Biomedical subjects

Y Qiu

Publications and source records attributed to Y Qiu.

At least 19 recordsLinked to original sources

PubMed2006

Field-induced order and spin waves in the pyrochlore antiferromagnet Tb2Ti207.

High resolution time-of-flight neutron scattering measurements on Tb(2)Ti(2)0(7) reveal a rich low temperature phase diagram in the presence of a magnetic field applied along [110]. In zero field at T = 0.4 K, Tb(2)Ti(2)0(7) is a highly correlated cooperative paramagnet with disordered spins residing on a pyrochlore lattice of corner-sharing tetrahedra. Application of a small field condenses much of the magnetic diffuse scattering, characteristic of the disordered spins, into a new Bragg peak characteristic of a polarized paramagnet. At higher fields, a magnetically ordered phase is induced, which supports spin wave excitations indicative of continuous, rather than Ising-like, spin degrees of freedom.

Journal Article↗

PubMed2006

JNJ-10280205 and JNJ-10287069: Novel PDE5 inhibitors as clinical candidates for erectile dysfunction.

Phosphodiesterase 5 (PDE5) inhibitors are efficacious in treating patients with erectile dysfunction. New PDE5 inhibitors with different selectivity and pharmacokinetic profiles have been vigorously pursued. Here we report two novel, potent, and selective PDE5 inhibitors, JNJ-10280205 and JNJ-10287069, with Ki values of 0.05 and 0.12 nM, respectively. Both compounds displayed superior selectivity against PDE1-4 and -6 when compared to sildenafil. In the anesthetized dogs, JNJ-10280205 and JNJ-10287069 exhibited similar efficacy as sildenafil in enhancing erectile functions, with no significant effect on cardiovascular parameters. Pharmacokinetic studies showed that JNJ-10287069 had better oral bioavailability than JNJ-10280205 in several animal species. In vitro study suggested that cytochrome P450 (CYP) 3A4 played a major role in the metabolism of both compounds. The compounds inhibited some of the CYP450 enzymes and the human ether-a-go-go (HERG) channel at much higher concentrations than that required to inhibit PDE5, thus, no cross inhibition would be expected at therapeutic doses. Both compounds are suitable clinical candidates.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2006

Dynamics of composite haldane spin chains in IPA-CuCl3.

Magnetic excitations in the quasi-one-dimensional antiferromagnet IPA-CuCl3 are studied by cold neutron inelastic scattering. Strongly dispersive gap excitations are observed. Contrary to previously proposed models, the system is best described as an asymmetric quantum spin ladder. The observed spectrum is interpreted in terms of composite Haldane spin chains. The key difference from actual S=1 chains is a sharp cutoff of the single-magnon spectrum at a certain critical wave vector.

Journal Article↗

PubMed2006

Nanomagnetic droplets and implications to orbital ordering in LA(1-x)Sr(x)CoO3.

Inelastic cold-neutron scattering on LaCoO3 provided evidence for a distinct low energy excitation at 0.6 meV coincident with the thermally induced magnetic transition. Coexisting strong ferromagnetic (FM) and weaker antiferromagnetic correlations that are dynamic follow the activation to the excited state, identified as the intermediate S = 1 spin triplet. This is indicative of dynamical orbital ordering favoring the observed magnetic interactions. With hole doping as in La(1-x)Sr(x)CoO3 , the FM correlations between Co spins become static and isotropically distributed due to the formation of FM droplets. The correlation length and condensation temperature of these droplets increase rapidly with metallicity due to the double exchange mechanism.

Journal Article↗

PubMed2006

The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs.

Protein kinase Pim-1 has been implicated in the development of hematopoietic and prostatic malignancies. Here, we present the evidence that two isoforms, the 44 and 33 kDa Pim-1, are expressed in all human prostate cancer cell lines examined. The subcellular localization of human 44 kDa Pim-1 is primarily on the plasma membrane, while the 33 kDa isoform is present in both the cytosol and nucleus in PCA cells. The 44 kDa Pim-1 contains the proline-rich motif at the N-terminus and directly binds to the SH3 domain of tyrosine kinase Etk. Such interaction leads to the activation of Etk kinase activity possibly by competing with the tumor suppressor p53. This is corroborated by the fact that overexpression of the 44 kDa Pim-1 in prostate cancer cells confers the resistance to chemotherapeutic drugs. Our results suggest that these two isoforms of Pim-1 kinase may regulate distinct substrates and the 44 kDa Pim-1 may play a more prominent role in drug resistance in prostate cancer cells.

