Search

As processor microarchitecture is getting complicated, an accurate analytic model becomes crucial for exploring large processor design space within limited development time. An interval simulation is a widely used analytic model for processor designs in the early stage. However, it cannot accurately model modern microarchitecture, which has an unbalanced pipeline. In this work, we introduce IntervalSim++, an accurate analytic model for a modern microarchitecture design based on the interval simulation. We identify key components highly related to the unbalanced pipeline and propose new modeling techniques atop the interval simulation without incurring significant overheads. Our evaluations show IntervalSim++ accurately models a modern out-of-order processor with minimal overheads, showing 1% average CPI error and only 8.8% simulation time increase compared to the baseline interval simulation. [ABSTRACT FROM AUTHOR]

Modern SoCs require increasingly complex embedded control deep within their numerous sub-blocks without adding significant die area. This motivated the creation of $\mu $ RTL, a novel toolset for systematically designing efficient pipelined implementations of embedded instruction sets originally intended for multicycle execution. $\mu $ RTL utilizes hardwired micro-op translation, a technique commonly used in the instruction decoders of large super-scalar microprocessors, however this technique has been overlooked for designing smaller, more efficient embedded microprocessors. Furthermore, the tools to develop instruction decoders with micro-op translation are proprietary and the techniques are trade secrets. The $\mu $ RTL toolset is open-source and this letter clearly presents the methodology. The methodology emphasizes direct opcode decoding from multiple synthesized Verilog blocks versus traditional microprogramming which uses sequential decoding from a ROM. Our results show that a pipelined $\mu $ RTL microarchitecture achieves a 21.8% reduction in size compared to a hardwired multicycle implementation of the same instruction set. Additionally, the performance of 0.75 DMIPS/MHz surpasses the RISC-V PicoRV32 by 44.2% and the AVR RISC by 82.9%. These improvements in performance, power, and area are of interest to embedded system architects. [ABSTRACT FROM AUTHOR]

The physiochemical, structural, and molecular characteristics of starch influence its functional properties, thereby dictating its utilization. The study aimed to profile the properties and quantity of resistant starch (RS) from 15 different banana varieties, extracted using a combination of alkaline and enzyme treatments. Granular structure and molecular organization were analyzed using light microscopy, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The physiochemical and functional properties were also investigated. RS content ranged from 49% to 80% without significant relationship to amylose (AM) (r = −0.1062). SEM revealed significant microarchitectural differences on the granules potentially affecting granule digestibility. FTIR and chemometrics identified differences in the crystalline peaks, yielding varying degrees of the molecular order of the RS polymers that aid in differentiating the RS sources. Despite similar solubility and swelling profiles, the pasting profiles varied across varieties, indicating high paste stability in hydrothermal processing. Clarity ranged from 43% to 93%, attributed to amylose leaching. This study highlights that RS from bananas varies in quantity, structure, and functionality, necessitating individualized approaches for processing and utilization. [ABSTRACT FROM AUTHOR]

The femoral head is one of the most commonly used bones for allografts and biomechanical studies. However, there are few reports on the trabecular bone microarchitectural parameters of freshly harvested trabecular bones. To our knowledge, this is the first study to characterize the microstructure of femoral heads tested immediately after surgery and compare it with the microstructure obtained with conventional freezing. This study aims to investigate whether freezing at −80 °C for 6 weeks affects the trabecular microstructure of freshly harvested bone tissue. This study was divided into two groups: one with freshly harvested human femoral heads and the other with the same human femoral heads frozen at −80 °C for 6 weeks. Each femoral head was scanned using an X-ray microcomputed tomography scanner (µCT) to obtain the microarchitectural parameters, including the bone volume fraction (BV/TV), the mean trabecular thickness (Tb.th), the trabecular separation (Tb.sp), the degree of anisotropy (DA), and the connectivity density (Conn.D). There was no statistically significant difference between the fresh and the frozen groups for any of the parameters measured. This study shows that freezing at −80 °C for 6 weeks does not alter bone microstructure compared with freshly harvested femoral heads tested immediately after surgery. [ABSTRACT FROM AUTHOR]

Research on slow-wave sleep (SWS) began almost a century ago, not long after the discovery of electroencephalography. From maintaining homeostasis to memory function, the pivotal role of SWS in health has been established. The elucidation of its mechanisms and functions is directly related to the fundamental question of why people sleep. This comprehensive review first summarizes the basic science of SWS from anatomical and physiological aspects. It describes the fundamental mechanisms and functions of SWS, including hormonal regulation, developmental changes in SWS across the lifespan, and associations between SWS and optimal physical, psychological, and cognitive functions. Next, the relationship between SWS and physical and mental disorders, for which increasing knowledge has accumulated in recent years, is discussed from both research and clinical perspectives. Conditions such as memory impairment, sleep-disordered breathing, neurodevelopmental disorders, and various psychiatric disorders are of concern. The relationship between SWS and the glymphatic system, which is responsible for waste clearance in the brain, has also been explored, highlighting the potential neuroprotective role of SWS. Finally, we discuss the future direction of the field regarding whether interventions in SWS can improve health. We also address the problem of the inconsistent definitions of SWS, slow-wave activity, and slow oscillations. This review emphasizes the importance of discussing SWS from both macro- and microarchitectural perspectives and highlights its potential clinical and research impacts. By reviewing these aspects, we aim to contribute to a deeper understanding of SWS and the future development of this research field. [ABSTRACT FROM AUTHOR]

