Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of Registration for Renal Dynamic Contrast Enhanced MRI Imaging

In Dynamic Contrast Enhanced Resonance Imaging (DCE-MRI), abdomen is scanned repeatedly and rapidly after injection of a contrast agent. During data acquisition, collected images suffer from the motion induced by the patient if he/she moves or breathes heavily during the scan. Therefore, these images should be aligned accurately to correct the motion. Recently, mutual information (MI) registration has become the first tool to register renal DCE-MRI images before any further processing. However, MI registration is sensitive to initial conditions and optimization methods, and it is bound to fail under certain conditions such as extreme movement or noise in the image. Therefore, if automated image analysis for renal DCE-MRI is to enter the clinical settings, it is necessary to have validation strategies that show the limitations of registration models on known datasets. In this study, two methods are introduced for the validation of registration of renal DCE-MRI images. The first method demonstrates how to use the inverse transform to generate realistic looking DCE-MRI kidney images and use them in validation. The second method shows how to generate checkerboard images and how to evaluate the goodness of registration for real DCE-MRI images. These validation methods can be incorporated into the registration studies to quantitatively and qualitatively demonstrate the success and the limitations of registration models.
Latest Advances in Understanding Preeclampsia

Preeclampsia is a relatively common pregnancy disorder that originates in the placenta and causes variable maternal and fetal problems. In the worst cases, it may threaten the survival of both mother and baby. We summarize recent work on the causes of preeclampsia, which reveals a new mode of maternal immune recognition of the fetus, relevant to the condition. The circulating factors derived from the placenta, which contributes to the clinical syndrome, are now better understood. This brief review on preeclampsia does not cover all aspects of this intriguing condition but focuses on some new and interesting findings.
Valuation Model Based on More Adequately Used Accounting Information——The Establishment and Application of RIR Model

Little accounting data is used in current valuation models on enterprise value, which results in omitting much crucial accounting information. To use existing accounting material adequately, the paper conducts a methamatic deduction on Residual Income Ration model (RIR)based on the DuPond System and Residual Income Valuation (RIV) theory: initially, trying to reveal the quantitative relationship between crucial financial data in existing financial statements and intrinsic value. The core content and innovation of RIR is, (1) to follow the value creation and use Ohlson model, accordance with the valuation thought of value creating angle; (2) to utilize the existing financial data; (3) to make use of more fundamental and reliable data.
The Complex Exocrine–Endocrine Relationship and Secondary Diabetes in Exocrine Pancreatic Disorders

The pancreas is a dual organ with exocrine and endocrine functions. The interrelationship of the endocrine-exocrine parts of the pancreas is a complex one, but recent clinical and experimental studies have expanded our knowledge. Many disorders primarily of the exocrine pancreas, often solely in the clinical realm of gastroenterologists are associated with diabetes mellitus (DM). Although, the DM becoming disorders are often grouped with type 2 diabetes, the pathogenesis, clinical manifestations and management differ. We review here data on the association of exocrine-endocrine pancreas, the many hormones of the pancreas and their possible effects on the exocrine functions followed by data on the epidemiology, pathogenesis, and management of DM in chronic pancreatitis, cystic fibrosis, pancreatic cancer, and clinical states after pancreatic surgery.
A Bifunctional Bacterial Protein Links GDI Displacement to Rab1 Activation

Rab guanosine triphosphatases (GTPases) regulate vesicle trafficking in eukaryotic cells by reversibly associating with lipid membranes. Inactive Rab GTPases are maintained in the cytosol by binding to GDP-dissociation inhibitor (GDI). It is believed that specialized proteins are required to displace GDI from Rab GTPases before Rab activation by guanosine diphosphate–guanosine 5′-triphosphate (GDP-GTP) exchange factors (GEFs). Here, we found that SidM from Legionella pneumophila could act as both GEF and GDI-displacement factor (GDF) for Rab1. Rab1 released from GDI was inserted into liposomal membranes and was used as a substrate for SidM-mediated nucleotide exchange. During host cell infection, recruitment of Rab1 to Legionella-containing vacuoles depended on the GDF activity of SidM. Thus, GDF and GEF activity can be promoted by a single protein, and GDF activity can coordinate Rab1 recruitment from the GDI-bound pool.
Preparation and in vivo safety evaluations of antileukemic homoharringtonine-loaded PEGylated liposomes

Abstract In order to improve the in vivo safety and specific delivery efficiency of the antileukemic homoharringtonine (HHT) at the targets, the long-circulating PEGylated liposomes loaded with HHT (LCLipo-HHT) were prepared. Their physical characteristics, in vitro drug release, in vivo pharmacokinetic properties and elementary toxicity were evaluated. The mean diameter of the prepared LCLipo-HHT is 75.6 ± 3.2 nm and the zeta potential is −16.9 ± 2.5 mV. The entrapment efficiency of HHT in the liposomes is 69.5 ± 1.7%. In pharmacokinetic experiments, an increased plasma concentration as well as blood circulation time was obtained when distearoyl phosphoethanolamine-PEG 2000 lipid was added in the formulation, which results in enhancing drug delivery efficiency. Hemolysis test, vascular irritation test and acute toxicity test were used to demonstrate toxicity of LCLipo-HHT. Compared with clinical HHT injection dosage, LCLipo-HHT indicated no vascular irritation, good hemocompatibility, as well as much better safety. Therefore, the prepared LCLipo-HHT can be used as a promising anticancer formulation for antileukemic therapy in the future.
Bisimilarity Control of Partially Observed Deterministic Systems

Control for safety and nonblockingness using a deterministic supervisor requires the specification language be controllable and observable (under the setting that marking is also decided by a supervisor). We argue that there exist cases where the above properties do not hold, yet a safe and nonblocking control can be synthesized by allowing the supervisor to be nondeterministic. Use of a nondeterministic supervisor yields a controlled system that is nondeterministic for which a language equivalence only preserve the safety but not the nonblocking property, and so instead we require the stronger equivalence of bisimilarity (which preserves "sequential" behavior such as safety as well as "branching" behavior such as nonblockingness). This motivates us to consider control of deterministic systems for achieving bisimulation equivalence to possibly nondeterministic specifications. We introduce the notions of state-achievability (SA) and state-achievability-bisimilar (SAB) as part of the existence condition, and develop effective algorithms for verify the existence conditions as well as for synthesizing a supervisor when the existence condition holds. We show that the complexity of verifying the existence of a controller is polynomial, whereas that of computing a controller (when one exists) is singly exponential. The proposed approach can be applied to enforce any property that depends on branching and sequential behavior.
Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats

Objectives The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). Methods Sitagliptin (40 mg/kg twice daily) was given by oral gavage to young (Y-SHR + IDPPIV) and adult (A-SHR + IDPPIV) SHRs for 8 days. Kidney function was assessed daily and compared with age-matched vehicle-treated SHR (Y-SHR and A-SHR) and with normotensive Wistar–Kyoto rats (Y-WKY and A-WKY). Arterial blood pressure was measured in these animals at the end of the experimental protocol. Additionally, Na+/H+ exchanger isoform 3 (NHE3) function and expression in microvilli membrane vesicles were assessed in young animals. Results Mean arterial blood pressure of Y-SHR + IDPPIV was significantly lower than that of Y-SHR (104 ± 3 vs. 123 ± 5 mmHg, P < 0.01) and was similar to Y-WKY (94 ± 4 mmHg, P > 0.05). Compared to Y-SHR, Y-SHR + IDPPIV exhibited enhanced cumulative urinary flow and sodium excretion and decreased NHE3 activity and expression in proximal tubule microvilli. In the A-SHR, sitagliptin treatment had no significant effect on either renal function or arterial blood pressure. Conclusion Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule.
The reformulation of emotional security theory: The role of children's social defense in developmental psychopathology

Abstract Although children's security in the context of the interparental relationship has been identified as a key explanatory mechanism in pathways between family discord and child psychopathology, little is known about the inner workings of emotional security as a goal system. Thus, the objective of this paper is to describe how our reformulation of emotional security theory within an ethological and evolutionary framework may advance the characterization of the architecture and operation of emotional security and, in the process, cultivate sustainable growing points in developmental psychopathology. The first section of the paper describes how children's security in the interparental relationship is organized around a distinctive behavioral system designed to defend against interpersonal threat. Building on this evolutionary foundation for emotional security, the paper offers an innovative taxonomy for identifying qualitatively different ways children try to preserve their security and its innovative implications for more precisely informing understanding of the mechanisms in pathways between family and developmental precursors and children's trajectories of mental health. In the final section, the paper highlights the potential of the reformulation of emotional security theory to stimulate new generations of research on understanding how children defend against social threats in ecologies beyond the interparental dyad, including both familial and extrafamilial settings.
TonB and the Gram‐negative dilemma