Amino Acid Sequence↗

PubMed2006

Influence of solid phase and formulation processing on stability of Abbott-232 tablet formulations.

Abbott-232 is a chemically stable, highly water soluble non-hygroscopic compound selected for development as a potent uroselective alpha(1A) agonist. An anhydrate, a monohydrate, and an amorphous phase were isolated. The anhydrate was chosen for formulation development based on solid-state characterization. Excipients for immediate release (IR) tablet formulations were selected according to compatibility studies. However, the prototype IR tablets designed for clinical trials were found to be chemically unstable. Thus, process-induced phase transformation was investigated as the likely cause of the observed instability. Since the drug loading in the formulations was low (1%), model granulations containing 30% drug were evaluated to test this hypothesis. Investigation using a variety of analytical techniques indicated that the observed degradation was, indeed, a result of a solution-mediated phase transformation from anhydrate to amorphous Abbott-232 during wet granulation. A new direct compression formulation was, therefore, developed to prevent the solution-mediated process induced phase transition. Since the drug loading was low, a polarized light microscope (PLM) method was used to evaluate the solid phase in the new formulation. PLM confirmed that the original anhydrate form remained unchanged in tablets manufactured by the dry process. Stability studies confirmed that both IR and extended release (ER) tablets of Abbott-232 were successfully developed for clinical trials using direct compression.

Adrenergic alpha-Agonists↗

PubMed2006

Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design.

There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (i.e. 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.

Adult↗

PubMed2006

The role of melatonin receptor 1B gene (MTNR1B) in adolescent idiopathic scoliosis--a genetic association study.

UNLABELLED: Many studies have demonstrated the role of melatonin in the etiology of AIS. Previous studies have shown that there is no evidence of mutations in the melatonin receptor 1A gene in AIS patients. In this study, we have examined the role of melatonin receptor 1B in predisposition for AIS. Using haplotype block tagging technique, a set of tagging SNPs were defined for MTNR1B from the Han Chinese data of the International HapMap project. The association between the tagging of single nucleotide polymorphisms (tSNPs) in MTNR1B region and the occurrence of AIS was studied. METHOD: 473 AIS girls and 311 normal controls were recruited. The age range of the patients was between 10 and 18 years old. The maximum Cobb was recorded at latest follow-up in AIS patients. Three of five tSNPs were studied; they were all located within the coding region of the MTNR1B gene. RESULTS: There was no significant difference in the genotype or allelic frequencies (AF) of the 3 tSNPs between AIS and controls. In a case-only analysis, no difference in curve severity in AIS patients was found among patients with different genotypes (by one-way ANOVA). DISCUSSION: The 3 tSNPs showed no association with either the occurrence of AIS or the maximum Cobb angle within AIS girls. Further analysis of the remaining tSNPs within the regulatory region of the MTNR1B gene and other related genes in the melatonin signaling pathway may provide further information on the role of the melatonin in AIS girls.

Adolescent↗

PubMed2005

Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor.

AIMS/HYPOTHESIS: Proliferative diabetic retinopathy results from excess blood vessel growth into the vitreous fluid of the eye. Retinal angiogenesis is regulated by expression of vascular endothelial growth factor (VEGF), and many studies have shown that VEGF is critically involved in proliferative diabetic retinopathy. VEGF is alternatively spliced to form the angiogenic (VEGF(xxx)) and potentially anti-angiogenic (VEGF(xxx)b) family of isoforms. The VEGF(xxx)b family is found in normal tissues, but down-regulated in renal and prostate cancer. Previous studies on endogenous expression of VEGF in the eye have not distinguished between the two families of isoforms. METHODS: We measured VEGF(xxx)b isoform expression in normal human eye tissue (lens, sclera, retina and iris) and vitreous fluid using enzyme-linked immunosorbent assay and Western blotting with a VEGF(xxx)b-specific antibody. RESULTS: VEGF(xxx)b protein was expressed in lens, sclera, retina, iris and vitreous fluid. Multiple isoforms were seen, including VEGF(165)b, VEGF(121)b, VEGF(145)b, VEGF(183)b and VEGF(189)b. In non-diabetic patients, 64+/-7% of the VEGF in the vitreous was VEGF(xxx)b (n=18), whereas in diabetic patients only 12.5+/-3.6% of total VEGF was VEGF(xxx)b. CONCLUSIONS/INTERPRETATION: Since VEGF(xxx)b inhibits VEGF(xxx)-induced angiogenesis in a one-to-one stoichiometric manner, these results show that in the eye of diabetic patients VEGF splicing was switched from an anti-angiogenic to a pro-angiogenic environment. This occurred through changes to the ratio of VEGF(xxx):VEGF(xxx)b. Alterations to splicing, and through that to the balance of VEGF isoforms, could therefore be a potential therapeutic strategy for diabetic retinopathy.

