This paper presents the design, fabrication, experimental results and related discussion of a portable bending enhancing silicone mold structure for biomedical applications in which a high-sensitive but low-cost force measurement structure with a large-dynamic range is required. Proposed system is composed of a replaceable parts like graphite coated Strathmore® 400 series Bristol paper and cheap RTV-2 silicone molds. The results shows that low-cost, portable and high-sensitive force and strain sensor systems can be realized for point-of-care biomedical applications in the future.

Poslednjih decenija sve je prisutnija pojava porasta problema u ponašanju kod djece i adolescenata. Cilj istraživanja je utvrditi razlike u porodičnoj orijentaciji i strukturi porodice između adolescenata sa eksternaliziranim i internaliziranim problemima i tipično razvijenih adolescenata. Uzorak ispitanika čini 587 adolescena oba spola. Istraživanje je realizovano u petnaest osnovnih škola na području Tuzle tako što je iz svake škole uključeno po dva odjeljenja, jedno sedmog i jedno osmog razreda. Uzorak je namjerni (samo sedmi i osmi razredi), a unutar njega metodom slučaja su izabirani razredi. U istraživanju su korištena dva mjerna instrumenta: Youth Self-Report – YRS (Achenbach, 2007) i Skala porodičnog okruženja, verzija za adolescente (Family Envinoment Scale – FES, Moos, Moos, 2009). Rezultati istraživanja upućuju na postojanje razlike između adolescenata koji žive sa oba roditelja i onih koji su iz nepotpune porodice. Statistički značajne razlike uočene su na skalama Agresivno ponašanje (t = - 2,23; p < 0,00), Ponašanje kojim se krše pravila (t = -3,22; p < 0,00) i dimenziji Eksternalizacije (t = -2,82; p < 0,00). Kod porodične orijentacije je također prisutna statistička razlika. Dovodeći u vezu strukturu porodice porodice sa internaliziranim problemima uočeno je da ne postoje statistički značajne razlike.

: T his paper provides a simple estimation of the Long Term Evolution (LTE) physical and Medium Access Control (MAC) layer peak transmission performanc e-the irr educible Block - Error - Rate (BLER) that determines the Hybrid Automatic Repeat Request (HARQ) residual channel available to higher - layer protocols. With this regard, the general pre - HARQ BLER prediction is developed for the redundancy version 0 (RV0) codeword transmission, expressed by the Bit - Error - Rate (BER)), considering the cyclic prefix protection against inter - symbol interference sufficient to prevent long error bursts. This implies only sporadic bit error occurrences, exhibiting moderate mutual interdependence that we modelled considering errored bits of each block of data as a sample without replacement and consequently describing it with the hypergeometric distribution instead of the mostly used binomial one. The HARQ BLER estimation model is verified by both problem - dedicated Monte - Carlo simulations and industry - standard LTE software simulation tool, specifically for the LTE FDD downlink channel environment, as the test results exhibit excellent matching with the residual BLER prediction.

Očuvanje porodice kao osnovne ćelije društva u savremenom načinu života je veliki izazov. Očuvanje i funkcionisanje porodice gdje je jedno dijete s oštećenjem sluha predstavlja ogroman pritisak roditeljima, koji moraju naučiti balansirati između djeteta koje ima teškoću i djeteta koje nema. Uočavanjem i dijagnostikovanjem teškoće kod djeteta roditelji se suočavaju sa potpuno novim načinom života. Odgajanje djeteta s teškoćama u razvoju za njih je put u nepoznato, nije rijetkost da brak zapadne u krizu, svakodnevno su izloženi stresu i brojnim obavezama. Uz nerazumijevanje šire porodice za probleme s kojima se suočavaju i društvene zajednice koja ne pruža adekvatnu podršku, moraju naučiti na koji način će odgajati i jedno i drugo dijete. Koliko će ravnopravno postupati u ophođenju prema njima je od presudnog značaja za razvijanje skladnih bratsko – sestrinskih odnosa. Adekvatnim pristupom i pravilnim odgojem, dijete s teškoćama u razvoju u porodici stvara posebne veze među članovima koji doprinose bržem sazrijevanju, većoj zrelosti, odgovornosti i samostalnosti braće i sestara.