TonB protein serves as an energy transducer to couple cytoplasmic membrane energy to high‐affinity active transport of iron siderophores and vitamin B12 across the outer membranes of Gram‐negative bacteria. The biochemical mechanism of the energy transduction remains to be determined, but important details are already known. TonB is targeted to and anchored in the cytoplasmic membrane by a single membrane‐spanning domain and spans the periplasm to physically interact with outer‐membrane receptors of the transport ligands. TonB‐dependent energy transduction is modulated by ExbB protein, which stabilizes TonB, and possibly by several other proteins including ExbC, ExbD, and TolQ. TonB has a relatively short functional half‐life that is accelerated when rates of active transport across the outer membrane are increased. A model that incorporates this information, as well as some tempered speculation, is presented.
Genomic profiling and identification of high-risk uveal melanoma by array CGH analysis of primary tumors and liver metastases.

PURPOSE Incurable metastases develop in approximately 50% of patients with uveal melanoma (UM). The purpose of this study was to analyze genomic profiles in a large series of ocular tumors and liver metastases and design a genome-based classifier for metastatic risk assessment. METHODS A series of 86 UM tumors and 66 liver metastases were analyzed by using a BAC CGH (comparative genomic hybridization) microarray. A clustering was performed, and correlation with the metastatic status was sought among a subset of 71 patients with a minimum follow-up of 24 months. The status of chromosome 3 was further examined in the tumors, and metastases with disomy 3 were checked with an SNP microarray. A prognostic classifier was constructed using a log-linear model on minimal regions and leave-one-out cross-validation. RESULTS The clustering divides the groups of tumors with disomy 3 and monosomy 3 into two and three subgroups, respectively. Same subgroups are found in primary tumors and in metastases, but with different frequencies. Isolated monosomy 3 was present in 0% of metastatic ocular tumors and in 3% of metastases. The highest metastatic rate in ocular tumors was observed in a subgroup defined by the gain of 8q with a proximal breakpoint, and losses of 3, 8p, and 16q, also most represented in metastases. A prognostic classifier that included the status of these markers led to an 85.9% classification accuracy. CONCLUSIONS The analysis of the status of these specific chromosome regions by genome profiling on SNP microarrays should be a reliable tool for identifying high-risk patients in future adjuvant therapy protocols.
Backing-Up Maneuvers of Autonomous Tractor-Trailer Vehicles using the Qualitative Theory of Nonlinear Dynamical Systems

This paper presents an approach, based on the qualitative theory of nonlinear dynamical systems, for the analysis and design of control systems for autonomous articulated vehicles. In particular, backing-up maneuvers are considered. These maneuvers are dangerous because the vehicles tend to `jackknife' when the angle between the tractor and the trailer is greater than a certain value. This danger is increased when the actuators are saturated because they can cause a lack of controllability in the state space and control becomes complicated. The paper proposes a two-level control system with an orientation controller in the lower level and a look-ahead controller in the higher. In the paper, a general orientation feedback controller is presented. This control strategy represents a wide family of different nonlinear controllers and can be applied with different particular control laws. The paper applies the qualitative theory of nonlinear dynamical systems to study the stability of the control system. Thus, the stability of the system under some constraints is demonstrated. The paper includes both simulation and experimental results of the implementation on the Romeo 4R autonomous vehicle, which is a full-size autonomous electrical golf cart with a trailer.
Sequoia: A High-Endurance NVM-Based Cache Architecture

Emerging nonvolatile memory technologies, such as spin-transfer torque RAM or resistive RAM, can increase the capacity of the last-level cache (LLC) in a latency and power-efficient manner. These technologies endure 109-1012 writes per cell, making a nonvolatile cache (NV-cache) with a lifetime of dozens of years under ideal working conditions. However, nonuniformity in writes to different cache lines considerably reduces the NV-cache lifetime to a few months. Writes to cache lines can be made uniformly by wear-leveling. A suitable wear-leveling for NV-cache should not incur high storage and performance overheads. We propose a novel, simple, and effective wear-leveling technique with negligible performance overhead of <;0.4% for memory-intensive workloads. Our proposal consists of two mechanisms: 1) a wear-leveling mechanism within each cache set that slightly increases main memory write-back traffic and LLC miss rate and 2) a novel technique to reduce cache interset variation which causes minimum interference with normal cache operation. Using these mechanisms, we show that the lifetime of the NV-cache is boosted up to 13× for different cache configurations.
A Novel Combined Mother-Infant Clinic to Optimize Post-Partum Maternal Retention, Service Utilization, and Linkage to Services in HIV Care in Rural Rwanda

