Miracle-dz/UniFAR-FTUs huggingface dataset:
Magnetic Resonance Imaging of Iron Deposition in Neurological Disorders

Deposition of iron in the brain is proposed to play a role in the pathophysiology of the normal aging process and neurodegenerative diseases. Whereas iron is required for normal neuronal metabolism, excessive levels can contribute to the formation of free radicals, leading to lipid peroxidation and neurotoxicity. Magnetic resonance imaging (MRI) is a powerful tool to detect excessive iron in the brain and longitudinally monitor changes in iron levels. Iron deposition is associated with a reduction in the T2 relaxation time, leading to hypointensity on spin-echo and gradient-echo T2-weighted images. The MRI changes associated with iron deposition have been observed both in normal aging and in various chronic neurological diseases, including multiple sclerosis, Alzheimer disease, and Parkinson disease. Magnetic resonance imaging metrics providing information about iron concentrations include R2, R2&vprime;, and R2*. The purpose of this review is to discuss the role of iron and its detection by MRI in various neurological disorders. We will review the basic biochemical properties of iron and its influence on MRI signal. We will also summarize the sensitivity and specificity of MRI techniques in detecting iron. The MRI and pathological findings pertaining to brain iron will be reviewed with respect to normal aging and a variety of neurological disorders. Finally, the biochemistry and pathophysiology surrounding iron, oxidative stress, free radicals, and lipid peroxidation in the brain will be discussed, including therapeutic implications. The potential role of iron deposition and its assessment by MRI provides exciting potential applications to the diagnosis, longitudinal monitoring, and therapeutic development for disorders of the brain.
Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas

An Eye on Metastasis Despite the considerable progress being made in elucidating the cell biology of metastasis, little is known about the genetic alterations that promote metastasis of human tumors, the cause of most cancer deaths. A potentially important clue now emerges from the work of Harbour et al. (p. 1410, published online 4 November), who used an exome-sequencing approach to search for genetic mutations in uveal melanomas, an eye cancer associated with a high rate of fatal metastasis. Remarkably, over 80% of tumor samples with a high metastatic risk had inactivating somatic mutations in the gene encoding BAP1 (BRCA1-associated protein 1), a nuclear protein involved in controlling protein degradation. Thus, in this tumor type, mutational inactivation of BAP1 may be a key event in the acquisition of metastatic competence. A gene implicated in the control of protein degradation is mutated at high frequency in a metastatic eye cancer. Metastasis is a defining feature of malignant tumors and is the most common cause of cancer-related death, yet the genetics of metastasis are poorly understood. We used exome capture coupled with massively parallel sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination and 5 affecting its ubiquitin carboxyl-terminal hydrolase domain. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest that the BAP1 pathway may be a valuable therapeutic target.
Simple method for the culture of glial cells from embryonic rat brain: Implications for regional heterogeneity and the radial glial lineage

A simple method is described for the production of glial cell cultures from specific regions of the day 13–15 embryonic rat brainstem and midbrain based on differential cell attachment to a relatively nonadhesive substrate, which inhibits the growth of neurons. Regional differences in the ability of specific populations of brainstem and midbrain cells to attach and spread on the substrate suggest that embryonic glial populations may differ in their cell surface properties even when they derive from the same general area of the developing brain. Based on observations of the spatiotemporal distribution of radial‐like glial cells and astrocytes with time in vitro, we suggest that this culture system may prove useful for investigation of the radial glial lineage.
Posttraumatic Morbidity of a Disaster: A Study of Cases Presenting for Psychiatric Treatment

The study of unsolicited psychiatric patients who became ill because of their experience in a natural disaster can assist in the design of future disaster research. A clinical report of 36 such patients illustrates the problems of case detection, the delayed presentation of much of the morbidity, and the need to separate stress-related symptoms which are common in disaster victims from psychiatric illness. Unless these issues are taken into account, estimates of the prevalence of psychiatric disorders after major disasters may be subject to substantial error. The role of vulnerability factors assessed to be operating in these patients suggests that exposure and losses sustained in the disaster alone are inadequate predictors of psychiatric disorder. The risk factors for the development of disaster-related psychiatric morbidity will be more accurately defined if the contribution of a range of constitutional, personality, and social factors as well as the personal impact of the disaster are investigated in future research.
Cyclosporin A renders target cells resistant to immune cytolysis

