169 research outputs found
Expert System for Mine Supervising Staff Fire Hazard Monitoring and Fire - Fighting
The paper presents the functions of an expert system designed for mine supervising staff responsible for fire hazard monitoring and fire-fighting. The essence of the system is to gather the complete data from hazard monitoring systems and the results of manual measurements made by ventilation staff in a common database. The database can be used for analysis and engineering calculation employed in mine ventilation supervision and also for the prevention against natural hazards, in particular fire and methane. Hardware and software tools developed within the framework of the system will also be used during rescue operation
Modelling hCDKL5 heterologous expression in bacteria
hCDKL5 refers to the human cyclin-dependent kinase like 5 that is primarily expressed in the brain. Mutations in its coding sequence are often causative of hCDKL5 deficiency disorder, a devastating neurodevelopmental disorder currently lacking a cure. The large-scale recombinant production of hCDKL5 is desirable to boost the translation of preclinical therapeutic approaches into the clinic. However, this is hampered by the intrinsically disordered nature of almost two-thirds of the hCDKL5 sequence, making this region more susceptible to proteolytic attack, and the observed toxicity when the enzyme is accumulated in the cytoplasm of eukaryotic host cells. The bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) is the only prokaryotic host in which the full-length production of hCDKL5 has been demonstrated. To date, a system-level understanding of the metabolic burden imposed by hCDKL5 production is missing, although it would be crucial for upscaling of the production process. Here, we combined experimental data on protein production and nutrients assimilation with metabolic modelling to infer the global consequences of hCDKL5 production in PhTAC125 and to identify potential overproduction targets. Our analyses showed a remarkable accuracy of the model in simulating the recombinant strain phenotype and also identified priority targets for optimised protein production
Personality, gender, and age in the language of social media: the open-vocabulary approach
We analyzed 700 million words, phrases, and topic instances collected from the Facebook messages of 75,000 volunteers, who also took standard personality tests, and found striking variations in language with personality, gender, and age. In our open-vocabulary technique, the data itself drives a comprehensive exploration of language that distinguishes people, finding connections that are not captured with traditional closed-vocabulary word-category analyses. Our analyses shed new light on psychosocial processes yielding results that are face valid (e.g., subjects living in high elevations talk about the mountains), tie in with other research (e.g., neurotic people disproportionately use the phrase âsick ofâ and the word âdepressedâ), suggest new hypotheses (e.g., an active life implies emotional stability), and give detailed insights (males use the possessive âmyâ when mentioning their âwifeâ or âgirlfriendâ more often than females use âmyâ with âhusbandâ or 'boyfriendâ). To date, this represents the largest study, by an order of magnitude, of language and personalit
Development of a Human Cytomegalovirus (HCMV)-Based Therapeutic Cancer Vaccine Uncovers a Previously Unsuspected Viral Block of MHC Class I Antigen Presentation
Human cytomegalovirus (HCMV) induces a uniquely high frequency of virus-specific effector/memory CD8+ T-cells, a phenomenon termed âmemory inflationâ. Thus, HCMV-based vaccines are particularly interesting in order to stimulate a sustained and strong cellular immune response against cancer. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high lethality and inevitable relapse. The current standard treatment does not significantly improve the desperate situation underlining the urgent need to develop novel approaches. Although HCMV is highly fastidious with regard to species and cell type, GBM cell lines are susceptible to HCMV. In order to generate HCMV-based therapeutic vaccine candidates, we deleted all HCMV-encoded proteins (immunoevasins) that interfere with MHC class I presentation. The aim being to use the viral vector as an adjuvant for presentation of endogenous tumor antigens, the presentation of high levels of vector-encoded neoantigens and finally the repurposing of bystander HCMV-specific CD8+ T cells to fight the tumor. As neoantigen, we exemplarily used the E6 and E7 proteins of human papillomavirus type 16 (HPV-16) as a non-transforming fusion protein (E6/E7) that covers all relevant antigenic peptides. Surprisingly, GBM cells infected with E6/E7-expressing HCMV-vectors failed to stimulate E6-specific T cells despite high level expression of E6/E7 protein. Further experiments revealed that MHC class I presentation of E6/E7 is impaired by the HCMV-vector although it lacks all known immunoevasins. We also generated HCMV-based vectors that express E6-derived peptide fused to HCMV proteins. GBM cells infected with these vectors efficiently stimulated E6-specific T cells. Thus, fusion of antigenic sequences to HCMV proteins is required for efficient presentation via MHC class I molecules during infection. Taken together, these results provide the preclinical basis for development of HCMV-based vaccines and also reveal a novel HCMV-encoded block of MHC class I presentation
Human papillomavirus and human cytomegalovirus infection and association with prognosis in patients with primary glioblastoma in Pakistan
