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"Martinez, W."
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The Big Book
This set presents an accurate reproduction of the unpublished magnum opus of W. Eugene Smith, an icon in the field of twentieth-century photography who is best known as the master of the humanistic photographic essay. In 1959, Smith created an extended photo-essay that he called \"The Big Book,\" a complex retrospective of his work that would reflect his philosophy of art and critique of the world. Smith's layout grouped photographs out of context and chronological order to form a series of connected \"visual chapters and subchapters\" that were intended to have a Joycean or Faulknerian literary quality. After three years, Smith completed two handmade folio-sized maquettes to send to publishers. This reproduction of \"The Big Book\" is an essential primary source document for the study of both the history of photography and the history of the photobook.
Book
Fabrication of Miniaturized Paper-Based Microfluidic Devices (MicroPADs)
Microfluidic paper-based analytical devices (microPADs) are emerging as cost-effective and portable platforms for point-of-care assays. A fundamental limitation of microPAD fabrication is the imprecise nature of most methods for patterning paper. The present work demonstrates that paper patterned via wax printing can be miniaturized by treating it with periodate to produce higher-resolution, high-fidelity microPADs. The optimal miniaturization parameters were determined by immersing microPADs in various concentrations of aqueous sodium periodate (NaIO
4
) for varying lengths of time. This treatment miniaturized microPADs by up to 80% in surface area, depending on the concentration of periodate and length of the reaction time. By immersing microPADs in 0.5-M NaIO
4
for 48 hours, devices were miniaturized by 78% in surface area, and this treatment allowed for the fabrication of functional channels with widths as small as 301 µm and hydrophobic barriers with widths as small as 387 µm. The miniaturized devices were shown to be compatible with redox-based colorimetric assays and enzymatic reactions. This miniaturization technique provides a new option for fabricating sub-millimeter-sized features in paper-based fluidic devices without requiring specialized equipment and could enable new capabilities and applications for microPADs.
Journal Article
Three-dimensional microfluidic devices fabricated in layered paper and tape
This article describes a method for fabricating 3D microfluidic devices by stacking layers of patterned paper and double-sided adhesive tape. Paper-based 3D microfluidic devices have capabilities in microfluidics that are difficult to achieve using conventional open-channel microsystems made from glass or polymers. In particular, 3D paper-based devices wick fluids and distribute microliter volumes of samples from single inlet points into arrays of detection zones (with numbers up to thousands). This capability makes it possible to carry out a range of new analytical protocols simply and inexpensively (all on a piece of paper) without external pumps. We demonstrate a prototype 3D device that tests 4 different samples for up to 4 different analytes and displays the results of the assays in a side-by-side configuration for easy comparison. Three-dimensional paper-based microfluidic devices are especially appropriate for use in distributed healthcare in the developing world and in environmental monitoring and water analysis.
Journal Article
The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration
There is a growing evidence describing a decline in adaptive homeostasis in aging-related diseases affecting the central nervous system (CNS), many of which are characterized by the appearance of non-native protein aggregates. One signaling pathway that allows cell adaptation is the integrated stress response (ISR), which senses stress stimuli through four kinases. ISR activation promotes translational arrest through the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) and the induction of a gene expression program to restore cellular homeostasis. However, depending on the stimulus, ISR can also induce cell death. One of the ISR sensors is the double-stranded RNA-dependent protein kinase [protein kinase R (PKR)], initially described as a viral infection sensor, and now a growing evidence supports a role for PKR on CNS physiology. PKR has been largely involved in the Alzheimer’s disease (AD) pathological process. Here, we reviewed the antecedents supporting the role of PKR on the efficiency of synaptic transmission and cognition. Then, we review PKR’s contribution to AD and discuss the possible participation of PKR as a player in the neurodegenerative process involved in aging-related pathologies affecting the CNS.
Journal Article
Investing Cash Transfers to Raise Long-Term Living Standards
Using data from a randomized experiment, we find that poor rural Mexican households invested part of their cash transfers from the Oportunidades program in productive assets, increasing agricultural income by almost 10 percent after 18 months of benefits. We estimate that for each peso transferred, households consume 74 cents and invest the rest, permanently increasing long-term consumption by about 1.6 cents. Results suggest that cash transfers can achieve long-term increases in consumption through investment in productive activities, thereby permitting beneficiary households to attain higher living standards that are sustained even after transitioning off the program.
Journal Article
Architecture of the RNA polymerase-Spt4/5 complex and basis of universal transcription processivity
Related RNA polymerases (RNAPs) carry out cellular gene transcription in all three kingdoms of life. The universal conservation of the transcription machinery extends to a single RNAP‐associated factor, Spt5 (or NusG in bacteria), which renders RNAP processive and may have arisen early to permit evolution of long genes. Spt5 associates with Spt4 to form the Spt4/5 heterodimer. Here, we present the crystal structure of archaeal Spt4/5 bound to the RNAP clamp domain, which forms one side of the RNAP active centre cleft. The structure revealed a conserved Spt5–RNAP interface and enabled modelling of complexes of Spt4/5 counterparts with RNAPs from all kingdoms of life, and of the complete yeast RNAP II elongation complex with bound Spt4/5. The N‐terminal NGN domain of Spt5/NusG closes the RNAP active centre cleft to lock nucleic acids and render the elongation complex stable and processive. The C‐terminal KOW1 domain is mobile, but its location is restricted to a region between the RNAP clamp and wall above the RNA exit tunnel, where it may interact with RNA and/or other factors.
