The Stable Entropy Hypothesis and Entropy-Aware Decoding: An Analysis and Algorithm for Robust Natural Language Generation

State-of-the-art language generation models can degenerate when applied to open-ended generation problems such as text completion, story generation, or dialog modeling. This degeneration usually shows up in the form of incoherence, lack of vocabulary diversity, and self-repetition or copying from the context. In this paper, we postulate that ``human-like'' generations usually lie in a narrow and nearly flat entropy band, and violation of these entropy bounds correlates with degenerate behavior. Our experiments show that this stable narrow entropy zone exists across models, tasks, and domains and confirm the hypothesis that violations of this zone correlate with degeneration. We then use this insight to propose an entropy-aware decoding algorithm that respects these entropy bounds resulting in less degenerate, more contextual, and "human-like" language generation in open-ended text generation settings

Development of an inducible mouse model of iRFP713 to track recombinase activity and tumour development in vivo

While the use of bioluminescent proteins for molecular imaging is a powerful technology to further our understanding of complex processes, fluorescent labeling with visible light fluorescent proteins such as GFP and RFP suffers from poor tissue penetration and high background autofluorescence. To overcome these limitations, we generated an inducible knock-in mouse model of iRFP713. This model was used to assess Cre activity in a Rosa Cre-ER background and quantify Cre activity upon different tamoxifen treatments in several organs. We also show that iRFP can be readily detected in 3D organoid cultures, FACS analysis and in vivo tumour models. Taken together we demonstrate that iRFP713 is a progressive step in in vivo imaging and analysis that widens the optical imaging window to the near-infrared spectrum, thereby allowing deeper tissue penetration, quicker image acquisition without the need to inject substrates and a better signal to background ratio in genetically engineered mouse models (GEMMs)

Spectrally Tailored Pulsed Thulium Fiber Laser System for Broadband Lidar CO2 Sensing

Thulium doped pulsed fiber lasers are capable of meeting the spectral, temporal, efficiency, size and weight demands of defense and civil applications for pulsed lasers in the eye-safe spectral regime due to inherent mechanical stability, compact "all-fiber" master oscillator power amplifier (MOPA) architectures, high beam quality and efficiency. Thulium fiber's longer operating wavelength allows use of larger fiber cores without compromising beam quality, increasing potential single aperture pulse energies. Applications of these lasers include eye-safe laser ranging, frequency conversion to longer or shorter wavelengths for IR countermeasures and sensing applications with otherwise tough to achieve wavelengths and detection of atmospheric species including CO2 and water vapor. Performance of a portable thulium fiber laser system developed for CO2 sensing via a broadband lidar technique with an etalon based sensor will be discussed. The fielded laser operates with approximately 280 J pulse energy in 90-150ns pulses over a tunable 110nm spectral range and has a uniquely tailored broadband spectral output allowing the sensing of multiple CO2 lines simultaneously, simplifying future potentially space based CO2 sensing instruments by reducing the number and complexity of lasers required to carry out high precision sensing missions. Power scaling and future "all fiber" system configurations for a number of ranging, sensing, countermeasures and other yet to be defined applications by use of flexible spectral and temporal performance master oscillators will be discussed. The compact, low mass, robust, efficient and readily power scalable nature of "all-fiber" thulium lasers makes them ideal candidates for use in future space based sensing applications

Systems-Level Comparison of Host-Responses Elicited by Avian H5N1 and Seasonal H1N1 Influenza Viruses in Primary Human Macrophages

Human disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1) or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1) virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN) and tumor necrosis factor (TNF)-α genes. A network-based analysis suggests that the synergy between IFN-β and TNF-α results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease

Mechanisms of breast cancer metastasis

Invasive breast cancer tends to metastasize to lymph nodes and systemic sites. The management of metastasis has evolved by focusing on controlling the growth of the disease in the breast/chest wall, and at metastatic sites, initially by surgery alone, then by a combination of surgery with radiation, and later by adding systemic treatments in the form of chemotherapy, hormone manipulation, targeted therapy, immunotherapy and other treatments aimed at inhibiting the proliferation of cancer cells. It would be valuable for us to know how breast cancer metastasizes; such knowledge would likely encourage the development of therapies that focus on mechanisms of metastasis and might even allow us to avoid toxic therapies that are currently used for this disease. For example, if we had a drug that targeted a gene that is critical for metastasis, we might even be able to cure a vast majority of patients with breast cancer. By bringing together scientists with expertise in molecular aspects of breast cancer metastasis, and those with expertise in the mechanical aspects of metastasis, this paper probes interesting aspects of the metastasis cascade, further enlightening us in our efforts to improve the outcome from breast cancer treatments

