cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
STRUCTURAL BIOLOGY OF ANTHRACYCLINE METABOLISM
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Anthracyclines are a large class of natural products which are used in chemotherapy to combat a wide variety of cancers. Despite being decades old, they are still considered to be highly effective and are used to treat a substantial fraction of all cancers so improvements would have wide-ranging effects. Before a significant fraction of the drug is able to exert its effects as a topoisomerase II inhibitor, DNA intercalator or inhibitor of RNA synthesis, the active carbonyl-containing form of the compound is enzymatically reduced to the corresponding alcohol which is much less active and is toxic to cardiac muscle. In humans, two enzymes in the NADPH-utilizing aldo-keto reductase (AKR) superfamily have previously been identified as being responsible for this reaction: aldose reductase (AR) and aldehyde reductase (ALR). Inhibiting the enzymes catalyzing this reaction could therefore enhance the therapeutic effects of these compounds and minimize the severe side effects which limit dosage. Alternatively, finding cytotoxic anthracyclines which are not reduced by AKRs may identify molecules with improved clinical activity. Prior work has shown that AR, ALR and the eight other human AKRs have substantially overlapping substrate specificities when other carbonyl-containing substrates have been examined. Most of these enzymes are expressed in various tumor cell lines and some have in fact been used as biomarkers for certain cancers. To determine which of them are capable of forming the less active and toxic alcohol, we will kinetically quantitate the activity of each versus several clinically relevant anthracyclines such as doxorubicin, daunorubicin and epirubicin. This information will be used to direct later efforts to develop inhibitors which are specific to this set of enzymes using a combinatorial strategy that has allowed us to successfully produce these in the past. After the target enzymes have been defined, crystal structures of dead-end complexes with each enzyme (i.e. AKR/NADP+/anthracycline ternary complex) will be determined. This information will then be used to guide attempts to computationally dock the ~2,000 known anthracyclines in an effort to screen for those that are unable to serve as substrates. Once these compounds are identified, assays will be done in the future to determine kinetic and/or binding constants for those deemed most promi
Udeina stuckenbergi Zicsi 1998
Creators: name: Csuzdi, Csaba
name: Szederjesi, Tímea
name: Sherlock, Emma
Publisher: name: Zenodo
Year: 2018
Subjects: Biodiversity
Taxonomy
Animalia
Annelida
Clitellata
Opisthopora
Acanthodrilidae
Udeina
Udeina stuckenbergi

description: Udeina stuckenbergi Zicsi, 1998
Udeina stuckenbergeri Zicsi, 1998a Mitt. Hamb. Zool. Mus. Inst. 95: 69.
Udeina stuckenbergi: Plisko 2004 Afr. Invert. 45: 311.
description: Published as part of Csuzdi, Csaba, Szederjesi, Tímea & Sherlock, Emma, 2018, Annotated checklist of earthworm species described by András Zicsi (Clitellata: Megadrili), pp. 11-42 in Zootaxa 4496 (1) on page 14, DOI: 10.11646/zootaxa.4496.1.4, http://zenodo.org/record/1447011
New York – New Jersey Highlands regional study: 2002 update
Creators: name: No Name Supplied
Publisher: name: No Publisher Supplied
Year: 2002

description: The purpose of this study update is to…1. Reassess the condition of natural resources in the Highlands region;2. Analyze land cover change and potential land use;3. Identify significant areas to be conserved and protected; and4. Develop strategies to protect the long-term integrity of the region.This updated study report builds on the foundation established by the 1992 study. It focuses on the location and priority of regional natural resources that are most critical, and on strategies that can be implemented by public and private sectors in the stewardship of the Highlands.This update was guided by the 1992 study in regard to the vision and goals for the Highlands region. The resource assessment and subsequent analyses were expanded, however, taking advantage of the availability of spatial data and improved analytical techniques using Geographic Information System (GIS) technology. The study team adopted the Highlands study area boundaries from the 1992 study and expanded them from the Hudson River eastward to the New York–Connecticut border using topography and geology as key determinants. The current study area encompasses approximately 1.5 million acres of Appalachian ridges and valleys and stretches from the Lower Hudson River Valley in New York to the Delaware River in New Jersey.
New Jersey land use/land cover update: 2000-2001
Creators: name: No Name Supplied
Publisher: name: No Publisher Supplied
Year: 2004

description: The rapid pace of development and land use change has resulted in a high demand for updated land use/land cover data to inform ongoing land use planning and growth management programs within New Jersey Department of Environmental Protection (NJDEP) and other state and local agencies. There were three main objectives for this research: 1) to use medium scale satellite remotely sensed imagery (i.e., 10 meter spatial resolution SPOT Panchromatic imagery) to provide a consistent mapping of newly developed urban lands as of Year 2000/2001 across the state; 2) to use medium scale satellite remotely sensed imagery (i.e., 30 meter Landsat Enhanced Thematic Mapper) to provide a consistent mapping of land cover and impervious surface cover as of Year 2000/2001 across the state; and 3) evaluate the applicability of using less-costly satellite imagery as a means to update NJDEP’s air-photo based Land Use/Land Cover (LULC) data in a cost-effective manner.
Yagansia covarrubiasi Zicsi 1989
Creators: name: Csuzdi, Csaba
name: Szederjesi, Tímea
name: Sherlock, Emma
Publisher: name: Zenodo
Year: 2018
Subjects: Biodiversity
Taxonomy
Animalia
Annelida
Clitellata
Opisthopora
Acanthodrilidae
Yagansia
Yagansia covarrubiasi

