Linear Interval Approximation of Sensor Characteristics with Inflection Points.

The popularity of smart sensors and the Internet of Things (IoT) is growing in various fields and applications. Both collect and transfer data to networks. However, due to limited resources, deploying IoT in real-world applications can be challenging. Most of the algorithmic solutions proposed so far to address these challenges were based on linear interval approximations and were developed for resource-constrained microcontroller architectures, i.e., they need buffering of the sensor data and either have a runtime dependency on the segment length or require the sensor inverse response to be analytically known in advance. Our present work proposed a new algorithm for the piecewise-linear approximation of differentiable sensor characteristics with varying algebraic curvature, maintaining the low fixed computational complexity as well as reduced memory requirements, as demonstrated in a test concerning the linearization of the inverse sensor characteristic of type K thermocouple. As before, our error-minimization approach solved the two problems of finding the inverse sensor characteristic and its linearization simultaneously while minimizing the number of points needed to support the characteristic.

Analysis of Polarization Images in the Microphysical Blood Parameters Research for the Hematocrit Diagnostics.

The development of non-invasive optoelectronic technologies for human blood monitoring is one of the important research areas for medicine. A critical analysis of optoelectronic methods of blood research and the micromechanical systems based on them is carried out in this article. A design realization of a polarizing portable system for non-invasive monitoring of hematocrit as one of the basic homeostatic constants of the human body containing information about the microphysical parameters of blood cells has been substantiated. A physical model of polarized radiation conversion in a video information system of laser sensing of a biological research object has been formed. Visual and quantitative differences in the spatial distribution of polarization parameters of the scattered radiation for the states of the body with different hematocrit levels have been revealed. A scheme of a multichannel imaging portable system, based on a smartphone using miniature optical and microelectronic components of information conversion for non-invasive monitoring of microphysical blood parameters, has been created. The system implements the principle of polarimetric blood photometry and a multiparametric analysis of the polarization properties of the laser radiation scattered by blood. The developed portable optoelectronic system, based on a smartphone, can be used for rapid blood diagnostics in disaster medicine and the presence of clinical contraindications to the formation of invasive tests. The proposed polarization-based approach is a promising automated alternative to traditional devices and systems for the research of microphysical blood parameters.

Intestinal adenocarcinoma originating from an undiagnosed Meckel's diverticulum.

Meckel's diverticulum is a congenital anomaly leading to the formation of a true diverticulum in the distal small intestine. Though most are asymptomatic and discovered incidentally, Meckel's diverticuli can give rise to a wide range of symptoms. Rarely, this can be a malignancy, most commonly a carcinoid tumor. Other cancers have also been reported, with adenocarcinomas being particularly rare. Here, we report the case of a 62-year-old man presenting to the emergency room with vague gastrointestinal symptoms. Subsequent workup revealed a 3 cm mass in the distal jejunum/proximal ileum, which was located within a previously undiagnosed Meckel's diverticulum. The mass was sent to pathology, who confirmed an adenocarcinoma arising from a small bowel diverticulum. This case serves as an important reminder of the malignant potential of a Meckel's diverticulum and adds to the ongoing discussion regarding whether prophylactic diverticulectomy should be recommended to patients with a known Meckel's diverticulum.

Analysis of Rail Passenger Flow in a Rail Station Concourse Prior to and During the COVID-19 Pandemic Using Event-Based Simulation Models and Scenarios.

During COVID-19, certain means were proposed to improve crowd management in the Birmingham New Street railway station. To validate the current system of crowd management in the station, this paper examines the rail passenger flow in the concourse of the Birmingham New Street railway station and the passenger interactions and queueing phenomena associated with it, mainly at the ticket machines, offices and gates, prior to and during the implementation of COVID-19 measures. The passenger behaviour in the concourse of the station was simulated using the SIMUL8 event-based simulation modelling package. Three different scenarios were modelled to analyse the changes and impacts from pre-COVID-19 and within the COVID-19 context. The results revealed that passenger behaviour in railway stations is changing due to COVID-19. Specifically, passengers are more likely to buy tickets using their smartphones or online prior to or whilst entering the station so that they can go through the station concourse with minimal queuing times and avoid contact with a facility of common use at the station, whereas those without tickets are more likely to be in a queue to buy their tickets in the station. For pre-COVID, the results showed that even with a reduced number of ticket machines, overcrowding inside the station was unlikely to occur, as 80% of all passengers in the simulation completed service within a 15-minute time frame. However, during implementation of COVID-19 measures, as the number of passengers using the station dropped significantly and more passengers bought their tickets using their smartphones and/or online, queueing times were also shorter, and thus passengers spent less time in the system. The simulation results were in accordance with the expected practice; hence the effectiveness of the simulation model was verified. Overall, as a result of this study, the following suggestions to improve crowd management in a railway passenger station concourse are proposed: encourage passengers to purchase tickets on their smartphones, remove ticket gates and replace them with sensors, and provide a one-way passenger flow system in the main concourse of the station.

