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Hurricane Maria was a disastrous weather event that devastated Puerto Rico (PR) in September 2017. Yet, little is known about people’s perceptions of this event. In this investigation, we offer insight about Hurricane Maria’s impact on PR’s inhabitants. More specifically, we study a sample (n = 542 responses) of individuals’ worry levels through four time points during the aftermath of Hurricane Maria: their variation through time, their relationship to decision making, and if and how certain demographic variables may influence them. For these purposes, we designed and implemented the Individual Emergency Response and Recovery Questionnaire, a web-based survey that measured several aspects of the objective and subjective experiences of individuals who underwent Hurricane Maria in PR. Results of a statistical analysis using nonparametric tests show that some of the demographic variables selected as factors of interest influence the worry levels reported by respondents. Most significant results coincide with conclusions drawn by literature: that time, age group, and the level of information influence worry levels. Another key finding is that the worry level may influence individual decision-making frequency. Understanding principal factors in people’s behavior and perceptions during hurricanes is crucial to help us learn how to better prepare for and respond to natural disasters in the future.

Augmented Reality is a promising technology to support safe pedestrian evacuation from buildings during earthquakes. The widespread availability of phone cameras makes this idea feasible. QR codes, for instance, can place virtual three-dimensional objects to guide people along a prescribed route. In this work, a prototypical system based on this premise was created in response to the 2020 sudden surge in seismic activity in Puerto Rico. The results point towards feasibility as well as to a series of areas that require improvement for a real-life implementation.

In 2017, approximately 5 million Americans were living with Alzheimer’s disease (AD), and it is estimated that by 2050 this number could increase to 16 million. In this study, we apply mathematical optimization to approach microarray analysis to detect differentially expressed genes and determine the most correlated structure among their expression changes. The analysis of {"type":"entrez-geo","attrs":{"text":"GSE4757","term_id":"4757"}}GSE4757 microarray dataset, which compares expression between AD neurons without neurofibrillary tangles (controls) and with neurofibrillary tangles (cases), was casted as a multiple criteria optimization (MCO) problem. Through the analysis it was possible to determine a series of Pareto efficient frontiers to find the most differentially expressed genes, which are here proposed as potential AD biomarkers. The Traveling Sales Problem (TSP) model was used to find the cyclical path of maximal correlation between the expression changes among the genes deemed important from the previous stage. This leads to a structure capable of guiding biological exploration with enhanced precision and repeatability. Ten genes were selected (FTL, GFAP, HNRNPA3, COX1, ND2, ND3, ND4, NUCKS1, RPL41, and RPS10) and their most correlated cyclic structure was found in our analyses. The biological functions of their products were found to be linked to inflammation and neurodegenerative diseases and some of them had not been reported for AD before. The TSP path connects genes coding for mitochondrial electron transfer proteins. Some of these proteins are closely related to other electron transport proteins already reported as important for AD.

Establishing the role that different genes play in the development of cancer is a daunting task. A step toward this end is the detection of genes that are important in the illness from high‐throughput biological experiments. Furthermore, it is safe to say that it is highly unlikely that these show expression changes independently, even with a list of potentially important genes. A biological signaling pathway is a more plausible underlying mechanism as favored in the literature. This work attempts to build a mathematical network problem through the analysis of microarray experiments. A preselection of genes is carried out with a multiple criteria optimization framework previously published by our research group 1. Afterward, application of the Traveling Salesperson Problem and Minimum Spanning Tree network optimization models are proposed to identify potential signaling pathways via the most correlated path among the genes of interest. Biological evidencing is provided to assess the effectiveness of the proposed methods. The capability of our analysis strategy is also demonstrated through the undertaking of meta‐analysis studies. Three important aspects are novel in this work: (1) our joint analyses of different groups of lung cancer states reveal new correlations, biologically evidenced, and previously undocumented; (2) computation of the correlation coefficients from expression differences leads to an effective use of network optimization methods; and (3) the methods yield mathematically optimal correlation structures: no other configuration is better correlated using the available information.

