Characteristics of Nasal Resonance and Perceptual Rating in Prelingual Hearing Impaired Adults

ObjectivesResonance problems in hearing impaired (HI) individuals have been described as aspects of nasality. However, there are limitations in being able to explain the range of resonance problems. Therefore, this study suggests a perceptual rating that will effectively explain the characteristics of resonance problems in HI individuals.MethodsNasalance scores were obtained from 32 subjects in each of HI and normal hearing (NH) groups using a nasometer. The subjects were categorized into groups based on normal and abnormal nasalance ranges. The abnormal nasalance range group was further divided into hyper-, hypo-, and mixed-nasal groups. Nasalance scores were based the individuals performance in a series of passage and syllable tasks. The perceptual rating was evaluated using a newly introduced tool, 'vertical focus of resonance' (VFR), which focuses on the resonance energy in the frontal, throat, pharyngeal and nasal locations.ResultsThe NH group demonstrated a significantly lower nasalance score in the oral coupling and passage tasks than the HI group. Based on the results of nasalance correlation analysis, the HI group showed highly significant correlations between syllable and passage tasks, as contrasted with the NH group. There were significant differences in VFR between the nasalance types in both the NH and the HI groups.ConclusionThe HI hyper-nasal group showed tendencies of velopharyngeal opening, as opposed to the HI hypo-nasal group which showed tendencies of velopharyngeal closure. The HI mixed-nasal group showed inappropriate coordination of velopharyngeal function. In the HI group, the results of VFR showed that the air flow and the resonance energy were not released from the cavity of resonance. The suggested VFR tool explains the focusing characteristics of resonance energy within a continuation of speech sound regardless of the phonetic environment. Therefore, VFR may be a useful tool in explaining the deviant resonance patterns of HI individuals

Compare and Contrast: How to Assess the Completeness of Mechanistic Explanation

Opponents of the new mechanistic account of scientific explanation argue that the new mechanists are committed to a ‘More Details Are Better’ claim: adding details about the mechanism always improves an explanation. Due to this commitment, the mechanistic account cannot be descriptively adequate as actual scientific explanations usually leave out details about the mechanism. In reply to this objection, defenders of the new mechanistic account have highlighted that only adding relevant mechanistic details improves an explanation and that relevance is to be determined relative to the phenomenon-to-be-explained. Craver and Kaplan (B J Philos Sci 71:287–319, 2020) provide a thorough reply along these lines specifying that the phenomena at issue are contrasts. In this paper, we will discuss Craver and Kaplan’s reply. We will argue that it needs to be modified in order to avoid three problems, i.e., what we will call the Odd Ontology Problem, the Multiplication of Mechanisms Problem, and the Ontic Completeness Problem. However, even this modification is confronted with two challenges: First, it remains unclear how explanatory relevance is to be determined for contrastive explananda within the mechanistic framework. Second, it remains to be shown as to how the new mechanistic account can avoid what we will call the ‘Vertical More Details are Better’ objection. We will provide answers to both challenges

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC

Mutator Suppression and Escape from Replication Error–Induced Extinction in Yeast

Cells rely on a network of conserved pathways to govern DNA replication fidelity. Loss of polymerase proofreading or mismatch repair elevates spontaneous mutation and facilitates cellular adaptation. However, double mutants are inviable, suggesting that extreme mutation rates exceed an error threshold. Here we combine alleles that affect DNA polymerase δ (Pol δ) proofreading and mismatch repair to define the maximal error rate in haploid yeast and to characterize genetic suppressors of mutator phenotypes. We show that populations tolerate mutation rates 1,000-fold above wild-type levels but collapse when the rate exceeds 10−3 inactivating mutations per gene per cell division. Variants that escape this error-induced extinction (eex) rapidly emerge from mutator clones. One-third of the escape mutants result from second-site changes in Pol δ that suppress the proofreading-deficient phenotype, while two-thirds are extragenic. The structural locations of the Pol δ changes suggest multiple antimutator mechanisms. Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer

Changes of T-lymphocyte subpopulation and differential expression pattern of the T-bet and GATA-3 genes in diffuse large B-cell lymphoma patients after chemotherapy

BACKGROUND AND OBJECTIVE: T cell-mediated immunity plays an important role in enhancing antitumor response.This study aimed to investigate the changes in the T-lymphocyte subpopulation and to characterize the differential expression pattern of corresponding regulatory genes in peripheral blood mononuclear cells (PBMCs) from diffuse large B cell lymphoma (DLBCL) patients before and after chemotherapy. METHODS: A total of 56 DLBCL patients were recruited for analysis of T-cell subset distribution in the peripheral blood using flow cytometry; serum interferon (IFN)-γ and interleukin (IL)-4 levels using enzyme-linked immunosorbent assays; and early growth response protein 1 (EGR-1), T-bet, GATA-binding protein 3 (GATA-3), and transforming growth factor (TGF)-β mRNA levels using quantitative reverse-transcription polymerase chain reaction. Twenty-six healthy subjects served as controls. RESULTS: The percentage of CD3(+)CD4(+)T lymphocytes in peripheral blood from DLBCL patients was significantly decreased, whereas the percentages of CD3(+)CD8(+)T and CD4(+)CD25(+)T cells were significantly increased compared to those in controls (p < 0.05). Serum levels of IFN-γ and IL-4 were also significantly lower in DLBCL patients than those in controls (p < 0.05), and the levels of EGR-1, T-bet, and GATA-3 mRNA in PBMCs were lower (2.69 ± 1.48, 9.43 ± 2.14, and 20.83 ± 9.05 fold, respectively) in DLBCL patients than those in controls. Furthermore, there was a positive association between the levels of EGR-1 and T-bet mRNA (p = 0.001). However, the level of TGF-β mRNA was significantly increased in DLBCL patients, which was inversely associated with the T-bet mRNA level (p = 0.008), but positively associated with the percentage of T regulatory cells in PBMCs (p = 0.011). After three cycles of chemotherapy, the distribution of T-lymphocyte subsets in DLBCL patients were changed, and the levels of EGR-1, T-bet, and GATA-3 mRNA were significantly increased (p < 0.05) compared to those before chemotherapy. CONCLUSIONS: These results demonstrate the changes in T-lymphocyte subpopulations and the altered expression 34 pattern of the corresponding regulatory genes in PBMCs from DLBCL patients after chemotherapy, which are associated with the response of patients to treatment. The preferential expression of the T-bet gene after chemotherapy was closely correlated with the increased expression of the EGR-1 gene and decreased expression of the TGF-β gene

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

A 2D dislocation dynamic approach to simulating dimensional change in irradiated graphite using anisotropic strain theory

A program using two-dimensional dislocation dynamics with anisotropic strain equations has been written to simulate the dimensional change and stored elastic energy of irradiated graphite. A dislocation based model is put forward as a vehicle for both the longstanding atomic displacement model for dimensional change in irradiated graphite and a new model based on basal slip. As expected the introduction of prismatic dislocation loops (climb dipoles in 2D) results in the expansion of the graphite crystal in the c-axis direction. Interestingly the stored elastic energy of the system was found to increase with number of dislocation dipoles and reached a maximum at the density which Burakovsky et al. (Phys. Rev. B 61, 15011-15018 (2000) [1]) predicted for melting. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

A 2D dislocation dynamic approach to simulating dimensional change in irradiated graphite using anisotropic strain theory

A program using two-dimensional dislocation dynamics with anisotropic strain equations has been written to simulate the dimensional change and stored elastic energy of irradiated graphite. A dislocation based model is put forward as a vehicle for both the longstanding atomic displacement model for dimensional change in irradiated graphite and a new model based on basal slip. As expected the introduction of prismatic dislocation loops (climb dipoles in 2D) results in the expansion of the graphite crystal in the c-axis direction. Interestingly the stored elastic energy of the system was found to increase with number of dislocation dipoles and reached a maximum at the density which Burakovsky et al. (Phys. Rev. B 61, 15011-15018 (2000) [1]) predicted for melting. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim