A Critical Review of the US State Department's 2015 Progress Report on Haiti

This review, published jointly by the Center for Economic and Policy Research and the Haiti Advocacy Working Group, looks at the US State Department's annual reports on US assistance to Haiti mandated under the 2014 Assessing Progress in Haiti Act. The review analyzes the various components of the reports and identifies significant omissions and deficiencies, including incomplete data, a failure to link projects and outcomes, and a failure to adequately identify mistakes and lessons learned.In addition, the review shares feedback from Haitian civil society groups and makes recommendations on how the US Agency for International Development and the State Department can improve future progress reports

Low-Cost, Commercial Scale Production of Sofosbuvir

Recent advances in antiviral therapeutics have produced highly effective small molecule drugs to treat Hepatitis C, a deadly infection of the liver. Sofosbuvir, a hepatitis C drug developed by Gilead Sciences, is a breakthrough treatment due to its low side effects and high cure rate. However, the cost of treatment is extraordinarily high, priced at $84,000 per treatment in the US. In response to backlash regarding the cost barriers in developing countries, Gilead has reached licensing agreements with generic pharmaceutical companies to produce the drug for markets in low-income countries such as India, Kenya, and Cuba among others. The report describes a cost-effective, commercial scale process design for the production of sofosbuvir. The proposed production facility is designed to deliver 350,000 kg/year of the active pharmaceutical ingredient, enough to treat 10 million patients per year. The production will be completed over one hundred batches, requiring operation of 120 days/year. Assuming an 11-year period of operation, detailed economic analysis suggests that this is a profitable venture with an IRR of 67.7$1.2 billion USD

Main Streets and Green Spaces: Creating a Community Vision in Indian Orchard

Main Street and Green Spaces takes a focused look at the neighborhood of Indian Orchard and provides strategies for urban design and landscape architecture to support residents’ visions for the future. With the Studio’s partnership between the Indian Orchard Citizen’s Council, Grow IO (Wellspring Harvest), and the Springfield Office of Planning and Economic Development, the overarching goal for each design team was to create a cohesive, phased plan for redeveloping Main Street around the Oak and Main intersection and Parker and the Ludlow Bridge. Special attention was requested for exploring traffic calming measures and ways to support the local businesses present

"Marker of Self" CD47 on lentiviral vectors decreases macrophage-mediated clearance and increases delivery to SIRPA-expressing lung carcinoma tumors

Lentiviruses infect many cell types and are now widely used for gene delivery in vitro, but in vivo uptake of these foreign vectors by macrophages is a limitation. Lentivectors are produced here from packaging cells that overexpress “Marker of Self” CD47, which inhibits macrophage uptake of cells when prophagocytic factors are also displayed. Single particle analyses show “hCD47-Lenti” display properly oriented human-CD47 for interactions with the macrophage's inhibitory receptor SIRPA. Macrophages derived from human and NOD/SCID/Il2rg−/− (NSG) mice show a SIRPA-dependent decrease in transduction, i.e., transgene expression, by hCD47-Lenti compared to control Lenti. Consistent with known “Self” signaling pathways, macrophage transduction by control Lenti is decreased by drug inhibition of Myosin-II to the same levels as hCD47-Lenti. In contrast, human lung carcinoma cells express SIRPA and use it to enhance transduction by hCD47-Lenti- as illustrated by more efficient gene deletion using CRISPR/Cas9. Intravenous injection of hCD47-Lenti into NSG mice shows hCD47 prolongs circulation, unless a blocking anti-SIRPA is preinjected. In vivo transduction of spleen and liver macrophages also decreases for hCD47-Lenti while transduction of lung carcinoma xenografts increases. hCD47 could be useful when macrophage uptake is limiting on other viral vectors that are emerging in cancer treatments (e.g., Measles glycoprotein-pseudotyped lentivectors) and also in targeting various SIRPA-expressing tumors such as glioblastomas

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.</p

A survey and classification of software-defined storage systems

The exponential growth of digital information is imposing increasing scale and efficiency demands on modern storage infrastructures. As infrastructure complexity increases, so does the difficulty in ensuring quality of service, maintainability, and resource fairness, raising unprecedented performance, scalability, and programmability challenges. Software-Defined Storage (SDS) addresses these challenges by cleanly disentangling control and data flows, easing management, and improving control functionality of conventional storage systems. Despite its momentum in the research community, many aspects of the paradigm are still unclear, undefined, and unexplored, leading to misunderstandings that hamper the research and development of novel SDS technologies. In this article, we present an in-depth study of SDS systems, providing a thorough description and categorization of each plane of functionality. Further, we propose a taxonomy and classification of existing SDS solutions according to different criteria. Finally, we provide key insights about the paradigm and discuss potential future research directions for the field.This work was financed by the Portuguese funding agency FCT-Fundacao para a Ciencia e a Tecnologia through national funds, the PhD grant SFRH/BD/146059/2019, the project ThreatAdapt (FCT-FNR/0002/2018), the LASIGE Research Unit (UIDB/00408/2020), and cofunded by the FEDER, where applicable