Background and Objectives: Despite recent improvements in accessibility of services to prevent mother-to-child transmission of HIV, maternal retention in HIV care remains a challenge in the post-partum period. This study assessed service utilization, program retention, and linkage to routine services, as well as clinical outcomes for mothers and infants, following implementation of an integrated mother-infant clinic in rural Rwanda. Methods: We conducted a retrospective cohort study of all HIV-positive mothers and their infants enrolled in the integrated clinics in two rural districts between July 1, 2012, and June 30, 2013. At 18 months post-partum, data on mother-infant service utilization and program outcomes were reported. Results: Of the 185 mother-infant pairs in the clinics, 98.4% of mothers were on antiretroviral therapy (ART) and 30.3% used modern contraception at enrollment. At 18 months post-partum, 98.4% of mothers were retained and linked back to adult HIV program. All mothers were on ART and 72.0% on modern contraception. For infants, 93.0% completed follow-up. Two (1.1%) infants tested HIV positive. Conclusion and Global Health Implication: An integrated clinic was successfully implemented in rural Rwanda with high mother retention in care and low mother to child HIV transmission rates. This model of integration of services may contribute to improved mother-infant retention in care during post-partum period and should be considered as one approach to addressing this challenge in similar settings.
Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation

Defects in WDR72 (WD repeat‐containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72‐knockout/lacZ‐knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild‐type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The null enamel layer was only a tenth as hard as wild‐type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin‐associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle‐ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 null mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.
Local recovery of Ca2+ release in rat ventricular myocytes

Excitation–contraction coupling in the heart depends on the positive feedback process of Ca2+‐induced Ca2+ release (CICR). While CICR provides for robust triggering of Ca2+ sparks, the mechanisms underlying their termination remain unknown. At present, it is unclear how a cluster of Ca2+ release channels (ryanodine receptors or RyRs) can be made to turn off when their activity is sustained by the Ca2+ release itself. We use a novel experimental approach to investigate indirectly this issue by exploring restitution of Ca2+ sparks. We exploit the fact that ryanodine can bind, nearly irreversibly, to an RyR subunit (monomer) and increase the open probability of the homotetrameric channel. By applying low concentrations of ryanodine to rat ventricular myocytes, we observe repeated activations of individual Ca2+ spark sites. Examination of these repetitive Ca2+ sparks reveals that spark amplitude recovers with a time constant of 91 ms whereas the sigmoidal recovery of triggering probability lags behind amplitude recovery by ∼80 ms. We conclude that restitution of Ca2+ sparks depends on local refilling of SR stores after depletion and may also depend on another time‐dependent process such as recovery from inactivation or a slow conformational change after rebinding of Ca2+ to SR regulatory proteins.
Profiling gene expression responses of coral larvae (Acropora millepora) to elevated temperature and settlement inducers using a novel RNA‐Seq procedure

Elevated temperatures resulting from climate change pose a clear threat to reef‐building corals; however, the traits that might influence corals’ survival and dispersal during climate change remain poorly understood. Global gene expression profiling is a powerful hypothesis‐forming tool that can help elucidate these traits. Here, we applied a novel RNA‐Seq protocol to study molecular responses to heat and settlement inducers in aposymbiotic larvae of the reef‐building coral Acropora millepora. This analysis of a single full‐sibling family revealed contrasting responses between short‐ (4‐h) and long‐term (5‐day) exposures to elevated temperatures. Heat shock proteins were up‐regulated only in the short‐term treatment, while the long‐term treatment induced the down‐regulation of ribosomal proteins and up‐regulation of genes associated with ion transport and metabolism (Ca2+ and CO32−). We also profiled responses to settlement cues using a natural cue (crustose coralline algae, CCA) and a synthetic neuropeptide (GLW‐amide). Both cues resulted in metamorphosis, accompanied by differential expression of genes with known developmental roles. Some genes were regulated only by the natural cue, which may correspond to the recruitment‐associated behaviour and morphology changes that precede metamorphosis under CCA treatment, but are bypassed under GLW‐amide treatment. Validation of these expression profiles using qPCR confirmed the quantitative accuracy of our RNA‐Seq approach. Importantly, qPCR analysis of different larval families revealed extensive variation in these responses depending on genetic background, including qualitative differences (i.e. up‐regulation in one family and down‐regulation in another). Future studies of gene expression in corals will have to address this genetic variation, which could have important adaptive consequences for corals during global climate change.