Classical Lines Research Articles

Topological State in Heterostructured Gap Waveguides and Their Transitions to Classical Transmission Line

AbstractGap waveguides play a crucial role in millimeter‐wave information transmission and processing for next‐generation wireless communication and radar sensing systems. However, they suffer from challenges, such as reflection and scattering losses at sharp bends and defects. While topological photonic crystals offer innovative solutions for robust signal transmission, their localized interface states and unique electromagnetic modes pose compatibility challenges with practical circuits and systems. In this paper, a novel heterostructured gap waveguide support valley‐locked topological guided wave transport is introduced. This design ensures robust propagation against defects and bends while maintaining compatibility with classical transmission lines. Its topological characteristic reduce sensitivity to fabrication and assembly errors. More importantly, an efficient transition structure is developed to seamlessly convert quasi‐transverse electromagnetic (quasi‐TEM) modes in planar transmission lines to topological guided wave states, thereby effectively exciting topological waves. All theoretical predictions are quantitatively verified by the simulations and experiments at millimeter wave frequency. This heterostructured gap waveguide can find unique applications, such as power divider, as verified numerically. By leveraging topological principles, the proposed gap waveguide offers a significant performance boost for antennas and passive/active components in millimeter‐wave applications, including automotive radar, 5G communication, and synthetic‐aperture radar for imaging.

Nasopharyngeal carcinoma with non-squamous phenotype may be a variant of nasopharyngeal squamous cell carcinoma after inhibition of EGFR/PI3K/AKT/mTOR pathway.

Nasopharyngeal carcinoma (NPC) is a cancerous tumor that develops in the nasopharynx epithelium and typically has squamous differentiation. The squamous phenotype is evident in immunohistochemistry, with diffuse nuclear positivity for p63 and p40. Nonetheless, a few NPCs have been identified by clinicopathological diagnosis that do not exhibit the squamous phenotype; these NPCs are currently referred to as non-squamous immunophenotype nasopharyngeal carcinomas (NSNPCs). In a previous work, we have revealed similarities between the histological appearance, etiology, and gene alterations of NSNPC and conventional NPC. According to ultrastructural findings, NSNPC still falls under the category of non-keratinized squamous cell carcinoma that is undifferentiated. NSNPC has an excellent prognosis and a low level of malignancy, according to a retrospective investigation. Based on prior research, we investigated the molecular mechanism of NSNPC not expressing the squamous phenotype and its biological behavior. IHC was used to determine the expression of EGFR, PI3K, AKT, p-AKT, mTOR, p-mTOR, Notch, STAT3 and p-STAT3 in a total of 20 NSNPC tissue samples and 20 classic NPC tissue samples. We obtained human NPC cell lines (CNE-2,5-8F) and used EGFR overexpression plasmid and shRNAs to transfect them. To find out whether mRNA and proteins were expressed in the cells, we used Western blotting and qRT-PCR. Cell biological behavior was discovered using the CCK-8 assay, cell migration assay, and cell invasion assay. EGFR, PI3K, p-AKT and p-mTOR proteins were lowly expressed in NSNPC tissues by immunohistochemistry, compared with classical NPC. In the classical NPC cell lines CNE-2 and 5-8F, overexpression EGFR can up-regulate the expression of p63 through the PI3K/AKT/mTOR pathway, and promote the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. At the same time, knockout of EGFR can down-regulate p63 expression through the PI3K/AKT/mTOR pathway, and inhibit the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. The lack of p63 expression in NSNPC was linked with the inhibition of the EGFR/PI3K/AKT/mTOR pathway, and NSNPC may be a variant of classical NPC.