Alternative Splicing↗

PubMed2005

Automatic wheeze detection based on auditory modelling.

Automatic wheeze detection has several potential benefits compared with reliance on human auscultation: it is experience independent, an automated historical record can easily be kept, and it allows quantification of wheeze severity. Previous attempts to detect wheezes automatically have had partial success but have not been reliable enough to become widely accepted as a useful tool. In this paper an improved algorithm for automatic wheeze detection based on auditory modelling is developed, called the frequency- and duration-dependent threshold algorithm. The mean frequency and duration of each wheeze component are obtained automatically. The detected wheezes are marked on a spectrogram. In the new algorithm, the concept of a frequency- and duration-dependent threshold for wheeze detection is introduced. Another departure from previous work is that the threshold is based not on global power but on power corresponding to a particular frequency range. The algorithm has been tested on 36 subjects, 11 of whom exhibited characteristics of wheeze. The results show a marked improvement in the accuracy of wheeze detection when compared with previous algorithms.

Algorithms↗

PubMed2005

Concentration and detection of SARS coronavirus in sewage from Xiao Tang Shan Hospital and the 309th Hospital of the Chinese People's Liberation Army.

A worldwide outbreak of severe acute respiratory syndrome (SARS) had been reported. Over 8439 SARS cases and 812 SARS-related deaths were reported to the World Health Organization from 32 countries around the world up to 5 July 2003. The mechanism of transmission of SARS-CoV has been limited only to close contacts with patients. Attention was focused on possible transmission by the sewage system because laboratory studies showed that patients excreted coronavirus RNA in their stools in Amoy Gardens in Hong Kong. To explore whether the stool of SARS patients or the sewage containing the stool of patients would transmit SARS-CoV or not, we used a style of electropositive filter media particle to concentrate the SARS-CoV from the sewage of two hospitals receiving SARS patients in Beijing, as well as cell culture, semi-nested RT-PCR and sequencing of genes to detect and identify the viruses from sewage. There was no live SARS-CoV detected in the sewage in these assays. The nucleic acid of SARS-CoV was found in the sewage before disinfection from both hospitals by PCR. After disinfection, SARS-CoV RNA could be detected from some samples from the 309th Hospital of the Chinese People's Liberation Army, but not from Xiao Tang Shan Hospital after disinfection. In this study, we found that the virus can survive for 14 days in sewage at 4 degrees C, 2 days at 20 degrees C, and its RNA can be detected for 8 days though the virus had been inactivated. In conclusion, this study demonstrates that the RNA of SARS-CoV could be detected from the concentrates of sewage of both hospitals receiving SARS patients before disinfection and occasionally after disinfection though there was no live SARS-CoV; thus much attention should be paid to the treatment of stools of patients and the sewage of hospitals receiving SARS patients.

Bacteriophages↗

PubMed2004

High-resolution study of spin excitations in the singlet ground state of SrCu2(BO3)2.

High-resolution, inelastic neutron scattering measurements on SrCu2(BO3)2, a realization of the Shastry-Sutherland model for two-dimensional Heisenberg antiferromagnets, reveal the dispersion of the three single triplet excitations continuously across the (H,0) direction within its tetragonal basal plane. These measurements also show distinct Q dependencies for the single and multiple triplet excitations, and that these excitations are largely dispersionless perpendicular to this plane. The temperature dependence of the intensities of these excitations is well described as the complement of the dc susceptibility of SrCu2(BO3)2.

Journal Article↗

PubMed2004

Orbital and Spin Chains in ZnV2O4.

Our powder inelastic neutron scattering data indicate that ZnV2O4 is a system of spin chains that are three-dimensionally tangled in the cubic phase above 50 K due to randomly occupied t(2g) orbitals of V3+ (3d(2)) ions. Below 50 K in the tetragonal phase, the chains become straight due to antiferro-orbital ordering. This is evidenced by the characteristic wave vector dependence of the magnetic structure factor that changes from symmetric to asymmetric at the cubic-to-tetragonal transition.

