Anomalous Josephson current through a topological noncoplanar ferromagnetic trilayer.

We present an anomalous Josephson effect in a TI-based Josephson junction with a ferromagnetic insulator (FI) trilayer which has noncoplanar magnetizations. It is shown that there exist equal fractional spin-singlet and -triplet correlations due to the magnetism-tuning chiral Dirac energy band structure. The consequent anomalous Josephson supercurrent is exhibited, in which a 0-πor similar 0-πstate transition through phase shift is induced only by exchange field strength of the first FI region, while theϕ0supercurrent and the maximum one gradually drop with the increase of exchange field strengths of the second and third FI regions without relative state transitions. With the increase of the FI region length, theϕ0supercurrent and the maximum one are also both decreased, are found, which is different from the situation for increasing the exchange filed strength. In addition, the corresponding free energies are presented and discussed.

Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China: an integrated data analysis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted.

Discrimination of novel bunyavirus infection using routine laboratory test.

The wide epidemic and high case fatality rate have made severe fever with thrombocytopenia syndrome (SFTS) a significant public health problem. The diagnosis and discrimination of SFTS virus (SFTSV) infection at an early stage of the disease is important for treatment choice. A prospective study was performed in an SFTS reference hospital during 2011-2013. Suspected SFTS patients were recruited and prospectively observed. Comparison between SFTSV-positive and -negative patients was made to identify the parameters that were related to positive detection by discriminant and classification tree analysis. A total of 538 SFTSV-positive and 396 negative patients were recruited and observed. Multiple logistic regression models demonstrated the significant parameters associated with positive detection, including decreased platelet counts and elevated aspartate aminotransferase (AST) level during the first stage (1∼4 days), decreased white blood cell and platelet counts, elevated creatine kinase (CK) and AST levels during the second stage (5∼7 days), and older age, decreased consciousness and elevated CK and AST during the third stage (8-11 days). The classification trees disclosed that the significant predictors for positive SFTSV detection were AST >50.6 U/L and AST/alanine transaminase (ALT) >1.3 at the first stage, CK >257 U/L or 57.7 U/L < CK ≤98.5 U/L with AST/ALT >1.6 at the second stage, as well as CK >630.7 U/L or 114.3 U/L < CK ≤630.7 U/L with decreased consciousness at the third stage. In making the clinically probable diagnosis of SFTS, the supplementation of AST and CK evaluations might remarkably improve the diagnostic capacity of routine laboratory tests, while the leukopenia is of limited use.

Identification of a major quantitative trait locus for ear size induced by space flight in sweet corn.

The development of molecular markers has contributed to progress in identifying the gene(s) responsible for favorable variations in maize studies. In this study, quantitative trait locus (QTL) mapping was conducted using simple sequence repeat markers in an F2 sweet corn population from a cross between parental line 1132 and space flight-induced mutant line 751 to identify the loci contributing to an increase in some yield traits. A primary mutated genomic region was located on chromosome 9. In total, 26 QTL were detected for eight yield-related traits and assembled into three clusters on chromosome 9. The largest QTL cluster at bin 9.02/03, primarily contributing to >10% of the phenotypic variation in ear and cob diameters, was likely due to a major QTL. Desired alleles of these QTL were provided by the mutant line 751. The primary action of the major mutant allele was an additive effect. Another mutant locus, which was induced in bin 9.01, increased cob and ear diameters by dominant genetic action.

Modified thoracoscopic versus minimally invasive oesophagectomy in curative resection of oesophageal cancer.

Conventional thoracoscopic oesophagectomy is time-consuming and requires sophisticated endoscopic skills. To reduce these problems we have modified the operating procedure, first by anastomosis of the oesophagus with the tubular stomach pulled up via the retrosternal route, followed by thoracoscopic oesophagectomy (modified thoracoscopic oesophagectomy). Outcomes were compared between the modified procedure and minimally invasive oesophagectomy. There were no significant differences in general preoperative clinical characteristics between the two patient groups. The modified thoracoscopic oesophagectomy group had significantly lower hospitalization expenses, significantly shorter operation times and significantly more lymph nodes removed compared with the minimally invasive oesophagectomy group, but there were no significant group differences in lengths of hospital and intensive care unit stays, morbidity and mortality. These results indicate that modified thoracoscopic oesophagectomy is feasible, simplifies operating procedures and reduces hospitalization expenses with acceptable morbidity.

Platelet-derived growth factor-AA mediates oligodendrocyte lineage differentiation through activation of extracellular signal-regulated kinase signaling pathway.

Platelet-derived growth factor-AA (PDGF-AA) has been used as a potent mitogen for the proliferation of oligodendrocyte progenitor cells (OPCs). Whether it plays a role in oligodendrocyte lineage differentiation of neural stem cells (NSCs) is unclear. Here we report that PDGF-AA is an instructional signal required for the differentiation of embryonic forebrain NSCs into O4-positive oligodendrocytes. Moreover, such PDGF-AA-induced oligodendrocyte differentiation appears to be mediated by the extracellular signal-regulated kinases 1 and 2 (Erk1/2) but not phosphatidylinositol-3 kinase (PI3K) pathway. Finally, PDGF-AA treatment resulted in a significant increase in the expression of the oligodendrocyte-specific transcriptional factor Olig2 in an Erk1/2-dependent mechanism at early stages of oligodendrogliogenesis. Together, our studies provide cellular and molecular evidence to suggest that PDGF-AA is a key molecule that regulates the differentiation of embryonic NSCs into oligodendrocytes. The action of PDGF-AA is mediated by the activation of Erk pathway which involves the downstream upregulation of transcriptional factor Olig2.

Glycosaminoglycan synthesis and secretion by the retinal pigment epithelium: polarized delivery of hyaluronan from the apical surface.

Hyaluronan and chondroitin sulfate glycosaminoglycan secretion from retinal pigment epithelial cells was established in confluent cultures with high transepithelial resistance. Cell cultures were maintained on Millicell-PCF culture plates, which allow separation of culture medium exposed to apical and basal epithelial surfaces. Following various times in culture, apical and basal culture media were sampled at three day intervals and the glycosaminoglycan content was quantified. Samples were digested with proteinase K to free the glycosaminoglycans from their core proteins, the glycosaminoglycans were ethanol precipitated, and subjected to hyaluronidase SD and chondroitinase ABC digestion to release hyaluronan and chondroitin sulfate disaccharides. Disaccharides were fluorotagged with 2-aminoacridone, separated on polyacrylamide gels and the molar fluorescence in each disaccharide band quantitated. Hyaluronan in the apical medium was significantly higher than in the basal medium (5-12 times) at all recovery intervals (P<0.0001). In contrast, the distribution of unsulfated chondroitin, 4-sulfated chondroitin and 6-sulfated chondroitin disaccharides in apical and basal media was non-polar. Confocal microscopy of cultures probed with a hyaluronan-specific fluorotag established that the HA evident in these cultures is restricted to the apical border of the RPE cultures. Collectively, these data indicate that hyaluronan synthesized by the retinal pigment epithelium is secreted preferentially from the apical surface, suggesting that this tissue is an important source of hyaluronan present in the interphotoreceptor matrix.

[Surgical treatment of 219 cases of primary tumor and cyst of the mediastinum].

Two hundred and nineteen patients with primary tumor and cyst in the mediastinum were retrospectively analysed. All patients received surgical treatment and pathologic examination. Results showed that: (1) the commonest mediastinal tumors was the thymoma (42.0%) (2) The second teratoma (20.1%). The incidence of neurogenic tumors was 16.4%. The over-all incidence of these three tumors was 78.5%. A total excision of the tumor was performed in 198 patients; incomplete excision was performed in 18 patients; 3 patients underwent biopsy only. The anatomic locations, clinical manifestations, complication and mortality of surgical treatment of these tumors were analysed.

[Surgical treatment of congenital heart defect complicating severe pulmonary infection in infants and young children].

OBJECTIVE: To review the experience of surgical management of left to right shunt congenital heart defect complicating severe pulmonary infection. METHOD: Twenty patients aged 4-17 months who weighed 3.6-11.6 kg were analysed. Among them, 16 underwent surgical treatment. RESULTS: The mortality rate of 4 who received conservative therapy was 75% (3/4). The mortality rate of the operative group 16 Cases, was 12. 5% (2/16), 14 were doing well by follow-up of 8-24 months. CONCLUSION: Infants of Congenital heart defect Complicating Severe Pulmonary infection, Should be performed operation actively.

[Repair of cardiac defects by minimal incision without aortic cross-clamp].

From July 1998 to June 1999, seventy two patients underwent repair of congenital heart defects by a partial sternal split and a limited skin incision(4-8 cm) under cardiopulmonary bypass without aortic cross-clamp at our institution. The average age of these patients was 4 years and 5 months(range: 7 months to 12 years), and the average weight was 15.6 kg(range: 7 kg to 30 kg). Fifty six patients had simple ventricular septal defects, sixteen suffered from atrial septal defects. The average bypass time was (21 +/- 20) min (range: 8-58 min). All patients recovered rapidly from the operation in an uneventful postoperative course. Our experience demonstrates that this technique is feasible and can be performed easily in young children with simple cardiac defects, and has excellent cosmetic results.

[Effects of aprotinin on TNF-alpha levels after cardiopulmonary bypass].

OBJECTIVE: This study evaluates the anti-inflammatory activity of full-dose and pump-prime-only(low-dose) aprotinin by means of comparing tumor necrosis factor alpha(TNF-alpha) levels of both groups after CPB. METHODS: Twenty-nine adults with rheumatic heart disease were randomized into three groups: (1) full-dose aprotinin-treated group(Group A, n = 10); (2) pump-prime-only aprotinin-treated group(Group B, n = 10), and (3) control group(Group C, n = 9). Plasma concentrations of TNF-alpha were measured by enzyme-linked immunosorbent assay technique at baseline(before operation), and at 2, 24 hours after CPB termination. RESULTS: A significant(P < 0.05) increase of TNF-alpha occurred in all three groups at 2 and 24 hours after CPB termination when compared with the same group at baseline. In Group A, TNF-alpha level was significantly lower than that in group C(P < 0.05) at 24 hours after CPB, but not in group B(P > 0.05). CONCLUSIONS: Both CPB and operative stimulus induce the increase of cytokine TNF-alpha after CPB. Full-dose aprotinin has the anti-inflammatory effect by means of reducing TNF-alpha level after CPB. Low-dose aprotinin dose not reduce TNF-alpha level. So it no significant anti-inflammatory effect.

[Surgical treatment for mitral valve prolapse].

OBJECTIVE: To determine the excellent operative procedure to treat mitral valve prolapse (MVP). METHODS: Fifty seven patients with MVP were divided into three groups: Group I received traditional chordal reconstruction; Group II underwent chordal replacement using expanded polytetrafluorethylene(e-PTFE) sutures and artificial ring valvuloplasty reconstruction; Group III submitted mitral valve replacement. RESULTS: Mitral regurgitation volume was reduced significantly in Group II [(1.3 +/- 3.8) ml] and Group III [(1.2 +/- 3.4) ml] than that in Group I [(4.7 +/- 7.7) ml] (P < 0.05). CONCLUSION: The utilization of e-PTFE sutures as artificial chordae and artificial ring valvuloplasty for MVP is a more reliable and safe procedure than traditional mitral valve reconstruction, and can avoid the complications of long term anticoagulant therapy after mechanical valve replacement.

Arginine activity in the proton-motive photocycle of bacteriorhodopsin: solid-state NMR studies of the wild-type and D85N proteins.

15N solid-state NMR (SSNMR) spectra of guanidyl-15N-labeled bacteriorhodopsin (bR) show perturbation of an arginine residue upon deprotonation of the retinal Schiff base during the photocycle. At the epsilon position, an upfield shift of 4 ppm is observed while the eta nitrogens develop a pair of 'wing' peaks separated by 24 ppm. Proton-driven spin diffusion between the two 'wing' peaks indicates that they arise from a single Arg residue. An unusually asymmetric environment for this residue is indicated by comparison with guanidyl-15N chemical shifts in a series of arginine model compounds. The 'wing' peaks are tentatively assigned to Arg-82 on the basis of the SSNMR investigations of the alkaline and neutral dark-adapted forms of the D85N bacteriorhodopsin mutant. Another, less asymmetric pair of eta signals, that is not affected by Schiff base deprotonation or D85 mutation, is tentatively assigned to Arg-134. The results are discussed in relation to existing models of bR structure and function.

Early and late M intermediates in the bacteriorhodopsin photocycle: a solid-state NMR study.