Exposure of cytolytically susceptible human target cells with therapeutic concentrations of the immunosuppressive drug cyclosporin A renders these cells highly resistant to T cell‐mediated, natural killer (NK) cell‐mediated, and complement‐mediated cytolysis. The resistance is dose dependent, time dependent and reversible. The resistance is accompanied by target cell growth inhibition as measured by thymidine uptake. Surprisingly, target cell growth inhibition induced by serum depletion is associated with cell‐mediated cytolytic resistance. These data suggest that cyclosporin A (CsA) may block some target cell biochemical pathway(s) important in the suicidal cytolytic process which is (are) linked to some G0/G1 cell cycle events. In addition, these results suggest that the increased risk of Epstein‐Barr virus (EBV)‐associated lymphoproliferative disease in human organ transplant recipients may be contributed to by CsA‐induced resistance of EBV‐transformed B lymphocytes to immune cytolysis.
Toll-like receptors: an overview from invertebrates to vertebrates

Toll-like receptors (TLRs) are membrane glycoproteins consisting of an ectodomain, encompassing tandem LRRs (leucine-rich repeats), a membrane spanning segment and a globular cytoplasmic Toll/Interleukin-1 Receptor (TIR) domain. They detect microbes on the basis of conserved Pathogen-Associated Molecular Patterns (PAMPs). TLRs share molecular architecture and common ancestors with arthropod Toll molecules, which show a dual role, in the dorsoventral patterning of the embryo, and in the immune response to fungal infections in the adult. During the metazoan evolution Toll/TLRs modified the number and the arrangment of LRRs (protostome- and vertebrate-type), the localization of the loops interacting with different ligands, the ability to reside in the cellular or endosomal membrane and the complexity of the signaling pathway. The evolutionary mechanisms of Toll/TLR gene diversification included gene duplication, retrotranscription, high gene expansion rate within species, and alternative splicing of the transcripts. The aim of this review is to supply a schematic representation of a very complex, but still, fascinating story.
Complementary/alternative medicine in gynecology: no simple messages please!

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Keloid Pathogenesis and Treatment

Background: Keloid management can be difficult and frustrating, and the mechanisms underlying keloid formation are only partially understood. Methods: Using original and current literature in this field, this comprehensive review presents the major concepts of keloid pathogenesis and the treatment options stemming from them. Results: Mechanisms for keloid formation include alterations in growth factors, collagen turnover, tension alignment, and genetic and immunologic contributions. Treatment strategies for keloids include established (e.g., surgery, steroid, radiation) and experimental (e.g., interferon, 5-fluorouracil, retinoid) regimens. Conclusion: The scientific basis and empiric evidence supporting the use of various agents is presented. Combination therapy, using surgical excision followed by intradermal steroid or other adjuvant therapy, currently appears to be the most efficacious and safe current regimen for keloid management.
Antibody‐Mediated Rejection in Kidney Transplantation: A Review of Pathophysiology, Diagnosis, and Treatment Options

Antibody‐mediated rejection (AMR), also known as B‐cell–mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently. With an improved understanding about the importance of the development of antibodies against allografts as well as complement activation, significant advances have occurred in the treatment of AMR. The standard of care for AMR includes plasmapheresis and intravenous immunoglobulin that remove and neutralize antibodies, respectively. Agents targeting B cells (rituximab and alemtuzumab), plasma cells (bortezomib), and the complement system (eculizumab) have also been used successfully to treat AMR in kidney transplant recipients. However, the high cost of these medications, their use for unlabeled indications, and a lack of prospective studies evaluating their efficacy and safety limit the routine use of these agents in the treatment of AMR in kidney transplant recipients.
TRIM28 mediates primer binding site-targeted silencing of Lys1,2 tRNA-utilizing retroviruses in embryonic cells

Murine leukemia viruses (MLVs) and related retroelements are potently restricted in embryonic cells by postintegration transcriptional silencing, likely to protect the germ line from insertional mutagenesis. This silencing is in large part attributable to the presence of a nuclear repression complex, which targets a sequence element of the proviral DNA, the repressor-binding site. The repressor-binding site closely overlaps the tRNA primer binding site, a highly conserved sequence essential for virus replication and defining the site of initiation of DNA synthesis during reverse transcription. We have recently demonstrated that the cellular corepressor TRIM28 is recruited to the proline tRNA primer-binding site used by many MLVs and is required to mediate this silencing. Here, we show that TRIM28 is also required for the restriction of retroviruses using a completely distinct tRNA for the priming of their DNA synthesis, namely Lys-1,2 tRNA. These results generalize the role of TRIM28 in retroviral restriction and suggest that this system has evolved to restrict multiple retroviruses.
A Method for Generating Arbitrary Optical Signal Constellations Using Direct Digital Drive

A digitally operated optical quadrature-amplitude modulation (QAM) modulator based on a single multielectrode Mach-Zehnder modulator is presented. Generation and performance of 64QAM are studied in detail. Simulation results show that a single modulator with 13 electrodes, each of which is driven by either one of the voltages 0 or 1.68 vπ, provides close-to-ideal 64QAM constellation despite the inherent nonlinearity of the modulator. Moreover, employing a sufficient number of electrodes, close to ideal error performance can be obtained for any constellation order, or shape. Simulations results are demonstrated for several different square constellations: 16QAM and 256QAM, and nonsquare constellations: 32QAM and 128QAM. A brief discussion on the utilization of the proposed scheme as a predistorter is also given.
A hybrid localization system in wireless sensor networks

Position information is of vital importance in the various applications in wireless sensor networks (WSNs). We analyze the features of localization methods considering both precision and energy consumption and propose the idea of hybrid localization system (HLS). HLS is composed of coarse-grained localization system (CGLS) and fine-grained localization system (FGLS). CGLS takes the wireless signal strength as the reference for distance and gets the rough area a unknown node located. According to the trade-off of position precision and energy consumption, FGLS is in charge of location refinement that takes image to localize the unknown node. The experiment results show that the proposed HLS can achieve high position precision and low energy consumption.
ADAMTS13 activity is decreased in a septic porcine model

Summary During sepsis, the balance between abundantly secreted von Wille-brand factor (VWF) and the activity of its size regulating protease ADAMTS13 is assumed to be involved in coagulation abnormalities. We aimed to establish a porcine model with haemorrhagic shock with consecutive sepsis and hypothesised that a decreased ADAMTS13-activity as well as an altered VWF multimer pattern is associated with renal failure. Animals (n=21) were subjected to haemorrhagic shock. After volume replacement, intraperitoneal Escherichia coli sepsis was induced. Blood samples were drawn at baseline, after haemorrhage and sepsis induction. Directly postmortem we examined renal tissue by JONES-silver, CD61, VWF and fibrin staining for characterisation of thrombi. Renal failure was analysed by scoring PAS-stained sections for acute tubular damage. Glomerular microthrombi were observed in six of 21 septic animals. Porcine ADAMTS13 activity declined significantly during sepsis, accompanied by a drop-off in platelet count. At 12 hours after sepsis induction, ADAMTS13 activity was significantly diminished compared to sham controls, and an elevated acute tubular damage score was associated with an increased proportion of high-molecular-weight VWF multimers. Compared to baseline the proportion of high-molecular-weight VWF multimers increased significantly in septic animals. Similar to human sepsis, diminished ADAMTS13 activity was observed in a septic porcine model associated with a shift to rather thrombogenic VWF multimers and deposition of microthrombi. Therefore, this porcine model seems to be appropriate for performing functional and therapeutic studies in sepsis-associated ADAMTS13 deficiency.
Concurrent fNIRS-fMRI measurement to validate a method for separating deep and shallow fNIRS signals by using multidistance optodes

Abstract. It has been reported that a functional near-infrared spectroscopy (fNIRS) signal can be contaminated by extracerebral contributions. Many algorithms using multidistance separations to address this issue have been proposed, but their spatial separation performance has rarely been validated with simultaneous measurements of fNIRS and functional magnetic resonance imaging (fMRI). We previously proposed a method for discriminating between deep and shallow contributions in fNIRS signals, referred to as the multidistance independent component analysis (MD-ICA) method. In this study, to validate the MD-ICA method from the spatial aspect, multidistance fNIRS, fMRI, and laser-Doppler-flowmetry signals were simultaneously obtained for 12 healthy adult males during three tasks. The fNIRS signal was separated into deep and shallow signals by using the MD-ICA method, and the correlation between the waveforms of the separated fNIRS signals and the gray matter blood oxygenation level–dependent signals was analyzed. A three-way analysis of variance (signal depth×Hb kind×task) indicated that the main effect of fNIRS signal depth on the correlation is significant [F(1,1286)=5.34, p<0.05]. This result indicates that the MD-ICA method successfully separates fNIRS signals into spatially deep and shallow signals, and the accuracy and reliability of the fNIRS signal will be improved with the method.
Optimal adaptive multiuser detection in unknown multipath channels

An optimal multiuser detector in the weighted least squares (WLS) sense is derived. This detector, which includes the maximum likelihood multiuser detector as a special case, consists of two parts: a bank of linear fractionally chip spaced minimum mean squared error (MMSE) filters, and a nonlinear WLS metric minimizer. It is shown that the symbol spaced samples at the output of the MMSE filter bank provide a set of sufficient statistics for WLS detection. The relationship between the taps of a centralized decision feedback detector and the MMSE filter bank is derived. It is proven that all the necessary parameters for implementing the WLS detector can be realized by adaptively training a centralized decision feedback detector. Therefore, the WLS detector achieves optimal joint synchronization and data detection even in the presence of colored noise, such as narrowband interference, without any a priori knowledge of the users' signatures, multipath channel taps or statistics of the colored noise. Significant features of the WLS detector are that: (1) the WLS detector is a generalization of the maximum likelihood multiuser detector that employs a bank of matched filters; (2) it is implemented adaptively; and (3) it has structural flexibility in terms of implementation complexity.
Functional roles of superoxide and hydrogen peroxide generated by mitochondrial DNA mutation in regulating tumorigenicity of HepG2 cells

Mitochondria are a major source of reactive oxygen species (ROS). Recent studies have estimated that mitochondrial DNA mutations inducing the overproduction of ROS are associated with human cancer. However, a substantial challenge in elucidating their diverse roles in regulating tumorigenesis is the lack of methods for probing ROS in living systems with molecular specificity. In this study, we reported the application of two fluorescent probes, 2‐chloro‐1,3‐dibenzothiazolinecyclohexene and naphthofluorescein disulfonate, which showed high selectivity for superoxide (O2•−) and hydrogen peroxide (H2O2). They were capable of detecting and visualizing O2•− and H2O2 overproduction caused by a mutation in the gene encoding nicotinamide adenine dinucleotide dehydrogenase subunit 6 (ND6) in HepG2 cells. The levels of O2•− and H2O2 in mitochondria isolated from HepG2 cells were found to be 0·63 ± 0·07 and 1·13 ± 0·05 μM, respectively. Using assays of tumorigenesis in mouse models, we found that treatment of the mice with different ROS scavengers suppressed tumour growth. These findings suggested that ROS generated by ND6 gene mutation do play an important role in regulating tumorigenesis and H2O2 may be a key modulator. Copyright © 2011 John Wiley & Sons, Ltd.
Leveraging Social Network Data for Analytical CRM Strategies - the Introduction of Social Bi

The skyrocketing trend for social media on the Internet greatly alters analytical Customer Relationship Management (CRM). Against this backdrop, the purpose of this paper is to advance the conceptual design of Business Intelligence (BI) systems with data identified from social networks. We develop an integrated social network data model, based on an in-depth analysis of Facebook. The data model can inform the design of data warehouses in order to offer new opportunities for CRM analyses, leading to a more consistent and richer picture of customers? characteristics, needs, wants, and demands. Four major contributions are offered. First, Social CRM and Social BI are introduced as emerging fields of research. Second, we develop a conceptual data model to identify and systematize the data available on online social networks. Third, based on the identified data, we design a multidimensional data model as an early contribution to the conceptual design of Social BI systems and demonstrate its application by developing management reports in a retail scenario. Fourth, intellectual challenges for advancing Social CRM and Social BI are discussed.
Reliability-aware design automation flow for analog circuits

Manually designing analog circuits is often considered as a difficult task that takes a lot of time. If a design automation environment is available for analog circuits, it is useful for designers to cope with the increasing challenges in advance process. In this paper, a reliability-aware circuit sizing technique is proposed to consider process variation, circuit aging, and layout-dependent effects simultaneously. A reliability-aware analog layout automation technique is also proposed to consider both placement and routing while improving the reliability of the generated layout. These reliability-aware design automation techniques have been integrated to build a complete synthesis environment from specifications to layout. As shown in the experimental results, the proposed automation flow does help designers solve the reliability issues efficiently.