Osteoporosis and cardiovascular disease frequently occur together in older adults; however, a causal relationship between these 2 common conditions has not been established. By the time clinical cardiovascular disease develops, it is often too late to test whether vascular dysfunction developed before or after the onset of osteoporosis. Therefore, we assessed the association of vascular function, measured by tonometry and brachial hemodynamic testing, with bone density, microarchitecture, and strength, measured by HR-pQCT, in 1391 individuals in the Framingham Heart Study. We hypothesized that decreased vascular function (pulse wave velocity, primary pressure wave, brachial pulse pressure, baseline flow amplitude, and brachial flow velocity) contributes to deficits in bone density, microarchitecture and strength, particularly in cortical bone, which is less protected from excessive blood flow pulsatility than the trabecular compartment. We found that individuals with increased carotid-femoral pulse wave velocity had lower cortical volumetric bone mineral density (tibia: −0.21 [−0.26, −0.15] standardized beta [95% CI], radius: −0.20 [−0.26, −0.15]), lower cortical thickness (tibia: −0.09 [−0.15, −0.04], radius: −0.07 [−0.12, −0.01]) and increased cortical porosity (tibia: 0.20 [0.15, 0.25], radius: 0.21 [0.15, 0.27]). However, these associations did not persist after adjustment for age, sex, height, and weight. These results suggest that vascular dysfunction with aging may not be an etiologic mechanism that contributes to the co-occurrence of osteoporosis and cardiovascular disease in older adults. Further study employing longitudinal measures of HR-pQCT parameters is needed to fully elucidate the link between vascular function and bone health. Lay Summary: Osteoporosis and heart disease are both medical conditions that commonly develop in older age. It is not known whether abnormal functioning of blood vessels contributes to the development of bone fragility with aging. In this study, we investigated the relationship between impaired blood vessel function and bone density and micro-structure in a group of 1391 people enrolled in the Framingham Heart Study. Blood vessel function was measured using specialized tools to assess blood flow and pressure. Bone density and micro-structure were measured using advanced imaging called HR-pQCT. We found that people with impaired blood vessel function tended to have lower bone density and worse deterioration in bone micro-structure. However, once we statistically controlled for age and sex and other confounders, we did not find any association between blood vessel function and bone measures. Overall, our results showed that older adults with impaired blood vessel function do not exhibit greater deterioration in the skeleton. [ABSTRACT FROM AUTHOR]

Additive manufacturing has emerged as a transformative tool in biomedical engineering, offering precise control over scaffold design for bone tissue engineering and regenerative medicine. While much attention has been focused on optimizing pore-based scaffold architectures, filament-based microarchitectures remain relatively understudied, despite the fact that the majority of 3D-printers generate filament-based structures. Here, we investigated the influence of filament characteristics on bone regeneration outcomes using a lithography-based additive manufacturing approach. Three distinct filament-based scaffolds (Fil050, Fil083, and Fil125) identical in macroporosity and transparency, crafted from tri-calcium phosphate (TCP) with varying filament thicknesses and distance, were evaluated in a rabbit model of bone augmentation and non-critical calvarial defect. Additionally, two scaffold types differing in filament directionality (Fil and FilG) were compared to elucidate optimal design parameters. Distance of bone ingrowth and percentage of regenerated area within scaffolds were measured by histomorphometric analysis. Our findings reveal filaments of 0.50 mm as the most effective filament-based scaffold, demonstrating superior bone ingrowth and bony regenerated area compared to larger size filament (i.e., 0.83 mm and 1.25 mm scaffolds). Optimized directionality of filaments can overcome the reduced performance of larger filaments. This study advances our understanding of microarchitecture's role in bone tissue engineering and holds significant implications for clinical practice, paving the way for the development of highly tailored, patient-specific bone substitutes with enhanced efficacy. [ABSTRACT FROM AUTHOR]

Triply periodic minimal surface microarchitectures (TPMS) were developed by mathematicians and evolved in all kingdoms of living organisms. Renowned for their lightweight yet robust attributes, TPMS structures find application in diverse fields, such as the construction of satellites, aircrafts, and electric vehicles. Moreover, these microarchitectures, despite their intricate geometric patterns, demonstrate potential for application as bone substitutes, despite the inherent gothic style of natural bone microarchitecture. Here, we produced three TPMS microarchitectures, D-diamond, G-gyroid, and P-primitive, by 3D printing from hydroxyapatite. We explored their mechanical characterization and, further, implanted them to study their bone augmentation and osteoconduction potential. In terms of strength, the D-diamond and G-gyroid performed significantly better than the P-primitive. In a calvarial defect model and a calvarial bone augmentation model, where osteoconduction is determined as the extent of bony bridging of the defect and bone augmentation as the maximal vertical bone ingrowth, the G-gyroid performed significantly better than the P-primitive. No significant difference in performance was observed between the G-gyroid and D-diamond. Since, in real life, the treatment of bone deficiencies in patients comprises elements of defect bridging and bone augmentation, ceramic scaffolds with D-diamond and G-gyroid microarchitectures appear as the best choice for a TPMS-based scaffold in bone tissue engineering. [ABSTRACT FROM AUTHOR]

In recent years, open-source RISC-V microprocessors represented by Hummingbird E203 have received widespread attention and application in both academia and industry due to their low power consumption and good performance. To improve the performance of microprocessors and reduce pipeline stalls caused by branch instructions, branch prediction technology has become one of the important techniques widely used in modern microprocessors. However, the branch predictor currently used in the Hummingbird E203 is a lightweight static branch predictor, facing the challenge of low branch prediction accuracy. Since using a dynamic branch predictor with higher prediction accuracy can further reduce the overhead caused by mispredictions leading to redirecting fetching, various implementations of dynamic branch predictors have been explored based on the original microarchitecture to improve branch prediction accuracy while considering resource overhead. Experimental results show that among various dynamic branch predictors, the one achieving the best results is the adaptive dynamic branch predictor combining static branch prediction with Branch History Register (BHR). On the Dhrystone benchmark program, its branch prediction accuracy can be increased from the original 84.6% to 94.8%, and the score from 1.296 463 to 1.314 418. On the Coremark benchmark program, its branch prediction accuracy can be increased from the original 67% to 78.7%, and the score from 2.120 000 to 2.138 008. [ABSTRACT FROM AUTHOR]

Severe conditions such as high-energy particle strikes may induce soft errors in on-chip memory, like cache and translation lookaside buffers (TLBs). As the key component of virtual-to-physical address translation, TLB directly affects processor performance. To protect the virtual page information stored in TLB, several studies have introduced error detection or correction codes. However, most schemes proposed for data TLB cannot support the detection of multi-bit upsets, which is reported as a serious issue in modern fault-tolerant processors due to the downscaling of CMOS process technology. In this paper, we propose a new two-dimensional protection technique, called the matrix protection tag (MaP-Tag), to provide stronger error detection and correction capability to TLB virtual page information. Our proposal reorganizes virtual page information into a matrix and employs adjacent check bits and interleaved check bits for error detection. The two-dimensional design offers one-bit error detection, burst multi-bit error detection, and even multi-bit error correction in some cases. The simulation results show that our proposal can detect almost all error patterns when injected with up to eight bit-flips. Furthermore, the technique provides a better error correction rate than conventional single error correction (SEC) codes. The reliability calculation shows that our proposal is powerful in both error detection and correction with affordable storage overhead. [ABSTRACT FROM AUTHOR]

The vertebral centra of sharks consist of cartilage, and many species' centra contain a bioapatite related to that in bone. Centra microarchitectures at the 0.5-50 µm scale do not appear to have been described previously. This study examines centrum microarchitecture in lamniform and carcharhiniform sharks with synchrotron microComputed Tomography (microCT), scanning electron microscopy and spectroscopy and light microscopy. The analysis centers on the blue shark (carcharhiniform) and shortfin mako (lamniform), species studied with all three modalities. Synchrotron microCT results from seven other species complete the report. The main centrum structures, the corpus calcareum and intermedialia, consist of fine, closely-spaced, mineralized trabeculae whose mean thicknesses and spacings range from 4.5 to 11.2 µm and 4.5 to 15.6 µm, respectively. A significant (p = 0.00001) positive linear relationship between and exists for multiple positions within one mako centrum. Carcharhiniform species' and exhibit an inverse linear relationship (p = 0.005) while in lamniforms these variables tend toward a positive relationship which does not reach statistical significance (p = 0.099). In all species, the trabeculae form an uninterrupted, interconnected network, and the unmineralized volumes are similarly interconnected. Small differences in mineralization level are observed in trabeculae. Centrum growth band pairs are found to consist of locally higher /lower mineral volume fraction. Within the intermedialia, radial canals and radial microrods were characterized, and compacted trabeculae are prominent in the mako intermedialia. The centra's mineralized central zones were non-trabecular and are also described. This study's novel result is the demonstration that the mineralized cartilage of sharks' vertebral bodies (centra) consists of a fine 3D array of interconnected plates (trabeculae) and an interpenetrating network of unmineralized tissue. This microstructure is radically different from that in tesserae or in teeth, the other main mineralized shark tissues. Using volumetric synchrotron microComputed Tomography, numerical values of mean trabecular thickness and spacing and their relationship were measured for nine species. Scanning electron microscopy added a higher resolution view of the microstructures, and histology provided complementary information on cartilage and cells. The present results suggest centra microstructure helps accommodate the very large in vivo strains and may prevent damage accumulation during millions of cycles of swimming-induced loading. [Display omitted] [ABSTRACT FROM AUTHOR]

Wood-derived TEMPO-oxidized cellulose nanofibrils (CNFs) have potential as scaffolding for bone tissue engineering. Although biocompatible, the material lacks osteoconductive and appropriate mechanical properties. Incorporation of nano-hydroxyapatite (nHA) and modification of scaffold preparation methods could improve applicability. In this study, freeze-dried porous scaffolds were prepared using a range of nHA (0, 20, 33, 50%) and CNF compositions. Not only the microarchitecture but also the chemical composition of the scaffolds was studied. Osteoblast-like osteosarcoma derived cells (Saos-2) were cultured on the scaffolds and their responses (viability, attachment, proliferation, and osteogenic phenotype) to the different scaffolds were documented. The results show that incorporation of nHA influenced the microarchitecture, mechanical stiffness and surface properties of the scaffolds. Moreover, biological characterization demonstrated good cell viability in all the groups. However, the increase of nHA concentration beyond 20% does not offer further advantages. It is concluded that the incorporation of 20% nHA resulted in the widest and most biomimetic pore size distribution, increased surface roughness and improved protein adsorption. These changes in material properties enhanced cell spreading and the osteogenic gene expression of osteoblast-like cells seeded on the scaffolds. Moreover, 20% nHA warrants further investigation as a potential scaffolding material for bone tissue engineering. [ABSTRACT FROM AUTHOR]

The use of analog models in microarchitecture design offers a series of benefits, from detailed exploration of small-scale elements to stimulating creativity and innovation. These enriching experiences significantly contribute to the design process and help develop more robust and effective architectural solutions. Models are tools that enhance haptic perception and play various roles in the analysis, experimentation, conceptualization, and teaching of microarchitectures. Their ability to provide a tangible and accessible representation of design makes them remarkable resources in the architectural design process.

