Miracle-dz/UniFAR-FTUs huggingface dataset:
Okazaki Fragment Processing-independent Role for Human Dna2 Enzyme during DNA Replication*

Background: Dna2 and FEN1 putatively cooperate in Okazaki fragment (OF) processing in yeast. Results: FEN1 depletion leads to OF maturation defects that do not impact replication fork kinetics, whereas hDna2 depletion leads to DNA damage independent of OF maturation. Conclusion: hDna2 participates in DNA replication in a manner distinct from FEN1. Significance: hDna2 participates in replication in a FEN1, OF maturation-independent manner. Dna2 is an essential helicase/nuclease that is postulated to cleave long DNA flaps that escape FEN1 activity during Okazaki fragment (OF) maturation in yeast. We previously demonstrated that the human Dna2 orthologue (hDna2) localizes to the nucleus and contributes to genomic stability. Here we investigated the role hDna2 plays in DNA replication. We show that Dna2 associates with the replisome protein And-1 in a cell cycle-dependent manner. Depletion of hDna2 resulted in S/G2 phase-specific DNA damage as evidenced by increased γ-H2AX, replication protein A foci, and Chk1 kinase phosphorylation, a readout for activation of the ATR-mediated S phase checkpoint. In addition, we observed reduced origin firing in hDna2-depleted cells consistent with Chk1 activation. We next examined the impact of hDna2 on OF maturation and replication fork progression in human cells. As expected, FEN1 depletion led to a significant reduction in OF maturation. Strikingly, the reduction in OF maturation had no impact on replication fork progression, indicating that fork movement is not tightly coupled to lagging strand maturation. Analysis of hDna2-depleted cells failed to reveal a defect in OF maturation or replication fork progression. Prior work in yeast demonstrated that ectopic expression of FEN1 rescues Dna2 defects. In contrast, we found that FEN1 expression in hDna2-depleted cells failed to rescue genomic instability. These findings suggest that the genomic instability observed in hDna2-depleted cells does not arise from defective OF maturation and that hDna2 plays a role in DNA replication that is distinct from FEN1 and OF maturation.
Research on the cable-pulley underactuated lower limb exoskeleton

A wide variety of lower limb exoskeletons have been applied in the fields of load-carrying augmentation, walking assistance, and rehabilitation training. The traditional exoskeleton based on fully actuated joints can provide powerful assistance for human motion, while it is bulky requiring a large energy consumption, which limits its application. The passive and quasi-passive exoskeletons are weak in the load-carrying condition due to the lack of active actuators. The traditional underactuated exoskeleton with only one joint actuated generally has limited power assistance. As for soft exoskeleton, uncomfortable feeling resulting from the pressure generated by cable tension on muscles are unavoidable. To compensate these drawbacks, this paper presents a lower limb exoskeleton based on the cable-pulley underactuated principle. By studying the synergies of torque and power assistance at the joints and designing the control strategy, a single cable will be able to drive the hip joint and the knee joint simultaneously, which can reduce the number of actuators. Considering the human-exoskeleton interactive dynamics, a biological method is utilized to evaluate the performance of the exoskeleton. Finally, the contrast simulation results demonstrate that the exoskeleton proposed in this paper can effectively provide power augmentation in load-carrying walking without interfering the human motion and the control strategy is feasible.
Mortgage product diversity: responding to consumer demand or protecting lender profit? An asymmetric panel analysis

ABSTRACT This article explores determinants of mortgage product diversity for owner-occupied and investment loans in the Australian housing mortgage market. From 2001 to 2012, 65 lenders introduced 1220 mortgage products in Australia. We examine whether the product proliferation was a result of consumer demand or a response to pressure to lower lending rates. We find that consumer demand for mortgages does not have a significant relationship with the number of mortgage products, but that decreases in the policy interest rate are highly significant as an explanatory variable for product proliferation. Such behaviour is consistent with information obfuscation, reducing the ease with which consumers can compare lending rates. Further, the relationship between mortgage products offered and the policy interest rate is asymmetric: decreases in the cash rate are associated with increased mortgage products offered, but increases in the cash rate have a more muted effect on decreasing the number of products.
Suicidal ideation and behaviors among youths in juvenile detention.

OBJECTIVE To examine suicidal ideation, suicide attempts, lethality of suicide attempts, and the relationship between psychiatric disorder and recent attempts in newly detained juveniles. METHOD The sample included 1,829 juveniles, ages 10 to 18 years, sampled after intake to a detention center in Chicago. Interviewers administered the Diagnostic Interview Schedule for Children to assess for thoughts of death, suicidal ideation, suicide plans, lifetime suicide attempts, number of attempts, age at first attempt, attempts within the past 6 months, method of suicide attempts, and psychiatric disorder. RESULTS More than one third of juvenile detainees and nearly half of females had felt hopeless or thought about death in the 6 months before detention. Approximately 1 in 10 (10.3%, 95% confidence interval: 7.7%-12.8%) juvenile detainees had thought about committing suicide in the past 6 months, and 1 in 10 (11.0%, 95% confidence interval: 8.3%-13.7%) had ever attempted suicide. Recent suicide attempts were most prevalent in females and youths with major depression and generalized anxiety disorder. CONCLUSIONS Fewer than half of detainees with recent thoughts of suicide had told anyone about their ideation. Identifying youths at risk for suicide, especially those suffering from depressive and anxiety disorders, is a crucial step in preventing suicide.
Fertility defects revealing germline biallelic nonsense NBN mutations

Biallelic mutations in the NBN/NBS1 gene are the cause of Nijmegen breakage syndrome (NBS), a severe pediatric disease characterized by dysmorphy with a bird‐like face, microcephaly, growth retardation, immune deficiency, and proneness to cancer. We here report two adult siblings that are compound heterozygotes for two previously unreported NBN nonsense mutations. These patients presented with the unique clinical symptom of fertility defects. Contrasting with the absence of any developmental abnormality, biological analyses revealed defects similar to those observed in NBS patients, including chromosomal instability, cellular hyperradiosensitivity and checkpoint defects as measured by radioresistant DNA synthesis (RDS). NBN mutations should thus be considered a new cause of infertility, and should be searched for if associated with the biological abnormalities of NBS. Hum Mutat 0, 1–7, 2008. © 2008 Wiley‐Liss, Inc.
Microsurgical Lymphatic Vessel Transplantation

Abstract Background Lymphedema often arises after a regional interruption during cancer treatment, for example after lymph node resection the axilla or the groin. Lymphatic vessels as vascular grafts may overcome these lymphatic gaps. Method Experiments in rats and dogs were performed for developing this method. Volume measurements, lymphoscintigraphies, proof of patency by MRI and radiology as well as quality of life studies were performed in patients. Results Long-term follow-up studies revealed significantly reduced volumes, significant improvement of lymphatic outflow shown by lymphoscintigraphy, long-term patency of the grafts for more than 10 years, and improved quality of life after surgery compared with the situation with conservative treatment before surgery. Conclusion Vascular grafts using the patients own lymphatic vessels are able to successfully reconstruct a locally interrupted lymphatic pathway.
Confocal Scanning Laser Microscopy Evidence of Biofilms in Patients With Chronic Rhinosinusitis

Objectives: The recent detection of bacterial biofilms on the sinus mucosa of patients with chronic rhinosinusitis (CRS) has implicated biofilms in the pathogenesis of this condition. Electron microscopy has been the main modality used to document the presence of biofilms on sinus tissue, however, it has inherent problems associated with tissue preparation and sampling. Recently, Confocal Scanning Laser Micrsocopy (CSLM) has emerged as a noninvasive, nondestructive technique for the analysis of biofilms. This study used CSLM as the means of investigating biofilm presence in CRS patients.
Sterol Regulation of Fatty Acid Synthase Promoter

The gene encoding fatty acid synthase, the essential multi-functional enzyme of fatty acid biosynthesis, is shown to be regulated by cellular sterol levels similar to genes that encode important proteins of cholesterol metabolism. We show that expression of the endogenous FAS gene is repressed when regulatory sterols are included in the culture medium of HepG2 cells and that the FAS promoter is subject to similar regulation when fused to the luciferase reporter gene. Mutational studies demonstrate that sterol regulation is mediated by binding sites for the sterol regulatory element-binding protein (SREBP) and transcription factor Sp1, making it mechanistically similar to sterol regulation of the low density lipoprotein receptor gene. It is also demonstrated that SREBP and Sp1 synergistically activate the FAS promoter in Drosophila tissue culture cells, which lack endogenous Sp1. These experiments provide key molecular evidence that directly links the metabolism of fatty acids and cholesterol together.
Polycystin-1 Distribution Is Modulated by Polycystin-2 Expression in Mammalian Cells*

Mutations in PKD1 and PKD2, the genes that encode polycystin-1 and polycystin-2 respectively, account for almost all cases of autosomal dominant polycystic kidney disease. Although the polycystins are believed to interact in vivo, the two proteins often display dissimilar patterns and gradients of expression during development. In an effort to understand this apparent discrepancy, we investigated how changes in polycystin-2 expression can affect the subcellular localization of polycystin-1. We show that, when polycystin-1 is expressed alone in a PKD2 null cell line, it localizes to the cell surface, as well as to the endoplasmic reticulum. When co-expressed with polycystin-2, however, polycystin-1 is not seen at the cell surface and co-localizes completely with polycystin-2 in the endoplasmic reticulum. The localization of a polycystin-1 fusion protein was similarly affected by changes in its level of expression relative to that of polycystin-2. This phenomenon was observed in populations as well as in individual COS-7 cells. Our data suggest that the localization of polycystin-1 can be regulated via the relative expression level of polycystin-2 in mammalian cells. This mechanism may help to explain the divergent patterns and levels of expression observed for the polycystins, and may provide clues as to how the function of these two proteins are regulated during development.
An information-estimation perspective of communications over Gaussian interference channels

The information-estimation relationship is used to gain insight into useful coding schemes operating over the Gaussian interference channel. After reviewing basic I-MMSE relations and their implications on point-to-point coding over the Gaussian channel, we focus on the Gaussian interference channel. Here the inflicted interference is measured by the associated minimum mean square error (MMSE). Structure of codes achieving reliable communication at some specific signal-to-noise ratio (snr) and constrained by the permitted MMSE at lower snr values, modeling the interference, are discussed. It is shown that layered superposition codes attain optimal performance, providing thus some engineering insight to the relative efficiency of the Han-Kobayashi coding strategy in the two-user interference scenario. We also address related research challenges.
Demonstration of an Na+/H+ exchanger in mouse keratinocytes measured by the novel pH‐sensitive fluorochrome SNARF‐calcein

In many cell types cytoplasmic alkalization is an early marker for cell activation. An amiloride‐sensitive Na+/H+ exchanger is an important regulator of this process. However, in keratinocytes the existence of a Na+/H+ exchanger nor a proliferation‐associated increase in intracellular pH (pHi) has been demonstrated.
Towards 100 Gbps over 100m MMF using a 850nm VCSEL

Employing MultiCAP signaling, successful 70.4 Gbps transmission over 100 m of OM3 MMF using off-the-shelf 850 nm VCSEL with 10.1 GHz 3-dB bandwidth is experimentally demonstrated indicating the feasibility of achieving 100 Gbps with a single 25 GHz VCSEL.
Comparative proteomics analysis of spermary and ovary in Hyriopsis schlegelii

We provide the first large-scale quantitative proteomics analysis in Hyriopsis schlegelii. To investigate the proteins expressed in the gonads, a quantitative proteomics approach has been utilized to analyze differentially expressed proteins between the spermary and ovary. In this study, we identified and quantified 2416 proteins in the gonads of Hyriopsis schlegelii. Of these, 559 proteins showed significantly different expression between the spermary and ovary. Some specific proteins expressed in either the spermary or ovary were identified in Hyriopsis schlegelii. In addition, a series of proteins related to gametogenesis were also identified. Compared with previous reports, many proteins in Hyriopsis schlegelii identified here have different expression patterns between the spermary and ovary. The special hermaphroditism in Hyriopsis schlegelii may contribute to these inconsistent results. The provided proteomics data could be considered as a starting point for subsequent studies focusing on the proteins involved in sexual gland development and maturity. Graphical abstract The distribution of 2416 proteins based on the differential expression between spermary and ovary.
Real-Time Technique for Improving Molecular Imaging and Guiding Drug Delivery in Large Blood Vessels: In Vitro and Ex Vivo Results

Ultrasound-based molecular imaging employs targeted microbubbles to image vascular pathology. This approach also has the potential to monitor molecularly targeted microbubble-based drug delivery. We present an image-guided drug delivery technique that uses multiple pulses to translate, image, and cavitate microbubbles in real time. This technique can be applied to both imaging of pathology in large arteries (sizes and flow comparable to those in humans) and guiding localized drug delivery in blood vessels. The microbubble translation (or pushing) efficacy of this technique was compared in a variety of flow media: saline, viscous saline (4 cp), and bovine blood. It was observed that the performance of this approach was marginally better (by 6, 4, and 2 dB) in viscous saline than in bovine blood with varying levels of hematocrit (40%, 30%, and 10%). The drug delivery efficacy of this technique was evaluated by in vitro and ex vivo experiments. High-intensity pulses mediated fluorophore (DiI) deposition on endothelial cells (in vitro) without causing cell destruction. Ex vivo fluorophore delivery experiments conducted on swine carotids of 2 and 5 mm cross-section diameter demonstrated a high degree of correspondence in spatial localization of the fluorophore delivery between the ultrasound and composite fluorescence microscopy images of the arterial cross sections.
Depth electrode implantation in the length axis of the hippocampus for the presurgical evaluation of medial temporal lobe epilepsy: a computed tomography-based stereotactic insertion technique and its accuracy.

OBJECTIVE An individualized computed tomography-based stereotactic technique for the longitudinal insertion of intrahippocampal electrodes is presented and its accuracy described. METHODS The technique makes use of one well reproducible target in the hippocampal head and of the approximate inclination of the anteroposterior length axis of the hippocampus, for which the orbital floor is taken as an auxiliary landmark. It was used in 141 patients with medically intractable complex partial seizures. In 106 patients, magnetic resonance imaging (MRI) was available for assessment of implantation accuracy. Each of the 212 electrodes was plotted on topographic drawings and its goodness of fit rated. RESULTS Whereas hippocampal head and body were hit by 97 and 96% of the electrodes, respectively, the amygdala was hit by only 75% of the electrodes and mainly at its basal margin. For 93% of the electrodes, the inclination in a sagittal plane corresponded exactly to that of the hippocampus. The implantation morbidity amounted to 5.7%, whereas permanent neurological deficit occurred in one (0.7%) of the 141 patients. CONCLUSION This computed tomography-based protocol proved to be reliable and hence can be considered as an adequate alternative to MRI-based stereotactic implantation if MRI is not available or if a single MRI-based stereotactic set-up is unreliable because of intolerable distortions.
Can sector specific REIT strategies outperform a diversified benchmark

Purpose We investigate the performance of different portfolios of REITs which specialise by property type compared to the performance of a diversified free-float market capitalisation weighted benchmark index to determine whether superior risk-adjusted returns can be achieved. Design/methodology/approach Firstly we examine the performance of portfolios constructed using the criteria of Equal Weight, Minimum Variance, Maximum Sharpe and Risk Parity rather than free-float market capitalisation. Secondly we apply an automated trading strategy of Trend Following to see if this filter will improve risk-adjusted returns. Findings The two step process of forming combinations of REIT sectors with the subsequent addition of a trend following overlay can offer clear benefits relative to a passive benchmark investment. Research limitations/implications Although three of the four strategies were shown to outperform the benchmark index on a risk-adjusted basis, one issue was that the efficient portfolios tended to ha.
A study of water uptake by selected superdisintegrants from the sub-molecular to the particulate level

Abstract Water diffusion through the matrix of three superdisintegrants, namely sodium starch glycolate (SSG), croscarmellose sodium (cCMC-Na) and crospovidone (cPVP), was studied at the sub-molecular level using Attenuated Total Reflectance (ATR)–FTIR spectroscopy and molecular dynamics simulations, and the results were correlated to water uptake studies conducted at the particulate level using Parallel Exponential Kinetics (PEK) modeling in dynamic moisture sorption studies and optical microscopy. ATR–FTIR studies indicated that water diffuses inside cPVP by a single fast acting process, while in SSG and cCMC-Na, a slow and a fast process acting simultaneously, were identified. The same pattern regarding the rate of water uptake for all superdisintegrants was found also at the particulate level by PEK modeling. Moreover, molecular dynamics simulation helped elucidate the hydrogen bonding patterns formed between water-SSG and water-cCMC-Na, mainly via their carboxylic oxygen atoms and secondarily via their hydroxyl groups, while cPVP formed hydrogen bonds only through carbonyl oxygen. Finally, cPVP chains showed significant flexibility during hydration, while cCMC-Na and SSG chains retain their conformation to some extent, explaining the extensive swelling observed also at the particulate level by optical microscopy hydration studies.
Prevention of voltage instability by adaptive determination of tap position in OLTCs

This paper introduces a robust and appropriate algorithm for dynamic voltage control by adaptive/predictive determination of tap position in OLTCs (according to their nonlinear behavior) for preventing voltage instability which may caused by them. The OLTCs can be destructive as much as their advantages, because they have not specified and linear characteristic (like capacitor banks) and it requires a predictive/adaptive manner for finding the appropriate and safe rate of changes of taps in OLTCs. To this end, an adaptive manner on the basis of sensitivity analysis is proposed in this paper. By employing this method, the appropriate changes in tap position of each OLTCs is determined at any time. The results of simulations in Nordic32 test system demonstrate effectiveness and robustness of the proposed scheme.
Cell Cycle Phase-Specific CHemotherapy: Computation Methods for Guiding Treatment

Computational models of cancer chemotherapy enhance the understanding of in vitro, in vivo, and clinical trial data and have the potential to contribute to the design of rational treatment regimens. In particular, mechanistic, predictive models are superior to statistical, phenomenological descriptions of data. Mechanistic models based on functional data from tumor biopsies will enable the response to treatment to be predicted for a specific patient, in contrast to statistical models in which the probability of response for a given patient may differ substantially from the population average. This review summarizes mathematical models developed to improve the design of treatment regimens using cell-cycle phase-specific chemotherapy. It starts with simple models of dose response, then moves to more complex models of scheduling cell-cycle phase-specific drugs, and finally discusses mechanistic models that incorporate both genetic drug resistance and cell cycle-mediated drug resistance. This last class of models will be most useful in designing treatment regimens tailored for individual patients. Key words Cell-cycle phase-specific drugs, Mathematical models, Cell kinetic, Drug resistance, Chemotherapy, Tumor heterogeneity
Examining empathy and its association with aggression in young Western Cape children

Objective: In a context of disturbing rates of violent crime, this pilot study initiated examination of the association between empathy and aggressive behaviour in young Western Cape children. Establishing which empathy measures are appropriate for our context was a primary concern. Method: To capture various aspects of empathy in young children we adopted a multi-method approach. We examined empathy scores in 65 lower middle socio-economic status (SES) English-speaking Grade 1 pupils (6.0–8.0 years old) and their association with aggressive externalising behaviour. Results: Parent report measures of callous-unemotional traits and aggression performed well, however, the Griffith Empathy Measure, a well-established parent report scale, proved problematic. Empathy scores, particularly those for callous-unemotional traits, were associated with aggression. We also found several associations between aspects of empathy, consistent with the international literature. Cognitive empathy, as measured by first-order false belief reasoning, was not well established, suggesting that other more complex social cognitive tasks were inappropriate for this age group in our context. Conclusion: The association between empathy and aggression warrants further investigation in this context. Appropriate measures for the South African context must be utilised.