Sequential Sections Research Articles

Abstract A077: The role of RhoV in basal-like pancreatic cancer

Abstract Background Pancreatic ductal adenocarcinoma is a devastating disease lacking targeted therapy. Basal-like pancreatic cancer is a tumor subtype with a worse clinical outcome than other subtypes. These cancers are characterized by the expression of basal keratins and mesenchymal markers. However, the genes that drive the basal-like phenotype are poorly understood. Ras homolog family member V (RhoV) is one of the Rho GTPases, and it has been demonstrated to drive the progression of lung and breast cancers. The current study aims to reveal the role of RhoV in basal-like pancreatic cancer. Design RhoV, p63, and CK5/6 were stained in sequential sections by immunohistochemistry. Expression of RhoV in pancreatic cancer and cell lines was reanalyzed based on the data from ProteinAtlas and Broad Insitute DepMap Portal. Basal cell line, BxPC3, and non-basal cell line, Panc1 were selected for functional evaluation based on their differentiated RhoV expression. RhoV gene was overexpressed and knocked down using the CRISPR/gRNA-based Lentiviral system, followed by sphere formation, colony formation, migration, and invasion assays. Results RhoV, p63, and CK5/6 were expressed in the same histologic location of basal pancreatic cancer. The gene expression level of RhoV was co-expressed with p63 (a classic basal marker) in four pancreatic cancer cell lines (broadinstitute.org). Knockout of RhoV by three runs of gRNAs in BxPC3 cells all significantly attenuated tumor sphere formation with less colony formation as compared to mock knockout. Overexpression of RhoV in non-basal-like cells, Panc 1, significantly increased the size of sphere formation, numbers of colony formation, and p38 activation compared to EV control. Cell migration and invasion assays showed the same RhoV-dependent migration and invasion in corresponding cells. Panc1 cells with RhoV knockout significantly generated smaller tumor xenografts in immunodeficient mice and RhoV overexpression led to larger tumor sizes. Conclusion Finding the driver of the basal-like phenotype helps to reveal the pathophysiology of the basal-like subtype of pancreatic cancer and facilitates the identification of new targets for therapeutic purposes. Our preliminary results indicated that RhoV, a small G protein from the Rho family of GTPases, played essential roles in tumor proliferation and progression, by activating the p38 signaling pathway. Further study will be focused on revealing Rhov's downstream pathways and exploring the role of RhoV in apoptosis/cell cycle, cell metabolism, autophagy, etc. in basel-like pancreatic cancer. Citation Format: Shang Wu, Jia Feng, Selina Gao, Ting Wang, Zebang Li, Yifei Liu, Chiung-Kuei Huang, Shaolei Lu. The role of RhoV in basal-like pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A077.

Kinematic evolution of the Huincul High, Neuquén basin (Argentina) - Sequential restoration and analysis of inversion structures

This research integrated sequential section restoration, detailed seismic attribute analysis, and quantitative fault analysis for key inversion structures along the western Huincul High, a prominent E-W basement discontinuity in the Mesozoic Neuquén Basin. Section restoration of this retroarc foreland basin, indicated that the area inherited a non-uniform basement with a c.a. 30 km wide trough likely related to the Palaeozoic Gondwanan orogeny. This, combined with important Early – Middle Jurassic subsidence (rates of 40mmy−1), provided accommodation for the deposition of the thick Lower – Middle Jurassic Los Molles formation. Restoration also showed the occurrence of two main phases of inversion characterised by distinct styles of accommodation of shortening. Middle to Late Jurassic inversion had a higher degree of horizontal shortening of around 1.18mmy−1, which was accommodated predominantly by newly created shallow thrust faults exhibiting limited vertical displacement. Meanwhile, Early Cretaceous inversion promoted folding and reactivation of normal faults with large, inverted structures attesting up to c.a.1500m of vertical displacement and non-uniform lateral propagation. Seismic attribute analysis highlighted that inversion promoted internal deformation in the hangingwall of the main inverted structures, in the form of a dense network of secondary fractures up to 1 km in length, perpendicular to the strike of the reactivated structures.

Weightbearing Computed Tomography Can Accurately Detect Subtle Lisfranc Injury.

