Final Step Research Articles

Investment attractiveness factors in the opinion of companies from Special Economic Zones in Poland

The purpose of the research is the identification of important determinants shaping the investment attractiveness of the country (region) from the point of view of potential investors and an assessment of the degree of stakeholder satisfaction with existing methods of examining the investment climate and their availability for practical use. In order to assess a set of determinants that exert the most significant influence on a country’s investment climate, a questionnaire was developed consisting of 25 questions of various orientations. These questions were designed to assess the opinions of potential investors regarding the degree of influence of various factors on their decision on capital allocation and the investment climate of a country. The survey was conducted among 506 enterprises and 14 management bodies of Special Economic Zones in Poland from June 10 to July 20, 2023. The final step involved the analysis of the survey results using statistical methods.

Point Cloud Densification Algorithm for Multiple Cameras and Lidars Data Fusion.

Fusing data from many sources helps to achieve improved analysis and results. In this work, we present a new algorithm to fuse data from multiple cameras with data from multiple lidars. This algorithm was developed to increase the sensitivity and specificity of autonomous vehicle perception systems, where the most accurate sensors measuring the vehicle's surroundings are cameras and lidar devices. Perception systems based on data from one type of sensor do not use complete information and have lower quality. The camera provides two-dimensional images; lidar produces three-dimensional point clouds. We developed a method for matching pixels on a pair of stereoscopic images using dynamic programming inspired by an algorithm to match sequences of amino acids used in bioinformatics. We improve the quality of the basic algorithm using additional data from edge detectors. Furthermore, we also improve the algorithm performance by reducing the size of matched pixels determined by available car speeds. We perform point cloud densification in the final step of our method, fusing lidar output data with stereo vision output. We implemented our algorithm in C++ with Python API, and we provided the open-source library named Stereo PCD. This library very efficiently fuses data from multiple cameras and multiple lidars. In the article, we present the results of our approach to benchmark databases in terms of quality and performance. We compare our algorithm with other popular methods.

Spirituality and family caregivers: Ethical considerations on the role as a spiritual guide

ABSTRACT In recent years, spirituality has become a key factor in the field of care and, even more precisely, in dealing with sick and dying people. Those affected find themselves in existentially threatening situations and are looking for advice, help, an ultimate meaning or simply want to cope with the situation. It is not uncommon for other individuals to provide support in these constellations. This article deals with an ethical perspective on spirituality in relation to family caregivers. In a first step, both family caregivers and the concept of spirituality are examined and placed in relation to each other. Then, in a second step, the role of these people who have taken on the care of a loved one is addressed. Consequently, it is shown that they can be assigned a task of guidance comparable but not identical to that of pastoral caregivers, insofar as they can contribute to spiritual experiences through constant presence, engagement with the person in need of care and caring interaction. In a final step, the extent to which family caregivers have good reasons to be available for the spiritual needs of the person receiving care is presented. Spirituality should be internalized as an ethically important guideline in the care of sick and dying people when this invaluable task is taken on.

To explore the postoperative nutritional status and factors influencing prognosis in patients with chronic constipation complicated by malnutrition.

Many patients with constipation also suffer from varying degrees of malnutrition, and the relationship between the two conditions is a vicious cycle. Surgery is the final step in the treatment of constipation, with a success rate of up to 95%. This study aims to investigate the effects of surgical treatment on the nutritional status of patients with chronic constipation and malnutrition. A total of 60 patients with chronic constipation and various degrees of malnutrition who underwent surgery in our department from January 2020 to March 2023 were included in this study. Biochemical tests including BMI, albumin, total protein, hemoglobin, cholesterol and lymphocyte count were conducted, as well as measurements of inflammatory markers such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), and C-reactive protein (CRP). Additionally, multiple nutritional risk screening scales (NRS2002, MUST, NRI, and MNA) and the prognostic nutritional index (PNI) were used to assess the nutritional status of patients before surgery, as well as at 1 month, 3 months, and 6 months post-surgery. Finally, we analyzed the factors influencing postoperative recovery outcomes in patients. Compared to pre-operation, the BMI of patients significantly increased at 1 month, 3 months, and 6 months after the operation, with statistically significant differences (p < 0.001). Multiple nutritional risk assessment tools (NRS2002, MUST, NRI, and MNA), as well as the prognostic nutritional index (NPI), indicated a reduction in nutritional risk and improvement in nutritional status at 1, 3, and 6 months post-surgery, compared to pre-surgery levels (p < 0.001). The levels of albumin, total protein, and hemoglobin in patients at 1, 3, and 6 months after the surgery were significantly higher than those before the surgery (p < 0.001). However, there was no significant change in the number of lymphocytes. Inflammatory markers such as IL-6, IL-8, and CRP exhibited a significant decrease after the surgery, reaching normal levels at 6 months post-surgery (p < 0.001). Low BMI, low PNI, and low cholesterol levels are independent risk factors for patient prognosis (p < 0.05). Surgical treatment can enhance the nutritional status of constipation patients with malnutrition, which in turn promotes the restoration of intestinal motility. The patient's nutritional status will impact the postoperative recovery outcomes.