Republication: Targeting PI3KC2ß Impairs Proliferation and Survival in Acute Leukemia, Brain Tumours and Neuroendocrine Tumours.

BACKGROUND: Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks. MATERIALS AND METHODS: The expression pattern and functions of the class II PI3KC2ß isoform were investigated in a panel of tumour samples and cell lines. RESULTS: Overexpression of PI3KC2ß was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2ß or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2ß also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents. CONCLUSION: Together, these data show that PI3KC2ß contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies.

Linear Interval Approximation for Smart Sensors and IoT Devices.

In this work, we introduce and use an innovative approach for adaptive piecewise linear interval approximation of sensor characteristics, which are differentiable functions. The aim is to obtain a discreet type of inverse sensor characteristic, with a predefined maximum approximation error, with minimization of the number of points defining the characteristic, which in turn is related to the possibilities for using microcontrollers with limited energy and memory resources. In this context, the results from the study indicate that to overcome the problems arising from the resource constraints of smart devices, appropriate "lightweight" algorithms are needed that allow efficient connectivity and intelligent management of the measurement processes. The method has two benefits: first, low-cost microcontrollers could be used for hardware implementation of the industrial sensor devices; second, the optimal subdivision of the measurement range reduces the space in the memory of the microcontroller necessary for storage of the parameters of the linearized characteristic. Although the discussed computational examples are aimed at building adaptive approximations for temperature sensors, the algorithm can easily be extended to many other sensor types and can improve the performance of resource-constrained devices. For prescribed maximum approximation error, the inverse sensor characteristic is found directly in the linearized form. Further advantages of the proposed approach are: (i) the maximum error under linearization of the inverse sensor characteristic at all intervals, except in the general case of the last one, is the same; (ii) the approach allows non-uniform distribution of maximum approximation error, i.e., different maximum approximation errors could be assigned to particular intervals; (iii) the approach allows the application to the general type of differentiable sensor characteristics with piecewise concave/convex properties.

Review of Microfluidic Methods for Cellular Lysis.

Cell lysis is a process in which the outer cell membrane is broken to release intracellular constituents in a way that important information about the DNA or RNA of an organism can be obtained. This article is a thorough review of reported methods for the achievement of effective cellular boundaries disintegration, together with their technological peculiarities and instrumental requirements. The different approaches are summarized in six categories: chemical, mechanical, electrical methods, thermal, laser, and other lysis methods. Based on the results derived from each of the investigated reports, we outline the advantages and disadvantages of those techniques. Although the choice of a suitable method is highly dependent on the particular requirements of the specific scientific problem, we conclude with a concise table where the benefits of every approach are compared, based on criteria such as cost, efficiency, and difficulty.

Synthesis, Characterization, Quantum-Chemical Calculations and Cytotoxic Activity of 1,8-Naphthalimide Derivatives with Non-Protein Amino Acids.

BACKGROUND: The 1,8-Naphthalimides constitute an important class of biologically active, DNAbinding compounds. There are no available data on the synthesis of 1,8-naphthalimide derivatives with nonprotein amino acids and their biological activity. The aim of this paper was to determine the synthesis, structural characterization and cytotoxic activity of new 1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)cycloalkane-1- carboxylic acids with 5-, 6-, 7-, 8- and 12-membered rings as well as 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)- yl)adamantane-2-carboxylic acid and 1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-1,2,3,4-tetrahydronaphthalene- 1-carboxylic acid. METHODS: The target compounds were obtained by an interaction of 1,8-naphthalic anhydride with a series of non-protein amino acids. The optimized geometry and harmonic vibrational frequencies have been calculated by DFT employing B3LYP functional using 6-31G(d,p) basis set. An ab initio (MP2 and Hartee-Fock) and DFT (different functionals) using several basis sets have been applied for NMR calculations. The cytotoxic effects of the synthesized compounds are assessed against two human tumor cell lines, namely K-562 (chronic myeloid leukemia) and HUT-78 (cutaneous T-cell lymphoma) after 72 h exposure, using the MTT-dye reduction assay. The apoptogenic effects and the ability to modulate the NFκB-signaling pathways were determined using commercially available ELISA kits. RESULTS: All compounds inhibited the growth of malignant cells at micromolar concentrations whereby compound 4b (1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)cyclohexane-1-carboxylic acid) demonstrated superior activity in both cell lines with IC50 values comparable to those of the reference anticancer drug melphalan. CONCLUSION: New 1,8-naphthalimide derivatives with non-protein amino acids were successfully synthesized. Quantum-chemical calculations were performed to elucidate the structure of the newly synthesized compounds. There is a proper alignment between theoretical and experimental results. The cytotoxicity of the synthesized products against two human tumor cell lines, namely K-562 and HUT-78 was evaluated. All compounds inhibited the growth of malignant cells at micromolar concentrations. The pharmacodynamics evaluation of compound 4b showed that its cytotoxicity is mediated by induction of apoptosis and inhibition of NFκB-signaling.

Cushing's Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century.

Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing's disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing's disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.

Optic Nerve Glioma in Two Sisters with Family History of Neurofibromatosis Type 1.

Optic nerve glioma (ONG) is associated in 10% of patients with neurofibromatosis (NF) type 1. To date no consensus has been reached regarding the therapeutic approach and prevention of visual impairment in these patients. Reports in the literature vary from a conservative approach (observation) to the use of single treatment modalities or multimodality protocols of surgical removal, radiotherapy, and/or chemotherapy. We present our experience with two siblings with ONG whose mother carries cutaneous stigmata of NF type 1. The younger sister was diagnosed 3 years after the treatment of the older sibling following recommended imaging for screening. Postoperative follow-up for 11 and 15 years, respectively, demonstrated lack of tumor regrowth and preserved vision in the contralateral eye. We discuss the treatment strategy in pediatric patients with orbital ONG associated with NF type 1.

Study on the Synthesis, Characterization and Bioactivities of 3-Methyl-9'-fluorenespiro-5-hydantoin.

This work describes a method for synthesis, as well as in vitro antiproliferative and antibacterial investigation of 3-methyl-9'-fluorenespiro-5-hydantoin. The structure of the substituted fluorenylspirohydantoin derivative was verified by UV-Vis, FT-IR, Raman, (1)H-NMR and (13)C-NMR spectroscopy, and by using a combination of 2D NMR experiments, which included (1)H-(1)H COSY, HMQC and HMBC sequences. The geometry of the compound was optimized by the B3LYP density functional with 6-31G(d) basis set and the (1)H and (13)C NMR spectra were predicted with the HF/6-31G(d) calculations at the optimized geometry. The anticancer activity of the 3-methyl-9'-fluorenespiro-5-hydantoin was determined in suspension cell lines originating from tumors in humans (WERI-Rb-1). The cytotoxic effect was evaluated by WST-assay (Roche Applied Science). The antimicrobial effect of the compound against Gram-negative, Gram-positive bacteria and the yeast Candida albicans was investigated.

New platinum(II) complexes of cycloalkanespiro-5-(2-thiohydantoins). Synthesis and quantum chemical investigation.

Synthesis and characterization of new Pt(II) complexes of cyclohexanespiro-5-(2-thiohydantoin) (L1) and cycloheptanespiro-5-(2-thiohydantoin) (L2) are discussed. The new complexes are studied by elemental analysis, IR, ATR FTIR spectroscopy. The free ligands are investigated by UV-Vis, FT-IR, (1)H NMR, (13)C NMR and Raman spectroscopy. The ground-state equilibrium geometries of the ligands L1 and L2 and their complexes with Pt(II) are optimized at the BLYP/CEP-31G theoretical level.