Journal Article↗

PubMed2004

Magnetic ordering in the spin-ice candidate Ho2Ru2O7.

Neutron scattering measurements on the spin-ice candidate material Ho2Ru2O7 have revealed two magnetic transitions at T approximately 95 and approximately 1.4 K to long-range ordered states involving the Ru and Ho sublattices, respectively. Between these transitions, the Ho3+ moments form short-ranged ordered spin clusters. The internal field provided by the ordered S=1 Ru4+ moments disrupts the fragile spin-ice state and drives the Ho3+ moments to order. We have directly measured a slight shift in the Ho3+ crystal field levels at 95 K from the Ru ordering.

Journal Article↗

PubMed2004

Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex modulates acute and chronic pain perception. The authors previously showed that rTMS over the primary motor cortex (M1) inhibited capsaicin-induced acute pain ascending through C-fibers. OBJECTIVE: To investigate the effects of 1-Hz rTMS over M1 on acute experimentally induced pain mediated by Adelta-fibers (i.e., another type of acute pain). METHODS: The authors examined whether rTMS over M1 affected laser evoked potentials (LEPs) in 13 normal subjects using thulium: yttrium-aluminum-garnet laser stimulation. Subjective pain-rating scores and LEPs obtained under three different conditions--rTMS, realistic sham stimulation, and a control condition with no stimulation--were compared. RESULTS: The authors found that 1-Hz rTMS over M1 significantly aggravated the subjective pain and enhanced the N2-P2 amplitudes compared with the sham or control sessions. Because the pain-rating scores and the N2-P2 amplitudes correlated positively, the N2-P2 amplitudes in the present study can be regarded as the cortical correlate of subjective pain. CONCLUSIONS: Together with the authors' previous study on C-fiber pain, this facilitatory effect of repetitive transcranial magnetic stimulation on Adelta-fiber-mediated further strengthens the notion of a relationship between repetitive transcranial magnetic stimulation over M1 and pain perception.

Acute Disease↗

PubMed2004

Emission direction of fast electrons in laser-solid interactions at intensities from the nonrelativistic to the relativistic.

The emission direction of outward-ejecting fast electrons generated in laser-solid interactions by 30 fs laser pulses is measured for laser intensities varying from the nonrelativistic to the relativistic. For an s-polarized incident laser beam at nonrelativistic intensities, the ejected electrons are close to the polarization direction of the laser beam. With the increase of the laser intensity, the ejected electrons are still mainly within the polarization plane, but turn away from the laser polarization direction towards the opposite direction of the incident laser beam. At relativistic intensities, electrons eject towards the direction of the reflected laser beam. The increasing ponderomotive force acceleration with the laser intensities might be responsible for the observed changes.

Journal Article↗

PubMed2004

Cortical responses to noxious stimuli during sleep.

We used magnetoencephalography to study effects of sleep on cortical responses to noxious stimuli and to clarify the mechanisms underlying pain perception. For a noxious stimulus, painful intra-epidermal electrical stimulation, which selectively activates A-delta fibers, was applied to the dorsum of the left hand. While awake, subjects were asked to count the number of stimuli silently (Attention) or ignore the stimuli (Control). During sleep, magnetic fields recorded in stage 1 sleep and stage 2 sleep were analyzed. One main component at a latency around 140-160 ms was identified in the awake condition. Multiple source analysis indicated that this main component was generated by activities in the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII) and insular cortex. The medial temporal area (MT) and cingulate cortex were activated later than the main component. Cortical responses in the contralateral SI, ipsilateral SII and MT, bilateral insula and cingulate cortex were significantly enhanced in Attention as compared with Control. The main component 1 M as well as later magnetic fields were markedly attenuated during sleep, suggesting that all these cortical areas are involved in pain cognition.

Attention↗

PubMed2004

Bipolar microscissors.

The authors present a novel bipolar-coagulation microscissors exclusively designed for microsurgical use which can be applied easily, safely and effectively. The device is particularly helpful in the management (coagulation and cutting) of cerebral microvessels during the resection of brain tumors rich in vascularity or AVMs. The advantages of the instrument are the avoidance of exchanges of bipolar and microscissors under the microscope, reduction of fatigue for the operator, and decreases of operative time and blood loss while still achieving a good result.

Astrocytoma↗