The Anatomy and Phylogeny of a New Large Plioplatecarpine Mosasaur From the Campanian Bearpaw Shale of Montana (USA)

In 2018, a large and associated plioplatecarpine mosasaur skull, pectoral girdle, and rib cage, whose total body length may have exceeded five meters, was uncovered in the Late Campanian Bearpaw Shale of Northeast Montana (USA). Phylogenetic analysis of this specimen, MOR 10855, recovers this individual as a basal member of the genus Plioplatecarpus. This specimen, is unique in that it is estimated to be nearly twice the size of any of the other species of Plioplatecarpus found in the Western Interior Seaway during this part of the Cretaceous. While the included phylogenetic study suggests MOR 10855 represents a new species within the genus Plioplatecarpus, as supported by the presence of diagnostic features in the frontal, quadrate, and scapula, a poor understanding of individual variation and ontogeny in the related species prevents the confident assignment of a new taxon at this time. In addition to the exceptionally well-preserved skull and anterior skeleton, this specimen also preserves two bite marks on the skull possibly inflicted by a similarly sized mosasaur. These bites exhibit evidence of healing, suggesting one of the first documented cases of non-lethal face biting in a plioplatecarpine mosasaur. The size disparity between this Plioplatecarpus specimen and other species of Plioplatecarpus known from the Bearpaw Shale (P. peckensis and P. primaevus) is reminiscent of size variance observed in some extant cetacean clades, including physeteroids and delphinids. The discovery of MOR 10855 suggests that this portion of the Western Interior Seaway was exceptionally productive during this part of the Cretaceous, and that ecological niche partitioning among the resident mosasaurs was probable

GUT-Scale Primordial Black Holes: Consequences and Constraints

A population of very light primordial black holes which evaporate before nucleosynthesis begins is unconstrained unless the decaying black holes leave stable relics. We show that gravitons Hawking radiated from these black holes would source a substantial stochastic background of high frequency gravititational waves ($10^{12}$ Hz or more) in the present universe. These black holes may lead to a transient period of matter dominated expansion. In this case the primordial universe could be temporarily dominated by large clusters of "Hawking stars" and the resulting gravitational wave spectrum is independent of the initial number density of primordial black holes.Comment: 4 pages; grey body factors included in graviton emission calculations, and a couple of references added, but the conclusions are unchanged. v3 Minor changes to references and wording; final versio

Hyperglycemia alters enzyme activity and cell number in spinal sensory ganglia

Peripheral sensory diabetic neuropathy is characterized by morphological, electrophysiological and neurochemical changes to a subpopulation of primary afferent neurons. Here, we utilized a transgenic mouse model of diabetes (OVE26) and age-matched controls to histologically examine the effect of chronic hyperglycemia on the activity or abundance of the enzymes acid phosphatase, cytochrome oxidase and NADPH-diaphorase in primary sensory neuron perikarya and the dorsal horn of the spinal cord. Quantitative densitometric characterization of enzyme reaction product revealed significant differences between diabetic, compared to control, animals for all three enzymes. Levels of acid phosphatase reaction product were found to be significantly reduced in both small diameter primary sensory somata and the dorsal horn. Cytochrome oxidase activity was found to be significantly lower in small primary sensory somata while NADPH-diaphorase labeling was found to be significantly higher in small primary sensory somata and significantly lower in the dorsal horn. In addition to these observed biochemical changes, ratiometric analysis of the number of small versus large diameter primary sensory perikarya in diabetic and control animals demonstrated a quantifiable decrease in the number of small diameter cells in the spinal ganglia of diabetic mice. These results suggest that the OVE26 model of diabetes mellitus produces an identifiable disturbance in specific metabolic pathways of select cells in the sensory nervous system and that this dysfunction may reflect the progression of a demonstrated cell loss

The Effects of Polarizing Current on Nerve Terminal Impulses Recorded from Polymodal and Cold Receptors in the Guinea-pig Cornea

It was reported recently that action potentials actively invade the sensory nerve terminals of corneal polymodal receptors, whereas corneal cold receptor nerve terminals are passively invaded (Brock, J.A., S. Pianova, and C. Belmonte. 2001. J. Physiol. 533:493–501). The present study investigated whether this functional difference between these two types of receptor was due to an absence of voltage-activated Na+ conductances in cold receptor nerve terminals. To address this question, the study examined the effects of polarizing current on the configuration of nerve terminal impulses recorded extracellularly from single polymodal and cold receptors in guinea-pig cornea isolated in vitro. Polarizing currents were applied through the recording electrode. In both receptor types, hyperpolarizing current (+ve) increased the negative amplitude of nerve terminal impulses. In contrast, depolarizing current (−ve) was without effect on polymodal receptor nerve terminal impulses but increased the positive amplitude of cold receptor nerve terminal impulses. The hyperpolarization-induced increase in the negative amplitude of nerve terminal impulses represents a net increase in inward current. In both types of receptor, this increase in inward current was reduced by local application of low Na+ solution and blocked by lidocaine (10 mM). In addition, tetrodotoxin (1 μM) slowed but did not reduce the hyperpolarization-induced increase in the negative amplitude of polymodal and cold nerve terminal impulses. The depolarization-induced increase in the positive amplitude of cold receptor nerve terminal impulses represents a net increase in outward current. This change was reduced both by lidocaine (10 mM) and the combined application of tetraethylammomium (20 mM) and 4-aminopyridine (1 mM). The interpretation is that both polymodal and cold receptor nerve terminals possess high densities of tetrodotoxin-resistant Na+ channels. This finding suggests that in cold receptors, under normal conditions, the Na+ conductances are rendered inactive because the nerve terminal region is relatively depolarized

