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We have analyzed the performance of several distortion compensation techniques in the scenario of ultra-high-speed dense wavelength division multiplexed channels. A new hybrid approach, which is a combination of optical back propagation and phase conjugation twin waves, is proposed for the compensation without any pump signal. One of the advantages of the proposed technique is not only its ability to be implemented inline but also that it will reduce the number of components in transmission systems. In addition, a dispersion compensation technique has been applied by using a dispersion compensating fiber. The performance of these different techniques is evaluated in a system of 32 channels, in which each channel is modulated with a quadrature phase shift keying format and transmits the data at a rate of 200 Gb/s per channel. We performed a comparative analysis of these techniques by evaluating their performance in terms of quality factor and eye diagrams.

En août 2020, l'Organisation mondiale de la santé (OMS) a annoncé l'existence de séquelles post-COVID-19. Dans la région Grand-Lomé, épicentre de la pandémie au Togo, aucune étude sur le sujet n'a été réalisée. Nous avons mené cette étude pour déterminer la prévalence et les facteurs associés aux séquelles post-COVID-19 de 2020 à 2021.

The potential involvement of CYP3A43 in systemic olanzapine (OLA) metabolism has been suggested by one reported association between the intronic polymorphism CYP3A43rs472660G>A and OLA clearance in 235 White and African-American patients. Trough plasma OLA concentrations in AA carriers were predicted on average 48 lower than in GG carriers. In the current study, we evaluated this finding by genotyping 374 White psychiatric patients on long-term OLA treatment. No significant difference in dose-adjusted trough serum OLA concentrations was observed between the seven AA carriers identified and the other two genotypes, without (P=0.6) or with (P=0.23) adjustment for additional covariates previously known to influence systemic OLA exposure. Because of the low prevalence of the rs472660 AA genotype in White populations (2), larger study cohorts are needed for future association confirmation. Overall, CYP3A43rs472660 is not likely to be a major contributor towards variability in systemic OLA exposure among White patients.

Metabolism of the atypical antipsychotic olanzapine (OLA) is partially catalyzed by cytochrome P450 (CYP) 1A2, a target of aryl hydrocarbon receptor (AHR)-mediated induction. We investigated the influence of four cis-acting polymorphisms (rs2470893C>T and rs2472297C>T between CYP1A1and CYP1A2loci, and rs762551C>A and rs2472304A>G within CYP1A2) as well as one trans-acting polymorphism upstream of the AHRlocus (rs4410790C>T) on interindividual variation in systemic OLA exposure.

Single phase ceramics in the vicinity of CaNdAlO4in CaO–Nd2O3–Al2O3ternary system, such as ternary oxide compound CaNdAl3O7and binary oxide compounds NdAlO3, CaAl2O4, Ca3Al2O6and Ca12Al14O33, were prepared by the standard solid state reaction route. The phases and structure of the ceramics were analysed through X-ray diffraction and scanning electron microscopy. The microwave dielectric characteristics of the ceramics were studied using a network analyser. High Qfvalues were obtained in CaNdAlO4, CaNdAl3O7, NdAlO3and CaAl2O4, while the Qfvalues in Ca3Al2O6and Ca12Al14O33were much lower. The best microwave dielectric characteristics (?r?=?8·9, Qf?=?90?800 GHz at ~9·40 GHz and tf˜-55·2 MK-1) were achieved for CaAl2O4ceramics sintered at 1425°C in air for 3 h. It could be expected as a promising new candidate for microwave dielectric ceramics. Moreover, the present results showed the direction for modification of CaNdAlO4microwave dielectric characteristics through composition tailoring.

Context. We investigate the joint evolution of active galactic nuclei and star formation in the Universe.Aims. In the 1.4?GHz survey with the Australia Telescope Compact Array of the Chandra Deep Field South and the European Large Area ISO Survey???S1 we have identified a class of objects which are strong in the radio but have no detectable infrared and optical counterparts. This class has been called Infrared-Faint Radio Sources, or IFRS. 53 sources out of 2002 have been classified as IFRS. It is not known what these objects are.Methods. To address the many possible explanations as to what the nature of these objects is we have observed four sources with the Australian Long Baseline Array.Results. We have detected and imaged one of the four sources observed. Assuming that the source is at a high redshift, we find its properties in agreement with properties of Compact Steep Spectrum sources. However, due to the lack of optical and infrared data the constraints are not particularly strong.