: T ime series data of GNSS point positioning are considerably used for the purpose of geophysical research. The velocity estimates and their uncertainties deriv e from time series data of GNSS point positioning affected by seasonal signals and the stochastic noise, contained in the series. D ata cleaning of GNSS time series is a prerequisite for the noise characterization and analysing. In this article one point positioning of time series was analysed in four different periods during the five year interval. The noise characteristics were estimated for all periods. By applying Lomb - Scargle algorithm the comparable results were also provided. Lomb - Scargle algorithm used to estimate the spectral strength density of unequal sampled data is a typical tool for this kind of analysis. S pectral indices have been estimated before cleaning data and after removing linear, annual and semi - annual signals and outliers. T he spectral indices estimated from time series data of GNSS point positioning were located in the area of fractional Gaussian noises , and stationary stochastic process was described for the whole research time period.

Rationale: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infancy, potentially aided by an inappropriate immune response. Sparse information is available for the distal lung, mostly because data arose from non-invasive samplings of peripheral blood and nasal aspirates. Objectives: To determine the neonatal immune response to RSV in the bronchoalveolar space and better understand why neonates are at greater risk of developing severe disease. Methods: We used the newborn lamb, a state-of-the-art translational model of human RSV infection, offering ease sampling and full accessibility to lower airways. Using a multiparameter flow cytometry assay, we evaluated the frequency and activation/maturation state of the major subsets of the developing T-cell compartment. Measurements and Main Results: The T-cell compartment of the healthy developing lung was very distinct to that seen in adults. We observed a high frequency of type 2 CD4+ (Th2) and CD8+ (Tc2) T-cells, both being a large source of IL-4, which declined progressively over time. Remarkably, RSV infection exacerbated this pro-type 2 environment, rather than inducing a type 2 response per se. Neonatal regulatory T-cell (Treg) suppressive functions occurred very early to dampen those Th2 and Tc2 responses, while γδ T-cells dropped and failed to produce IL-17. The disease severity was related to the magnitude of these T-cell responses. Conclusion: The atypical neonatal immune response to RSV consists of distinct T-cell subsets that tightly cooperate, namely a combined bronchoalveolar influx of Treg, Th2 and Tc2 cells, associated with a depletion of γδ T-cells.

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the specific features of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a state-of-the-art model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4 and CD8 T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity. AUTHOR SUMMARY By using a state-of-the-art translational model with full accessibility to the small airways at defined early life periods, we provide an unpreceded characterization of the developing T cell compartment in the distal lungs of healthy and RSV-infected neonates. This process is highly dynamic and tightly regulated, characterized by colonizing T-cell subsets that synergize towards a narrow pro-tolerogenic immunological window. We believe our work constitutes a solid basis to clarify the age dependency of RSV immunopathogenesis, and should be considered in vaccine design, which remains challenging after five decades of effort.

PURPOSE We aimed to determine the association of two of the most important functional polymorphisms of IL-8 and IL-10 with the clinical course and outcome of acute pancreatitis. METHOD Ninety-three patients with acute pancreatitis were genotyped for IL-8-251T>A and IL-10-1082G>A using PCR-RFLP. The severity of the disease was determined based on the Atlanta Classification system. RESULTS In patients treated with opioids, the odds for severe form of acute pancreatitis, its complications, and death were increased. Advanced age was associated with higher odds of organ/multiple organ failure and other systemic complications. Multivariate logistic regression analyses confirmed the observed effect of age and use of opioids, and revealed higher odds for the development of severe form of acute pancreatitis [P = 0.017, odds ratio (OR): 4.324, 95% confidence interval (CI): 1.305-14.323], its complications in general (P = 0.011, OR: 4.936, 95% CI: 1.442-16.897), pancreatic necrosis (P = 0.032, OR: 3.922, 95% CI: 1.122-13.707) and systemic inflammatory response syndrome (P = 0.037, OR: 3.838, 95% CI: 1.085-13.583) in the absence of IL-10-1082G>A variant allele. The effect of IL-8 -251T>A on acute pancreatitis severity or mortality was not detected. CONCLUSION Our study suggests the IL-10 -1082A allele as a protective factor in acute pancreatitis. Opioid analgesics treatment in acute pancreatitis is associated with severity, complications and mortality, while advanced age increases the risk of systemic complications.

We apply topological data analysis, specifically the Mapper algorithm, to the U.S. COVID-19 data. The resulting Mapper graphs provide visualizations of the pandemic that are more complete than those supplied by other, more standard methods. They encode a variety of geometric features of the data cloud created from geographic information, time progression, and the number of COVID-19 cases. They reflect the development of the pandemic across all of the U.S. and capture the growth rates as well as the regional prominence of hot-spots. The Mapper graphs allow for easy comparisons across time and space and have the potential of becoming a useful predictive tool for the spread of the coronavirus.

