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Background: Defining the tumor immune microenvironment (TIME) of patients using transcriptome analysis is gaining more popularity. Here, we examined and discussed the pros and cons of using RNA sequencing for fresh frozen samples and targeted gene expression immune profiles (NanoString) for formalin-fixed, paraffin-embedded (FFPE) samples to characterize the TIME of ependymoma samples. Results: Our results showed a stable expression of the 40 housekeeping genes throughout all samples. The Pearson correlation of the endogenous genes was high. To define the TIME, we first checked the expression of the PTPRC gene, known as CD45, and found it was above the detection limit in all samples by both techniques. T cells were identified consistently using the two types of data. In addition, both techniques showed that the immune landscape was heterogeneous in the 6 ependymoma samples used for this study. Conclusions: The low-abundant genes were detected in higher quantities using the NanoString technique, even when FFPE samples were used. RNA sequencing is better suited for biomarker discovery, fusion gene detection, and getting a broader overview of the TIME. The technique that was used to measure the samples had a considerable effect on the type of immune cells that were identified. The limited number of tumor-infiltrating immune cells compared to the high density of tumor cells in ependymoma can limit the sensitivity of RNA expression techniques regarding the identification of the infiltrating immune cells. [ABSTRACT FROM AUTHOR]

Considers the modeling and optimal control of the wafer temperatures in cylindrical resistance furnaces called diffusion furnaces. Description of the radiative heat transfer that should serve as a basis for the furnace model; Control algorithm that was designed to control wafer temperatures; Postulates that simplify the computation of the radiative exchange between surfaces.

Provides information on a study which examined the heat transfer inside cylindrical resistance diffusion and low-pressure chemical vapor deposition furnaces aimed at developing an improved temperature controller. Model of thermal behavior; Thermal behavior of the thermocouples; Model of an alternative temperature controller of the linear quadratic Gaussian type model.

This short paper argues that energy, the potential to realize change, taking place through interaction, is the essence of everything. Nonduality and emergence play a key role in explaining why energy should be conceived as the single source of everything. The very nature of space and time also follows from it. The whole universe is just energy, and everything emerges from this energy. So the essence of everything is energy. [ABSTRACT FROM AUTHOR]

A very simple, fundamental physical explanation is presented of time dilation and length contraction. This explanation is obtained from a classical model of physics that is Galilean. It assumes the existence of a medium (ether) that acts as an absolute reference in accordance with Mach's principle. Time and space are conventional, i.e., a three-dimensional space independent of time. In addition, the explanation relies on the assumption that all physics, including matter such as clocks and measuring rods, has a scalar wave structure. Matter is assumed to consist of locally stable scalar wave structures, specifically scalar standing wave structures. The scalar waves are just variations in space and time of medium density. Also, an element of special relativity is used, namely, the one taking into account the finite velocity of light. [ABSTRACT FROM AUTHOR]

The answer lies right in front of us, but we refuse to see it. Both relativity and quantum theory, the two pillars of fundamental physics, are modified in this paper to make them also explain the physical phenomena they describe. With this explanation, all current inconsistencies between the two vanish. The modifications relate to the presence of a medium, which is in fact potential energy, in three-dimensional space. This medium acts as a reference system, in accordance with Mach's principle. The speed of light, therefore, is not absolute but relative to the medium and thus to the observer. It is also dependent on medium density. Quantum waves are real scalar waves occurring in the potential energy medium, not probabilities of particles being present. Real scalar quantum waves in three-dimensional space make up the whole of physics representing manifest energy. Particles therefore do not exist; they are local manifestations of real scalar quantum waves. As a result, the Doppler effect and wave interference play a central role in physics. Moreover, the dependence of quantum wave velocity (speed of light) on medium density provides the energy exchange mechanism that is central to physics because all physical phenomena, including observation, concern energy exchange, or interaction. The conceptual simplicity of the model of physics proposed in this paper is shown to clarify a series of paradoxes and ill-understood phenomena at the fundamental level of physics such as wave-particle duality, the twins paradox, and the double slit experiment. As to entanglement, superposition, and nonlocality, the model implies that only weak versions of these properties exist. [ABSTRACT FROM AUTHOR]

Using the delta operator, the strengthened discrete-time optimal projection equations for optimal reduced-order compensation of systems with white stochastic parameters are formulated in the delta domain. The delta domain unifies discrete time and continuous time. Moreover, when formulated in this domain, the efficiency and numerical conditioning of algorithms improves when the sampling rate is high. Exploiting the unification, important theoretical results, algorithms and compensatability tests concerning finite and infinite horizon optimal compensation of systems with white stochastic parameters are carried over from discrete time to continuous time. Among others, we consider the finite-horizon time-varying compensation problem for systems with white stochastic parameters and the property mean-square compensatability (ms-compensatability) that determines whether a system with white stochastic parameters can be stabilised by means of a compensator. In continuous time, both of these appear to be new. This also holds for the associated numerical algorithms and tests to verify ms-compensatability. They are illustrated with three numerical examples that reveal several interesting theoretical and numerical issues. A fourth example illustrates the improvement of both the efficiency and numerical conditioning of the algorithms. This is of vital practical importance for digital control system design when the sampling rate is high. [ABSTRACT FROM AUTHOR]

