Balancing a force on the fingertip of a two-dimensional finger model without intrinsic muscles

A slightly flexed human middle finger can balance an external force on the fingertip. Internal stabilization is also possible, which means that the externally unloaded finger can be kept stiff. We want to analyse whether in these situations the intrinsic hand muscles are needed. Distances from tendons to flexion axes are taken from the literature and are substituted in the moment equilibrium equations of a two-dimensional finger model. Diagrams illustrate the statically indeterminate problem of solving tendon forces. The possibilities for equilibrium without intrinsics appear to depend mainly on four tendon-to-joint distances. These distances determine to which of two groups a finger belongs: (1) one in which intrinsics are not necessary for internal stabilization nor for balancing a force on the fingertip in any direction in the sagittal plane; (2) one in which, without intrinsics, internal stabilization is impossible and only dorso-distally directed forces on the fingertip can be balanced.     

A mathematical framework for examining whether a minimum number of chiasmata is required per metacentric chromosome or chromosome arm in human

We introduce a piecewise linear regression called "hockey stick regression" to model the relationship between genetic and physical lengths of chromosomes in a genome. This piecewise linear regression is an extension of the two-parameter linear regression we proposed earlier [W. Li and J. Freudenberg, Two-parameter characterization of chromosome-scale recombination rate, Genome Res., 19 (2009) 2300-2307]. We use this, as well as the one-piece regression with a fixed y-intercept, to compare the two competing hypotheses concerning the minimum number of required chiasmata for meiosis: minimum one chiasma per chromosome (PC) and per chromosome arm (PA). Using statistical model selection and testing, we show that for human genome data, one-piece PC (PC1) is often in a statistical tie with two-piece PA model (PA2). If an upper bound for the segmentation point in two-piece regression is imposed, PC is usually the preferred model. This indicates that a presence of more than one chiasmata is rather caused by the relationship between chromosome size and chiasma formation than by cytogenetic constraints.     

Multiple glomus tumors associated with arteriovenous fistulas and with nodular lesions of the finger joints.

A patient is reported with an extremely unusual clinical presentation comprising painful subungual glomus tumors, hemangioma-like skin lesions of the trunk, and nodular lesions of the finger joints. Prominent arteriovenous shunting also was present. The etiology of all these abnormalities was thought to be extensive proliferation of glomus cells.     

Evaluation of a course for general practitioners on muscles and joints.

We attempted to evaluate a course on muscle and joint problems for general practitioners using a practice log diary and a factual test paper, which were completed both before and after the course by the doctors attending. A significant improvement was shown in the group score in the test paper taken after the course (p less than 0.001). Scores in the tests before and after had a negative correlation with age (p less than 0.001). In comparing the data in the second log diary with those in the first there was a significant reduction in the prescribing of drugs (p less than 0.001), use of heat treatment (p less than 0.001), and in "other" forms of treatment (p less than 0.01). No appreciable change in investigations or number of hospital referrals was shown. Those doctors who had low scores in the first factual test referred appreciably more patients to hospital and requested more x ray examinations (p less than 0.01).     

Bounds on the minimum number of recombination events in a sample history

Recombination is an important evolutionary factor in many organisms, including humans, and understanding its effects is an important task facing geneticists. Detecting past recombination events is thus important; this article introduces statistics that give a lower bound on the number of recombination events in the history of a sample, on the basis of the patterns of variation in the sample DNA. Such lower bounds are appropriate, since many recombination events in the history are typically undetectable, so the true number of historical recombinations is unobtainable. The statistics can be calculated quickly by computer and improve upon the earlier bound of Hudson and Kaplan 1985. A method is developed to combine bounds on local regions in the data to produce more powerful improved bounds. The method is flexible to different models of recombination occurrence. The approach gives recombination event bounds between all pairs of sites, to help identify regions with more detectable recombinations, and these bounds can be viewed graphically. Under coalescent simulations, there is a substantial improvement over the earlier method (of up to a factor of 2) in the expected number of recombination events detected by one of the new minima, across a wide range of parameter values. The method is applied to data from a region within the lipoprotein lipase gene and the amount of detected recombination is substantially increased. Further, there is strong clustering of detected recombination events in an area near the center of the region. A program implementing these statistics, which was used for this article, is available from http://www.stats.ox.ac.uk/mathgen/programs.html.     

Breeding without breeding: minimum fingerprinting effort with respect to the effective population size

We present a probabilistic model to minimize the fingerprinting effort associated with the implementation of the “breeding without breeding” scheme under partial pedigree reconstruction. Our approach is directed at achieving a declared target population’s minimum effective population size (N _e ), following the pedigree reconstruction and genotypic selection and is based on the graph theory algorithm. The primary advantage of the proposed method is to reduce the cost associated with fingerprinting before the implementation of the pedigree reconstruction for seed parent–offspring derived from breeding arboreta and production or natural populations. Stochastic simulation was conducted to test the method’s efficiency assuming a simple polygenic model and a single trait. Hypothetical population consisted of 30 parental trees that were paired at random (selfing excluded), resulting in 600 individuals (potential candidates for forwards selection). The male parentage was assumed initially unknown. The model was used to estimate the minimum genotyping sample size needed to reaching the prescribed N _e . Results were compared with the known pedigree data. The model was successful in revealing the true relationship pattern over the whole range of N _e . Two to three offspring entered genotyping to meet the N _e  = 2 while 41 to 43 were required to satisfy the N _e  = 14. Importantly, genetic gain was affected at the lower limits of the genotyping effort. Doubling the number of parents resulted in considerable reduction of the genotyping effort at higher N _e values.     