Early detection of Lisfranc injury is critical for improving clinical outcomes, but diagnosing subtle injury can be difficult. Weightbearing computed tomography (WBCT) allows evaluation of such injuries in 3 dimensions (3D) under physiologic load. This study aimed to assess the utility of 1-, 2-, and 3-dimensional measurements on WBCT to diagnose subtle injury in isolated ligamentous Lisfranc injuries. Ten cadaveric specimens underwent WBCT evaluation of the Lisfranc joint complex in the intact state and subsequently with sequential sectioning of the dorsal Lisfranc ligament and interosseous Lisfranc ligament (IOL) to create subtle Lisfranc injury, and finally after transectioning of plantar Lisfranc ligament (PLL) to create the injury conditions for complete ligamentous Lisfranc injury. Measurements under static vertical tibial load of 80 kg were performed on WBCT images including (1) Lisfranc joint (medial cuneiform-base of second metatarsal) volume, (2) Lisfranc joint area, (3) C1-C2 intercuneiform area, (4) C1-M2 distance, (5) C1-C2 distance, (6) M1-M2 intermetatarsal distance, (7) first tarsometatarsal (TMT1) alignment, (8) second tarsometatarsal (TMT2) alignment, (9) TMT1 dorsal step-off distance, and (10) TMT2 dorsal step-off distance. In the subtle Lisfranc injury state, Lisfranc joint volume and area, C1-M2 distance, and M1-M2 distance measurements on WBCT significantly increased, when compared with the intact state (P values .001 to .014). Additionally, Lisfranc joint volume and area, C1-M2 distance, M1-M2 distance, TMT2 alignment, and TMT2 dorsal step-off measurements were increased in the complete Lisfranc injury state. Of all measurements, C1-M2 distance had the largest area under the curve (AUC) of 0.96 (sensitivity = 90%; specificity = 90%), followed by Lisfranc volume (AUC = 0.90; sensitivity = 80%; specificity = 80%) and Lisfranc area (AUC = 0.89; sensitivity = 80%; specificity = 100%). In a cadaveric model we found that WBCT scan can increase the diagnostic accuracy for subtle Lisfranc injury. Among the measurements, C1-M2 distance exhibited the highest level of accuracy. The 2D joint area and 3D joint volume also proved to be accurate, with 3D volume measurements of the Lisfranc joint displaying the most significant absolute difference between the intact state and increasing severity of Lisfranc injury. These findings suggest that 2D joint area and 3D joint volume may have potential as supplementary measurements to more accurately diagnose subtle Lisfranc injuries. WBCT may help surgeons detect subtle Lisfranc injuries.

Digital Pathology Identifies Associations between Tissue Inflammatory Biomarkers and Multiple Sclerosis Outcomes.

Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS. Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38-98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology. Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death. Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.

Single cell RNA-sequencing and RNA-tomography of the avian embryo extending body axis.

Introduction: Vertebrate body axis formation initiates during gastrulation and continues within the tail bud at the posterior end of the embryo. Major structures in the trunk are paired somites, which generate the musculoskeletal system, the spinal cord-forming part of the central nervous system, and the notochord, with important patterning functions. The specification of these different cell lineages by key signalling pathways and transcription factors is essential, however, a global map of cell types and expressed genes in the avian trunk is missing. Methods: Here we use high-throughput sequencing approaches to generate a molecular map of the emerging trunk and tailbud in the chick embryo. Results and Discussion: Single cell RNA-sequencing (scRNA-seq) identifies discrete cell lineages including somites, neural tube, neural crest, lateral plate mesoderm, ectoderm, endothelial and blood progenitors. In addition, RNA-seq of sequential tissue sections (RNA-tomography) provides a spatially resolved, genome-wide expression dataset for the avian tailbud and emerging body, comparable to other model systems. Combining the single cell and RNA-tomography datasets, we identify spatially restricted genes, focusing on somites and early myoblasts. Thus, this high-resolution transcriptome map incorporating cell types in the embryonic trunk can expose molecular pathways involved in body axis development.