If one demystifies entropy the second law of thermodynamics comes out as an emergent property entirely based on the simple dynamic mechanical laws that govern the motion and energies of system parts on a micro-scale. The emergence of the second law is illustrated in this paper through the development of a new, very simple and highly efficient technique to compare time-averaged energies in isolated conservative linear large scale dynamical systems. Entropy is replaced by a notion that is much more transparent and more or less dual called ectropy. Ectropy has been introduced before but we further modify the notion of ectropy such that the unit in which it is expressed becomes the unit of energy. The second law of thermodynamics in terms of ectropy states that ectropy decreases with time on a large enough time-scale and has an absolute minimum equal to zero. Zero ectropy corresponds to energy equipartition. Basically we show that by enlarging the dimension of an isolated conservative linear dynamical system and the dimension of the system parts over which we consider time-averaged energy partition, the tendency towards equipartition increases while equipartition is achieved in the limit. This illustrates that the second law is an emergent property of these systems. Finally from our large scale linear dynamic model we clarify Loschmidt’s paradox concerning the irreversible behavior of ectropy obtained from the reversible dynamic laws that govern motion and energy at the micro-scale. [ABSTRACT FROM AUTHOR]

From the state-space approach to linear systems, promoted by Kalman, we learned that minimality is equivalent with reachability together with observability. Our past research on optimal reduced-order LQG controller synthesis revealed that if the initial conditions are non-zero, minimality is no longer equivalent with reachability together with observability. In the behavioural approach to linear systems promoted by Willems, that consider systems as exclusion laws, minimality is equivalent with observability. This article describes and explains in detail these apparently fundamental differences. Out of the discussion, the system properties weak reachability or excitability, and the dual property weak observability emerge. Weak reachability is weaker than reachability and becomes identical only if the initial conditions are empty or zero. Weak reachability together with observability is equivalent with minimality. Taking the behavioural systems point of view, minimality becomes equivalent with observability when the linear system is time invariant. This article also reveals the precise influence of a possibly stochastic initial state on the dimension of a minimal realisation. The issues raised in this article become especially apparent if linear time-varying systems (controllers) with time-varying dimensions are considered. Systems with time-varying dimensions play a major role in the realisation theory of computer algorithms. Moreover, they provide minimal realisations with smaller dimensions. Therefore, the results of this article are of practical importance for the minimal realisation of discrete-time (digital) controllers and computer algorithms with non-zero initial conditions. Theoretically, the results of this article generalise the minimality property to linear systems with time-varying dimensions and non-zero initial conditions. [ABSTRACT FROM AUTHOR]

The synthesis of finite-horizon digital optimal reduced-order compensators is presented, for asynchronous and aperiodically sampled continuous-time systems. The dimensions of the compensator state are a priori fixed and may be time varying. Asynchronous and aperiodic sampling refers to a deterministic sampling scheme where an arbitrary, but a priori known, number of control variables is updated, and/or an arbitrary, but a priori known, number of outputs is sampled, at arbitrary, but a priori known, time instants. This sampling scheme generalizes most deterministic sampling schemes considered in the control literature. Through the use of an integral criterion the intersample behaviour is explicitly considered in the design. As a result, frequent, synchronous and periodic sampling is no longer necessary, which can be highly relevant in practice. Also the synthesis enables comparison of the optimal performance of reduced-order compensators as a function of their dimensions and the sampling scheme. The synthesis is illustrated with a numerical example. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients. In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour. Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15–32 months). Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens. • Pancreatic cancer is an immune-deserted tumour and responses to immunotherapy are rare. • Allogeneic-tumour lysate-dendritic cell vaccination is feasible and safe in patients with pancreatic cancer. • Dendritic cell vaccination was immunogenic and demonstrated T-cell activation after therapy. • Therapy-induced cross-reactive T-cell responses against autologous tumour were found. [ABSTRACT FROM AUTHOR]

Since the 1980s treatment techniques for congenital heart disease (ConHD) have gradually evolved. Therefore, actual information on the outcomes, including quality of life is required. Health-related quality of life was assessed long-term in four diagnostic groups of children, who underwent invasive treatment for ConHD between 1990 and 1995. The scores on the TNO-AZL Child Quality of Life Questionnaire (TACQOL) of both children with ConHD and their parents were compared with those of a same-aged reference group. The total sample of ConHD children (n = 113, 8-15 years old) obtained significantly lower mean scores on motor functioning, cognitive functioning, and positive emotional functioning than reference peers, reflecting an experience of poorer functioning. ConHD children, aged 8-11 years, obtained lower mean scores on 5 of the 7 TACQOL scales than reference peers. They also had a lower score on positive emotional functioning than 12- to 15-year-old ConHD children. The total sample of ConHD children obtained lower outcomes compared to their parents on 4 of the 7 TACQOL scales. No significant differences were found in health-related quality of life between ConHD boys and girls, neither between different diagnostic groups. Overall, this sample of recently treated ConHD children showed a worse health-related quality of life compared to reference groups. These findings deserve further attention. [ABSTRACT FROM AUTHOR]