Nickel-based perovskite-catalysed direct phenol-to-aniline liquid-phase transformations.

Liquid phase direct amination of phenols to primary anilines with hydrazine was achieved using commercial NiLa-perovskite catalysts as bifunctional Lewis acid/redox-active catalysts without adding any external hydride sources. The amination strategy took place efficiently in the absence of any amount of reducing gasses (H2/NH3) and noble metals under mild conditions.

Influence of Machining Parameters on the Dimensional Accuracy of Drilled Holes in Engineering Plastics.

This paper explores the interaction between cutting parameters and the geometric accuracy of machined holes in a variety of engineering plastics, with the aim of improving manufacturing processes in the plastic processing industry. In the context of fast and precise manufacturing technology, the accuracy of drilled holes in polymers is of paramount importance, given their essential role in the assembly and functionality of finished parts. The objective of this research was to determine the influence of cutting speed and feed rate on the diameter and cylindricity of machined holes in six diverse types of plastics using a multilevel factorial design for analysis. The key message conveyed to the reader highlights that careful selection of cutting parameters is crucial to achieving high standards of accuracy and repeatability in plastic processing. The methodology involved structured experiments, looking at the effect of changing cutting parameters on a set of six polymer materials. A CNC machining center for drills and high-precision measuring machines were used to evaluate the diameter and cylindricity of the holes. The results of ANOVA statistical analysis showed a significant correlation between cutting parameters and hole sizes for some materials, while for others the relationship was less evident. The conclusions drawn highlight the importance of optimizing cutting speed and feed rate according to polymer type to maximize accuracy and minimize deviations from cylindricity. It was also observed that, under selected processing conditions, high- and medium-density polyurethane showed the best results in terms of accuracy and cylindricity, suggesting potential optimized directions for specific industrial applications.

Mesangial Expansion by Morphometry at 5 y After Kidney Transplantation: Incidence, Risk Factors, and Association With Graft Loss.

Background: Mesangial expansion (ME) is an understudied histologic lesion in renal allografts. The current Banff mm score is not reproducible and may miss important ME features. The study aimed to improve the quantification of ME using morphometry, assess changes over time, and determine its association with allograft loss. Methods: We studied ME in 1-y and 5-y surveillance biopsies in 835 kidney transplants performed between January 2000 and December 2013. ME was assessed using the Banff mm score by a central pathologist and by morphometry. We derived 3 different morphometric measures: (1) %ME mm (%glomeruli with ME in ≥2 lobules, like Banff mm); (2) %MEany (%glomeruli with any ME lesion); and (3) %ME area (sum of all ME areas/all glomerular tuft areas). Unadjusted and adjusted Cox models assessed the risk of death-censored allograft loss. Results: From 1- to 5-y biopsies, the mean Banff mm score increased from 0.18 to 0.34, whereas %ME mm increased from 2.5% to 13.3%. Banff mm score had modest correlations with morphometric ME measures. Moderate-severe %ME mm was present in 20.1% of 5-y biopsies, whereas only 6.6% of Banff mm scores were. In general, higher ME on both 1- and 5-y biopsies was associated with a deceased donor, older recipient age, recipient diabetes/obesity (present in >50% of severely affected biopsies), higher hemoglobin A1c at 5 y posttransplant, and recurrent kidney disease. Higher ME on 5-y biopsies was associated with delayed graft function. A higher Banff mm score at 1-y biopsy and morphometry ME measures at 5-y biopsy were associated with rejection during the first year posttransplant. Morphometric ME measures were associated with allograft loss independent of Banff scores and all clinical characteristics, including kidney function and recurrent disease. The model with %MEany had the highest c-statistic (0.872). Conclusions: Banff mm score underestimates the pervasiveness of ME in 5-y biopsies. ME is common and associated with alloimmune and nonalloimmune causes of graft loss.

Phenotypic and Genotypic Features of the FAN1 Mutation-Related Disease in a Large Hungarian Family.