Inverted drop test is a dynamic roof crush test which is simple, realistic, reliable and easily implemented. It can produce repeatable roof impacts that can be used to compare one test run with another and has long been used by the automotive industry and researchers to test roof integrity. However, practical full-scale vehicle roof crush tests are always very costly, especially for finding out the impact orientation for the worst structural behaviour. Computer simulation can provide an effective solution, since it is highly repeatable, and under different environmental conditions permits the variation of parameters to evaluate sensitivity. A full-scale Finite Element model of Ford Fiesta that was originally modelled in parts by Ford Motor Company using Radioss code was translated into LS-DYNA3D and refined through extensive employment of better elements and spotwelds formulation. The inverted drop-test simulation, therefore, was made using a combination of different pitch and roll angles in the search of the worst-case rollover condition. These parametric studies show the critical vehicle orientation at roof impact that causes the highest amount of roof crush to be 10° pitch angle and 12.5° roll angle. This is similar to the test conditions employed in the experimental test using a Renault Clio. The results obtained from simulating these two different vehicles show the existence of some design problems, i.e., a very weak roof that is supported by weak roof rails and weak reinforcing plates. Furthermore, the inverted drop-test simulation results depict clearly the differences between static roof crush tests based on FMVSS No. 216 that is loaded along a fixed orientation and only reflects the roof strength, rather than the pillar's strengths, response in that direction. The dynamic test in that sense is more realistic and closer in nature to a number of recorded real-world accidents.

Grey system theory can effectively deal with incomplete and uncertain information. The grey model (GM) is the core of grey system theory, which collects available data to obtain the internal regularity without using any assumptions. The forecasting accuracy is related to the sample number n in GM. However, there always exists a time lag just the same as other forecasting methods do although its application can yield exact prediction that is of high repeatability with characteristics depicting high reliability and efficiency. To minimise the lag time for the results of grey prediction (GP), a three-point moving average has been developed and applied on them. Its application to the UK and USA datasets has been proved to be greatly successful and reliable. The mean and maximum errors of the outcomes of GP are tremendously reduced, hence greatly improving the accuracy of prediction. Thus, the combination of grey model GM(1, 1) with three-point moving average has been proved to be a more powerful forecasting tool and yields far much better predictions for vehicle fatality risk rates.

Sakamoto et al. (Langmuir 2002, 18, 5713) conducted AFM force measurements between silica sphere and fused-silica plate in aqueous octadecyltrimethylammonium chloride (C18TACl) solutions and concluded that long-range attractive force is not observed in carefully degassed solutions. In the present work, AFM force measurements were conducted by following the procedures described by Sakamoto et al. The results showed the presence of an attractive force that was much stronger than the van der Waals force both in air-saturated and degassed solutions. The force was most attractive at 5 × 10^-6 M C18TACl, where contact angle was maximum. At this concentration, which is close to the charge compensation point (ccp) of the glass sphere, the long-range decay lengths (D) were 34 and 38 nm in air-saturated and degassed solutions, respectively. At 10^-5 M, the decay length decreased from 30 to 4 nm upon degassing. This decrease in decay length can be explained by a pH increase (from 5.7 to 6.6), which in turn causes additional surfactant molecules to adsorb on the surface with inverse orientation. The attractive force was screened by an added electrolyte (NaCl), indicating that the attractive force may be of electrostatic origin. Therefore, the very long decay lengths observed in the absence of electrolyte may be ascribed to the fact that the ccp occurs at a very low surfactant concentration.

We introduce a new method for the stabilization of colloidal particles via the synthesis and adsorption of unnatural proteins. Biosynthesis of protein-based polymers offers the advantages of preparation of complex sequences through control of the primary sequence, monodisperse polymers, ease of combinatorial search for anchor blocks, environmentally friendly synthesis, use of water as the solvent, and incorporation of a palette of known natural proteins. We have synthesized an unnatural protein with the sequence thioredoxin-Pro39Glu10 for modification of the forces between alumina particles. The polyglutamate sequence, Glu10, is anionic (pH >3) and is designed to anchor the protein to positively charged solids, e.g. alumina in water (pH <9). The polyproline sequence, Pro39, is neutral. The thioredoxin is a recombinant form of the natural globular protein with a histidine patch (His-patch-thioredoxin) and is zwitterionic. The combined thioredoxin-Pro39 sequence is hydrophilic with pI ~ 6.3. This block is designed to remain in solution, thereby providing a steric barrier to the approach of two particles in a range of salt and pH conditions. Ellipsometry experiments show that thioredoxin-Pro39Glu10 does adsorb to alumina. Force measurements with the atomic force microscopy (AFM) colloid probe technique show that adsorption of thioredoxin-Pro39Glu10 leads to repulsive forces that decay exponentially with the separation between the surfaces and are independent of salt concentration in the range 0.001−0.1 M KNO3. This demonstrates that the repulsive forces are not electrostatic. We hypothesize that the repulsion is due to confinement and loss of solvent for the adsorbed polymer; the forces are similar to those expected for a polymer brush. Force measurements between thioredoxin-coated alumina surfaces also show a repulsive force, but the force has a decay length that is consistent with electrostatic double-layer forces:  the thioredoxin has not neutralized the surface charge of the underlying alumina. Our results point to interesting future experiments where recombinant DNA technology could be used to synthesize fusion proteins containing useful natural proteins and an anchor. This may allow preparation, via single-step aqueous self-assembly, of anchored proteins that maintain their natural structure. Our technique is not limited to homopolymer blocks; more complex primary sequences can be used.

Quasi-static roof crush simulations based on FMVSS 216 have been carried out successfully on a small European car, and different loading conditions have been tested. Results show that bonded windscreens contribute at least 30% of roof strength based on FMVSS 216. This confirms experimental test results carried out by other researchers. Furthermore, results show that the roll and pitch angles are a function of roof strength and greatly influence the overall behaviour. For instance, with the same pitch angle, the roof strength greatly drops as the roll angle goes up from 15° to 45°; but the magnitude of roof strength drop is minimal as the pitch angle increases. While for the same roll angle, the roof strength is seen to decrease as the pitch angle increases from 0° to 10°; but it does not mean that the bigger the pitch angle, the weaker the roof strength becomes. In fact in the case of a 10° pitch angle, the roof strength exhibits worst results. The recommendations on the updated FMVSS 216 are a roll angle of 45° (not 25°) and a pitch angle of 10° (not 5°). These constitute more realistic test angles that replicate real world accident data. In addition to quasi-static virtual testing, some dynamic simulations are also carried out based on two dynamic test methodologies, namely the inverted car drop in a cylindrical ditch and on a flat ground. Results show severe roof damage to occur in the former test scenario despite both having same initial conditions. The paper has also defined corridors for the best design of a car roof.

Optical measurements using an ellipsometer are inconsistent with the existence of continuous air films that are greater than about 0.1 nm in thickness at the interface between water and silicon wafers that have been rendered hydrophobic through the adsorption of silane agents. If adsorbed air consists of discrete bubbles, then the separation between the bubbles must be much greater than the radius of a bubble. For example, an approximate calculation for 80 nm radius bubbles that are attached with the macroscopic contact angle shows that the minimum spacing consistent with our data is in the range of 5 μm to infinite separation, depending on the sample. Although these putative bubbles would be sparsely distributed, we cannot rule out a density that is great enough to affect surface force apparatus measurements. A new variant of the multiple incidence method for ellipsometry is described and used to decrease the error in determining the thickness of adsorbed films.

The phase behavior as well as the microstructures of the dodecyltrimethylammonium bromide (DTAB)/sodium laurate (SL) aqueous two-phase system has been studied. By using FF-TEM, dynamic light scattering (DLS), a viscosity meter, and polarization microscopy, the effects of surfactant concentration and mixing ratio, temperature, salt concentration, and additives (octanol and toluene) on the phase separation have been systematically investigated. The phase separation is found to be strongly dependent on the variation of the surfactant aggregates. The different kinds of aqueous surfactant two-phase system can transit between each other upon the variation of the mixing ratio, the change of the salt concentration, and the addition of toluene and octanol.