Bearing fault detection using second-order moment spectrum and adaptive time-varying morphological filtering

The second-order moment spectrum is a method designed to simplify the complex shape of the spectrum, thus facilitating its interpretation for the identification and localization of defects based on peak frequency. Generally used as a final step in defect detection methods, this method offers the advantage of a more easily interpretable spectral shape. Compared to the shape of the spectrum of the vibration signal defined by the Fourier transform, which includes sidebands composed of peaks of large amplitude at different frequencies, the spectrum generated by the second-order moment spectrum method stands out for its simplicity. Starting from the mean and standard deviation of the vibration signal, the second-order moment can be defined as the power of the ratio between the standard deviation and the difference between the signal and the mean. Next, the Fourier transform is applied to express the second-order moment spectrum. The performance of the second-order moment spectrum is evaluated using the principle of comparison with the envelope spectrum obtained by the Hilbert transform. Vibration signals are analyzed using two methods: adaptive time-varying morphological filtering and second-order moment spectrum. After applying these methods to the signals from the database, we observe high-amplitude peaks at the frequencies corresponding to inner ring and ball defects. The second-order moment spectrum gives similar results to those obtained with the Hilbert transform envelope.

On the geometry at infinity of manifolds with linear volume growth and nonnegative Ricci curvature

We prove that an open noncollapsed manifold with nonnegative Ricci curvature and linear volume growth always splits off a line at infinity. This completes the final step to prove the existence of isoperimetric sets for given large volumes in the above setting. We also find that under our assumptions, the diameters of the level sets of any Busemann function are uniformly bounded as opposed to a classical result stating that they can have sublinear growth when the end is collapsing. Moreover, some equivalent characterizations of linear volume growth are given. Finally, we construct an example to show that for manifolds in our setting, although their limit spaces at infinity are always cylinders, the cross sections can be nonhomeomorphic.

Potent and Selective Oxidatively Labile Ether‐Based Prodrugs through Late‐Stage Boronate Incorporation

AbstractThis manuscript describes a new strategy for prodrug synthesis in which a relatively inert ether group is introduced at an early stage in a synthetic sequence and functionalized in the final step to introduce a prodrug‐activating group through a chemoselective process. Boryl allyloxy (BAO) ether groups are synthesized through several metal‐mediated processes to form entities that are readily cleaved under oxidative conditions commonly found in cancer cells. The high cleavage propensity of the BAO group allows for ether cleavage, making these compounds substantially more hydrolytically stable in comparison to acyl‐linked prodrugs while retaining the ability to release alcohols. We report the preparation of prodrug analogues of the natural products camptothecin and pederin from acetal precursors that serve as protecting groups in their synthetic sequences. The BAO acetal groups cleave in the presence of hydrogen peroxide to release the cytotoxic agents. The pederin‐based prodrug shows dramatically greater cytotoxicity than negative controls and outstanding selectivity and potency toward cancer cell lines in comparison to non‐cancerous cell lines. This late‐stage functionalization approach to prodrug synthesis should be applicable to numerous systems that can be accessed through chemoselective processes.

Rational Engineering of a β-Glucosidase (H0HC94) from Glycosyl Hydrolase Family I (GH1) to Improve Catalytic Performance on Cellobiose.

The conversion of lignocellulosic feedstocks by cellulases to glucose is a critical step in biofuel production. β-Glucosidases catalyze the final step in cellulose breakdown, producing glucose, and are often the rate-limiting step in biomass hydrolysis. The specific activity of most natural and engineered β-glucosidase is higher on the artificial substrate p-nitrophenyl β-d-glucopyranoside (pNPGlc) than on the natural substrate, cellobiose. We report an engineered β-glucosidase (Q319A H0HC94) with a 1.8-fold higher specific activity (366.3 ± 36 μmol/min/mg), a 1.5-fold increase in kcat (340.8 ± 27 s-1), and a 3-fold increase in catalytic efficiency (236.65 mM-1 s-1) over H0HC94 (WT) on cellobiose. Molecular dynamic simulations and protein structure network analysis indicate that the Q319A H0HC94 active site pocket is significantly remodeled compared to the WT, leading to changes in enzyme conformation, better accessibility of cellobiose inside the active site pocket, and higher enzymatic activity. This study shows the impact of rational engineering of a nonconserved residue to increase β-glucosidase substrate accessibility and catalytic efficiency by reducing crowding interaction between cellobiose and active site pocket residues near the gatekeeper region and increasing pocket volume and surface area. Thus, rational engineering of previously characterized enzymes could be an excellent strategy to improve cellulose hydrolysis.

Potent and Selective Oxidatively Labile Ether-Based Prodrugs through Late-Stage Boronate Incorporation.

This manuscript describes a new strategy for prodrug synthesis in which a relatively inert ether group is introduced at an early stage in a synthetic sequence and functionalized in the final step to introduce a prodrug-activating group through a chemoselective process. Boryl allyloxy (BAO) ether groups are synthesized through several metal-mediated processes to form entities that are readily cleaved under oxidative conditions commonly found in cancer cells. The high cleavage propensity of the BAO group allows for ether cleavage, making these compounds substantially more hydrolytically stable in comparison to acyl-linked prodrugs while retaining the ability to release alcohols. We report the preparation of prodrug analogues of the natural products camptothecin and pederin from acetal precursors that serve as protecting groups in their synthetic sequences. The BAO acetal groups cleave in the presence of hydrogen peroxide to release the cytotoxic agents. The pederin-based prodrug shows dramatically greater cytotoxicity than negative controls and outstanding selectivity and potency toward cancer cell lines in comparison to non-cancerous cell lines. This late-stage functionalization approach to prodrug synthesis should be applicable to numerous systems that can be accessed through chemoselective processes.

Alternative payment models in Dutch hospital care: what works, how, why and under what circumstances? Protocol for a realist evaluation study

IntroductionThe predominant provider payment models in healthcare, particularly fee-for-service, hinder the delivery of high-value care and can encourage healthcare providers to prioritise the volume of care over the value of...

Full-reference calibration-free image quality assessment

Objective Image Quality Assessment (IQA) methods often lack of linearity of their quality estimates with respect to scores expressed by human subjects and therefore IQA metrics undergo a calibration process based on subjective quality examples. However, example-based training presents a challenge in terms of generalization hampering result comparison across different applications and operative conditions. In this paper, new Full Reference (FR) techniques, providing estimates linearly correlated with human scores without using calibration are introduced. We show that on natural images, application of estimation theory and psychophysical principles to images degraded by Gaussian blur leads to a so-called canonical IQA method, whose estimates are linearly correlated to both the subjective scores and the viewing distance. Then, we show that any mainstream IQA methods can be reconducted to the canonical method by converting its metric based on a unique specimen image. The proposed scheme is extended to wide classes of degraded images, e.g. noisy and compressed images. The resulting calibration-free FR IQA methods allows for comparability and interoperability across different imaging systems and on different viewing distances. A comparison of their statistical performance with respect to state-of-the-art calibration prone methods is finally provided, showing that the presented model is a valid alternative to the final 5-parameter calibration step of IQA methods, and the two parameters of the model have a clear operational meaning and are simply determined in practical applications. The enhanced performance are achieved across multiple viewing distance databases by independently realigning the blur values associated with each distance.

PKM2 regulates metabolic flux and oxidative stress in the murine heart.

Cardiac metabolism ensures a continuous ATP supply, primarily using fatty acids in a healthy state and favoring glucose in pathological conditions. Pyruvate kinase muscle (PKM) controls the final step of glycolysis, with PKM1 being the main isoform in the heart. PKM2, elevated in various heart diseases, has been suggested to play a protective role in cardiac stress, but its function in basal cardiac metabolism remains unclear. We examined hearts from global PKM2 knockout (PKM2-/-) mice and found reduced intracellular glucose. Isotopic tracing of U-13C glucose revealed a shift to biosynthetic pathways in PKM2-/- cardiomyocytes. Total ATP content was two-thirds lower in PKM2-/- hearts, and functional analysis indicated reduced mitochondrial oxygen consumption. Total reactive oxygen species (ROS) and mitochondrial superoxide were also increased in PKM2-/- cardiomyocytes. Intriguingly, PKM2-/- hearts had preserved ejection fraction compared to controls. Mechanistically, increased calcium/calmodulin-dependent kinase II activity and phospholamban phosphorylation may contribute to higher sarcoendoplasmic reticulum calcium ATPase 2 pump activity in PKM2-/- hearts. Loss of PKM2 led to altered glucose metabolism, diminished mitochondrial function, and increased ROS in cardiomyocytes. These data suggest that cardiac PKM2 acts as an important rheostat to maintain ATP levels while limiting oxidative stress. Although loss of PKM2 did not impair baseline contractility, its absence may make hearts more sensitive to environmental stress or injury.

Model of Tsunami Mitigation and Evacuation Routes in Pancer Banyuwangi

Banyuwangi has the largest tsunami disaster risk in East Java, about 45,305 affected people, Rp. 160,886,000,- for the risk of physical losses, Rp. 106,414,000,- for the risk of economic losses and 84 ha of environmental losses (BNPB, 2023). In addition, according to historical data, Banyuwangi was hit by tsunami on June 9, 1994 with magnitude of 7.8 which caused a maximum run up of 14.0 m and killed 238 lives (BNPB, 2023). Also based on Undang- undang No. 24 Tahun 2007 concerning Disaster Management, Indonesia should have preventive and mitigation measures for tsunami disasters both before and after as an effort to reduce the disaster risk (Putra, 2009) . Tsunami modeling in southern Java using COMCOT v1.7 as tsunami worst case scenario in Banyuwangi is the first step for mitigation. The initial results of COMCOT were then used for preparing tsunami disaster evacuation route planning based on the Tsunami Natural Disaster Evacuation Route Planning Guidelines, Dirjen Bina Marga, 2023. The final step is validation/routing survey of the 8 (eight) routes that have been determined. 2 (two) of the 8 (eight) routes fulfill the guidelines for planning tsunami mitigation routes. However, all routes can be considered due to the distribution of settlements, the number of affected residents and the number of routes needed

Elevated cerebrospinal fluid glial fibrillary acidic protein levels in Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a rare, multiple malformation/intellectual disability disorder caused by pathogenic variants of DHCR7. DHCR7 catalyzes the reduction of 7-dehydrocholesterol (7DHC) to cholesterol in the final step of cholesterol biosynthesis. This results in accumulation of 7DHC and a cholesterol deficiency. Although the biochemical defect is well delineated and multiple mechanisms underlying developmental defects have been explored, the post developmental neuropathological consequences of altered central nervous system sterol composition have not been studied. Preclinical studies suggest that astroglial activation may occur in SLOS. To determine if astroglial activation is present in individuals with SLOS, we quantified cerebrospinal fluid (CSF) glial fibrillary acidic protein using a Quanterix Simoa® GFAP Discovery Kit for SR-X™. Relative to an age-appropriate comparison group, we found that CSF GFAP levels were elevated 3.9-fold in SLOS (3980 ± 3732 versus 1010 ± 577 pg/ml, p = 0.0184). Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, has previously been shown to increase expression of hypomorphic DHCR7 alleles and in a placebo-controlled trial improved serum sterol levels and decreased irritability. Using archived CSF samples from that prior study, we observed a significant decrease (p = 0.0119) in CSF GFAP levels in response to treatment with simvastatin. Although further work needs to be done to understand the potential contribution of neuroinflammation to SLOS neuropathology and cognitive dysfunction, these data confirm astroglial activation in SLOS and suggest that CSF GFAP may be a useful biomarker to monitor therapeutic responses.

