Search

In the 2019 Guidelines for the Management of Hypertension by the Japanese Society for Hypertension, lifestyle modification is recommended for all individuals except those with normal blood pressure. However, no detailed methods have been established to achieve the target blood pressure and resolve clinical inertia. CureApp HT, a digital therapeutic for hypertension that contributes to blood pressure reduction through lifestyle modification, was approved as software as a medical device for reimbursement by Japanese national health insurance in September 2022. This study aimed to survey physicians who implemented CureApp HT to assess how it changes physician-patient communication and contributes to clinical inertia resolution. A questionnaire survey was conducted at three time points: before the first prescription (first survey), 3 months (second survey), and 6 months (third survey) after the first prescription for physicians who had implemented CureApp HT. The primary outcome was the total score of five items on a Likert scale related to physician-patient communication, and it was analyzed based on the 47 physicians who responded to all three questionnaires. The total score of physician-patient communication significantly improved after 6 months of the introduction of CureApp HT, reflecting that physicians observed positive changes in patients' knowledge and attitudes regarding hypertension treatment. Furthermore, the number of physicians who set a target home blood pressure of 125/75 mmHg for their patients significantly increased. CureApp HT allows physicians to recognize changes in patients' disease knowledge and treatment attitudes, enabling them to set more stringent blood pressure targets and addressing clinical inertia. Physicians who implemented CureApp HT recognized changes in the patients' stages of behavioral change through improvements in patients' knowledge of the disease and their attitudes towards treatment, and by experiencing more effective communication, they set stricter blood pressure targets., Competing Interests: Compliance with ethical standards. Conflict of interest: Author TK received honoraria from CureApp, Inc. FH, MA, YH, YT, YI, and TT are employees of CureApp, Inc., (© 2024. The Author(s).)

Population preferences for video advertisements vary across short video clips. What underlies these differences? Repeatedly watching a video clip may produce a consistent spatiotemporal pattern of neural activity that is dependent on the individual and the stimulus. Moreover, such consistency may be associated with the degree of engagement and memory of individual viewers. Since the population preferences are associated with the engagement and memory of the individual viewers, the consistency observed in a smaller group of viewers can be a predictor of population preferences. To test the hypothesis, we measured the degree of inter-trial consistency in participants' electroencephalographic (EEG) responses to repeatedly presented television commercials. We observed consistency in the neural activity patterns across repetitive views and found that the similarity in the spatiotemporal patterns of neural responses while viewing popular television commercials predicts population preferences obtained from a large audience. Moreover, a regression model that used two datasets, including two separate groups of participants viewing different stimulus sets, showed good predictive performance in a leave-one-out cross-validation. These findings suggest that universal spatiotemporal patterns in EEG responses can account for population-level human behaviours., (© 2023. The Author(s).)

Calcium acts as a second messenger to regulate many cellular functions, including cell motility. In Dictyostelium discoideum, the cytosolic calcium level oscillates synchronously, and calcium waves propagate through the cell population during the early stages of development, including aggregation. In the unicellular phase, the calcium response through Piezo channels also functions in mechanosensing. However, calcium dynamics during multicellular morphogenesis are still unclear. Here, live imaging of cytosolic calcium revealed that calcium wave propagation, depending on cAMP relay, disappeared at the onset of multicellular body (slug) formation. Later, other forms of occasional calcium bursts and their propagation were observed in both anterior and posterior regions of migrating slugs. This calcium signaling also occurred in response to mechanical stimuli. Two pathways-calcium release from the endoplasmic reticulum via IP3 receptor and calcium influx from outside the cell-were involved in calcium signals induced by mechanical stimuli. These data suggest that calcium signaling is involved in mechanosensing in both the unicellular and multicellular phases of Dictyostelium development using different molecular mechanisms., (© 2022. The Author(s).)

