Towards determination of power loss at a rowing blade: Validation of a new method to estimate blade force characteristics.

To analyze on-water rowing performance, a valid determination of the power loss due to the generation of propulsion is required. This power los can be calculated as the dot product of the net water force vector ([Formula: see text]) and the time derivative of the position vector of the point at the blade where [Formula: see text] is applied ([Formula: see text]). In this article we presented a method that allows for accurate determination of both parameters using a closed system of three rotational equations of motion for three different locations at the oar. Additionally, the output of the method has been validated. An oar was instrumented with three pairs of strain gauges measuring local strain. Force was applied at different locations of the blade, while the oar was fixed at the oarlock and the end of the handle. Using a force transducer and kinematic registration, the force vector at the blade and the deflection of the oar were measured. These data were considered to be accurate and used to calibrate the measured strain for bending moments, the deflection of the oar and the angle of the blade relative to its unloaded position. Additionally, those data were used to validate the output values of the presented method plus the associated instantaneous power output. Good correspondence was found between the estimated perpendicular blade force and its reference (ICC = .999), while the parallel blade force could not be obtained (ICC = .000). The position of the PoA relative to the blade could be accurately obtained when the perpendicular force was ≥ 5.3 N (ICC = .927). Instantaneous power output values associated with the perpendicular force could be obtained with reasonable accuracy (ICC = .747). These results suggest that the power loss due to the perpendicular water force component can be accurately obtained, while an additional method is required to obtain the power losses due to the parallel force.

Experimental velocity study of non-Boussinesq Rayleigh-Bénard convection.

The effects of strongly varying fluid properties, beyond the validity range of the so-called Boussinesq approximation, were experimentally studied in Rayleigh-Bénard (RB) convection. Two experiments were conducted in the same cubical RB convection cell at similar Rayleigh and Prandtl numbers. In one experiment water was used as working fluid and the imposed temperature difference between the top and bottom plates of the cell was such to ensure non-Boussinesq conditions. In the other experiment, taken as a reference for Boussinesq conditions, methanol was used as working fluid, allowing a smaller temperature difference between the plates. In both experiments the instantaneous and time-averaged flow fields were determined experimentally in a vertical cross section of the cell by using particle image velocimetry. Results show a non-Boussinesq effect that manifests itself as an increase of the time-averaged horizontal velocity component close to the bottom wall of the cell and as a global top-bottom asymmetry of the velocity field. This is an experimental study of the whole velocity field of RB convection at non-Boussinesq conditions.

Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins.

CONTEXT: Sirtuins (SIRTs) regulate cellular metabolism and mitochondrial function according to the energy state of the cell reflected by NAD(+) levels. OBJECTIVE: Our aim was to determine whether expressions of SIRTs and NAD(+) biosynthesis genes are affected by acquired obesity and how possible alterations are connected with metabolic dysfunction while controlling for genetic and familial factors. DESIGN AND PARTICIPANTS: We studied a cross-sectional sample of 40 healthy pairs of monozygotic twins, including 26 pairs who were discordant for body mass index (within-pair difference > 3 kg/m(2)), from the FinnTwin12 and FinnTwin16 cohorts. MAIN OUTCOME MEASURES: Subcutaneous adipose tissue (SAT) transcriptomics was analyzed by using Affymetrix U133 Plus 2.0 chips, total SAT (poly-ADP) ribose polymerase (PARP) activity by an ELISA kit, body composition by dual-energy x-ray absorptiometry and magnetic resonance imaging/spectroscopy, and insulin sensitivity by an oral glucose tolerance test. RESULTS: SIRT1, SIRT3, SIRT5, NAMPT, NMNAT2, NMNAT3, and NRK1 expressions were significantly down-regulated and the activity of main cellular NAD(+) consumers, PARPs, trended to be higher in the SAT of heavier co-twins of body mass index-discordant pairs. Controlling for twin-shared factors, SIRT1, SIRT3, NAMPT, NMNAT3, and NRK1 were significantly negatively correlated with adiposity, SIRT1, SIRT5, NMNAT2, NMNAT3, and NRK1 were negatively correlated with inflammation, and SIRT1 and SIRT5 were positively correlated with insulin sensitivity. Expressions of genes involved in mitochondrial unfolded protein response were also significantly down-regulated in the heavier co-twins. CONCLUSIONS: Our data highlight a strong relationship of reduced NAD(+)/SIRT pathway expression with acquired obesity, inflammation, insulin resistance, and impaired mitochondrial protein homeostasis in SAT.

Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+ progenitors.

The continuously growing mouse incisor serves as a valuable model to study stem cell regulation during organ renewal. Epithelial stem cells are localized in the proximal end of the incisor in the labial cervical loop. Here, we show that the transcription factor Sox2 is a specific marker for these stem cells. Sox2+ cells became restricted to the labial cervical loop during tooth morphogenesis, and they contributed to the renewal of enamel-producing ameloblasts as well as all other epithelial cell lineages of the tooth. The early progeny of Sox2-positive stem cells transiently expressed the Wnt inhibitor Sfrp5. Sox2 expression was regulated by the tooth initiation marker FGF8 and specific miRNAs, suggesting a fine-tuning to maintain homeostasis of the dental epithelium. The identification of Sox2 as a marker for the dental epithelial stem cells will facilitate further studies on their lineage segregation and differentiation during tooth renewal.

Sostdc1 defines the size and number of skin appendage placodes.

Mammary glands and hair follicles develop as ectodermal organs sharing common features during embryonic morphogenesis. The molecular signals controlling the initiation and patterning of skin appendages involve the bone morphogenetic proteins and Wnt family members, which are commonly thought to serve as inhibitory and activating cues, respectively. Here, we have examined the role of the Bmp and Wnt pathway modulator Sostdc1 in mammary gland, and hair and vibrissa follicle development using Sostdc1-null mice. Contrary to previous speculations, loss of Sostdc1 did not affect pelage hair cycling. Instead, we found that Sostdc1 limits the number of developing vibrissae and other muzzle hair follicles, and the size of primary hair placodes. Sostdc1 controls also the size and shape of mammary buds. Furthermore, Sostdc1 is essential for suppression of hair follicle fate in the normally hairless nipple epidermis, but its loss also promotes the appearance of supernumerary nipple-like protrusions. Our data suggest that functions of Sostdc1 can be largely attributed to its ability to attenuate Wnt/ß-catenin signaling.

Tooth morphogenesis and ameloblast differentiation are regulated by micro-RNAs.

Teeth form as appendages of the ectoderm and their morphogenesis is regulated by tissue interactions mediated by networks of conserved signal pathways. Micro-RNA (miRNA) pathway has emerged as important regulator of various aspects of embryonic development, but its function in odontogenesis has not been elucidated. We show that the expression of RNAi pathway effectors is dynamic during tooth morphogenesis and differentiation of dental cells. Based on microarray profiling we selected 8 miRNAs expressed during morphogenesis and 7 miRNAs in the incisor cervical loop containing the stem cell niche. These miRNAs were mainly expressed in the dental epithelium. Conditional deletion of Dicer-1 in the epithelium (Dcr(K14)(-)(/)(-)) resulted in rather mild but significant aberrations in tooth shape and enamel formation. The cusp patterns of the Dcr(K14)(-)(/)(-) molar crowns resembled the patterns of both ancestral muroid rodents and mouse mutants with modulated signal pathways. In the Dcr(K14)(-)(/)(-) incisors, longitudinal grooves formed on the labial surface and these were shown to result from ectopic budding of the progenitor epithelium in the cervical loop. In addition, ameloblast differentiation was impaired and resulted in deficient enamel formation in molars and incisors. To help the identification of candidate target genes of the selected tooth enriched miRNAs, we constructed a new ectodermal organ oriented database, miRTooth. The predicted targets of the selected miRNAs included several components of the main morphogenetic signal pathways regulating tooth development. Based on our findings we suggest that miRNAs modulate tooth morphogenesis largely by fine tuning conserved signaling networks and that miRNAs may have played important roles during tooth evolution.

Prime modes of fluid circulation in large-aspect-ratio turbulent Rayleigh-Bénard convection.

Based on a detailed experimental investigation in an aspect-ratio-4 rectangular cell in the range 3.7 x 10(7)

The dynamic interest in topics within the biomedical scientific community.

