Machine learning algorithms predict experimental output of chaotic lasers.

We apply an artificial neural network (ANN) of 20 hidden layers and backpropagation regression to the forecast of experimental time series from a Kerr lens mode locking (KLM) Ti:sapphire laser and a Nd:vanadate with modulation losses. In both cases the neural network is able to predict up to 10 steps ahead. In the Ti:sapphire laser the prediction in pulse amplitude is accurate even when the pulse is an extreme event. In the Nd:vanadate laser we forecast both pulse amplitude and pulse-to-pulse time separation. In both cases the prediction goes beyond the Lyapunov prediction horizon.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

The association between 11C-methionine uptake, IDH gene mutation, and MGMT promoter methylation in patients with grade II and III gliomas.

AIM: To evaluate the association between 11C-methionine positron-emission tomography (11C-methionine PET) findings, isocitrate dehydrogenase (IDH) gene mutation, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with grade II and III gliomas. MATERIALS AND METHODS: Data were collected from 40 patients with grade II and III gliomas who underwent both magnetic resonance imaging (MRI) and 11C-methionine PET as part of their pre-surgical examination. IDH mutation was examined via DNA sequencing, and MGMT promoter methylation via quantitative methylation-specific polymerase chain reaction (PCR). RESULTS: A threshold of MGMT promoter methylation of 1% was significantly associated with tumour/normal tissue (T/N) ratio. The T/N ratio in samples with MGMT promoter methylation ≥1% was higher than that in samples with MGMT promoter methylation <1%, and the difference was statistically significant (p=0.011). Reliable prediction of MGMT promoter methylation (<1% versus ≥1%) was possible using the T/N ratio under the receiver operator characteristic (ROC) curve with a sensitivity and specificity of 75% each (cut-off value=1.6: p=0.0226, area under the ROC curve [AUC]=0.76172). Conversely, the T/N ratio had no association with IDH mutation (p=0.6). The ROC curve revealed no reliable prediction of IDH mutation using the T/N ratio (p=0.606, AUC=0.60577). CONCLUSION: 11C-methionine PET parameters can predict MGMT promoter methylation but not IDH mutation status. 11C-methionine uptake may have limited potential to reflect DNA methylation processes in grade II and III gliomas.

2D:4D and spatial abilities: From rats to humans.

Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.

Effect of vitamin D supplementation on pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b: a randomized controlled trial.

Chronic HCV-infected patients tend to have vitamin D deficiency, suggesting that vitamin D supplementation may enhance the efficacy of treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). We therefore assessed the effects of vitamin D supplementation on viral response to PEG-IFN/RBV. Eighty-four patients with HCV genotype 1b were randomized, 42 to oral vitamin D supplementation (1000 IU/day) and 42 to nonsupplementation (control), from week 8 to the end of PEG-IFN/RBV therapy. The primary end point was undetectable HCV RNA at week 24 (viral response [VR]). VR rate at week 24 was significantly higher in the vitamin D than in the control group (78.6% vs 54.8% P = 0.037). Adverse events were similar in both groups. When patients were subdivided by IL28B SNP rs8099917 genotype, those with the TT genotype group showed a significantly higher VR rate at week 24 with than without vitamin D supplementation (86.2% vs 63.3% vs P = 0.044). Although patients with the TG/GG genotype, who were relatively resistant to PEG-IFN treatment, had similar VR rates at week 24 with and without vitamin D supplementation, the decline in viral load from week 8 to week 24 was significantly greater with than without vitamin D supplementation. Multivariate analysis showed that rs8099917 genotype and vitamin D supplementation contributed significantly to VR at week 24. SVR rates were similar in the vitamin D and control groups [64.3% (27/42) vs 50% (21/42), P = 0.19]. Vitamin D supplementation may enhance the effects of PEG-IFN/RBV in HCV genotype 1b-infected patients.

Development of inverted pendulum thrust stand with spring-shaped wire for high power electric thrusters.