Accurate simulation techniques are indispensable to efficiently propose new memory or architectural organizations. As implementing new hardware concepts in real systems is often not feasible, cycle-accurate simulators employed together with certain benchmarks are commonly used. However, detailed simulators may take too much time to execute these programs until completion. Therefore, several techniques aimed at reducing this time are usually employed. These schemes select fragments of the source code considered as representative of the entire application’s behaviour–mainly in terms of performance, but not plenty considering the behaviour of cache memory levels–and only these intervals are simulated. Our hypothesis is that the different simulation windows currently employed when evaluating microarchitectural proposals, especially those involving the last level cache (LLC), do not reproduce the overall cache behaviour during the entire execution, potentially leading to wrong conclusions on the real performance of the proposals assessed. In this work, we first demonstrate this hypothesis by evaluating different cache replacement policies using various typical simulation approaches. Consequently, we also propose a simulation strategy, based on the applications’ LLC activity, which mimics the overall behaviour of the cache much closer than conventional simulation intervals. Our proposal allows a fairer comparison between cache-related approaches as it reports, on average, a number of changes in the relative order among the policies assessed – with respect to the full simulation – more than 30% lower than that of conventional strategies, maintaining the simulation time largely unchanged and without losing accuracy on performance terms, especially for memory-intensive applications.

The physiochemical, structural, and molecular characteristics of starch influence its functional properties, thereby dictating its utilization. The study aimed to profile the properties and quantity of resistant starch (RS) from 15 different banana varieties, extracted using a combination of alkaline and enzyme treatments. Granular structure and molecular organization were analyzed using light microscopy, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The physiochemical and functional properties were also investigated. RS content ranged from 49% to 80% without significant relationship to amylose (AM) (r = −0.1062). SEM revealed significant microarchitectural differences on the granules potentially affecting granule digestibility. FTIR and chemometrics identified differences in the crystalline peaks, yielding varying degrees of the molecular order of the RS polymers that aid in differentiating the RS sources. Despite similar solubility and swelling profiles, the pasting profiles varied across varieties, indicating high paste stability in hydrothermal processing. Clarity ranged from 43% to 93%, attributed to amylose leaching. This study highlights that RS from bananas varies in quantity, structure, and functionality, necessitating individualized approaches for processing and utilization.

In-vivo bone microstructure measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) is gaining importance in research and clinical practice. Second-generation HR-pQCT (XCT2) shows improved image quality and shorter measurement duration compared to the first generation (XCT1). Predicting and understanding the occurrence of motion artifacts is crucial for clinical practice. We retrospectively analyzed data from HR-pQCT measurements at the distal radius and tibia of 1,000 patients (aged 20 to 89) evenly distributed between both generations of HR-pQCT. Motion artifacts were graded between 1 (no motion) and 5 (severe motion), with grades greater 3 considered unusable. Additionally, baseline characteristics and patients' muscle performance and balance were measured. Various group comparisons between the two generations of HR-pQCT and regression analyses between patient characteristics and motion grading were performed. The study groups of XCT1 and XCT2 did not differ by age (XCT1: 64.9 vs. XCT2: 63.8 years, p = 0.136), sex (both 74.5% females, p > 0.999), or BMI (both 24.2 kg/m2, p = 0.911) after propensity score matching. XCT2 scans exhibited significantly lower motion grading in both extremities compared to XCT1 (Radius: p < 0.001; Tibia: p = 0.002). In XCT2 motion-corrupted scans were more than halved at the radius (XCT1: 35.3% vs. XCT2: 15.5%, p < 0.001), and at the tibia the frequency of best image quality scans was increased (XCT1: 50.2% vs. XCT2: 63.7%, p < 0.001). The strongest independent predictor for motion-corrupted images is the occurrence of high motion grading at the other scanning site during the same consultation. The association between high motion grading in one scan and a corresponding high motion grading in another scan within the same session suggests a non-resting patient. Additionally, aged, female, and patients with smaller stature tend towards higher motion grading, requiring special attention to a correct extremity fixation. [ABSTRACT FROM AUTHOR]

Background: The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture, such as follicular hyperplasia (FH), sinus histiocytosis (SH), or paracortical hyperplasia (PH), may be triggered by the anti-tumour immune response. However, the prognostic value of these changes in GaC patients is unclear. Methods: A systematic search in multiple databases was conducted to identify studies on the prognostic value of microarchitecture changes in regional tumour-negative and tumour-positive LNs measured on histopathological slides. Since the number of GaC publications was very limited, the search was subsequently expanded to include junctional and oesophageal cancer (OeC). Results: A total of 28 articles (17 gastric cancer, 11 oesophageal cancer) met the inclusion criteria, analyzing 26,503 lymph nodes from 3711 GaC and 1912 OeC patients. The studies described eight different types of lymph node microarchitecture changes, categorized into three patterns: hyperplasia (SH, FH, PH), cell-specific infiltration (dendritic cells, T cells, neutrophils, macrophages), and differential gene expression. Meta-analysis of five GaC studies showed a positive association between SH in tumour-negative lymph nodes and better 5-year overall survival. Pooled risk ratios for all LNs showed increased 5-year overall survival for the presence of SH and PH. Conclusions: This systematic review suggests that sinus histiocytosis and paracortical hyperplasia in regional tumour-negative lymph nodes may provide additional prognostic information for gastric and oesophageal cancer patients. Further studies are needed to better understand the lymph node reaction patterns and explore their impact of chemotherapy treatment and immunotherapy efficacy. [ABSTRACT FROM AUTHOR]

BackgroundDespite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology.MethodsTo test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF μPET/μCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry.ResultsResults showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold.ConclusionThese findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