Objective: Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. Human cytomegalovirus (HCMV) has been studied for the past decade, and conflicting results have been reported with no conclusive role established yet. Human papillomavirus (HPV) is involved in the pathogenesis of many cancers and has a high prevalence in patients with cervical and oral cancer in Pakistan. The objective of our study was to identify the prevalence of HCMV and HPV in Pakistani patients with primary GBM.Methods: In total, 112 primary GBM biopsies were analyzed. HCMV and HPV infection was investigated using nested and conventional polymerase chain reaction, respectively. Positive HPV samples were further confirmed through sequencing. HPV status was correlated with histology and expression of other frequently mutated GBM molecular markers.Results: Our study comprised of 68% male and 32% female patients. HCMV was detected in only 1 patient whereas HPV infection was present in 28% of patients with no cases of HPV and HCMV coinfection. We report for the first time that a majority of HPV-positive patients with GBM harbored types 16 and 18 both. Among them, 16% were HPV-type 16 and 20% were HPV-type 18. Patients infected with HPV had longer survival times, but this was not statistically significant. The most commonly overexpressed molecular marker in HPV-positive patients was cyclo-oxygenase-2, and no histologic changes were seen in HPV-positive GBM cases.Conclusions: The presence of a single HCMV positive is intriguing. In addition, we discovered a substantially high 28% prevalence of HPV in GBM patients. The role of viruses in gliomagenesis warrants further investigation
Pituitary insufficiency after operation of supratentorial intra- and extraaxial tumors outside of the sellarâparasellar region?
Recent studies investigating pituitary function after non-sellar brain tumor surgery showed that up to 38.2% of patients have pituitary insufficiency (PI). It has been assumed that the operation causes the PI, but preoperative hormone testing, which would have been necessary to prove this assumption, was not performed. The objective of this study is to answer the question if indeed microsurgery is the culprit of PI in patients with operatively treated non-sellar brain tumors. In this prospective trial, 54 patients with supratentorial non-sellar tumors were included. The basal levels of cortisol, prolactin, testosterone, estrogen, IGF-1, fT3, fT4, STH, TSH, ACTH, FSH, and LH were recorded preoperatively on days 1 and 7 after surgery. If basal hormone screening revealed an abnormality, a releasing hormone assay was performed. Before surgery, 24 of the 54 patients (44.4%) already had PI. Additional 25 patients showed either hypocortisolism or hypothyreoidism. As those patients had been pre-treated with dexamethasone and l-thyroxine, these findings were considered not to represent PI but drug effects. Hormone testing on days 1 and 7 after surgery revealed no changes. With 44.4% PI is a frequent finding in brain tumor patients already before surgery. The factors causing preoperative PI remain yet to be identified. The endocrine results after surgery are unchanged which rules out that surgery is the cause of PI
The genesis of material transported in the channel in the light of the integrated model of soil erosion in the lowland catchment
This paper presents new concept of integrated model of soil erosion in the catchment. There is one input (rainfall transformed into effective rainfall) and three outputs: hydrograph of runoff, sediment yield in a form of sedimentgraph and spatial distribution of erosion in the catchment. The main body of the model is represented by sedimentgraph, which is constructed using instantaneous unit hydrograph (IUH) and instantaneous unit sedimetgraph (IUSG). The mathematical formula of IUSG was developed. The map of erosion in a catchment is modeled using USLE formula. To verify described model measurements in Olszanka watershed were organized by author. Verification showed that new version of IUSG gives satisfactory results and requires further research both in the modeling of erosion in a catchment scale and monitoring of sources of material transported in the channel
Recommended from our members
Relations among Parental Responding to Offspring Emotion, Emotion Approach Coping, and Posttraumatic Stress Symptoms among Trauma-Exposed College Students
The present investigation evaluated whether dispositional use of emotional approach coping partially accounts for the association between parental response to emotional expression and posttraumatic stress symptoms (PTSS) in a sample of 252 trauma-exposed individuals drawn from a pool of college students and college-age members of the community at-large. An online survey assessed parental reactions to participants' negative emotions during childhood (i.e., offspring retrospective report), as well as participant trauma history, PTSS, and use of emotional approach coping. Findings complement literature illustrating the long-lasting implications of the parent-child relationship, such that both supportive and unsupportive parenting were related to PTSS. Supportive parental reactions also were related to emotional expression, but not emotional processing, and unsupportive reactions did not significantly relate to either aspect of emotional approach coping. Notably, emotional approach coping strategies were unrelated to PTSS in the full sample, and thus the indirect effects models were not supported. Post hoc analyses indicated preliminary support for the indirect effect of emotional expression on the relation between supportive parenting and PTSS in the local college student sample (n = 117). Limitations and implications for future research are discussed
- âŠ