We have investigated the self-assembly of a strong dipolar molecule (LDipCC) on the semiconducting Si(111)-B surface with scanning tunneling microscopy (STM), density functional theory (DFT) calculations and STM simulations. Although the formation of an extended two-dimensional network was clearly revealed by STM under ultra-high vacuum, the assignment of a specific STM signature to the different terminal groups from the LDipCC molecular unit required a complete analysis by numerical simulations. The overall observed assembly is explained in terms of STM contrasts associated with the molecular structure of LDipCC and the molecule-surface interactions. To distinguish the relative arrangement of the dipolar molecules within the assembly, a rational combination of experimental results and electronic structure calculations allows us to identify a single adsorbed LDipCC phase in which the molecular dipoles are homogeneously arranged into a parallel fashion on the Si(111)-B surface.

Este trabalho apresenta uma análise da obra Capitães da Areia, de Jorge Amado, abordando a constituição social do sujeito e sua conformação política dentro de um contexto ficcional. A partir da observação das dificuldades enfrentadas pelo personagem Pedro Bala, tendo-o como personagem principal desta pesquisa, analisa-se sua trajetória ao longo do enredo no contexto sociocultural a que este estava inserido.  O trabalho foi realizado por meio de pesquisa do tipo revisão bibliográfica, com a seleção de textos relacionados ao contexto e a obra em si. Foram lidos textos de José Murilo de Carvalho (2015), Karl Marx (1998), entre outros, pois estes se aproximam direta e indiretamente dos temas estruturantes abordados na trama.  A estrutura da pesquisa foi desenvolvida a fim de propor uma reflexão, trazendo à tona questões sociais ainda bem evidentes em nossa atual sociedade. Por fim, vimos Pedro Bala tornando-se um militante que representou um grupo que estava à margem da sociedade, dando voz, questionando e lutando por direitos que todos os cidadãos devem ter em uma sociedade, dando demonstração que a construção do sujeito é histórica e não determinada previamente.

Background: Clonal neoantigens are formed early in cancer evolution and have been identified as a subset of patient specific mutations that are associated with improved clinical benefit and represent great promise as targets for the next generation of T cell therapies. Developing T cell therapies that target multiple clonal neoantigens represents a unique personalized approach to treating solid cancer, as they are present on all cancer cells, minimizing the risk of tumour escape, and absent from healthy tissue, potentially eliminating off-target toxicities. Access to sequencing data from over 600 NSCLC patients enrolled in the UK TRACERx study has enabled the development of the Achilles PELEUSTM bioinformatic platform. By opening an ethically approved tissue collection study NCT03517917, enabling access to matched tumour and blood samples from patients with selected cancers, our clonal neoantigen reactive T cell (cNeT) manufacturing process and supply chain has been validated for use in clinical trials. Methods: Matched tumor and blood samples were procured at the time of routine surgery from ten patients (eight with newly diagnosed stage I-III NSCLC and two with metastatic melanoma) for at-scale GMP runs. Briefly, TIL were isolated from tumor fragments and immature dendritic cells (DCs) generated from whole blood, prior to cryopreservation as intermediate products. Patient-specific clonal neoantigens were predicted using our proprietary PELEUSTM bioinformatic platform, enabling the manufacture of synthetic peptide masterpools to be used for the enrichment of cNeT in the VELOSTM manufacturing process. Co-culture of pre-expanded TIL and patient DCs loaded with clonal neoantigen peptides drives the selective expansion of cNeT, eliminating the requirement for high non-physiological levels of IL-2. Results: Here we present the successful scaled GMP production of cNeT from both primary and metastatic tumors using the VELOSTM manufacturing process in ten patients. All final products met QC release criteria and were composed of both CD4+ and CD8+ T cells. Extensive characterization of T cell responses showed cNeT exhibited functional responses determined by cytokine secretion following re-challenge, and specificity in response to clonal neoantigen peptides. Peptide deconvolution of masterpools identified multiple single T cell clone reactivities to clonal neoantigens in the final product. Conclusions: The VELOSTM process incorporating the PELEUSTM bioinformatic platform for prediction of clonal neoantigens is a novel platform for generating personalized T cell products directed at multiple cancer clonal neoantigen targets and has the potential to be utilized across a variety of solid tumors. This study demonstrates the feasibility of generating cNeT for the treatment of both advanced NSCLC and recurrent or metastatic melanoma and supported the successful regulatory approval in two first-in-human studies (NCT04032847 and NCT03997474) which opened in the UK in 2019. Citation Format: Henrieta Fraser, Rebecca Pike, Sarah Thirkell, Asiya Arshad, Sam Jide-Banwo, Hollie Bartley, Evi Rologi, Michal Pruchniak, Shreenal Patel, Jennine Mootien, Jane Robertson, Andrew Craig, Max Salm, Katy Newton, Luke Goodsell, Fong Chan, Gareth Wilson, Stephen Frenk, Iraj Ali, Karl Peggs, Mark W. Lowdell, Lyra Del Rosio, Andrew Hayes, Samra Turajlic, Farah Islam, David Lawrence, Mariam Jamal-Hanjani, Martin D. Forster, Edward Samuel. The development of a personalized autologous clonal neoantigen T cell therapy for the treatment of solid cancer using the VELOSTM manufacturing platform generates highly potent and reactive CD8+ and CD4+ T cells for clinical use [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT054.

