in recent decades and allowed for the preservation of important collection specimens alongside detailed visualization of bony and soft-tissue structures. Despite the benefits associated with these newer imaging techniques, there remains a need for more "tra- ditional"methods of morphological examination in many comparative studies. In this paper, we describe the costs and benefits of the various methods of visualizing, examining, and comparing morphological structures. There are significant differences not only in the costs associated with these different methods (monetary, time, equipment, and software), but also in …

Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari

Department of Orthopaedic Surgery Faculty Papers

Herein, a multifunctional nanobiocomposite was designed for biological application, amongst which hyperthermia cancer therapy application was specifically investigated. This nanobiocomposite was fabricated based on chitosan hydrogel (CS), silk fibroin (SF), water-soluble polymer polyvinyl alcohol (PVA) and iron oxide magnetic nanoparticles (Fe₃O₄ MNPs). CS and SF as natural compounds were used to improve the biocompatibility, biodegradability, adhesion and cell growth properties of the nanobiocomposite that can prepare this nanocomposite for the other biological applications such as wound healing and tissue engineering. Since the mechanical properties are very important in biological applications, PVA polymer was used to increase the …

Rhythmic Eating Pattern Preserves Fruit Fly Muscle Function Under Obese Conditions, Public Relations

Browse All News

No abstract provided.

Reflect To Connect, Sophia Rae Guzules

Liberal Arts and Engineering Studies

Engineering statics is an important course and a prerequisite for many subsequent courses for many engineering majors. It is often students’ first exposure to technical engineering sciences. Most statics concepts are addressed in ways disconnected from students’ prior experiences and interests. Utility Value Interventions (UVIs) have been employed in fields like biology and chemistry to help students connect concepts in class and their lives outside the classroom. However, UVI usage in engineering so far has been limited. In this Senior Project paper, I will describe the process that the team Critical Research in Engineering and Technology Education (CREATE) and I …

The Microbiome And Its Impact On Allogeneic Hematopoietic Cell Transplantation, Florent Malard, Robert R Jenq

Faculty, Staff and Student Publications

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to …

Synthesis, Structural, Magnetic And Computational Studies Of A One-Dimensional Ferromagnetic Cu(Ii) Chain Assembled From A New Schiff Base Ligand, Anne Worrell, Gabriele Delle Monache, Mark M. Turnbull, Jeremy M. Rawson, Theocharis C. Stamatatos, Melanie Pilkington

Chemistry

A new asymmetrically substituted ONOO Schiff base ligand N-(2′-hydroxy-1′-naphthylidene)-3-amino-2-naphthoic acid (nancH₂) was prepared from the condensation of 2–hydroxy–1–naphthaldehyde and 3–amino–2–naphthoic acid. nancH₂ reacts with Cu₂(O₂CMe)₄·2H₂O in the presence of Gd(O₂CMe)₃·6H₂O to afford a uniform one-dimensional homometallic chain, [Cu^II(nanc)]_n (1). The structure of 1 was elucidated via single crystal X-ray diffraction studies, which revealed that the Cu(II) ions adopt distorted square planar geometries and are coordinated in a tridentate manner by an [ONO] donor set from one nanc²⁻ ligand and …

Understanding Environmental Art: A Case Study Of Jason Decaires Taylor's Coral Greenhouse (2019), Laura Dean Hinson

Theses

This thesis highlights the need for a new way to analyze environmental art. In the past, environmental artwork has been discussed in terms of the abstract concepts that drove their creation and the role they played in moving artists outside of the gallery space in the1960s and 70s. However, in recent years environmental artists are increasingly driven by themes of environmental conservation and preservation, using scientific research as the basis of their designs. Because of the shift in focus, developing a new way to discuss environmental art that takes into consideration the influence scientific research has on art production and …

Method Development Biological Agent Personal Decontamination Effectiveness For Airman Battle Uniform Fabric Material: Ms2 Bacteriophage, Alisha Helm

