428 research outputs found
The developmental dynamics of terrorist organizations
We identify robust statistical patterns in the frequency and severity of
violent attacks by terrorist organizations as they grow and age. Using
group-level static and dynamic analyses of terrorist events worldwide from
1968-2008 and a simulation model of organizational dynamics, we show that the
production of violent events tends to accelerate with increasing size and
experience. This coupling of frequency, experience and size arises from a
fundamental positive feedback loop in which attacks lead to growth which leads
to increased production of new attacks. In contrast, event severity is
independent of both size and experience. Thus larger, more experienced
organizations are more deadly because they attack more frequently, not because
their attacks are more deadly, and large events are equally likely to come from
large and small organizations. These results hold across political ideologies
and time, suggesting that the frequency and severity of terrorism may be
constrained by fundamental processes.Comment: 28 pages, 8 figures, 4 tables, supplementary materia
Optical Spectroscopy of Supernova 1993J During Its First 2500 Days
We present 42 low-resolution spectra of Supernova (SN) 1993J, our complete
collection from the Lick and Keck Observatories, from day 3 after explosion to
day 2454, as well as one Keck high-dispersion spectrum from day 383. SN 1993J
began as an apparent SN II, albeit an unusual one. After a few weeks, a
dramatic transition took place, as prominent helium lines emerged in the
spectrum. SN 1993J had metamorphosed from a SN II to a SN IIb. Nebular spectra
of SN 1993J closely resemble those of SNe Ib and Ic, but with a persistent
H_alpha line. At very late times, the H_alpha emission line dominated the
spectrum, but with an unusual, box-like profile. This is interpreted as an
indication of circumstellar interaction.Comment: 19 pages plus 13 figures, AASTeX V5.0. One external table in AASTeX
V4.0, in landscape format. Accepted for publication in A
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Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.
Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor
An Integrated-Photonics Optical-Frequency Synthesizer
Integrated-photonics microchips now enable a range of advanced
functionalities for high-coherence applications such as data transmission,
highly optimized physical sensors, and harnessing quantum states, but with
cost, efficiency, and portability much beyond tabletop experiments. Through
high-volume semiconductor processing built around advanced materials there
exists an opportunity for integrated devices to impact applications cutting
across disciplines of basic science and technology. Here we show how to
synthesize the absolute frequency of a lightwave signal, using integrated
photonics to implement lasers, system interconnects, and nonlinear frequency
comb generation. The laser frequency output of our synthesizer is programmed by
a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and
traceability to the SI second. This is accomplished with a heterogeneously
integrated III/V-Si tunable laser, which is guided by dual
dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through
out-of-loop measurements of the phase-coherent, microwave-to-optical link, we
verify that the fractional-frequency instability of the integrated photonics
synthesizer matches the reference-clock instability for a 1
second acquisition, and constrain any synthesis error to while
stepping the synthesizer across the telecommunication C band. Any application
of an optical frequency source would be enabled by the precision optical
synthesis presented here. Building on the ubiquitous capability in the
microwave domain, our results demonstrate a first path to synthesis with
integrated photonics, leveraging low-cost, low-power, and compact features that
will be critical for its widespread use.Comment: 10 pages, 6 figure
CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.
Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases
How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers
Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program
Discovery of permuted and recently split transfer RNAs in Archaea
Background: As in eukaryotes, precursor transfer RNAs in Archaea often contain introns that are removed in tRNA maturation. Two unrelated archaeal species display unique pre-tRNA processing complexity in the form of split tRNA genes, in which two to three segments of tRNAs are transcribed from different loci, then trans-spliced to form a mature tRNA. Another rare type of pre-tRNA, found only in eukaryotic algae, is permuted, where the 3 ’ half is encoded upstream of the 5 ’ half, and must be processed to be functional. Results: Using an improved version of the gene-finding program tRNAscan-SE, comparative analyses and experimental verifications, we have now identified four novel trans-spliced tRNA genes, each in a different species of the Desulfurococcales branch of the Archaea: tRNA Asp(GUC) in Aeropyrum pernix and Thermosphaera aggregans, and tRNA Lys(CUU) in Staphylothermus hellenicus and Staphylothermus marinus. Each of these includes features surprisingly similar to previously studied split tRNAs, yet comparative genomic context analysis and phylogenetic distribution suggest several independent, relatively recent splitting events. Additionally, we identified the first examples of permuted tRNA genes in Archaea: tRNA iMet(CAU) and tRNA Tyr(GUA) in Thermofilum pendens, which appear to be permuted in the same arrangement seen previously in red alga. Conclusions: Our findings illustrate that split tRNAs are sporadically spread across a major branch of the Archaea
Impacts of air pollutants from rural Chinese households under the rapid residential energy transition
Rural residential energy consumption in China is experiencing a rapid transition towards clean energy, nevertheless, solid fuel combustion remains an important emission source. Here we quantitatively evaluate the contribution of rural residential emissions to PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 μm) and the impacts on health and climate. The clean energy transitions result in remarkable reductions in the contributions to ambient PM2.5, avoiding 130,000 (90,000-160,000) premature deaths associated with PM2.5 exposure. The climate forcing associated with this sector declines from 0.057 ± 0.016 W/m2 in 1992 to 0.031 ± 0.008 W/m2 in 2012. Despite this, the large remaining quantities of solid fuels still contributed 14 ± 10 μg/m3 to population-weighted PM2.5 in 2012, which comprises 21 ± 14% of the overall population-weighted PM2.5 from all sources. Rural residential emissions affect not only rural but urban air quality, and the impacts are highly seasonal and location dependent
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