The increase in the size of the scientific community created an explosion in scientific production. We have analyzed the dynamics of biomedical scientific output during 1957-2007 by applying a bibliometric analysis of the PubMed database using different keywords representing specific biomedical topics. With the assumption that increased scientific interest will result in increased scientific output, we compared the output of specific topics to that of all scientific output. This analysis resulted in three broad categories of topics; those that follow the general trend of all scientific output, those that show highly variable output, and attractive topics which are new and grow explosively. The analysis of the citation impact of the scientific output resulted in a typical longtail distribution: the majority of journals and articles are of very low impact. This distribution has remained unchanged since 1957, although the interests of scientists must have shifted in this period. We therefore analyzed the distribution of articles in top journals and lower impact journals over time for the attractive topics. Novelty is rewarded by publication in top journals. Over time more articles are published in low impact journals progressively creating the longtail distribution, signifying acceptance of the topic by the community. There can be a gap of years between novelty and acceptance. Within topics temporary novelty is created with new subtopics. In conclusion, the longtail distribution is the foundation of the scientific output of the scientific community and can be used to examine different aspects of science practice.

The role of the dental lamina in mammalian tooth replacement.

We have applied the ferret, Mustela putorius furo, as a model for tooth replacement. Ferret has a heterodont dentition, which includes all tooth families, and all antemolar teeth are replaced. Compared with mouse, the ferret therefore has a less derived mammalian dentition resembling that of humans. We have studied tooth replacement in serial histological sections in embryonic and young postnatal ferrets. Our observations indicate that the replacement teeth form from the dental lamina that is intimately connected to the lingual aspect of the deciduous tooth enamel organ. It grows as an offshoot from the enamel organ, elongates in cervical direction and later buds to give rise to the replacement tooth. The extent of the dental lamina growth, preceding replacement tooth budding, varied between different teeth. The dynamic gene expression patterns of Sostdc1, Shh and Axin2 brought new insight into the signal networks regulating the tooth replacement process. The distinct expression of Sostdc1 at the interface between the dental lamina and the deciduous tooth is the first indication of a specific tissue identity of the dental lamina. We suggest that the reactivation of a competent dental lamina is pivotal for the replacement tooth formation.

Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction.

Like epithelial organs in general, tooth development involves inductive crosstalk between the epithelium and the mesenchyme. Classically, the inductive potential for tooth formation is considered to reside in the mesenchyme during the visible morphogenesis of teeth, and dental mesenchyme can induce tooth formation even when combined with non-dental epithelium. Here, we have investigated induction of mouse incisors using Sostdc1 (ectodin), a putative antagonist of BMP signaling in the mesenchymal induction of teeth. Deletion of Sostdc1 leads to the full development of single extra incisors adjacent to the main incisors. We show that initially, Sostdc1 expression is limited to the mesenchyme, suggesting that dental mesenchyme may limit supernumerary tooth induction. We test this in wild-type incisors by minimizing the amount of mesenchymal tissue surrounding the incisor tooth germs prior to culture in vitro. The cultured teeth phenocopy the extra incisors phenotype of the Sostdc1-deficient mice. Furthermore, we show that minimizing the amount of dental mesenchyme in cultured Sostdc1-deficient incisors causes the formation of additional de novo incisors that resemble the successional incisor development that results from activated Wnt signaling. Finally, Noggin and Dkk1 prevent individually the formation of extra incisors, and we therefore suggest that inhibition of both BMP and Wnt signaling contributes to the inhibitory role of the dental mesenchyme. Considering the role of mesenchyme in tooth induction and the design of tissue engineering protocols, our work may have uncovered how delicate control of tissue quantities alone influences the outcome between induction and inhibition.

The importance of signal pathway modulation in all aspects of tooth development.

