Acceleration of sub-relativistic electrons with an evanescent optical wave at a planar interface.

We report on a theoretical and experimental study of the energy transfer between an optical evanescent wave, propagating in vacuum along the planar boundary of a dielectric material, and a beam of sub-relativistic electrons. The evanescent wave is excited via total internal reflection in the dielectric by an infrared (λ = 2 µm) femtosecond laser pulse. By matching the electron propagation velocity to the phase velocity of the evanescent wave, energy modulation of the electron beam is achieved. A maximum energy gain of 800 eV is observed, corresponding to the absorption of more than 1000 photons by one electron. The maximum observed acceleration gradient is 19 ± 2 MeV/m. The striking advantage of this scheme is that a structuring of the acceleration element's surface is not required, enabling the use of materials with high laser damage thresholds that are difficult to nano-structure, such as SiC, Al2O3 or CaF2.

Removal of body surface area normalisation improves raw-measured glomerular filtration rate estimation by the Chronic Kidney Disease Epidemiology Collaboration equation and drug dosing in the obese.

BACKGROUND/AIM: We aimed to compared estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), with (mL/min/1.73 m(2) ) and without body surface area (BSA) normalisation (CKD-EPI_noBSA, mL/min) against measured (99m) Technetium - diethylenepentaacetic acid (Tc-DTPA GFR) (mL/min) in 222 individuals, including 80 with malignancy. METHODS: BSA was calculated for each individual using the Du Bois equation. The CKD-EPI and CKD-EPI_noBSA equations were compared with measured Tc-DTPA GFR with respect to bias, proportion within 30% of GFR (P30) and root mean square error for predicting levels of GFR, and concordance in relation to carboplatin dosing. RESULTS: The mean (SD) for BSA and measured GFR for the entire group was 1.99 (0.25) m(2) and 127 (41) mL/min respectively. The P30 for Tc-DTPA GFR was significantly higher with the CKD-EPI_noBSA (80%) than with the CKD-EPI equation (63%, P = 0.0001). In those with body mass index (BMI) > 30 kg/m(2) , the P30 values for the CKD-EPI_noBSA and CKD-EPI were 74% and 42% respectively (P < 0.0001). Carboplatin dosing concordance for the cancer patients using the CKD-EPI and CKD-EPI_noBSA equation was 71% and 56% respectively (P = 0.07). In 78 individuals with BMI > 30 kg/m(2) , concordance in relation to carboplatin dosing using CKD-EPI_noBSA was 65% compared with 26% with the CKD-EPI (P < 0.0001). CONCLUSION: The CKD-EPI without normalisation (CKD-EPI_noBSA) equation was superior to the CKD-EPI equation in estimating raw-measured Tc-DTPA GFR (mL/min).

Lean mass modulates glomerular filtration rate in males of normal and extreme body composition.

BACKGROUND: Understanding determinants of glomerular filtration rate (GFR) is important in aiding prediction and interpretation of kidney function. Body composition is known to affect GFR but is not included in current screening of kidney disease. We investigated the association between GFR and body composition in healthy young men with differing body mass but without known diabetes or kidney injury. METHODS: Three groups were recruited: normal BMI (n = 22) with a body mass index (BMI) <25 kg/m(2) , muscular (n = 23) with BMI ≥30 kg/m(2) and bioelectrical impedance body fat ≤20% and obese (n = 22) with BMI ≥30 kg/m(2) and bioelectrical impedance body fat ≥30%. Dietary analyses, GFR clearance by (99m) Tc-DTPA, urine protein and body composition by dual-energy X-ray absorptiometry were measured in all participants. Linear and nonlinear associations of constituents of body composition with GFR were assessed. RESULTS: Muscular men had a higher GFR (mean 186.4 mL/min; 95% CI 171.7-201.1) than normal BMI and obese groups (P = 0.0007). Urine protein and albumin excretion were not elevated in any participants. On multiple regression analysis (r(2) = 0.60), the variables with strong associations with GFR were age (P = 0.0009) and lean mass (P = 0.0001). Fat mass, protein intake and smoking status were not associated. Skeletal muscle mass correlated significantly with GFR in all subgroups. CONCLUSION: Age and lean mass were strong determinants of GFR. Estimates of GFR should therefore be indexed to an estimate of lean mass.