Adoptive transfer of tumor infiltrating lymphocytes (TIL) has generated objective clinical responses in patients with advanced metastatic cancers. Therapeutic exploitation of neoantigens as targets can potentially lead to safer and more effective treatment modalities with reduced toxicities. The Achilles Therapeutics trial NCT03517917 enabled the acquisition of matched tumor specimens and peripheral blood samples from patients undergoing routine surgery and facilitated the development of the proprietary VELOSTM manufacturing process, generating a personalized clonal neoantigen specific T cell product. An in-depth characterization of T cells expanded with the VELOSTM process was performed and compared to a standard TIL product. Samples were obtained from patients with primary NSCLC or metastatic melanoma. TIL were expanded from tumor fragments after dissection in the presence of IL-2. Peptide pools corresponding to the clonal mutations that were identified using the PELEUSTM bioinformatics platform were used to pulse dendritic cells (DC) generated from peripheral blood monocytes from each patient. Clonal neoantigen specific T cells (cNeT) were expanded using the VELOSTM process by co-culture of TIL with the peptide-pulsed autologous DC. As a comparison, TIL were expanded with a rapid expansion protocol (REP-TIL) in the presence of allogeneic feeders, anti-CD3 antibody and high-dose IL-2. Intracellular cytokine staining was performed following rechallenge with individual peptide pools encoding the clonal mutations. Single peptide reactivities were identified using ELISPOT and extended flow cytometric analysis of markers associated with T cell fitness or dysfunction was performed to phenotypically characterize the cNeT, TIL and REP-TIL. Analysis of the immune cell composition showed that cNeT, TIL and REP-TIL have similar CD3+ T cell content (median cNeT 90.2%, TIL 87.3%, REP-TIL 95%, n=6) and are composed of CD4+ and CD8+ T cells (median CD4:CD8 ratio- cNeT 11.1, TIL 2.03 and REP-TIL 4.7, n=6). cNeT showed superior clonal neoantigen specificity compared to TIL or REP-TIL. The proportion of CD3+ T cells responding to clonal neoantigen rechallenge was increased in cNeT (median 24.3%) compared to TIL (median 0.6%) and REP-TIL (median 1.8%) (n=5). The VELOSTM process incorporating the PELEUSTM platform for prediction of clonal neoantigens generates T cell products enriched for clonal neoantigen reactivities and superior phenotypic characteristics compared to conventional TIL. The VELOSTM process is currently being used to manufacture cNeT for two first-in-human studies including NSCLC and melanoma patients (NCT04032847, NCT03997474). Ethical approval: The samples for the study were collected under an ethically approved protocol (NCT03517917). Citation Format: Eleni Kotsiou, Tie Zheng Hou, Joseph Robinson, Sonal Varsani, Theres Oakes, Pablo D. Becker, Shreenal Patel, Jennine Mootien, Andrew Craig, Jane Robertson, Edward Samuel, James Reading, Lyra Del Rosario, Andrew Haynes, Samra Turajlic, Farah Islam, David Lawrence, Mariam Jamal-Hanjani, Martin Foster, Sergio A. Quezada, Katy Newton. Next generation clonal neoantigen targeting T cells, generated using the PELEUSTM bioinformatics platform and the VELOSTM manufacturing method show superior reactivity and phenotypic characteristics than classical TIL products [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 875.