Most characteristics of tooth shape and pattern can be altered by modulating the signal pathways mediating epithelial-mesenchymal interactions in developing teeth. These regulatory signals function in complex networks, characterized by an abundance of activators or inhibitors. In addition, multiple specific inhibitors of all conserved signal pathways have been identified as modulators in tooth development. The number of teeth as well as molar cusp patterns can be modified by tinkering with several different signal pathways. The inhibition of any of the major conserved signal pathways in knockout mice leads to arrested tooth formation. On the other hand, the stimulation of the Wnt pathway in the oral epithelium in transgenic mice leads to abundant de novo tooth formation. The modulation of some of the signal pathways can rescue the development of vestigial tooth rudiments in the incisor and molar regions resulting in extra premolar-like teeth. The size and the degree of asymmetry of the continuously growing mouse incisor can be modulated by modifying the complex network of FGF, bone morphogenetic protein, and Activin signals, which regulate the proliferation and differentiation of epithelial stem cells. Follistatin, Sprouty, and Sostdc1 are important endogenous inhibitors antagonizing these pathways and they are also involved in regulation of enamel formation, and patterning of teeth in crown and root domains. All these findings support the hypothesis that the diversity of tooth types and dental patterns may have resulted from tinkering with the conserved signal pathways, organized into complex networks, during evolution.

Spectral analysis of boundary layers in Rayleigh-Bénard convection.

A combined experimental and numerical study of the boundary layer in a 4:1 aspect-ratio Rayleigh-Bénard cell over a four-decade range of Rayleigh numbers has been undertaken aimed at gaining a better insight into the character of the boundary layers. The experiments involved the simultaneous laser Doppler anemometry measurements of fluid velocity at two locations, i.e., in the boundary layer and far away from it in the bulk, for Rayleigh numbers varying between 1.6x10(7) and 2.4x10(9) . In parallel, direct numerical simulations have been performed for the same configuration for Rayleigh numbers between 7.0x10(4) and 7.7x10(7) . The temperature and velocity probability density functions and the power spectra of the horizontal velocity fluctuations measured in the boundary layer and in the bulk flow are found to be practically identical. Except for the smallest Rayleigh numbers, the spectra in the boundary layer and in the bulk central region are continuous and have a wide range of active scales. This indicates that both the bulk and the boundary layers are turbulent in the Ra number range considered. However, molecular effects can still be observed and the boundary layer does not behave like a classical shear-driven turbulent boundary layer.

Observations on continuously growing roots of the sloth and the K14-Eda transgenic mice indicate that epithelial stem cells can give rise to both the ameloblast and root epithelium cell lineage creating distinct tooth patterns.

Root development is traditionally associated with the formation of Hertwig's epithelial root sheath (HERS), whose fragments give rise to the epithelial cell rests of Malassez (ERM). The HERS is formed by depletion of the core of stellate reticulum cells, the putative stem cells, in the cervical loop, leaving only a double layer of the basal epithelium with limited growth capacity. The continuously growing incisor of the rodent is subdivided into a crown analog half on the labial side, with a cervical loop containing a large core of stellate reticulum, and its progeny gives rise to enamel producing. The lingual side is known as the root analog and gives rise to ERM. We show that the lingual cervical loop contains a small core of stellate reticulum cells and suggest that it acts as a functional stem cell niche. Similarly we show that continuously growing roots represented by the sloth molar and K14-Eda transgenic incisor maintain a cervical loop with a small core of stellate reticulum cells around the entire circumference of the tooth and do not form a HERS, and still give rise to ERM. We propose that HERS is not a necessary structure to initiate root formation. Moreover, we conclude that crown vs. root formation, i.e. the production of enamel vs. cementum, and the differentiation of the epithelial cells into ameloblasts vs. ERM, can be regulated independently from the regulation of stem cell maintenance. This developmental flexibility may underlie the developmental and evolutionary diversity in tooth patterning.

Oscillating large-scale circulation in turbulent Rayleigh-Bénard convection.

We report on the dynamics and structure of the turbulent velocity field in a high-Rayleigh-number (Ra = 5.9 x 10(8))thermal convection cell with an aspect ratio of 4. Spectral density functions (measured with laser Doppler velocimetry) indicated the existence of a large-scale periodic component. The long-time mean flow field (measured with particle image velocimetry) revealed that the large-scale circulation in the aspect-ratio-4 cell consists of two corotating rolls. The periodicity in the flow could be traced back to the alternating growth and decay of these rolls.

p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation.