Optical emission of a strained direct-band-gap Ge quantum well embedded inside InGaAs alloy layers.

We studied the optical properties of a strain-induced direct-band-gap Ge quantum well embedded in InGaAs. We showed that the band offsets depend on the electronegativity of the layer in contact with Ge, leading to different types of optical transitions in the heterostructure. When group-V atoms compose the interfaces, only electrons are confined in Ge, whereas both carriers are confined when the interface consists of group-III atoms. The different carrier confinement results in different emission dynamics behavior. This study provides a solution to obtain efficient light emission from Ge.

Widely tunable midinfrared difference frequency generation in orientation-patterned GaAs pumped with a femtosecond Tm-fiber system.

We demonstrate a midinfrared source tunable from 6.7 to 12.7 µm via difference frequency generation (DFG) in orientation-patterned GaAs, with 1.3 mW average output power. The input pulses are generated via Raman self-frequency shift of a femtosecond Tm-doped-fiber laser system in a fluoride fiber. We numerically model the DFG process and show good agreement between simulations and experiments. We use this numerical model to show an improved design using longer pump pulses.

Optical gating and streaking of free electrons with sub-optical cycle precision.

The temporal resolution of ultrafast electron diffraction and microscopy experiments is currently limited by the available experimental techniques for the generation and characterization of electron bunches with single femtosecond or attosecond durations. Here, we present proof of principle experiments of an optical gating concept for free electrons via direct time-domain visualization of the sub-optical cycle energy and transverse momentum structure imprinted on the electron beam. We demonstrate a temporal resolution of 1.2±0.3 fs. The scheme is based on the synchronous interaction between electrons and the near-field mode of a dielectric nano-grating excited by a femtosecond laser pulse with an optical period duration of 6.5 fs. The sub-optical cycle resolution demonstrated here is promising for use in laser-driven streak cameras for attosecond temporal characterization of bunched particle beams as well as time-resolved experiments with free-electron beams.

High-power source of THz radiation based on orientation-patterned GaAs pumped by a fiber laser.

We demonstrate a new source of frequency-tunable THz wave packets based on parametric down-conversion process in orientation-patterned GaAs (OP-GaAs) that produces muW-level THz average powers at the repetition rate of 100 MHz. The OP-GaAs crystal is pumped by a compact all-fiber femtosecond laser operating at the wavelength of 2 mum. Such combination of fiber laser and OP-GaAs technologies promises a practical source of THz radiation which should be suitable for many applications including imaging and spectroscopy.

Guanine nucleotide metabolism in a mutant strain of Escherichia coli with a temperature sensitive lesion in rRNA synthesis.

We have described a mutant of Escherichia coli (designated 2S142) which shows specific inhibition of rRNA synthesis at 42 degrees C. ppGpp levels increase at the restrictive temperature, as expected. However, when the cells are returned to 30 degrees C, rRNA synthesis resumes before ppGpp levels have returned to normal. Furthermore, when ppGpp levels are decreased by the addition of tetracycline or choramphenicol, rRNA synthesis does not resume at 42 degrees C. Also, a derivative of 2S142 with a temperature-sensitive G factor (which cannot synthesize either protein or ppGpp at 42 degrees C) shows identical kinetics of rRNA shut-off at 42 degrees C as 2S142. Thus, the elevated ppGpp levels in this mutant do not appear to be directly responsible for the cessation of rRNA synthesis at 42 degrees C.

Aminoacylation of undermethylated mammalian transfer RNA.