Abstract 5498: Multi-modal examination of spatial heterogeneity in the astrocytoma microenvironment

Abstract Astrocytoma is a diffuse tumor that infiltrates the brain. Despite post-operative therapy including radiation and chemotherapy, 52% of patients’ tumors recur within five-years of surgery. These tumors are characterized by mutations in the IDH1 or IDH2 gene that confer metabolic alterations, most notably the production of the onco-metabolite 2-hydroxyglutarate. To reveal the metabolic alterations and their upstream regulation across the tumor microenvironment, we applied spatial metabolomics and spatial transcriptomics to sequential sections from resected tumor samples of patients with low grade astrocytoma. This necessitated extensive optimization of atmospheric-pressure MALDI-TOF, including the establishment of a custom automated computational pipeline with abilities to identify metabolic niches. Additionally, using sequential sections of the same tumor, we also compared all commercially available imaging-based spatial transcriptomic technologies (10x Genomics Xenium, Nanostring CosMx, Vizgen MERSCOPE) to evaluate their suitability with regards to building a multi-modal model of metabolic activity and regulation across the tumor microenvironment. We found that 10x Genomics Xenium was most suited for this task as image registration across sequential sections was comparatively straight-forward. Combining spatial transcriptomics generated with 10x Genomics Xenium and spatial metabolomics across 8 matched sequential slices of the same tumor, we identified metabolic niches associated with distinct cell type composition and transcriptional regulation. Citation Format: Joel Moffet, Jurgen Kriel, Tianyao Lu, Lutz Freytag, James Whittle, Sarah Best, Saskia Freytag. Multi-modal examination of spatial heterogeneity in the astrocytoma microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5498.

Factorization and resummation for sequential recombination jet cross sections

We extend the class of factorization theorems for non-global observables from fixed angular constraints to cross sections defined in terms of sequential jet clustering. The associated hard and soft functions depend not only on the directions of the hard partons, but also on their energy fractions. We derive the one-loop anomalous dimension of the hard functions that drives the leading-logarithmic resummation. The anomalous dimension imposes energy ordering, which simplifies the clustering sequence. We perform resummations for gap-between-jet observables defined with different jet algorithms and explain the effects of the clustering on the importance of secondary emissions and on the effective gap size.

Myeloid spatial and transcriptional molecular signature of ischemia-reperfusion injury in human liver transplantation.

Ischemia-reperfusion injury (IRI) is a significant clinical concern in liver transplantation, with a key influence on short-term and long-term allograft and patient survival. Myeloid cells trigger and sustain tissue inflammation and damage associated with IRI, but the mechanisms regulating these activities are unknown. To address this, we investigated the molecular characteristics of intragraft myeloid cells present in biopsy-proven IRI- and IRI+ liver transplants. RNA-sequencing was performed on 80 pre-reperfusion and post-reperfusion biopsies from 40 human recipients of liver transplantation (23 IRI+, 17 IRI-). We used transcriptional profiling and computational approaches to identify specific gene coexpression network modules correlated with functional subsets of MPO+, lysozyme+, and CD68+ myeloid cells quantified by immunohistochemistry on sequential sections from the same patient biopsies. A global molecular map showed gene signatures related to myeloid activation in all patients regardless of IRI status; however, myeloid cell subsets differed dramatically in their spatial morphology and associated gene signatures. IRI- recipients were found to have a natural corticosteroid production and response profile from pre-reperfusion to post-reperfusion, particularly among monocytes/macrophages. The pre-reperfusion signature of IRI+ recipients included acute inflammatory responses in neutrophils and increased translation of adaptive immune-related genes in monocytes/macrophages coupled with decreased glucocorticoid responses. Subsequent lymphocyte activation at post-reperfusion identified transcriptional programs associated with the transition to adaptive immunity found only among IRI+ recipients. Myeloid subset-specific genes and related signaling pathways provide targets for the development of therapeutic strategies aimed at limiting IRI in the clinical setting of liver transplantation.

Downregulation of the GABAA receptor β2 subunit in a rat model of autism

Introduction: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain, and GABA type A receptor (GABAA) activation mediates fast inhibitory actions. Numerous studies have shown that individual with autism spectrum disorder (ASD) exhibit abnormalities in the expression of GABAA receptors in various brain areas. Additionally, animal models of ASD have suggested alterations in GABAergic neurotransmission and a dysregulation in the balance between inhibitory and excitatory systems. Objective: We investigated the immunolabeling of the GABAA receptor β2 subunit (GARB2) in the hippocampus, the amygdala, and thalamus of infant rats prenatally exposed to valproic acid (VPA) as an ASD model. Methods: Pregnant females were injected with VPA (600mg/Kg, i.p.) during the twelfth embryonic day; control rats were injected with saline. On the fourteen-postnatal-day, rats from both experimental groups were anesthetized, transcardially perfused with 0.9% NaCl and 4% paraformaldehyde, and sequential coronal brain sections (40μm thickness) were obtained. Immunohistochemistry was performed to detect GARB2 and the relative optical density (OD) of expression was analyzed. Results: Our data showed a statistically significant downregulation of GARB2 in the lateral amygdaloid nucleus, as well as in the ventral and lateral thalamic nuclei when compared to control rats. No statistically significant differences were detected in the hippocampus. Discussion: Our findings suggest that prenatal exposure to VPA reduces GARB2 expression in limbic brain regions involved in social-emotional behaviors, like previous reports in individuals with ASD. Conclusion These results support for the involvement of the GABAergic system in the pathogenesis of ASD.