description: Yagansia covarrubiasi Zicsi, 1989
Yagansia covarrubiasi Zicsi, 1989a Acta Zool. Hung. 35 (3/4): 420.
description: Published as part of Csuzdi, Csaba, Szederjesi, Tímea & Sherlock, Emma, 2018, Annotated checklist of earthworm species described by András Zicsi (Clitellata: Megadrili), pp. 11-42 in Zootaxa 4496 (1) on page 14, DOI: 10.11646/zootaxa.4496.1.4, http://zenodo.org/record/1447011
Microgobius miraflorensis Gilbert & Starks 1904
Creators: name: Angulo, Arturo
name: Betts, Joel T.
name: González-Alemán, Néstor J.
name: Castañeda, Edgar
name: Berghe, Eric Van Den
name: Elías, Diego J.
name: Mcmahan, Caleb D.
name: Matamoros, Wilfredo A.
Publisher: name: Zenodo
Year: 2023
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Perciformes
Gobiidae
Microgobius
Microgobius miraflorensis

description: Microgobius miraflorensis Gilbert & Starks 1904. Miraflores Goby; Gobio de Miraflores, Gobio Jupón
Vouchers: Not available. Distribution: Eastern Pacific Ocean; from the Gulf of California, Mexico, to northern Peru; entering estuaries and littoral lagoons and ascending river courses; (Nicaragua) PN (Pacific); 0–8 masl; Per, Dia, Amp. Occurrence and conservation status: Nat; LC (2019), population trend unknown. Literature: Villa (1982: 230; detailed description, including illustrations and an identification key, and information on distribution and ecology), Robertson & Allen (2015: 2067; detailed description, including illustrations, and information on distribution, with a map, and ecology) and Angulo (2021: 39; listed, including information on distribution).
description: Published as part of Angulo, Arturo, Betts, Joel T., González-Alemán, Néstor J., Castañeda, Edgar, Berghe, Eric Van Den, Elías, Diego J., Mcmahan, Caleb D. & Matamoros, Wilfredo A., 2023, Continental fishes of Nicaragua: diversity, distribution and conservation status; with an annotated and illustrated checklist of species and an identification guide to families, pp. 1-89 in Zootaxa 5376 (1) on page 37, DOI: 10.11646/zootaxa.5376.1.1, http://zenodo.org/record/10208788
Investigate the Hippo pathway in stress response and cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Two decades of studies in multiple model organisms have established the Hippo as a key signaling pathway in organ size control and cancer prevention. Hippo dysregulation exerts a significant impact on tissue homeostasis and cancer development; therefore, further investigation of the functions and regulatory mechanisms of this key signaling pathway will be sure to unveil the mystery of organ size control and more importantly develop novel therapeutic strategies for cancer treatment. The Hippo pathway can sense growth conditions including perceived physical signals from cell microenvironment, growth factors/mitogenic hormones and recently discovered metabolic status, to control cell proliferation and survival by restricting its downstream effector YAP. Excitingly, our preliminary studies have revealed an unexpected role of the Hippo pathway in heavy metal stress response, where inhibition of Hippo signaling significantly protect cells against heavy metal-induced toxicity. Mechanistically, the Hippo pathway can directly target metal-responsive transcription factor 1 (MTF-1), a transcription factor that plays an essential role in heavy metal response. Notably, this Hippo-mediated regulation of MTF-1 is independent of its downstream effector YAP, suggesting a YAP-independent function of Hippo signaling in heavy metal response. Interestingly, the Hippo pathway can be mutually regulated by heavy metals, where targeting metal homeostasis significantly suppresses YAP-dependent oncogenic activities by activating the Hippo pathway. Based on these preliminary findings, we propose to 1) establish the role of Hippo signaling in heavy metal response; 2) elucidate the mechanism underlying the interplay between Hippo and heavy metal homeostasis; and 3) investigate the translational potential by targeting heavy metal homeostasis for YAP-dependent cancer treatment. My current research on the Hippo signaling pathway serves not only as a paradigm but also as a stable platform to pave a way for me to become a leader in the Hippo field. My proposed studies will further inspire my endeavor in the Hippo signaling exploration and allow me to generate solid preliminary data to secure the external funding (e.g., R01, DoD, ACS) in the near future.
Studying tumor heterogeneity using single-cell epigenomics
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: While mutations and copy number variations in the genome are known drivers of cancer, there is increasing evidence that dysregulation in epigenetic marks such as DNA methylation (5-methylcytosine or 5mC) and disruption of the 3-dimensional organization of chromosomes within the nucleus of a cell play a critical role in the progression of tumors. In addition to these complex genome-wide transformations, tumors are also characterized by dramatic cellular heterogeneity that remain one of the major challenges in the effective treatment of cancer. However, it remains unclear how the epigenome influences tumor heterogeneity. This is because current measurements are typically made from a bulk population that fail to capture the cell-to-cell variability in 5mC or genome organization and the resulting gene expression heterogeneity. Further, while bulk studies in tumor cells have shown that large blocks of hypomethylation in 5mC appear to correlate with regions of the genome that interact with the nuclear periphery (known as lamina-associated domains or LAD), these experiments cannot distinguish if these profiles occur in the same cell or unrelated cells. Therefore, it remains unknown if a causal relationship exists between 5mC and genome organization, and how dynamic changes in such epigenetic features regulate cellular phenotypes. To overcome the technical challenges in addressing these questions and to understand how dysregulation in 5mC and genome organization together alter gene expression in tumor cells, we propose the following aims: (1) Develop a novel single-cell sequencing technology to simultaneously quantify 5mC, LAD organization and mRNA from the same cell. Integrated measurements of both the epigenetic features and the transcriptome will allow us to directly correlate 5mC to LAD structure and how they combine to regulate gene expression in a single cell. (2) Employ a recently developed model of tumor progression in intestinal organoids to study how simultaneous reprogramming of 5mC and LAD organization directly influences the dynamics of aberrant gene expression by the sequential introduction of mutations in APC, P53, KRAS and SMAD4 genes. This seed grant will lay the foundation for further systematic exploration into the potential mechanisms that mediate the cross-talk between 5mC and genome organization and its influence on gene regulatory networks.
Measuring land use change in New Jersey: Land use update to year 2000
Creators: name: Lathrop, Richard G.
Publisher: name: No Publisher Supplied
Year: 2004

description: The objective of this research was to use medium scale satellite imagery to provide a consistent mapping of land use and land cover change as of Year 2000/2001 across the state. As a supplement to the research, this report is an assessment of the major trends in the land use changes occurring between 1995/199& and Year 2000.The overall trends revealed in the 2000 Land Use Update show that New Jersey’s urban development continues at a pace comparable with the 1986 to 1995 time period.Taken on an annual basis (based on unadjusted figures from the map analysis), New Jersey adds approximately 14,640 acres of new urban land use and 4,1&0 acres in transition to future development or mining while losing approximately 9,590 acres of forest, 5,180 acres of farmland, and 1,020 acres of natural wetlands. These results suggest for the 1995 to 2000 time period that the annual rate of forest loss to development has remained relatively steady, while the rate of farmland and wetland loss has declined.
An astroglial mechanism of radiation-induced brain injury
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cranial radiation therapy (RT) for the treatment of primary and secondary malignancies of the brain are often associated with severe cognitive dysfunction. This is a particularly critical problem for survivors of childhood cancer who frequently live long post-RT but experience reductions in IQ by as much as 3 points per year that seriously impact quality of life. This situation is confounded by the absence of satisfactory treatments for reducing neurocognitive side effects. RT induces progressive neurodegenerative changes including oxidative stress, reduced neurogenesis, increased inflammation, and astrogliosis. However, many of the molecular mechanisms underlying RT-induced cognitive decline remain to be resolved. Astrocytes form complex astroglial networks by contacting thousands of synapses (memory units) that are actively involved in modulating synaptic plasticity. We have shown that RT-induced cognitive disruption coincides with astrocytic hypertrophy, elevated expression of astrogliosis genes and microglial activation. Therefore, we hypothesize that detrimental changes in astrocyte function contribute significantly to cognitive dysfunction. The complement system is a potent mediator of microglial and astrogial activation, but it also has a range of non-immune functions in the CNS, including synaptic pruning. Complement proteins are produced by neurons, microglia and astrocytes. Particularly, global elevation in the expression of complement protein C1q in the CNS has been reported in neurodegenerative conditions including the Alzheimer’s disease or epileptic brain. These proteins play important roles in maintaining cellular viability and synaptic function in the CNS. Our preliminary data indicate that cranial RT leads to a chronic upregulation in the gene expression profile of reactive (harmful) astrocytes, microgliosis with elevated C1q which was co-incident with cognitive impairments. We will characterize cranial RT-induced changes in the astrocytic and microglial complement protein (C1q) and cognitive function after 9 Gy head only irradiation. To better understand the differences in the contribution of astrocyte-mediated and microglia-mediated regulation of the complement (C1q) cascade, we will utilize gene silencing and transgenic mouse approaches to study the CNS-radiation response and its impact on cognitive function.
Sicydium altum Meek 1907
Creators: name: Angulo, Arturo
name: Betts, Joel T.
name: González-Alemán, Néstor J.
name: Castañeda, Edgar
name: Berghe, Eric Van Den
name: Elías, Diego J.
name: Mcmahan, Caleb D.
name: Matamoros, Wilfredo A.
Publisher: name: Zenodo
Year: 2023
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Perciformes
Gobiidae
Sicydium
Sicydium altum

description: Sicydium altum Meek 1907. Atlantic Titi Goby; Chupapiedras, Tití, Gobio, Gobio de Río, Lamearenas, Dormilón
Vouchers: UCR 3225-007 (1). Distribution: Western Atlantic Ocean; from southern Nicaragua to (probably) western Panama; entering estuaries and littoral lagoons and ascending river courses; (Nicaragua) IM (Atlantic); 0–780 masl; Per, Dia, Amp. Occurrence and conservation status: Nat; VU B1ab(iii,v) (2020), population trend unknown. Literature: Bussing (1998: 402; brief description, including illustrations and an identification key, and information on distribution, with a map, and ecology) and Angulo (2021: 39; listed, including information on distribution). Remarks: This species was reported from northern Costa Rica to western Panama (Angulo 2021), including the binational (Costa Rica-Nicaragua) San Juan watershed. Our record in the Indio Maíz hydrogeographic unit represents a range extension in the known distribution of the species.
description: Published as part of Angulo, Arturo, Betts, Joel T., González-Alemán, Néstor J., Castañeda, Edgar, Berghe, Eric Van Den, Elías, Diego J., Mcmahan, Caleb D. & Matamoros, Wilfredo A., 2023, Continental fishes of Nicaragua: diversity, distribution and conservation status; with an annotated and illustrated checklist of species and an identification guide to families, pp. 1-89 in Zootaxa 5376 (1) on page 38, DOI: 10.11646/zootaxa.5376.1.1, http://zenodo.org/record/10208788
Building the NSDI at the Base: Establishing best sharing andcoordination practices among local governments
Creators: name: No Name Supplied
Publisher: name: No Publisher Supplied
Year: 2003

description: How do local governments successfully share geospatial data and coordinate geographic information activities? The answers to this question are extremely relevant for improving the involvement of local governments in the National Spatial Data Infrastructure (NSDI). Knowing the issues, potentials, and problems that local governments face is the key to establishing programs and policy support to address local government needs and develop better opportunities for them to participate in geographic information infrastructures connected to the NSDI.The research project relied on two forms of data acquisition. In-depth interviews were held in 6 areas. These in-depth interviews provided great detail complemented by more tightly-focused polling of local governments. Overall, 91 individuals were surveyed using a basic set of thirteen questions. Responses were either collected by phone, fax-back, or email. Most polling was conducted in the summer of 2002 whereas the interviews were dispersed through the year. The interviews and survey methodologies are discussed in more detail.
Teratodinae Brunner von Wattenwyl 1893
Creators: name: Sultana, Riffat
name: Song, Hojun
Publisher: name: Zenodo
Year: 2024
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Orthoptera
Acrididae

description: Teratodinae Brunner von Wattenwyl, 1893
Genus Kabulia Ramme, 1928
164. Kabulia balucha Uvarov, 1931 165. Kabulia evansi Uvarov, 1931 166. Kabulia kostylev i Bey-Bienko, 1949
description: Published as part of Sultana, Riffat & Song, Hojun, 2024, Annotated catalogue of Pakistani Acrididae (Orthoptera: Caelifera: Acridoidea), pp. 1-47 in Zootaxa 5486 (1) on page 10, DOI: 10.11646/zootaxa.5486.1.1, http://zenodo.org/record/13209743
MOESM4 of Genome-wide association studies and genomic prediction of breeding values for calving performance and body conformation traits in Holstein cattle
Creators: name: Abo-Ismail, Mohammed
name: Luiz Brito
name: Miller, Stephen
name: Sargolzaei, Mehdi
name: Grossi, Daniela
name: Moore, Steve
name: Plastow, Graham
name: Stothard, Paul
name: Nayeri, Shadi
name: Schenkel, Flavio
Publisher: name: Figshare
Year: 2017
Subjects: subject: Biophysics
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences

description: Additional file 4: Figure S4. Genomic inflation factor (lambda) used for the test statistic (P-value) from the GWAS methods using the generalized linear mixed model accounting for reliability values associated with the de-regressed EBV. The traits are direct calf survival (cow) (SCSc); direct calf survival (heifer) (SCSh); direct calving ease (cow) (SCEc); direct calving ease (heifer) (SCEh); maternal calf survival (cow) (CSc); set of rear legs (SRL): calf survival (heifer) (CSh); daughter calving ability (DCA); heel depth (HD); calving ease (cow) (CEc); pin setting (PS); foot angle (FAN); calving ease (heifer) (CEh); leg rear view (LRV); median suspensory ligament (MSL); udder texture (UT); feet & legs (FL); rear attachment width (RAW); chest width (CW); rump (RU); rear attachment height (RAH); leg side view (LSV); mammary system (MS); loin strength (LS); angularity (ANG); height at front end (FE); conformation (CONF); fore udder attachment (FA); teat length (TL); rear teat placement (RTP); calving ability (CA); bone quality (BQ); front teat placement (FTP); body depth (BD); pin width (PW); dairy strength (DS); rump angle (RAN); udder depth (UD); and stature (ST).
4D Dynamic PET of Renal Cell Carcinoma
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Renal cell carcinoma (RCC) is one of the top ten cancer types in the US. One-third of RCCs are metastatic and associated with a poor 5-year survival rate of 8%. Targeted therapy has become the first-line treatment for metastatic RCC with more than twelve drugs now available. Effective identification of the most appropriate drugs for a patient relies on noninvasive imaging to assess early response to the drugs. However, current practice by anatomical imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) can only assess the response at two months after initialing targeted therapy. Because targeted drugs are commonly expensive and with risks of significant toxicities, the delay in identifying an ineffective treatment can result in high medical costs, harms from drug toxicities, and the delay in switching to other better drugs. We hypothesize that functional perfusion imaging by positron emission tomography (PET) can enable RCC response assessment as early as at two weeks given that RCC is highly related to angiogenesis and most targeted drugs for RCC are antiangiogenic. While dynamic contrast-enhanced CT or MRI can be used for perfusion imaging, their use is limited because 30% of RCC patients have chronic kidney diseases with renal dysfunction and are at higher risk for contrast-induced nephropathy and nephrogenic systemic fibrosis. Existing PET radiotracers (e.g., 15O-water) for perfusion imaging are short-lived and generally unavailable for clinical use. This project proposes a new PET method for renal perfusion imaging using the widely accessible 18F-fluorodeoxyglucose (FDG). FDG-PET is conventionally for metabolic imaging and has been rarely used for imaging kidneys because physiological excretion of FDG into renal pelvis contaminates image quality for renal tumor detection. We explore the potential of FDG for imaging renal perfusion by employing four-dimensional (4D: 3D space plus 1D time) dynamic scanning and tracer kinetic modeling to enable parametric imaging of FDG perfusion kinetics without being affected by renal excretion. The focus of this proposal is to conduct a pilot clinical study to demonstrate the method in targeted therapy of RCC. The outcome will support the feasibility of 4D dynamic PET perfusion imaging for early RCC response assessment.
Investigating the psychological foundations of moral judgment
Creators: name: Saunders, Katharine
Publisher: name: No Publisher Supplied
Year: 2014

description: Is there an early developing neuro-cognitive structure that is specific to our moral sense?  Recent research has begun to explore this question using a classic thought experiment known as the trolley problem.  These “trolley studies” have uncovered what appears to be a universal pattern of moral intuitions in adults that some argue can only be explained by assuming implicit knowledge of complex moral principles.  In this dissertation, I build on this work by testing preschoolers’ and adults’ tacit knowledge of the principle of double effect – a principle that has a long history within the fields of philosophy, religion, and law, and which has recently been proposed to underlie our moral intuitions in the trolley problem.  I also investigate the role of perceived ingroup/outgroup structure in moral judgment – a factor which others have hypothesized to be a foundation of moral judgment.    Across three studies, preschoolers (studies 1 and 2) and adults (study 3) were tested on a series of dilemmas that were similar in structure to the traditional trolley problems, but involved property violations and assault (i.e. the apprehension of bodily harm) rather than “personal” violations such as battery or homicide.  In all three studies, participants showed a strong and stable pattern of intuitions consistent with the principle of double effect: dilemmas in which an individual was harmed as a foreseen side effect of saving five people were judged favorably, but dilemmas in which an individual was intentionally harmed as a means to saving five people were judged unfavorably.  Four-year-olds and adults (but not three-year-olds) also disapproved of scenarios in which an agent knowingly allowed a preventable harm to occur.  Manipulations of minimal ingroup/outgroup structure had little to no effect on either preschoolers’ or adults’ moral judgments in these dilemmas.  Implications for the structure and development of moral judgment are discussed.
Enhanced immunotherapy against breast cancer with biguanides
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Triple-negative breast cancer (TNBC) occurs in 10-15% of patients, yet it accounts for almost half of all breast cancer (BC) deaths. Although initially responsive to chemotherapy, TNBCs tend to relapse and metastasize early, leading to poor survival. An emerging approach to promote immune responses against several cancers is blockade of immune checkpoints. While these treatments show promising responses for a fraction of TNBC patients, significant progress is needed to achieve more durable responses. Evidence from epidemiologic, preclinical and early clinical trial studies suggests that the metformin, a biguanide drug widely used to treat type 2 diabetes, exerts anticancer activity in breast cancer. Despite modest antitumor effects as a single agent in the clinic, metformin exhibits immune-mediate effects in the tumor microenvironment by inducing increased trafficking of cytotoxic tumor-infiltrating lymphocytes (TIL) to tumors and protecting TILs from programmed cell death. We recently developed novel biguanides that exert more potent antitumor effects in vivo at lower doses than metformin and minimal non-target toxicity. Evidence that CD8+ TILs are targets of metformin and that its analogue, phenformin, inhibits myeloid-derived suppressor cell (MDSC) expansion and activity provide a rationale to study the potentially synergistic effects of these potent biguanides when combined with established immune therapeutics. We will evaluate our novel biguanides (metformin analogues) for enhanced immune cell trafficking and inhibition of MDSC expansion and activity using a TNBC syngeneic mouse model. We will assess if the biguanides amplify responses to current immunotherapeutics. Further, a molecular imaging tool to detect changes in systemic and tumor-infiltrating CD8 expression and non-invasively evaluate immune responses throughout the course of treatment could have profound implications in patient selection and stratification. Bivalent antibody fragments, cys-diabodies (cDb), that exhibit high target uptake and rapid, controlled systemic clearance provide a versatile platform for targeting CD8-expressing T cells, major components of immune response. We will prepare 89Zr-labeled CD8-specific cDb to monitor the immune system in vivo via antibody-based positron emission tomography (immunoPET) imaging studies.
Prediction of cost overruns using ensemble methods in data mining and text mining algorithms
Creators: name: Ramesh, Prathiksha
Publisher: name: No Publisher Supplied
Year: 2014

