Exploiting Contextual Information for Prosodic Event Detection Using Auto-Context

Prosody and prosodic boundaries carry significant information regarding linguistics and paralinguistics and are important aspects of speech. In the field of prosodic event detection, many local acoustic features have been investigated; however, contextual information has not yet been thoroughly exploited. The most difficult aspect of this lies in learning the long-distance contextual dependencies effectively and efficiently. To address this problem, we introduce the use of an algorithm called auto-context. In this algorithm, a classifier is first trained based on a set of local acoustic features, after which the generated probabilities are used along with the local features as contextual information to train new classifiers. By iteratively using updated probabilities as the contextual information, the algorithm can accurately model contextual dependencies and improve classification ability. The advantages of this method include its flexible structure and the ability of capturing contextual relationships. When using the auto-context algorithm based on support vector machine, we can improve the detection accuracy by about 3% and F-score by more than 7% on both two-way and four-way pitch accent detections in combination with the acoustic context. For boundary detection, the accuracy improvement is about 1% and the F-score improvement reaches 12%. The new algorithm outperforms conditional random fields, especially on boundary detection in terms of F-score. It also outperforms an n-gram language model on the task of pitch accent detection

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma

We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G(4)S)(n) (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G(4)S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: [Formula: see text]. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity

Research Progress on the Fish Complement C3 Gene

Complement (C) is a serum protein with immunity-related functions and enzymatic activities. It can induce inflammatory responses and antibody formation following activation by substances such as pathogens. Moreover, it is a crucial molecule in the congenital immune defense system. Complement manifests earlier than immunoglobulin in the evolutionary process of fish's immune system. Therefore, the complement system of fish is vital for congenital and acquired immunities. A complement system is a polymolecule system comprising more than 30 soluble proteins, membrane-bound proteins, and complement receptors. It can be activated through three pathways for immunoregulation, the clearance of the immune complex, etc. The liver primarily produces the fish complement C3, which is a significant component of the complement system of fishes. C3 is the hub of three activation pathways. Research works concerning the structure, generation process, expression, and functions of C3 in fishes are reviewed in this study

Polycystic ovary syndrome in patients with epilepsy: A study in 102 Chinese women

AbstractPurposeThe incidence of polycystic ovary syndrome (PCOS) increases in women with epilepsy (WWE), which appears to vary with ethnicity. This study was conducted to determine the incidence and risk factors of PCOS in Chinese WWE.MethodsThe study was carried out in 102 of 139 Chinese WWE at reproductive ages, with 32 receiving valproic acid (VPA), 40 receiving other antiepileptic drugs (AEDs), and 30 without AEDs therapy. PCOS was defined as having 2 or more of the following components: polycystic ovaries, hyperandrogenism, and amenorrhoea or oligomenorrhoea (a/oligomenorrhoea).ResultsOne or more isolated components of PCOS were found in 56 (54.9%) patients, with 29 (28.4%) having polycystic ovaries, 20 (19.6%) with a/oligomenorrhea, 7 (6.9%) with hyperandrogenism, and 13 (12.7%) with defined PCOS. Their average age at the start of seizure was 13.8±6.5years, younger than that of patients without these disorders (16.9±8.6years, p<0.05). VPA therapy increased the incidence of PCOS (11/32, 34.4%), in addition to increased blood levels of testosterone and luteinizing hormone (LH) as well as LH to FSH (follicle-stimulating hormone) ratio. No significant relationship was found between the incidence of PCOS and the type, duration, or frequency of seizures in these WWE.ConclusionThere is an increased incidence of PCOS in Chinese WWE at reproductive ages, by more than 2 times of that in the general population. Risk factors include seizures starting at a young age and VPA therapy

Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B‐cell lymphoma

This phase 1b/2, multicenter, open‐label study evaluated ibrutinib plus durvalumab in relapsed/refractory follicular lymphoma (FL) or diffuse large B‐cell lymphoma (DLBCL). Patients were treated with once‐daily ibrutinib 560 mg plus durvalumab 10 mg/kg every 2 weeks in 28‐day cycles in phase 1b without dose‐limiting toxicities, confirming the phase 2 dosing. Sixty‐one patients with FL (n = 27), germinal center B‐cell (GCB) DLBCL (n = 16), non‐GCB DLBCL (n = 16), and unspecified DLBCL (n = 2) were treated. Overall response rate (ORR) was 25% in all patients, 26% in patients with FL, 13% in patients with GCB DLBCL, and 38% in patients with non‐GCB DLBCL. Overall, median progression‐free survival was 4.6 months and median overall survival was 18.1 months; both were longer in patients with FL than in patients with DLBCL. The most frequent treatment‐emergent adverse events (AEs) in patients with FL and DLBCL, respectively, were diarrhea (16 [59%]; 16 [47%]), fatigue (12 [44%]; 16 [47%]), nausea (9 [33%]; 12 [35%]), peripheral edema (7 [26%]; 13 [38%]), decreased appetite (8 [30%]; 11 [32%]), neutropenia (6 [22%]; 11 [32%]), and vomiting (5 [19%]; 12 [35%]). Investigator‐defined immune‐related AEs were reported in 12/61 (20%) patients. Correlative analyses were conducted but did not identify any conclusive biomarkers of response. In FL, GCB DLBCL, and non‐GCB DLBCL, ibrutinib plus durvalumab demonstrated similar activity to single‐agent ibrutinib with the added toxicity of the PD‐L1 blockade; the combination resulted in a safety profile generally consistent with those known for each individual agent.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152736/1/ajh25659_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152736/2/ajh25659.pd