What is the carbon footprint of reverse osmosis in water treatment plants? A systematic review protocol.

"Carbon footprint" (CF) is a direct measure of greenhouse gas emissions caused by a defined activity and can demonstrate global warming effects. The emissions of Greenhouse gases (GHGs) in water projects start from the primary water sources, followed by transportation, construction, and operation phases in the final treatment plants. Due to their possible environmental impacts, the water treatment plants equipped with Reverse Osmosis (RO) units will be investigated for their carbon footprint. The research question is "What is the carbon footprint of reverse osmosis in water treatment plants?". The literature search in this study will be divided into two sequential sections; in the first section, the search will be limited to Scopus, Science Direct, EMBASE, and PubMed databases. The keywords of water, "water treatment plants", "water purification", desalination, "reverse osmosis", RO, "carbon emission", "carbon dioxide/CO2 emission", "carbon footprint", "Life Cycle Assessment" and, LCA will be used. The carbon footprint of RO will be expressed based on the direct and indirect effects based on RO capacity. In the second section, the internet and specialist search will be done, and the search will be updated. No date limitation will be considered, and the main search will be done in English. When the search is completed, the screening will be performed. After removing duplicates, the title and abstract will be examined. The full text will be read if the title and abstract are not helpful for decision-making. In addition, the bibliography and references will proceed after the full-text screening. The Collaboration for Environmental Evidence (CEE) Critical Appraisal Tool will be used for risk of bias checking and study validity assessment. After full-text evaluation, data will be collected and categorized by two authors. If there is enough data, meta-analysis will be performed. Systematic review registration PROSPERO CRD42022327572.

Current sensor-based single MPPT controller using sequential golden section search algorithm for hybrid solar PV generator-TEG in isolated DC microgrid

A current sensor-based single maximum power point tracking (SMPPT) controller is proposed for extracting the maximum power (MP) from a hybrid solar photovoltaic (PV) generator-thermoelectric generator (TEG) supplying an isolated DC microgrid. The proposed SMPPT controller tracks the maximum power points (MPPs) of the hybrid solar PV generator-TEG using the sequential golden section search (SGSS) algorithm. Faster and guaranteed convergence are the major advantages of this SGSS algorithm for tracking the MPPs of hybrid solar PV generator-TEG sequentially. Further, the proposed SMPPT controller requires a single sensing and signal conditioning circuit (SSCC) and a digital controller for successful operation. Thus, it requires less investment cost, reduces control complexity, consumes less power, and improves reliability. Extensive simulations, experiments, and comparative studies have demonstrated the effectiveness of the proposed SMPPT controller using the SGSS algorithm.

The effect of current and lambda on white-etch-crack failures

White etching cracks (WECs) have been associated with premature failure of wind turbine roller bearings. Various drivers for the generation of WECs have been identified such as loading conditions, slip, steel quality, lubrication, hydrogen embrittlement, corrosion fatigue cracking, and stray electrical currents passing through the surface. In this work, a benchtop test rig utilizing a three-ring-on-roller test configuration was used to investigate the effect of electrical current and operation in different lubricating regimes, defined by lambda (λ), on high-quality bearing steel samples tested in a commercially available power transmission EP gear lubricant. It was observed that there is an inverse correlation between the magnitude of electric current applied to the ring/roller system and time-to-failure. Higher current magnitudes lead to shorter time-to-failure than lower current magnitudes, with macropitting as the main failure mode. Sub-surface investigation revealed the presence of WECs in all cases. For the same current magnitude, tests conducted in boundary and mixed lubrication regimes showed that time-to-failure increased as λ increased, and the tests resulted in WEC related macropits, whereas tests conducted in near-hydrodynamic regime resulted in surface damage with no macropit. It was also noted that a shift toward near-hydrodynamic lubrication resulted in a distinct surface distress on the roller surface. Furthermore, there seems to be a transition in the mixed regime during which the surface distress occurred. The damage on the surface of the test samples resembled non-spatially, periodic, groove-like corrugations and, in some cases, crater-like depressions. Sub-surface imaging, performed by sequential sectioning, revealed the presence of WECs in all cases, and broad, branching cracks that were more prevalent under the more severe boundary conditions.

Greater Knee Rotatory Instability After Posterior Meniscocapsular Injury Versus Anterolateral Ligament Injury: A Proposed Mechanism of High-Grade Pivot Shift.

For anterolateral rotatory instability as a result of secondary soft tissue injuries in anterior cruciate ligament (ACL)-deficient knees, there is increasing interest in secondary stabilizers to prevent internal rotation (IR) of the tibia. To determine which secondary stabilizer is more important in anterolateral rotatory instability in ACL-deficient knees. Controlled laboratory study. The lower extremities of 10 fresh-frozen cadavers (20 extremities) without anterior-posterior or rotational instability were included. Matched-pair randomization was performed, with each side per specimen assigned to 1 of 2 groups. In group 1, the ACL was sectioned, followed by the anterolateral ligament (ALL); in group 2, the ACL was sectioned, followed by sequential sectioning of the posterolateral meniscocapsular complex (PLMCC) and posteromedial meniscocapsular complex (PMMCC). The primary outcome was the change in relative tibial IR during a simulated pivot-shift test with 5 N·m of IR torque and 8.9 N of valgus force. The secondary outcomes were the International Knee Documentation Committee grade in the pivot-shift test and the incidence of the grade 3 pivot shift. In group 1, compared with baseline, the change in relative tibial IR at 0° of knee flexion was 1.4° (95% CI, -0.1° to 2.9°; P = .052) after ALL release. In group 2, it was 2.5° (95% CI, 0.4° to 4.8°; P = .007) after PLMCC release and 4.1° (95% CI, 0.5° to 7.8°; P = .017) after combined PLMCC and PMMCC release. Combined PLMCC and PMMCC release resulted in greater change of tibial IR with statistical significance at 0°, 15°, and 30° of knee flexion (P = .008, .057, and .004, respectively) compared with ALL release. The incidence of grade 3 pivot shifts was 10% in group 1 and 90% in group 2. Posterior meniscocapsular laxity caused an increase in relative tibial IR as much as ALL injury in ACL-deficient knees in our simulated laboratory test, and greater anterolateral rotatory instability occurred with posterior meniscocapsular injury compared with ALL injury. Repair of the injured posterior meniscocapsular complex may be an important treatment option for reducing anterolateral rotatory instability in the ACL-deficient knee.

3D reconstruction of skin and spatial mapping of immune cell density, vascular distance and effects of sun exposure and aging

Mapping the human body at single cell resolution in three dimensions (3D) is important for understanding cellular interactions in context of tissue and organ organization. 2D spatial cell analysis in a single tissue section may be limited by cell numbers and histology. Here we show a workflow for 3D reconstruction of multiplexed sequential tissue sections: MATRICS-A (Multiplexed Image Three-D Reconstruction and Integrated Cell Spatial - Analysis). We demonstrate MATRICS-A in 26 serial sections of fixed skin (stained with 18 biomarkers) from 12 donors aged between 32–72 years. Comparing the 3D reconstructed cellular data with the 2D data, we show significantly shorter distances between immune cells and vascular endothelial cells (56 µm in 3D vs 108 µm in 2D). We also show 10–70% more T cells (total) within 30 µm of a neighboring T helper cell in 3D vs 2D. Distances of p53, DDB2 and Ki67 positive cells to the skin surface were consistent across all ages/sun exposure and largely localized to the lower stratum basale layer of the epidermis. MATRICS-A provides a framework for analysis of 3D spatial cell relationships in healthy and aging organs and could be further extended to diseased organs.

Anatomic and Biomechanical Study of the Forearm Interosseous Membrane, Distal Oblique Bundle, and Triangular Fibrocartilage Complex: Role in Galeazzi Fracture Dislocation

The purpose of this study was to measure distal radioulnar joint (DRUJ) dislocation and radioulnar displacement associated with sequential sectioning of the different bands of the interosseous membrane and triangular fibrocartilage complex in the simulation of a Galeazzi fracture dislocation. Twelve fresh-frozen cadaver forearms were dissected. We examined the anatomy and function of the forearm interosseous membrane. Each forearm was then mounted onto a biomechanical wrist and forearm device. In the control group, radial osteotomy was performed and the degree of DRUJ displacement with progressive loads was measured. In addition to radial osteotomy, in group 1, the central band (CB) was sectioned; in group 2, the CB, distal membranous portion of the interosseous membrane, and distal oblique bundle were sectioned; and in group 3, the CB, distal membranous portion of the interosseous membrane, distal oblique bundle, and triangular fibrocartilage complex were sectioned. The radioulnar displacement (mm) at 25 N, 50 N, and 75 N was recorded. In group 1, applying progressive loads resulted in an average DRUJ displacement of 4.3, 5.9, and 7.9 mm, respectively. In group 2, the displacement was 5.2, 5.7, and 6.9 mm, respectively. In group 3, the displacement was 6.2, 8.1, and 9.9 mm, respectively. Our study showed a correlation between increase in the load applied to the same injury and the degree of displacement (P= .001). In group 3, the degree of DRUJ displacement was statistically increased compared to the other groups (P= .04). Migration of the radius under loads implies disruption of both the CB and triangular fibrocartilage complex. The distal oblique bundle by itself does not seem to have a relevant role in radioulnar displacement at the DRUJ. This study provides insights into the interosseous membrane and stability of the DRUJ, which can contribute to a better understanding of Galeazzi fracture-dislocations.

Dynamic sequential radar cross section properties of airborne corner reflector in array

AbstractWith the spread of airborne corner reflector (ACR) in the field of shipborne equipment, radar guided anti‐ship missile is facing new challenges. In order to achieve the mastery of the jamming principle of this apparatus, the paper studied its motion properties and sequential Radar Cross Section (RCS) properties. Firstly, the motion model of the ACR was obtained under certain constraints, by deriving the centroid dynamics equation and rotation dynamics equation according to the theoretical mechanics. Then, the dynamic sequential RCS model of ACR array was established by combining the motion model with the modified geometric optics method and coherent synthesis method. Through the simulation and analysis of the motion model, it was found that the flight process of the ACR can be divided into two stages: fast falling and steady falling. In the fast falling stage, the variables of the ACR system change rapidly, while the ACR rotates slowly and falls smoothly in the steady falling stage. From simulation of dynamic sequential RCS model, the results showed that the obvious depolarisation effect is occur in the fast falling stage. Further statistical analysis showed that, the omnidirectivity of single ACR is well from the dynamic perspective, meanwhile array placement can effectively enhance RCS amplitude and improve the probability density distribution.

Domestic cat nose functions as a highly efficient coiled parallel gas chromatograph.

The peripheral structures of mammalian sensory organs often serve to support their functionality, such as alignment of hair cells to the mechanical properties of the inner ear. Here, we examined the structure-function relationship for mammalian olfaction by creating an anatomically accurate computational nasal model for the domestic cat (Felis catus) based on high resolution microCT and sequential histological sections. Our results showed a distinct separation of respiratory and olfactory flow regimes, featuring a high-speed dorsal medial stream that increases odor delivery speed and efficiency to the ethmoid olfactory region without compromising the filtration and conditioning purpose of the nose. These results corroborated previous findings in other mammalian species, which implicates a common theme to deal with the physical size limitation of the head that confines the nasal airway from increasing in length infinitely as a straight tube. We thus hypothesized that these ethmoid olfactory channels function as parallel coiled chromatograph channels, and further showed that the theoretical plate number, a widely-used indicator of gas chromatograph efficiency, is more than 100 times higher in the cat nose than an "amphibian-like" straight channel fitting the similar skull space, at restful breathing state. The parallel feature also reduces airflow speed within each coil, which is critical to achieve the high plate number, while feeding collectively from the high-speed dorsal medial stream so that total odor sampling speed is not sacrificed. The occurrence of ethmoid turbinates is an important step in the evolution of mammalian species that correlates to their expansive olfactory function and brain development. Our findings reveal novel mechanisms on how such structure may facilitate better olfactory performance, furthering our understanding of the successful adaptation of mammalian species, including F. catus, a popular pet, to diverse environments.

