University of Puerto Rico at Cayey

NASA's Black Marble nighttime lights product suite (VNP46) is available at 500 m resolution since January 2012 with data from the Visible Infrared Imaging Radiometer Suite (VIIRS) Day/Night Band (DNB) onboard the Suomi National Polar-orbiting Platform (SNPP). The retrieval algorithm, developed and implemented for routine global processing at NASA's Land Science Investigator-led Processing System (SIPS), utilizes all high-quality, cloud-free, atmospheric-, terrain-, vegetation-, snow-, lunar-, and stray light-corrected radiances to estimate daily nighttime lights (NTL) and other intrinsic surface optical properties. Key algorithm enhancements include: (1) lunar irradiance modeling to resolve non-linear changes in phase and libration; (2) vector radiative transfer and lunar bidirectional surface anisotropic reflectance modeling to correct for atmospheric and BRDF effects; (3) geometric-optical and canopy radiative transfer modeling to account for seasonal variations in NTL; and (4) temporal gap-filling to reduce persistent data gaps. Extensive benchmark tests at representative spatial and temporal scales were conducted on the VNP46 time series record to characterize the uncertainties stemming from upstream data sources. Initial validation results are presented together with example case studies illustrating the scientific utility of the products. This includes an evaluation of temporal patterns of NTL dynamics associated with urbanization, socioeconomic variability, cultural characteristics, and displaced populations affected by conflict. Current and planned activities under the Group on Earth Observations (GEO) Human Planet Initiative are aimed at evaluating the products at different geographic locations and time periods representing the full range of retrieval conditions.

UNLABELLED: Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students' interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training. IMPORTANCE: Engagement of undergraduate students in scientific research at early stages in their careers presents an opportunity to excite students about science, technology, engineering, and mathematics (STEM) disciplines and promote continued interests in these areas. Many excellent course-based undergraduate research experiences have been developed, but scaling these to a broader impact with larger numbers of students is challenging. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunting Advancing Genomics and Evolutionary Science (SEA-PHAGES) program takes advantage of the huge size and diversity of the bacteriophage population to engage students in discovery of new viruses, genome annotation, and comparative genomics, with strong impacts on bacteriophage research, increased persistence in STEM fields, and student self-identification with learning gains, motivation, attitude, and career aspirations.

Senile plaques (SPs) and neurofibrillary tangles (NFTs) are hallmark pathologies accompanying the neurodegeneration involved in Alzheimer's disease (AD), for which beta-amyloid (Abeta) peptide is a major constituent of SPs. Our laboratories previously developed the hydrophobic, fluorescent molecular-imaging probe 2-(1-(6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malononitrile ([(18)F]FDDNP), which crosses the blood-brain barrier and determines the localization and load of SPs and NFTs in vivo in AD patients. In this report, we used fluorimetric and radioactive binding assays to determine the binding affinities of FDDNP and its analog, 1-(6-[(2-[(18)F]fluoroethyl)(methyl)amino]naphthalen-2-yl)ethanone ([(18)F]FENE), to synthetic fibrils of Abeta(1-40). FDDNP and FENE both appeared to bind to two kinetically distinguishable binding sites on Abeta(1-40) fibrils. Fluorescence titrations yielded apparent K(d) values of 0.12 and 0.16 nm for high-affinity binding sites for FDDNP and FENE, respectively, and apparent K(d) values of 1.86 and 71.2 nm for the low-affinity binding sites. The traditional radioactive binding assays also produced apparent K(d) values in the low nanomolar range. The presence of two kinetically distinguishable binding sites for FDDNP and FENE suggests multiple binding sites for SPs and identifies the parameters that allow for the structural optimization of this family of probes for in vivo use. The high-affinity binding of the probes to multiple binding sites on fibrils are consistent with results obtained with digital autoradiography, immunohistochemistry, and confocal fluorescence microscopy using human brain specimens of AD patients.

Quenching of fluorophores by the same proteins that they covalently label is a phenomenon that is neither well-known nor well-characterized. It is often assumed that fluorophores are unperturbed by their target proteins. However, it has been observed that attached fluorophores can be quenched by contact with amino acids within the same protein, and this property has been exploited to report on changing conformational states or intramolecular dynamics of proteins. We show in this communication that fluorescence of Alexa dyes is, in fact, quenched by interactions with Trp, Tyr, Met, and His residues through a combination of static and dynamic quenching mechanisms. In light of this finding, the potential effect of intramolecular quenching should be considered in the interpretation of data that involves quantitative measurements of fluorescence intensity in proteins.