Additive manufacturing has emerged as a transformative tool in biomedical engineering, offering precise control over scaffold design for bone tissue engineering and regenerative medicine. While much attention has been focused on optimizing pore-based scaffold architectures, filament-based microarchitectures remain relatively understudied, despite the fact that the majority of 3D-printers generate filament-based structures. Here, we investigated the influence of filament characteristics on bone regeneration outcomes using a lithography-based additive manufacturing approach. Three distinct filament-based scaffolds (Fil050, Fil083, and Fil125) identical in macroporosity and transparency, crafted from tri-calcium phosphate (TCP) with varying filament thicknesses and distance, were evaluated in a rabbit model of bone augmentation and non-critical calvarial defect. Additionally, two scaffold types differing in filament directionality (Fil and FilG) were compared to elucidate optimal design parameters. Distance of bone ingrowth and percentage of regenerated area within scaffolds were measured by histomorphometric analysis. Our findings reveal filaments of 0.50 mm as the most effective filament-based scaffold, demonstrating superior bone ingrowth and bony regenerated area compared to larger size filament (i.e., 0.83 mm and 1.25 mm scaffolds). Optimized directionality of filaments can overcome the reduced performance of larger filaments. This study advances our understanding of microarchitecture’s role in bone tissue engineering and holds significant implications for clinical practice, paving the way for the development of highly tailored, patient-specific bone substitutes with enhanced efficacy.

Relative Energy Deficiency in Sport (REDs) is a syndrome describing the relationship between prolonged and/or severe low energy availability and negative health and performance outcomes. The high energy expenditures incurred during training and competition put endurance athletes at risk of REDs. The objective of this study was to investigate differences in bone quality in winter endurance athletes classified as either low-risk versus at-risk for REDs. Forty-four participants were recruited (M = 18; F = 26). Bone quality was assessed at the distal radius and tibia using high resolution peripheral quantitative computed tomography (HR-pQCT), and at the hip and spine using dual X-ray absorptiometry (DXA). Finite element analysis was used to estimate bone strength. Participants were grouped using modified criteria from the REDs Clinical Assessment Tool Version 1. Fourteen participants (M = 3; F = 11), were classified as at-risk of REDs (≥ 3 risk factors). Measured with HR-pQCT, cortical bone area (radius) and bone strength (radius and tibia) were 6.8%, 13.1% and 10.3% lower (p = 0.025, p = 0.033, p = 0.027) respectively, in at-risk compared with low-risk participants. Using DXA, femoral neck areal bone density was 9.4% lower in at-risk compared with low-risk participants (p = 0.005). At-risk male participants had 21.9% lower femoral neck areal bone density (via DXA) than low-risk males (p = 0.020) with no significant differences in females. Overall, 33.3% of athletes were at-risk for REDs and had lower bone quality than those at low-risk. [ABSTRACT FROM AUTHOR]

Purpose of Review: Rigid image registration is an important image processing tool for the assessment of musculoskeletal chronic disease. In this paper, we critically review applications of rigid image registration in terms of similarity measurement methods over the past three years (2019–2022) in the context of monitoring longitudinal changes to bone microstructure and mechanical properties using computed tomography. This review identifies critical assumptions and trade-offs underlying different similarity measurement methods used in image registration and demonstrates the effect of using different similarity measures on registration outcomes. Recent Findings: Image registration has been used in recent studies for: correcting positional shifts between longitudinal scans to quantify changes to bone microstructural and mechanical properties over time, developing registration-based workflows for longitudinal assessment of bone properties in pre-clinical and clinical studies, and developing and validating registration techniques for longitudinal studies. Summary: In evaluating the recent literature, it was found that the assumptions at the root of different similarity measures used in rigid image registration are not always confirmed and reported. Each similarity measurement has its advantages and disadvantages, as well as underlying assumptions. Breaking these assumptions can lead to poor and inaccurate registration results. Thus, care must be taken with regards to the choice of similarity measurement and interpretation of results. We propose that understanding and verifying the assumptions of similarity measurements will enable more accurate and efficient quantitative assessments of structural changes over time. [ABSTRACT FROM AUTHOR]

Background: Cone-beam computed tomography (CBCT) systems are frequently used to image bones for research purposes to investigate trabecular and cortical changes in bone disorders. A unique technique that may be used for the early diagnosis of bone lesions is fractal dimension (FD) analysis and bone architecture analysis using CBCT scans. Aim: To assess and compare the changes in trabecular bone architecture in fibro-osseous lesions by bone image analysis and FD analysis in CBCT scans of fibro-osseous lesions. Materials and Methods: This retrospective analysis included the CBCT scans of 25 patients from archival records of the Department of Oral Medicine and Radiology. As per specific exclusion and inclusion criteria, the radiographs were chosen. To establish a noninvasive assessment of the bone structure, CBCT scans were subjected to bone architecture analysis and FD analysis using box-counting (with ImageJ software). Results and Conclusions: The FD values and bone parameter values on the affected and the normal side will be recorded and analyzed using SPSS version 22. There was a statistically significant difference in the FD values between the normal and abnormal sides in all fibro-osseous lesions. Five parameters in fibrous dysplasia showed a significant statistical difference in comparison to the normal and abnormal sides. It can be concluded that FD analysis provides a novel technique for the early detection of fibro-osseous lesions.

Over the course of recent years, microarchitectural side-channel attacks emerged as one of the most novel and thought-provoking attacks to exfiltrate information from computing hardware. These attacks leverage the unintended artefacts produced as side-effects to certain architectural design choices and proved difficult to be effectively mitigated without incurring significant performance penalties. In this work, we undertake a systematic mapping study of the academic literature related to the aforementioned attacks. We, in particular, pose four research questions and study 104 primary works to answer those questions. We inquire about the origins of artefacts leading up to exploitable settings of microarchitectural side-channel attacks; the effectiveness of the proposed countermeasures; and the lessons to be learned that would help build secure systems for the future. Furthermore, we propose a classification scheme that would also serve in the future for systematic mapping efforts in this scope.

