Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma.

BACKGROUND: Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA. OBJECTIVES: To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue. METHODS: Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction. RESULTS: Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0·001). CONCLUSIONS: The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas.

Beltsville poultry semen extender. 7. Comparison of commercial diluents for holding turkey semen six hours at 15 C.

The ability of three commercial semen diluents (Minnesota, I.M.V.-French and Universal) and the Beltsville Poultry Semen Extender (BPSE) to maintain the fertilizing capacity of turkey semen held 6 hr at 15 C was examined. Hens were inseminated weekly for 20 wk and hatchability of eggs was determined. Neither candling nor true fertility of semen diluted 1:1 in BPSE, the Minnesota, or I.M.V.-French diluent and held for 6 hr differed significantly from each other. Fertility of semen held 6 hr in BPSE or Universal diluent was lower than their respective unstored controls. No difference in fertility was observed between semen held in Minnesota or I.M.V.-French diluent and their unstored controls. Significantly higher hatch of fertile eggs and of all eggs set was obtained from hens inseminated with semen diluted (0 hr) with BPSE (90 and 86%) than all other diluents. Hatch of fertile eggs was higher from hens inseminated with semen held 6 hr in Universal (90%) and French (86%) extenders and lower for the Minnesota (78%) extender. No difference was observed in hatch of fertile eggs between the BPSE (84%) and French (86%) extender. Hatchability of all eggs set was higher when hens were inseminated with semen held 6 hr in the I.M.V.-French diluent (81%) when compared to hens inseminated with the Minnesota (75%) or Universal diluent (75%). No differences in hatch of all eggs set were noted when BPSE (77%) and the commercial extenders were compared.

Beltsville poultry semen extender. 9. Effect of storage temperature on turkey semen held eighteen hours.

Turkey semen was collected, diluted 1:1 with Beltsville Poultry Semen Extender, and held for 0 or 18 hr at 5, 15, 25, or 35 C. Changes in spermatozoa motility and sperm numbers were monitored before and after holding. All hens were artificially inseminated (AI) with 250 X 10(6) spermatozoa three times the first week and once weekly thereafter for a total of 20 weeks. No significant differences were observed in candling fertility (85 vs. 82%) of hens AI with unstored semen or semen held at 5 C for 18 hr. Significant depression of fertility levels to 41 and 40% were noted in hens AI with semen stored at 15 and 25 C, respectively. No fertile eggs were obtained from hens AI with semen held at 35 C for 18 hr. Sperm motility scores were not different between the unstored controls and samples held at 5 C (62 vs. 64%). Samples held at 15 and 25 C had motility scores of 40 and 8%, respectively. Samples held at 35 C for 18 hr were immotile. As semen holding temperature increased from 5 to 35 C, sperm numbers decreased during the 18 hr holding period by 11, 16, 28, and 45% of the unstored control. The decrease in sperm numbers during the 18-hr holding period was speculated to be the result of sperm aging which was compounded by sample agitation during storage. The methodology used for determining sperm numbers did not adversely influence the results.

Beltsville Poultry Semen Extender. 8. Factors affecting turkey semen held six hours at 15 C.

Several experiments were conducted to measure the effects of extender pH, size and type of storage vessel, insemination dose volume, and frequency of insemination on the motility and fertilizing capacity of turkey semen held 6 hr at 15 C. The fertilizing capacity and motility of both unstored and stored turkey sperm were depressed more when diluted in Beltsville Poultry Semen Extender at pH 5.5 than at pH 6.5 or 6.0. The fertility of stored semen was impaired when agitated for 6 hr regardless of the type of storage vessel used. Sperm motility was higher when semen was held in flasks than when held in tubes. There were no differences in fertility of hens inseminated with .025, .05, or .10 cm3 of either unstored or stored semen during the first 10 weeks of egg production. However, fertility differences between unstored and stored semen were noted with all insemination doses late in the production period. Hens inseminated every 7 days with unstored semen maintained a constant level of fertility (+90%) for the 20-week production period, whereas the fertility of hens inseminated at 10- or 14-day intervals was lower in Weeks 11 to 20. Regardless of insemination interval, fertility of stored semen was lower than fertility of unstored semen in the latter stages of egg production.

Effect of time of day of artificial insemination and oviposition-insemination interval of the fertility of broiler breeder hens.

Two experiments using two populations of 160 broiler-type females in each were conducted to study the effect of time of day of artificial insemination and the effect of oviposition-insemination interval on fertility. Each population was subdivided into eight groups of 20 hens and inseminated with .05 ml of semen once a week at one of the following times: 2400, 0300, 0600, 0900, 1200, 1500, 1800, or 2100 hr for 5 weeks in Experiment 1 and for 6 weeks in Experiment 2. In Experiment 1, the highest level of fertility was obtained from hens inseminated at 2100 hr, while in Experiment 2, significantly higher levels of fertility were obtained from hens inseminated at 2100, 2400, and 0300 hr. In both experiments, fertility of females inseminated in mid-morning and mid-afternoon did not differ significantly and lower levels of fertility were obtained when hens oviposited within 3 hr after insemination. Lower fertility occurred when morning and mid-day inseminations were followed by oviposition within 3 hr after insemination.