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. An alumni survey revealed that time spent on a research project is also a significant factor in the value former students assign to the experience one or more years later. We conclude: 1) implementation of a bioinformatics project within the biology curriculum provides a mechanism for successfully engaging large numbers of students in undergraduate research; 2) benefits to students are achievable at a wide variety of academic institutions; and 3) successful implementation of course-based research experiences requires significant investment of instructional time for students to gain full benefit.

Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4-99.7 kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for α-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies.

A conventional thermal emitter exhibits a broad emission spectrum with a peak wavelength depending upon the operation temperature. Recently, narrowband thermal emission was realized with periodic gratings or single microstructures of polar crystals supporting distinct optical modes. Here, we exploit the coupling of adjacent phonon-polaritonic nanostructures, demonstrating experimentally that the nanometer-scale gaps can control the thermal emission frequency while retaining emission line widths as narrow as 10 cm–1. This was achieved by using deeply subdiffractional bowtie-shaped silicon carbide nanoantennas. Infrared far-field reflectance spectroscopy, near-field optical nanoimaging, and full-wave electromagnetic simulations were employed to prove that the thermal emission originates from strongly localized surface phonon-polariton resonances of nanoantenna structures. The observed narrow emission line widths and exceptionally small modal volumes provide new opportunities for the user-design of near- and far-field radiation patterns for advancements in infrared spectroscopy, sensing, signaling, communications, coherent thermal emission, and infrared photodetection.

We report the observation and manipulation of hydrogen atoms beneath the surface of a Pd[111] crystal by using low-temperature scanning tunneling microscopy. These subsurface hydride sites have been postulated to have critical roles in hydrogen storage, metal embrittlement, fuel cells, and catalytic reactions, but they have been neither observed directly nor selectively populated previously. We demonstrate that the subsurface region of Pd can be populated with hydrogen atoms from the bulk by applying voltage pulses from a scanning tunneling microscope tip. This phenomenon is explained with an inelastic excitation mechanism, whereby hydrogen atoms in the bulk are excited by tunneling electrons and are promoted to more stable sites in the subsurface region. We show that this selectively placed subsurface hydride affects the electronic, geometric, and chemical properties of the surface. Specifically, we observed the effects of hydride formation on surface deformation and charge and on adsorbed hydrogen on the surface. Hydrogen segregation and overlayer vacancy ordering on the Pd[111] have been characterized and explained in terms of the surface changes attributable to selective hydrogen occupation of subsurface hydride sites in Pd[111].

Candida biofilm infections pose an increasing threat in the health care setting due to the drug resistance associated with this lifestyle. Several mechanisms underlie the resistance phenomenon. In Candida albicans, one mechanism involves drug impedance by the biofilm matrix linked to β-1,3 glucan. Here, we show this is important for other Candida spp. We identified β-1,3 glucan in the matrix, found that the matrix sequesters antifungal drug, and enhanced antifungal susceptibility with matrix β-1,3 glucan hydrolysis.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.

// Jessian L. Munoz 1, 2 , Vivian Rodriguez-Cruz 3 , Shakti H. Ramkissoon 4 , Keith L. Ligon 4 , Steven J. Greco 1 , Pranela Rameshwar 1, 2 1 New Jersey Medical School, Rutgers, Newark, NJ, USA 2 Graduate School of Biomedical Science, Rutgers School of Biomedical Health Sciences, Newark, NJ, USA 3 University of Puerto Rico, Chemistry Department, Cayey, Puerto Rico 4 Department of Pathology, Brigham and Women’s Hospital, Boston Children’s Hospital and Harvard Medical School, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Correspondence to: Pranela Rameshwar, e-mail: rameshwa@njms.rutgers.edu Keywords: glioblastoma, MicroRNA-9, PTCH, Temozolomide, P-gp Received: October 11, 2014      Accepted: November 19, 2014      Published: February 06, 2015 ABSTRACT Glioblastoma Multiforme (GBM), the most common and lethal adult primary tumor of the brain, showed a link between Sonic Hedgehog (SHH) pathway in the resistance to temozolomide (TMZ). PTCH1, the SHH receptor, can tonically represses signaling by endocytosis. We asked how the decrease in PTCH1 in GBM cells could lead to TMZ-resistance. TMZ resistant GBM cells have increased PTCH1 mRNA and reduced protein. Knockdown of Dicer, a Type III RNAase, indicated that miRNAs can explain the decreased PTCH1 in TMZ resistant cells. Computational studies, real-time PCR, reporter gene studies, western blots, target protector oligos and ectopic expression identified miR-9 as the target of PTCH1 in resistant GBM cells with concomitant activation of SHH signaling. MiR-9 mediated increases in the drug efflux transporters, MDR1 and ABCG2. MiR-9 was increased in the tissues from GBM patients and in an early passage GBM cell line from a patient with recurrent GBM but not from a naïve patient. Pharmacological inhibition of SHH signaling sensitized the GBM cells to TMZ. Taken together, miR-9 targets PTCH1 in GBM cells by a SHH-independent method in GBM cells for TMZ resistance. The identified pathways could lead to new strategies to target GBM with combinations of drugs.