Pathogenic variants in the FAN1 gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features of a FAN1 mutation-related disease involving five members of a Hungarian Caucasian family are presented. Each had adult-onset chronic kidney disease of unknown cause treated with renal replacement therapy and elevated liver enzymes. Short stature, emaciation, latte-colored skin, freckles, and a hawk-like nose in four patients, a limited intellect in two patients, and chronic restrictive lung disease in one patient completed the phenotype. Severe infections occurred in four patients. All five patients had ceased. Four patients underwent autopsy. KIN and extrarenal karyomegaly were observed histologically; the livers showed no specific abnormality. The genotyping using formalin-fixed tissue samples detected a hitherto undescribed homozygous FAN1 mutation (c.1673_1674insT/p.Met558lfs*4; exon 5) in three of these patients and a heterozygous FAN1 mutation in one patient. The reason for the heterozygosity is discussed. In addition, 56 family members consented to the screening for FAN1 mutation from which 17 individuals proved to be heterozygous carriers; a blood chemistry evaluation of their kidney and liver function did not find any abnormality. The clinical presentation of FAN1-related disease was multifaceted, and not yet described manifestations were observed besides kidney and liver disease. Mutation in this gene should be suspected in adults with small kidneys of unknown cause, elevated liver enzymes, and recurrent infections, even without a family history.

Assessment of trace and macroelement accumulation in cyprinid juveniles as bioindicators of aquatic pollution: effects of diets and habitat preferences.

Juveniles of three cyprinids with various diets and habitat preferences were collected from the Szamos River (Hungary) during a period of pollution in November 2013: the herbivorous, benthic nase (Chondrostoma nasus), the benthivorous, benthic barbel (Barbus barbus), and the omnivorous, pelagic chub (Squalius cephalus). Our study aimed to assess the accumulation of these elements across species with varying diets and habitat preferences, as well as their potential role in biomonitoring efforts. The Ca, K, Mg, Na, Cd, Cr, Cu, Fe, Mn, Pb, Sr, and Zn concentration was analyzed in muscle, gills, and liver using MP-AES. The muscle and gill concentrations of Cr, Cu, Fe, and Zn increased with trophic level. At the same time, several differences were found among the trace element patterns related to habitat preferences. The trace elements, including Cd, Pb, and Zn, which exceeded threshold concentrations in the water, exhibited higher accumulations mainly in the muscle and gills of the pelagic chub. Furthermore, the elevated concentrations of trace elements in sediments (Cr, Cu, Mn) demonstrated higher accumulation in the benthic nase and barbel. Our findings show habitat preference as a key factor in juvenile bioindicator capability, advocating for the simultaneous use of pelagic and benthic juveniles to assess water and sediment pollution status.

2-Step-Scores with optional nephropathology for the prediction of adverse outcomes for brain-dead donor kidneys in Eurotransplant.

BACKGROUND AND HYPOTHESIS: The decision for acceptance or discard of the increasingly rare and marginal brain-dead donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores called 2-Step Scores for the prognosis of delayed graft function (DGF) and one-year death-censored transplant loss (1y-tl) reflecting the current practice of six ET countries including Croatia and Belgium. METHODS: The training set was n=620 for DGF and n=711 for 1y-tl, with validation sets n=158 and n=162. In step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology. RESULTS: Step 1 revealed an increased risk of DGF with increased cold ischaemia time, donor and recipient BMI, dialysis vintage, number of HLA-DR mismatches or recipient CMV IgG positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c statistics of 0.696 and 0.701, respectively).Risk of 1y-tl increased in recipients with cold ischaemia time, sum of HLA-A. -B, -DR mismatches and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set. CONCLUSION: Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pump use.

Fundamental drying and agglomeration experiments with bio-fraction and refuse derived fuel for the development of pyrolysis reactor feed.

The EU's circular economy concept necessitates increasing the recycling ratio of municipal solid wastes. There are many existing mechanical-biological processing plants in Hungary for the preparation of residual municipal solid wastes (RMSWs). The two most important products of these plants are the bio-fraction and the refuse derived fuel (RDF). Currently, there are problems with both of these material streams in Hungary, since most of the bio-fraction is still landfilled, and the local thermal utilisation of the RDF has not been implemented yet. The high moisture content of the produced bio-fraction and RDF causes difficulties for the downstream operations; therefore, there is recent engineering interest in drying and agglomeration of these materials. The authors have carried out systematic and parallel drying and briquetting experimental series to study the effect of the material, material composition, mass (volume or surface) of the material, particle size distribution and pre-treatment with a cutting mill on drying intensity in a 1 m3 oven and their effect on briquettability by a laboratory briquette press. The initial slope of the relative moisture loss as function of time was determined. Process engineering design methods of convective hot air-drying can be further developed taking into account the research results. Results can be used for the design of the feed of a pyrolysis reactor once reactor experiments have provided the optimal feed requirements.