description: In competitive bidding in the United States, the lowest bid is most often than not selected to perform the project. However, the lowest bidder tends to undervalue the costs in order to win the bid and as a result may incur significant cost increases during the construction life cycle due to change orders. For project owners to accurately estimate the actual project cost and to predict the bid that is close to the actual project, there is an urgent need for new decision aids to analyze the bidding patterns.    The goal of this research has been to select the predictive features in a bid package to help minimize the cost overruns with the help of open source data mining software. The features were selected based on correlation and regression analysis by studying the p-values and r-squared values. The data set was then prepared with only the features that were affecting the output, which in our case were the cost overruns. The output is divided into 4 classes depending on the percentage of overrun. The learning algorithms used for prediction were neural networks, support vector machines, decision trees along with the ensemble methods. The empirical study of the prediction models suggest an efficiency of up to 50% in predicting whether a project will have cost overruns and what is the approximate range of percentage overrun.
Study of structural integrity of interstellar spacecraft reaction chamber and thrust structure in support of Project Icarus
Creators: name: Reddy, Srikanth K.
Publisher: name: No Publisher Supplied
Year: 2014

description: This thesis supports studies of the international effort of Project Icarus, dedicated to the unmanned, interstellar exploration of nearby stellar systems within the next century. The target system is 5.9 light years away, with a required velocity of 12% the speed of light. This study primarily focuses on the structural analysis of the reaction chamber and supporting structure of the Icarus interstellar spacecraft, which will be powered by nuclear fusion reactions to achieve the required velocity and time-frame for the mission. First, a computational finite element analysis is conducted on the reaction chamber in terms of loading, vibration, and fatigue. Different configurations and assumptions are studied for the reaction chamber as well. Present-day manufacturing considerations are also taken into account, with a modest extrapolation for future manufacturing technologies that are currently not in existence. Next, the thrust supporting structure for the reaction chamber is incorporated into the analysis. This study serves as a precursor for the multi-level analysis into the eventual detailed design and production of an interstellar spacecraft, and is the first such study.
Yagansia dicastrii Zicsi 1989
Creators: name: Csuzdi, Csaba
name: Szederjesi, Tímea
name: Sherlock, Emma
Publisher: name: Zenodo
Year: 2018
Subjects: Biodiversity
Taxonomy
Animalia
Annelida
Clitellata
Opisthopora
Acanthodrilidae
Yagansia
Yagansia dicastrii

description: Yagansia dicastrii Zicsi, 1989
Yagansia dicastrii Zicsi, 1989a Acta Zool. Hung. 35 (3/4): 418.
description: Published as part of Csuzdi, Csaba, Szederjesi, Tímea & Sherlock, Emma, 2018, Annotated checklist of earthworm species described by András Zicsi (Clitellata: Megadrili), pp. 11-42 in Zootaxa 4496 (1) on page 14, DOI: 10.11646/zootaxa.4496.1.4, http://zenodo.org/record/1447011
Synthesis of Strictosidine, a Precursor to Vinblastine
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cancer remains the 2nd leading cause of death in the United States. In 2018, it is estimated that over 1.7 million Americans will be diagnosed with cancer, and over 600,000 will die from the malicious disease. More than 50% of cancer patients rely on costly chemotherapeutics to treat cancer effectively. Vinblastine is a frontline cancer therapeutic used to treat multiple forms of the disease. The industrial production still relies on isolation from its natural source, Catharanthus roseus, which renders the process inefficient and source-dependent. Although this approach accesses the drug, vinblastine remains one of the most expensive small molecule, off-patent chemotherapeutics. Vinblastine could be made affordable with an efficient method of production; however, typical approaches most commonly used in drug manufacturing have failed. For example, an efficient chemical synthesis of vinblastine remains elusive due to the compound’s structural complexity. Further complicating matters is the fact that numerous details of vinblastine’s biosynthesis remain unresolved, thus making a fully bioengineered synthesis impossible at present. The overarching aim of this project is to develop a chemoenzymatic means to access vinblastine. Toward this long-term goal, we propose to first develop an efficient synthesis of strictosidine, an important biosynthetic precursor to vinblastine. The highly functionalized six-membered ring of secologanin will be accessed via an asymmetric inverse-electron-demand hetero-Diels–Alder reaction. After further elaboration, an enzyme-mediated Pictet-Spengler reaction will be used to arrive at strictosidine. It is envisioned that these studies will lay the foundation for future studies directed toward the conversion of strictosidine to vinblastine using enzymatic machinery. Thus, the proposed studies would represent a significant milestone toward a scalable and affordable means for the chemoenzymatic production of an important chemotherapeutic.
Sicydium salvini Ogilvie-Grant 1884
Creators: name: Angulo, Arturo
name: Betts, Joel T.
name: González-Alemán, Néstor J.
name: Castañeda, Edgar
name: Berghe, Eric Van Den
name: Elías, Diego J.
name: Mcmahan, Caleb D.
name: Matamoros, Wilfredo A.
Publisher: name: Zenodo
Year: 2023
Subjects: Biodiversity
Taxonomy
Animalia
Chordata
Perciformes
Gobiidae
Sicydium
Sicydium salvini