To study the role of 5-methylcytidine in the aminoacylation of mammalian tRNA, bulk tRNA specifically deficient in 5-methylcytidine was isolated from the livers of mice treated with 5-azacytidine (18 mg/kg) for 4 days. For comparison, more extensively altered tRNA was isolated from the livers of mice treated with DL-ethionine (100 mg/kg) plus adenine (48 mg/kg) for 3 days. The amino acid acceptor capacity of these tRNAs was determined by measuring the incorporation of one of eight different 14C-labeled amino acids or a mixture of 14C-labeled amino acids in homologous assays using a crude synthetase preparation isolated from untreated mice. The 5-methylcytidine-deficient tRNA incorporated each amino acid to the same extent as fully methylated tRNA. The tRNA from DL-ethionine-treated livers showed an overall decreased amino-acylation capacity for all amino acids tested. The 5-methylcytidine-deficient tRNA from DL-ethionine-treated mice were further characterized as substrates in homologous rate assays designed to determine the Km and V of the aminoacylation reaction using four individual 14C-labeled amino acids and a mixture of 14C-labeled amino acids. The Km and V of the reactions for all amino acids tested using 5-methylcytidine-deficient tRNA as substrate were essentially the same as for fully methylated tRNA. However, the Km and V were increased when liver tRNA from mice treated with DL-ethionine plus adenine was used as substrate in the rate reaction with [14C]lysine as label. Our results suggest that although extensively altered tRNA is a poorer substrate than control tRNA in both extent and rate of aminoacylation, 5-methylcytidine in mammalian tRNA is not involved in the recognition of the tRNA by the synthetase as measured by aminoacylation activity.

Efficient continuous wave second harmonic generation pumped at 1.55 microm in quasi-phase-matched AlGaAs waveguides.

We have fabricated quasi-phase-matched AlGaAs waveguides for continuous-wave second-harmonic generation (SHG) pumped around 1.55 microm. We find that the losses, which limit the conversion efficiency of this type of waveguide, are resulted from two corrugations--the initial template corrugation and the regrowth-induced domain-boundary corrugations. We are able to reduce the waveguide loss by improving the growth conditions. The waveguide loss is 6-7 dB/cm at 1.55 microm, measured using the Fabry-Perot method. A record internal SHG conversion efficiency of 23 %W-1 for AlGaAs waveguides is achieved using a 5-mm-long waveguide with a pump wavelength of 1.568 microm.

Study of Dy-doped Bi2Te3: thin film growth and magnetic properties.

Breaking the time-reversal symmetry (TRS) in topological insulators (TIs) through ferromagnetic doping is an essential prerequisite for unlocking novel physical phenomena and exploring potential device applications. Here, we report the successful growth of high-quality (Dy(x)Bi(1-x))2Te3 thin films with Dy concentrations up to x = 0.355 by molecular beam epitaxy. Bulk-sensitive magnetisation studies using superconducting quantum interference device magnetometry find paramagnetic behaviour down to 2 K for the entire doping series. The effective magnetic moment, µeff, is strongly doping concentration-dependent and reduces from ∼12.6 µ(B) Dy(-1) for x = 0.023 to ∼4.3 µ(B) Dy(-1) for x = 0.355. X-ray absorption spectra and x-ray magnetic circular dichroism (XMCD) at the Dy M4,5 edge are employed to provide a deeper insight into the magnetic nature of the Dy(3+)-doped films. XMCD, measured in surface-sensitive total-electron-yield detection, gives µ(eff )= 4.2 µ(B) Dy(-1). The large measured moments make Dy-doped films interesting TI systems in which the TRS may be broken via the proximity effect due to an adjacent ferromagnetic insulator.

Massive Dirac Fermion Observed in Lanthanide-Doped Topological Insulator Thin Films.

The breaking of time reversal symmetry (TRS) in three-dimensional (3D) topological insulators (TIs), and thus the opening of a 'Dirac-mass gap' in the linearly dispersed Dirac surface state, is a prerequisite for unlocking exotic physical states. Introducing ferromagnetic long-range order by transition metal doping has been shown to break TRS. Here, we present the study of lanthanide (Ln) doped Bi2Te3, where the magnetic doping with high-moment lanthanides promises large energy gaps. Using molecular beam epitaxy, single-crystalline, rhombohedral thin films with Ln concentrations of up to ~35%, substituting on Bi sites, were achieved for Dy, Gd, and Ho doping. Angle-resolved photoemission spectroscopy shows the characteristic Dirac cone for Gd and Ho doping. In contrast, for Dy doping above a critical doping concentration, a gap opening is observed via the decreased spectral intensity at the Dirac point, indicating a topological quantum phase transition persisting up to room-temperature.

Cerebral metabolic and vasopressin and oxytocin responses during osmotic stimulation in conscious rats.