The Curve of Compactified 6D Gauge Theories and Integrable Systems

We analyze the Seiberg-Witten curve of the six-dimensional N=(1,1) gauge theory compactified on a torus to four dimensions. The effective theory in four dimensions is a deformation of the N=2* theory. The curve is naturally holomorphically embedding in a slanted four-torus--actually an abelian surface--a set-up that is natural in Witten's M-theory construction of N=2 theories. We then show that the curve can be interpreted as the spectral curve of an integrable system which generalizes the N-body elliptic Calogero-Moser and Ruijsenaars-Schneider systems in that both the positions and momenta take values in compact spaces. It turns out that the resulting system is not simply doubly elliptic, rather the positions and momenta, as two-vectors, take values in the ambient abelian surface. We analyze the two-body system in some detail. The system we uncover provides a concrete realization of a Beauville-Mukai system based on an abelian surface rather than a K3 surface.Comment: 22 pages, JHEP3, 4 figures, improved readility of figures, added reference

Disentangling superconducting and magnetic orders in NaFe_1-xNi_xAs using muon spin rotation

Muon spin rotation and relaxation studies have been performed on a "111" family of iron-based superconductors NaFe_1-xNi_xAs. Static magnetic order was characterized by obtaining the temperature and doping dependences of the local ordered magnetic moment size and the volume fraction of the magnetically ordered regions. For x = 0 and 0.4 %, a transition to a nearly-homogeneous long range magnetically ordered state is observed, while for higher x than 0.4 % magnetic order becomes more disordered and is completely suppressed for x = 1.5 %. The magnetic volume fraction continuously decreases with increasing x. The combination of magnetic and superconducting volumes implies that a spatially-overlapping coexistence of magnetism and superconductivity spans a large region of the T-x phase diagram for NaFe_1-xNi_xAs . A strong reduction of both the ordered moment size and the volume fraction is observed below the superconducting T_C for x = 0.6, 1.0, and 1.3 %, in contrast to other iron pnictides in which one of these two parameters exhibits a reduction below TC, but not both. The suppression of magnetic order is further enhanced with increased Ni doping, leading to a reentrant non-magnetic state below T_C for x = 1.3 %. The reentrant behavior indicates an interplay between antiferromagnetism and superconductivity involving competition for the same electrons. These observations are consistent with the sign-changing s-wave superconducting state, which is expected to appear on the verge of microscopic coexistence and phase separation with magnetism. We also present a universal linear relationship between the local ordered moment size and the antiferromagnetic ordering temperature TN across a variety of iron-based superconductors. We argue that this linear relationship is consistent with an itinerant-electron approach, in which Fermi surface nesting drives antiferromagnetic ordering.Comment: 20 pages, 14 figures, Correspondence should be addressed to Prof. Yasutomo Uemura: [email protected]

Ad hoc influenza vaccination during years of significant antigenic drift in a tropical city with 2 seasonal peaks

We evaluated the acceptability of an additional ad hoc influenza vaccination among the health care professionals following seasons with significant antigenic drift. Self-administered, anonymous surveys were performed by hard copy questionnaires in public hospitals, and by an on-line platform available to all healthcare professionals, from April 1st to May 31st, 2015. A total of 1290 healthcare professionals completed the questionnaires, including doctors, nurses, and allied health professionals working in both the public and private systems. Only 31.8% of participating respondents expressed an intention to receive the additional vaccine, despite that the majority of them agreed or strongly agreed that it would bring benefit to the community (88.9%), save lives (86.7%), reduce medical expenses (76.3%), satisfy public expectation (82.8%), and increase awareness of vaccination (86.1%). However, a significant proportion expressed concern that the vaccine could disturb the normal immunization schedule (45.5%); felt uncertain what to do in the next vaccination round (66.0%); perceived that the summer peak might not occur (48.2%); and believed that the summer peak might not be of the same virus (83.5%). Furthermore, 27.8% of all respondents expected that the additional vaccination could weaken the efficacy of previous vaccinations; 51.3% was concerned about side effects; and 61.3% estimated that there would be a low uptake rate. If the supply of vaccine was limited, higher priority groups were considered to include the elderly aged ≥65 years with chronic medical conditions (89.2%), the elderly living in residential care homes (87.4%), and long-stay residents of institutions for the disabled (80.7%). The strongest factors associated with accepting the additional vaccine included immunization with influenza vaccines in the past 3 years, higher perceived risk of contracting influenza, and higher perceived severity of the disease impact. The acceptability to an additional ad hoc influenza vaccination was low among healthcare professionals. This could have a negative impact on such additional vaccination campaigns since healthcare professionals are a key driver for vaccine acceptance. The discordance in perceived risk and acceptance of vaccination regarding self versus public deserves further evaluation

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al