How citation boosts promote scientific paradigm shifts and Nobel Prizes

Nobel Prizes are commonly seen to be among the most prestigious achievements of our times. Based on mining several million citations, we quantitatively analyze the processes driving paradigm shifts in science. We find that groundbreaking discoveries of Nobel Prize Laureates and other famous scientists are not only acknowledged by many citations of their landmark papers. Surprisingly, they also boost the citation rates of their previous publications. Given that innovations must outcompete the rich-gets-richer effect for scientific citations, it turns out that they can make their way only through citation cascades. A quantitative analysis reveals how and why they happen. Science appears to behave like a self-organized critical system, in which citation cascades of all sizes occur, from continuous scientific progress all the way up to scientific revolutions, which change the way we see our world. Measuring the "boosting effect" of landmark papers, our analysis reveals how new ideas and new players can make their way and finally triumph in a world dominated by established paradigms. The underlying "boost factor" is also useful to discover scientific breakthroughs and talents much earlier than through classical citation analysis, which by now has become a widespread method to measure scientific excellence, influencing scientific careers and the distribution of research funds. Our findings reveal patterns of collective social behavior, which are also interesting from an attention economics perspective. Understanding the origin of scientific authority may therefore ultimately help to explain, how social influence comes about and why the value of goods depends so strongly on the attention they attract.Comment: 6 pages, 6 figure

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Spin-photon interface and spin-controlled photon switching in a nanobeam waveguide

Access to the electron spin is at the heart of many protocols for integrated and distributed quantum-information processing [1-4]. For instance, interfacing the spin-state of an electron and a photon can be utilized to perform quantum gates between photons [2,5] or to entangle remote spin states [6-9]. Ultimately, a quantum network of entangled spins constitutes a new paradigm in quantum optics [1]. Towards this goal, an integrated spin-photon interface would be a major leap forward. Here we demonstrate an efficient and optically programmable interface between the spin of an electron in a quantum dot and photons in a nanophotonic waveguide. The spin can be deterministically prepared with a fidelity of 96\%. Subsequently the system is used to implement a "single-spin photonic switch", where the spin state of the electron directs the flow of photons through the waveguide. The spin-photon interface may enable on-chip photon-photon gates [2], single-photon transistors [10], and efficient photonic cluster state generation [11]

The Cost-Effectiveness of Reclassification Sampling for Prevalence Estimation

Typically, a two-phase (double) sampling strategy is employed when classifications are subject to error and there is a gold standard (perfect) classifier available. Two-phase sampling involves classifying the entire sample with an imperfect classifier, and a subset of the sample with the gold-standard.In this paper we consider an alternative strategy termed reclassification sampling, which involves classifying individuals using the imperfect classifier more than one time. Estimates of sensitivity, specificity and prevalence are provided for reclassification sampling, when either one or two binary classifications of each individual using the imperfect classifier are available. Robustness of estimates and design decisions to model assumptions are considered. Software is provided to compute estimates and provide advice on the optimal sampling strategy.Reclassification sampling is shown to be cost-effective (lower standard error of estimates for the same cost) for estimating prevalence as compared to two-phase sampling in many practical situations

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Mites Parasitic on Australasian and African Spiders Found in the Pet Trade; a Redescription of Ljunghia pulleinei Womersley

Parasitic mites associated with spiders are spreading world-wide through the trade in tarantulas and other pet species. Ljunghia pulleinei Womersley, a mesostigmatic laelapid mite originally found in association with the mygalomorph spider Selenocosmia stirlingi Hogg (Theraphosidae) in Australia, is redescribed and illustrated on the basis of specimens from the African theraphosid spider Pterinochilus chordatus (Gersta¨cker) kept in captivity in the British Isles (Wales). The mite is known from older original descriptions of Womersley in 1956; the subsequent redescription of Domrow in 1975 seems to be questionable in conspecificity of treated specimens with the type material. Some inconsistencies in both descriptions are recognised here as intraspecific variability of the studied specimens. The genus Arachnyssus Ma, with species A. guangxiensis (type) and A. huwenae, is not considered to be a valid genus, and is included in synonymy with Ljunghia Oudemans. A new key to world species of the genus Ljunghia is provided

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Alternative Splicing Events Are a Late Feature of Pathology in a Mouse Model of Spinal Muscular Atrophy

Spinal muscular atrophy is a severe motor neuron disease caused by inactivating mutations in the SMN1 gene leading to reduced levels of full-length functional SMN protein. SMN is a critical mediator of spliceosomal protein assembly, and complete loss or drastic reduction in protein leads to loss of cell viability. However, the reason for selective motor neuron degeneration when SMN is reduced to levels which are tolerated by all other cell types is not currently understood. Widespread splicing abnormalities have recently been reported at end-stage in a mouse model of SMA, leading to the proposition that disruption of efficient splicing is the primary mechanism of motor neuron death. However, it remains unclear whether splicing abnormalities are present during early stages of the disease, which would be a requirement for a direct role in disease pathogenesis. We performed exon-array analysis of RNA from SMN deficient mouse spinal cord at 3 time points, pre-symptomatic (P1), early symptomatic (P7), and late-symptomatic (P13). Compared to littermate control mice, SMA mice showed a time-dependent increase in the number of exons showing differential expression, with minimal differences between genotypes at P1 and P7, but substantial variation in late-symptomatic (P13) mice. Gene ontology analysis revealed differences in pathways associated with neuronal development as well as cellular injury. Validation of selected targets by RT–PCR confirmed the array findings and was in keeping with a shift between physiologically occurring mRNA isoforms. We conclude that the majority of splicing changes occur late in SMA and may represent a secondary effect of cell injury, though we cannot rule out significant early changes in a small number of transcripts crucial to motor neuron survival

Impact of insecticide-treated nets on wild pyrethroid resistant Anopheles epiroticus population from southern Vietnam tested in experimental huts

<p>Abstract</p> <p>Background</p> <p>In this study, the efficacy of insecticide-treated nets was evaluated in terms of deterrence, blood-feeding inhibition, induced exophily and mortality on a wild resistant population of <it>Anopheles epiroticus </it>in southern Vietnam, in order to gain insight into the operational consequences of the insecticide resistance observed in this malaria vector in the Mekong delta.</p> <p>Method</p> <p>An experimental station, based on the model of West Africa and adapted to the behaviour of the target species, was built in southern Vietnam. The study design was adapted from the WHO phase 2 guidelines. The study arms included a conventionally treated polyester net (CTN) with deltamethrin washed just before exhaustion, the WHO recommended long-lasting insecticidal net (LLIN) PermaNet 2.0^®unwashed and 20 times washed and PermaNet 3.0^®, designed for the control of pyrethroid resistant vectors, unwashed and 20 times washed.</p> <p>Results</p> <p>The nets still provided personal protection against the resistant <it>An. epiroticus </it>population. The personal protection ranged from 67% for deltamethrin CTN to 85% for unwashed PermaNet 3.0. Insecticide resistance in the <it>An. epiroticus </it>mosquitoes did not seem to alter the deterrent effect of pyrethroids. A significant higher mortality was still observed among the treatment arms despite the fact that the <it>An. epiroticus </it>population is resistant against the tested insecticides.</p> <p>Conclusion</p> <p>This study shows that CTN and LLINs still protect individuals against a pyrethroid resistant malaria vector from the Mekong region, where insecticide resistance is caused by a metabolic mechanism. In the light of a possible elimination of malaria from the Mekong region these insights in operational consequences of the insecticide resistance on control tools is of upmost importance.</p