The ‘Galilean Style in Science’ and the Inconsistency of Linguistic Theorising

Chomsky’s principle of epistemological tolerance says that in theoretical linguistics contradictions between the data and the hypotheses may be temporarily tolerated in order to protect the explanatory power of the theory. The paper raises the following problem: What kinds of contradictions may be tolerated between the data and the hypotheses in theoretical linguistics? First a model of paraconsistent logic is introduced which differentiates between week and strong contradiction. As a second step, a case study is carried out which exemplifies that the principle of epistemological tolerance may be interpreted as the tolerance of week contradiction. The third step of the argumentation focuses on another case study which exemplifies that the principle of epistemological tolerance must not be interpreted as the tolerance of strong contradiction. The reason for the latter insight is the unreliability and the uncertainty of introspective data. From this finding the author draws the conclusion that it is the integration of different data types that may lead to the improvement of current theoretical linguistics and that the integration of different data types requires a novel methodology which, for the time being, is not available

The ‘Galilean Style in Science’ and the Inconsistency of Linguistic Theorising

Chomsky’s principle of epistemological tolerance says that in theoretical linguistics contradictions between the data and the hypotheses may be temporarily tolerated in order to protect the explanatory power of the theory. The paper raises the following problem: What kinds of contradictions may be tolerated between the data and the hypotheses in theoretical linguistics? First a model of paraconsistent logic is introduced which differentiates between week and strong contradiction. As a second step, a case study is carried out which exemplifies that the principle of epistemological tolerance may be interpreted as the tolerance of week contradiction. The third step of the argumentation focuses on another case study which exemplifies that the principle of epistemological tolerance must not be interpreted as the tolerance of strong contradiction. The reason for the latter insight is the unreliability and the uncertainty of introspective data. From this finding the author draws the conclusion that it is the integration of different data types that may lead to the improvement of current theoretical linguistics and that the integration of different data types requires a novel methodology which, for the time being, is not available

Gα11 mutation in mice causes hypocalcemia rectifiable by calcilytic therapy

Heterozygous germline gain-of-function mutations of G-protein subunit α11 (Gα11), a signaling partner for the calcium-sensing receptor (CaSR), result in autosomal dominant hypocalcemia type 2 (ADH2). ADH2 may cause symptomatic hypocalcemia with low circulating parathyroid hormone (PTH) concentrations. Effective therapies for ADH2 are currently not available and a mouse model for ADH2 would help in assessment of potential therapies. We hypothesised that a previously reported dark skin mouse mutant (Dsk7), which has a germline hypermorphic Gα11 mutation, Ile62Val, may be a model for ADH2 and allow evaluation of calcilytics, which are CaSR negative allosteric modulators, as a targeted therapy for this disorder. Mutant Dsk7/+ and Dsk7/Dsk7 mice were shown to have hypocalcemia and reduced plasma PTH concentrations, similar to ADH2 patients. In vitro studies showed the mutant Val62 Gα11 to upregulate CaSR-mediated intracellular calcium and MAPK signaling, consistent with a gain-offunction. Treatment with NPS-2143, a calcilytic compound, normalised these signaling responses. In vivo, NPS-2143 induced a rapid and marked rise in plasma PTH and calcium concentrations in Dsk7/Dsk7 and Dsk7/+ mice, which became normocalcemic. Thus, these studies have established Dsk7 mice, which harbor a germline gain-of-function Gα11 mutation, as a model for ADH2; and demonstrated calcilytics as a potential targeted therapy

СОВЕРШЕНСТВОВАНИЕ МОТИВАЦИИ РАБОТНИКОВ СЕЛЬСКОХОЗЯЙСТВЕННЫХ ОРГАНИЗАЦИЙ В КОНТЕКСТЕ РЕФОРМ АПК БЕЛАРУСИ

In the article modern market mechanisms of labour motivation in the agrarian sector are considered and assessed. The experience of the use of commercial calculation is generalized, and the ways of its improvement for the increase of economic efficiency of the performance of agricultural organizations are determined.В статье рассматриваются и оцениваются современные рыночные механизмы мотивации труда в аграрном секторе, обобщается опыт использования коммерческого расчета и определяются пути его совершенствования в современных условиях для повышения экономической эффективности деятельности сельско­хозяйственных организаций.

HOST GENETICS OF SUSCEPTIBILITY Mutations in genes underlying atypical familial mycobacteriosis are not found in tuberculosis patients from Siberian populations

s u m m a r y Objectives: Atypical familial mycobacteriosis (AFM, OMIM #209950) is caused by mutations in genes regulating IL12/IFNG pathway. Some of the mutations exhibit incomplete penetrance, and they have been proposed to be involved in the common (polygenic) predisposition to tuberculosis (TB). We set out to test this hypothesis in two populations from Siberian region of Russia with high prevalence of TB. Material and methods: The prevalence of twelve mutations in IL12/IFNG pathway genes of were analysed in 331 Russians and 238 Tuvinians TB patients and in 279 healthy Russians and 265 healthy Tuvinians. A screening for new mutations and rare polymorphisms was carried out in 10 children with severe generalized TB and severe BCG-vaccine complications using Sanger's bidirectional sequencing. Results: Twelve mutations most commonly identified in AFM patients appeared to be "wild-type" monomorphic in the studied groups. No new mutations or rare polymorphisms were identified by sequencing. However, 15 common single nucleotide polymorphisms were found, none of which was associated with TB after correction for multiple testing. Conclusion: The results of the study contradict with a hypothesis that mutations underlying AFM syndrome are involved in the predisposition to TB