L1 0 -ordered FeNi alloy (tetrataenite), a promising candidate for rare-earth-free and low-cost permanent magnet applications, is attracting increasing attention from academic and industrial communities. Highly ordered single-phase L1 0 -FeNi is difficult to synthesis efficiently because of its low chemical order-disorder transition temperature (200-320 °C). A non-equilibrium synthetic route utilizing a nitrogen topotactic reaction has been considered a valid approach, although the phase transformation mechanism is currently unknown. Herein, we investigated the basis of this reaction, namely the formation mechanism of the tetragonal FeNiN precursor phase during the nitridation of FeNi nanopowders. Detailed microstructure analysis revealed that the FeNiN precursor phase could preferentially nucleate at the nanotwinned region during nitridation and subsequently grow following a massive transformation, with high-index irrational orientation relationships and ledgewise growth motion detected at the migrating phase interface. This is the first report of a massive phase transformation detected in an Fe-Ni-N system and provides new insights into the phase transformation during the nitriding process. This work is expected to promote the synthetic optimization of fully ordered FeNi alloys for various magnetic applications., (© 2022. The Author(s).)

Cardiac accessory pathways (APs) in Wolff-Parkinson-White (WPW) syndrome are conventionally diagnosed with decision tree algorithms; however, there are problems with clinical usage. We assessed the efficacy of the artificial intelligence model using electrocardiography (ECG) and chest X-rays to identify the location of APs. We retrospectively used ECG and chest X-rays to analyse 206 patients with WPW syndrome. Each AP location was defined by an electrophysiological study and divided into four classifications. We developed a deep learning model to classify AP locations and compared the accuracy with that of conventional algorithms. Moreover, 1519 chest X-ray samples from other datasets were used for prior learning, and the combined chest X-ray image and ECG data were put into the previous model to evaluate whether the accuracy improved. The convolutional neural network (CNN) model using ECG data was significantly more accurate than the conventional tree algorithm. In the multimodal model, which implemented input from the combined ECG and chest X-ray data, the accuracy was significantly improved. Deep learning with a combination of ECG and chest X-ray data could effectively identify the AP location, which may be a novel deep learning model for a multimodal model.

To identify the decoherence origin, frequency spectra using multiple π-pulses have been extensively studied. However, little has been discussed on how to define the spectral intensities from multiple-echo decays and how to incorporate the Hahn-echo T 2 in the noise spectra. Here, we show that experiments based on two theories solve these issues. As proved in the previous theory, the spectral intensity is given as the decay in the long-time limit. Unlike the initial process of decays, this definition is not only theoretically proven but also validated experimentally, since long-time behaviors are generally free from experimental artifacts. The other is the fluctuation-dissipation theory, with which the Hahn-echo T 2 is utilized as the zero-frequency limit of the noise spectrum and as an answer to the divergent issue on the 1/f n noises. As a result, arsenic nuclear spins are found to exhibit 1/f 2 dependences over two orders of magnitude in all the substrates of un-doped, Cr-doped semi-insulating and Si-doped metallic GaAs at 297 K. The 1/f 2 dependence indicates that the noise is dominated by a single source with characteristic frequency f c un  = 170 ± 10 Hz, f c Cr  = 210 ± 10 Hz and f c Si  = 460 ± 30 Hz. These f c values are explained by a model that the decoherence is caused by the fluctuations of next-nearest-neighboring nuclear spins.

Sucralfate is effective for the treatment of gastric and duodenal ulcers owing to its protective gel-forming ability. However, the mechanism by which sucralfate protects the oesophageal mucosa against reflux oesophagitis has not been clarified. We aimed to investigate the mechanisms of action of sucralfate and sucrose octasulfate (SOS), a component of sucralfate. SOS and sucralfate were administered to oesophagitis-induced rats, and the ulcer lesion size was macroscopically examined and scored. Effective pepsin activity in the gastric juices obtained from the animal model was evaluated by a casein digestion test. Sucralfate and SOS improved the pathology scores in a dose-dependent manner, whereas gastric juice pepsin activity was not impaired by therapeutic doses of SOS. As SOS lacks the ability to form a thick gel layer by polymerisation, we examined the distribution of SOS in the mucosal lumen by imaging mass spectrometry (IMS) to determine whether SOS directly adheres to the mucosal surface. A clear homogeneous thin-layer SOS film (>100 μm thick) was visualized on the oesophageal mucosal surface. Moreover, this SOS film formation was enhanced at ulcer lesion sites. Taken together, SOS appears to protect oesophageal mucosa against reflux oesophagitis via thin-layer formation on the mucosal surface.

Serum 1,25(OH) 2 D and 24,25(OH) 2 D are decreased in CKD. Megalin in proximal tubular epithelial cells reabsorbs glomerular-filtered 25(OH)D-DBP complex to convert 25(OH)D to 1,25(OH) 2 D and 24,25(OH) 2 D. Urinary C-megalin excretion is increased via exocytosis from injured nephrons overloaded with megalin-mediated protein metabolism. This study investigated the significance of urinary C-megalin excretion in vitamin D metabolism in 153 pre-dialysis CKD patients. Urinary C-megalin was positively associated with urinary protein, β 2 MG and α 1 MG, and exhibited negative correlations with serum 25(OH)D, 1,25(OH) 2 D and 24,25(OH) 2 D. Multiple regression analysis showed that urinary C-megalin had a significantly negative association with 25(OH)D. Serum 1,25(OH) 2 D and 24,25(OH) 2 D, as well as 1,25(OH) 2 D/25(OH)D and 24,25(OH) 2 D/25(OH)D ratios, showed positive correlations with eGFR. Additionally, wholePTH was positively associated with 1,25(OH) 2 D/25(OH)D and 1,25(OH) 2 D/24,25(OH) 2 D, while FGF23 was positively associated with 24,25(OH) 2 D/25(OH)D and negatively with 1,25(OH) 2 D/24,25(OH) 2 D. Urinary C-megalin emerged as an independent factor positively associated with 1,25(OH) 2 D/25(OH)D and 1,25(OH) 2 D/24,25(OH) 2 D. Although 1,25(OH) 2 D and 24,25(OH) 2 D are decreased in CKD patient serum, our findings suggest that PTH and FGF23 retain their effects to regulate vitamin D metabolism even in the kidneys of these patients, while production of 1,25(OH) 2 D and 24,25(OH) 2 D from 25(OH)D is restricted due to either impairment of megalin-mediated reabsorption of the 25(OH)D-DBP complex or reduced renal mass.

We previously showed that bladder functions are controlled by clock genes with circadian rhythm. The sensation of bladder fullness (SBF) is sensed by mechano-sensor such as Piezo1 and TRPV4 in the mouse bladder urothelium. However, functional circadian rhythms of such mechano-sensors remain unknown. To investigate functional circadian changes of these mechano-sensors, we measured circadian changes in stretch-evoked intracellular Ca 2+ influx ([Ca 2+ ] i ) using mouse primary cultured urothelial cells (MPCUCs). Using Ca 2+ imaging, stretch-evoked [Ca 2+ ] i was quantified every 4 h in MPCUCs derived from wild-type (WT) and Clock Δ19/Δ19 mice, which showed a nocturia phenotype. Furthermore, a Piezo1 inhibitor GsMTx4 and a TRPV4 inhibitor Ruthenium Red were applied and stretch-evoked [Ca 2+ ] i in MPCUCs was measured to investigate their contribution to SBF. Stretch-evoked [Ca 2+ ] i showed a circadian rhythm in the WT mice. In contrast, Clock Δ19/Δ19 mice showed disrupted circadian rhythm. The administration of both GsMTx4 and Ruthenium Red eliminated the circadian rhythm of stretch-evoked [Ca 2+ ] i in WT mice. We conclude that SBF may have a circadian rhythm, which is created by functional circadian changes of Piezo1 and TRPV4 being controlled by clock genes to be active during wakefulness and inactive during sleep. Abnormalities of clock genes disrupt SBF, and induce nocturia.