To enforce vectorial proton transport in bacteriorhodopsin (bR), it is necessary that there be a change in molecular structure between deprotonation and reprotonation of the chromophore-i.e., there must be at least two different M intermediates in the functional photocycle. We present here the first detection of multiple M intermediates in native wild-type bacteriorhodopsin by solid-state NMR. Illumination of light-adapted [zeta-15N-Lys]-bR at low temperatures shifts the 15N signal of the retinal Schiff base (SB) downfield by about 150 ppm, indicating a deprotonated chromophore. In 0.3 M Gdn-HCl at pH 10.0, two different M states are obtained, depending on the temperature during illumination. The M state routinely prepared at the lower temperature, Mo, decays to the newly observed M state, Mn, and the N intermediate, as the temperature is increased. Both relax to bR568 at 0 degreesC. A unique reaction sequence is derived: bR568-->Mo-->(Mn+N)-->bR568. Mo and Mn have similar chemical shifts at [12-13C]ret, [14-13C]ret, and [epsilon-13C]Lys216, indicating that Mn, like Mo, has a 13-cis and C=N anti chromophore. However, a small splitting in the [14-13C]ret signal of Mo reveals that it has at least two substates. The 7 ppm greater shielding of the SB nitrogen in Mn compared to Mo suggests an increase in basicity and/or hydrogen bonding. Probing the peptide backbone of the protein, via [1-13C]Val labeling, reveals a substantial structural change between Mo and Mn including the relaxation of perturbations at some sites and the development of new perturbations at other sites. The combination of the change in the protein structure and the increase in the pKa of the SB suggests that the demonstrated Mo-->Mn transition may function as the "reprotonation switch" required for vectorial proton transport.

The predischarge chromophore in bacteriorhodopsin: a 15N solid-state NMR study of the L photointermediate.

The L550 intermediate in the bacteriorhodopsin (bR) photocycle has drawn much attention with respect to the mechanism of light-driven proton transport because it selectively releases the Schiff base (SB) proton to the extracellular proton channel in the L-->M transition. Here we extend our solid-state NMR studies of bR photocycle intermediates to the L state. Under conditions that stabilize L550, a new SB signal is detected in the 15N NMR spectrum which disappears upon thermal relaxation. This signal is in the range for a protonated SB, but downfield from the SB signals of bR568 and N520. Since steric interactions would have the opposite effect on shielding, the data argue against a 13,14-dicis chromophore in L550. Comparison with the 15N chemical shifts of halide salts of protonated Schiff bases (pSB's) of retinal suggests that the interaction of the SB with its counterion is significantly stronger in L550 than in N520 (which in turn is stronger than in bR568). This is consistent with models of the early photocycle in which the electrostatic interaction between the SB and its counterion constitutes an important constraint. Although the L counterion interaction is comparable to that of a 6-s-trans,13-cis chloride salt, the visible spectrum is strongly red-shifted from the lambdamax = 491 nm of the chloride. This suggests some double bond strain in L550, particularly about the C=N bond. This strain is apparently gone in the N intermediate, which has a normal relationship between the 15N chemical shift and lambdamax. Such a relaxed chromophore is consistent with orientation of the SB proton toward the cytoplasmic surface in the N intermediate.

Chloride transport in cultured fetal human retinal pigment epithelium.

This study identifies bumetanide-sensitive chloride transport in cultured fetal human retinal pigment epithelium (RPE). Ion flux and electrophysiologic studies were performed on fetal human RPE grown to confluence on microporous culture wells mounted in modified Ussing chambers. Unidirectional transepithelial Cl- fluxes were measured along with the transepithelial potential (TEP), resistance (Rt), and short circuit current (Isc). In separate experiments the apical and basal membrane voltages (Vap and Vba) and membrane resistance ratio (Rap/Rba) were measured using standard electrophysiological techniques. The average electrical parameters under control conditions were TEP = 3.6 +/- 2.1 mV, Rt = 385 +/- 98 ohm cm2, and Isc = 8.8 +/- 3.6 microA cm-2. Apical bumetanide (10(-5) M) reduced the TEP and Isc an average of 0.6 +/- 0.4 mV and 1.6 +/- 0.8 microA cm-2, respectively. Under open-circuit conditions, we measured a net apical to basal 36Cl flux of 0.30 microEq cm-2 hr-1. Bumetanide reduced this net Cl- flux by 83% by reducing the unidirectional apical-to-basal Cl- flux. Apical bumetanide hyperpolarized Vba from -58 +/- 14 to -66 +/- 17 mV and reduced Rap/Rba from 1.17 +/- 0.50 to 0.85 +/- 0.38, consistent with blockade of Cl- uptake and reduction of the Cl- equilibrium potential at a basal membrane Cl- channel. Basal bumetanide had no effect on electrical parameters. We identified a bumetanide sensitive Cl- uptake mechanism at the apical membrane which may represent the Na-K-2Cl cotransporter reported in explant and other cultured preparations of mammalian RPE.