The development of an efficient, low-cost synthesis of the novel wheat fungicide silthiofam (1) is described. Improvements to the original Discovery route allowed 300 kg of material to be prepared in two, overlapping pilot-plant campaigns. Thereafter, efforts were focused on further optimizing the pilot-plant route, and on devising alternate, lower cost routes to silthiofam. One potential new route involved a cycloaddition reaction between 3-mercapto-2-butanone and N-(2-propenyl)-3-trimethylsilylpropynamide. The cyclic product could be directly dehydrated to silthiofam, however the overall yield was modest, raw material costs were high, and there were purification problems. The route ultimately selected for development proceeds in 6 chemical steps and about 60% yield from the inexpensive precursors 3-chloro-2-butanone and methyl 3-methoxyacrylate. Key features of the route are a novel thiophene-3-carboxylate synthesis involving cycloaddition of 3-mercapto-2-butanone with the acrylate followed by acid catalyzed aromatization, the room temperature formation and silylation of a thiophene-3-carboxylate dianion, and conversion of the resulting carboxylic acid into silthiofam with negligible loss of the silyl group. The process involves isolation of just two intermediates, only one of which is purified, and uses only three organic solvents, all of which are recycled. It can be run safely on large scale to give high-purity silthiofam.

The transition from vesicles to micelles by adding octane into the dodecyl-pyridinium chloride (DPCl)/sodium laurate (SL), and dodecyltrimethylammonium bromide (DTAB)/SL aqueous two-phase systems has been studied. The two-phase systems were transformed into single-phase isotropic solutions with the addition of a certain amount of octane. The results of dynamic light scattering (DLS) demonstrate the decrease of large aggregates (vesicles) and the increase of the small aggregates (spherical micelles) upon octane addition. Such transformation of the surfactant aggregates was also corroborated by the results of time-resolved fluorescence quenching (TRFQ) and viscometry. The change of the phase behavior was discussed on the basis of the interaggregate interactions influenced by the variation of organized assemblies.

Abstract: The formation of self-organized assemblies by CnH2n+1NH2·HCl and C12H25SO4 Na in polar solvents was studied. By adding 1-propanol or 2-propanol, the precipitation formed in aqueous solution was resolved and a bilayer structure was discovered. Furthermore, multilamellar vesicle formation could be observed by methods of adjusting the molar ratio of CnH2n+1NH2·HCl to C12H25SO4Na, changing the length of the hydrocarbon chain of CnH2n+1NH2·HCl, or adding 1-octanol to the mixed surfactant systems.

The ultrafast gain dynamics in an electrically pumped InAs/InGaAs/GaAs quantum-dot amplifier are measured at room temperature with femtosecond resolution, and compared with results on an InGaAsP bulk amplifier. The role of spectral hole burning and carrier heating in the recovery of the gain compression is investigated. Reduced carrier heating for both gain and refractive index dynamics of the quantum-dot device is found, which is a promising prerequisite for high-speed applications.

The room temperature dephasing in InAs/InGaAs/GaAs self-assembled quantum dots, embedded in a waveguide for laser applications, is measured using two independent methods: spectral hole burning and four-wave mixing. Without the application of bias current for electrical carrier injection, a dephasing time of 260 fs, weakly dependent on the optical excitation density, is found and attributed to phonon interaction. The application of a bias current, leading to population inversion in the dot ground state and optical gain, strongly decreases the dephasing time to less than 50 fs, likely due to enhanced carrier–carrier scattering in the presence of the electrically injected carriers.

To clone zinc finger genes expressed in hematopoietic system, we designed primers based on conserved Cys(2)/His(2) zinc finger sequences to amplify corresponding domains from mRNA of normal bone marrow and leukemia cell line NB4. DNA fragments of novel zinc finger genes were chosen and used as probe pool to screen cDNA libraries or subject to rapid amplification of cDNA ends in order to obtain full-length cDNA. Six cDNAs including whole open reading frame of zinc finger proteins, named as ZNF191, ZNF253 (BMZF-1), ZNF255 (BMZF-2), ZNF256 (BMZF-3), ZNF257 (BMZF-4), and ZNF254 (BMZF-5) were obtained. All six belong to the Krüppel-like zinc finger gene family, and typical transcriptional regulatory motifs exist in the N-terminal moiety, such as the SCAN box in ZNF191, and the KRAB domains in ZNF253, ZNF254, ZNF256, and ZNF257. A previously undefined sequence nominated as Krüppel-related novel box, which may represent a new transregulatory motif, was revealed at the N terminus of ZNF255. The transregulatory function of non-zinc finger regions of ZNF191, ZNF253, and ZNF255 were addressed in yeast and mammalian cells. The results indicated that ZNF255 might be a conditional transactivator, whereas ZNF253 and ZNF191 displayed a suppressive effect on the transcription in yeast and/or mammalian systems.