Pendulum thrust stands are used to measure the thrust of electric propulsion systems for spacecraft. A thruster is mounted on a pendulum and operated, and the pendulum displacement due to thrust is measured. In this type of measurement, the pendulum is also affected by nonlinear tensions due to wiring and piping that deteriorate the accuracy of the measurement. This influence cannot be ignored in high power electric propulsion systems because complicated piping and thick wirings are required. Therefore, to reduce the influence of tension due to wires and tubes, we developed an inverted pendulum-type thrust stand with pipes and wirings as springs. In this paper, we first derive the design guidelines for spring-shaped wires; the necessary conditions for sensitivity, responsivity, spring shape, and electric wire were formulated. Next, a thrust stand was designed and fabricated based on these guidelines, and the performance of the stand was evaluated through calibration and thrust measurements using a 1 kW-class magneto-plasma-dynamics thruster. The sensitivity of the thrust stand was 17 mN/V, the normalized standard deviation of the variation of the measured values owing to the structure of the thrust stand was 1.8 × 10-3, and the thermal drift during the long-time operation was ∼4.5 × 10-3 mN/s.

[Benign tracheal stenosis treated by T-tube in a patient with autism; report of a case].

A female with autism, aged over 40 years, who had been hospitalized in a nursing home, developed descending necrotizing mediastinitis requiring tracheostomy. Subsequently, tracheal stenosis was observed. She was referred to our hospital. T-tube therapy was selected, and there has been no recurrence during the 3-year follow-up. We report a patient in whom a T-tube was useful for treating benign tracheal stenosis in the presence of autism.

Suppression of hapten-specific delayed-type hypersensitivity responses in mice by idiotype-specific suppressor T cells after administration of anti-idiotypic antibodies.

Delayed-type hypersensitivity (DTH) responses specific for the phosphorylcholine (PC) hapten were induced in BALB/c mice by immunization with syngeneic peritoneal exudate cells (PEC) coupled with diazotized phenyl-phosphoryl-choline. PC-specific DTH responses were elicited in such immunized mice after footpad challenge with PC-derivatized syngeneic spleen cells. Moreover, PC-immune lymph node cells could passively transfer PC-specific DTH responses to naive BALB/c mice and it was possible to demonstrate that the cells responsible for such passively transferred responses were T lymphocytes. Because the T-15 idiotypic determinant displayed on the TEPC-15 PC-binding myeloma protein is known to be a dominant idiotype associated with anti-PC antibody responses in BALB/c mice, an analysis was made of the effects of anti-T-15 idiotypic antibodies on the induction and expression of murine PC-specific DTH responses. Repeated injections of anti-T-15 idiotypic antiserum, raised in A/J mice by immunization with TEPC-15 myeloma protein, into recipient BALB/c mice both immediately before and after sensitization with PC-PEC virtually abolished the development of PC-specific DTH responses. Although administration of anti-T-15 antiserum effectively inhibited the induction phase of PC-specific DTH responses, these anti-idiotypic antibodies had no suppressive activity at the effector phase of these responses. The inhibition observed with anti-T-15 antibodies was highly specific for the PC hapten, and for PC-specific DTH responses of BALB/c but not A/J mice. Studies were conducted to address the possibility that anti-Id treatment induced suppressor T lymphocytes capable of specifically inhibiting the activity of PC-specific T cells participating in DTH responses. The results demonstrate that idiotype-specific suppressor T cells are, indeed, induced by treatment with anti-Id; moreover, such suppressor T cells, once induced, are highly effective in abrogating both the induction and the effector phases of PC-specific T cell-mediated DTH responses in BALB/c mice.

Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells.

We have described here two distinct types of carrier-specific helper T cells which act independently and synergistically to augment the B-cell response to a hapten. They are separable by passage through a nylon wool column. The first type of helper T cell, which we designate as Th1, is nylon nonadherent, and can help the response of hapten-primed B cells only if the haptenic and carrier determinants are present on a single molecule (cognate interaction). The second type of helper T cell, Th2, adheres to the nylon wool column, and can help the B-cell response to a hapten coupled to a heterologous carrier upon stimulation with unconjugated relevant carrier (polyclonal interaction). The addition of a small number of Th2 to the mixture of Th1 and B cells significantly augmented the net response to the hapten carrier conjugate. Both Th1 and Th2 cells belong to the Lyt-1+,2-,3- subclass. Th1 has no detectable Ia antigen, whereas Th2 is killed by certain anti-Ia antisera and complement. The Ia antigen detected on Th2 was found to be controlled by a locus in the I-J subregion. The results clearly established the fact that there are two distinct pathways in the T- and B-cell collaboration, which involves two different subsets of carrier-specific helper T cells.

Stimulation of primary in vitro IgE antibody responses in culture of human peripheral mononuclear cells.