Unsupervised meta-analysis on chemical elements and atomic energy prediction: A case study on the periodic table

This paper presents an artificial classification and atomic energy correlation analysis of the chemical components. The choice of data mining is due to its robustness, which can explore intrinsic or hidden relationships between chemical components and their properties. The Mendeleev table is conceivably the earliest example of the data analysis technique in materials science. However, the classical periodic table represents the arrangement of chemical elements based on particular periodicities, which has the issue of property progression for a few chemical components. In this investigation, we utilized one of the unsupervised data mining methods (principal component analysis) to explore knowledge from the chemical components database based on all the prepared properties. The main objective is to make an artificial classification of chemical components depending on their accessible physical and energetic properties. The results revealed the effectiveness of the data mining method in appreciating the relationships between the variables and properties that offer a new approach to seeing a Mendeleev table. The final step of this work highlights the significance of predictive polynomials that permit the scientific community to make atomic total energy predictions for each chemical component, from helium to lawrencium.

Assessment of Cement Mortar Strength Mixed with Waste Copper Mine Tailings (CT) by Applying Gradient Boosting Regressor and Grid Search Optimization Machine Learning Approach

Growing environmental concerns and resource scarcity, the construction industry must investigate sustainable materials that reduce waste while improving building material properties. This study investigates the viability of using waste copper mine tailings (CT) as a partial replacement for river sand in cement mortar, assessing the impact on mechanical strength and developing a predictive model using a Gradient Boosting Regressor (GBR) and Grid Search Optimization (GSO). Copper tailings mix designs ranging from 0% to 50% replacement by volume (river sand) were developed, with a constant cement quantity while varying the proportions of sand and tailings. The experiments were carried out at Poornima University in Jaipur, using standard protocols to prepare specimens and measure their compressive strength for 0% CT to 50% CT as volume percent in the mixture. The results showed that the addition of copper tailings up to 20% (3CT2) had highly increased the mortar strength, while mix design 6CT3 showed the best strength at 30% CT. Beyond this threshold, strength declined, thus indicating an optimal replacement level. In the final step of the research, the GBR-GSO-based machine learning approach was employed for developing the predictive model for compressive strength in mortar with different contents of copper tailing for mix types 3CT and 6CT. The predictions obtained by the developed model were in very good agreement with empirical data, thus supporting the potential of machine learning to predict material performance for guiding the use of unconventional additives in construction. It could be said that this work not only represents the material properties of copper-tailing-infused mortar but also showcases state-of-the-art machine learning techniques in the building materials science domain while opening new paths for more innovative and sustainable building practices.

Our House Won't Rebuild Itself: Peace, Love, and Hope as Tools to Transform Graduate Medical Education.

Graduate medical education (GME), the period of specialty and subspecialty training following attainment of a medical degree, is the final step in a continuum of medical education culminating in independent physician practice. This manuscript uses the metaphor "our house" to describe all aspects of the GME environment in which health care professionals and trainees learn and work. Our house's inhabitants have unequivocally stated that our house is in a state of disrepair. While physicians-in-training inevitably face challenges on their journey to independent practice, those from historically marginalized backgrounds face these challenges compounded by the disproportionate impact of identity-based harms. The authors use critical and liberatory theories to explore dominant power dynamics in GME, classifying identity-based harms as silence, pain, and despair. To strive for true transformation, the authors advocate for a new set of house rules, a different way of co-existing based on the principles of liberatory design. The authors call on readers to rebuild the house of GME by drawing parallels between the foundational human values of peace, love, and hope and the educational principles of psychological safety, identity safety, and belonging. To transform GME, our community must make space in our house for all individuals to join, and indeed, to rebuild together.

Evaluation of the detection method by a flotation method using a wire loop for gastrointestinal parasites.