BackgroundFebrile urinary tract infection (fUTI) in children may cause renal scarring. This study aimed to investigate the usefulness of urinary biomarkers for diagnosing renal scarring after fUTI.MethodsThirty-seven children (median age: 1.36 years, range: 0.52-12.17 years, 25 boys) with a history of fUTI, who underwent renal scintigraphy for 4 months or longer after the last episode of fUTI, were analyzed. A spot urine sample was obtained on the day of renal scintigraphy to measure levels of total protein, N-acetyl-β-D-glucosaminidase (NAG), β 2 -microglobulin (BMG), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and C-megalin (full-length megalin). Results were corrected for urinary creatinine (Cr) and compared between the group with renal scarring (n=23) and that without scarring (n=14). Urinary levels of C-megalin were also measured in healthy control subjects.ResultsNo significant differences in total protein, NGAL, L-FABP, NAG, and BMG levels were found between the groups. However, C-megalin levels were significantly higher in the renal scarring group than in the non-renal scarring group and healthy controls (P<0.001). A cutoff value of 6.5 pmol/nmol of urinary C-megalin/Cr yielded 73.9% of specificity and 92.9% of sensitivity.ConclusionUrinary C-megalin is useful for diagnosing renal scarring caused by fUTI.

Podocalyxin is a cell surface sialomucin, which is expressed in not only glomerular podocytes but also vascular endothelial cells. Urinary podocalyxin is used as a marker for glomerular disease. However, there are no reports describing serum podocalyxin (s-Podxl) levels. Therefore, the association between s-Podxl levels and clinical parameters were examined with 52 patients. s-Podxl level was evaluated using enzyme-linked immunosorbent assay. The median s-Podxl level was 14.2 ng/dL (interquartile range: 10.8-22.2 ng/dL). There were significant correlations (correlation coefficient: r > 0.2) of s-Podxl levels with carotid intima media thickness (IMT) (r = 0.30, p = 0.0307). Multiple logistic regression analysis showed that s-Podxl levels remained significantly associated with carotid IMT > 1 mm (OR: 1.15; 95% CI 1.02-1.31, p = 0.026) after adjustments for traditional cardiovascular risk factors such as age, sex, current smoking status, hypertension, dyslipidemias, and diabetes. In conclusion, s-Podxl is independently associated with carotid IMT and might be used as a novel biomarker for cardiovascular disease.

The manipulation of a nuclear spin by an electron spin requires the energy to flip the electron spin to be vanishingly small. This can be realized in a many electron system with degenerate ground states of opposite spin polarization in different Landau levels. We present here a microscopic theory of a domain wall between spin unpolarized and spin polarized quantum Hall ferromagnet states at filling factor two with the Zeeman energy comparable to the cyclotron energy. We determine the energies and many-body wave functions of the electronic quantum Hall droplet with up to N = 80 electrons as a function of the total spin, angular momentum, cyclotron and Zeeman energies from the spin singlet ν = 2 phase, through an intermediate polarization state exhibiting a domain wall to the fully spin-polarized phase involving the lowest and the second Landau levels. We demonstrate that the energy needed to flip one electron spin in a domain wall becomes comparable to the energy needed to flip the nuclear spin. The orthogonality of orbital electronic states is overcome by the many-electron character of the domain - the movement of the domain wall relative to the position of the nuclear spin enables the manipulation of the nuclear spin by electrical means.

The fundamental properties of valleys are recently attracting growing attention due to electrons in new and topical materials possessing this degree-of-freedom and recent proposals for valleytronics devices. In silicon MOSFETs, the interest has a longer history since the valley degree of freedom had been identified as a key parameter in the observation of the controversial "metallic behaviour" in two dimensions. However, while it has been recently demonstrated that lifting valley degeneracy can destroy the metallic behaviour, little is known about the role of intervalley scattering. Here, we show that the metallic behaviour can be observed in the presence of strong intervalley scattering in silicon on insulator (SOI) quantum wells. Analysis of the conductivity in terms of quantum corrections reveals that interactions are much stronger in SOI than in conventional MOSFETs, leading to the metallic behaviour despite the strong intervalley scattering.