Synthesis of 3',4'-dihydro-2H,2'H,5H-spiro [imidazolidine-4,1'-naphthalene]-2,5-dione and its derivatives.

The synthesis of two novel compounds, 1-amino-3',4'-dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione and 1,3-bis(hydroxymethyl)-3',4'-dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, was reported. The structures of the compounds were verified by (1)H, (13)C NMR and IR spectroscopy and quantum-chemical calculations at DFT level.

Synthesis and in vitro activity of platinum(II) complexes of two fluorenylspirohydantoins against a human tumour cell line.

This paper presents a method for synthesis and cytotoxicity of new platinum(II) complexes of (9'-fluorene)-spiro-5-hydantoin (L1) and (9'-fluorene)-spiro-5-(2-thiohydantoin) (L2). The new obtained complexes were studied by elemental analysis: ultraviolet-visible, attenuated total reflection Fourier transform infrared (ATR-FTIR), and 1H- and 13C-NMR for Pt(II) compounds and additionally Raman spectroscopy for free ligands. Based on the experimental data, the most probable structure of the complexes is suggested. In the present study, we have examined cytotoxic activity of (9'-fluorene)-spiro-5-hydantoin (L1) and (9'-fluorene)-spiro-5-(2-thiohydantoin) (L2) and their Pt(II) complexes on the retinoblastoma cell line WERI-Rb-1.

Evaluation of prognostic utility of MIB-1 and p53 expression in pituitary adenomas: correlations with clinical behaviour and follow-up results.

Pituitary adenomas (PAs) show a broad clinicomorphological spectrum. The proliferation activity, evaluated by MIB-1 labelling index (LI), and p53 expression have been pointed as predictive markers for invasiveness and progression. The aim of this study was to evaluate the proliferation rate and p53 expression and to look for any relationships with the clinical behaviour and follow-up results in a series of Bulgarian patients with PAs. A total of 93 patients with PAs (81 hormone-secreting, 12 non-functioning), who were operated on and followed up for a period of five years, were included. The MIB-1 LI and p53 expressions were determined by immunohistochemistry and correlated with various clinical and tumour variables. The whole group of PAs showed a low proliferation rate with evident variations in a small number of cases (MIB-1 LI - 0.50 ± 0.56, from 0.1 to 3.30). MIB-1 LI correlated with tumour size (p = 0.012) and was positively related with male gender (p = 0.23) and partial surgical resection (p = 0.036). We found no significant differences regarding the age, functional activity, invasion (n = 33), expansion (n = 37) and tumour recurrences (seven cases). Only 10 cases (10.8%) showed a focal, nuclear p53 immunoreactivity. The p53 positive tumours had higher proliferation rate (p = 0.0001) but no relationship with the other clinical and tumour variables. Among all cases, there was only one case with higher MIB-1 LI (3.3%), positive p53 expression and tumour recurrence after surgery. Our results show that most PAs have a low proliferation rate and lack of p53 expression, as well as no relationship with tumour invasion or postsurgical progression.

Phosphoinositide 3-kinase C2ß regulates RhoA and the actin cytoskeleton through an interaction with Dbl.

The regulation of cell morphology is a dynamic process under the control of multiple protein complexes acting in a coordinated manner. Phosphoinositide 3-kinases (PI3K) and their lipid products are widely involved in cytoskeletal regulation by interacting with proteins regulating RhoGTPases. Class II PI3K isoforms have been implicated in the regulation of the actin cytoskeleton, although their exact role and mechanism of action remain to be established. In this report, we have identified Dbl, a Rho family guanine nucleotide exchange factor (RhoGEF) as an interaction partner of PI3KC2ß. Dbl was co-immunoprecipitated with PI3KC2ß in NIH3T3 cells and cancer cell lines. Over-expression of Class II phosphoinositide 3-kinase PI3KC2ß in NIH3T3 fibroblasts led to increased stress fibres formation and cell spreading. Accordingly, we found high basal RhoA activity and increased serum response factor (SRF) activation downstream of RhoA upon serum stimulation. In contrast, the dominant-negative form of PI3KC2ß strongly reduced cell spreading and stress fibres formation, as well as SRF response. Platelet-derived growth factor (PDGF) stimulation of wild-type PI3KC2ß over-expressing NIH3T3 cells strongly increased Rac and c-Jun N-terminal kinase (JNK) activation, but failed to show similar effect in the cells with the dominant-negative enzyme. Interestingly, epidermal growth factor (EGF) and PDGF stimulation led to increased extracellular signal-regulated kinase (Erk) and Akt pathway activation in cells with elevated wild-type PI3KC2ß expression. Furthermore, increased expression of PI3KC2ß protected NIH3T3 from detachment-dependent death (anoikis) in a RhoA-dependent manner. Taken together, these findings suggest that PI3KC2ß modulates the cell morphology and survival through a specific interaction with Dbl and the activation of RhoA.