espanolLos sistemas hidroponicos existen desde hace ya varios anos en una amplia variedad de disenos y configuraciones. El proyecto que aqui se describe comprende el diseno de un sistema hidroponico modular apilable para uso domestico, con miras a que sea uno con alta productividad. Una impresora 3D se utilizo para desarrollar el prototipo que consta de elementos cilindricos, cada uno con tres receptaculos. A los elementos cilindricos apilables se les puede rotar con respecto de su eje, anadiendo asi mayor flexibilidad de configuracion. Convenientemente, la tapa del sistema esta formada por medio elemento cilindrico. Para la prueba preliminar que aqui se describe, se depositaron semillas de cilantro por un periodo de 14 dias en Rockwool. En su fase prototipica, se determino la factibilidad del sistema, aunque se reconoce que es aun necesario optimizar el diseno y afinar su operacion. Esto implicara conciliar dos objetivos en conflicto: maximizar la productividad del sistema y minimizar su costo total EnglishHydroponic systems have been around for many years and there is a large variety of designs. This project approaches the design of a stackable hydroponic system for domestic use aiming for high yield. The 3-D printed prototype consisted of cylindrical elements each with three entries for seeding. These elements can be stacked up and rotated around one another providing configuration flexibility. In addition, the cap of our system is a half cylindrical element. A preliminary test included the use of Rockwool to grow coriander for 14 days. Being a prototype, it is still necessary to optimize the design, fine-tune its operation beyond its initial feasibility to both, maximize yield and minimize cost, which implies compromising on these two conflicting objectives.

Microarrays can provide large amounts of data for genetic relative expression in illnesses of interest such as cancer in short time. These data, however, are stored and often times abandoned when new experimental technologies arrive. This work reexamines lung cancer microarray data with a novel multiple criteria optimization‐based strategy aiming to detect highly differentially expressed genes. This strategy does not require any adjustment of parameters by the user and is capable to handle multiple and incommensurate units across microarrays. In the analysis, groups of samples from patients with distinct smoking habits (never smoker, current smoker) and different gender are contrasted to elicit sets of highly differentially expressed genes, several of which are already associated to lung cancer and other types of cancer. The list of genes is provided with a discussion of their role in cancer, as well as the possible research directions for each of them.

M32 carboxypeptidases are a distinct family of HEXXH metalloproteases whose structures exhibit a narrow substrate groove that is blocked at one end. Structural alignments with other HEXXH metalloprotease-peptide complexes suggested an orientation in which the substrate is directed towards the back of the groove. This led us to hypothesize, and subsequently confirm that the maximum substrate length for M32 carboxypeptidases is restricted. Structural and sequence analyses implicate a highly conserved Arg at the back of the groove as being critical for this length restriction. However, the Thermus thermophilus and Bacillus subtilis M32 members lack this conserved Arg. Herein, we present the biochemical and structural characterization of these two proteins. Our findings support the important role of the conserved Arg in maintaining the length restriction, and reveal a proline-rich loop as an alternate blocking strategy. Based on our results, we propose that M32 carboxypeptidases from Bacilli belong to a separate subfamily. Proteins 2009. © 2009 Wiley-Liss, Inc.

Establishing how a series of potentially important genes might relate to each other is relevant to understand the origin and evolution of illnesses, such as cancer. High-throughput biological experiments have played a critical role in providing information in this regard. A special challenge, however, is that of trying to conciliate information from separate microarray experiments to build a potential genetic signaling path. This work proposes a two-step analysis pipeline, based on optimization, to approach meta-analysis aiming to build a proxy for a genetic signaling path.

Structures of the Bradyrhizobium japonicum FixL heme domain have been determined in the absence and presence of specific ligands to elucidate the detailed features of its O2 sensing mechanism. The putative roles of spin-state and steric hindrance were evaluated by the structure determination of ferrous CO-bound BjFixLH and correlating its features with other ligand-bound structures. As found for NO-BjFixLH, no protein conformational change was observed in CO-BjFixLH, suggesting a more complicated mechanism than solely spin state or ligand sterics. To evaluate the role of oxidation state, the structure of the ferrous deoxy-BjFixLH was determined. The structure of deoxy-BjFixLH was found to be virtually identical to the structure of the ferric met-BjFixLH. The role of hydrogen bonding of substrates to a heme-pocket water was evaluated by determining the structure of BjFixLH bound to 1-methyl-imidazole that cannot form a hydrogen bond with this water. In this case, the heme-mediated conformational change was observed, limiting the potential importance of this interaction. Finally, the structure of cyanomet-BjFixLH was revisited to rule out concerns regarding the partial occupancy of the cyanide ligand in a previous structure. In the revised structure, Arg 220 was found to move into the heme pocket to form a hydrogen bond to the bound cyanide ligand. The implications of these results on FixL's sensing mechanism are discussed.