A randomized, double-blind, placebo-controlled, parallel-group multicenter study was conducted to evaluate the antihypertensive efficacy and safety of 8-week treatment with one of three fixed-dose combinations-losartan 50 mg plus hydrochlorothiazide 12.5 mg, losartan 50 mg plus hydrochlorothiazide 6.25 mg, or losartan 25 mg plus hydrochlorothiazide 6.25 mg-in comparison with those of hydrochlorothiazide 12.5 mg alone, losartan 50 mg alone, or placebo in Japanese patients with essential hypertension. Significant reductions in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were seen in all three combination groups compared with the placebo group (each p<0.001). The greatest reductions in DBP and SBP were observed in the losartan 50 mg plus hydrochlorothiazide 12.5 mg group (12.7 and 18.0 mmHg, respectively). The reductions in the losartan 50 mg plus hydrochlorothiazide 12.5 mg group were significantly greater (each p<0.001) than those in the placebo group and each of the monotherapy groups. There were no significant differences in the incidences of clinical and laboratory drug-related adverse events between any of the combination groups and the placebo group. All combination groups showed improved hypokalemia and hyperuricemia compared to the hydrochlorothiazide 12.5 mg group. These results demonstrated that once-daily, fixed-dose combination therapy with losartan 50 mg plus hydrochlorothiazide 12.5 mg is well tolerated and more efficacious in lowering DBP and SBP than monotherapy in Japanese hypertensive patients.

We conducted a prospective study to examine the effects of alterations of the metabolic syndrome detection status on the rate of progression of arterial stiffness, which is recognized as a marker of arterial damage and an indicator of cardiovascular risk. Brachial-ankle pulse wave velocity as an index of arterial stiffening was recorded twice over a 3-year period in 2080 Japanese men (age, 42 +/- 9 years). At the start of the prospective study, pulse wave velocity was higher in the subjects with metabolic syndrome (n=125) than in those without metabolic syndrome (n=1,955) even after adjusting for mean blood pressure. The annual rate of increase of the pulse wave velocity was higher in the group with persistent metabolic syndrome (27 +/- 51 cm/s/year, n=71) than in the group with regression of metabolic syndrome (6 +/- 39 cm/s/year, n=54) or the group in which metabolic syndrome was absent (13 +/- 37 cm/s/year, n=1843; p < 0.05) after adjustment for changes in blood pressure. In conclusion, the changes in the metabolic syndrome detection status of the subjects during the study period affected the annual rate of progression of arterial stiffening, and persistent metabolic syndrome during the study period was associated with acceleration of arterial stiffening in middle-aged Japanese men. On the other hand, resolution of metabolic syndrome may be associated with attenuation of the progression of arterial damage. Therefore, the increased cardiovascular risk associated with the presence of metabolic syndrome may be at least partly mediated by acceleration of the progression of arterial stiffening.

This cross-sectional study was conducted to examine whether the obstructive sleep apnea syndrome (OSAS) is associated with elevation of the pulse wave velocity (PWV) and increase in the plasma levels of C-reactive protein (CRP), both of which are known markers of cardiovascular risk, and also to determine if the concurrent presence of the metabolic syndrome might exacerbate this elevation in the levels of these cardiovascular risk markers in subjects with OSAS. With these objectives, the PWV and serum CRP were measured in 184 subjects attending a sleep clinic. It was found that the PWV and CRP were higher in the subjects with OSAS (n=94) than in those without OSAS (n=90). Furthermore, among the subjects with OSAS, the PWV and CRP were higher in those with the concurrent presence of the metabolic syndrome (n= 41; PWV=1,562+/-19 cm/s; CRP=1.8+/-0.2 mg/l) than in those without metabolic syndrome (n=53; PWV=1,432+/-21 cm/s; CRP=1.2+/-0.1 mg/l) (p<0.05). A general linear model analysis demonstrated that OSAS and metabolic syndrome were independently associated with elevated PWV and increase of the plasma levels of CRP. OSAS appears to be associated with increased cardiovascular risk, as reflected by both elevated PWV and increase of the plasma CRP. The concurrent presence of metabolic syndrome may exacerbate this increase in cardiovascular risk in subjects with OSAS. Therefore, the concurrent presence of metabolic syndrome may constitute an additive cardiovascular risk factor in subjects with OSAS.

The analytical technique of nuclear magnetic resonance (NMR) is based on coherent quantum mechanical superposition of nuclear spin states. Recently, NMR has received considerable renewed interest in the context of quantum computation and information processing, which require controlled coherent qubit operations. However, standard NMR is not suitable for the implementation of realistic scalable devices, which would require all-electrical control and the means to detect microscopic quantities of coherent nuclear spins. Here we present a self-contained NMR semiconductor device that can control nuclear spins in a nanometre-scale region. Our approach enables the direct detection of (otherwise invisible) multiple quantum coherences between levels separated by more than one quantum of spin angular momentum. This microscopic high sensitivity NMR technique is especially suitable for probing materials whose nuclei contain multiple spin levels, and may form the basis of a versatile multiple qubit device.

While arterial stiffness is known to be related to atherosclerosis, the association between arterial stiffness and cardiac systolic and diastolic function in hypertension has not been fully evaluated. The present study was conducted to simultaneously evaluate the relationship of brachial-ankle pulse wave velocity (PWV) to parameters reflecting atherosclerosis and to those reflecting the risk of congestive heart failure in patients with hypertension. In 147 patients with hypertension, the left ventricular ejection fraction, the ratio of the peak velocity of early rapid filling and the peak velocity of atrial filling (E/A ratio), and left ventricular mass index were obtained from echocardiographs, the intima-media thickness of the common carotid artery was obtained by ultrasonography, the plasma B-type natriuretic peptide (BNP) level was measured by radioimmunoassay, and the brachial-ankle PWV was measured by the volume rendering method. Brachial-ankle PWV correlated positively with the intima-media thickness of the carotid artery, E/A ratio and BNP. Multiple linear regression analysis demonstrated that the relationship between the brachial-ankle PWV and the E/A ratio was significantly independent from other clinical variables. The receiver operator characteristic curve demonstrated that a brachial-ankle PWV of 1,600 cm/s was useful to discriminate mild cardiac diastolic dysfunction (E/A ratio of < or =0.75) (sensitivity=78% and specificity=58%). The present study demonstrated that increased brachial-ankle PWV relates not only to the parameters reflecting atherosclerosis but also to those reflecting cardiac diastolic dysfunction. Therefore, increased arterial stiffness is a possible simultaneous risk for atherosclerotic cardiovascular disease and diastolic heart failure in patients with hypertension.

Functional inactivation of tuberous sclerosis 2 gene (Tsc2) leads to renal carcinogenesis in the hereditary renal carcinoma Eker rat models. Recent studies revealed a role of tuberin, a TSC2 product, in suppressing the p70 S6 kinase (p70S6K) activity via inhibition of mammalian target of rapamycin (mTOR). Phosphorylated S6 protein, a substrate of p70S6K, was expressed in the early lesions in Eker rats, and this expression was suppressed by the treatment of rapamycin, an inhibitor of mTOR. We previously isolated the novel gene Niban expressed in renal carcinogenesis of Eker rats. In this study, we demonstrated that the expression of Niban was detected from early preneoplastic lesions in Eker rats. Interestingly, in contrast to the phosphorylated S6 protein, the expression of Niban was unchanged and early lesions still remained even after treatment with rapamycin. These results might suggest the existence of another pathway independent of mTOR-S6K pathway in Tsc2 mutant renal carcinogenesis. In addition, Niban was also expressed in other renal carcinoma models, including Tsc1 and Tsc2 knockout mice, and various types of human renal cell carcinomas. Thus, Niban was commonly expressed in renal carcinomas and might be a new marker for renal carcinogenesis., (Copyright 2004 Nature Publishing Group)