Infections by gastrointestinal parasites are found in a variety of animals worldwide. For the diagnosis of such infections, the flotation method is commonly used to detect parasitic microorganisms, such as oocysts or eggs, in feces. Instead of adding a flotation solution after the final centrifugation step and using a cover slip to collect the parasites, the method using a wire loop for the recovery of the organisms has been reported as one of alternative methods. However, the recovery rates of microorganisms from the flotation method have not been analysed. In the present study, the utility of a flotation method with the use of a wire loop of 8mm in diameter (the loop method) was evaluated using different numbers of E. tenella oocysts and Heterakis gallinarum eggs, and chicken fecal samples collected at the farms. Consequently, we found that the oocysts and eggs in tubes could be collected at a ratio of 2.00 to 3.08. Thus, our results indicate that the loop method is a simple and time saving method, implicating the application for the estimated OPG/ EPG (Oocysts/Eggs per gram) of the samples.

Genome-wide characterization and expression analysis of the CINNAMYL ALCOHOL DEHYDROGENASE gene family in Triticum aestivum.

CINNAMYL ALCOHOL DEHYDROGENASE (CAD) catalyzes the NADPH-dependent reduction of cinnamaldehydes into cinnamyl alcohols and is a key enzyme found at the final step of the monolignol pathway. Cinnamyl alcohols and their conjugates are subsequently polymerized in the secondary cell wall to form lignin. CAD genes are typically encoded by multi-gene families and thus traditionally organized into general classifications of functional relevance. In silico analysis of the hexaploid Triticum aestivum genome revealed 47 high confidence TaCAD copies, of which three were determined to be the most significant isoforms (class I) considered bone fide CADs. Class I CADs were expressed throughout development both in RNAseq data sets as well as via qRT-PCR analysis. Of the 37 class II TaCADs identified, two groups were observed to be significantly co-expressed with class I TaCADs in developing tissue and under chitin elicitation in RNAseq data sets. These co-expressed class II TaCADs were also found to be phylogenetically unrelated to a separate clade of class II TaCADs previously reported to be an influential resistance factor to pathogenic fungal infection. Lastly, two groups were phylogenetically identified as class III TaCADs, which possess distinct conserved gene structures. However, the lack of data supporting their catalytic activity for cinnamaldehydes and their bereft transcriptional presence in lignifying tissues challenges their designation and function as CADs. Taken together, our comprehensive transcriptomic analyses suggest that TaCAD genes contribute to overlapping but nonredundant functions during T. aestivum growth and development across a wide variety of agroecosystems and provide tolerance to various stressors.

Generation and application of novel hES cell reporter lines for the differentiation and maturation of hPS cell-derived islet-like clusters

The significant advances in the differentiation of human pluripotent stem (hPS) cells into pancreatic endocrine cells, including functional β-cells, have been based on a detailed understanding of the underlying developmental mechanisms. However, the final differentiation steps, leading from endocrine progenitors to mono-hormonal and mature pancreatic endocrine cells, remain to be fully understood and this is reflected in the remaining shortcomings of the hPS cell-derived islet cells (SC-islet cells), which include a lack of β-cell maturation and variability among different cell lines. Additional signals and modifications of the final differentiation steps will have to be assessed in a combinatorial manner to address the remaining issues and appropriate reporter lines would be useful in this undertaking. Here we report the generation and functional validation of hPS cell reporter lines that can monitor the generation of INS+ and GCG+ cells and their resolution into mono-hormonal cells (INSeGFP, INSeGFP/GCGmCHERRY) as well as β-cell maturation (INSeGFP/MAFAmCHERRY) and function (INSGCaMP6). The reporter hPS cell lines maintained strong and widespread expression of pluripotency markers and differentiated efficiently into definitive endoderm and pancreatic progenitor (PP) cells. PP cells from all lines differentiated efficiently into islet cell clusters that robustly expressed the corresponding reporters and contained glucose-responsive, insulin-producing cells. To demonstrate the applicability of these hPS cell reporter lines in a high-content live imaging approach for the identification of optimal differentiation conditions, we adapted our differentiation procedure to generate SC-islet clusters in microwells. This allowed the live confocal imaging of multiple SC-islets for a single condition and, using this approach, we found that the use of the N21 supplement in the last stage of the differentiation increased the number of monohormonal β-cells without affecting the number of α-cells in the SC-islets. The hPS cell reporter lines and the high-content live imaging approach described here will enable the efficient assessment of multiple conditions for the optimal differentiation and maturation of SC-islets.