Spt5 and NusG play a conserved role in stimulating RNA polymerase II transcription elongation and processivity. Here, the crystal structure of Spt4/5 bound to the RNA polymerase clamp domain reveals that the factor binds above DNA and RNA in the active centre cleft preventing premature dissociation of the polymerase.
Journal Article
Motion of continental slivers and creeping subduction in the northern Andes
Regions of intense continental deformation, termed continental slivers, have been identified in Chile, Bolivia and Ecuador. Analyses of GPS data now identify another large sliver in Peru, the Inca Sliver, that is moving away from a neighbouring sliver in Ecuador—implying that moving continental slivers control the deformation of almost the entire Andean mountain range.
Along the western margin of South America, plate convergence is accommodated by slip on the subduction interface and deformation of the overriding continent
1
,
2
,
3
,
4
,
5
,
6
. In Chile
1
,
2
,
3
,
4
, Bolivia
6
, Ecuador and Colombia
5
,
7
, continental deformation occurs mostly through the motion of discrete domains, hundreds to thousands of kilometres in scale. These continental slivers are wedged between the Nazca and stable South American plates. Here we use geodetic data to identify another large continental sliver in Peru that is about 300–400 km wide and 1,500 km long, which we call the Inca Sliver. We show that movement of the slivers parallel to the subduction trench is controlled by the obliquity of plate convergence and is linked to prominent features of the Andes Mountains. For example, the Altiplano is located at the boundary of converging slivers at the concave bend of the central Andes, and the extending Gulf of Guayaquil is located at the boundary of diverging slivers at the convex bend of the northern Andes. Motion of a few large continental slivers therefore controls the present-day deformation of nearly the entire Andes mountain range. We also show that a 1,000-km-long section of the plate interface in northern Peru and southern Ecuador slips predominantly aseismically, a behaviour that contrasts with the highly seismic neighbouring segments. The primary characteristics of this low-coupled segment are shared by
∼
20% of the subduction zones in the eastern Pacific Rim.
Journal Article
Paper miniaturization via periodate oxidation of cellulose
Cellulose-based paper is a versatile material with a diverse array of applications. While paper is not commonly thought of as a material that shrinks, here we present a method for miniaturizing paper via periodate oxidation. Chromatography paper was exposed to varying concentrations of periodate (0.1–0.5 M) over a 96-h period. Following optimization of miniaturization parameters, fourteen different types of paper were miniaturized and reductions in surface area ranging from 60 to 80% were observed. All cellulose paper types, but not cellulose-derivatives, displayed successful miniaturization. Results were highly tunable dependent upon periodate concentration and reaction time. Potential applications of the technique are discussed, including its use as a microfabrication method.
Graphical Abstract
Journal Article
Batzelladine D, a Marine Natural Product, Reverses the Fluconazole Resistance Phenotype Mediated by Transmembrane Transporters in Candida albicans and Interferes with Its Biofilm: An In Vitro and In Silico Study
Numerous Candida species are responsible for fungal infections; however, Candida albicans stands out among the others. Treatment with fluconazole is often ineffective due to the resistance phenotype mediated by transmembrane transporters and/or biofilm formation, mechanisms of resistance commonly found in C. albicans strains. A previous study by our group demonstrated that batzelladine D can inhibit the Pdr5p transporter in Saccharomyces cerevisiae. In the present study, our aim was to investigate the efficacy of batzelladine D in inhibiting the main efflux pumps of Candida albicans, CaCdr1p and CaCdr2p, as well as to evaluate the effect of the compound on C. albicans biofilm. Assays were conducted using a clinical isolate of Candida albicans expressing both transporters. Additionally, to allow the study of each transporter, S. cerevisiae mutant strains overexpressing CaCdr1p or CaCdr2p were used. Batzelladine D was able to reverse the fluconazole resistance phenotype by acting on both transporters. The compound synergistically improved the effect of fluconazole against the clinical isolate when tested in the Caenorhabditis elegans animal model. Moreover, the compound disrupted the preformed biofilm. Based on the obtained data, the continuation of batzelladine D studies as a potential new antifungal agent and/or chemosensitizer in Candida albicans infections can be suggested.
Journal Article
Wax-Printed Fluidic Time Delays for Automating Multi-Step Assays in Paper-Based Microfluidic Devices (MicroPADs)
Microfluidic paper-based analytical devices (microPADs) have emerged as a promising platform for point-of-care diagnostic devices. While the inherent wicking properties of microPADs allow for fluid flow without supporting equipment, this also presents a major challenge in achieving robust fluid control, which becomes especially important when performing complex multi-step assays. Herein, we describe an ideal method of fluid control mediated by wax-printed fluidic time delays. This method relies on a simple fabrication technique, does not utilize chemicals/reagents that could affect downstream assays, is readily scalable, and has a wide temporal range of tunable fluid control. The delays are wax printed on both the top and bottom of pre-fabricated microPAD channels, without subsequent heating, to create hemi-/fully-enclosed channels. With these wax printed delays, we were able to tune the time it took aqueous solutions to wick across a 25 mm-long channel between 3.6 min and 13.4 min. We then employed these fluid delays in the sequential delivery of four dyes to a test zone. Additionally, we demonstrated the automation of two simple enzymatic assays with this fluid control modality. This method of fluid control may allow future researchers to automate more complex assays, thereby further advancing microPADs toward real-world applications.
Journal Article