Experiments are presented herein that demonstrate the capacity to stimulate human peripheral mononuclear cells to synthesize and secrete significant quantities of IgE molecules in vitro by exposure to appropriate concentrations of 2,4-dinitrophenyl (DNP)-protein conjugates, pokeweed mitogen (PWM), or a combination of DNP-proteins and PWM. Cultures stimulated in this fashion synthesize increased quantities of both total IgE and DNP-specific IgE antibody molecules. This in vitro human IgE antibody system should provide a useful tool for further exploration of regulatory control of IgE responses in both normal humans and those manifesting various forms of IgE-mediated allergic disorders.

Monoclonal suppressor factor specific for lactate dehydrogenase B. I. Mechanism of interaction between the factor and its target cells.

Hybridomas secreting a monoclonal T suppressor-effector factor (TseF) were produced by fusion of a lactate dehydrogenase B (LDHB)-specific long-term T suppressor-effector (Tse) cell line with the BW5147 thymoma. A short exposure (4 h) to TseF completely suppresses the antigen-specific and A-restricted proliferation of LDHB-primed Lyt-1+2- [possibly helper (Th)] cells. The action of TseF on Th cells, as that of the Tse cells themselves, is antigen-specific and A-restricted. The interaction of TseF with Th cells involves two binding events, of which one occurs via antigen bridge, and the other represents the recognition of a factor-derived Ak-like moiety by the anti-Ak receptor of Th cells. The Ak-like moiety of the TseF carries the determinants that serve as restriction elements for antigen recognition by Th cells, and additional determinants demonstrable by T cell-specific monoclonal "anti-Ak" antibodies, however, it lacks serologically detectable determinants of the B cell-derived A alpha A beta class II Mhc molecules.

[Emergency operation and hypothermic therapy for Stanford type A acute aortic dissection in the state of coma].

We report of a 77-year-old woman who was admitted to our hospital in coma by emergency. A computed tomography scan revealed acute aortic dissection (Stanford type A). We established selective antegrade cerebral perfusion within 3 hours of the onset and then performed ascending aortic replacement. In the state of hypothermia (35 degrees C), the patient was weaned from cardiopulmonary bypass. The patient was kept hypothermic until the operation was completed. We kept mild hypothermia (34.5 degrees C) in intensive care unit (ICU) for 40 hours. The patient was extubated at 94 hours after the operation. The patient was discharged from the hospital on foot on postoperative day 21.

Far-reaching effects of the Hawaiian Islands on the Pacific Ocean-atmosphere system.

Using satellite data, we detected a wind wake trailing westward behind the Hawaiian Islands for 3000 kilometers, a length many times greater than observed anywhere else on Earth. This wind wake drives an eastward ocean current that draws warm water from the Asian coast 8000 kilometers away, leaving marked changes in surface and subsurface ocean temperature. Standing in the path of the steady trade winds, Hawaii triggers an air-sea interaction that provides the feedback to sustain the influence of these small islands over a long stretch of the Pacific Ocean.

Heterogeneous response of nasal and lung fibroblasts to transforming growth factor-beta 1.

BACKGROUND: Nasal polyposis is characterized by marked oedema, sparse extracellular matrix (ECM) and proliferating blood vessels. Pulmonary fibrosis is characterized by inflammatory cells accumulation, considerable ECM deposition and vascular abnormalities. Although lung fibrosis is not only and necessarily an inflammatory disorder, we hypothesized that the difference between nasal polyposis and pulmonary fibrosis may, in part, be due to the heterogeneity between nasal and lung fibroblasts. Fibroblasts participate in the inflammatory response by releasing ECM proteins and cytokines. TGF-beta is thought to participate in chronic inflammation and fibrosis. Myofibroblasts are the activated form of fibroblasts. A phenotypic hallmark of myofibroblasts is the expression of smooth muscle alpha-actin (SMA). OBJECTIVE: We examined whether there is any heterogeneity between nasal and lung fibroblasts upon stimulation with TGF-beta(1) with regard to the synthesis of SMA, pro-collagen type I and vascular endothelial growth factor (VEGF) as well as translocation of Smad proteins. METHODS: Fibroblasts lines were established from human biopsy tissue. The expression of SMA, pro-collagen type I, VEGF mRNA was evaluated by reverse transciptase RT-PCR. The amount of pro-collagen type I and VEGF was measured by ELISA. By immunocytochemistry, we analysed the expression of SMA and Smad2, 3, 4 in cultured fibroblasts. RESULTS: TGF-beta(1) induced SMA and pro-collagen type I synthesis in lung, but not in nasal fibroblasts. By contrast, TGF-beta(1) induced VEGF synthesis in both lung and nasal fibroblasts. After stimulation with TGF-beta(1), Smad2, 3, 4 were translocated from the cytoplasm to the nucleus in lung fibroblasts, whereas only Smad3 was translocated in nasal fibroblasts. CONCLUSION: These results establish the heterogeneous responsiveness of fibroblast populations in the airways to TGF-beta(1) and that such a heterogeneity may contribute, at least in part, to the different pathological outcomes of inflammation in the upper and lower airways.

Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis.

Systemic lupus erythematosus (SLE) is associated with the presence of complement proteins and immune complexes in affected organs. Since complement proteins are synthesized in hepatic and extrahepatic sites, we studied a murine model of SLE to ascertain the relative importance of local and humoral (liver) synthesis of complement. C3, C4, and C2 mRNA increase in kidney coincident with the development of nephritis in the MRL lpr/lpr mouse, a strain that spontaneously develops SLE. Two factor B messenger RNA transcripts are expressed in kidney and intestine; SLE nephritis is associated with decrease in the long factor B mRNA and increase in the short form. Increased local synthesis of C3 and B protein and a concomitant glomerular and renal interstitial macrophage infiltrate paralleled the increase in mRNA content in the (lpr/lpr) mice. In addition to kidney, an increase in C3, C4, C2 and factor B mRNA was noted in the lung, heart and intestine and to a lesser extent in liver of (lpr/lpr) in comparison to the MRL (+/+) animals. These results suggest that in SLE local expression of complement genes plays a role in the pathogenesis of chronic glomerulonephritis and in the autoimmune arteritis of other organs.

Evolution of the complement system.

The origin of the complement system is much more ancient than that of adaptive immunity, which is only found in jawed vertebrates. Recently, complement components of the alternative and lectin pathways have been identified in jawless fishes, and even in some deuterostome invertebrates. The primitive complement system of these animals is one of the most highly organized innate immune systems.

Complement-related serine proteases in tunicates and vertebrates.

Serum mannose-binding lectin binds to pathogens in association with a serine protease termed MASP, and in this form, plays a crucial role in innate immunity by activating complement in a manner similar to activation via the classical pathway. MASP, C1r and C1s belong to the same family of serine proteases. In addition to its presence in advanced species, MASP also exists in primitive life forms such as tunicates and may be an evolutionary prototype of this family.

Interleukin-1-mediated enhancement of mouse factor B gene expression via NF kappa B-like hepatoma nuclear factor.

Complement factor B, a serine protease playing a pivotal role in alternative pathway activation, is an acute-phase plasma protein. Previous studies have revealed that interleukin-1 (IL-1) mediates, at least in part, the acute-phase induction of factor B expression and that the IL-1-responsive element resides in the region between -553 and -478 relative to the transcription initiation site of the mouse factor B gene. In this paper, we demonstrate a specific binding site for a nuclear factor of human hepatoma HepG2 cells in this region of the factor B gene, using gel shift and methylation interference analysis. The nucleotide sequence of the binding site is closely similar to the NF kappa B or H2TF1 binding motif. The binding activity of HepG2 showed very similar specificity to that of NF kappa B or H2TF1, as shown by a competition binding assay, and was induced by IL-1 alpha treatment. A synthetic oligonucleotide corresponding to this binding site, as well as a similar sequence found in another class III complement C4 gene, conferred IL-1 responsiveness on the minimal factor B promoter. In contrast, a mutated oligonucleotide that could not bind to the HepG2 nuclear factor did not confer IL-1 responsiveness. These results suggest that IL-1 induces factor B expression via NF kappa B or a closely related factor in hepatocyte nuclei.

Cystic lymphangioma arising in the tip of the tongue in an adult.

Cystic lymphangioma is a benign malformation of the lymphatic channels. Most cystic lymphangiomas are present at birth and are usually diagnosed in infancy or early childhood. The head and neck region appears to be the favored site for cystic lymphangiomas. We present the first reported case of a cystic lymphangioma arising from the tip of the tongue in a 75-year-old male.

Induction of apoptosis by paclitaxel in human oral carcinoma cells.

The present study investigated induction of apoptosis in NB-1 oral carcinoma cells by paclitaxel and the expression of Bcl-2 and Bax in relation to this apoptotic cell death. Paclitaxel induced apoptotic cell death in NB-1 cells in a dose- and a time-dependent manner. The present results suggest that paclitaxel can induce apoptosis of NB-1 cells, which may be mediated by down-regulation of Bcl-2 together with up-regulation of Bax.