The design of Networks-on-Chip (NoCs) components implies a wide range of techniques and methods to address the microarchitecture of the packet-forwarding components, where routers and switches are the most complex because they constitute the NoC’s backbone. Due to this complex design space, several works use approaches limiting architectural exploration, focusing only on achieving high-performance levels; therefore, they are inadequate for designing NoC components when particular functionalities are demanded, as in real applications with specific protocols and interfaces. This paper presents a design methodology based on a top-down approach with NoC-oriented abstraction levels to systematically generate a microarchitecture and its hardware description according to system requirements. The design flow transforms a high-level functional model into a microarchitecture model through a refinement process at each abstraction level. This structured approach involves integrating details on how the data is functionally managed within the component according to the system requirements and the processing granularity of each level, allowing testing alternatives in the early stages of the design when necessary. The models of each abstraction level can be described and simulated using the simulator OMNet++. Thus, the obtained microarchitecture model will be directly translated into a Hardware Description Language (HDL). The methodology is tested via the design of a NoC switch for a Software Defined Radio (SDR) system. Performance analysis and implementation results in a field-programmable gate array (FPGA) show that the proposed design is functional and comparable in both area and frequency to other similar state-of-the-art components, and it is also configurable to build star topologies of up to 16 nodes.

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix (ECM) deposition around the injury site. Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation. In this study, we used a decellularized nerve matrix scaffold (DNM-S) to prevent against the formation of painful neuroma after sciatic nerve transection in rats. Our results showed that the DNM-S effectively reduced abnormal deposition of ECM, guided the regeneration and orderly arrangement of axon, and decreased the density of regenerated axons. The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue, greatly reduced the invasion of α-smooth muscle actin-positive myofibroblasts into nerve stumps, effectively inhibited scar formation, which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals. These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

Abstract Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy. Arch Endocrinol Metab. 2022;66(5):756-64

As the value of Bitcoin increases, the difficulty level of mining keeps increasing. This is generally addressed with application-specific integrated circuits (ASIC), but block candidates are still created by the software. The overhead of block candidate generation is relatively growing because the hash computation is boosted by ASIC. Additionally, it is getting harder to find the target nonce; If it is not found for a block candidate, a new block candidate must be generated. A new candidate can be generated to reduce the overhead of block candidate generation by modifying the coinbase without selecting and verifying transactions again. To this end, we propose a hardware accelerator for generating Merkle trees efficiently. The hash computation for Merkle tree generation is conducted with ASIC to reduce the overhead of block candidate generation, and the tree with only the modified coinbase is rapidly regenerated by reusing the intermediate results of the previously generated tree. Our simulation results demonstrate that the execution time can be reduced by up to 98.92% and power consumption by up to 99.73% when the number of transactions in a tree is 2048. [ABSTRACT FROM AUTHOR]

Covert channels based on processor microarchitecture have become a major threat to modern processors by bypassing existing security detection to transmit or leak secrets. Based on the storage time of covert channels, this paper divides microarchitecture-based covert channels into two types: persistent covert channels and volatile covert channels. The principle of the attack, runtime characteristics, typical attacks and attack conditions of the two types of covert channels are introduced and the existing covert channels are evaluated by the existing metrics. Based on the analysis of the attack conditions, a new analysis method on how to find the potential covert channel in microprocessor resources is proposed, and the microprocessor resources that are not used by existing covert channels are analyzed. The analysis shows that, the front-end bus in the Intel processors meets the conditions for creating a new transient covert channel. Based on the working principle of microarchitecture-based covert channel, many strategies of protection and detection methods have been proposed, and they are classified according to the working principles. The working principle, existing strategies and application scope of each type are introduced in detail. Moreover, reasonable and feasible protection suggestions are proposed for potential microarchitecture-based covert channels that may exist in the future. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine the effect of an antibody to vascular endothelial growth factor (VEGF) on bone blood flow, bone strength, and bone mass in the young adult mouse.MethodsTen-week-old male BALB/cJ mice were body weight-randomized into either a rodent anti-VEGF monoclonal antibody (anti-VEGF, B20-4.1.1; 5 mg/kg 2×/wk.; n = 12) group or a vehicle (VEH; n = 12) group. After 42 days, mice were evaluated for bone blood flow at the distal femur by 18F-NaF-PET/CT and then necropsied. Samples from trabecular and cortical bone regions were evaluated for bone strength by mechanical testing, bone mass by peripheral quantitative computed tomography (pQCT), and micoarchitecture (MicroCT). Hydration of the whole femur was studied by proton nuclear magnetic resonance relaxometry (1H NMR).ResultsDistal femur blood flow was 43% lower in anti-VEGF mice than in VEH mice (p = 0.009). Ultimate load in the lumbar vertebral body was 25% lower in anti-VEGF than in VEH mice (p = 0.013). Bone mineral density (BMD) in the trabecular region of the proximal humeral metaphysis by pQCT, and bone volume fraction and volumetric BMD by MicroCT were the same in the two groups. Volume fraction of bound water (BW) of the whole femur was 14% lower in anti-VEGF than in VEH mice (p = 0.003). Finally, BW, but not cortical tissue mineral density, helped section modulus explain the variance in the ultimate moment experienced by the femur in three-point bending.ConclusionAnti-VEGF caused low bone blood flow and bone strength in trabecular bone regions without influencing BMD and microarchitecture. Low bone strength was also associated with low bone hydration. These data suggest that bone blood flow is a novel bone property that affects bone quality.

ABSTRACT: The effect of milk on bone health is controversial. In this study, the effects of yak milk in mice with retinoic acid-induced osteoporosis (OP) were evaluated. Yak milk was provided to OP mice as a nutrition supplement for 6 wk. The results showed that yak milk significantly reduced bone turnover markers (tartrate acid phosphatase and alkaline phosphatase). The yak milk treatment was also associated with remarkably increased bone mineral density, bone volume, trabecular thickness, and trabecular number, as well as improved biomechanical properties (maximum load and stress) of the tibia. Furthermore, yak milk mitigated the deterioration of the network and thickness of trabecular bone in treated OP mice compared with the OP model group. The results indicated that yak milk could improve bone mass and microarchitecture through the inhibition of bone resorption in OP mice.