ABSTRACT A Linear Finite Dynamical System (LFDS) is a pair (E, f) where E is a finite dimensional space over a finite field k. A complete description of the dynamics of f, the behavior of f's iterates, is given, based on the natural decomposition of any linear map into a nilpotent and bijective components. The results can be used for studying the dynamics of any linear map.

In their 2012 report, the President's Council of Advisors on Science and Technology advocated "replacing standard science laboratory courses with discovery-based research courses"-a challenging proposition that presents practical and pedagogical difficulties. In this paper, we describe our collective experiences working with the Genomics Education Partnership, a nationwide faculty consortium that aims to provide undergraduates with a research experience in genomics through a scheduled course (a classroom-based undergraduate research experience, or CURE). We examine the common barriers encountered in implementing a CURE, program elements of most value to faculty, ways in which a shared core support system can help, and the incentives for and rewards of establishing a CURE on our diverse campuses. While some of the barriers and rewards are specific to a research project utilizing a genomics approach, other lessons learned should be broadly applicable. We find that a central system that supports a shared investigation can mitigate some shortfalls in campus infrastructure (such as time for new curriculum development, availability of IT services) and provides collegial support for change. Our findings should be useful for designing similar supportive programs to facilitate change in the way we teach science for undergraduates.

An early proposal was that for rapid ATP synthesis by the rotational ATP synthase, a specific second site must bind ADP and P(i), and for rapid ATP hydrolysis a different second site must bind ATP. Such bi-site activation was considered to occur whether or not an ADP or ATP was at a third site. In contrast, a more recent proposal is that rapid ATP hydrolysis requires that all three sites have bound ADP or ATP present. However, discovery that one second site binds ADP better than ATP, together with other data and considerations support the earlier proposal. The retention or rebinding of ADP can explain why three sites fill during hydrolysis as ATP concentration is increased although bi-site activation still prevails.

Icons are used widely in human-computer interfaces. The level of abstractness-concreteness of an icon and its effect upon performance is of widespread interest. The authors have devised a quantitative measure for abstractness based on the complexity of the icon. They test their metric against subjective judgments of abstractness as identified by two different groups of subjects. After ranking two sets of ‘abstract’ and ‘concrete’ icons, the authors examined how well the icons were matched to the Pascal constructs that they represented. Further experiments were conducted using different groups of subjects to check whether correct matching of the icons with constructs was influenced by context. In summary the authors found that their metric was a good match for subjective measures of abstractness-concreteness. They also found that there is a better identification of concrete icons than abstract icons. Finally, it was shown that context does affect the correct identification of icons.

This study assessed the effectiveness of a model for diffusing the Life Skills Training (LST) Program into middle schools, examined implementation fidelity, and explored factors associated with involvement in training and program implementation. A convenience sample of master trainers (n = 44) and teachers (n = 45) from 16 Kentucky counties participated. Teachers were observed for content and process fidelity, and trainers and teachers completed questionnaires to assess factors related to training and program implementation. More than one-fourth (27%) of master trainers conducted training sessions, and 60% of teachers taught the curriculum. While implementation fidelity was relatively high, teachers were less likely to use the more innovative elements of the program. Trainers and teachers who conducted training and/or taught the LST Program were more enthusiastic toward the program than those who did nothing beyond being trained.