description: Sicydium salvini Ogilvie-Grant 1884. Pacific Titi Goby; Chupapiedras, Tití, Gobio, Gobio de Río, Gobio de Río del Pacífico, Lamearenas, Dormilón
Vouchers: UCR 0184-005 (49) and 0466-008 (2). Distribution: Eastern Pacific Ocean; from El Salvador to Ecuador; entering estuaries and littoral lagoons and ascending river courses; (Nicaragua) Ch, Ne, ER, PN, Ni (Pacific); 0–319 masl; Per, Dia, Cat. Occurrence and conservation status: Nat; NE, population trend unknown. Literature: Villa (1982: 230; detailed description, including illustrations and an identification key, and information on distribution and ecology), Carr & Giovannoli (1994: 113, as Sicydium multipunctatum Regan 1906 —synonym; brief description, including information on distribution and ecology), Bussing (1998: 405; brief description, including illustrations and an identification key, and information on distribution, with a map, and ecology) and Angulo (2021: 39; listed, including information on distribution).
description: Published as part of Angulo, Arturo, Betts, Joel T., González-Alemán, Néstor J., Castañeda, Edgar, Berghe, Eric Van Den, Elías, Diego J., Mcmahan, Caleb D. & Matamoros, Wilfredo A., 2023, Continental fishes of Nicaragua: diversity, distribution and conservation status; with an annotated and illustrated checklist of species and an identification guide to families, pp. 1-89 in Zootaxa 5376 (1) on page 38, DOI: 10.11646/zootaxa.5376.1.1, http://zenodo.org/record/10208788
Checkpoint blockade and central tolerance in tumor immunity
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Immunotherapy to fight cancer has shown great promise. Antibodies that inhibit T cell checkpoints like anti-CTLA-4 or anti-PD-1 are effective in curing a fraction of patients with advanced melanoma and other types of cancers. These antibodies work by breaking T cell peripheral tolerance. Although autoimmunity may ensue, the treatment allows T cells to attack tumors. However, a significant % of patients with these ‘treatable’ tumors are nevertheless resistant to the checkpoint inhibitors. Similarly, many other types of tumors are also refractory to this approach. One idea to overcome this is to increase T cell repertoire (thereby increasing tumor-specific T cells) through inhibition of T cell central tolerance, a process where potential autoreactive T cells are removed by apoptosis in the thymus. Recently, two groups showed that T cells from mice with mutation in AIRE, the immune regulator of central tolerance to tissue specific antigens, could synergize with anti-CTLA-4 to eliminate otherwise resistant melanoma. We have been studying apoptosis accompanying central tolerance, which involves the BH3-only Bcl-2 family proteins, Bim and Puma, as well as the Nur77 orphan steroid receptors. The latter may kill through conversion of Bcl-2 into a pro-apoptotic protein. Transgenic mice expressing a Bcl-2-BH3* mutant protein that blocks all three pathways or Bim-/-/Puma-/- mice exhibit increased T cell repertoire and autoimmunity in old mice. Here, we hypothesize that inhibiting apoptosis accompanying central tolerance can enhance the efficacy of checkpoint inhibitors against many types of tumors. In this proposal, we will test the ability of T cells from Bcl-2-BH3* transgenic mice to synergize with anti-CTLA-4 or anti-PD1 antibodies for anti-tumor immunity to several syngeneic mouse tumor lines, including melanoma, fibrosarcoma and colon adenocarcinoma. Both Bcl-2-BH3* mice and purified Bcl-2-BH3* T cells adoptively transferred into lymphocyte-deficient mice will be used. The kinetics of tumor development, mouse lethality and anti-tumor immune responses will be determined. If successful, future experiments will include testing mice with milder defects in central tolerance and identification of reagents that block central tolerance. The latter could eventually be used in human where active T cell development was found in individuals up to 85 years old.
Simple modeling solutions for complex conservation problems
Creators: name: Robinson, Orin J.
Publisher: name: No Publisher Supplied
Year: 2014

