Local spinfoam expansion in loop quantum cosmology

The quantum dynamics of the flat Friedmann-Lemaitre-Robertson-Walker and Bianchi I models defined by loop quantum cosmology have recently been translated into a spinfoam-like formalism. The construction is facilitated by the presence of a massless scalar field which is used as an internal clock. The implicit integration over the matter variable leads to a nonlocal spinfoam amplitude. In this paper we consider a vacuum Bianchi I universe and show that by choosing an appropriate regulator a spinfoam expansion can be obtained without selecting a clock variable and that the resulting spinfoam amplitude is local.Comment: 12 page

On the gravitational production of superheavy dark matter

The dark matter in the universe can be in the form of a superheavy matter species (WIMPZILLA). Several mechanisms have been proposed for the production of WIMPZILLA particles during or immediately following the inflationary epoch. Perhaps the most attractive mechanism is through gravitational particle production, where particles are produced simply as a result of the expansion of the universe. In this paper we present a detailed numerical calculation of WIMPZILLA gravitational production in hybrid-inflation models and natural-inflation models. Generalizing these findings, we also explore the dependence of the gravitational production mechanism on various models of inflation. We show that superheavy dark matter production seems to be robust, with Omega_X h^2 ~ (M_X / (10^11 GeV))^2 (T_RH / (10^9 GeV)), so long as M_X < H_I, where M_X is the WIMPZILLA mass, T_RH is the reheat temperature, and H_I is the expansion rate of the universe during inflation.Comment: 26 pages, 7 figures; LaTeX; submitted to Physical Review D; minor typographical error correcte

Temperatures achieved in human and canine neocortex during intraoperative passive or active focal cooling

Focal cortical cooling inhibits seizures and prevents acquired epileptogenesis in rodents. To investigate the potential clinical utility of this treatment modality, we examined the thermal characteristics of canine and human brain undergoing active and passive surface cooling in intraoperative settings. Four patients with intractable epilepsy were treated in a standard manner. Before the resection of a neocortical epileptogenic focus, multiple intraoperative studies of active (custom-made cooled irrigation-perfused grid) and passive (stainless steel probe) cooling were performed. We also actively cooled the neocortices of two dogs with perfused grids implanted for 2 hours. Focal surface cooling of the human brain causes predictable depth-dependent cooling of the underlying brain tissue. Cooling of 0.6–2°C was achieved both actively and passively to a depth of 10–15 mm from the cortical surface. The perfused grid permitted comparable and persistent cooling of canine neocortex when the craniotomy was closed. Thus, the human cortex can easily be cooled with the use of simple devices such as a cooling grid or a small passive probe. These techniques provide pilot data for the design of a permanently implantable device to control intractable epilepsy

Microgeometry capture using an elastomeric sensor

We describe a system for capturing microscopic surface geometry. The system extends the retrographic sensor [Johnson and Adelson 2009] to the microscopic domain, demonstrating spatial resolution as small as 2 microns. In contrast to existing microgeometry capture techniques, the system is not affected by the optical characteristics of the surface being measured---it captures the same geometry whether the object is matte, glossy, or transparent. In addition, the hardware design allows for a variety of form factors, including a hand-held device that can be used to capture high-resolution surface geometry in the field. We achieve these results with a combination of improved sensor materials, illumination design, and reconstruction algorithm, as compared to the original sensor of Johnson and Adelson [2009].National Science Foundation (U.S.) (Grant 0739255)National Institutes of Health (U.S.) (Contract 1-R01-EY019292-01

Malaria Life Cycle Intensifies Both Natural Selection and Random Genetic Drift

Analysis of genome sequences of 159 isolates of Plasmodium falciparum from Senegal yields an extraordinarily high proportion (26.85%) of protein-coding genes with the ratio of nonsynonymous to synonymous polymorphism greater than one. This proportion is much greater than observed in other organisms. Also unusual is that the site-frequency spectra of synonymous and nonsynonymous polymorphisms are virtually indistinguishable. We hypothesized that the complicated life cycle of malaria parasites might lead to qualitatively different population genetics from that predicted from the classical Wright-Fisher (WF) model, which assumes a single random-mating population with a finite and constant population size in an organism with nonoverlapping generations. This paper summarizes simulation studies of random genetic drift and selection in malaria parasites that take into account their unusual life history. Our results show that random genetic drift in the malaria life cycle is more pronounced than under the WF model. Paradoxically, the efficiency of purifying selection in the malaria life cycle is also greater than under WF, and the relative efficiency of positive selection varies according to conditions. Additionally, the site-frequency spectrum under neutrality is also more skewed toward low-frequency alleles than expected with WF. These results highlight the importance of considering the malaria life cycle when applying existing population genetic tools based on the WF model. The same caveat applies to other species with similarly complex life cycles.Organismic and Evolutionary Biolog

Paraneoplastic thrombocytosis in ovarian cancer

&lt;p&gt;Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear.&lt;/p&gt; &lt;p&gt;Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.&lt;/p&gt; &lt;p&gt;Results: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumorderived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti–interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis.&lt;/p&gt; &lt;p&gt;Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. &lt;/p&gt

Spatially Resolved Ultraviolet Spectroscopy of the Great Dimming of Betelgeuse

The bright supergiant, Betelgeuse (Alpha Orionis, HD 39801) experienced a visual dimming during 2019 December and the first quarter of 2020 reaching an historic minimum 2020 February 7$-$13. During 2019 September-November, prior to the optical dimming event, the photosphere was expanding. At the same time, spatially resolved ultraviolet spectra using the Hubble Space Telescope/Space Telescope Imaging Spectrograph revealed a substantial increase in the ultraviolet spectrum and Mg II line emission from the chromosphere over the southern hemisphere of the star. Moreover, the temperature and electron density inferred from the spectrum and C II diagnostics also increased in this hemisphere. These changes happened prior to the Great Dimming Event. Variations in the Mg II k-line profiles suggest material moved outwards in response to the passage of a pulse or acoustic shock from 2019 September through 2019 November. It appears that this extraordinary outflow of material from the star, likely initiated by convective photospheric elements, was enhanced by the coincidence with the outward motions in this phase of the $\sim$400 day pulsation cycle. These ultraviolet observations appear to provide the connecting link between the known large convective cells in the photosphere and the mass ejection event that cooled to form the dust cloud in the southern hemisphere imaged in 2019 December, and led to the exceptional optical dimming of Betelgeuse in 2020 February.Comment: 11 pages, 8 figures, Astrophysical Journal, accepte

Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy

The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide increased blood flow as early as 3 days after administration, whereas paclitaxel induced a transient blood flow decrease at 1 day after administration. Early blood flow changes correlated strongly with the treatmePeer ReviewedPostprint (published version

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online