Brown marmorated stink bug, Halyomorpha halys (Stål), genome: putative underpinnings of polyphagy, insecticide resistance potential and biology of a top worldwide pest

Background Halyomorpha halys (Stål), the brown marmorated stink bug, is a highly invasive insect species due in part to its exceptionally high levels of polyphagy. This species is also a nuisance due to overwintering in human-made structures. It has caused significant agricultural losses in recent years along the Atlantic seaboard of North America and in continental Europe. Genomic resources will assist with determining the molecular basis for this species’ feeding and habitat traits, defining potential targets for pest management strategies. Results Analysis of the 1.15-Gb draft genome assembly has identified a wide variety of genetic elements underpinning the biological characteristics of this formidable pest species, encompassing the roles of sensory functions, digestion, immunity, detoxification and development, all of which likely support H. halys’ capacity for invasiveness. Many of the genes identified herein have potential for biomolecular pesticide applications. Conclusions Availability of the H. halys genome sequence will be useful for the development of environmentally friendly biomolecular pesticides to be applied in concert with more traditional, synthetic chemical-based controls

Demonstration of surface electron rejection with interleaved germanium detectors for dark matter searches

The following article appeared in Applied Physics Letters 103.16 (2013): 164105 and may be found at http://scitation.aip.org/content/aip/journal/apl/100/26/10.1063/1.4729825The SuperCDMS experiment in the Soudan Underground Laboratory searches for dark matter with a 9-kg array of cryogenic germanium detectors. Symmetric sensors on opposite sides measure both charge and phonons from each particle interaction, providing excellent discrimination between electron and nuclear recoils, and between surface and interior events. Surface event rejection capabilities were tested with two 210 Pb sources producing ∼130 beta decays/hr. In ∼800 live hours, no events leaked into the 8–115 keV signal region, giving upper limit leakage fraction 1.7 × 10−5 at 90% C.L., corresponding to < 0.6 surface event background in the future 200-kg SuperCDMS SNOLAB experiment.This work is supported in part by the National Science Foundation (Grant Nos. AST-9978911, NSF-0847342, PHY-1102795,NSF-1151869, PHY-0542066, PHY-0503729, PHY-0503629, PHY-0503641, PHY-0504224, PHY-0705052,PHY-0801708, PHY-0801712, PHY-0802575, PHY-0847342, PHY-0855299, PHY-0855525, and PHY-1205898), by the Department of Energy (Contract Nos. DE-AC03-76SF00098, DE-FG02-92ER40701, DE-FG02-94ER40823,DE-FG03-90ER40569, DE-FG03-91ER40618, and DESC0004022),by NSERC Canada (Grant Nos. SAPIN 341314 and SAPPJ 386399), and by MULTIDARK CSD2009-00064 and FPA2012-34694. Fermilab is operated by Fermi Research Alliance, LLC under Contract No. De-AC02-07CH11359, while SLAC is operated under Contract No. DE-AC02-76SF00515 with the United States Department of Energy

Drum Synthesis and Rhythmic Transformation with Adversarial Autoencoders

Creative rhythmic transformations of musical audio refer to automated methods for manipulation of temporally-relevant sounds in time. This paper presents a method for joint synthesis and rhythm transformation of drum sounds through the use of adversarial autoencoders (AAE). Users may navigate both the timbre and rhythm of drum patterns in audio recordings through expressive control over a low-dimensional latent space. The model is based on an AAE with Gaussian mixture latent distributions that introduce rhythmic pattern conditioning to represent a wide variety of drum performances. The AAE is trained on a dataset of bar-length segments of percussion recordings, along with their clustered rhythmic pattern labels. The decoder is conditioned during adversarial training for mixing of data-driven rhythmic and timbral properties. The system is trained with over 500000 bars from 5418 tracks in popular datasets covering various musical genres. In an evaluation using real percussion recordings, the reconstruction accuracy and latent space interpolation between drum performances are investigated for audio generation conditioned by target rhythmic patterns

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data