Multiple paternity: determining the minimum number of sires of a large brood

We describe an efficient algorithm for determining exactly the minimum number of sires consistent with the multi-locus genotypes of a mother and her progeny. We consider cases where a simple exhaustive search through all possible sets of sires is impossible in practice because it would take too long to complete. Our algorithm for solving this combinatorial optimization problem avoids visiting large parts of search space that would not result in a solution with fewer sires. This improvement is of particular importance when the number of allelic types in the progeny array is large and when the minimum number of sires is expected to be large. Precisely in such cases, it is important to know the minimum number of sires: this number gives an exact bound on the most likely number of sires estimated by a random search algorithm in a parameter region where it may be difficult to determine whether it has converged. We apply our algorithm to data from the marine snail, Littorina saxatilis.     

The zinc finger repressor, ZBP-89, binds to the silencer element of the human vimentin gene and complexes with the transcriptional activator, Sp1

Vimentin is a component of the eukaryotic cytoskeleton belonging to the family of intermediate filament proteins. It exhibits a complex pattern of tissue- and development-specific expression. It is also a marker of the metastatic potential of many tumor cells. Previously, the human vimentin promoter was shown to contain several regions for the binding of positive and negative acting regulatory factors. Until now, the silencer element, which shuts down vimentin synthesis in selected tissues during development, was not precisely localized; nor was its binding protein known. In vivo DMS footprinting by ligation-mediated PCR delineated the position of guanine residues important to vimentin expression. Transient transfection assays in HeLa cells of various vimentin 5'-end promoter sequences and mutants thereof precisely defined two regulatory elements, a negative element and an adjoining positive acting element. Band shift assays, UV cross-linking, and Southwestern blot analysis confirm that the silencer element specifically binds a protein. Several lines of evidence show that ZBP-89, a zinc finger, Kruppel-like repressor protein is vimentin's silencer element binding factor. Co-immunoprecipitation and DNA affinity chromatography prove that Sp1 heterodimerizes with ZBP-89 when bound to the silencer element to yield a DNA-protein complex whose mobility is indistinguishable from that displayed by HeLa nuclear extract in band shift assays.     

The psychological effect of mastectomy with or without breast reconstruction: a prospective,multicenter study

A multicenter, prospective study ( = 103) examined the psychological implications of women's decisions for or against breast reconstruction. Recognized measures of anxiety, depression, body image, and quality of life were completed before the operation, and 6 and 12 months later. A reduction in psychological distress over the year following the operation was evident in each surgical group (mastectomy alone or immediate or delayed reconstruction), indicating that reconstructive surgery can offer psychological benefits to some women; however, others report improved psychological functioning without this surgical procedure. In contrast to existing retrospective research, the prospective design enabled the process of adjustment during the first year after the operation to be examined. The results indicate that breast reconstruction is not a universal panacea for the emotional and psychological consequences of mastectomy. Women still reported feeling conscious of altered body image 1 year postoperatively, regardless of whether or not they had elected breast reconstruction. Health professionals should be careful of assuming that breast reconstruction necessarily confers psychological benefits compared with mastectomy alone.     

Growth and differentiation of human keratinocytes without a feeder layer or conditioned medium

Summary An improved procedure has been developed for clonal growth of normal human epidermal keratinocytes (HK) without feeder cells or conditioned medium. The use of medium 199, supplemented with 0.4 μg/ml hydrocortisone (HC) and 20% (v/v) whole fetal bovine serum (wFBS) and conditioned overnight by 3T3 cells, eliminated the need for a feeder layer of lethally irradiated 3T3 cells for HK growth. Several other media with equivalent conditioning and supplementation failed to support satisfactory multiplication of HK, including Dulbecco's modified Eagle's medium, which is normally used for growth of HK with a feeder layer. Increasing the concentration of HC to 10 μg/ml (2.8×10⁻⁵ M) made possible clonal growth of HK without any conditioning of the medium. The addition of 10⁻⁵ M putrescine, 10⁻⁵ M vitamin B₁₂, or 3.7×10⁻⁶ M β-estradiol further enhanced growth in unconditioned medium. Substantially greater improvement was obtained by the addition of pituitary extract or fractions prepared from pituitary extract. In medium 199 supplemented with 10 μg/ml HC, 20% (v/v) wFBS, and 0.15 mg/ml each of two pituitary fractions, single HK attach with a colony-forming efficiency equal to that in conditioned medium and form stratified, keratinized colonies that grow to confluency and can be subcultured. These results make it clear that HK do not require special “conditioning factors” from fibroblasts for clonal growth and differentiation in culture. Thus, factors directly involved in growth and the expression of differentiation can be analyzed without the interfering effects of any other type of cell. Preliminary studies with epidermal growth factor (EGF), which stimulates growth and extends life span of HK grown in the presence of fibroblasts, have shown that, in the absence of fibroblasts, EGF has no effect either on clonal growth or on cumulative multiplication potential of HK. This paper contains material from a thesis submitted to the Graduate School of the University of Colorado, Boulder, by Donna M. Peehl in partial fulfillment of the requirements for the Ph.D. degree. This work was supported by Grant CA 15305 from the National Cancer Institute and Grant AG 00310 from the National Institute on Aging.