BACKGROUND: MicroRNAs (miRNA) are short non-protein-coding RNAs that regulate gene expression at the post-transcriptional level via binding to 3′-untranslated regions of protein-coding transcripts. Some miRNAs have been used as diagnostic, prognostic and therapeutic markers of breast cancer (BC). It is well established that dysregulation of DNA repair capacity (DRC) is an important risk factor of BC. However, there is little published information as to what specific miRNAs are associated with DRC in women with BC. OBJECTIVE: The main objective of this study was to identify candidate miRNAs associated with dysregulation of DRC in women with BC. METHODS: Plasma samples from 30 BC cases and 30 controls selected based on their DRC levels (low, high) using a proprietary algorithm. Samples were analyzed for miRNA expression utilizing protocols from Applied Biosystems (Life Technologies). The miRNA expression profiling was performed utilizing the RT-PCR TaqMan Array Human MicroRNA A Cards v 2.0 (Applied Biosystems) containing 383 miRNA probes. Single-stranded cDNA was synthesized from 200 ng of total RNA in 8 Multiplex RT primer pool reactions containing stem-looped RT primers that were specific to mature miRNAs. U6 snRNA-001973 was selected for normalization based on our own experimental validations. To quantify the association of the miRNA expression the fold change () was estimated for every detector with the p-values calculated using the t-test. RESULTS: Candidate miRNAs that showed a statistically significant expression were: miR-146, miR-34a, miR-221, Let-7b, miR-193b, miR-132, miR-192, miR-21, miR-197, miR-24, miR-26b, miR-29c were identified based on a false discovery rate of 4%. The results showed that twelve miRNAs differentially expressed in patients with BC. Candidate miRNAs have been reported associated with the expression of twenty seven DNA repair genes. Two of these genes are part of the NER pathway which has been identified by previous studies as important in BC. CONCLUSION: Our preliminary data suggests that differential expression of specific miRNAs might be associated with dysregulation of DRC in BC. The molecular mechanisms by which miRNAs regulate DNA repair genes remain to be elucidated. However, our results lend further promise to the concept of miRNAs as a tool to study the regulation of DRC. We see potentialfuture applications in prognosis and therapy of women with BC. Supported by grants S06 GM008239-20 and 1SCA157250 from the NCI Center to Reduce Health Disparities and NIH-MBRS Program (NIGMS) and NIH-NIGMS #GM082406 (CO). Citation Format: Jaime Matta, Clara Isaza, Carmen Ortiz, Erick Suarez, Luisa Morales. miRNAs associated with DNA repair capacity in Puerto Rican women with breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-06-05.

A new method using Multiple Criteria Optimization (MCO) proposed by our research group has shown evidence of being able to identify gene-based biomarkers for the detection of cancer using microarray data. Herein, we explore this method, considering more than two conflicting criteria for the MCO problem. Using this method would result in stronger outcomes when using different results from microarray analyses. It would also demonstrate that the method is suitable for carrying out meta-analysis.Statistical comparisons between normal and cancer tissues were performed using a colon cancer microarray database. The different comparisons were carried out with a Mann-Whitney non-parametric test using partial permutations of the data. An MCO problem was built using the different p-values obtained. The associated solution was the set of genes reaching the best compromises between the p-values under consideration that were located in the so-called efficient frontier. Data Envelopment Analysis (DEA) was used to find the efficient frontier of the MCO problem. The capacity of DEA was explored using different numbers of p-values (criteria) in the model.The set of identified genes was consistent across the instances using different numbers of p-values in the DEA model, thereby providing evidence of the outcome stability of the proposed strategy. It was also observed that convergence to a larger number of potential biomarkers is faster with additional criteria, i.e., more p-values.The MCO problem proposed for the cancer biomarker search using microarray data can be solved efficiently with DEA using more than two conflicting criteria. This approach can result in robust results when using different analyses of microarray data and, indeed, in a faster convergence to highly potential biomarkers.

High throughput biological experiments such as DNA Microarrays are very powerful tools to understand and characterize multiple illnesses. These types of experiments, however, have also been described as large, complex, expensive and hard to analyze. For these reasons, analyses with linear assumptions are frequently bypassed for more sophisticated procedures with higher complexity. In this work, a search procedure for potential biomarkers using data from microarray experiments is proposed under purely linear assumptions. The method shows a high discrimination rate and does not require the adjustment of parameters by the user, thus preserving analysis objectivity and repeatability. A case study in the identification of potential biomarkers for cervix cancer is presented to illustrate the application of the proposed procedure.