Is the proton radius a player in the redefinition of the International System of Units?

It is now recognized that the International System of Units (SI units) will be redefined in terms of fundamental constants, even if the date when this will occur is still under debate. Actually, the best estimate of fundamental constant values is given by a least-squares adjustment, carried out under the auspices of the Committee on Data for Science and Technology (CODATA) Task Group on Fundamental Constants. This adjustment provides a significant measure of the correctness and overall consistency of the basic theories and experimental methods of physics using the values of the constants obtained from widely differing experiments. The physical theories that underlie this adjustment are assumed to be valid, such as quantum electrodynamics (QED). Testing QED, one of the most precise theories is the aim of many accurate experiments. The calculations and the corresponding experiments can be carried out either on a boundless system, such as the electron magnetic moment anomaly, or on a bound system, such as atomic hydrogen. The value of fundamental constants can be deduced from the comparison of theory and experiment. For example, using QED calculations, the value of the fine structure constant given by the CODATA is mainly inferred from the measurement of the electron magnetic moment anomaly carried out by Gabrielse's group. (Hanneke et al. 2008 Phys. Rev. Lett. 100, 120801) The value of the Rydberg constant is known from two-photon spectroscopy of hydrogen combined with accurate theoretical quantities. The Rydberg constant, determined by the comparison of theory and experiment using atomic hydrogen, is known with a relative uncertainty of 6.6×10(-12). It is one of the most accurate fundamental constants to date. A careful analysis shows that knowledge of the electrical size of the proton is nowadays a limitation in this comparison. The aim of muonic hydrogen spectroscopy was to obtain an accurate value of the proton charge radius. However, the value deduced from this experiment contradicts other less accurate determinations. This problem is known as the proton radius puzzle. This new determination of the proton radius may affect the value of the Rydberg constant . This constant is related to many fundamental constants; in particular, links the two possible ways proposed for the redefinition of the kilogram, the Avogadro constant N(A) and the Planck constant h. However, the current relative uncertainty on the experimental determinations of N(A) or h is three orders of magnitude larger than the 'possible' shift of the Rydberg constant, which may be shown by the new value of the size of the proton radius determined from muonic hydrogen. The proton radius puzzle will not interfere in the redefinition of the kilogram. After a short introduction to the properties of the proton, we will describe the muonic hydrogen experiment. There is intense theoretical activity as a result of our observation. A brief summary of possible theoretical explanations at the date of writing of the paper will be given. The contribution of the proton radius puzzle to the redefinition of SI-based units will then be examined.

Algebraic approach to characterizing paraxial optical systems.

The paraxial propagation formalism for ABCD systems is reviewed and written in terms of quantum mechanics. This formalism shows that the propagation based on the Collins integral can be generalized so that, in addition, the problem of beam quality degradation that is due to aberrations can be treated in a natural way. Moreover, because this formalism is well elaborated and reduces the problem of propagation to simple algebraic calculations, it seems to be less complicated than other approaches. This can be demonstrated with an easy and unitary derivation of several results, which were obtained with different approaches, in each case matched to the specific problem. It is first shown how the canonical decomposition of arbitrary (also complex) ABCD matrices introduced by Siegman [Lasers, 2nd ed. (Oxford U. Press, London, 1986)] can be used to establish the group structure of geometric optics on the space of optical wave functions. This result is then used to derive the propagation law for arbitrary moments in eneral ABCD systems. Finally a proper generalization to nonparaxial propagation operators that allows us to treat arbitrary aberration effects with respect to their influence on beam quality degradation is presented.

Simple high-precision method for measuring the specular reflectance of optical components.

We present a simple method to determine precisely the specular reflectance of optical components. The absence of transmissive elements in this method makes a wide spectral range available. High accuracy and precision are achieved with a fast, periodic change between the reference beam and the probe beam. Special efforts were made to eliminate inhomogeneities of beam intensity and detector sensitivity. With our experimental setup we obtain a precision of ±3 × 10(-4) at the wavelength of 10.6 µm and ±3 × 10(-5) at 1.06 µm for a single-bounce-measuring setup.

Propagation analysis of self-convergent beam width and characterization of hard-edge diffracted beams.

For a laser beam diffracted by a hard-edge aperture, propagation of the beam width, defined by the second-order moment of its irradiance distribution truncated according to the self-convergent-width criterion, obeys the familiar hyperbolic law. It is demonstrated numerically that, with the self-convergent-width approach, the beam-propagation parameters for three beam types (Gaussian, Hermite-Gaussian, and flattened Gaussian) diffracted by hard-edge apertures can be determined with the second-moment-based procedure that is recommended by the present draft standard only for unapertured laser beams.

Multiwatt diode-pumped Yb:YAG thin disk laser continuously tunable between 1018 and 1053 nm.

A new powerful source of broadly (35-nm) tunable laser radiation in the near-infrared (near 1030 nm) wavelength range is presented. Inserting a birefringent filter into a 10-W diode-pumped Yb:YAG thin disk laser resonator gives several watts of narrow-linewidth (0.07-nm) continuously tunable cw output power. By taking advantage of the power scalability of the thin disk concept, even hundreds of watts of tunable power with near-diffraction-limited beam quality and high efficiency are feasible. Generation and amplification of subpicosecond pulses with high average and peak powers are also promising applications of the Yb:YAG thin disk laser.

