Miracle-dz/UniFAR-FTUs huggingface dataset:
The practical application of reflectance spectrophotometry for the demonstration of haemoglobin and its degradation in bruises

Aims: To develop a non-invasive method to demonstrate the presence of haemoglobin and its degradation products in bruises in live human subjects for the purposes of objectively assisting in the determination of the age of a bruise. Methods: The cuvette holder unit of a Cary 100 Bio UV-Visible Spectrophotometer was replaced with the manufacture’s fibre optic cable and optical reflectance probe. The probe was placed on the skin surface. The absorption spectrum from 780 to 380 nm was collected and transformed into the first derivative. Calculation of the first derivative permits absorption attributed to haemoglobin degradation (primarily to bilirubin, but also haemosiderin) to be separated from absorption by haemoglobin. First derivative and colorimetry values, expressed as CIEL*a*b data, were derived from scans of 50 bruises. Results: The fibre optic cable and probe allowed the spectrophotometer to collect reproducible absorption spectra of bruises in the skin of living subjects. A bruise at three days has greater negative first derivative values at 480 and 490 nm than does a fresh bruise, indicating the local degradation of haemoglobin. Correlation between the first derivative and the CIEL*a*b “b” values in a series of bruises indicates that the yellow colour in a bruise is proportional to the amount of local haemoglobin breakdown. Conclusion: The ability to demonstrate the presence of haemoglobin and measure its degradation in bruises in living human subjects by a non-invasive method has not been described previously, and may be of use in the objective ageing of bruises for forensic purposes.
Non-asymptotic analysis of scaled largest eigenvalue based spectrum sensing

In this paper, we analyze the non-asymptotic performance of scaled largest eigenvalue based detection, which is an optimal detector in the presence of a single primary user. Exact distributions of the test statistics have been derived, which lead to finite-dimensional characterizations of the false alarm probability. These results are obtained by taking advantage of the properties of the Mellin transform for products of independent random variables. Simulations are provided to verify the derived results, and to compare with the asymptotic result in literature.
Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions

Osteoclasts are bone‐resorbing cells derived from the myeloid lineage that play a central role in bone remodeling and inflammatory bone erosion diseases. The receptor activator of NF‐κB ligand (RANKL) produced by osteoblasts and activated immune cells initiates the development of osteoclasts in the bone marrow. Using time series gene expression data, the intrinsic processes and the extrinsic factors that control osteoclastogenesis were identified. The gene expression profiles display distinct commitment and differentiation phases. Analysis of the time course revealed several mechanistic details, including the complex role of cholesterol in osteoclast development. Epistatic interactions and the coordination between cellular processes that regulate development were inferred from the coexpression network. The coexpression network indicated that osteoclasts induce angiogenesis and recruit T‐cells to the site of osteoclastogenesis early in the commitment phase. The resulting model provides an essential framework for a better understanding of the epigenetic program of osteoclastogenesis. Developmental Dynamics 236:2181–2197, 2007. © 2007 Wiley‐Liss, Inc.
Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin

Target of Rapamycin (TOR) is involved in cellular and organismal aging. Rapamycin extends lifespan and delays cancer in mice. It is important to determine the minimum effective dose and frequency of its administration that still extends lifespan and prevents cancer. Previously we tested 1.5 mg/kg of rapamycin given subcutaneously 6 times per two weeks followed by a two-week break (1.5 × 6/bi-weekly schedule: total of 6 injections during a 4-week period). This intermittent treatment prolonged lifespan and delayed cancer in cancer-prone female FVB/N HER-2/neu mice. Here, the dose was decreased from 1.5 mg/kg to 0.45 mg/kg per injection. This treatment was started at the age of 2 months (group Rap-2), 4 months (Rap-4), and 5 months (Rap-5). Three control groups received the solvent from the same ages. Rapamycin significantly delayed cancer and decreased tumor burden in Rap-2 and Rap-5 groups, increased mean lifespan in Rap-4 and Rap-5 groups, and increased maximal lifespan in Rap-2 and Rap-5 groups. In Rap-4 group, mean lifespan extension was achieved without significant cancer prevention. The complex relationship between life-extension and cancer-prevention depends on both the direct effect of rapamycin on cancer cells and its anti-aging effect on the organism, which in turn prevents cancer indirectly. We conclude that total doses of rapamycin that are an order of magnitude lower than standard total doses can detectably extend life span in cancer-prone mice.
Improvement in health utility among patients with rheumatoid arthritis treated with adalimumab (a human anti-TNF monoclonal antibody) plus methotrexate.

