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K. Litchfield, J. Reading, C. Puttick, C. Abbosh, R. Bentham, T. Watkins, R. Rosenthal, D. Biswas et al.

Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumour cell intrinsic and microenvironmental features underpinning CPI sensitization. Here we collated whole-exome and transcriptomic data for >1000 CPI-treated patients across eight tumor-types, utilizing standardized bioinformatics-workflows and clinical outcome-criteria to validate multivariate predictors of CPI-sensitization. Clonal-TMB was the strongest predictor of CPI response, followed by TMB and CXCL9 expression. Subclonal-TMB, somatic copy alteration burden and HLA-evolutionary divergence failed to attain significance. Discovery analysis identified two additional determinants of CPI-response supported by prior functional evidence: 9q34.3 (TRAF2) loss and CCND1 amplification, both independently validated in >1600 CPI-treated patients. We find evidence for collateral sensitivity, likely mediated through selection for CDKN2A-loss, with 9q34.3 loss as a passenger event leading to CPI-sensitization. Finally, scRNA sequencing of clonal neoantigen-reactive CD8-TILs, combined with bulk RNAseq analysis of CPI responding tumors, identified CCR5 and CXCL13 as T cell-intrinsic mediators of CPI-sensitisation.

A. Fendler, L. Boos, L. Au, S. Shepherd, F. Byrne, K. Edmonds, E. Carlyle, L. D. Rosario et al.

Olivera Kalajdžić, J. Pavlović

BACKGROUND: Psychological support for patients and their families is of great importance at times when they go through shock, stress, and fear at moments when confronted with diagnosis and treatment. AIM: Aim to this study was to examine the influence of family attitudes on psychosocial adaptation and the effect of treatment of patients with malignancies to preserve the integrity of the diseased person in Bosnia and Herzegovina. METHODS: The cross-sectional study included 100 patients who were hospitalized at Foca University Hospital, Department of Oncology between September 2019 and December 2019. The survey used a sociodemographic questionnaire as well as a standardized questionnaire to evaluate communication with patients with malignant diseases for the patient and family (CCAT-PF). RESULTS: More than half of the respondents (69%) accepted the malignancy. When it comes to communication between health-care professionals and patients, 51% are satisfied with the communication and 49% are not satisfied. Most respondents (62%) hesitate to talk about side effects during treatment with health-care professionals, with a statistically significant difference observed between male and female respondents (χ2 = 6,014; p = 0.014). CONCLUSION: The time devoted to the subjects by the physicians as well as the willingness to listen to the patient is important aspects that influence the adaptation of the disease as well as the treatment.

Elma Satrovic, Adnan Muslija, Sadeq J. Abul, Dragan Gligorić, Tamanna Dalwai

ABSTRACT This paper outlines the roles of gross domestic spending on research and development (R&D) and gross capital formation in the innovation process and detects their contribution to this improvement. The analysis is conducted for Turkey for the period 1990-2017 using annual time-series data. Our findings suggest a bidirectional causal link between all variables of interest and prove that R&D can be a significant driving force for the Turkish innovation process. Most of the research and development activities in Turkey have been performed by universities. Herein, it is of key importance for the Turkish government to increase public expenditure, especially on education, since human capital plays an important role in building innovation capacity.

T. Uzunović, A. Sabanoviç, Minoru Yokoyama, T. Shimono

The paper introduces a novel control strategy for simultaneous control of position and interaction force for multi-degrees of freedom robotic systems (multi-DOF). The strategy enables both position control in free motion, and interaction force control during contact with an environment. In that sense, it differs from classical control algorithms which are switching between two different controllers, namely, position controller and force controller. The transition between position control mode and force control mode in the newly proposed structure is smooth, removing oscillations often present in the classical algorithms. This improves safety of the interaction between a controlled system and its environment.

Evan Dunwoodie, R. Mutlu, B. Ugurlu, M. C. Yildirim, T. Uzunović, E. Sariyildiz

Compared to the traditional industrial robots that use rigid actuators, the advanced robotic systems are mobile and physically interact with unknown and dynamic environments. Therefore, they need intrinsically safe and compact actuators. In the last two decades, Series Elastic Actuators (SEAs) have been one of the most popular compliant actuators in advanced robotic applications due to their intrinsically safe and compact mechanical structures. The mobility and functionality of the advanced robotic systems are highly related to the torque-density of their actuators. For example, the amount of assistance an exoskeleton robot can provide is determined by the trade-off between the weight and output-torque, i.e., torque-density, of its actuators. As the torque outputs of the actuators are increased, the exoskeleton can expand its capacity yet it generally becomes heavier and bulkier. This has significant impact on the mobility of the advanced robotic systems. Therefore, it is essential to design light-weight actuators which can provide high-output torque. However, this still remains a big challenge in engineering. To this end, this paper proposes a high-torque density SEA for physical robot environment interaction (p-REI) applications. The continuous (peak) output-torque of the proposed compliant actuator is 147Nm (467 Nm) and its weight is less than 2.5kg. It is shown that the weight can be lessened to 1.74, but it comes at cost. The performance of the proposed compliant actuator is experimentally verified.