Real-Time Cone-Growth Model for Determination of Pharmaceutical Powder Flow Properties.

The flow properties of pellets or granules are crucial for further processing drug dosage forms. Optimal compression or filling of multiparticulate dosage forms into capsules is influenced by forces between discrete particles, which could be partially characterized by flow properties. Several techniques have been developed to examine flowability, including static and dynamic methods applying empirical studies and up-to-date chaos theory; however, the newest methods seem only to be powerful with the supplementation of empirical principles. Our experiments try to refine both the technique of analysis and the methods, by finding new, alternative ways. Our approach to the flowability measurements was to set up a dynamic time-dependent model that combined empirical observations and chaos theory on a geometrical basis, thus finding new characteristics regarding the flow properties of pellets and granules that could be relevant for drug developers. Our findings indicate that sphericity and particle size are the most significant factors influencing the flowability of pharmaceutical multiparticular preparations. Furthermore, this study confirms that integrating chaos theory and empirical observations in a time-dependent dynamic model provides a comprehensive understanding of particle flow behavior, pivotal for optimizing manufacturing processes.

Reference data on estrogen metabolome in healthy pregnancy.

INTRODUCTION: Estrogen hormones and their metabolites are implicated in the maintenance of healthy pregnancy and adequate fetal development. Abnormal levels were related to increased risk of pregnancy complications, particularly preeclampsia. Our aims were (1) to develop a methodological platform for the comprehensive assessment of estrogen metabolome in pregnancy; (2) to collect healthy reference data for relevant elements of estrogen metabolome in each trimester; (3) to assess unconjugated fractions of the estrogen metabolome, (4) to assess the dominant metabolic pathways of estrogen compounds. METHODS: We enrolled healthy pregnant mothers between gestational week 5-15 (on the confirmation of pregnancy; 79 samples), gestational weeks 19-27 (70 samples), and gestational week 34-39 (54 samples). A method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to assess estrone, 17-beta-estradiol, estriol levels, and their metabolites as conjugated and unconjugated forms. Descriptive statistics were used to characterize the level of compounds in each trimester. RESULTS: Estrone, 17-beta-estradiol and estriol levels are dramatically increasing with the advancement of pregnancy. Measured levels were in a very wide range. 17-beta-estradiol is neither glucuronated nor sulphated. To the contrary, estriol and estrone are significantly conjugated; unconjugated fraction is <15% of total hormone levels in any trimester. Regarding metabolism, 4-methoxy-estradiol and 17-epiestriol were not detected. CONCLUSION: We concluded that (1) the levels of estrogen compounds and metabolites increase with advancing gestational age; (2) the wide ranges of levels challenge the establishment of a healthy reference range for clinical purposes; (3) 17-beta-estradiol is not conjugated significantly; (4) 4-methylation and 17-epimerization pathways of estrogens are negligible with our LC-MS/MS method.

Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia.

Introduction: Preeclampsia (PE) is a severe obstetrical syndrome characterized by new-onset hypertension and proteinuria and it is often associated with fetal intrauterine growth restriction (IUGR). PE leads to long-term health complications, so early diagnosis would be crucial for timely prevention. There are multiple etiologies and subtypes of PE, and this heterogeneity has hindered accurate identification in the presymptomatic phase. Recent investigations have pointed to the potential role of small regulatory RNAs in PE, and these species, which travel in extracellular vesicles (EVs) in the circulation, have raised the possibility of non-invasive diagnostics. The aim of this study was to investigate the behavior of exosomal regulatory small RNAs in the most severe subtype of PE with IUGR. Methods: We isolated exosomal EVs from first-trimester peripheral blood plasma samples of women who later developed preterm PE with IUGR (n=6) and gestational age-matched healthy controls (n=14). The small RNA content of EVs and their differential expression were determined by next-generation sequencing and further validated by quantitative real-time PCR. We also applied the rigorous exceRpt bioinformatics pipeline for small RNA identification, followed by target verification and Gene Ontology analysis. Results: Overall, >2700 small RNAs were identified in all samples and, of interest, the majority belonged to the RNA interference (RNAi) pathways. Among the RNAi species, 16 differentially expressed microRNAs were up-regulated in PE, whereas up-regulated and down-regulated members were equally found among the six identified Piwi-associated RNAs. Gene ontology analysis of the predicted small RNA targets showed enrichment of genes in pathways related to immune processes involved in decidualization, placentation and embryonic development, indicating that dysregulation of the induced small RNAs is connected to the impairment of immune pathways in preeclampsia development. Finally, the subsequent validation experiments revealed that the hsa_piR_016658 piRNA is a promising biomarker candidate for preterm PE associated with IUGR. Discussion: Our rigorously designed study in a homogeneous group of patients unraveled small RNAs in circulating maternal exosomes that act on physiological pathways dysregulated in preterm PE with IUGR. Therefore, our small RNA hits are not only suitable biomarker candidates, but the revealed biological pathways may further inform us about the complex pathology of this severe PE subtype.

Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value.

Miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1-5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-ß-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL (n = 14) and controls undergoing elective termination of pregnancy (n = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free ß-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free ß-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-ß-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.

Cinchona-Based Hydrogen-Bond Donor Organocatalyst Metal Complexes: Asymmetric Catalysis and Structure Determination.

In this study, we describe the synthesis of cinchona (thio)squaramide and a novel cinchona thiourea organocatalyst. These catalysts were employed in pharmaceutically relevant catalytic asymmetric reactions, such as Michael, Friedel-Crafts, and A3 coupling reactions, in combination with Ag(I), Cu(II), and Ni(II) salts. We identified several organocatalyst-metal salt combinations that led to a significant increase in both yield and enantioselectivity. To gain insight into the active catalyst species, we prepared organocatalyst-metal complexes and characterized them using HRMS, NMR spectroscopy, and quantum chemical calculations (B3LYP-D4/def2-TZVP), which allowed us to establish a structure-activity relationship.

Classification of preeclampsia according to molecular clusters with the goal of achieving personalized prevention.

The prevention of pre-eclampsia is difficult due to the syndromic nature and multiple underlying mechanisms of this severe complication of pregnancy. The current clinical distinction between early- and late-onset disease, although clinically useful, does not reflect the true nature and complexity of the pathologic processes leading to pre-eclampsia. The current gaps in knowledge on the heterogeneous molecular pathways of this syndrome and the lack of adequate, specific diagnostic methods are major obstacles to early screening and tailored preventive strategies. The development of novel diagnostic tools for detecting the activation of the identified disease pathways would enable early, accurate screening and personalized preventive therapies. We implemented a holistic approach that includes the utilization of different proteomic profiling methods of maternal plasma samples collected from various ethnic populations and the application of systems biology analysis to plasma proteomic, maternal demographic, clinical characteristic, and placental histopathologic data. This approach enabled the identification of four molecular subclasses of pre-eclampsia in which distinct and shared disease mechanisms are activated. The current review summarizes the results and conclusions from these studies and the research and clinical implications of our findings.

Phenotype-Genotype Correlations in Three Different Cases of Adult-Onset Genetic Focal Segmental Glomerulosclerosis.

This study highlights the importance of a combined diagnostic approach in the diagnosis of rare diseases, such as adult-onset genetic FSGS. We present three adult patient cases evaluated with kidney biopsy for proteinuria, chronic kidney disease, and hypertension, which were suggestive of adult-onset genetic FSGS. Renal biopsy samples and formalin-fixed, paraffin-embedded fetal kidneys were evaluated using standard light microscopical stainings, direct immunofluorescence on cryostat sections, and electron microscopy. Clinical exome sequencing was performed for each case, and 45 FSGS-related genes were analyzed. Identifying mutations in the PAX2, ACTN4, and COL4A5 genes have prompted a re-evaluation of the previous histopathological examinations. The PAX2 mutation led to a thinner nephrogenic zone and decreased number of glomeruli, resulting in oligohydramnios during fetal development and oligomeganephronia and adaptive focal-segmental glomerulosclerosis in adulthood. The ACTN4 mutation caused distinct electron-dense aggregates in podocyte cell bodies, while the COL4A5 mutation led to segmental sclerosis of glomeruli with marked interstitial fibrosis and tubular atrophy. The identification of specific mutations and their histopathological consequences can lead to a better understanding of the disease and its progression, as well as potential treatment options.

