Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells

Ammonia is a toxic by-product of metabolism that causes cellular stresses. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism to survive against its toxicity have yet to be identified. We demonstrated that the hypoxia-inducible factor-1α (HIF-1α) is stabilized and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1α counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1α in a biphasic ammonia stress management in the cancer stem-like cells where GS facilitates cell proliferation and HIF-1α contributes to the metabolic remodeling in energy fuel usage resulting in attenuated proliferation but conversely promoting cell survival.
Analysis of weekend effect on 30-day mortality among patients with acute myocardial infarction

Objectives Several publications have demonstrated increased 30-day mortality in patients admitted on Saturdays or Sundays compared with weekdays. We sought to determine whether this was true for two different cohorts of patients admitted with acute myocardial infarction (MI). Methods and results Thirty-day mortality data were obtained for 3757 patients who had been admitted to the Belfast Health and Social Care Trust with acute MI between 2009 and 2015. They were subdivided into those presenting with ST elevation MI (n=2240) and non-ST elevation MI (n= 1517). We observed no excess 30-day mortality in those admitted over weekends. Conclusion Excess mortality in patients admitted at weekends is not a universal finding. This may mean that that there are patient subgroups with proportionately greater weekend hazard and points to the need for more detailed understanding of the weekend effect.
An Empirical Study of Cohesion and Coupling: Balancing Optimization and Disruption

Search-based software engineering has been extensively applied to the problem of finding improved modular structures that maximize cohesion and minimize coupling. However, there has, hitherto, been no longitudinal study of developers’ implementations, over a series of sequential releases. Moreover, results validating whether developers respect the fitness functions are scarce, and the potentially disruptive effect of search-based remodularization is usually overlooked. We present an empirical study of 233 sequential releases of ten different systems; the largest empirical study reported in the literature so far, and the first longitudinal study. Our results provide evidence that developers do, indeed, respect the fitness functions used to optimize cohesion/coupling (they are statistically significantly better than arbitrary choices with ${p\ll 0.01}$ ), yet they also leave considerable room for further improvement (cohesion/coupling can be improved by 25% on average). However, we also report that optimizing the structure is highly disruptive (on average more than 57% of the structure must change), while our results reveal that developers tend to avoid such disruption. Therefore, we introduce and evaluate a multiobjective (MO) evolutionary approach that minimizes disruption while maximizing cohesion/coupling improvement. This allows developers to balance reticence to disrupt existing modular structure, against their competing need to improve cohesion and coupling. The MO approach is able to find modular structures that improve the cohesion of developers’ implementations by 22.52%, while causing an acceptably low level of disruption (within that already tolerated by developers).
Typology of “Fatigue” by Heart Rate Variability Analysis in Elite Nordic-skiers

Abstract This study investigated changes in heart rate variability (HRV) in elite Nordic-skiers to characterize different types of “fatigue” in 27 men and 30 women surveyed from 2004 to 2008. R-R intervals were recorded at rest during 8 min supine (SU) followed by 7 min standing (ST). HRV parameters analysed were powers of low (LF), high (HF) frequencies, (LF+HF) (ms2) and heart rate (HR, bpm). In the 1 063 HRV tests performed, 172 corresponded to a “fatigue” state and the first were considered for analysis. 4 types of “fatigue” (F) were identified: 1. F(HF−LF−)SU_ST for 42 tests: decrease in LFSU (− 46%), HFSU (− 70%), LFST (− 43%), HFST (− 53%) and increase in HRSU (+ 15%), HRST (+ 14%). 2. F(LF+ SULF− ST) for 8 tests: increase in LFSU (+ 190%) decrease in LFST (− 84%) and increase in HRST (+ 21%). 3. F(HF− SUHF+ ST) for 6 tests: decrease in HFSU (− 72%) and increase in HFST (+ 501%). 4. F(HF+ SU) for only 1 test with an increase in HFSU (+ 2161%) and decrease in HRSU (− 15%). Supine and standing HRV patterns were independently modified by “fatigue”. 4 “fatigue”-shifted HRV patterns were statistically sorted according to differently paired changes in the 2 postures. This characterization might be useful for further understanding autonomic rearrangements in different “fatigue” conditions.
Lyme Borreliosis in Human Patients in Florida and Georgia, USA

The aim of this study was to determine the cause of illness in several human patients residing in Florida and Georgia, USA, with suspected Lyme disease based upon EM-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. Using polymerase chain reaction (PCR) assays developed specifically for Lyme group Borrelia spp. , followed by DNA sequencing for confirmation, we identified Borrelia burgdorferi sensu lato DNA in samples of blood and skin and also in lone star ticks (Amblyomma americanum) removed from several patients who either live in or were exposed to ticks in Florida or Georgia. This is the first report to present combined PCR and DNA sequence evidence of infection with Lyme Borrelia spp. in human patients in the southern U.S., and to demonstrate that several B. burgdorferi sensu lato species may be associated with Lyme disease-like signs and symptoms in southern states. Based on the findings of this study, we suggest that human Lyme borreliosis occurs in Florida and Georgia, and that some cases of Lyme-like illness referred to as southern tick associated rash illness (STARI) in the southern U.S. may be attributable to previously undetected B. burgdorferi sensu lato infections.
Endothelial Progenitor Cells and Endothelial Vesicles – What Is the Significance for Patients with Chronic Kidney Disease?

Endothelial progenitor cells are cells derived from the bone marrow that circulate in the bloodstream and can exhibit phenotypic characteristics of endothelial cells. They are thought to be involved in postnatal vasculogenesis and to potentially help repair injured endothelium. Circulating endothelial cells are mature endothelial cells in the circulation, and endothelial vesicles or microparticles are thought to be derived from the membranes of endothelial cells as a result of injury or activation. Recent research has focused on using these markers of endothelial injury and repair to assess the state of endothelial health. These efforts have been hampered by lack of uniformity in methodology and terminology. Recent developments in flow cytometry techniques have allowed better characterization and definition of these cells. We review the common techniques used to identify and isolate these cells, clinical studies in patients with chronic kidney disease (CKD) where they serve as markers of endothelial health and predictors of outcome, and possible mechanisms of progenitor cell dysfunction in CKD.
Sensitivity and specificity of the high fluorescent lymphocyte count-gate on the Sysmex XE-5000 hematology analyzer for detection of peripheral plasma cells

Abstract Background: Plasma cells are one of the end products of the B-lymphocyte mediated immune response. These cells normally reside in the bone marrow or some peripheral lymphoid tissues. Increased numbers of plasma cells in the blood, usually indicates pathology such as infection, auto-immunity or haematological malignancy. Therefore, the ability to measure plasma cells (PCs) on an automated cell analyzer might be advantageous. Methods: The performance of the Sysmex XE-5000 leukocyte differential channel [high fluorescent lymphocyte count (HFLC) area] was evaluated for the ability to detect plasma cells in peripheral blood and compared to the detection of plasma cells by flow cytometric analyses. Results: Our results show that the HFL count from the XE-5000 correlates (R2=0.8) with the number of PCs in peripheral blood, but detects PCs with moderate to good sensitivity (88.9%) and specificity (87.8%). Conclusions: The Sysmex XE-5000 is suitable for screening blood samples for the presence of elevated number of plasma cells in peripheral blood, but the actual quantification needs to be confirmed by flow cytometry.
Active pointing control for short range free-space optical communication

Maintaining optical alignment between stations of a free-space optical link requires an active pointing mechanism to persistently aim an optical beam toward the receiving station with an acceptable accuracy. This mechanism ensures delivery of maximum optical power to the receiving station in spite of the relative motion of the stations. In the active pointing scheme proposed in the present paper, the receiving station estimates the center of the incident optical beam based on the output of a position-sensitive photodetector. The transmitting station receives this estimate via an independent communication link and uses it to accurately aim at the receiving station. The overall mechanism which implements this scheme can be described in terms of a diffusion process which modulates the rate of a doubly stochastic space-time Poisson process. At the receiving station, observation of the space-time process over a subset of R 2 is provided in order to control the diffusion process. Our goal is to determine a control law, measurable with respect to the history of the space-time process, which minimizes a quadratic cost functional.
Multiple-part cyclic hoist scheduling using a sieve method

The paper proposes an algorithm for generating optimal cyclic schedules of hoist moves in a printed circuit board electroplating facility where transportation of parts between workstations is performed by a computer-controlled hoist. The objective of the scheduling problem is to maximize the throughput rate. Unlike many previous algorithms which consider 1-part cyclic schedules, the proposed algorithm provides an exact solution for the more complicated case of r-part cyclic schedules where r>1. The algorithm is illustrated with numerical examples comparing 1-part and multiple-part optimal schedules.
Dual Regulation of Diacylglycerol Kinase (DGK)-θ

Background: Diacylglycerol kinases are important regulators of signaling diacylglycerol, but regulation of enzymatic activity is unclear. Results: DGK-θ activity, but not vesicle binding, is dependent on a polybasic protein for substrate binding and an acidic phospholipid for high turnover rates. Conclusion: DGK-θ vesicle association and catalytic activity are independently regulated. Significance: Polybasic proteins and acidic phospholipids stimulate DGK-θ substrate binding and catalytic activity. Diacylglycerol kinases are important mediators of lipid signaling cascades, and insight into their regulation is of increasing interest. Using purified DGK-θ, we show that this isoform is subject to dual regulation and that the previously characterized stimulation by acidic phospholipids is dependent on the presence of a positively charged protein or peptide. Polybasic cofactors lowered the Km for diacylglycerol at the membrane surface (Km(surf)), and worked synergistically with acidic phospholipids to increase activity 10- to 30-fold, suggesting that the purified enzyme is autoinhibited. Vesicle pulldown studies showed that acidic phospholipids recruit polybasic cofactors to the vesicle surface but have little effect on the membrane association of DGK-θ, suggesting that a triad of enzyme, acidic lipid and basic protein are necessary for interfacial activity. Importantly, these data demonstrate that the interfacial association and catalytic activity of DGK-θ are independently regulated. Finally, we show that DGK-θ directly interacts with, and is activated by, basic proteins such as histone H1 and Tau with nm affinity, consistent with a potential role for a polybasic protein or protein domain in the activation of this enzyme.
The D‐lactate dehydrogenase MoDLD1 is essential for growth and infection‐related development in Magnaporthe oryzae

Rice blast disease caused by Magnaporthe oryzae is initiated by the attachment of conidia to plant surfaces. Germ tubes emerging from conidia develop melanized appressoria to physically penetrate the host surface. Previous studies revealed that appressorium development requires the breakdown of storage lipids and glycogen that occur in peroxisomes and the cytosol respectively, culminating in production of pyruvate. However, the downstream product(s) entering the mitochondria for further oxidation is unclear. In this study, we aimed to investigate the molecular basis underlying the metabolic flux towards the mitochondria associated with the infectious-related development in M. oryzae. We showed that D-lactate is a key intermediate metabolite of the mobilization of lipids and glycogen, and its oxidative conversion to pyruvate is catalysed by a mitochondrial D-lactate dehydrogenase MoDLD1. Deletion of MoDLD1 caused defects in conidiogenesis and appressorium formation, and subsequently the loss of fungal pathogenicity. Further analyses demonstrated that MoDLD1 activity is involved in the maintenance of redox homeostasis during conidial germination. Thus, MoDLD1 is a critical modulator that channels metabolite flow to the mitochondrion coupling cellular redox state, and contributes to development and virulence of M. oryzae.
An Image Inpainting Technique Based on the Fast Marching Method

Abstract Digital inpainting provides a means for reconstruction of small damaged portions of an image. Although the inpainting basics are straightforward, most inpainting techniques published in the literature are complex to understand and implement. We present here a new algorithm for digital inpainting based on the fast marching method for level set applications. Our algorithm is very simple to implement, fast, and produces nearly identical results to more complex, and usually slower, known methods. Source code is available online.
Components of the Basal Lamina and Dystrophin–Dystroglycan Complex in the Neurointermediate Lobe of Rat Pituitary Gland: Different Localizations of β-Dystroglycan, Dystrobrevins, α1-Syntrophin, and Aquaporin-4

The so-called neurointermediate lobe is composed of the intermediate and neural lobes of the pituitary. The present immunohistochemical study investigated components of the basal lamina (laminin, agrin, and perlecan), the dystrophin–dystroglycan complex (dystrophin, β-dystroglycan, α1-dystrobrevin, β-dystrobrevin, utrophin, and α1-syntrophin), and the aquaporins (aquaporin-4 and −9). Glia markers (GFAP, S100, and glutamine synthetase) and components of connective tissue (collagen type I and fibronectin) were also labeled. In the neurohypophysis, immunostaining of basal lamina delineated meningeal invaginations. In these invaginations, vessels were seen to penetrate the organ without submerging into its parenchyma. On the parenchymal side of the invaginations, β-dystroglycan was detected, whereas utrophin was detected in the walls of vessels. Immunostaining of α1-dystrobrevin and α1-syntrophin did not delineate the vessels. The cells of the intermediate lobe were fully immunoreactive to α1-dystrobrevin and α1-syntrophin, whereas components of the basal lamina delineated the contours of the cells. GFAP-immunoreactive processes surrounded them. Aquaporin-4 localized at the periphery of the neurohypophysis, mainly adjacent to the intermediate lobe but not along the vessels. It colocalized only partially with GFAP and not at all with α1-syntrophin. Aquaporin-9 was not detected. These results emphasize the possibility that the components of the dystrophin–dystroglycan complex localize differently and raise the question about the roles of dystrobrevins, α1-syntrophin, and aquaporin-4 in the functions of the intermediate and neural lobes, respectively.
The Individual Within the Group: Balancing the Need to Belong With the Need to Be Different

Many theorists have wrestled with the notion of how people balance their need to be included in social groups with their need to be different and distinctive. This question is particularly salient to researchers from the social identity perspective, who have traditionally viewed individual differentiation within groups as being inimical to group identification. In this article we present a number of strategies that people can use to balance their need to belong and their need to be different, without violating social identity principles. First, drawing from optimal distinctiveness theory, we discuss 4 ways in which the need for belonging and the need to be different can be resolved by maximizing group distinctiveness. We then discuss 4 ways in which it is possible to achieve individual differentiation within a group at the same time demonstrating group identification. These strategies are discussed and integrated with reference to recent empirical research and to the social identity perspective.
Efficient Computation of Reverse Skyline Queries

In this paper, for the first time, we introduce the concept of Reverse Skyline Queries. At first, we consider for a multidimensional data set P the problem of dynamic skyline queries according to a query point q. This kind of dynamic skyline corresponds to the skyline of a transformed data space where point q becomes the origin and all points of P are represented by their distance vector to q. The reverse skyline query returns the objects whose dynamic skyline contains the query object q. In order to compute the reverse skyline of an arbitrary query point, we first propose a Branch and Bound algorithm (called BBRS), which is an improved customization of the original BBS algorithm. Furthermore, we identify a super set of the reverse skyline that is used to bound the search space while computing the reverse skyline. To further reduce the computational cost of determining if a point belongs to the reverse skyline, we propose an enhanced algorithm (called RSSA) that is based on accurate pre-computed approximations of the skylines. These approximations are used to identify whether a point belongs to the reverse skyline or not. Through extensive experiments with both real-world and synthetic datasets, we show that our algorithms can efficiently support reverse skyline queries. Our enhanced approach improves reversed skyline processing by up to an order of magnitude compared to the algorithm without the usage of pre-computed approximations.
Professional ethics in complementary and alternative medicines in management of Parkinson’s disease

The practice of complementary and alternative medicine (CAM) is not, at present, considered an integral part of conventional medicine. As the popularity of CAM grows and access to information about CAM increases through the media and internet where CAMs are often promoted, patients are at risk of exposure unvalidated information. Therefore, there is a need for physicians to examine objectively the efficacy and safety of CAM, compare it with current medications, and become actively involved in the CAM treatment with patients. In accordance with these needs, this manuscript reviews the utility, scientific evidence, safety and cost-effectiveness of CAM in the treatment of Parkinson’s disease (PD). We also address the ethical issues of CAM practices.
Substrate noise analysis and techniques for mitigation in mixed-signal RF systems

Mixed-signal circuit design has historically been a challenge for several reasons. Parasitic interactions between analog and digital systems on a single die are one such challenge. Switching transients induced by digital circuits inject noise into the common substrate creating substrate noise. Analog circuits lack the large noise margins of digital circuits, thus making them susceptible to substrate voltage variations. This problem is exacerbated at higher frequencies as the effectiveness of standard isolation technique diminishes considerably. Historically, substrate noise was not a problem because each system was fabricated in its own package shielding it from such interactions. The work in this thesis spans all areas of substrate noise: generation, propagation, and reception. A set of guidelines in designing isolation structures was developed to assist designers in optimizing these structures for a particular application. Furthermore, the effect of substrate noise on two key components of the RF front end, the voltage controlled oscillator (VCO) and the low noise amplifier (LNA), was analyzed. Finally, a CAD tool (SNAT) was developed to efficiently simulate large digital designs to determine substrate noise performance. Existing techniques have prohibitively long simulation times and are only suitable for final verification. Determination of substrate noise coupling during the design phase would be extremely beneficial to circuit designers who can incorporate the effect of the noise and re-design accordingly before fabrication. This would reduce the turn around time for circuits and prevent costly redesign. SNAT can be used at any stage of the design cycle to accurately predict (less than 12% error when compared to measurements) the substrate noise performance of any digital circuit with a large degree of computational efficiency. Thesis Supervisor: Anantha P. Chandrakasan Title: Professor of Electrical Engineering and Computer Science Thesis Supervisor: Rafael Reif Title: Department Head/Professor of Electrical Engineering and Computer Science
The Priming of Face Recognition after Metric Transformations

Four experiments were performed to test whether the perceptual priming of face recognition would show invariance to changes in size, position, reflectional orientation (mirror reversal), and picture-plane rotation. In all experiments, subjects recognized faces in two blocks of trials; in the second block, some of the faces were identical to those in the first, and others had undergone metric transformations. The results show that subjects were equally fast to recognize faces whether or not the faces had changed in size, position, or reflectional orientation between the first and second presentations of the faces. In contrast, subjects were slower to recognize both faces and objects when they were planar-rotated between the first and second presentations. The results suggest that the same metric invariances are shown by both face recognition and basic-level object recognition.