Intravenous infusion of hypertonic saline increased plasma [Na (+) ] and osmolality and induced a short-latency drinking response. These changes were associated with increased glucose utilization in the supraoptic and paraventricular nuclei and neural lobe, and decreases in the medial septum and nucleus ambiguus. The increases in glucose utilization were more accentuated in the supraoptic nuclei than in paraventricular nuclei, indicating that they are more sensitive to osmotic stimulation than the paraventricular nuclei. In association with enhanced activity in the hypothalamo-neurohypophysial system, plasma vasopressin and oxytocin concentrations increased, with a preferential increase of oxytocin over vasopressin. The hormonal contents in the neural lobe were not depleted by the osmotic stimulus despite the large increases of their concentrations in the plasma.

Specific effects of 5-fluoropyrimidines and 5-azapyrimidines on modification of the 5 position of pyrimidines, in particular the synthesis of 5-methyluracil and 5-methylcytosine in nucleic acids.

5-Fluoropyrimidines and 5-azapyrimidines were found in our laboratory to be specific inhibitors of modification reactions taking place at the 5 position of pyrimidines in nucleic acids. Thus, 5-fluorouracil and 5-fluorouridine specifically inhibit the formation of 5-methyluracil, pseudouridine, and 5,6-dihydrouracil in tRNA. 5-Fluorocytidine, which is partially biotransformed to 5-fluorouracil derivatives in mammalian cells, inhibits the formation of 5-methyluracil, pseudouridine, 5,6-dihydrouracil, and 5-methylcytosine, and 5-azacytidine is a specific inhibitor of the formation of 5-methylcytosine in tRNA and DNA. Inhibitory effects on tRNA modifications require RNA synthesis, as shown by the observation that various inhibitors of RNA synthesis block the drug effects. An inhibitory low-molecular-weight (4-7S) RNA, consisting mainly of tRNA and pre-tRNA, was isolated from livers of mice after treatment with 5-azacytidine. This RNA, when added to an in vitro tRNA methyltransferase assay, specifically interfered with the formation of 5-methylcytosine in substrate tRNA. Similarly, a DNA inhibiting the synthesis of 5-methylcytosine in an in vitro DNA methylation assay was isolated from L1210 leukemic cells treated with a high dose of 5-azacytidine for a short time. Our data are consistent with the hypothesis that incorporation of 5-azacytosine into positions that are normally occupied by C residues destined to become methylated is required for the inhibition to occur, and a similar situation probably applies to the 5-fluoropyrimidine analogs. Analog base moieties occupying such sites are likely to bind strongly, perhaps irreversibly, to the active sites of the particular modifying enzymes. All our observations with the 5-fluoro- and 5-azapyrimidines are in accord with this hypothesis. It was also observed that administration of 5-azacytidine to mice led to strong inhibition of tRNA cytosine-5-methyltransferase, while at the same time the activities and capacities of purine-specific tRNA methyltransferases became strongly elevated after an initial lag period. We speculate that such increases may represent a response of the cell to the methylation defect induced by the drug. Undermodified tRNAs present in neoplastic cells may also trigger an increased synthesis of modifying enzymes. A scheme has been presented which explains increased tRNA turnover and increased activities of modifying enzymes in neoplastic cells as a consequence of a primary defect in tRNA modification.

Method for measuring the activities of cholesteryl ester transfer protein (lipid transfer protein).

A continuous recording fluorescence assay was developed for cholesteryl ester transfer protein (CETP). The assay measures the increase in fluorescence accompanying the relocation of fluorescent lipids, cholesteryl esters and triglycerides, from a donor emulsion to an acceptor emulsion. In the absence of CETP, the quantum yields of the fluorescent lipids is low because their high concentrations in the donor emulsions result in self-quenching. CETP catalyzes the redistribution of the fluorescent lipids from the donor to the acceptor emulsions and fluorescence increases substantially. Efficient sonication and incorporation of apolipoproteins from human HDL into the emulsions significantly increased the transfer rates. Under optimal conditions, the redistribution of fluorescent compounds reaches equilibrium within < 30 min and the kinetics of this process are consistent with a simple, first-order reaction pathway. The redistribution kinetics support a mechanism of adsorption --> exchange --> desorption --> diffusion.