Theses and Dissertations

This article presents a study that investigates the effectiveness of a common decontamination (decon) strategy used by Airmen in the United States Air Force who may find themselves in a densely populated area during an emergency evacuation. Ultimately, this study addresses the following questions: Is there a significant difference in the number of viral particles being re-aerosolized before and after the applied decon strategy, and is this difference significant enough to consider the decon strategy effective? The study entails using MS2 bacteriophage to contaminate swatches of Airman Battle Uniform (ABU) fabric. Swatches were secured to a vortex centered in the …

Civilian And Military Civil Engineer Mission In The Space Domain, Linda E. Kuster

Theses and Dissertations

Military and civil interest in space-based operations has increased dramatically in recent years due to the discovery of life sustaining properties such as water on Mars and advancements in cyber technology. Civilian sector discussions and research have centered on the establishment of permanent extraterrestrial infrastructure, while discussions from the military perspective have focused on providing reliable, resilient infrastructure, capable of withstanding cyber-based and kinetic attacks. Both perspectives account for known threats and sustainment methods required to ensure success in the space domain. With the existence of threats for the military and civilian missions, civil engineers will undoubtedly be critical to …

Knockout Of Ace-N Facilitates Improved Cardiac Function After Myocardial Infarction, Hamid Suhail, Hongmei Peng, Jiang Xu, Hani N. Sabbah, Khalid Matrougui, Tang-Dong Liao, Pablo A. Ortiz, Kenneth E. Bernstein, Nour-Eddine Rhaleb

Hypertension and Vascular Research Articles

Angiotensin-converting enzyme (ACE) hydrolyzes N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) into inactive fragments through its N-terminal site (ACE-N). We previously showed that Ac-SDKP mediates ACE inhibitors' cardiac effects. Whether increased bioavailability of endogenous Ac-SDKP caused by knocking out ACE-N also improves cardiac function in myocardial infarction (MI)-induced heart failure (HF) is unknown. Wild-type (WT) and ACE-N knockout (ACE-NKO) mice were subjected to MI by ligating the left anterior descending artery and treated with vehicle or Ac-SDKP (1.6 mg/kg/day, s.c.) for 5 weeks, after which echocardiography was performed and left ventricles (LV) were harvested for histology and molecular biology studies. ACE-NKO mice showed increased plasma …

Approximating Scaffold Printability Utilizing Computational Methods, Ashkan Sedigh, Pejman Ghelich, Jacob Quint, Evelyn C Mollocana-Lara, Mohamadmahdi Samandari, Ali Tamayol, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Bioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for various applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of materials (bioinks) that can be utilized, either individually or in combination. However, each bioink has unique material properties and extrusion characteristics that affect bioprinting utility, accuracy, and precision. Here, we have extended our previous work to achieve high precision (i.e. repeatability) and printability across samples by optimizing bioink-specific printing parameters. Specifically, we hypothesized that a fuzzy inference system (FIS) could be used as a computational method to address …

Multifunctional Microgel-Based Cream Hydrogels For Postoperative Abdominal Adhesion Prevention, Bo Liu, Yunfan Kong, Olawale A. Alimi, Mitchell Kuss, Huiyin Tu, Wenfeng Hu, Abu Rafay, Kumar Vikas, Wen Shi, Megan Lerner, William L. Berry, Yulong Li, Mark A. Carlson, Bin Duan

Department of Mechanical and Materials Engineering: Faculty Publications

Postoperative abdominal adhesions are a common problem after surgery and can produce serious complications. Current anti-adhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable cream-like hydrogels with multiple functionalities, including rapid gelation, self-healing, anti-oxidation, anti-inflammation, and anti-cellular adhesion. The multifunctional hydrogels were facilely formed by the conjugation reaction of epigallocatechin gallate (EGCG) and hyaluronic acid (HA)-based microgels and polyvinyl alcohol (PVA) based on the dynamic boronic ester bond. The physicochemical properties of the hydrogels including anti-oxidative and anti-inflammatory activities were systematically characterized. A mouse cecum-abdominal wall adhesion model …

Senate Meeting, February 22, 2023, Academic Senate

Academic Senate Minutes

No abstract provided.

Repurposing Atovaquone As A Therapeutic Against Acute Myeloid Leukemia (Aml): Combination With Conventional Chemotherapy Is Feasible And Well Tolerated, Alexandra Mclean Stevens, Eric S Schafer, Minhua Li, Maci Terrell, Raushan Rashid, Hana Paek, Melanie B Bernhardt, Allison Weisnicht, Wesley T Smith, Noah J Keogh, Michelle C Alozie, Hailey H Oviedo, Alan K Gonzalez, Tamilini Ilangovan, Alicia Mangubat-Medina, Haopei Wang, Eunji Jo, Cara A Rabik, Claire Bocchini, Susan Hilsenbeck, Zachary T Ball, Todd M Cooper, Michele S Redell

Center for Medical Ethics and Health Policy Staff Publications

Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The pneumocystis jiroveci pneumonia (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients. Patients with de novo AML were enrolled at two hospitals. Daily AQ at established PJP dosing was combined with standard AML therapy, based on the Medical Research Council backbone. AQ compliance, adverse events (AEs), ease of administration score (scale: 1 (very difficult)-5 (very easy)) …

New Nsaid Conjugates As Potent And Selective Cox-2 Inhibitors: Synthesis, Molecular Modeling And Biological Investigation, Riham M. Bokhtia, Siva S. Panda, Adel S. Girgis, Nermin Samir

Faculty Journal Articles

No abstract provided.

Effects Of Date Seed (Phoenix Dactylifera) Extract In An Animal Model Of Diabetes Mellitus, Sara Refaat

Theses and Dissertations

Diabetes mellitus is a chronic illness and a global epidemic. The commercial diabetic medicines available are expensive and have several adverse effects. Alternative natural products are still being sought for. Date seeds ( Phoenix dactylifera) are either thrown away as garbage or utilized as animal feed. The use of seed extract as an alternative therapy for diabetes offers a cost-effective and all-natural method for managing the disease. Methods Sprague dawley rats were randomly distributed into groups with a sample size of 4 rats per group. Date seed powder was boiled producing a 10% date seed extract which was administered in …

Barriers To Using Legally Authorized Representatives In Clinical Research With Older Adults, Jessica Mozersky, Erin D Solomon, Kari Baldwin, Matthew Wroblewski, Meredith Parsons, Melody Goodman, James M Dubois

2020-Current year OA Pubs

BACKGROUND: Older adults are at increased risk of cognitive impairments including Alzheimer's disease dementia. Legally authorized representatives (LARs) can provide informed consent when a participant is no longer able to, but little is known about barriers to incorporating them in research.

OBJECTIVE: Explore reasons for not asking and documenting participant decisions to appoint LARs among researchers conducting clinical intervention trials studying older adults or individuals with cognitive impairments.

METHODS: Mixed method design consisting of a survey (

RESULTS: 37% (

CONCLUSION: Resources and education to increase awareness and knowledge of LARs are needed. Researchers studying older adults should, at minimum, …

The Position Of Insider (Emic) And Outsider (Etic): A Review Of Deborah Court And Randa Khair Abbas’ Insider-Outsider Research In Qualitative Inquiry: New Perspectives On Method And Meaning, Elih Sutisna Yanto, Moses Pandin Mop

The Qualitative Report

In their book, Insider-Outsider Research in Qualitative Inquiry: New Perspectives on Method and Meaning by Deborah Court and Randa Khair Abbas, they deconstruct the outdated or puzzling terminology associated with this type of research, examine ethical challenges, and recommend methodological approaches. This book also situates qualitative insider-outsider research, by its very nature, within the larger research ecology. The authors describe in full a researcher partnership—a relationship that is more personal and fruitful than a team and significantly more than the sum of its parts. Through their nearly two-decade-long research collaboration and study of the Israeli Druze, the authors have established …

Discovery Of Novel Bioactive Tanshinones And Carnosol Analogues Against Breast Cancer, Miguel A. González-Cardenete, Natalia González-Zapata, Lucinda Boyd, Fatima Rivas

Faculty Publications

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC50 …