Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets

RELATIVE SENSITIVITY OF SELECTED DISTRIBUTED LAG ESTIMATORS TO MEASUREMENT AND SPECIFICATION ERROR

Research Methods/ Statistical Methods,

UMS Transforms Update, Memo 1

Over the coming months we will regularly write memos like this one to update you about the work taking place to implement the UMS TRANSFORMS initiatives. These memos are designed to update you on what’s happening, provide you with opportunities to express your interest in the initiatives, indicate your interest in getting involved, and suggest ideas that can deepen and expand the work already underway in the many dimensions of this program. Regular updates and additional information are online. Each of the four project areas will provide regular updates, announcements, and information on that site regularly

Are young stars always associated with cold massive disks? A CO and millimeter interferometric continuum survey

The results of a combined millimeter-spectral-line and continuum survey of cold far-infrared sources selected to favor embedded young stars in the Galaxy are presented. The spectral-line observations were performed with the 5 meter antenna of the University of Texas Millimeter-Wave Observatory. High resolution continuum observations were obtained with the Owens Valley (OVRO) Millimeter-Wave Interferometer. The goal of the survey was to gain insight into the mass, temperature, and distribution of cold dust which envelopes stars during the earliest stages of their evolution. The first phase of our survey involved 1.2 arcmin resolution observations of CO-12 and CO-13 emission lines toward each source. All but two sources had detectable CO emission. We found that 40% of the sources appear to be associated with star formation as evidenced by the presence of enhanced CO-12 line widths or broad wings. At least five of these objects are associated with bipolar molecular outflows. The second phase of our survey involves high resolution 2.7 mm continuum observations with 3 interferometer baselines ranging from 15 to 55 m in length. Preliminary results indicate that about 25% of the sources in our sample have detectable continuum emission on scales less than 30 arcsec. The high percentage of sources with enhanced CO-12 line widths or broad wings indicates that a significant fraction of our samples, 40%, are likely to be young stars. The lower detection percentage in the continuum observations, 25%, suggest that such objects are not always surrounded by large concentrations of gas and dust. The continuum detection percentage for actual dust emission could be lower than that given above since emission from ionized gas could be responsible for the observed 2.7 mm emission in some objects. To get an understanding of the type of object detected in our survey, a map of one of the survey sources, L1689N, has been made using the OVRO mm interferometer

Infant Responding to Joint Attention, Executive Processes, and Self-Regulation in Preschool Children

Infant joint attention is related to behavioral and social outcomes, as well as language in childhood. Recent research and theory suggests that the relations between joint attention and social–behavioral outcomes may reflect the role of executive self-regulatory processes in the development of joint attention. To test this hypothesis two studies were conducted. The first, cross-sectional study examined the development of responding to joint attention (RJA) skill in terms of increasing executive efficiency of responding between 9 and 18 months of age. The results indicated that development of RJA was characterized by a decreased latency to shift attention in following another person\u27s gaze and head turn, as well as an increase in the proportion of correct RJA responses exhibited by older infants. The second study examined the longitudinal relations between 12-month measures of responding to joint attention and 36-month attention regulation in a delay of gratification task. The results indicated that responding to joint attention at 12-months was significantly related to children\u27s use of three types of self-regulation behaviors while waiting for a snack reward at 36 months of age. These observations are discussed in light of a developmental theory of attention regulation and joint attention in infancy

A Geometrical Characterization of the Twin Paradox and its Variants

The aim of this paper is to provide a logic-based conceptual analysis of the twin paradox (TwP) theorem within a first-order logic framework. A geometrical characterization of TwP and its variants is given. It is shown that TwP is not logically equivalent to the assumption of the slowing down of moving clocks, and the lack of TwP is not logically equivalent to the Newtonian assumption of absolute time. The logical connection between TwP and a symmetry axiom of special relativity is also studied.Comment: 22 pages, 3 figure

Bulgac-Kusnezov-Nos\'e-Hoover thermostats

In this paper we formulate Bulgac-Kusnezov constant temperature dynamics in phase space by means of non-Hamiltonian brackets. Two generalized versions of the dynamics are similarly defined: one where the Bulgac-Kusnezov demons are globally controlled by means of a single additional Nos\'e variable, and another where each demon is coupled to an independent Nos\'e-Hoover thermostat. Numerically stable and efficient measure-preserving time-reversible algorithms are derived in a systematic way for each case. The chaotic properties of the different phase space flows are numerically illustrated through the paradigmatic example of the one-dimensional harmonic oscillator. It is found that, while the simple Bulgac-Kusnezov thermostat is apparently not ergodic, both of the Nos\'e-Hoover controlled dynamics sample the canonical distribution correctly

Vienna Circle and Logical Analysis of Relativity Theory

In this paper we present some of our school's results in the area of building up relativity theory (RT) as a hierarchy of theories in the sense of logic. We use plain first-order logic (FOL) as in the foundation of mathematics (FOM) and we build on experience gained in FOM. The main aims of our school are the following: We want to base the theory on simple, unambiguous axioms with clear meanings. It should be absolutely understandable for any reader what the axioms say and the reader can decide about each axiom whether he likes it. The theory should be built up from these axioms in a straightforward, logical manner. We want to provide an analysis of the logical structure of the theory. We investigate which axioms are needed for which predictions of RT. We want to make RT more transparent logically, easier to understand, easier to change, modular, and easier to teach. We want to obtain deeper understanding of RT. Our work can be considered as a case-study showing that the Vienna Circle's (VC) approach to doing science is workable and fruitful when performed with using the insights and tools of mathematical logic acquired since its formation years at the very time of the VC activity. We think that logical positivism was based on the insight and anticipation of what mathematical logic is capable when elaborated to some depth. Logical positivism, in great part represented by VC, influenced and took part in the birth of modern mathematical logic. The members of VC were brave forerunners and pioneers.Comment: 25 pages, 1 firgure

Simian immunodeficiency virus infection in wild-caught chimpanzees from Cameroon

Simian immunodeficiency viruses (SIVcpz) infecting chimpanzees (Pan troglodytes) in west central Africa are the closest relatives to all major variants of human immunodeficiency virus type 1 ([HIV-1]; groups M, N and O), and have thus been implicated as the source of the human infections; however, information concerning the prevalence, geographic distribution, and subspecies association of SIVcpz still remains limited. In this study, we tested 71 wild-caught chimpanzees from Cameroon for evidence of SIVcpz infection. Thirty-nine of these were of the central subspecies (Pan troglodytes troglodytes), and 32 were of the Nigerian subspecies (Pan troglodytes vellerosus), as determined by mitochondrial DNA analysis. Serological analysis determined that one P. t. troglodytes ape (CAM13) harbored serum antibodies that cross-reacted strongly with HIV-1 antigens; all other apes were seronegative. To characterize the newly identified virus, 14 partially overlapping viral fragments were amplified from fecal virion RNA and concatenated to yield a complete SIVcpz genome (9,284 bp). Phylogenetic analyses revealed that SIVcpzCAM13 fell well within the radiation of the SIVcpzPtt group of viruses, as part of a clade including all other SIVcpzPtt strains as well as HIV-1 groups M and N. However, SIVcpzCAM13 clustered most closely with SIVcpzGAB1 from Gabon rather than with SIVcpzCAM3 and SIVcpzCAM5 from Cameroon, indicating the existence of divergent SIVcpzPtt lineages within the same geographic region. These data, together with evidence of recombination among ancestral SIVcpzPtt lineages, indicate long-standing endemic infection of central chimpanzees and reaffirm a west central African origin of HIV-1. Whether P. t. vellerosus apes are naturally infected with SIVcpz requires further study