OBJECTIVES To compare health-related quality of life (HRQoL), as measured by health utility, in patients with rheumatoid arthritis (RA) treated with adalimumab (a human anti-tumour necrosis factor (anti-TNF) monoclonal antibody) plus methotrexate or placebo plus methotrexate. METHODS HRQoL data were obtained in two randomized, double-blind, placebo-controlled, multidose clinical trials conducted in the United States and Canada. The Health Utilities Index Mark 3 (HUI3) was administered in both studies at baseline, at the end of the study and at two time points in between. Patients' HUI3 scores were compared with population norm scores. Change in HUI3 was defined as the end-of-study score minus the baseline score. Utility gained throughout the study was measured by area under the utility curve and expressed as quality-adjusted life years (QALYs). Statistical testing adjusted for confounders and used the Dunnett test to account for multiple comparisons. RESULTS Patients' utility scores at baseline were low (range of treatment group means 0.38-0.44) compared with population norms (0.88). HUI3 mean changes from baseline scores for adalimumab-treated patients were 0.22 and 0.21 in the two trials, whereas placebo patients' changes were 0.04 and 0.07. The rate of QALYs gained per year in the treatment group compared with the placebo group were 0.145 in the ARMADA trial and 0.104 in the DE019 trial. All gains were clinically important and statistically significant. CONCLUSIONS Treatment with adalimumab plus methotrexate provides clinically important and statistically significant improvements in HRQoL as measured by health utility in patients with RA. This translates into measurable and important gains in QALYs.
Smart phone technologies and ecological momentary data: is this the way forward on depression management and research?

PURPOSE OF REVIEW Depression is a complex and burdensome condition; it often leads to personal, societal and economic costs. Despite advances in treatments, its management over time remains a challenge; many treated for depression do not achieve full recovery or remain well for long. Novel ways to monitor patients are warranted, as well as better understanding of contributors to relapse or sustained wellness. Mobile health technologies (m-Health) are emerging as useful tools for real-time assessments of moods, behaviours and activities in a more convenient and less burdensome manner. Yet, there are numerous questions around privacy, reliability and accuracy of data collected via mobile apps. This review provides a critical overview of advances in m-Health and evaluate the future potential of smartphone technology in the assessment and treatment of depression. RECENT FINDINGS There is an abundance of apps in the market that claim to exert beneficial effects on the management of depression; to date, only a small fraction has been validated in clinical trials or has had the support of academic centers. SUMMARY Although promising, the use of mobile health applications in depression warrants further investigation and incorporation into mainstream research to facilitate greater adoption and validation of its clinical utility.
A Synergistic Concealed Information Test With Novel Approach for EEG Channel Selection and SVM Parameter Optimization

In the era of data, it is a challenging task to classify continuous data such as electroencephalographic data. The electroencephalographic signal maps several thoughts going in an individual’s brain by connecting a device to the human brain. In this paper, we have proposed a deceit identification system using a test called “concealed information test. ” The electroencephalographic data have been recorded when the concealed information test is performed for experimental analysis. To enhance the performance of the deceit identification system, the optimization of support vector machine (SVM) parameters and the selection of the EEG channels are performed. This paper implements a binary version of the BAT algorithm (binary BAT algorithm) and the conventional BAT algorithm on the electroencephalography (EEG) data. A novel cost function is also proposed, which utilizes the results of continuous BAT and binary BAT to enhance the system performance. In this synergistic approach, BAT is used for the SVM parameters optimization, and the binary BAT algorithm is applied for the EEG channel selection. The performance of the system is improved, and it is inferred that the channels placed at the occipital lobe of the brain consist of the artifacts. After removing the channels placed on the occipital lobe, i.e., O1, Oz, and O2, and using the optimized SVM parameters, the system’s average accuracy increases from 94.11% to 96.8%.
Feasibility of haloperidol-anchored albumin nanoparticles loaded with doxorubicin as dry powder inhaler for pulmonary delivery

Abstract Haloperidol (Hal) is a ligand that can target sigma 2 receptors over-expressed in non-small cell lung cancer. Hal targeted nanoparticles of bovine serum albumin (BSA) were prepared for pulmonary delivery of doxorubicin (DOX). The conjugation was confirmed by Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) spectroscopic methods. Nanoparticles were prepared by desolvation method from BSA–Hal and were loaded with DOX. They were characterized for their morphology, particle size, zeta potential, drug loading and release efficiency. The optimized nanoparticles were spray-dried using trehalose, l-leucin and mannitol as dry powder inhaler (DPI) in different inlet temperatures between 80 and 120 °C. The obtained nanocomposites were characterized for their aerodynamic diameter, specific surface area (cm2/g) and fine particle fraction (FPF) by a Cascade Impactor device. The optimized nanoparticles showed particle size of 218 nm, zeta potential of −25.4 mV, drug entrapment efficiency of 89% and release efficiency of 56% until 2 h. After spray drying of these nanoparticles, the best results were obtained from mannitol with an inlet temperature of 80 °C which produced a mean aerodynamic diameter of 4.58 μm, FPF of 66% and specific surface area of 6302.99 cm2/g. The obtained results suggest that the designed DPI could be a suitable inhaler for targeted delivery of DOX in pulmonary delivery.
Omega-3 Fatty Acid Supplementation Does Not Reduce Risk of Atrial Fibrillation After Coronary Artery Bypass Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background—Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported to reduce the risk of sudden cardiac death presumed to be due to fatal ventricular arrhythmias, but their effect on atrial arrhythmias is unclear. Methods and Results—Patients (n=108) undergoing coronary artery bypass graft surgery were randomly assigned to receive 2 g/d n-3 PUFA or placebo (olive oil) for at least 5 days before surgery (median, 16 days; range, 12 to 21 days). Phospholipid n-3 PUFA were measured in serum at study entry and at surgery and in right atrial appendage tissue at surgery. Echocardiography was used to assess left ventricular function and left atrial dimensions. Postoperative continuous ECG monitoring (Lifecard CF) for 5 days or until discharge, if earlier, was performed with a daily 12-lead ECG and clinical review if patients remained in the hospital beyond 5 days. Lifecard recordings were analyzed for episodes of atrial fibrillation (AF) ≥30 seconds (primary outcome). Clinical AF, AF burden (% time in AF), hospital stay, and intensive care/high dependency care stay were measured as secondary outcomes. One hundred three patients completed the study (51 in the placebo group and 52 in the n-3 PUFA group). There were no clinically relevant differences in baseline characteristics between groups. n-3 PUFA levels were higher in serum and right atrial tissue in the active treatment group. There was no significant difference between groups in the primary outcome of AF (95% confidence interval [CI], −6% to 30%, P=0.28) in any of the secondary outcomes or in AF-free survival. Conclusions—Omega-3 PUFA do not reduce the risk of AF after coronary artery bypass graft surgery. Clinical Trial Registration—www.ukcrn. org.uk. Identifier: 4437.
Female Lethality and Apoptosis of Spermatocytes in Mice Lacking the UBR2 Ubiquitin Ligase of the N-End Rule Pathway

ABSTRACT Substrates of the ubiquitin-dependent N-end rule pathway include proteins with destabilizing N-terminal residues. UBR1−/− mice, which lacked the pathway's ubiquitin ligase E3α, were viable and retained the N-end rule pathway. The present work describes the identification and analysis of mouse UBR2, a homolog of UBR1. We demonstrate that the substrate-binding properties of UBR2 are highly similar to those of UBR1, identifying UBR2 as the second E3 of the mammalian N-end rule pathway. UBR2 −/− mouse strains were constructed, and their viability was found to be dependent on both gender and genetic background. In the strain 129 (inbred) background, the UBR2 −/− genotype was lethal to most embryos of either gender. In the 129/B6 (mixed) background, most UBR2 −/− females died as embryos, whereas UBR2 −/− males were viable but infertile, owing to the postnatal degeneration of the testes. The gross architecture of UBR2 −/− testes was normal and spermatogonia were intact as well, but UBR2 −/− spermatocytes were arrested between leptotene/zygotene and pachytene and died through apoptosis. A conspicuous defect of UBR2 −/− spermatocytes was the absence of intact synaptonemal complexes. We conclude that the UBR2 ubiquitin ligase and, hence, the N-end rule pathway are required for male meiosis and spermatogenesis and for an essential aspect of female embryonic development.
Islet-Expressed CXCL10 Promotes Autoimmune Destruction of Islet Isografts in Mice With Type 1 Diabetes

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells in the pancreas. Thereby, the chemokine CXC-motif ligand 10 (CXCL10) plays an important role in the recruitment of autoaggressive lymphocytes to the islets of Langerhans. Transplantation of isolated islets as a promising therapy for T1D has been hampered by early graft rejection. Here, we investigated the influence of CXCL10 on the autoimmune destruction of islet isografts using RIP-LCMV mice expressing a lymphocytic choriomeningitis virus (LCMV) protein in the β-cells. RIP-LCMV islets express CXCL10 after isolation and maintain CXCL10 production after engraftment. Thus, we isolated islets from either normal or CXCL10-deficient RIP-LCMV mice and transferred them under the kidney capsule of diabetic RIP-LCMV mice. We found that the autoimmune destruction of CXCL10-deficient islet isografts was significantly reduced. The autoimmune destruction was also diminished in mice administered with an anti-CXCL10 antibody. The persistent protection from autoimmune destruction was paralleled by an increase in FoxP3+ regulatory T cells within the cellular infiltrates around the islet isografts. Consequently, CXCL10 might influence the cellular composition locally in the islet graft, thereby playing a role in the autoimmune destruction. CXCL10 might therefore constitute a potential therapeutic target to prolong islet graft survival.
Essays on perishable inventory management

My dissertation addresses a number of challenges in perishable inventory management in supply chains, providing both theoretical results and managerial insights. Essay 1: In this essay, we review the literature on supply chain management of perishable products that have a fixed or random lifetime, primarily focusing on challenges introduced by aging of such products. We start with a review of the literature on capacity and production planning. We then review the literature on inventory management at a single location. The research on single-location models provides a basis for research on multi-echelon/multi-location models, that are also reviewed in this chapter, along with transshipment and distribution models. The chapter also covers research involving modeling novelties, in terms of demand-fulfillment, information sharing, and centralized vs. decentralized planning. We provide several directions for future research by identifying the gaps in the literature and the needs of industries where perishable products are commonly stocked. Essay 2: We consider a discrete-time supply chain for perishable goods where there are separate demand streams for items of different ages. We compare two practical replenishment policies: replenishing inventory according to order-up-to level policies based on either (i) total inventory in system or (ii) new items only. Given these policies, we concentrate on four different ways of fulfilling demand: (1) demand for an item can only be satisfied by an item of that age (No-Substitution); (2) demand for new items can only be satisfied by new ones, but excess demand for old items can be satisfied by new (Downward-Substitution); (3) demand for old items can only be satisfied by old, but excess demand for new items can be satisfied by old (Upward-Substitution); (4) both downward and upward substitution are employed (Full-Substitution). We compare these substitution options analytically in terms of their infinite horizon time-average costs, providing conditions on cost parameters that determine when (if at all) one substitution option is more profitable than the others, for an item with a two-period lifetime. We also prove that inventory is “fresher” whenever downward substitution is employed. Our results are based on sample-path analysis, and as such make no assumptions on the joint distribution of demand, save for ergodicity. We complement our results with numerical experiments exploring the effect of problem parameters on performance.
Homeodomain Transcription Factor Phox2a, via Cyclic AMP-Mediated Activation, Induces p27Kip1 Transcription, Coordinating Neural Progenitor Cell Cycle Exit and Differentiation

ABSTRACT Mechanisms coordinating neural progenitor cell cycle exit and differentiation are incompletely understood. The cyclin-dependent kinase inhibitor p27Kip1 is transcriptionally induced, switching specific neural progenitors from proliferation to differentiation. However, neuronal differentiation-specific transcription factors mediating p27Kip1 transcription have not been identified. We demonstrate the homeodomain transcription factor Phox2a, required for central nervous system (CNS)- and neural crest (NC)-derived noradrenergic neuron differentiation, coordinates cell cycle exit and differentiation by inducing p27Kip1 transcription. Phox2a transcription and activation in the CNS-derived CAD cell line and primary NC cells is mediated by combined cyclic AMP (cAMP) and bone morphogenetic protein 2 (BMP2) signaling. In the CAD cellular model, cAMP and BMP2 signaling initially induces proliferation of the undifferentiated precursors, followed by p27Kip1 transcription, G1 arrest, and neuronal differentiation. Small interfering RNA silencing of either Phox2a or p27Kip1 suppresses p27Kip1 transcription and neuronal differentiation, suggesting a causal link between p27Kip1 expression and differentiation. Conversely, ectopic Phox2a expression via the Tet-off expression system promotes accelerated CAD cell neuronal differentiation and p27Kip1 transcription only in the presence of cAMP signaling. Importantly, endogenous or ectopically expressed Phox2a activated by cAMP signaling binds homeodomain cis-acting elements of the p27Kip1 promoter in vivo and mediates p27Kip1-luciferase expression in CAD and NC cells. We conclude that developmental cues of cAMP signaling causally link Phox2a activation with p27Kip1 transcription, thereby coordinating neural progenitor cell cycle exit and differentiation.
Substitution of methionine 35 inhibits apoptotic effects of Abeta(31-35) and Abeta(25-35) fragments of amyloid-beta protein in PC12 cells.

BACKGROUND Amyloid-beta peptide (AbetaP), the central constituent of senile plaques in Alzheimer's disease (AD) brain, has been shown to be toxic to neuronal cells and that this toxicity is responsible for the progressive cognitive decline associated with this neurodegenerative disease. The precise mechanism of AbetaP action remains to be determined; however, it has been reported that the methionine residue at position 35 plays a pivotal role in the toxicity of the peptide. With this in mind, the present study examines the effect of mutating the methionine to norleucine in the fragments (31-35) and (25-35) of AbetaP, which have methionine at the C-terminal, in order to investigate the influence of this residue on Abeta-mediated toxic effects on PC12 cells. MATERIAL/METHODS The toxic and apoptotic effects (release of Cyt c, caspase activation, and DNA fragmentation) exerted by the Abeta(31-35) and Abeta(25-35) wild-type peptides and Abeta(31-35)Met-->Nle, Abeta(25-35)Met-->Nle peptides where methionine was substituted with norleucine were investigated on PC12 cells. RESULTS The results obtained shown that both peptides induce neurotoxicity in PC12 cells via an apoptotic cell death pathway, including cytochrome c release, caspase activation, and DNA fragmentation. Furthermore, this study reveals that these events were completely abrogated in cells exposed to Abeta peptides in which methionine 35 was substituted by a norleucine residue. CONCLUSIONS On the basis of the results obtained in this study, an additional hypothesis involving the amyloid-beta peptide and the role of Met-35 has been proposed to clarify the mechanisms responsible of neurodegeneration in Alzheimer's disease.