Responses of Fanconi anemia fibroblasts to adenine and purine analogues.

Fanconi anemia (FA) fibroblasts are known to be exceptionally sensitive to the cytotoxic action of mitomycin C (MMC). The survival of FA cells was enhanced significantly when 0.5 mM caffeine or 0.5 mM adenine was added for 72 h after the cells were exposed to MMC. In other experiments in which MMC was not used, FA fibroblasts were shown to be significantly more sensitive than control cells to 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), and 6-azauridine (6-AU). These observations offer a new approach to defining the basic biochemical defect in FA.

Development, use, and evaluation of clinical practice guidelines.

The development and use of practice guidelines, if framed as recommendations for best practices in the prevention, diagnosis, treatment, and management of occupationally related health concerns and disability, can improve the quality of occupational medical practice and worker health and well being. Adherence to guidelines should improve the efficiency and effectiveness of prevention, care, and disability management by reducing the present wide variance in practices and then by moving the mean or median of process and outcome statistics toward recommended levels. The information developed for guidelines can also be used for patient discussion and expectation management. Practicing in evidence-based, agreed-upon ways should also make occupational medical practices more defensible. Guidelines should be explicit, be based on a review of the available evidence and benefits vs risks, have clear medical logic, link findings to diagnosis to treatment ot prevention, be time-based, and avoid recommending unproven approaches as a last resort. If possible, they should be reviewed and tested for usability. Guidelines that start with common occupational health concerns are best suited to prevention and outpatient care, because patients present in this way. The contents of a useful occupational health guideline would include a statement of purpose and scope, the method of development; the authors' and reviewers names and affiliations; an analysis of the specificity, sensitivity, and predictive power of mechanisms of illness or injury, symptoms, signs and tests; findings that point to a serious or emergent condition requiring immediate referral or treatment; diagnostic criteria; and initial treatment, including work with the patient in a therapeutic partnership. The guideline should also present information on factors known to be associated with work, and predictors of delayed recovery. Disability-duration statistics and methods of matching job requirements with worker abilities are also helpful. Guidelines should then outline reassessment of those patients whose health concerns remain after a reasonable recovery period. The recommendations should again be evidence-based and conform to the other attributes listed above. A discussion of management after reassessment, including behavioral referral, further testing, and procedures, is also quite useful. Recommendations for restoration of function and return to work complete guidelines focused on diagnosing, treating, and resolving activity limitations among workers. Simply developing and publishing guidelines has not resulted in improvement in practice. However, if used as the basis for peer-group interactions and actions by occupational health opinion leaders, guidelines can contribute to marked improvements in quality, worker satisfaction, and worker health.

Evidence-based design: the ACOEM Practice Guidelines Dissemination Project.

A steering committee and investigators from the American College of Occupational and Environmental Medicine (ACOEM) designed and carried out the ACOEM Practice Guidelines Dissemination Project to encourage adoption of the ACOEM Occupational Medicine Practice Guidelines. The project also involved research on guideline acceptance as well as potential improvements and additions to the guidelines. To increase guideline adoption and use in improving the appropriateness and consistency of practice and case management, the design was based on existing research on guideline format, education, and adoption efforts. This article summarizes that information and the needs assessment done prior to case-based guidelines training. Other articles in this issue report on guideline adoption and use and the results of the market research on the ACOEM guidelines.

Acceptance and self-reported use of national occupational medicine practice guidelines.

The authors conducted a survey to ascertain post-training attitudes and self-reported use of the American College of Occupational and Environmental Medicine occupational medicine practice guidelines. Trainees were surveyed 3 to 4 months after completing a case-based practice ACOEM occupational practice guidelines seminar. Of 96 physician respondents, 95% reported that the guidelines improved their practice in some manner. Fifty-two percent of physicians thought that guideline use decreased medical costs. Seventy-one percent reported that their care complied with the guidelines in 70% or more of their cases; however, "actually considering the guidelines in particular cases" was reported by only 47%. Discussion of cases was frequent (92%) and involved physicians, patients, and other health care providers. We concluded that physicians' attitudes toward the guidelines are positive and that reported compliance is high. Guidelines are discussed frequently.