Miracle-dz/UniFAR-FTUs huggingface dataset:
Cramer-Rao bounds for target parameters in space-based radar applications

The Cramer-Rao (CR) bounds for target Doppler and power are presented when detecting targets using a space-based radar (SBR) platform. The target in noise-only case is considered first and the results are compared with those obtained for a centro-symmetric uniform linear pulse array. When clutter is also present, the effect of the Earth's rotation and range foldover becomes significant; and they must be taken into consideration. The CR bounds are computed for target Doppler and power, and compared with their variance estimates obtained from simulation results corresponding to various airborne and SBR situations. From the simulation results, the Earth's rotation together with range foldover significantly increase the CR bounds for both target Doppler and power. This is in agreement with other results that show the Earth's rotation and range foldover together degrade the clutter suppression performance of adaptive processing algorithms. It is shown that when both the Earth's rotation effect and range foldover effect are present in the data, target detection is difficult, and it is necessary to introduce waveform diversity into the transmit design to minimize the effect of clutter and other interference. In this context, using waveform diversity on transmit, it is possible to compensate the degradation in terms of the CR bounds and achieve performance close to the ideal case.
Diet and Sleep Physiology: Public Health and Clinical Implications

This mini-review examines the complex relationship between diet and sleep and explores the clinical and public health implications of the current evidence. Dietary quality and intake of specific nutrients can impact regulatory hormonal pathways to alter sleep quantity and quality. Sleep, in turn, affects the intake of total energy, as well as of specific foods and nutrients, through biological and behavioral mechanisms. Initial research in this field focused primarily on the effects of short sleep duration on nutritional quality. However, more recent studies have explored the dynamic relationship between long sleep duration and diet. Current evidence suggests that extremes of sleep duration alter sleep patterns, hormonal levels, and circadian rhythms, which contribute to weight-related outcomes and obesity, and other risk factors for the development of chronic disease such as type 2 diabetes and cardiovascular disease. These patterns may begin as early as childhood and have impacts throughout the life course. Given that non-communicable diseases are among the leading causes of death globally, deeper understanding of the interactions between sleep and nutrition has implications for both public health and clinical practice.
p38 Mitogen-Activated Protein Kinase-Dependent and -Independent Signaling of mRNA Stability of AU-Rich Element-Containing Transcripts

ABSTRACT Adenylate/uridylate-rich element (ARE)-mediated mRNA turnover is an important regulatory component of gene expression for innate and specific immunity, in the hematopoietic system, in cellular growth regulation, and for many other cellular processes. This diversity is reflected in the distribution of AREs in the human genome, which we have established as a database of more than 900 ARE-containing genes that may utilize AREs as a means of controlling cellular mRNA levels. The p38 mitogen-activated protein kinase (MAP kinase) pathway has been implicated in regulating the stability of nine ARE-containing transcripts. Here we explored the entire spectrum of ARE-containing genes for p38-dependent regulation of ARE-mediated mRNA turnover with a custom cDNA array containing probes for 950 ARE mRNAs. The human monocytic cell line THP-1 treated with lipopolysaccharide (LPS) was used as a reproducible cellular model system that allowed us to precisely control the conditions of mRNA induction and decay in the absence and presence of the p38 inhibitor SB203580. This approach allowed us to establish an LPS-induced ARE mRNA expression profile in human monocytes and determine the half-lives of 470 AU-rich mRNAs. Most importantly, we identified 42 AU-rich genes, previously unrecognized, that show p38-dependent mRNA stabilization. In addition to a number of cytokines, several interesting novel AU-rich transcripts likely to play a role in macrophage activation by LPS exhibited p38-dependent transcript stabilization, including macrophage-specific colony-stimulating factor 1, carbonic anhydrase 2, Bcl2, Bcl2-like 2, and nuclear factor erythroid 2-like 2. Finally, the identification of the p38-dependent upstream activator MAP kinase kinase 6 as a member of this group identifies a positive feedback loop regulating macrophage signaling via p38 MAP kinase-dependent transcript stabilization.
Analysis of the collagen VI assemblies associated with Sorsby's fundus dystrophy.

Age-related macular degeneration is the leading cause of blindness in the Western world, and the pathophysiology of the condition is largely unknown. However, it shares many clinical and pathological features with Sorsby's fundus dystrophy (SFD), an autosomal dominant disease, known to be associated with mutations in the TIMP-3 gene. In Bruch's membrane of both conditions, there are molecular assemblies with distinct transverse bands occurring with a periodicity of about 100 nm. Similar assemblies were also found in the vitreous of a patient with full-thickness macular holes and were identified as being made of collagen VI. The assemblies found in the eye with SFD can be classified into two types, both with a 105-nm axial repeat, but one showing pairs of narrow bands about 30 nm apart and the other showing a single broad band in every repeat. By comparison with the assemblies in the vitreous, collagen VI is considered to be the most likely protein in these assemblies. Furthermore, both of the assemblies associated with SFD can be explained in terms of collagen VI tetramers, one in which the tetramers bind to the mutant tissue inhibitor of metalloproteinases-3 (the gene product of TIMP-3) and the other in which little or no binding occurs. TIMP-3 bound to collagen VI may be more resistant to degradation and create an imbalance between the normal amount of TIMP-3 and matrix metalloproteinases (the substrate of TIMPs) in Bruch's membrane with consequent disruption of the normal metabolic processes. Understanding the structure of these collagen VI/TIMP assemblies in Bruch's membrane may prove to be important for understanding the pathophysiology of age-related macular degeneration.
Unobtrusive monitoring of learners' interactions with educational games for measuring their working memory capacity

Working memory capacity (WMC) plays an important role in the learning process, because learners need to hold and process some information in the short-term memory while they are engaged in learning activities. Measuring learners' WMC can be helpful to support and enhance their learning. For example, teachers can use this information to adapt their teaching strategies according to learners' level of WMC. In addition, information about learner's WMC can be exploited by adaptive e-learning systems for providing recommendations to support learners with low and high WMC. Furthermore, early detection of the level of individual learner's WMC is a very important step to be able to provide appropriate intervention for the learners. In this context, a number of tools are available in the literature to explicitly measure learner's WMC. However, most of them require considerable experience in the administration and interpretation of results. This study proposes an approach based on fuzzy logic for measuring learner's WMC in an unobtrusive manner, from learner's interactions with an educational game. Results of experiments proved the effectiveness of this method in measuring WMC. The educational game, used in this work, could help parents and teachers to know the WMC of their kids and learners. In addition, the proposed approach could be adapted by researchers working in this field to measure learners' WMC using other educational games. [ABSTRACT FROM AUTHOR]
Canonical NF-κB signaling is uniquely required for the long-term persistence of functional mature B cells

Significance Mature B cells are long-lived cells responsible for the Ab production in the immune system. Canonical NF-κB signaling, one of the two discrete pathways activating transcription factors of the NF-κB family, participates in the generation of a normal mature B-cell compartment. However, the role of these signals specifically in mature B cells is still imperfectly defined. Notably, their role in the persistence of follicular B cells, the main mature B-cell subset, is controversial. Here, we show that canonical NF-κB signaling does not contribute to immediate (short-term) survival of follicular B cells, contrasting with the crucial tonic B-cell antigen receptor survival signals, but is required for their long-term persistence as well as functional fitness. Although canonical NF-κB signaling is crucial to generate a normal mature B-cell compartment, its role in the persistence of resting mature B cells is controversial. To resolve this conflict, we ablated NF-κB essential modulator (NEMO) and IκB kinase 2 (IKK2), two essential mediators of the canonical pathway, either early on in B-cell development or specifically in mature B cells. Early ablation severely inhibited the generation of all mature B-cell subsets, but follicular B-cell numbers could be largely rescued by ectopic expression of B-cell lymphoma 2 (Bcl2), despite a persisting block at the transitional stage. Marginal zone (MZ) B and B1 cells were not rescued, indicating a possible role of canonical NF-κB signals beyond the control of cell survival in these subsets. When canonical NF-κB signaling was ablated specifically in mature B cells, the differentiation and/or persistence of MZ B cells was still abrogated, but follicular B-cell numbers were only mildly affected. However, the mutant cells exhibited increased turnover as well as functional deficiencies upon activation, suggesting that canonical NF-κB signals contribute to their long-term persistence and functional fitness.
MD-2 and Der p 2 — a tale of two cousins or distant relatives?

MD-2, an LPS-binding protein is essential for the recognition of LPS by TLR4. MD-2 belongs to the ML superfamily of lipid-binding proteins. The tertiary structure of mite allergen protein Der p 2 was identified as having the protein fold most compatible with the sequence of MD-2. Comparison of MD-2 and Der p 2 reveals that they have many common biochemical characteristics: they are both rich in β-structure and they are both very stable proteins as they both unfold only above 90°C. In Der p 2, six cysteine residues form three disulfide bridges. We determined one free cysteine residue per recombinant biologically active MD-2 molecule, supporting similar disulfide topology with three disulfides bridges as in Der p 2. MD-2 binds LPS with high affinity; however, only weak binding of LPS was detected with Der p 2. Comparison of electrostatic potentials of the structural model of MD-2 and Der p 2 indicates a region of high positive potential on MD-2 and its absence in Der p 2, which may be the reason for its weak binding of LPS. We suggest that Der p 2 and its homologues probably do not have a role in response to Gram-negative bacteria in insects and that MD-2 family members with their specific role in innate immunity probably evolved from an ML ancestor only in higher vertebrates.
Hydraulic Transients Analysis in Pipe Networks by the Method of Characteristics (MOC)

The paper presents results of an experimental and theoretical study of the hydraulic transients in straight pipes and numerical simulations of unsteady flow in pipe networks. A mathematical model consists of a set of partial differential equations of hyperbolic type, which have been transformed by the method of characteristics into ordinary differential equations which are solved by the predictor-corrector method. Experimental tests have been performed, in order to examine the hydraulic transients phenomenon, in a single straight steel pipe. The experiments were carried out in the hydraulic laboratory of the Institute of Water Supply and Water Engineering, Environmental Engineering Faculty, Warsaw University of Technology. The numerical results show that the presented one dimensional model for a single pipe correctly describes the phenomenon since there is a good agreement with experimental maximum and minimum oscillations. In the paper, selected exemplary equations in a difference form for the pipe networks are also presented. One calculation example is given relating to the complex water-pipe network consisting of 17 loops, 48 pipelines and 33 nodes, supplied by two independent sources. Water-hammer throughout the whole pipeline network was caused by closing the gate valve at mid-point of one selected pipe. The results of the numerical calculations are presented in graphic form with respect to the final cross-sections of pipes.
Functional Avidity and IL-2/Perforin Production Is Linked to the Emergence of Mutations within HLA-B*5701–Restricted Epitopes and HIV-1 Disease Progression

Viral escape from HIV-1–specific CD8+ T cells has been demonstrated in numerous studies previously. However, the qualitative features driving the emergence of mutations within epitopes are still unclear. In this study, we aimed to distinguish whether specific functional characteristics of HLA-B*5701–restricted CD8+ T cells influence the emergence of mutations in high-risk progressors (HRPs) versus low-risk progressors (LRPs). Single-genome sequencing was performed to detect viral mutations (variants) within seven HLA-B*5701–restricted epitopes in Gag (n = 4) and Nef (n = 3) in six untreated HLA-B*5701 subjects followed from early infection up to 7 y. Several well-characterized effector markers (IFN-γ, IL-2, MIP-1β, TNF, CD107a, and perforin) were identified by flow cytometry following autologous (initial and emerging variant/s) epitope stimulations. This study demonstrates that specific functional attributes may facilitate the outgrowth of mutations within HLA-B*5701–restricted epitopes. A significantly lower fraction of IL-2–producing cells and a decrease in functional avidity and polyfunctional sensitivity were evident in emerging epitope variants compared with the initial autologous epitopes. Interestingly, the HRPs mainly drove these differences, whereas the LRPs maintained a directed and maintained functional response against emerging epitope variants. In addition, LRPs induced improved cell-cycle progression and perforin upregulation after autologous and emerging epitope variant stimulations in contrast to HRPs. The maintained quantitative and qualitative features of the CD8+ T cell responses in LRPs toward emerging epitope variants provide insights into why HLA-B*5701 subjects have different risks of HIV-1 disease progression.
Mechanoregulation of h2-Calponin Gene Expression and the Role of Notch Signaling*

Background: Mechanical forces regulate gene expression. The mechanisms are not well understood. Results: A HES-1 site in the promoter of h2-calponin gene is a tension-regulated repressor responsive to Notch signaling. Conclusion: Notch regulation plays a role in the mechanoregulation of h2-calponin. Significance: The findings demonstrated a novel mechanism in the mechanoregulation of h2-calponin gene expression. The essential role of mechanical signals in regulating the function of living cells is universally observed. However, how mechanical signals are transduced in cells to regulate gene expression is largely unknown. We previously demonstrated that the gene encoding h2-calponin (Cnn2) is sensitively regulated by mechanical tension. In the present study, mouse genomic DNA containing the Cnn2 promoter was cloned, and a nested set of 5′ truncations was studied. Transcriptional activity of the Cnn2 promoter-reporter constructs was examined in transfected NIH/3T3, HEK293, and C2C12 cells for their responses to the stiffness of culture substrate. The results showed significant transcriptional activities of the −1.00- and −1.24-kb promoter constructs, whereas the −0.61-kb construct was inactive. The −1.38-, −1.57-, and −2.12-kb constructs showed higher transcriptional activity, whereas only the −1.57- and −2.12-kb constructs exhibited repression of expression when the host cells were cultured on low stiffness substrate. Internal deletion of the segment between −1.57 and −1.38 kb in the −2.12-kb promoter construct abolished the low substrate stiffness-induced repression. Site-specific deletion or mutation of an HES-1 transcription factor binding site in this region also abolished this repression effect. The level of HES-1 increased in cells cultured under a low tension condition, corresponding to the down-regulation of h2-calponin. h2-Calponin gene expression is further affected by the treatment of cells with Notch inhibitor and activator, suggesting an upstream signaling mechanism.
Validation of PCR for the detection of Pseudomonas aeruginosa from corneal samples.

AIM To determine a species-specific real-time polymerase chain reaction (PCR) assay to detect Pseudomonas aeruginosa (PA), a secondary DNA target for PA that may provide a universal target for other bacterial pathogens, and validate both assays for diagnostic testing. METHODS PCR detection was established against the ecfX PA gene and the 16S rRNA gene using known PA keratitis isolates. The outcome parameters for both assays were "limit of detection" (LOD), amplification efficiency (AE), and PAGE amplified product analysis. Both assays were validated against 20 true-positive clinical samples positive for PA DNA and 20 true-negative samples containing no PA DNA. Descriptive statistics and PAGE analysis were used as outcome parameters. RESULTS AE of the ecfX assay was 96.6%, and LOD was 33.6 copies of target DNA per microliter. AE of the 16S rRNA assay was 103.4%, and LOD was 8.12 copies per microliter. The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency for the ecfX and 16S rRNA assays were [75%, 95%, 94%, 79%, and 85%], and [70%, 100%, 100%, 77%, and 85%], respectively. Both PCR assays were validated, followed by confirmation of DNA patterns from PAGE analysis. CONCLUSION The PCR methodology described here may be a useful adjunct to standard methods in the diagnosis of PA keratitis.
PS-HEMA latex fractionation by sedimentation and colloidal crystallization

A poly(styrene-co-hydroxyethylmethacrylate) latex underwent sedimentation under gravity followed by an spontaneous and extensive colloidal crystallization. It was then fractionated in three visually distinguishable layers. Latex aliquots layers were sampled at different heigths and the particles were characterized by PCS, microelectrophoresis, infrared spectra and analytical electron microscopy. The major fraction was opalescent and contained the colloidal crystals settled in the bottom of the liquid. Two other latex fractions were obtained, which differed in their chemical compositions, particle sizes and topochemical features from the self-arraying particles. Macrocrystallization of the fractionated latex yielded high quality crystals with a low frequency of defects, which confirms that particle chemical homogeneity is an important factor for particle self-arraying.
Distortion Product Otoacoustic Emissions as a Prognostic Factor for Idiopathic Sudden Sensorineural Hearing Loss

We investigated distortion product otoacoustic emissions (DPOAE) as a prognostic factor in idiopathic sudden sensorineural hearing loss (ISSHL) patients with the time-dependent Cox proportional-hazards model. We also compared the importance of the prognostic factors that are reported in the literature. 108 patients with ISSHL were included. Both DPOAE and pure tone audiometry were performed everyday for a maximum of 7 days during admission and followed every other week or monthly after discharge. All DPOAE amplitudes were analyzed at 2f1-f2 – namely 1093, 1375, 1750, 2187, 2781, 3500, 4375, and 5500 Hz. The average of two series of DPOAE intensity corrected for the noise level in eight frequencies was coded as dichotomous at ≧6 or <6 dB. We selected the most updated DPOAE at 3 days or more before the assessment of recovery into the analysis. The potential confounders including age, sex, history of vertigo at onset, history of hypertension, diabetes, coronary arterial disease, and stroke, configuration and severity of initial pure tone audiometry, the duration from onset to treatment, auditory brainstem response (ABR), vestibular evoked myogenic potential (VEMP), and plasma triglyceride and cholesterol levels, hemoglobin level, and erythrocyte sedimentation rate were collected for evaluation. The results showed that a better DPOAE amplitude was a significantly good prognostic indicator both in univariate analysis (recovery rate ratio = 3.626, 95% CI = 2.119–6.205, p < 0.0001) and multivariate analysis (recovery rate ratio = 2.94, 95% CI = 1.537–5.624, p = 0.0011). The Kaplan-Meier estimates showed that the younger age group (≤40 years) with better initial pure tone audiometry (<65 dB) represented a better prognosis that was compatible with previous literature (log-rank test, p = 0.0297 and p = 0.0019 respectively). In the univariate analysis, normal ABR and VEMP waveforms were associated with a better prognosis (ABR: recovery rate ratio = 2.984, 95% CI = 1.742–5.112, p < 0.0001; VEMP: recovery rate ratio = 1.978, 95% CI = 1.183–3.305, p = 0.0093). The configuration of initial audiometry was also a significant prognostic factor that patients with scale-out type (recovery rate ratio = 0.228, 95% CI = 0.089–0.584, p = 0.002) and tent type (recovery rate ratio = 0.081, 95% CI = 0.008–0.778, p = 0.0295) were associated with a poorer prognosis than those with the flat type in the multivariate analysis. In this study, the time-dependent Cox proportional-hazards model established the prognostic value of DPOAE for ISSHL patients. This model can also be used for comparison of different treatment protocols. In addition, the further development of a predictive model based on this method is worthy of being investigated.