Performance and limitations of a supervised deep learning approach for the histopathological Oxford Classification of glomeruli with IgA nephropathy.

BACKGROUND AND OBJECTIVE: The Oxford Classification for IgA nephropathy is the most successful example of an evidence-based nephropathology classification system. The aim of our study was to replicate the glomerular components of Oxford scoring with an end-to-end deep learning pipeline that involves automatic glomerular segmentation followed by classification for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S) and active crescents (C). METHODS: A total number of 1056 periodic acid-Schiff (PAS) whole slide images (WSIs), coming from 386 kidney biopsies, were annotated. Several detection models for glomeruli, based on the Mask R-CNN architecture, were trained on 587 WSIs, validated on 161 WSIs, and tested on 127 WSIs. For the development of segmentation models, 20,529 glomeruli were annotated, of which 16,571 as training and 3958 as validation set. The test set of the segmentation module comprised of 2948 glomeruli. For the Oxford classification, 6206 expert-annotated glomeruli from 308 PAS WSIs were labelled for M, E, S, C and split into a training set of 4298 glomeruli from 207 WSIs, and a test set of 1908 glomeruli. We chose the best-performing models to construct an end-to-end pipeline, which we named MESCnn (MESC classification by neural network), for the glomerular Oxford classification of WSIs. RESULTS: Instance segmentation yielded excellent results with an AP50 ranging between 78.2-80.1 % (79.4 ± 0.7 %) on the validation and 75.1-77.7 % (76.5 ± 0.9 %) on the test set. The aggregated Jaccard Index was between 73.4-75.9 % (75.0 ± 0.8 %) on the validation and 69.1-73.4 % (72.2 ± 1.4 %) on the test set. At granular glomerular level, Oxford Classification was best replicated for M with EfficientNetV2-L with a mean ROC-AUC of 90.2 % and a mean precision/recall area under the curve (PR-AUC) of 81.8 %, best for E with MobileNetV2 (ROC-AUC 94.7 %) and ResNet50 (PR-AUC 75.8 %), best for S with EfficientNetV2-M (mean ROC-AUC 92.7 %, mean PR-AUC 87.7 %), best for C with EfficientNetV2-L (ROC-AUC 92.3 %) and EfficientNetV2-S (PR-AUC 54.7 %). At biopsy-level, correlation between expert and deep learning labels fulfilled the demands of the Oxford Classification. CONCLUSION: We designed an end-to-end pipeline for glomerular Oxford Classification on both a granular glomerular and an entire biopsy level. Both the glomerular segmentation and the classification modules are freely available for further development to the renal medicine community.

The value of PLA2R antigen and IgG subclass staining relative to anti-PLA2R seropositivity in the differential diagnosis of membranous nephropathy.

BACKGROUND: The diagnostic performance of PLA2R and IgG subclass staining of kidney biopsies relative to anti-PLA2R seropositivity in the differentiation of primary and secondary membranous nephropathy (pMN, sMN) was examined. Besides PLA2R staining - which has a lower specificity than anti-PLA2R antibody serology - there is insufficient knowledge to decide which IgG1-4 subtype immunohistological patterns (IgG4-dominance, IgG4-dominance/IgG1-IgG4-codominance or IgG4-dominance/IgG4-codominance with any IgG subtype) could be used to distinguish between pMN and sMN. METHODS: 87 consecutive Hungarian patients (84 Caucasians, 3 Romas) with the biopsy diagnosis of MN were classified clinically as pMN (n = 63) or sMN (n = 24). The PLA2R and IgG subclass staining was part of the diagnostic protocol. Anti-PLA2R antibodies were determined by an indirect immunofluorescence test in 74 patients with disease activity. RESULTS: For pMN, the sensitivity of anti-PLA2R seropositivity was 61.1%, and the specificity was 90.0%; and similar values for PLA2R staining were 81.0%, and 66.7%, respectively. In all stages of pMN, IgG4-dominance was the dominant subclass pattern, while the second most frequent was IgG3/IgG4-codominance. The sensitivity and specificity scores were: IgG4-dominance 52.2% and 91.7%, IgG4-dominance/IgG3-IgG4-codominance 76.2% and 87.5%, IgG4-dominance/IgG1-IgG4-codominance 64.2% and 75%, and IgG4-dominance/codominance with any IgG subclass 92.1% and 70.8%, respectively. Anti-PLA2R seropositivity, glomerular PLA2R, and IgG4-dominance/codominance significantly correlated with each other. The IgG4 subclass was rarely encountered in sMN. CONCLUSION: In our series, IgG4-dominance had the highest specificity in the differentiation of MN, just as high as that for anti-PLA2R seropositivity. The specificity values of PLA2R staining and IgG4-dominance/codominance with any IgG subclass or IgG4-dominance/IgG1-IgG4 codominance were ≤ 75%. Apart from IgG4 dominance, IgG4-dominance/IgG3-IgG4-codominance also had good statistical value in differentiating pMN from sMN. As IgG subclass switching during the progression of pMN was not the feature of our cohort, pMN in Hungarian patients is presumed to be an IgG4-related disorder right from the start. Although anti-PLA2R seropositivity has become the cornerstone for diagnosing pMN, if a kidney biopsy evaluation is conducted, besides the staining of PLA2R antigen, the evaluation of IgG subclasses provides relevant information for a differential diagnosis. Even in cases with IgG4-dominance, however, malignancy should be thoroughly checked.

Determination of Processing Precision of Hole in Industrial Plastic Materials.

The precision of the thread processed by tapping is closely related to the precision of the pre-drilling of the blank. Currently, the technologies for processing threads with the tap in the case of metals are well established. In this sense, there are tables and clear recommendations about the tool pairs-helical drill-tap, depending on the size of the thread, but in the case of plastics, no correlations or recommendations have been found. A well-known aspect concerns the fact that the hole made in plastics is obtained with a smaller diameter than the diameter of the drill bit used. To determine the differences between the drill bit and the diameter of the resulting hole, and its precision on different types of plastic materials, experimental research was started. At the same time, the tolerance of the resulting hole was checked and the influence of the cutting regime on the processing precision was studied. During the experiments, plastic materials often used in the aeronautical and car-building industries were used: POM-C, PA6, PEHD1000, Sika Block 700, Sika Block 960, and Sika Block 980. Following the experiments, differences in the diameter of the holes processed were found according to the plastic mass of even 0.3 mm, which is 4.4% of the diameter of the hole. Based on the experimental results and the design of the experiment, recommendations could be made about the diameter of the drill to use to obtain the desired diameter of the hole after processing.

Final-note expectancy and humor: an empirical investigation.

BACKGROUND: Melodic expectations were manipulated to investigate the nature of tonally incongruent melodic final notes that may elicit humor in listeners. To our knowledge, this is the first experiment aiming at studying humor elicitation in music with the use of empirical, quantitative methods. To this aim, we have based the experiment on the incongruency/resolution theory of humor and the violations of expectations in music. Our goal was to determine the amount of change, that is, the degree of incongruency required to elicit humor. METHODS: We composed two simple, 8-bar long melodies, and changed their final notes so that they could randomly finish on any semitone between an octave upwards and downwards with respect to the original, tonic final note. This resulted in 25 versions for both melodies, including the original final notes, for each semitone. Musician and non-musician participants rated each version of each melody on five 7-point bipolar scales according to goodness of fit, humor, beauty, playfulness, and pleasantness. RESULTS AND CONCLUSIONS: Our results showed that even a single change of the final note can elicit humor. No strong connection was found between humor elicitation and the level of incongruency (i.e., the amount of violation of expectation). Instead, changes to the major-mode melody were more likely to be found humorous than those to the minor-mode melody, implying that a so-called playful context is necessary for humor elicitation as the major melody was labelled playful by the listeners. Furthermore, final notes below the original tonic end note were also found to be less humorous and less fitting to the melodic context than those above it.

Cocrystals of tuberculosis antibiotics: Challenges and missed opportunities.

Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis medications are among those commonly reported. This review provides a summary of the tuberculosis antibiotic cocrystals reported in the literature, providing the main results on current tuberculosis medications utilized in cocrystals. Moreover, anti-tuberculosis cocrystals limitations and advantages are described, including evidence for enhanced solubility, stability and effect. Opportunities to enhance anti-tuberculosis medications and fixed dose combinations using cocrystals are given. Several cocrystal pairs are suggested to enhance the effectiveness of anti-tuberculosis drugs.