Somayeh Jolany vangah, C. Katalani, Hannah A. Booneh, A. Hajizade, Adna Sijerčić, G. Ahmadian

Interest in CRISPR technology, an instrumental component of prokaryotic adaptive immunity which enables prokaryotes to detect any foreign DNA and then destroy it, has gained popularity among members of the scientific community. This is due to CRISPR’s remarkable gene editing and cleaving abilities. While the application of CRISPR in human genome editing and diagnosis needs to be researched more fully, and any potential side effects or ambiguities resolved, CRISPR has already shown its capacity in an astonishing variety of applications related to genome editing and genetic engineering. One of its most currently relevant applications is in diagnosis of infectious and non-infectious diseases. Since its initial discovery, 6 types and 22 subtypes of CRISPR systems have been discovered and explored. Diagnostic CRISPR systems are most often derived from types II, V, and VI. Different types of CRISPR-Cas systems which have been identified in different microorganisms can target DNA (e.g. Cas9 and Cas12 enzymes) or RNA (e.g. Cas13 enzyme). Viral, bacterial, and non-infectious diseases such as cancer can all be diagnosed using the cleavage activity of CRISPR enzymes from the aforementioned types. Diagnostic tests using Cas12 and Cas13 enzymes have already been developed for detection of the emerging SARS-CoV-2 virus. Additionally, CRISPR diagnostic tests can be performed using simple reagents and paper-based lateral flow assays, which can potentially reduce laboratory and patient costs significantly. In this review, the classification of CRISPR-Cas systems as well as the basis of the CRISPR/Cas mechanisms of action will be presented. The application of these systems in medical diagnostics with emphasis on the diagnosis of COVID-19 will be discussed.

Somayeh Jolany vangah, C. Katalani, Hannah A. Boone, A. Hajizade, Adna Sijerčić, G. Ahmadian

Interest in CRISPR technology, an instrumental component of prokaryotic adaptive immunity which enables prokaryotes to detect any foreign DNA and then destroy it, has gained popularity among members of the scientific community. This is due to CRISPR’s remarkable gene editing and cleaving abilities. While the application of CRISPR in human genome editing and diagnosis needs to be researched more fully, and any potential side effects or ambiguities resolved, CRISPR has already shown its capacity in an astonishing variety of applications related to genome editing and genetic engineering. One of its most currently relevant applications is in diagnosis of infectious and non-infectious diseases. Since its initial discovery, 6 types and 22 subtypes of CRISPR systems have been discovered and explored. Diagnostic CRISPR systems are most often derived from types II, V, and VI. Different types of CRISPR-Cas systems which have been identified in different microorganisms can target DNA (e.g. Cas9 and Cas12 enzymes) or RNA (e.g. Cas13 enzyme). Viral, bacterial, and non-infectious diseases such as cancer can all be diagnosed using the cleavage activity of CRISPR enzymes from the aforementioned types. Diagnostic tests using Cas12 and Cas13 enzymes have already been developed for detection of the emerging SARS-CoV-2 virus. Additionally, CRISPR diagnostic tests can be performed using simple reagents and paper-based lateral flow assays, which can potentially reduce laboratory and patient costs significantly. In this review, the classification of CRISPR-Cas systems as well as the basis of the CRISPR/Cas mechanisms of action will be presented. The application of these systems in medical diagnostics with emphasis on the diagnosis of COVID-19 will be discussed.

This paper investigated the effect of the tenon length on the strength and stiffness of the standard mortise and tenon joints, as well of the double mortise and tenon joints, that were bonded by poly(vinyl acetate) (PVAc) and polyurethane (PU) glues. The strength was analyzed by measuring applied load and by calculating ultimate bending moment and bending moment at the proportional limit. Stiffness was evaluated by measuring displacement and by calculating the ratio of applied force and displacement along the force line. The results were compared with the data obtained by the simplified static expressions and numerical calculation of the orthotropic linear-elastic model. The results indicated that increasing tenon length increased the maximal moment and proportional moment of the both investigated joints types. The analytically calculated moments were increased more than the experimental values for both joint types, and they had generally lower values than the proportional moments for the standard tenon joints, as opposed to the double tenon joints. The Von Mises stress distribution showed characteristic zones of the maximum and increased stress values. These likewise were monitored in analytical calculations. The procedures could be successfully used to achieve approximate data of properties of loaded joints.

Dragica Šalamon, A. Džidić, N. Antunac, S. Ivanković, V. Batinić

Milk of Kupres, Privor and Stolac dairy ewe breeds is used for the production of the fine cheese varieties. To the best of our knowledge there are no information about milk production and milk composition of these pasture-based dairy ewes. The aim was to determine the best lactation curve model in autochthonous pasture-based dairy ewes in Bosnia and Herzegovina. Milk production was recorded and milk composition sampled (milk fat and protein) during early, mid and late lactation in 129 Kupres, 141 Privor and 129 Stolac pramenka ewes. Four lactation models (Wilmink, Cubic, Ali-Shaeffer and Guo-Swalve) were compared and selected based on the lowest coefficient of determination and root mean square error. The Guo-Swalve model described all of the measured variables most successfully. Kupres pramenka dairy ewe was the highest producing breed with 139 kg of milk during 175 days of lactation (0.79 kg/d; between lactation day 50 to 225) and showed the standard lactation curve. Privor pramenka produced 118 kg of milk during 175 days of lactation (0.67 kg/d) and Stolac pramenka 101 kg of milk during 175 days of lactation (0.58 kg/d). Both showed atypical constantly decreasing shape of the lactation curve common in low producing dairy ewes. The prediction of milk yield and milk composition from the Guo-Swalve model could be used by the national breeding program for the Kupres, Privor and Stolac pramenka sheep breeds. Additional research during a more stable management conditions is recommended for Privor and Stolac pramenka.

V. Borish, O. Marković, Jacob A. Hines, Shankari V. Rajagopal, M. Schleier-Smith

Rydberg dressing provides optically controllable interactions between neutral atoms, of interest for generating many-body entanglement. We demonstrate these interactions and emulate transverse-field Ising dynamics in a cold gas of cesium atoms.

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