Scaphoid, lunate and capitate kinematics in the normal and ligament deficient wrist: A bi-plane X-ray fluoroscopy study

The ligamentous structures of the wrist stabilise and constrain the interactions of the carpal bones during active wrist motion; however, the three-dimensional translations and rotations of the scaphoid, lunate and capitate in the normal and ligament deficient wrist during planar and oblique wrist motions remain poorly understood. This study employed a computer-controlled simulator to replicate physiological wrist motion by dynamic muscle force application, while carpal kinematics were simultaneously measured using bi-plane x-ray fluoroscopy. The aim was to quantify carpal kinematics in the native wrist and after sequential sectioning of the scapholunate interosseous ligament (SLIL) and secondary scapholunate ligament structures. Seven fresh-frozen cadaveric wrist specimens were harvested, and cycles of flexion–extension, radial-ulnar deviation and dart-thrower’s motion were simulated. The results showed significant rotational and translational changes to these carpal bones in all stages of disruptions to the supporting ligaments (p < 0.05). Specifically, following the disruption of the dorsal SLIL (Stage II), the scaphoid became significantly more flexed, ulnarly deviated, and pronated relative to the radius, whereas the lunate became more extended, supinated and volarly translated (p < 0.05). Sectioning of the dorsal intercarpal (DIC), dorsal radiocarpal (DRC), and scaphotrapeziotrapezoid (STT) ligaments (Stage IV) caused the scaphoid to collapse further into flexion, ulnar deviation, and pronation. These findings highlight the importance of all the ligamentous attachments that relate to the stability of the scapholunate joint, but more importantly, the dorsal SLIL in maintaining scapholunate stability, and the preservation of the attachments of the DIC and DRC ligaments during dorsal surgical approaches. The findings will be useful in diagnosing wrist pathology and in surgical planning.

Impact of an SLC30A8 loss-of-function variant on the pancreatic distribution of zinc and manganese: laser ablation-ICP-MS and positron emission tomography studies in mice.

Common variants in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8 (expressed largely in pancreatic islet alpha and beta cells), are associated with altered risk of type 2 diabetes. Unexpectedly, rare loss-of-function (LoF) variants in the gene, described in heterozygous individuals only, are protective against the disease, even though knockout of the homologous SLC30A8 gene in mice leads to unchanged or impaired glucose tolerance. Here, we aimed to determine how one or two copies of the mutant R138X allele in the mouse SLC30A8 gene impacts the homeostasis of zinc at a whole-body (using non-invasive 62Zn PET imaging to assess the acute dynamics of zinc handling) and tissue/cell level [using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to map the long-term distribution of zinc and manganese in the pancreas]. Following intravenous administration of [62Zn]Zn-citrate (~7 MBq, 150 μl) in wild-type (WT), heterozygous (R138X+/-), and homozygous (R138X+/+) mutant mice (14-15 weeks old, n = 4 per genotype), zinc dynamics were measured over 60min using PET. Histological, islet hormone immunohistochemistry, and elemental analysis with LA-ICP-MS (Zn, Mn, P) were performed on sequential pancreas sections. Bulk Zn and Mn concentration in the pancreas was determined by solution ICP-MS. Our findings reveal that whereas uptake into organs, assessed using PET imaging of 62Zn, is largely unaffected by the R138X variant, mice homozygous of the mutant allele show a substantial lowering (to 40% of WT) of total islet zinc, as anticipated. In contrast, mice heterozygous for this allele, thus mimicking human carriers of LoF alleles, show markedly increased endocrine and exocrine zinc content (1.6-fold increase for both compared to WT), as measured by LA-ICP-MS. Both endocrine and exocrine manganese contents were also sharply increased in R138X+/- mice, with smaller increases observed in R138X+/+ mice. These data challenge the view that zinc depletion from the beta cell is the likely underlying driver for protection from type 2 diabetes development in carriers of LoF alleles. Instead, they suggest that heterozygous LoF may paradoxically increase pancreatic β-cell zinc and manganese content and impact the levels of these metals in the exocrine pancreas to improve insulin secretion.

Characterization of intratumoral tertiary lymphoid structures in pancreatic ductal adenocarcinoma: cellular properties and prognostic significance

BackgroundTumor-associated tertiary lymphoid structures (TLSs) are functional immune-responsive niches that are not fully understood in pancreatic ductal adenocarcinoma (PDAC).MethodsFluorescent multiplex immunohistochemistry was performed on sequential sections of surgically resected tumor...