Terlipressin May Decrease In-Hospital Mortality of Cirrhotic Patients with Acute Gastrointestinal Bleeding and Renal Dysfunction: A Retrospective Multicenter Observational Study

Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment. In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 μmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points. The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P < 0.001) and ICA-AKI stages 1B, 2, and 3 (11.1% vs. 2.8%, P = 0.011), but not any stage ICA-AKI (5.7% vs. 2.7%, P = 0.083). The in-hospital mortality was significantly decreased by terlipressin in patients with renal dysfunction (3.6% vs. 20.0%, P = 0.044), but not in those with any stage ICA-AKI (4.5% vs. 6.0%, P = 0.799) or ICA-AKI stages 1B, 2, and 3 (0.0% vs. 14.3%, P = 0.326). Renal dysfunction increased the in-hospital mortality of cirrhotic patients with acute GIB. Terlipressin might decrease the in-hospital mortality of cirrhotic patients with acute GIB and renal dysfunction. NCT03846180 ( https://clinicaltrials.gov )

Baicalin Depresses the Sympathoexcitatory Reflex Induced by Myocardial Ischemia via the Dorsal Root Ganglia

Myocardial ischemia (MI) is one of the major causes of death in cardiac diseases. Purinergic signaling is involved in bidirectional neuronal-glial communication in the primary sensory ganglia. The sensory neuritis of cardiac afferent neurons in cervical dorsal root ganglion (cDRG) interacts with cardiac sympathetic efferent postganglionic neurons, forming feedback loops. The P2Y12 receptor is expressed in satellite glial cells (SGCs) of DRG. Baicalin is a major active ingredient extracted from natural herbal medicines, which has anti-inflammatory and strong anti-oxidation properties. In this study we investigated the effect of baicalin on P2Y12 receptor in the cervical DRG SGC-mediated sympathoexcitatory reflex, which is increased during MI. The results showed that the expression of P2Y12 receptor mRNA and protein in DRG, and the co-localization values of P2Y12 receptor and glial fibrillary acidic protein (GFAP) in cDRG SGCs were increased after MI. The activated SGCs increased IL-1β protein expression and elevated Akt phosphorylation in cDRG. Baicalin treatment inhibited the upregulation of the P2Y12 receptor, GFAP protein and Akt phosphorylation in cDRG neurons/SGCs. The stellate ganglia (SG) affect cardiac sympathetic activity. Baicalin treatment also decreased the upregulation of the P2Y12 receptor, GFAP protein in the SG. The P2Y12 agonist, 2Me-SADP, increased [Ca2+]i in HEK293 cells transfected with the P2Y12 receptor plasmid and SGCs in cDRG. These results indicate that application of baicalin alleviates pathologic sympathetic activity induced by MI via inhibition of afferents in the cDRG

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

III IlIlIllIllIllIll 111111 Computation of Flutter of Turbomachinery Cascades Using a Parallel Unsteady Navier-Stokes Code

Abstract A quasi-three-dimensional multigrid Navier-Stokes solver on single and multiple passage domains is presented for solving unsteady flows around oscillating turbine and compressor blades. The conventional &quot;direct store&quot; method is used for applying the phase-shifted periodic boundary condition over a single blade passage. A parallel version of the solver using the Message Passing Interface (MPI) standard is developed for multiple passage computations. In the parallel multiple passage computations, the phase-shifted periodic boundary condition is converted to simple in-phase periodic condition. Euler and Navier-Stokes solutions are obtained for unsteady flows through an oscillating turbine cascade blade row with both the sequential and the parallel code. It is found that the parallel code offers almost linear speedup with multiple CPUs. In addition, significant improvement is achieved in convergence of the computation to a periodic unsteady state in the parallel multiple passage computations due to the use of in-phase periodic boundary conditions as compared to that in the single passage computations with phase-lagged periodic boundary conditions via the &quot;direct store&quot; method. The parallel Navier-Stokes code is also used to calculate the flow through an oscillating compressor cascade. Results are compared with experimental data and computations by other authors

Hot corrosion of borate melt and interface chemistry of borate-coated steel under tribological stimulation

Hot corrosion mechanism of Sodium Borate was investigated on mild-carbon steel at 800 °C by multiple surface characterizations. In addition, effects of tribological exposure on the interface chemistry were also examined in details by mean of ball-on-disk testing. The occurrence of interfacial reaction is characterized by the formation of a Sodium-rich film on the borate melt/oxide phase boundary. The basic dissolution reaction is accompanied by fluxing action of the protective scale in the case of static oxidation. External stressed shearing profoundly modifies the interface chemistry by establishing a hierarchical boundary film with remarkably low Oxygen density which renders improved oxidation resistance