Diagnosing cancer using microarray analysis to study differential gene expression has been a recent focus of intense research Although several very sophisticated analysis tools have been developed with this aim in mind, it still remains a challenge to keep these methods free of parametric adjustments as well as maintain their transparency for the final user. Nonparametric methods in general have been associated with these last two characteristics, thus becoming attractive tools for microarray analysis in cancer research. In particular, diagnosing cancer via microarray analysis is an exercise whereby tissue is characterized according to its differential gene expression levels. In this manuscript, two novel nonparametric methods for cancer diagnosis using microarray data are described and their performance assessed against a baseline approach that utilizes the Mann-Whitney test for median differences. Both methods show promising results in terms of their potential use in making diagnoses.

Skin cancers are common, and there has recently been a dramatic increase in their incidence, particularly in the occurrence of melanoma. Furthermore, relapse after curative surgical treatment of melanoma remains a significant clinical challenge and accounts for most of the mortality of this disease.The aim of this study was to determine whether IMMUNEPOTENT CRP affects B16F10 melanoma cells and tumors growth and vascular endothelial growth factor (VEGF) production in vivo and in vitro.B16F10 cells and B16F10-inoculated mice were treated with different concentrations of IMMUNEPOTENT CRP. Outcomes were then evaluated using MTT, TUNEL, Caspase-3, senescence, ELISA and colorimetric assays. Parameters related to survival and tumor weight were also assessed.IMMUNEPOTENT CRP decreased the viability of B16F10 cells by increasing apoptosis of the treated cells, and VEGF production was decreased both in vitro and in vivo. Furthermore, treatment prevented metastasis, delayed the appearance of tumors, decreased tumor weight and improved the survival of tumor-bearing mice.These observations suggest that IMMUNEPOTENT CRP can be used to suppress growth and metastasis by using targeting proteins such as VEGF.

M32 carboxypeptidases are a distinct family of HEXXH metalloproteases whose structures exhibit a narrow substrate groove that is blocked at one end. Structural alignments with other HEXXH metalloprotease-peptide complexes suggested an orientation in which the substrate is directed towards the back of the groove. This led us to hypothesize, and subsequently confirm that the maximum substrate length for M32 carboxypeptidases is restricted. Structural and sequence analyses implicate a highly conserved Arg at the back of the groove as being critical for this length restriction. However, the Thermus thermophilus and Bacillus subtilis M32 members lack this conserved Arg. Herein, we present the biochemical and structural characterization of these two proteins. Our findings support the important role of the conserved Arg in maintaining the length restriction, and reveal a proline-rich loop as an alternate blocking strategy. Based on our results, we propose that M32 carboxypeptidases from Bacilli belong to a separate subfamily.

Leishmaniasis is a tropical disease caused by Leishmania, eukaryotic parasites transmitted to humans by sand flies. Towards the development of new chemotherapeutic targets for this disease, biochemical and in vivo expression studies were performed on one of two M32 carboxypeptidases present within the Leishmania major (LmaCP1) genome. Enzymatic studies reveal that like previously studied M32 carboxypeptidases, LmaCP1 cleaves substrates with a variety of C-terminal amino acids - the primary exception being those having C-terminal acidic residues. Cleavage assays with a series of FRET-based peptides suggest that LmaCP1 exhibits a substrate length restriction, preferring peptides shorter than 9–12 amino acids. The in vivo expression of LmaCP1 was analyzed for each major stage of the L. major life cycle. These studies reveal that LmaCP1 expression occurs only in procyclic promastigotes – the stage of life where the organism resides in the abdominal midgut of the insect. The implications of these results are discussed.

The methyl-accepting chemotaxis protein, DcrH, from the anaerobic sulfate-reducing bacterium, Desulfovibrio vulgaris (Hildenborough), has a hemerythrin-like domain, DcrH-Hr, at its C terminus. DcrH-Hr was previously shown to contain a diiron site that binds O2, suggesting an O2-sensing function. X-ray crystal structures of diferric (met-), azido-diferric (azidomet-), and diferrous (deoxy-) DcrH-Hr reveal a "substrate tunnel" distinct from that in invertebrate hemerythrins. This tunnel is proposed to facilitate the rapid autoxidation of oxy-DcrH-Hr and suggests that sensing is triggered by O2 binding and subsequent oxidation of the diferrous active site. The N-terminal loop of DcrH-Hr is highly ordered in both met- and azidomet-DcrH-Hr but is disordered in deoxy-DcrH-Hr. These redox-dependent conformational differences presumably transduce the sensory signal of DcrH-Hr to the neighboring methylation domain in the full-length receptor. Given the putative cytoplasmic localization of its Hr-like O2-sensing domain, DcrH is proposed to serve a role in negative aerotaxis (anaerotaxis).