Abstract: The vesicle formations of 1:1 cationic-anionic surfactants in various nonaqueous polar solvents and their aqueous mixtures were investigated. Outstanding vesicle-forming capability and stability of cationic and anionic surfactants were found in nonaqueous polar solvents and their aqueous mixtures except for in formamide. A small amount of formamide destroys the vesicles formed by cationic-anionic surfactants in aqueous solutions. These results could be very well explained based on the effect of the medium dielectric constant.

This article presents the theory and experimental results of an optical imaging technique that simultaneously measures the deflections of a focal plane array of bimaterial microcantilevers that are used as thermomechanical infrared sensors. Based on Fourier optics, this technique is used for infrared vision of room-temperature objects with a noise-equivalent temperature difference (NETD) in the range of 2-5 K. Efforts are currently underway to improve the NETD to the range of 30-50 mK.

Y2Fe17-xSix compounds withx=0, 0.5, 1.0, 1.5, 2.0, 2.5 and3.0 were investigated by magnetic measurement andNMR. It is found that with increasing Si content the Curie temperatureTC increases while the average Fe magnetic moment µFe decreases. NMR study indicates that Si preferentially substitute the Fe atoms at 4f sites, which is responsible for the increase ofTC.

In vivo all-trans-retinoic acid (ATRA), a differentiation inducer, is capable of causing clinical remission in about 90% of patients with acute promyelocytic leukemia (APL). The molecular basis for the differentiation of APL cells after treatment with ATRA remains obscure and may involve genes other than the known retinoid nuclear transcription factors. We report here the ATRA-induced gene expression in a cell line (NB4) derived from a patient with APL. By differential display-PCR, we isolated and characterized a novel gene (RIG-E) whose expression is up-regulated by ATRA. The gene is 4.0 kb long, consisting of four exons and three introns, and is localized on human chromosome region 8q24. The deduced amino acid sequence predicts a cell surface protein containing 20 amino acids at the N-terminal end corresponding to a signal peptide and an extracellular sequence containing 111 amino acids. The RIG-E coded protein shares some homology with CD59 and with a number of growth factor receptors. It shares high sequence homology with the murine LY-6 multigene family, whose members are small cysteine-rich proteins differentially expressed in several hematopoietic cell lines and appear to function in signal transduction. It seems that so far RIG-E is the closest human homolog of the LY-6 family. Expression of RIG-E is not restricted to myeloid differentiation, because it is also present in thymocytes and in a number of other tissues at different levels.

Field data obtained in the measurement of typhoon-generated waves in Gulf of Bei Bu, a semi-enclosed shallow water bay, is used in the validation of a 'third generation' spectral model which employs an accurate numerical solution algorithm. The linear bottom dissipation expression obtained in the JONSWAP study is adopted since it produces a more reasonable wave growth characteristics in an ideal test case as compared to the dissipation formulation based on quadratic friction law. Computational efficiency of the model is enhanced by employing digital filtering technique to suppress the numerical instability arisen from using large time step (up to about 30 minutes) and to maintain an acceptable accuracy. The performance of the model is good and provides a further support to the 'third generation' formulation of spectral models.

A direct numerical procedure is developed for analyzing the refraction of a flexural wave which impinges on a finite region of variable mechanical impedance in an elastic bar. This region is approximated by a set of uniform impedance elements, regarded as Timoshenko beams, to which the methods of geometric acoustics are applied. The analysis is performed for an infinite harmonic wave train and is extended to the case of a pulse by means of numerical Fourier synthesis. Numerical results are obtained for several examples in which experiments were performed and the calculated pulses are in close agreement with those observed experimentally. It is found that the contribution of the continuing interaction between propagating and nonpropagating waves accumulates within a nonuniform region and can significantly affect the net pulses of transmission and reflection.

Abstract: Experiments are performed to study the amplification of longitudinal pulses which propagate along tapered elastic bars in the direction of decreasing cross-sectional area. Each bar specimen is composed of two uniform cylindrical end sections of different radius joined by a tapered transition in the form of a cone frustrum. The amplification of a pulse which propagates from the large end to the small end in such a bar is shown to depend on the spatial pulse length (nondimensionalized with respect to the length of the transition region) for a given ratio of the terminating cross-sectional areas. The observed amplification is plotted over a wide range of nondimensionalized pulse lengths for several choices of the overall area ratio. For very short and very long pulses, the amplification approaches the limiting values given by simple equations which involve only the geometric parameters of the bar. The factors which influence the amplitude and shape of pulses which are reflected from the cone frustrum are discussed briefly.

Stress pulse propagation along homogeneous but nonuniform bars is investigated. The bars have two uniform end sections of different diameter joined by a finite transition region. When a pulse is incident on the transition it is distributed over an infinite network of paths leading to transmission and reflection. In the analysis the transition is approximated by a set of discrete steps in area. A finite set of paths which contribute significantly to the pulses of reflection and transmission are identified and included in the calculations for the two pulses. The basic analysis is suitable for elastic pulses of arbitrary shape and is reformulated in harmonic form for use in viscoelastic bars. Calculated and experimental results are found to be in good agreement.

In order to investigate the carbonation resistance of concrete with fly ash as fine aggregate (CFA), the rapid carbonation test was conducted to explore the influence of the curing age, water-to-cement (w/c) ratio, fly ash replacement rate and the activator on the carbonation depth. The experimental results show that prolonging the curing time is beneficial to improving the carbonation resistance of the CFA. The carbonation depth of the CFA correlates positively with the w/c ratio. With an increase in the fly ash replacement rate and w/c ratio, the carbonation resistance of the CFA increases to a remarkable extent. After 28 days of standard maintenance of the CFA, the compactness of the CFA is boosted due to the pozzolanic effect of the fly ash, and its carbonation resistance is enhanced compared to that of ordinary concrete. In addition, the incorporation of the activator marginally contributes to the improvement of the carbonation resistance of the CFA.

The authors compare the threshold current density jth against the laser length of a single layer quantum dot (SLQD) laser with a sixfold multilayer quantum dot (MLQD) laser. Gain saturation is not observed in the MLQD laser. They calculate jth against the number of dot layers including gain saturation. The strong impact of thermal coupling of carriers on jth is demonstrated.

The high frequency response of self-organised stacked InAs/GaAs quantum dot lasers grown by MOCVD is investigated through relaxation oscillation measurements at room temperature. The highest relaxation oscillation frequency for a 265 µm cavity laser at room temperature is 5.3 GHz, corresponding to a 3 dB cutoff frequency of 8.2 GHz. Good static properties, such as high intemal quantum efficiency (91%) and low transparency current density (40 A/cm2) at room temperature are also obtained.

Context.Infrared-faint radio sources (IFRS) are objects that have flux densities of several mJy at 1.4 GHz, but that are invisible at 3.6 μm when using sensitive Spitzer observations with μJy sensitivities. Their nature is unclear and difficult to investigate since they are only visible in the radio.

Objectives: To explore the changes of Ghrelin mRNA and protein expression in fundus of stomach of rats born small for gestational age (SGA) and to analyze the relationship with the catch-up growth of postnatal SGA rats.Methods: The SGA and appropriate for gestational age (AGA) rat models were established by food restriction during pregnancy. The newborn rats were acquired after delivery, among which 10 rats were selected randomized from SGA group and control group at postnatal day 0, day 20 and day 40. The fundus of stomach were taken to determine Ghrelin mRNA and protein expression.Results: At postnatal day 0, stomach fundus Gherlin mRNA expression is higher in SGA rats than those in AGA rats. At postnatal day 20 and day 40, there is no significant difference in Gherlin mRNA expression among SGA non-catching-up rats, SGA catching-up rats and normal AGA rats. At postnatal day 0, Gherlin IOD in SGA rats is higher than that in AGA rats. Ghrelin IOD in SGA catching-up rats is higher than that in SGA non-catching-up rats and normal AGA rats (p< 0.05) at postnatal day 20, and there is no significant difference among them at postnatal day 40.Conclusion: Ghrelin might be involved in the physiological regulation or pathological process of IUGR, and intrauterine nutritional status or endocrine circumstances may have effects on the cells of gastric fundus of the fetuses, which results in the up-regulation of Ghrelin expression. Ghrelin might also be involved in the regulation of catch-up growth in their early life.