Targeting PI3KC2ß impairs proliferation and survival in acute leukemia, brain tumours and neuroendocrine tumours.

BACKGROUND: Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks. MATERIALS AND METHODS: The expression pattern and functions of the class II PI3KC2ß isoform were investigated in a panel of tumour samples and cell lines. RESULTS: Overexpression of PI3KC2ß was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2ß or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2ß also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents. CONCLUSION: Together, these data show that PI3KC2ß contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies.

Two methods for spirothiohydantoin synthesis.

Two methods for spirothiohydantoin synthesis are presented. The title compounds were prepared with reaction of the corresponding 1-aminocycloalkanecarboxylic acids and thiourea. These compounds were also prepared by a hydrolysis of the relevant spirodithiohydantoins with barium hydroxide. The structures of the compounds obtained were verified by comparison of 1H, and 13C NMR, IR and MS spectral data.

A complete 1H and 13C NMR data assignment for 3-phenylmethylene-1H,3H-naphtho-[1,8-c,d]-pyran-1-one.

Complete assignments of the 1H and 13C NMR chemical shifts for 3-phenylmethylene-1H,3H-naphtho-[1,8-c,d]-pyran-1-one were done by means of one- and two-dimensional NMR techniques, including 1H-(1)H COSY, HMQC and HMBC spectra. Ab initio quantum chemistry calculations and a shift prediction by an incremental method provided values close to the proposed assignments. All mid-IR spectral bands are given as reference data. The DRIFT FTIR, ATR FTIR and Raman spectra are given as a Supplementary data in JCAMP-DX format, version 4.24. In addition, a method of compound's synthesis, that has the product yield higher as compared to already known data in the literature, is given.

AKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001.

PURPOSE: The Akt/mammalian target of rapamycin (mTOR) pathway is frequently activated in human cancers and plays an important role in small cell lung cancer (SCLC) biology. We investigated the potential of targeting mTOR signaling as a novel antitumor approach in SCLC. EXPERIMENTAL DESIGN: The expression of mTOR in patient specimens and in a panel of SCLC cell lines was analyzed. The effects on SCLC cell survival and downstream signaling were determined following mTOR inhibition by the rapamycin derivative RAD001 (Everolimus) or down-regulation by small interfering RNA. RESULTS: We found elevated expression of mTOR in patient specimens and SCLC cell lines, compared with normal lung tissue and normal lung epithelial cells. RAD001 treatment impaired basal and growth factor-stimulated cell growth in a panel of SCLC cell lines. Cells with increased Akt pathway activation were more sensitive to RAD001. Accordingly, a constitutive activation of the Akt/mTOR pathway was sufficient to sensitize resistant SCLC cells to the cytotoxic effect of RAD001. In the sensitive cells, RAD001 showed a strong additive effect to the proapoptotic action of the chemotherapeutic agent etoposide. Intriguingly, we observed low Bcl-2 family proteins levels in the SCLC cells with a constitutive Akt pathway activation, whereas an increased expression was detected in the RAD001-resistant SCLC cells. An antisense construct targeting Bcl-2 or a Bcl-2-specific inhibitor was able to sensitize resistant SCLC cells to RAD001. Moreover, SCLC tumor growth in vivo was significantly inhibited by RAD001. CONCLUSION: Together, our data show that inhibiting mTOR signaling with RAD001 potently disrupts growth and survival signaling in human SCLC cells.