A review of the ecological effectiveness of subtidal marine reserves in Central California, Part I: Synopsis of scientific investigations

Marine reserves, often referred to as no-take MPAs, are defined as areas within which human activities that can result in the removal or alteration of biotic and abiotic components of an ecosystem are prohibited or greatly restricted (NRC 2001). Activities typically curtailed within a marine reserve are extraction of organisms (e.g., commercial and recreational fishing, kelp harvesting, commercial collecting), mariculture, and those activities that can alter oceanographic or geologic attributes of the habitat (e.g., mining, shore-based industrial-related intake and discharges of seawater and effluent). Usually, marine reserves are established to conserve biodiversity or enhance nearby fishery resources. Thus, goals and objectives of marine reserves can be inferred, even if they are not specifically articulated at the time of reserve formation. In this report, we review information about the effectiveness of the three marine reserves in the Monterey Bay National Marine Sanctuary (Hopkins Marine Life Refuge, Point Lobos Ecological Reserve, Big Creek Ecological Reserve), and the one in the Channel Islands National Marine Sanctuary (the natural area on the north side of East Anacapa Island). Our efforts to objectively evaluate reserves in Central California relative to reserve theory were greatly hampered for four primary reasons; (1) few of the existing marine reserves were created with clearly articulated goals or objectives, (2) relatively few studies of the ecological consequences of existing reserves have been conducted, (3) no studies to date encompass the spatial and temporal scope needed to identify ecosystem-wide effects of reserve protection, and (4) there are almost no studies that describe the social and economic consequences of existing reserves. To overcome these obstacles, we used several methods to evaluate the effectiveness of subtidal marine reserves in Central California. We first conducted a literature review to find out what research has been conducted in all marine reserves in Central California (Appendix 1). We then reviewed the scientific literature that relates to marine reserve theory to help define criteria to use as benchmarks for evaluation. A recent National Research Council (2001) report summarized expected reserve benefits and provided the criteria we used for evaluation of effectiveness. The next step was to identify the research projects in this region that collected information in a way that enabled us to evaluate reserve theory relative to marine reserves in Central California. Chapters 1-4 in this report provide summaries of those research projects. Contained within these chapters are evaluations of reserve effectiveness for meeting specific objectives. As few studies exist that pertain to reserve theory in Central California, we reviewed studies of marine reserves in other temperate and tropical ecosystems to determine if there were lessons to be learned from other parts of the world (Chapter 5). We also included a discussion of social and economic considerations germane to the public policy decision-making processes associated with marine reserves (Chapter 6). After reviewing all of these resources, we provided a summary of the ecological benefits that could be expected from existing reserves in Central California. The summary is presented in Part II of this report. (PDF contains 133 pages.

A randomised trial of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients: the UK-Vanguard Study

Objective: The objective of the trial was to evaluate in a pilot setting the safety and efficacy of interleukin-2 (IL-2) therapy when used without concomitant antiretroviral therapy as a treatment for HIV infection. Design and Setting: This was a multicentre randomised three-arm trial conducted between September 1998 and March 2001 at three clinical centres in the United Kingdom. Participants: Participants were 36 antiretroviral treatment naive HIV-1-infected patients with baseline CD4 T lymphocyte counts of at least 350 cells/mm(3). Interventions: Participants were randomly assigned to receive IL-2 at 15 million international units (MIU) per day ( 12 participants) or 9 MIU/day ( 12 participants) or no treatment ( 12 participants). IL-2 was administered by twice-daily subcutaneous injections for five consecutive days every 8 wk. Outcome Measures: Primary outcome was the change from baseline CD4 T lymphocyte count at 24 wk. Safety and plasma HIV RNA levels were also monitored every 4 wk through 24 wk. The two IL-2 dose groups were combined for the primary analysis. Results: Area under curve (AUC) for change in the mean CD4 T lymphocyte count through 24 wk was 129 cells/mm(3) for those assigned IL-2 ( both dose groups combined) and 13 cells/mm(3) for control participants (95% CI for difference, 51.3 - 181.2 cells/mm(3); p = 0.0009). Compared to the control group, significant increases in CD4 cell count were observed for both IL-2 dose groups: 104.2/mm(3) ( p = 0.008) and 128.4 cells/mm(3) ( p = 0.002) for the 4.5 and 7.5 MIU dose groups, respectively. There were no significant differences between the IL-2 (0.13 log(10) copies/ ml) and control (0.09 log(10) copies/ml) groups for AUC of change in plasma HIV RNA over the 24-wk period of follow- up ( 95% CI for difference, - 0.17 to 0.26; p = 0.70). Grade 4 and dose-limiting side effects were in keeping with those previously reported for IL-2 therapy. Conclusions: In participants with HIV infection and baseline CD4 T lymphocyte counts of at least 350 cells/mm(3), intermittent subcutaneous IL-2 without concomitant antiretroviral therapy was well tolerated and produced significant increases in CD4 T lymphocyte counts and did not adversely affect plasma HIV RNA levels

Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver

Background: Colorectal cancer is the third most frequently diagnosed cancer and the third cause of cancer deaths in the United States. Despite the fact that tumor cell-intrinsic mechanisms controlling colorectal carcinogenesis have been identified, novel prognostic and diagnostic tools as well as novel therapeutic strategies are still needed to monitor and target colon cancer progression. We and others have previously shown, using mouse models, that the extracellular matrix (ECM), a major component of the tumor microenvironment, is an important contributor to tumor progression. In order to identify candidate biomarkers, we sought to define ECM signatures of metastatic colorectal cancers and their metastases to the liver. Methods: We have used enrichment of extracellular matrix (ECM) from human patient samples and proteomics to define the ECM composition of primary colon carcinomas and their metastases to liver in comparison with normal colon and liver samples. Results: We show that robust signatures of ECM proteins characteristic of each tissue, normal and malignant, can be defined using relatively small samples from small numbers of patients. Comparisons with gene expression data from larger cohorts of patients confirm the association of subsets of the proteins identified by proteomic analysis with tumor progression and metastasis. Conclusions: The ECM protein signatures of metastatic primary colon carcinomas and metastases to liver defined in this study, offer promise for development of diagnostic and prognostic signatures of metastatic potential of colon tumors. The ECM proteins defined here represent candidate serological or tissue biomarkers and potential targets for imaging of occult metastases and residual or recurrent tumors and conceivably for therapies. Furthermore, the methods described here can be applied to other tumor types and can be used to investigate other questions such as the role of ECM in resistance to therapy

New Lower Bound on Fermion Binding Energies

We derive a new lower bound for the ground state energy $E^{\rm F}(N,S)$ of N fermions with total spin S in terms of binding energies $E^{\rm F}(N-1,S \pm 1/2)$ of (N-1) fermions. Numerical examples are provided for some simple short-range or confining potentials.Comment: 4 pages, 1 eps figur

Virtual volatility

We introduce the concept of virtual volatility. This simple but new measure shows how to quantify the uncertainty in the forecast of the drift component of a random walk. The virtual volatility also is a useful tool in understanding the stochastic process for a given portfolio. In particular, and as an example, we were able to identify mean reversion effect in our portfolio. Finally, we briefly discuss the potential practical effect of the virtual volatility on an investor asset allocation strategy.Comment: 15 pages, 2 figures, elsart.cls, Accepted to Physica A. Added few comments that clarify data used for empirical wor

Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis.

BACKGROUND: The genetic contribution to the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not well defined. Across different autoimmune diseases some genes with immunomodulatory roles, such as PTPN22, are frequently associated with multiple diseases, whereas specific HLA associations, such as HLA-B27, tend to be disease restricted. We studied ten candidate loci on the basis of their immunoregulatory role and prior associations with type 1 diabetes (T1D). These included PTPN22, CTLA4 and CD226, which have previously been associated with AAV. METHODS: We genotyped the following 11 SNPs, from 10 loci, in 641 AAV patients using TaqMan genotyping: rs2476601 in PTPN22, rs1990760 in IFIH1, rs3087243 in CTLA4, rs2069763 in IL2, rs10877012 in CYP27B1, rs2292239 in ERBB3, rs3184504 in SH2B3, rs12708716 in CLEC16A, rs1893217 and rs478582 in PTPN2 and rs763361 in CD226. Where possible, we performed a meta-analysis with previous analyses. RESULTS: Both CTLA4 rs3087243 and PTPN22 rs2476601 showed association with AAV, P = 6.4 x 10-3 and P = 1.4 x 10-4 respectively. The minor allele (A) of CTLA4 rs3087243 is protective (odds ratio = 0.84), whereas the minor allele (A) of PTPN22 rs2476601 confers susceptibility (odds ratio = 1.40). These results confirmed previously described associations with AAV. After meta-analysis, the PTPN22 rs2476601 association was further strengthened (combined P = 4.2 x 10-7, odds ratio of 1.48 for the A allele). The other 9 SNPs, including rs763361 in CD226, showed no association with AAV. CONCLUSION: Our study of T1D associated SNPs in AAV has confirmed CTLA4 and PTPN22 as susceptibility loci in AAV. These genes encode two key regulators of the immune response and are associated with many autoimmune diseases, including T1D, autoimmune thyroid disease, celiac disease, rheumatoid arthritis, and now AAV