Glioblastoma multiforme (GBM) commonly resists the frontline chemotherapy treatment temozolomide. The multidrug resistance gene (MDR1) and its protein, P-glycoprotein (P-gp), are associated with chemoresistance. This study investigated the mechanisms underlying MDR1-mediated resistance by GBM to temozolomide. P-gp trafficking was studied by flow cytometry and Western blot analysis. MDR1 expression was analyzed by real-time PCR and reporter gene assays. AP-1 interaction with MDR1 was studied by chromatin immunoprecipitation assay. EGF production was analyzed by ELISA, EGFR signaling was determined by Western blot analysis, and in vivo response to erlotinib and/or temozolomide was studied in nude mice. During the early phase of temozolomide treatment, intracellular P-gp was trafficked to the cell membrane, followed by conformational change into active P-gp. At the later phase, gene transcription of MDR1 was induced by temozolomide-mediated production of EGF. EGF activated ERK1/2-JNK-AP-1 cofactors (c-jun and c-fos). An inhibitor of EGFR kinase (erlotinib) given to nude mice with GBM prevented temozolomide-induced resistance. The results identified an essential role for activated EGFR in the resistance of GBM to temozolomide. Temozolomide resistance occurred through a biphasic response; first, by a conformational change in P-gp into the active form and, second, by releasing EGF, which caused autocrine stimulation of GBM cells to induce MDR1. Pharmacologic inhibition of EGFR kinase blunted the ability of GBM cells to resist temozolomide. These findings may explain reports on the common occurrence of mutant EGFR (EGFRvIII) and EGFR expansion in the resistance of GBM cells.

MoonProt 3.0 (http://moonlightingproteins.org) is an updated open-access database storing expert-curated annotations for moonlighting proteins. Moonlighting proteins have two or more physiologically relevant distinct biochemical or biophysical functions performed by a single polypeptide chain. Here, we describe an expansion in the database since our previous report in the Database Issue of Nucleic Acids Research in 2018. For this release, the number of proteins annotated has been expanded to over 500 proteins and dozens of protein annotations have been updated with additional information, including more structures in the Protein Data Bank, compared with version 2.0. The new entries include more examples from humans, plants and archaea, more proteins involved in disease and proteins with different combinations of functions. More kinds of information about the proteins and the species in which they have multiple functions has been added, including CATH and SCOP classification of structure, known and predicted disorder, predicted transmembrane helices, type of organism, relationship of the protein to disease, and relationship of organism to cause of disease.

Understanding the effect of vibronic coupling on electron transfer (ET) rates is a challenge common to a wide range of applications, from electrochemical synthesis and catalysis to biochemical reactions and solar energy conversion. The Marcus–Jortner–Levich (MJL) theory offers a model of ET rates based on a simple analytic expression with a few adjustable parameters. However, the MJL equation in conjunction with density functional theory (DFT) has yet to be established as a predictive first-principles methodology. A framework is presented for calculating transfer rates modulated by molecular vibrations, that circumvents the steep computational cost which has previously necessitated approximations such as condensing the vibrational manifold into a single empirical frequency. Our DFT–MJL approach provides robust and accurate predictions of ET rates spanning over 4 orders of magnitude in the 106–1010 s–1 range. We evaluate the full MJL equation with a Monte Carlo sampling of the entire active space of thermally accessible vibrational modes, while using no empirical parameters. The contribution to the rate of individual modes is illustrated, providing insight into the interplay between vibrational degrees of freedom and changes in electronic state. The reported findings are valuable for understanding ET rates modulated by multiple vibrational modes, relevant to a broad range of systems within the chemical sciences.

Calls for decolonizing knowledge have been heard from multiple fronts for some time. At issue are questions regarding who gets to claim knowledge, how knowledge is claimed, and how is one to go about gaining knowledge. This article raises questions about the actual practice of decolonizing academic knowledge focusing on the implications of having to claim sanctioned intellectual traditions to be considered a legitimate player. The author wrestles with the fact that people like Graciela, a woman who became an actor in her ethnographic work and shared her reflections about social life, are among the many nonacademics who are typically the subject of research but are rarely considered worth citing as part of one's intellectual grounding. The author brings her own experience doing a critical ethnography with Graciela and other Mexican nonacademics, including issues they raised, as a way of anchoring her questions in praxis.