Unveiling compact planetary nebulae: Broad-band survey analysis and LAMOST confirmation

Planetary nebulae (PNe) are pivotal for advancing our knowledge of stellar evolution and galactic chemical enrichment. Recent progress in surveys and data analysis has revolutionized PN research, leading to the discovery of new objects and deeper insights into their properties. We have devised a novel photometric selection method, integrating GAIA and Pan-STARRS photometry, to identify compact PN candidates. This approach utilizes color–color diagrams, specifically (G−g) versus (GBP−GRP) and (G−r) versus (GBP−GRP), as primary criteria for candidate selection. The subsequent verification step involves confirming these candidates through LAMOST spectroscopic data. By cross-referencing a comprehensive dataset of PNe, GAIA, Pan-STARRS, and LAMOST DR7 spectra, we explore the potential of our approach and the crucial role played by these surveys in the field of PN research. The LAMOST spectra provide compelling evidence supporting our selection criteria, especially for compact PNe characterized by strong emission lines and low continuum. This characteristic spectral profile in LAMOST data underscores its effectiveness in confirming compact PNe, enabling clear differentiation based on distinctive spectral features. Applying these criteria to a catalog of emission line objects, we have selected a PN candidate. Detailed analysis of its LAMOST spectrum unveiled classical Balmer emission lines and high-ionization lines (Heii, [Arv], [Ariii], and [Neiii]), characteristic of high-ionization PNe, with an absence of low-excitation lines. Utilizing the 1D-photoionization code cloudy, our modeling revealed crucial parameters, including an ionizing source with an effective temperature of 180×103 K, luminosity around 3,400 L⊙, and gas abundances encompassing various elements. Comparing the PN’s evolution track, the progenitor star was estimated to have a mass of 2M⊙. Our findings show the greatest promise for cleanly separating compact PNe from other objects and provide a robust framework for further exploration of these surveys in the context of planetary nebulae.

Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype‑specific transcriptomic and phenotypical changes.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced tumor stages with chemotherapy as the only treatment option. Transcriptomic analysis has defined a classical and basal‑like PDAC subtype, which are regulated by epigenetic modification. The present study aimed to determine if drug‑induced epigenetic reprogramming of pancreatic cancer cells affects PDAC subtype identity and chemosensitivity. Classical and basal‑like PDAC cell lines PaTu‑S, Capan‑1, Capan‑2, Colo357, PaTu‑T, PANC‑1 and MIAPaCa‑2, were treated for a short (up to 96h) and long (up to 30weeks) period with histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors. The cells were analyzed using gene expression approaches, immunoblot analysis, and various cell assays to assess cell characteristics, such as proliferation, colony formation, cell migration and sensitivity to chemotherapeutic drugs. Classical and basal‑like PDAC cell lines showed pronounced epigenetic regulation of subtype‑specific genes through acetylation of lysine 27 on Histone H3 (H3K27ac). Moreover, classical cell lines revealed a significantly decreased expression of HDAC2 and increased total levels of H3K27ac in comparison with the basal‑like cell lines. Following HAT inhibitor treatment, classical cell lines exhibited a loss of epithelial marker gene expression, decreased chemotherapy response gene score and increased cell migration invitro, indicating a tumor‑promoting phenotype. HDAC inhibitor treatment, however, exerted minimal reprogramming effects in both subtypes. Epigenetic reprogramming of classical and basal‑like tumor cells did not have a major impact on gemcitabine response, although the gemcitabine transporter gene SLC29A1 (solute carrier family 29 member 1) was epigenetically regulated.

Abstract C103: Differential acquisition of extracellular lipid correlates with pancreatic cancer subtype and metastatic tropism

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease, and the third leading cause of cancer-related death with a 5-year overall survival rate of less than 5%. Recent studies have identified two major subtypes of pancreatic cancer, basal and classical, that are predictive of patient prognosis, with basal tumors corresponding with more aggressive disease. While transcriptional signatures define basal and classical tumors and cell lines, little is known regarding the metabolic vulnerabilities linked to the basal versus classical state. Using unbiased computational interrogation to uncover metabolic genes correlating with known markers of classical PDAC, we identified high expression of Proprotein convertase subtilisin/kexin type-9 (PCSK9) – a negative regulator of receptor mediated uptake of cholesterol containing low-density lipoprotein (LDL) – as correlating with several established markers of classical PDAC. In contrast, PCSK9 expression is suppressed in Basal PDAC. Accordingly, basal PDAC uptake high levels of LDL, are sensitive to LDL depletion and show higher dependence on cholesterol uptake, relative to classical PDAC. As lipoproteins are produced in the liver, we hypothesized that basal PDAC cells may more efficiently seed and grow within the liver. Consistent with this hypothesis, low PCSK9 expression is correlated with liver metastasis in mouse models of PDAC and patient PDAC specimens. Ongoing studies will interrogate the role of PCSK9 and cholesterol uptake and utilization in metastatic tropism, and uncover unique features and vulnerabilities of the most aggressive variant of PDAC. Citation Format: Gilles Rademaker, Grace A. Hernandez, Longhui Qiu, Kwun W. Wen, Aakriti Jain, Grace A. Kim, Roberto Zoncu, Rushik M. Perera. Differential acquisition of extracellular lipid correlates with pancreatic cancer subtype and metastatic tropism [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C103.

Abstract A095: ZNF274 suppresses the mesenchymal state, thereby causing intrinsic resistance to CDK7 inhibition

Abstract Pancreatic Ductal Adenocarcinoma (PDA) can be characterized by two distinct transcriptional subtypes: classical and basal. The basal PDA subtype is more aggressive and has the worst overall survival. We have previously shown that the histone deacetylase (HDAC) Sirtuin 6 (SIRT6), a marker of the classical PDA subtype, can control sensitivity to CDK7 inhibitors. Interestingly, SIRT6 is part of the KAP1 repressive complex where it functions as an HDAC. This complex functions to maintain heterochromatin at specific regions of the genome by removing marks of open chromatin and installing marks of repressive chromatin with histone methyltransferases (HMT) and DNA methyltransferases (DNMT). The complex relies on a KRAB-Zinc Finger protein to bind DNA directly and modify chromatin at those regions. Since we found that SIRT6 can control sensitivity to CDK7 inhibition, we hypothesized that the KAP1 repressive complex is crucial for maintaining subtype-specific chromatin states and that manipulation of any part of this complex could alter subtype, thereby changing sensitivity to CDK7 inhibition. In a survey of basal and classical PDA cell lines, we found that the KRAB-Zinc Finger ZNF274 showed substantial differential expression, similar to SIRT6, and correlated with overall patient survival. We validated ZNF274 expression in PDA cell lines and organoids by western blot and immunofluorescence and found that classical PDA expressed high levels of ZNF274. Next, we investigated how loss of ZNF274 would affect classical PDA cells and found that knockdown of this protein induced an epithelial-to-mesenchymal (EMT) transition through increased ZEB1 expression. We analyzed protein and RNA expression of more EMT regulators and identified morphological changes representative of EMT. Therefore, this induction of EMT upon loss of ZNF274 could be initiating a subtype switch from classical PDA to basal. To determine if loss of ZNF274 and induction of the mesenchymal state could sensitize cells to CDK7 inhibition as we have previously shown, we performed ZNF274 knockdown in classical PDA and saw a dramatic increase in sensitivity to CDK7 inhibitors. Therefore, we have shown the KAP1 repressive complex to be important in regulating cell state and sensitivity of classical PDA to CDK7 inhibitors which we hope to exploit to improve patient responses to CDK7 inhibition therapy. Citation Format: Jessica Gianopulos, Adrianne Wallace-Povirk, Sita Kugel. ZNF274 suppresses the mesenchymal state, thereby causing intrinsic resistance to CDK7 inhibition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A095.

Molecular Characterization of Mare Families in the Serbian Population of the Lipizzan Horse

Summary The Lipizzan horse breed was established in the 16th century in Lipica and later spread throughout Central and Eastern Europe. In addition to six classical stallion lines, 17 classical mare family lines were established in the old Lipica stud. Additional 44 mare family lines, including local lines, were established in other Lipizzan studs. The founders of the classical Lipizzan mare family lines date back to the period between the 18th and 20th century and came from various breeds, including the Karst, Spanish, Italian, Kladruber and Arabian horses. The history of the Lipizzan mare family lines is well described and supported by the availability of 44 nucleotide sequences of the mtDNA control region. In this study, the mtDNA control region of 23 Serbian Lipizzans, representing the established Lippizan mare family lines, as well as the local mare family line Zora, have been sequenced. The objective of this study was to test whether the Zora mare family line could be distinguished from other Lipizzan mare family lines according to the mtDNA sequence. Sequences were aligned to the entire set of mtDNA control region sequences representing 44 Lipizzan mtDNA haplotypes. Based on the alignment, a median-joining network was constructed. The individuals in this study formed a cluster with the existing Lipizzan mare family lines. However, a total of ten individuals belonging to the local Zora mare family line formed a compact cluster close to the mtDNA haplotypes, representing the classical mare family lines Wera, Betalka, and Monteaura. Additional pedigree data are needed to clarify the origin of the mtDNA haplotype variant identified in this study.

Changing Patterns of Zygomaticomaxillary Complex Fractures: A Retrospective Study

Limited research exists regarding the incidence and variations of zygomaticomaxillary complex (ZMC) fracture patterns and their correlation with the mechanism of injury. Hence, further research is indicated. The purpose of this study was to analyze the different ZMC fracture patterns in relation to its etiology using computed tomography scans. This retrospective cohort study was conducted at a single institution. The medical records of maxillofacial trauma patients from 2016 to 2020 were analyzed. Patients from any gender and all age groups with complete records diagnosed with isolated ZMC fractures were included in the study. The primary predictor variable was the etiology of trauma. It was categorized as road traffic accidents (RTAs), falls, interpersonal violence, fall from height, sports injuries, etc. MAIN OUTCOME VARIABLES: The primary outcome variable was the ZMC fracture patterns observed and was defined as similar to or different from the classical fracture patterns. Any type of variation noted from the classical fracture lines was defined as the secondary outcome variable. Covariates included demographic variables such as age, gender, the type of vehicle involved, the type of RTA, side of fracture, associated orbital fractures, and number of ZMC points fractured. Descriptive and bivariate statistics were used to measure association between the predictor and outcome variables using multiple proportions χ2 test. Statistical significance was defined at P value of <.05. Out of the 232 scans assessed, a total of 163 cases were included in this study. A majority of the cases belonged to a range of 21 to 30years and showed a male predilection. The most common mode of injury was found to be RTAs (88.3%). Most cases had fracture patterns different from the classical fracture patterns (65.64%). A statistically significant association was found between the types of ZMC fracture patterns and etiology of trauma (RTA P= <.0001, falls P=.0001, and interpersonal violence P=.0001). Five different variations in ZMC fracture patterns were found and had a statistically significant association with the classical fracture lines (P<.0001). The authors conclude that the variations in fracture patterns encountered today may be attributed to the mechanism of injury. With due consideration to the limitations of this study, the authors suggest that the treatment plan may require slight modification based on the variation of the fracture pattern. Additional intervention may also be indicated.

Changing trends in central midface fracture – A proposal for revised classification and holistic management

BackgroundMidface fractures are one of the common facial fractures encountered in the current era. High energy impact injuries that lead to gross comminution of the midface warranting modification of the standard treatment plan, often cannot be categorized by existing classification systems. The aim of the current paper is to describe the changing trends in midface fracture patterns and propose a modification for the current classification system and describe the holistic approach for management. Materials and methodsA retrospective study was conducted at our center to include all the patients who reported to us for the management of maxillofacial trauma between 2020 and 2022. The details of the cause of facial trauma and pattern of injury, clinical presentation, diagnosis were retrieved from the medical records and the radiographic details including computed tomography details of the fracture pattern were tabulated for evaluation. The Fractures which could not be classified based on the classical Le fort fracture lines were isolated and were classified based on the current classification system and the modifications in the treatment plan and management were recorded. ResultsA total of 673 trauma cases reported between the given time frame. Out of which 205 were midface fractures. 109 patients from the foresaid group had central mid face fracture. 62 fractures of these cases could not be classified based on conventional Le fort classification due to fragmentation, bone loss and combination with other Le fort level injury of the opposite side of the midface and involvement of orbit/ anterior cranial fossa. The modified Le fort classification (Table 1) was used to reclassify these fractures and according to the same 12 cases of Le fort IA, 9 cases of le fort IB, 4 cases of Le fort IIA, 20 cases of Le fort IIB, 4 cases of Le fort IIIA, 9 cases of Le fort IIIB and 4 cases of Le fort IV fracture.The details of the management strategy along with the timing of repair are discussed. ConclusionWith continual rise in the high impact injuries, the pattern of midface fracture presentation is changing. Advanced fixation modalities that are currently available can be applied only when a precise diagnosis and planning can be performed. The current modification of the midface fractures provides a better insight in defining the fracture patterns which will enable the surgeon to plan the midface reconstruction adequately.

High-order field theory and a weak Euler–Lagrange–Barut equation for classical relativistic particle-field systems

In both quantum and classical field systems, conservation laws such as the conservation of energy and momentum are widely regarded as fundamental properties. A broadly accepted approach to deriving conservation laws is built using Noether’s method. However, this procedure is still unclear for relativistic particle-field systems where particles are regarded as classical world lines. In the present study, we establish a general manifestly covariant or geometric field theory for classical relativistic particle-field systems. In contrast to quantum systems, where particles are viewed as quantum fields, classical relativistic particle-field systems present specific challenges. These challenges arise from two sides. The first comes from the mass-shell constraint. To deal with the mass-shell constraint, the Euler–Lagrange–Barut (ELB) equation is used to determine the particle’s world lines in the four-dimensional (4D) Minkowski space. Besides, the infinitesimal criterion, which is a differential equation in formal field theory, is reconstructed by an integro-differential form. The other difficulty is that fields and particles depend on heterogeneous manifolds. To overcome this challenge, we propose using a weak version of the ELB equation that allows us to connect local conservation laws and continuous symmetries in classical relativistic particle-field systems. By applying a weak ELB equation to classical relativistic particle-field systems, we can systematically derive local conservation laws by examining the underlying symmetries of the system. Our proposed approach provides a new perspective on understanding conservation laws in classical relativistic particle-field systems.

Characterization of unidirectional and bidirectional transparencies in -symmetric quantum and classical systems

We studied the scattering state behavior of tight-binding quantum system and classical electrical transmission lines. We distributed on-site energies ϵ n and resistances R n , respectively, according to a parity-time -symmetric distribution. Using the formalism of scattering matrix S and transfer matrix M, we derived analytical expressions for components of transfer matrix M, and through them, we found transmission coefficient T and left (R L ) and right (R R ) reflectance. In addition, we found a generalized conservation relation that relates T, R L and R R , valid for quantum and classical -symmetric systems. We numerically studied the general behavior of T, R L , R R and eigenvalues s ± of scattering matrix S in the full range of possible values of the gain and loss parameters. We observed the existence of unidirectional and bidirectional transparency for specific energies E (quantum case) and specific frequencies Ω (transmission line case), for which the following conditions were simultaneously fulfilled: i) T was unitary (T = 1), ii) eigenvalues s ± were degenerate and unimodular , iii) the product of reflectances tended to zero, , and iv) phases ϕ of one or both reflection amplitudes showed abrupt change of π. This way, we characterized the unidirectional and bidirectional transparency for classical and quantum systems as a function of the gain and loss parameters that describe both models. In addition, the theoretical results showed complete agreement with the numerical calculation. We hope that our work contributes to a better understanding of the influence of the -symmetric distribution of gain and loss parameters on the scattering properties of quantum and classical systems.

Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease.

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. The highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g., EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression in classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.

Review: The Content of Our Caricature: African American Comic Art and Political Belonging, by Rebecca Wanzo

Review: <i>The Content of Our Caricature: African American Comic Art and Political Belonging</i>, by Rebecca Wanzo

An N-heterocyclic carbene iridium(III) complex as a potent anti-cancer stem cell therapeutic

Cancer stem cells (CSCs) represent a difficult to treat cellular niche within tumours due to their unique characteristics, which give them a high propensity for resistance to classical anti-cancer treatments and the ability to repopulate the tumour mass. An attribute that may be implicated in the high rates of recurrence of certain tumours. However, other characteristics specific to these cells, such as their high dependence on mitochondria, may be exploited for the development of new therapeutic agents that are effective against the niche. As such, a previously described phosphorescent N-heterocyclic carbene iridium(III) compound which showed a high level of cytotoxicity against classical tumour cell lines with mitochondria-specific effects was studied for its potential against CSCs. The results showed a significantly higher level of activity against several CSC lines compared to non-CSCs. Mitochondrial localisation and superoxide production were confirmed. Although the cell death involved caspase activation, their role in cell death was not definitive, with a potential implication of other, non-apoptotic pathways shown. A cytostatic effect of the compound was also displayed at low mortality doses. This study thus provides important insights into the mechanisms and the potential for this class of molecule in the domain of anti-CSC therapeutics.

Notes on the accumulation and utilization of capital: Some theoretical issues

AbstractThis paper discusses some issues related to the triangle between capital accumulation, distribution, and capacity utilization. First, it explains why utilization is a crucial variable for the various theories of growth and distribution, and, more precisely, with regards to their ability to combine an autonomous role for demand (along Keynesian lines) and an institutionally determined distribution (along classical lines). Second, it responds to some recent criticism by Girardi and Pariboni (2019) and I explain that their interpretation of the model in Nikiforos (2013) is misguided, and that the results of the model can be extended to the case of a monopolist. Third, it provides some concrete examples on why demand is a determinant for the long‐run rate of utilization of capital. Finally, it argues that when it comes to the normal rate of utilization it is the expected growth rate of demand that matters, and not the level of demand. This insight provides a more straightforward way to link the adjustment at the micro and the macro level.

Loss of FGFR4 promotes the malignant phenotype of PDAC

Transcriptomic analyses of pancreatic ductal adenocarcinoma (PDAC) have identified two major epithelial subtypes with distinct biology and clinical behaviours. Here, we aimed to clarify the role of FGFR1 and FGFR4 in the definition of aggressive PDAC phenotypes. We found that the expression of FGFR4 is exclusively detected in epithelial cells, significantly elevated in the classical PDAC subtype, and associates with better outcomes. In highly aggressive basal-like/squamous PDAC, reduced FGFR4 expression aligns with hypermethylation of the gene and lower levels of histone marks associated with active transcription in its regulatory regions. Conversely, FGFR1 has more promiscuous expression in both normal and malignant pancreatic tissues and is strongly associated with the EMT phenotype but not with the basal-like cell lineage. Regardless of the genetic background, the increased proliferation of FGFR4-depleted PDAC cells correlates with hyperactivation of the mTORC1 pathway both in vitro and in vivo. Downregulation of FGFR4 in classical cell lines invariably leads to the enrichment of basal-like/squamous gene programs and is associated with either partial or full switch of phenotype. In sum, we show that endogenous levels of FGFR4 limit the malignant phenotype of PDAC cells. Finally, we propose FGFR4 as a valuable marker for the stratification of PDAC patients.

Relative response factors and multiple regression models in liquid chromatography to quantify low-dosed components using alternative standards-proof of concept: total Δ9-THC content in cannabis flowers using CBD as reference.

A classical quantitative analysis in liquid chromatography is performed using either a one-point calibration or a calibration line, prepared using a reference standard of the compound(s) of interest. However, in some cases, adequate reference standards may be very expensive, rare to obtain, or have limited shelf-life properties. Also, in herbal matrices, multiple compounds could be necessary to be quantified, needing a whole series of different (related) reference standards. In these cases, the use of relative response (sometimes called relative correction factors) factors (RRFs) towards reference standards, different of the compound to be quantified, gained attraction. This study performed a comparison of the use of RRFs and linear relative response factor models (LRRFM) for the quantification of targeted low-dosed compounds using an alternative standard, since it is known that classical RRFs often fail in lower concentration ranges. For this purpose, the determination of the total Δ9-tetrahydrocannabinol (Δ9-THC + Δ9-THC-A) content in dried cannabis flowers, using UHPLC-DAD, was used as a case study. A chromatographic method was implemented and validated, and the use of classical calibration lines, classical RRF, and the LRRFM was applied and compared, with special focus on the concentration around 0.2% (w/w) total Δ9-THC, the legal limit (in most European countries) in these products. Results showed that the newly presented and validated LRRFM approach outperformed the classical RRFs, especially in the low-concentration ranges and that concentrations obtained with the LRRFM were in accordance with the interpolation results obtained with a calibration line.

Model-dependent task assignment in multi-manned mixed-model assembly lines with walking workers

Due to mass customization and extensive market changes, manufacturing companies seek to enhance the flexibility and reconfigurablility of their assembly lines. For instance, to adjust and adapt the line’s capacity to different products and production requirements, workers may move along the stations, or the tasks may be re-assigned. This paper studies the impact of model-dependent task assignment, workforce reconfiguration, and equipment duplication in mixed-model assembly lines. The studied line is paced, and it can process different product models with different sets of tasks and precedence relations. Task and worker assignments to stations may change in each takt, and the goal is to design a line able to handle a predefined set of situations corresponding to different flows of products entering the line. The paper provides a new Mixed Integer Linear Programming (MILP) formulation to minimize the workforce and equipment costs in mixed-model assembly lines with model-dependent task assignment. We provide an efficient reformulation of the MILP by relying on the dualization approach commonly used in robust optimization. In addition, we employ a constructive matheuristic (CM) and a fix-and-optimize heuristic (FOH) to deal with large-scale instances. Extensive computational experiments performed with well-known benchmarks from the literature show that the suggested approaches perform well in terms of solution quality and computational time. In addition, the results reveal that model-dependent task assignment reduces significantly the equipment cost and the number of workers when compared to the classical mixed-model assembly lines with fixed task assignment and walking workers.

Utilization of Plant Architecture Genes in Soybean to Positively Impact Adaptation to High Yield Environments.

Optimization of plant architecture by modifying stem termination and timing of flowering and maturity of soybean is a promising strategy to improve its adaptability to specific production environments. Therefore, it is important to choose a proper stem termination type and to understand morphological differences between each stem termination type under various environmental conditions. Variations in abruptness of stem termination have been generally classified into three classical genetic types, indeterminate (Dt1), determinate (dt1), and semi-determinate (Dt2). However, an additional stem termination type, termed tall determinate, and its genetic symbol, dt1-t, were introduced about 25 years ago. The tall determinate soybean lines show delayed cessation of apical stem growth and about 50% taller plant heights than the typical determinate soybeans, even though the genetic control of the tall determinate phenotype was found to be allelic to dt1. Despite the potential agronomic merits of the alternative stem termination type, knowledge about the tall determinate soybean remains limited. We clarified the molecular basis of the tall determinate stem termination type and examined potential agronomic merits of the alternative stem type under three different production environments in the US. Sequence analysis of the classical tall determinate soybean lines revealed that the dt1-t allele responsible for tall determinate stem architecture is caused by two of the identified independent missense alleles of dt1, dt1-t1 (R130K), and dt1-t2 (R62S). Also, from the comparison among soybean accessions belonging to each of the genotype categories for stem termination types, soybean accessions with tall determinate alleles were found to have a high discrepancy rate in phenotyping. Newly developed tall determinate late-maturing soybean germplasm lines had taller plant heights and a greater number of nodes with a similar stem diameter and similar pod density at the apical stem compared to typical determinate soybeans having dt1 (R166W) alleles in Southern environments in the US. The phenotype of increased pod-bearing nodes with lodging resistance has the potential to improve yield, especially grown in high yield environments. This study suggests an alternative strategy to remodel the shape of soybean plants, which can possibly lead to yield improvement through the modification of soybean plant architecture.

Stationary scattering theory on manifolds

Based on our previous work we develop a stationary scattering theory for the Schrödinger operator on a manifold possessing an escape function. A particular class of examples are manifolds with Euclidean and/or hyperbolic ends. Scattering by obstacles, possibly non-smooth and/or unbounded in a certain manner, is included in the theory. We develop the theory largely along the classical lines of Jäger, Saitō and Constantin, and derive in particular WKB-asymptotics of minimal generalized eigenfunctions. As an application we prove a conjecture of Hempel, Post and Weder on cross-ends transmissions in its natural and strong form within the framework of our theory.