Power-scalable system of phase-locked single-mode diode lasers.

The direct use of diode lasers for high-power applications in material processing is limited to applications with relatively low beam quality and power density requirements. To achieve high beam quality one must use single-mode diode lasers, however with the drawback of relatively low optical output powers from these components. To realize a high-power system while conserving the high beam quality of the individual emitters requires coherent coupling of the emitters. Such a power-scalable system consisting of 19 slave lasers that are injection locked by one master laser has been built and investigated, with low-power diode lasers used for system demonstration. The optical power of the 19 injection-locked lasers is coupled into polarization-maintaining single-mode fibers and geometrically superimposed by a lens array and a focusing lens. The phase of each emitter is controlled by a simple electronic phase-control loop. The coherence of each slave laser is stabilized by computer control of the laser current and guarantees a stable degree of coherence of the whole system of 0.7. An enhancement factor of 13.2 in peak power density compared with that which was achievable with the incoherent superposition of the diode lasers was observed.

Treatment of hyperhomocysteinemia in children on dialysis by folic acid.

Adult patients with renal failure have a high total homocysteine concentration in plasma. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Folic acid lowers the homocysteine concentrations in plasma in hyperhomocysteinemia. Whether this results in a reduced risk for cardiovascular diseases remains to be proven by intervention studies. In the present study we investigated: (1) if homocysteine concentrations are elevated in the plasma of children with renal failure and (2) the influence of folic acid administration on the plasma homocysteine concentration. The plasma homocysteine concentration was measured in 21 children, 9 on hemodialysis and 12 on peritoneal dialysis, before and 4 weeks after treatment with 2.5 mg folic acid daily. Healthy children (234) constituted the control group. In controls the median homocysteine concentration was 9.1 micromol/l (range 4.3-20.0 micromol/l). The median plasma homocysteine concentration in patients before folic acid treatment was 20.0 micromol/l (Q1-Q3 13.7-26.0; Q, quartile). After 4 weeks of folic acid treatment the median plasma homocysteine concentration was 12.0 micromol/l [Q1-Q3 9.8-14.3 (P<0.0001 Wilcoxon signed rank test)]. There was no significant difference between hemodialysis and peritoneal dialysis patients. Children with renal failure treated with hemodialysis or peritoneal dialysis have elevated plasma homocysteine concentrations, but this is significantly reduced after administration of 2.5 mg folic acid daily for 4 weeks. It is suggested that folic acid be added to the treatment of children with renal failure, although a beneficial effect still has to be proven. The required dose needs further study.

16.2-W average power from a diode-pumped femtosecond Yb:YAG thin disk laser.

We demonstrate a power-scalable concept for high-power all-solid-state femtosecond lasers, based on passive mode locking of Yb:YAG thin disk lasers with semiconductor saturable-absorber mirrors. We obtained 16.2 W of average output power in pulses with 730-fs duration, 0.47-muJ pulse energy, and 560-kW peak power. This is to our knowledge the highest average power reported for a laser oscillator in the subpicosecond regime. Single-pass frequency doubling through a 5-mm-long lithium triborate crystal (LBO) yields 8-W average output power of 515-nm radiation.

Widely tunable pulse durations from a passively mode-locked thin-disk Yb:YAG laser.

We demonstrate a passively mode-locked thin-disk Yb:YAG laser that generates solitonlike pulses with durations that are continuously tunable in a very wide range from 3.3 to 89 ps or from 0.83 to 1.57 ps. The average powers are typically ~12 W . Previously [Opt. Lett. 25, 859 (2000)], only pulse durations in a narrow range near 0.7 ps could be obtained from such lasers because of the effect of spatial hole burning. We achieved this much wider range by constructing a laser cavity with two different angles of incidence on the thin disk, which greatly reduces the effect of spatial hole burning.

Measurement of one-bond 1H-13C, couplings in backbone-labelled proteins.

NMR dipole-dipole couplings between protein backbone nuclei (1H(alpha), 13C(alpha), 15N, 1H(N), 13C') offer enormous scope for the rapid determination of protein global folds. Here, we show that measurement of one-bond splittings in the protein backbone is facilitated by use of protein that is selectively isotopically enriched only in the backbone atoms. In particular, 1H(alpha)-13C(alpha) couplings can be measured simply and with high sensitivity by use of conventional heteronuclear single quantum correlation (HSQC) techniques.

240-fs pulses with 22-W average power from a mode-locked thin-disk Yb:KY(WO(4))(2) laser.

We demonstrate what is to our knowledge the first passively mode-locked thin-disk Yb:KY(WO(4))(2) laser. The laser produces pulses of 240-fs duration with an average power of 22 W at a center wavelength of 1028 nm. At a pulse repetition rate of 25 MHz, the pulse energy is 0.9microJ , and the peak power is as high as 3.3 MW. The beam quality is very close to the diffraction limit, with M(2)=1.1 .