RetinaNet Object Detector based on Analog-to-Spiking Neural Network Conversion

The paper proposes a method to convert a deep learning object detector into an equivalent spiking neural network. The aim is to provide a conversion framework that is not constrained to shallow network structures and classification problems as in state-of-the-art conversion libraries. The results show that models of higher complexity, such as the RetinaNet object detector, can be converted with limited loss in performance.Comment: 5 pages, submitted to ISCMI 2021 conferenc

Plant proteinaceous inhibitors of proteinases and alpha-amylases

Plant proteins which are inhibitory towards various types of enzymes from a wide range of organisms have been extensively studied for many years. Proteinas e inhibitors have received particular attention and accordingly a number of reviews concerning their structure, activity, evolution, possible physiological roles and nutritional properties have appeared regularly in the literature (Ryan, 1973, 1981, 1984; Laskowski and Kato, 1980; Richardson, 1981; Boisen, 1983). Recent technical advances in molecular biology have accelerated the output of information about these inhibitors to the extent that entirely new types have been uncovered and previously unsuspected relationships have been established. These developments justify the present review that will emphasize the novel aspects, glossing over many important topics that have been adequately covered before. Among the most striking recent findings is the structural and evolutionary relationships of different ct-amylase inhibitors with different types of proteinase inhibitors, which is the reason for their joint consideration in this survey

Genetics of the alpha-amylase/trypsin inhibitor family in wheat and related species

Several members of an inhibitor family of heterologous a-amylases and of trypsin have been isolated from wheat, barley and rye endosperms. Comparisons of the amino acid sequences of these inhibitors together with the chromosomal locations of their structural genes in the three species, indícate that they are encoded by a disperse multi-gene family that must have originated both by translocations and intrachromosomal duplications events that took place in common ancestors of wheat, barley and probably rye. Homology among some members of the inhibitor family and various proteins of maize, ragi, castor bean and others, indícate that this protein family extends to other phylogenetically distant species

Polyadenylation site heterogeneity in mRNA encoding the precursor of the barley toxin β-hordothionin

Two cDNA clones, pTH2 and pTH3, encoding the precursor of the barley toxin β-hordothionin have been identified and their nucleotide sequences determined. These sequences are identical, except that pTH2 is 22 bp longer than pTH3 at the 5'-end and that the cleavage/poly(A) site of the mRNA represented by pTH3 is 4 positions further downstream from the single 5'-AAUAAA-3' polyadenylation signal than that of the pTH2 mRNA. In contrast, the cleavage/poly(A) site of the α-hordothionin mRNA is 30 positions downstream from a second polyadenylation signal. The deduced amino acid sequence of the β-hordothionin precursor differs from that of α-hordothionin at 13 out of 127 positions

Trypsin/α-amylase inhibitors and thionins: possible defence proteins from barley

This chapter reviews recent work on the trypsin/α-amylase inhibitor and thionin protein families. The genomic distribution of protein genes in barley and related species, gene expression and in vitro activities are considered. Some of the evidence of a possible defence role against stored products pests for inhibitors and thionins is briefly discusse

Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide

Cancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments

Health Benefits of an Innovative Exercise Program for Mitochondrial Disorders

Purpose We determined the effects of an innovative 8-wk exercise intervention (aerobic, resistance, and inspiratory muscle training) for patients with mitochondrial disease. Methods Several end points were assessed in 12 patients (19–59 yr, 4 women) at pretraining, posttraining, and after 4-wk detraining: aerobic power, muscle strength/power and maximal inspiratory pressure (main end points), ability to perform activities of daily living, body composition, quality of life, and blood myokines (secondary end points). Results The program was safe, with patients’ adherence being 94% ± 5%. A significant time effect was found for virtually all main end points (P ≤ 0.004), indicating a training improvement. Similar findings (P ≤ 0.003) were found for activities of daily living tests, total/trunk/leg lean mass, total fat mass, femoral fracture risk, and general health perception. No differences were found for blood myokines, except for an acute exertional increase in interleukin 8 at posttraining/detraining (P = 0.002) and in fatty acid binding protein 3 at detraining (P = 0.002). Conclusions An intervention including novel exercises for mitochondrial disease patients (e.g., inspiratory muscle training) produced benefits in numerous indicators of physical capacity and induced a previously unreported shift toward a healthier body composition phenotype

What Lies behind the Wish to Hasten Death? A Systematic Review and Meta-Ethnography from the Perspective of Patients

BACKGROUND: There is a need for an in-depth approach to the meaning of the wish to hasten death (WTHD). This study aims to understand the experience of patients with serious or incurable illness who express such a wish. METHODS AND FINDINGS: Systematic review and meta-ethnography of qualitative studies from the patient's perspective. Studies were identified through six databases (ISI, PubMed, PsycINFO, CINAHL, CUIDEN and the Cochrane Register of Controlled Trials), together with citation searches and consultation with experts. Finally, seven studies reporting the experiences of 155 patients were included. The seven-stage Noblit and Hare approach was applied, using reciprocal translation and line-of-argument synthesis. Six main themes emerged giving meaning to the WTHD: WTHD in response to physical/psychological/spiritual suffering, loss of self, fear of dying, the desire to live but not in this way, WTHD as a way of ending suffering, and WTHD as a kind of control over one's life ('having an ace up one's sleeve just in case'). An explanatory model was developed which showed the WTHD to be a reactive phenomenon: a response to multidimensional suffering, rather than only one aspect of the despair that may accompany this suffering. According to this model the factors that lead to the emergence of WTHD are total suffering, loss of self and fear, which together produce an overwhelming emotional distress that generates the WTHD as a way out, i.e. to cease living in this way and to put an end to suffering while maintaining some control over the situation. CONCLUSIONS: The expression of the WTHD in these patients is a response to overwhelming emotional distress and has different meanings, which do not necessarily imply a genuine wish to hasten one's death. These meanings, which have a causal relationship to the phenomenon, should be taken into account when drawing up care plans

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study

Background: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability.Aims: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome.Methods: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed.Results: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300 mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24 h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality.Conclusions: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE

An international consensus definition of thewish to hasten death and Its related factors

Abstract Background The desire for hastened death or wish to hasten death (WTHD) that is experienced by some patients with advanced illness is a complex phenomenon for which no widely accepted definition exists. This lack of a common conceptualization hinders understanding and cooperation between clinicians and researchers. The aim of this study was to develop an internationally agreed definition of the WTHD. Methods Following an exhaustive literature review, a modified nominal group process and an international, modified Delphi process were carried out. The nominal group served to produce a preliminary definition that was then subjected to a Delphi process in which 24 experts from 19 institutions from Europe, Canada and the USA participated. Delphi responses and comments were analysed using a pre-established strategy. Findings All 24 experts completed the three rounds of the Delphi process, and all the proposed statements achieved at least 79% agreement. Key concepts in the final definition include the WTHD as a reaction to suffering, the fact that such a wish is not always expressed spontaneously, and the need to distinguish the WTHD from the acceptance of impending death or from a wish to die naturally, although preferably soon. The proposed definition also makes reference to possible factors related to the WTHD. Conclusions This international consensus definition of the WTHD should make it easier for clinicians and researchers to share their knowledge. This would foster an improved understanding of the phenomenon and help in developing strategies for early therapeutic intervention