The measurement of brachial-ankle pulse wave velocity (baPWV) is simple and applicable for general population studies. The present study was conducted to evaluate the applicability of baPWV for screening cardiovascular risk as well as for use as a marker of the severity of atherosclerotic vascular damage in a general population. baPWV was measured in a cross-sectional study involving two cohorts constituting a total of 10,828 subjects who underwent annual health screening check up examinations (6,716 males and 4,112 females; age 30 to 74 years). The Framingham risk score and Pocock's score were obtained. Multivariate analysis demonstrated that baPWV was associated with both scores, independently from conventional atherosclerotic risk factors. The receiver-operator characteristic curve demonstrated that a baPWV of 14.0 m/s is useful for risk stratification by Framingham score and to discriminate patients with either stroke or coronary heart disease (n=143), but the likelihood ratios were less than 5.0. Logistic regression analysis demonstrated that a baPWV>14.0 m/s is an independent variable for the risk stratification by Framingham score and for the discrimination of patients with atherosclerotic cardiovascular disease. Thus, baPWV has potential as a new marker of cardiovascular risk and may be more useful than other conventional markers; in addition, baPWV is easy to obtain and serves as an indicator of either atherosclerotic cardiovascular risk or severity of atherosclerotic vascular damage; thus it is useful to screen the general population. While the discriminating powers are not sufficiently high, a cutoff value of 14.0 m/s serves to screen subjects, especially in middle-aged ones, of either gender.

The strength of radiative transitions in atoms is governed by selection rules that depend on the occupation of atomic orbitals with electrons. Experiments have shown similar electron occupation of the quantized energy levels in semiconductor quantum dots--often described as artificial atoms. But unlike real atoms, the confinement potential of quantum dots is anisotropic, and the electrons can easily couple with phonons of the material. Here we report electrical pump-and-probe experiments that probe the allowed and 'forbidden' transitions between energy levels under phonon emission in quantum dots with one or two electrons (artificial hydrogen and helium atoms). The forbidden transitions are in fact allowed by higher-order processes where electrons flip their spin. We find that the relaxation time is about 200 micro s for forbidden transitions, 4 to 5 orders of magnitude longer than for allowed transitions. This indicates that the spin degree of freedom is well separated from the orbital degree of freedom, and that the total spin in the quantum dots is an excellent quantum number. This is an encouraging result for potential applications of quantum dots as basic entities for spin-based quantum information storage.

Peripheral blood stem cells (PBSC) are a good source for bone marrow reconstitution after intensive chemotherapy. The ability to transplant PBSC between allogeneic subjects would be a key step forward in the application of this procedure. For this purpose, we examined the mobilization and recovery of PBSC in healthy volunteers who were given recombinant human granulocyte colony-stimulating factor (G-CSF). Three informed healthy volunteers were injected with G-CSF subcutaneously at a dose of 2.5 micrograms/kg for 6 successive days and at 5.0 micrograms/kg for the following 4 days. The concentration of PBSC was assessed daily by CFU-GM and BFU-E assays, both of which peaked on the sixth to seventh day of G-CSF administration. Comparison between colony assays and hematological parameters revealed that flow cytometry analysis of CD34+ cells by mononuclear cell gating is a rapid and convenient method to quantify mobilized stem cells. The maximum numbers of CFU-GM were 432, 665, and 1386 colonies/ml blood. It is calculated that sufficient amounts of stem cells for transplantation (at least 1.0 x 10(5) CFU-GM/kg) could be obtained by leukapheresis of 5 to 201 blood when the peak was attained. This trial confirmed the feasibility of allogeneic transplantation using PBSC from healthy volunteers who have received G-CSF.

From the complete nucleotide sequence of the genome of the avian sarcoma virus Y73, we have predicted amino acid sequence of p90 gag-yes, the product of the transforming gene. Contrary to previous evidence from molecular hybridization studies p90 gag-yes was found to have much homology with the transforming gene product p60 src of Rous sarcoma virus, suggesting that the cellular counterparts of the two (c-yes and c-src) originated from a common prototype sequence.