In this work, the simultaneous analysis of two publicly-available affymetrix microarray databases for colon cancer is carried out with the objective to detect potential biomarkers. Gene selection is approached here through its formulation as a multiple criteria optimization (MCO) problem. This formulation allows (i) removing the need for parameter adjustment by the user -thereby preserving the objectivity of the results in terms of gene selection-, and (ii) analyzing several databases with different characteristics in a concurrent manner. The key idea to adopt an MCO approach is the representation of each gene under analysis through multiple performance measurement values. The performance measures in this work are statistical p_values obtained through nonparametric statistical comparison. A gene with minimal p_values across all instances can be deemed to be a potentially dominant gene. However, due to the nature of the analysis based on experimental data, the simultaneous consideration of multiple p_values will lead to conflicting behavior among them. With this in mind, the objective of the MCO problem is to identify the genes that are demonstrably the best compromises among all genes. These best compromises are termed efficient solutions and are located in the so-called Pareto efficient frontier of the optimization problem. An efficient solution can improve in a performance measure only when worsening at least another performance measure. The concurrent analysis of the afore-mentioned microarray databases results in the consistent identification of 13 genes, all of which were found to have roles on cancer in our literature search and review. Among the thirteen genes detected through the application of our method, the tumor suppressor activator GSN and the metastasis suppressor NME1 showed significantly different expression levels in cancer tissues when contrasted to normal tissues. HSPD1, which has been already reported as potential biomarker gene for prostate cancer, was also included in the final selection. GTF3A, DES, NPM1, CSRP1 and MT1G were picked by the analysis and have been reported to significantly change their expression levels in other cancers, albeit not specifically in colon cancer. MYL9 and VIP have not been reported as potential cancer biomarkers, however, their cellular roles indicate that they might be related to the illness. Finally, completing the list, CFD, GUCA2B and one EST have not been formally related to cancer. These last five genes could represent important research opportunities in the search for colon cancer biomarkers. These results allow appreciating two important qualities of the proposed method: (i) high discrimination rate and (ii) independence of parameter adjustment by the user. Its use for secondary analyses of existing microarray databases is proposed to enhance the objectivity of the identification of potential biomarkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 42. doi:10.1158/1538-7445.AM2011-42

The purpose of this work is to introduce an approach to identify potential biomarkers from the analysis of microarray experiments. The proposed approach does not require the adjustment of any parameters, thus favoring results’ consistency and reproducibility across different analysts. The key idea in this approach is to represent the biomarker identification task as a multicriteria mathematical optimization problem. The solution of this problem to optimality implies the determination of a set of genes that significantly change their expression level across different experiments. In order to enable such representation, a series of performance measures are obtained for each gene under analysis. It is proposed that these performance measures be statistical p values obtained through nonparametric statistical comparison. A gene with minimal p values across all instances can be considered a potentially dominant gene. Due to the nature of data-based analysis, however, considering multiple p values at a time will lead to conflicting behavior among them. This conflicting behavior introduces a considerable amount of subjectivity in the selection of important genes since different researchers will use different techniques to deal with it. It is our hypothesis that an optimization-based approach can resolve this conflict with consistent and objective results. Preliminary results on the application of the proposed approach to cervix cancer publicly available data from Wong, et al (2003), include the following prioritized lists of accession numbers for potential biomarkers of cervix cancer. The list with the first priority includes {AA488645, H22826}. The list with the second priority includes {AI553969, AA243749, T71316, AA460827}. The list with the third priority is {AA454831, AA913408}. The list with the fourth priority is {AA487237, AA446565}, and the list with the fifth priority includes {H23187}. A literature search on these genes indicates that there is a high likelihood for some of them to be biomarkers with at least H23187 being a confirmed biomarker for gastrointestinal stromal tumors as reported by Parkkila, et al (2010). The initial results are encouraging in terms of the high discrimination rate shown by the approach, the lack of parameters involved to identify potential biomarkers, and the hierarchical structure in which the final information can be shown. A validation experiment on the list of genes here presented is currently under consideration by our research group. The proposed method can be used to perform secondary analysis of existing microarray databases with more objectivity. References: 1. Y. F. Wong, et al, “Expression Genomics of Cervical Cancer: Molecular Classification and Prediction of Radiotherapy Response by DNA Microarray,” Clinical Cancer Research, vol 9, pp. 5486-5492. July 2003. 2. Parkkila S, et al, ”Carbonic anhydrase II. A novel biomarker for gastrointestinal stromal tumors,” Modern Pathology (2010) 23, 743-750. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B45.