Abstract Background It is well known that skeletal integrity is influenced by the musculature. Poor muscle strength (i.e. sarcopenia) is considered a major predictor of fragility fractures. While this observation appears particularly relevant for older women with increased risk of osteoporosis, there has been no comprehensive investigation to determine the influence of muscle performance on compartment‐specific bone microarchitecture in multiple body regions. Methods We retrospectively analysed data from different muscle performance and bone microarchitecture assessments in 230 women (aged 21 to 87 years) at high risk of osteoporosis. Muscle performance tests included grip strength and chair rising test (CRT) combined with mechanography. Balance was determined by Romberg posturography. Areal bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry (DXA) at the hip and lumbar spine. Compartment‐specific volumetric BMD, microarchitecture, and geometry were assessed by second‐generation high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at multiple skeletal sites (distal radius, tibia, and fibula). Regression models were applied to test for interactions between muscle and bone parameters. Subgroups were defined to compare women with osteoporosis and osteosarcopenia regarding BMD and microarchitecture. Results While osteoporosis was diagnosed in 115/230 (50.0%) women, sarcopenia was detected in 38/230 (16.5%). Positive associations of both grip strength and CRT maximum force with cortical geometric and microarchitectural parameters were detected at all measured sites, with the strongest effect applying to CRT maximum force and tibial parameters (e.g. tibial cortical area R2 = 0.36, P

The growing variety of computing systems, the rapid increase in their complexity, their integration into objects and processes of the physical world require a dramatic increase in the productivity of their creators. It is noted that the quality, timing, and degree of reuse of design results in the field of information technologies strongly depend on design methodologies and routes at the stages of choosing and/or creating stacks of platforms, technologies and tools. The most important role belongs to the ways of describing the organization of the computing system at various levels and to the used systems of abstractions. The problem of filling the semantic gap between the conceptual (architectural) level and the implementation levels is still very acute. So, it requires the creation of industrial techniques and design tools at these “intermediate” levels. The paper suggests ways of presenting design solutions that are aimed at a holistic, end-to-end description of both the logic of the computing process organization and the steps, technologies, and tools of the design process. The content and the necessity of the stages of microarchitectural design of computing systems is justified and explained in detail. Classification of projects in the field of information technologies according to the degree of variability of the project platform is introduced. Several concepts representing a set of abstractions for microarchitectural design within projects with great variability are suggested. The following abstractions are described in detail: project, design and aspect spaces, project platforms and cross-level mechanisms. Examples of several proposed abstractions presentations (design documentation tools) of microarchitectural design stages are discussed that are most relevant in the design of computing systems in the “limited resources” model: embedded systems, cyber-physical systems, “edge” and “fog” levels of Internet of Things systems.

The early phase of bone healing is a complex and poorly understood process. With additive manufacturing, we can generate a specific and customizable library of bone substitutes to explore this phase. In this study, we produced tricalcium phosphate-based scaffolds with microarchitectures composed of filaments of 0.50 mm in diameter, named Fil050G, and 1.25 mm named Fil125G, respectively. The implants were removed after only 10 days in vivo followed by RNA sequencing (RNAseq) and histological analysis. RNAseq results revealed upregulation of adaptive immune response, regulation of cell adhesion, and cell migration-related genes in both of our two constructs. However, significant overexpression of genes linked to angiogenesis, regulation of cell differentiation, ossification, and bone development was observed solely in Fil050G scaffolds. Moreover, quantitative immunohistochemistry of structures positive for laminin revealed a significantly higher number of blood vessels in Fil050G samples. Furthermore, µCT detected a higher amount of mineralized tissue in Fil050G samples suggesting a superior osteoconductive potential. Hence, different filament diameters and distances in bone substitutes significantly influence angiogenesis and regulation of cell differentiation involved in the early phase of bone regeneration, which precedes osteoconductivity and bony bridging seen in later phases and as consequence, impacts the overall clinical outcome. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the associations between the cortical bone‐to‐implant contact (CBIC), bone microstructure derived from cone‐beam computed tomography (CBCT), and the primary stability of the implant. Materials and Methods: Twenty‐two patients with 65 implants were enrolled in this study. The peak insertion torque values (ITVs) were measured during implant insertion, and the implant stability quotient (ISQ) values were measured immediately after implant placement and 3 months after surgery. The profiles of the peri‐implant bone structure were outlined using the volumetric reconstruction of the CBCTs and superimposition of the virtual models, and the features of CBIC and bone microstructure parameters were measured. The linear mixed effects model and generalized estimating equation were used to explore the predictors for implant primary stability. Results: The average ITV, baseline, and secondary ISQ values were 31.44 ± 6.54 N·cm, 73.34 ± 7.39, and 80.32 ± 4.58, respectively. Statistically significant correlations were found between ITV and surface area of CBIC (r =.340, p =.006), bone volume fraction (r =.294, p =.017), and bone surface fraction (r = −.278, p =.039). Implants with buccolingual CBIC had a higher ITV than implants without CBIC (p =.016). None of the parameters were associated with baseline and secondary ISQ values in generalized estimating equation analysis (all p >.05). Conclusions: Within the limitations of the study, preoperative CBCT measurements might enable the prediction of ITV and therefore of implant primary stability values. [ABSTRACT FROM AUTHOR]

U.S. Army Basic Combat Training (BCT) improves tibial volumetric bone mineral density (BMD) and structure in most, but not all soldiers. Few studies have investigated whether changes in serum bone biomarkers during BCT are associated with changes in tibial BMD and bone structure following BCT. To characterize bone biomarker changes during BCT and to investigate the relationship between changes in bone biomarkers and changes in tibial BMD and bone structure. We enrolled 235 trainees entering BCT in this ten-week prospective observational study. Trainees provided fasted blood samples and questionnaires weekly throughout BCT. Procollagen type 1 N-terminal propeptide (PINP) and C-terminal telopeptide of type 1 collagen (CTX) were measured by enzyme-linked immunoabsorbent assays every two weeks during BCT. We evaluated body composition and mass via dual-energy X-ray absorptiometry and bone structure, microarchitecture, and mineral density at the distal tibia via high-resolution peripheral quantitative computed tomography at baseline and post-BCT. Both male (n = 110) and female trainees (n = 125) were young (20.9 ± 3.7 and 20.7 ± 4.3 years, respectively), with normal to overweight BMIs (25.2 ± 4.1 and 24.2 ± 3.6 kg/m2, respectively). In female trainees, PINP increased during and post-BCT compared to baseline, with the greatest increase in PINP at week four (45.4 % ± 49.6, p < 0.0001), whereas there were no changes in CTX. PINP also increased in male trainees, but only at weeks two and four (21.9 % ± 24.5, p = 0.0027 and 35.9 % ± 35.8, p < 0.0001, respectively). Unlike female trainees, in males, CTX was lower than baseline at weeks four, eight, and post-BCT. The change in PINP from baseline to week four of BCT was positively associated with changes in tibial BMD, Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po from the baseline to post-BCT. The bone formation marker PINP increases during U.S. Army BCT, especially during the first four weeks. Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia. • U.S. Army Basic Combat Training (BCT) improves tibial vBMD and structure in most, but not all soldiers. • In females, PINP increased during and post-BCT compared to baseline: with the greatest increase in PINP at week 4, no changes in CTX. • Unlike female trainees, in males, CTX was lower than baseline at weeks 4, 8, and post-BCT. • The change in PINP from baseline to week 4was associated with changes in Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po. • Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia. [ABSTRACT FROM AUTHOR]

GPU architectures have become popular for executing general-purpose programs. In particular, they are some of the most efficient architectures for machine learning applications which are among the most trendy and demanding applications nowadays. This paper presents SIMIL (SIMple Issue Logic for GPUs), an architectural modification to the issue stage that replaces scoreboards with a Dependence Matrix to track dependencies among instructions and avoid data hazards. We show that a Dependence Matrix is more effective in the presence of repetitive use of source operands, which is common in many applications. Besides, a Dependence Matrix with minor extensions can also support a simplistic out-of-order issue. Evaluations on an NVIDIA Tesla V100-like GPU show that SIMIL provides a speed-up of up to 2.39 in some machine learning programs and 1.31 on average for various benchmarks, while it reduces energy consumption by 12.81%, with only 1.5% area overhead. We also show that SIMIL outperforms a recently proposed approach for out-of-order issue that uses register renaming. [ABSTRACT FROM AUTHOR]

Currently, a variety of laboratory tools and strategies have been developed to investigate in vivo processes using in vitro models. Amongst these, microfabrication represents a disruptive technology that is currently enabling next-generation biomedical research through the development of complex laboratory approaches (e.g., microfluidics), engineering of micrometer scale sensors and actuators (micropillars for traction force microscopy), and the creation of environments mimicking cell, tissue, and organ-specific contexts. Although microfabrication has been around for some time, its application in dental and oral research is still incipient. Nevertheless, in recent years multiple lines of research have emerged that use microfabrication-based approaches for the study of oral diseases and conditions with micro- and nano-scale sensitivities. Furthermore, many investigations are aiming to develop clinically relevant microfabrication-based applications for diagnostics, screening, and oral biomaterial manufacturing. Therefore, the objective of this review is to summarize the current application of microfabrication techniques in oral sciences, both in research and clinics, and to discuss possible future applications of these technologies for in vitro studies and practical patient care. Initially, this review provides an overview of the most employed microfabrication methods utilized in biomedicine and dentistry. Subsequently, the use of micro- and nano-fabrication approaches in relevant fields of dental research such as endodontic and periodontal regeneration, biomaterials research, dental implantology, oral pathology, and biofilms was discussed. Finally, the current and future uses of microfabrication technology for clinical dentistry and how these approaches may soon be widely available in clinics for the diagnosis, prevention, and treatment of relevant pathologies are presented.

It remains uncertain which skeletal sites and parameters should be analyzed in rodent studies evaluating bone health and disease. In this cross-sectional mouse study using micro-computed tomography (µCT), we explored: (1) which microstructural parameters can be used to discriminate female from male bones and (2) whether it is meaningful to evaluate more than one bone site. Microstructural parameters of the trabecular and/or cortical compartments of the femur, tibia, thoracic and lumbar vertebral bodies, and skull were evaluated by µCT in 10 female and 10 male six-month-old C57BL/6J mice. The trabecular number (TbN) was significantly higher, while the trabecular separation (TbSp) was significantly lower in male compared to female mice at all skeletal sites assessed. Overall, bone volume/tissue volume (BV/TV) was also significantly higher in male vs. female mice (except for the thoracic spine, which did not differ by sex). Most parameters of the cortical bone microstructure did not differ between male and female mice. BV/TV, TbN, and TbSp at the femur, and TbN and TbSp at the tibia and lumbar spine could fully (100%) discriminate female from male bones. Cortical thickness (CtTh) at the femur was the best parameter to detect sex differences in the cortical compartment (AUC = 0.914). In 6-month-old C57BL/6J mice, BV/TV, TbN, and TbSp can be used to distinguish male from female bones. Whenever it is not possible to assess multiple bone sites, we propose to evaluate the bone microstructure of the femur for detecting potential sex differences. [ABSTRACT FROM AUTHOR]