description: Species are going extinct at a rate far higher than pre-human levels. For many species that are endangered, basic biological information may not be available to conservation managers.  In these situations, mathematical models can be useful in providing insight into the biological requirements of species and to make credible predictions about how management actions may. Here, I present three modeling techniques that help to show the efficacy of management actions (Chapters 1&2) and the effects of exploitation on species with unique life histories (Chapter 3). I show that combining two foundational elements of ecological theory (matrix population models and functional responses) into one coupled model provides a flexible approach to determining the best conservation strategy to recover prey under threat from an invasive predator. I suggest a simple addition to existing population viability models that allows managers to calculate the probability that management action will improve the status of a declining population and the probability that enacting management will be no more effective than doing nothing. I illustrate the method by using previously published population viability analyses. For some management situations, doing nothing may be just as effective as enacting an expensive management strategy. Calculating these probabilities can provide tangible ways to balance risk and reward when making management decisions. Last, I present a game theoretic approach to model the behavior of sex changing fish. I produced estimates of maximum sustainable yield (MSY), biomass at maximum sustainable yield (BMSY), and sex ratio for sex changing and non-sex changing stocks at different levels of fishing pressure and varying fertilization rates. The results suggest that sex changing stocks may be as robust to fishing as non-sex changing stocks. This game theoretic approach to evaluating hermaphroditic stocks can accommodate a wide variety of sex changing cues and allows a flexible model for understanding the effects of exploitation on hermaphroditic stocks.  Models have proven useful in many conservation situations and will continue to aid managers. I have shown that simple additions to traditional models can provide more insight on the efficacy of management and how unique breeding behavior may be incorporated into conservation decision-making.
Tropidopolinae Jacobson 1905
Creators: name: Sultana, Riffat
name: Song, Hojun
Publisher: name: Zenodo
Year: 2024
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Insecta
Orthoptera
Acrididae

description: Tropidopolinae Jacobson, 1905
Tribe Tristriini Mistshenko, 1945
Genus Tristria Stål, 1873
167. Tristria pulvinata (Uvarov, 1921)
168. Tristria pisciformis (Serville, 1838)
Tribe Tropidopolini Jacobson, 1905
Genus Tropidopola Stål, 1873
169. Tropidopola longicornis (Fieber, 1853)
description: Published as part of Sultana, Riffat & Song, Hojun, 2024, Annotated catalogue of Pakistani Acrididae (Orthoptera: Caelifera: Acridoidea), pp. 1-47 in Zootaxa 5486 (1) on pages 10-11, DOI: 10.11646/zootaxa.5486.1.1, http://zenodo.org/record/13209743
MOESM4 of Population structure and genomic inbreeding in nine Swiss dairy cattle populations
Creators: name: Signer-Hasler, Heidi
name: Burren, Alexander
name: Neuditschko, Markus
name: Frischknecht, Mirjam
name: Garrick, Dorian
name: Stricker, Christian
name: Gredler, Birgit
name: Bapst, Beat
name: Flury, Christine
Publisher: name: Figshare
Year: 2017
Subjects: subject: Evolutionary Biology
subject: FOS: Biological sciences
subject: Ecology
subject: 69999 Biological Sciences not elsewhere classified
subject: Computational Biology

description: Additional file 4: Figure S3. Levelplot of pair-wise genomic relationship within and between populations.
Photoacoustic Ultrasound to Detect/Monitor Ovarian Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Screening for ovarian cancer in high risk women is rational because the disease is treatable in early stages, but very deadly in late stages. CA125 testing and transvaginal ultrasound imaging have encouraging metrics including sensitivity and specificity of 89.4% and 99.8%, but have positive predictive values below 50% and are insufficient for use in the general population. Folate binding proteins are highly expressed in ovarian cancer; hence, these targets can be used to increase the specificity and sensitivity of ovarian cancer screening. My central hypothesis is that nanoparticles targeted to the folate receptor will increase tumor signal and contrast above background greater than non-targeted nanoparticles—this will increase the sensitivity and specificity of screening. Because folate receptors are expressed on the cell surface, it is critical to use a contrast agent that leaves the vasculature. My expertise is in nanoparticle imaging agents that do just that—these contrast agents are built from the clinically approved indocyanine green and poly-lactic-co-glutamic acid. I will now use them for ultrasound-based molecular imaging of ovarian cancer. I will image folate binding proteins with both conventional ultrasound and novel photoacoustic ultrasound that combines the high contrast of optical imaging with the resolution of ultrasound. I will evaluate the performance metrics of both through the following steps. Step 1. We will make the nanoparticles via an emulsification process. Step 2. We will add a cloaking polymer and folate. Step 3. We will validate the contrast agent with cell culture experiments. Step 4. We will image an orthotopic model of human ovarian cancer. Ultrasound already provides excellent anatomical information, and the small size of nanoparticles facilitates imaging the sensitive and specific biomarkers present on the cell surface. Although deployed here for ovarian cancer, this imaging agent will have broad utility across many cancer types. This work is also easily reconfigurable to other imaging targets as they emerge in the literature. I will use this pilot data to seek additional funds from the NIH at the conclusion of this project, e.g. PAR-13-185 and PAR-13-189.