Potassium conductances in cultured bovine and human retinal pigment epithelium.

PURPOSE: To identify K+ conductances on the apical and basolateral membranes in cultured monolayers of fetal bovine and human retinal pigment epithelium (RPE). METHODS: Bovine and human RPE cells were grown on a permeable substrate for an average of 4 and 25 months, respectively, mounted in a modified Ussing chamber that allowed rapid solution changes at both membranes, and perfused with modified Ringer's solutions. Conventional microelectrode recording techniques were used to record intracellularly from RPE cells. RESULTS: Electrical parameters under control conditions for bovine (n = 11) and human (n = 7) cultures respectively, were: transepithelial potential, 0.6 +/- 0.2 and 3.2 +/- 0.5 mV; Rt, 70 +/- 12 and 227 +/- 30 ohm.cm2; and Vap, -61 +/- 3 and -51 +/- 2 mV (mean +/- SEM). The relative K+ conductance (TK) was estimated from responses to 10-fold increases in [K+]o. For the apical and basal membranes, the values for TK were 0.65 and 0.37, respectively, in bovine and 0.33 and 0.45, respectively, in human RPE. Barium applied to either surface of the cultures produced membrane depolarizations and suppressed the responses significantly to K+. In bovine, a 10-fold decrease in basal [K+]o hyperpolarized Vba by 2 +/- 1 mV; a similar decrease in apical [K+]o hyperpolarized Vap by 14 +/- 1 mV. At both membranes, perfusion with Ba2+ unmasked a significant membrane depolarization induced by lowering [K+]o; this phenomenon, observed previously at the apical membrane in fresh explant bovine, frog, and toad RPE, appears to be an unmasking of Na+/K+ pump modulation by K+. CONCLUSIONS: These results indicate the presence of Ba2+ sensitive K+ conductances at the apical and basal membranes of confluent monolayers of cultured fetal human and bovine RPE and the presence of Na+/K+ pump sites at both membranes of cultured bovine cells.

[Timing of radical operation on Hirschsprung's disease in newborns].

From June 1987 to June 1993, 42 neonates with Hirschsprung's disease (NHD) were treated with modified Duhamel's procedure. The follow-up from 2 months to 5 years (mean 30 mons) showed satisfactory results in all survivors. Comparing with 21 infants with Hirschsprung's disease treated (IHD) with modified Swenson's method showed that: (1) The follow-up results of NHD were better than IHD; (2) The extent and degree of hypertrophy and dilatation of proximal and transitional segment were less serious in NHD and the length of resection was shorter than that of IHD (NHD: 14.5-24.1 cm, IHD: 33-40.5 cm); (3) The degree of pathological changes such as mucosal inflammation, ulcer formation, and degeneration of ganglion cells was related to the age, duration and the length of agangliosis. Hirschsprung's disease has a chronic progressive course. Early operation can decrease the secondary structural and functional damage to the intestine.

Localization of NaK ATPase on cultured human retinal pigment epithelium.

PURPOSE: To localize NaK ATPase sites on cultured human retinal pigment epithelium (RPE). METHODS: Cultured human RPE from fetal, 2-year-old, and 21-year-old donors was grown to confluence in microporous culture wells for 4 months to 2 years, mounted in a small-volume Ussing chamber, and perfused with growth medium. Ouabain (10(-5)-M) was applied to the basal and apical sides of the RPE. Changes in transepithelial resistance (Rt), transepithelial potential (TEP), and apical and basal membrane potentials were measured. RESULTS: Application of ouabain to the basal side of RPE produced a small sustained increase in TEP after 6 minutes and, simultaneously, small depolarizations of both apical and basal membranes. During the continued presence of ouabain on the basal side, application of ouabain to the apical side produced a significantly larger TEP decrease and greater depolarization of both membranes. Significant changes in Rt were not observed. CONCLUSIONS: These results indicate that NaK ATPase sites are present on both the apical and basolateral membranes of cultured human RPE. The greater effect of ouabain when applied to the apical side suggests that functional NaK ATPase sites are more abundant on the apical membrane.