Heterozygous germline mutations in p63, a transcription factor of the p53 family, result in abnormal morphogenesis of the skin and its associated structures, including hair follicles and teeth. In mice lacking p63, all ectodermal organs fail to develop, and stratification of the epidermis is absent. We show that the ectodermal placodes that mark early tooth and hair follicle morphogenesis do not form in p63-deficient embryos, although the multilayered dental lamina that precedes tooth placode formation develops normally. The N-terminally truncated isoform of p63 (DeltaNp63) was expressed at high levels in embryonic ectoderm at all stages of tooth and hair development, and it was already dominant over the transactivating TAp63 isoform prior to epidermal stratification. Bmp7, Fgfr2b, Jag1 and Notch1 transcripts were co-expressed with DeltaNp63 in wild-type embryos, but were not detectable in the ectoderm of p63 mutants. In addition, beta-catenin and Edar transcripts were significantly reduced in skin ectoderm. We also demonstrate that BMP2, BMP7 and FGF10 are potent inducers of p63 in cultured tissue explants. Hence, we suggest that p63 regulates the morphogenesis of surface ectoderm and its derivatives via multiple signalling pathways.

Stem cells and tissue engineering: prospects for regenerating tissues in dental practice.

In general, human tissues have a very limited potential to regenerate. However, recent progress in stem cell research and in tissue engineering promises novel prospects for tissue regeneration in dental practice in the future. Stem cells have been discovered in many adult tissues, including teeth, and stem cells from embryos have the potential to form all adult tissues. Embryonic stem cells can now be cultured and even produced from adult cells by the nuclear transfer method. Due to the rapid progress of research in molecular biology, particularly in the field of developmental biology, we are now starting to understand at the level of genes and molecules how the development of dental tissues is regulated. For instance, specific signal molecules have been identified which regulate the development of teeth and bones from progenitor cells. This information is already being used for the generation of dentoalveolar tissues in vitro and in vivo. Could we perhaps grow new enamel, dentine, periodontal ligament, bone, or even whole new teeth for our patients in the future?

Root or crown: a developmental choice orchestrated by the differential regulation of the epithelial stem cell niche in the tooth of two rodent species.

The rodent incisor grows continuously throughout its lifetime. The epithelial stem cell niche is located at the apical end of the tooth and its progeny gives rise to the ameloblasts that form the hard enamel. Previously, mesenchymal FGF10 was shown to support the niche, in conjunction with epithelial Notch signaling. Here we show that in a different continuously growing tooth type, the molar of the sibling vole, a similar regulatory system is in place. Moreover, the identical expression pattern of Bmp4 compared to Fgf10 suggests that BMP4 could also be involved in the regulation of the epithelial stem cell niche. Notch and FGF10 signaling is mainly absent in the mouse molar, which stops growing and develops roots. The regulation of the epithelial stem cell niche seems to be flexible allowing for the existence of different tooth types, such as continuously growing teeth, and high and low crowned molars.

Lunatic fringe, FGF, and BMP regulate the Notch pathway during epithelial morphogenesis of teeth.

Teeth develop as epithelial appendages, and their morphogenesis is regulated by epithelial-mesenchymal interactions and conserved signaling pathways common to many developmental processes. A key event during tooth morphogenesis is the transition from bud to cap stage when the epithelial bud is divided into specific compartments distinguished by morphology as well as gene expression patterns. The enamel knot, a signaling center, forms and regulates the shape and size of the tooth. Mesenchymal signals are necessary for epithelial patterning and for the formation and maintenance of the epithelial compartments. We studied the expression of Notch pathway molecules during the bud-to-cap stage transition of the developing mouse tooth. Lunatic fringe expression was restricted to the epithelium, where it formed a boundary flanking the enamel knot. The Lunatic fringe expression domains overlapped only partly with the expression of Notch1 and Notch2, which were coexpressed with Hes1. We examined the regulation of Lunatic fringe and Hes1 in cultured explants of dental epithelium. The expression of Lunatic fringe and Hes1 depended on mesenchymal signals and both were positively regulated by FGF-10. BMP-4 antagonized the stimulatory effect of FGF-10 on Lunatic fringe expression but had a synergistic effect with FGF-10 on Hes1 expression. Recombinant Lunatic fringe protein induced Hes1 expression in the dental epithelium, suggesting that Lunatic fringe can act also extracellularly. Lunatic fringe mutant mice did not reveal tooth abnormalities, and no changes were observed in the expression patterns of other Fringe genes. We conclude that Lunatic fringe may play a role in boundary formation of the enamel knot and that Notch-signaling in the dental epithelium is regulated by mesenchymal FGFs and BMP.