Imatinib mesylate (IM) has dramatically changed the treatment approach for patients with chronic myeloid leukemia (CML). However, ~20% of chronic phase (CP) patients are initially resistant to IM, and among patients who achieve a complete cytogenetic response (CCyR), a small minority relapse back into CP or progress to advanced disease. Abl tyrosine kinase domain mutations are the major cause of secondary resistance. Oligonucleotide microarray analysis was used to study gene expression patterns associated with primary IM resistance and relapse after initial successful response to IM. Samples included total RNA from diagnostic samples of 25 CML CP patients within 6 months of diagnosis and at the time of failure (7 patients); total RNA from 18 patients who relapsed after initial CCyR with documented Abl point mutations (12 CP and 6 BC); and 10 myeloid progenitor samples (sorted by CD34 and CD38 status) from an IM naïve and IM resistant (R) patient, both in blast crisis. Results: For primary IM resistance, analysis of paired samples before and after treatment revealed that primary failure was associated with the differential expression of genes associated with RNA post-transcriptional modification, protein synthesis, cellular growth and proliferation, and cell death. Two genes with the highest differential expression included the apotosis resistance genes API5 and TRAF5. TRAF5 was also increased in patients who relapsed after initial CCyR, while API5 showed significantly increased expression in sorted CD34+ cells from an IMR patient. In secondary resistance patients, a set of drug transporters including ABCA2, ABCA3, MDR1, and ABCC3 had increased expression and hOCT1 decreased expression relative to 42 IM naïve CP patients. In vitro experiments compared K562 resistant (R) and sensitive (S) cell lines over time exposed to IM. The K562 IMR cell line showed a 1.5 log higher expression of ABCG2 and a 1 log higher expression of TRAF5 compared to the K562 IMS cells. However, sequential clinical samples of 16 IM non-responders vs. 14 CCyR patients showed no change in ABCG2 expression, possibly because ABCG2 is expressed only in early progenitor cells, not differentiated cells. The importance of using CD34+ cells was demonstrated in 7 array studies comparing gene expression in CD34+ selected cells from an IMR patient compared to an IM naïve patient. IM resistance was associated with increased expression of genes associated with cell cycle, DNA recombination and repair, and proliferation. Genes associated with apoptosis resistance included increased expression of API5, survivin, and decreased expression of BAK1. Protein serine/threonine and tyrosine kinases associated with cell proliferation/survival and tumor progression with increased expression in the IMR patient included: AURKB, AKT3, BUB1B, CDC2, CHEK1, MAPK9, STK6, TTK, and WEE1. Conclusion: Gene expression studies suggest that primary resistance to IM therapy is associated with resistance to apoptosis; relapse on IM is associated with activation of drug transporter genes and genes associated with disease progression; in studying disease response and resistance, primitive hematopoetic cells are critical for analysis.

Reaction of o‐acetylbenzoic acid (I) with the α‐amino acids (II) results in the formation of the methylene lactams (III) and the fused oxazolidinones (IV).

We have realized injection lasers based on InAs-GaAs and InGaAs-GaAs quantum pyramids (QPs) with a lateral size ranging from 80 to 140 Å. The structures with relatively small dots (?80 Å) exhibit properties predicted earlier for quantum dot (QD) lasers such as low threshold current densities (below 100 Acm-2) and ultrahigh characteristic temperatures (T0=350-425 K). For operation temperatures above 100-130 K, T0decreases and the threshold current density increases (up to 0.95-3.3 kAcm-2at room temperature) due to carrier evaporation from QPs. Larger InAs QPs (?140 Å) providing better carrier localization exhibit saturation of the ground-state emission and enhanced nonradiative recombination rate at high excitation densities. The radiative lifetime shows a weak dependence on the dot size in the range 80-140 Å being close to ?1.8-2 ns, respectively. A significant decrease in radiative lifetime is realized in vertically coupled quantum dots formed by a QP shape-transformation effect. The final arrangement corresponds to a three-dimensional tetragonal array of InAs islands inserted in a GaAs matrix each composed of several vertically merging InAs parts. We achieved injection lasing in such an array for the first time.