Insights into corn genes derived from large-scale cDNA sequencing

We present a large portion of the transcriptome of Zea mays, including ESTs representing 484,032 cDNA clones from 53 libraries and 36,565 fully sequenced cDNA clones, out of which 31,552 clones are non-redundant. These and other previously sequenced transcripts have been aligned with available genome sequences and have provided new insights into the characteristics of gene structures and promoters within this major crop species. We found that although the average number of introns per gene is about the same in corn and Arabidopsis, corn genes have more alternatively spliced isoforms. Examination of the nucleotide composition of coding regions reveals that corn genes, as well as genes of other Poaceae (Grass family), can be divided into two classes according to the GC content at the third position in the amino acid encoding codons. Many of the transcripts that have lower GC content at the third position have dicot homologs but the high GC content transcripts tend to be more specific to the grasses. The high GC content class is also enriched with intronless genes. Together this suggests that an identifiable class of genes in plants is associated with the Poaceae divergence. Furthermore, because many of these genes appear to be derived from ancestral genes that do not contain introns, this evolutionary divergence may be the result of horizontal gene transfer from species not only with different codon usage but possibly that did not have introns, perhaps outside of the plant kingdom. By comparing the cDNAs described herein with the non-redundant set of corn mRNAs in GenBank, we estimate that there are about 50,000 different protein coding genes in Zea. All of the sequence data from this study have been submitted to DDBJ/GenBank/EMBL under accession numbers EU940701–EU977132 (FLI cDNA) and FK944382-FL482108 (EST)

Patients' and Observers' Perceptions of Involvement Differ. Validation Study on Inter-Relating Measures for Shared Decision Making

OBJECTIVE: Patient involvement into medical decisions as conceived in the shared decision making method (SDM) is essential in evidence based medicine. However, it is not conclusively evident how best to define, realize and evaluate involvement to enable patients making informed choices. We aimed at investigating the ability of four measures to indicate patient involvement. While use and reporting of these instruments might imply wide overlap regarding the addressed constructs this assumption seems questionable with respect to the diversity of the perspectives from which the assessments are administered. METHODS: The study investigated a nested cohort (N = 79) of a randomized trial evaluating a patient decision aid on immunotherapy for multiple sclerosis. Convergent validities were calculated between observer ratings of videotaped physician-patient consultations (OPTION) and patients' perceptions of the communication (Shared Decision Making Questionnaire, Control Preference Scale & Decisional Conflict Scale). RESULTS: OPTION reliability was high to excellent. Communication performance was low according to OPTION and high according to the three patient administered measures. No correlations were found between observer and patient judges, neither for means nor for single items. Patient report measures showed some moderate correlations. CONCLUSION: Existing SDM measures do not refer to a single construct. A gold standard is missing to decide whether any of these measures has the potential to indicate patient involvement. PRACTICE IMPLICATIONS: Pronounced heterogeneity of the underpinning constructs implies difficulties regarding the interpretation of existing evidence on the efficacy of SDM. Consideration of communication theory and basic definitions of SDM would recommend an inter-subjective focus of measurement. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN25267500

Молекулярно–генетические аспекты различных фенотипов хронической обструктивной болезни легких и бронхиальной астмы

Genetic aspects of different phenotypes of COPD and asthma.Молекулярно–генетические аспекты различных фенотипов хронической обструктивной болезни легких и бронхиальной астмы

CUT-PCR: CRISPR-mediated, ultrasensitive detection of target DNA using PCR

Circulating tumor DNA (ctDNA) has emerged as a tumor-specific biomarker for the early detection of various cancers. To date, several techniques have been devised to enrich the extremely small amounts of ctDNA present in plasma, but they are still insufficient for cancer diagnosis, especially at the early stage. Here, we developed a novel method, CUT (CRISPR-mediated, Ultrasensitive detection of Target DNA)-PCR, which uses CRISPR endonucleases to enrich and detect the extremely small amounts of tumor DNA fragments among the much more abundant wild-type DNA fragments by specifically eliminating the wild-type sequences. We computed that by using various orthologonal CRISPR endonucleases such as SpCas9 and FnCpf1, the CUT-PCR method would be applicable to 80% of known cancer-linked substitution mutations registered in the COSMIC database. We further verified that CUT-PCR together with targeted deep sequencing enables detection of a broad range of oncogenes with high sensitivity (<0.01%) and accuracy, which is superior to conventional targeted deep sequencing. In the end, we successfully applied CUT-PCR to detect sequences with oncogenic mutations in the ctDNA of colorectal cancer patients' blood, suggesting that our technique could be adopted for diagnosing various types of cancer at early stages

Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma