bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical characterization of high volume fraction Al7075-Al2O3 composite fabricated by semisolid powder processing
Authors: Aghajani Saeed , Pouyafar Vahid , Meshkabadi Ramin , Volinsky Alex A. , Bolouri Amir 
Published: January 2023

Abstract
The mechanical properties and physical characteristics of aluminum alloy composites can be significantly improved by adding reinforcing phases. However, the high loading of the reinforcement phase in Al7075-Al2O3 composites has not been thoroughly studied. In this work, a combination of semisolid metal powder processing and powder metallurgy is used to process and manufacture Al7075-Al2O3 composites with a high reinforcement fraction of > 40 vol.%. The effects of processing parameters on the microstructures and mechanical properties of the composite material are discussed in detail. The loading limits of the high volume Al2O3 reinforcement in Al7075 composites are identified and linked to the processing parameters. A methodology is introduced to estimate the consolidation temperature of Al7075 alloy using compaction testing. Al2O3 particles (the average particle size of 120 µm) were mechanically milled with Al7075 powder (the average particle size of 20 µm) for 10 min and 5 h using a high-energy planetary ball mill. The mixture was then compacted in the semisolid state at 615 °C under the compaction pressures of 50 MPa and 100 MPa. By increasing the milling time from 10 min to 5 h, the deformation of aluminum powders and the fracture of Al2O3 reinforcement particles occur, restricting the loading limit of reinforcement. The milling time also shows a dominant effect on the powder morphology, microstructure, and mechanical properties of Al7075-Al2O3 composites. Increasing compaction pressure from 50 to 100 MPa significantly improved the compressive strength of the composite from 218 to 652 MPa. Al7075-Al2O3 composite with 40 vol.% of reinforcing phase exhibits the highest hardness of 198.2 HV and 96.9% relative density when it is milled for 5 h and compacted at 100 MPa. However, this composite shows the highest strength of 652 MPa when it is milled for 10 min. By increasing the reinforcing phase to 50 vol.% and 60 vol.%, the hardness, density, and compressive strength of composites decreased. The composites with 60 vol.% of reinforcing phase appeared overloaded. Results show that semisolid metal powder processing has huge potential for the fabrication of high loading Al2O3 in Al7075 matrix with near theoretical density.
Measurement and identification of translational static stiffness in workspace of a machine tool
Authors: Jastrzębska Joanna , Parus Arkadiusz , Jastrzębski Daniel , Pawełko Piotr 
Published: January 2023

AbstractThis work presents a measurement for the identification of translational quasi-static stiffness of machine tool using Stiffness Workspace System (SWS). The novelty of this work is a significant modification of the SWS. The changes in measurement procedure and data analysis as well as new technical solutions are described in detail. A methodology for generalised translational static stiffness determination is presented. The major purpose of this paper is to provide the information about quasi-static stiffness values that characterise a typical machine tool. The measurement procedure is implemented in a case study on a 5-axis machining centre. Measurement results were used to determine the generalised translational stiffness indicators of points in the workspace. Then, the static stiffness distribution on the XY plane over machining space was estimated. The obtained results confirm the importance of analyses of static stiffness distribution as they point out areas where some possible changes occur. In the conclusion of the paper the utility value of the information of translational static stiffness is emphasised.
Transcriptional profiling of the developing rat ovary following intrauterine exposure to the endocrine disruptors diethylstilbestrol and ketoconazole
Authors: Kugathas Indusha , Johansson Hanna K. L. , Chan Sock Peng Edith , Toupin Maryne , Evrard Bertrand , Darde Thomas A. , Boberg Julie , Draskau Monica K. , Rolland Antoine D. , Mazaud-Guittot Séverine , Chalmel Frédéric , Svingen Terje 
Published: January 2023

AbstractExposure to endocrine-disrupting chemicals (EDCs) during development may cause reproductive disorders in women. Although female reproductive endpoints are assessed in rodent toxicity studies, a concern is that typical endpoints are not sensitive enough to detect chemicals of concern to human health. If so, measured endpoints must be improved or new biomarkers of effects included. Herein, we have characterized the dynamic transcriptional landscape of developing rat ovaries exposed to two well-known EDCs, diethylstilbestrol (DES) and ketoconazole (KTZ), by 3’ RNA sequencing. Rats were orally exposed from day 7 of gestation until birth, and from postnatal day 1 until days 6, 14 or 22. Three exposure doses for each chemical were used: 3, 6 and 12 µg/kg bw/day of DES; 3, 6, 12 mg/kg bw/day of KTZ. The transcriptome changed dynamically during perinatal development in control ovaries, with 1137 differentially expressed genes (DEGs) partitioned into 3 broad expression patterns. A cross-species deconvolution strategy based on a mouse ovary developmental cell atlas was used to map any changes to ovarian cellularity across the perinatal period to allow for characterization of actual changes to gene transcript levels. A total of 184 DEGs were observed across dose groups and developmental stages in DES-exposed ovaries, and 111 DEGs in KTZ-exposed ovaries across dose groups and developmental stages. Based on our analyses, we have identified new candidate biomarkers for female reproductive toxicity induced by EDC, including Kcne2, Calb2 and Insl3.
Development of a quantitative proteomics approach for cyclooxygenases and lipoxygenases in parallel to quantitative oxylipin analysis allowing the comprehensive investigation of the arachidonic acid cascade
Authors: Hartung Nicole M. , Mainka Malwina , Pfaff Rebecca , Kuhn Michael , Biernacki Sebastian , Zinnert Lilli , Schebb Nils Helge 
Published: January 2023

AbstractOxylipins derived from the cyclooxygenase (COX) and lipoxygenase (LOX) pathways of the arachidonic acid (ARA) cascade are essential for the regulation of the inflammatory response and many other physiological functions. Comprehensive analytical methods comprised of oxylipin and protein abundance analysis are required to fully understand mechanisms leading to changes within these pathways. Here, we describe the development of a quantitative multi-omics approach combining liquid chromatography tandem mass spectrometry–based targeted oxylipin metabolomics and proteomics. As the first targeted proteomics method to cover these pathways, it enables the quantitative analysis of all human COX (COX-1 and COX-2) and relevant LOX pathway enzymes (5-LOX, 12-LOX, 15-LOX, 15-LOX-2, and FLAP) in parallel to the analysis of 239 oxylipins with our targeted oxylipin metabolomics method from a single sample. The detailed comparison between MRM3 and classical MRM-based detection in proteomics showed increased selectivity for MRM3, while MRM performed better in terms of sensitivity (LLOQ, 16–122 pM vs. 75–840 pM for the same peptides), linear range (up to 1.5–7.4 μM vs. 4–368 nM), and multiplexing capacities. Thus, the MRM mode was more favorable for this pathway analysis. With this sensitive multi-omics approach, we comprehensively characterized oxylipin and protein patterns in the human monocytic cell line THP-1 and differently polarized primary macrophages. Finally, the quantification of changes in protein and oxylipin levels induced by lipopolysaccharide stimulation and pharmaceutical treatment demonstrates its usefulness to study molecular modes of action involved in the modulation of the ARA cascade.
Graphical Abstract
Evolution of TOP1 and TOP1MT Topoisomerases in Chordata
Authors: Moreira Filipa , Arenas Miguel , Videira Arnaldo , Pereira Filipe 
Published: January 2023

AbstractType IB topoisomerases relax the torsional stress associated with DNA metabolism in the nucleus and mitochondria and constitute important molecular targets of anticancer drugs. Vertebrates stand out among eukaryotes by having two Type IB topoisomerases acting specifically in the nucleus (TOP1) and mitochondria (TOP1MT). Despite their major importance, the origin and evolution of these paralogues remain unknown. Here, we examine the molecular evolutionary processes acting on both TOP1 and TOP1MT in Chordata, taking advantage of the increasing number of available genome sequences. We found that both TOP1 and TOP1MT evolved under strong purifying selection, as expected considering their essential biological functions. Critical active sites, including those associated with resistance to anticancer agents, were found particularly conserved. However, TOP1MT presented a higher rate of molecular evolution than TOP1, possibly related with its specialized activity on the mitochondrial genome and a less critical role in cells. We could place the duplication event that originated the TOP1 and TOP1MT paralogues early in the radiation of vertebrates, most likely associated with the first round of vertebrate tetraploidization (1R). Moreover, our data suggest that cyclostomes present a specialized mitochondrial Type IB topoisomerase. Interestingly, we identified two missense mutations replacing amino acids in the Linker region of TOP1MT in Neanderthals, which appears as a rare event when comparing the genome of both species. In conclusion, TOP1 and TOP1MT differ in their rates of evolution, and their evolutionary histories allowed us to better understand the evolution of chordates.
Multivalent adaptor proteins specifically target NK cells carrying a universal chimeric antigen receptor to ErbB2 (HER2)-expressing cancers
Authors: Pfeifer Serrahima Jordi , Zhang Congcong , Oberoi Pranav , Bodden Malena , Röder Jasmin , Arndt Claudia , Feldmann Anja , Kiefer Anne , Prüfer Maren , Kühnel Ines , Tonn Torsten , Bachmann Michael , Wels Winfried S. 
Published: January 2023

AbstractChimeric antigen receptor (CAR)-engineered immune effector cells constitute a promising approach for adoptive cancer immunotherapy. Nevertheless, on-target/off-tumor toxicity and immune escape due to antigen loss represent considerable challenges. These may be overcome by adaptor CARs that are selectively triggered by bispecific molecules that crosslink the CAR with a tumor-associated surface antigen. Here, we generated NK cells carrying a first- or second-generation universal CAR (UniCAR) and redirected them to tumor cells with so-called target modules (TMs) which harbor an ErbB2 (HER2)-specific antibody domain for target cell binding and the E5B9 peptide recognized by the UniCAR. To investigate differential effects of the protein design on activity, we developed homodimeric TMs with one, two or three E5B9 peptides per monomer, and binding domains either directly linked or separated by an IgG4 Fc domain. The adaptor molecules were expressed as secreted proteins in Expi293F cells, purified from culture supernatants and their bispecific binding to UniCAR and ErbB2 was confirmed by flow cytometry. In cell killing experiments, all tested TMs redirected NK cell cytotoxicity selectively to ErbB2-positive tumor cells. Nevertheless, we found considerable differences in the extent of specific cell killing depending on TM design and CAR composition, with adaptor proteins carrying two or three E5B9 epitopes being more effective when combined with NK cells expressing the first-generation UniCAR, while the second-generation UniCAR was more active in the presence of TMs with one E5B9 sequence. These results may have important implications for the further development of optimized UniCAR and target module combinations for cancer immunotherapy.
Low on-treatment levels of serum soluble CD8 (sCD8) predict better outcomes in advanced non-small cell lung cancer patients treated with atezolizumab
Authors: Siemiątkowska Anna , Bryl Maciej , Kosicka-Noworzyń Katarzyna , Tvrdoň Jakub , Gołda-Gocka Iwona , Główka Franciszek K. 
Published: January 2023

Abstract
Background
Immunotherapy has changed the paradigm of treating non-small cell lung cancer (NSCLC). But, selecting patients who will achieve long-term benefits from treatment remains unsatisfactory. Here, we investigated the possible use of the soluble form of CD8 antigen (sCD8) in predicting durable disease control after PD-1/PD-L1 blockade. CD8 is a marker of the cytotoxic T lymphocytes. Its soluble form (sCD8) is secreted under activation of the immune system but also has immunosuppressive properties. The data about serum sCD8 in patients dosed with anti-PD-1/PD-L1 drugs are lacking.

Methods and results
We included 42 NSCLC patients and collected samples at baseline and for the first 3 months of atezolizumab immunotherapy. The serum sCD8 concentrations were measured with the ELISA kit and correlated with treatment outcomes. Patients with durable (≥ 12 months) disease control presented lower serum sCD8 than those without long-term benefits. The sCD8 levels measured at the end of cycle 2 (sCD8.2) were the earliest time point that successfully differentiated patients (3.76 vs. 9.68 ng/mL, respectively, p < 0.001). Individuals with low sCD8.2 (≤ 4.09 ng/mL) presented longer progression-free survival (HR = 0.061, p < 0.001) and overall survival (HR = 0.104, p < 0.05) compared to individuals with high sCD8.2 (median values unreached vs. 4.4 months and 14.4 months for PFS and OS, respectively).

Conclusions
Serum sCD8 could be an early biomarker of durable disease control after anti-PD-L1 treatment. Higher sCD8 in patients with worse outcomes could suggest the inhibitory effect of sCD8 on cytotoxic T-cells activation.
Cribriform morular thyroid carcinoma: a case report with pathological, immunohistochemical, and molecular findings suggesting an origin from follicular cells (or their endodermal precursors)
Authors: Echegoyen-Silanes Ana , Pineda-Arribas José Javier , Sánchez-Ares María , Cameselle-García Soledad , Sobrino Beatriz , Ruíz-Ponte Clara , Piso-Neira Magalí , Anda Emma , Cameselle-Teijeiro José Manuel 
Published: January 2023

Abstract
Cribriform morular thyroid carcinoma (CMTC) is a rare malignant thyroid tumor with a peculiar growth pattern secondary to permanent activation of the WNT/β-catenin pathway. CMTC may be associated with familial adenomatous polyposis or sporadic; it shares morphological features with papillary thyroid carcinoma (PTC) and was considered a variant of PTC in the 2017 WHO classification of tumors of endocrine organs. The new 5th edition of the WHO classification of endocrine and neuroendocrine tumors considered CMTC an independent thyroid neoplasm of uncertain histogenesis. A thymic/ultimobranchial pouch-related differentiation in CMTC has been recently postulated. We, however, have used the pathological and immunohistochemical features of this case of CMTC with 2 novel oncogenic somatic variants (c.3428_3429insA, p.(Tyr1143Ter) and c.3565del, p. (Ser1189Hisfs*76) of the APC gene to propose an origin from follicular cells (or their endodermal precursors). As usual in CMTC, the morular component of this tumor was positive for CDX2. Given the fact that WNT/β-catenin signaling, through CDX2, activates large intestine and small intestine gene expression, we postulate that in CMTC, the tumor cells have their terminal differentiation blocked, thus showing a peculiar primitive endodermal (intestinal-like) phenotype negative for sodium-iodide symporter, thyroperoxidase, and thyroglobulin. Establishing the histogenesis of CMTC is very relevant for the development of appropriate therapies of redifferentiation, particularly in patients where the tumor cannot be controlled by surgery.
MTA1 as negative prognostic marker in vulvar carcinoma
Authors: Wanka Giulia , Jueckstock Julia , Wild Carl Mathis , Vattai Aurelia , Fürst Sophie , Heidegger Helene H. , Kuhn Christina , Schmoeckel Elisa , Jeschke Udo , Dannecker Christian 
Published: January 2023

Abstract
Purpose
Vulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In 2020 there were registered more than 17,000 deaths worldwide related to vulvar carcinoma. Data about target-based therapies and predictive biomarkers for vulva carcinomas are rare so far. The metastasis-associated gene MTA1 is a transcriptional repressor with a potential effect on cancer. Expression of MTA1 was found to be significantly enhanced in gynecological malignancies as breast or ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of those tumor entities. Due to the lack of information around MTA1 and its significance regarding vulvar carcinoma, this study focuses on the expression of MTA1 in vulvar carcinoma and its correlation to clinicopathological characteristics and prognosis.

Methods
A total of 157 paraffin-embedded vulvar cancer tissues were immunohistochemically stained and examined for MTA1 expression by using the immunoreactive score. Subsequently, the values were correlated with clinicopathological parameters.

Results
MTA1 was found to be expressed in 94% of the patients in the cytoplasm and 91% in the nucleus. Cytoplasmatic expression of MTA1 was significantly increased in non-keratinizing squamous cell carcinoma and in vulvar carcinoma of the condylomatous type, compared to keratinizing squamous cell carcinoma and vulvar carcinoma of the verrucous type. High MTA1 expression in the nucleus was associated with advanced tumor size as well as higher FIGO grading. In addition, p16 negative vulvar carcinomas showed a higher nuclear expression of MTA1 compared to p16 positive vulvar carcinomas. Suprisingly, Kaplan–Meier analysis showed a significantly lower disease-free survival in tumor samples without a nuclear expression of MTA1.

Conclusions
MTA1 was identified as a negative prognostic marker for vulvar carcinoma associated with advanced tumor stage and FIGO grading. A possible explanation could be that the antibody used for this study does not bind to a possible mutation in the C terminal region of MTA leading to negative immunohistochemical staining and this can be correlated with early recurrence in patients with vulvar carcinoma.
Anisotropic Poroelastic Modelling of Depletion-Induced Pore Pressure Changes in Valhall Overburden
Authors: Duda Marcin Ireneusz , Bakk Audun , Holt Rune Martin , Stenebråten Jørn Fredrik 
Published: January 2023

AbstractStress and pore pressure changes due to depletion of or injection into a reservoir are key elements in stability analysis of overburden shales. However, the undrained pore pressure response in shales is often neglected but needs to be considered because of their low permeability. Due to the anisotropic nature of shales, the orientation of both rock and stresses should be considered. To account for misalignment of the medium and the stress tensor, we used anisotropic poroelasticity theory to derive an angle-dependent expression for the pore pressure changes in transversely isotropic media under true-triaxial stress conditions. We experimentally estimated poroelastic pore pressure parameters of a shale from the Lista formation at the Valhall field. We combined the experimental results with finite element modelling to estimate the pore pressure development in the Valhall overburden over a period of nearly 40 years. The results indicate non-negligible pore pressure changes several hundred meters above the reservoir, as well as significant differences between pore pressure and effective stress estimates obtained using isotropic and anisotropic pore pressure parameters. We formulate a simple model approximating the undrained pore pressure response in low permeable overburden. Our results suggest that in the proximity of the reservoir the amplitude of the undrained pore pressure changes may be comparable to effective stresses. Combined with the findings of joint analysis of locations of casing deformation and total and effective stresses, the results suggest that pore pressure modelling may become an important element of casing collapse and caprock failure risk analysis and mitigation.
Synchro-Sub, an adaptive multi-algorithm framework for real-time subtitling synchronisation of multi-type TV programmes
Authors: Masiello-Ruiz Jose Manuel , Ruiz-Mezcua Belen , Martinez Paloma , Gonzalez-Carrasco Israel 
Published: January 2023

AbstractSubtitles are critical elements in making TV as accessible as possible for people with hearing impairment, elderly people and other end-users that could need this kind of service. Moreover, delay in live-originated TV captions or subtitles is a significant factor in the audience’s perception of the absence of quality for the deaf and hard of hearing. This lack of synchronisation leads to poor quality broadcasts because of the inconsistency between images and subtitles presented to the viewer. In some cases, this situation leads to a misunderstanding of the message. Subtitling is a reactive process that starts once a minimum of audio information has been generated and ends when an insertion time, deletion time and text are allocated. Therefore, there will always be a delay associated with this process, related to the audio duration being subtitled and the subtitle production time. Moreover, in live TV programmes, unsynchronised audio and subtitles are inherent to the subtitling process because the broadcasting is performed in real-time. In this paper, the authors present the Synchro-Sub framework for synchronising subtitles with the audio-visual contents for live-captioned TV programs. For doing this, and considering the knowledge obtained in previous approaches defined by the authors, several improvements have been included in the transcription and chronization phases of the framework that increase the percentage of correctly timed subtitles.
A minimally invasive tubular retractor–assisted retropleural approach for thoracic disc herniations — case series and technical note
Authors: Hubertus Vanessa , Selhausen Peter , Meinert Franziska , Meyer Frerk , Onken Julia S. , Schneider Ulf C. , Hecht Nils , Czabanka Marcus , Vajkoczy Peter , Woitzik Johannes 
Published: January 2023

Abstract
Purpose
Thoracic disc herniations are uncommon and carry a high risk for neurological deterioration. Traditional surgical approaches include thoracotomy, costotransversectomy or posterior approaches with considerable morbidity. In this technical note with case series, we describe a minimally invasive tubular retractor–assisted retropleural approach for simple and less invasive microsurgical exploration of thoracic disc herniations from a lateral angle.

Methods
Surgical technique consisted of partial rib resection and retropleural dissection followed by the placement of a tubular retractor (METRx Tubes, Medtronic) for an anterior-lateral exposure of the disc and neuroforamen. Epidemiological, clinical and surgical patient data were acquired.

Results
Between 2017 and 2020, six patients were surgically treated using the minimally invasive tubular retractor–assisted retropleural approach. Microsurgical exposure of the disc and neural structures was achieved from a lateral direction without requiring thoracotomy or lung deflation. Control imaging confirmed resection in all cases without relevant residuum. As postoperative complications, one dural injury and one postoperative pneumothorax occured. No neurologic deterioration or recurrence occurred during a median follow-up of 3 months.

Conclusion
The described tubular retractor–assisted retropleural exposure serves as a feasible minimally invasive microsurgical approach to the anterior-lateral thoracic spine.