Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural correlates of fear: insights from neuroimaging

Fear anticipates a challenge to one's well-being and is a reaction to the risk of harm. The expression of fear in the individual is a constellation of physiological, behavioral, cogni- tive, and experiential responses. Fear indicates risk and will guide adaptive behavior, yet fear is also fundamental to the symptomatology of most psychiatric disorders. Neuroimaging studies of normal and abnormal fear in humans extend knowledge gained from animal experiments. Neuroimaging permits the empirical evaluation of theory (emotions as response tendencies, mental states, and valence and arousal dimensions), and improves our understanding of the mechanisms of how fear is controlled by both cognitive processes and bodily states. Within the human brain, fear engages a set of regions that include insula and anterior cingulate cortices, the amygdala, and dorsal brain-stem centers, such as periaqueductal gray matter. This same fear matrix is also implicated in attentional orienting, mental planning, interoceptive mapping, bodily feelings, novelty and motivational learning, behavioral prioritization, and the control of autonomic arousal. The stereotyped expression of fear can thus be viewed as a special construc- tion from combinations of these processes. An important motivator for understanding neural fear mechanisms is the debilitating clinical expression of anxiety. Neuroimaging studies of anxiety patients highlight the role of learning and memory in pathological fear. Posttraumatic stress disorder is further distinguished by impairment in cognitive control and contextual memory. These processes ultimately need to be targeted for symptomatic recovery. Neuroscientific knowledge of fear has broader relevance to understanding human and societal behavior. As yet, only some of the insights into fear, anxiety, and avoidance at the individual level extrapolate to groups and populations and can be meaningfully applied to economics, prejudice, and politics. Fear is ultimately a contagious social emotion.
Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma.

PURPOSE We tested the hypothesis that the combination of tremelimumab and interferon alfa-2b acting via different and possibly synergistic mechanisms would overcome tumor immune tolerance and lead to significant and durable clinical responses. PATIENTS AND METHODS We conducted a phase II study in which patients were administered tremelimumab 15 mg/kg/course (three cycles [one cycle = 4 weeks]) intravenously every 12 weeks. High-dose interferon alfa-2b (HDI) was administered concurrently, including intravenous induction at 20 MU/m2/d for 5 d/wk for 4 weeks followed by maintenance at 10 MU/m2/d subcutaneously three times a week for 8 weeks per course. From course 2 onward, HDI maintenance was administered subcutaneously. RESULTS Thirty-seven patients with American Joint Committee on Cancer stage IV (9M1a, 6M1b, and 22M1c) were enrolled. Two patients had previously treated brain metastases. Grades 3 and 4 toxicities included neutropenia (six patients; 17%), diarrhea/colitis (four patients; 11%), liver enzyme increase (four patients; 11%), rash (four patients; 11%), fatigue (15 patients; 40%), and anxiety/depression (five patients; 14%). Response data were available for 35 patients. The best objective response rate (RR; Response Evaluation Criteria in Solid Tumors) by intention to treat was 24% (90% CI, 13% to 36%; four complete responses [CRs] and five partial responses [PRs] that lasted 6, 6, > 12, > 14, > 18, 20, > 28, 30, and > 37 months, respectively). Fourteen patients (38%) had stable disease (SD) that lasted 1.5 to 21 months. The median progression-free survival was 6.4 months (95% CI, 3.3 to 12.1 months). The median overall survival (OS) was 21 months (95% CI, 9.5 to not reached). There was a weak association between therapy-induced autoimmunity and clinical benefits (CR/PR/SD; P = .0059), baseline C-reactive protein (CRP) less than or equal to 2.7× the upper limit of normal and clinical benefits (P = .0494) and improved probability of survival (P = .0032), and baseline lymphocyte count of at least 1,000/μL and response (CR/PR; P = .0183) and clinical benefits (CR/PR/SD; P = .0255). Biomarker associations were not significant after adjustment for multiple comparisons. CONCLUSION HDI can be administered combined with tremelimumab with acceptable toxicity and promising durable antitumor efficacy that warrant further testing in a randomized trial.
Toward the development of a universal grading system for ovarian epithelial carcinoma

Most published series of ovarian carcinoma find a correlation between histologic grade and survival, but the grading system used commonly is not specified, and several different systems exist, some of which use different criteria for different histologic types. However, several studies have shown marked interobserver variability in distinguishing among the histologic types of ovarian carcinoma. The authors attempted to derive a universal grading system for all invasive ovarian carcinomas (IOC), based on the Nottingham system for grading all types of mammary carcinoma.
Association between short-term exposure to ultrafine particles and hospital admissions for stroke in Copenhagen, Denmark.

AIMS The relevance of ultrafine particles (UFPs, particles <0.1 microm diameter), the smallest fraction of ambient particulate matter, on stroke morbidity has not been documented. We studied the effects of short-term changes in exposure to these particles on stroke, separately for ischaemic and haemorrhagic strokes, mild and severe strokes, and ischaemic strokes with (likely embolic) and without (likely thrombotic) atrial fibrillation (AF). METHODS AND RESULTS We used a time-stratified case-crossover design to study the association between short-term exposure to UFPs, particulate matter <10 microm in diameter (PM(10)), nitrogen oxides (NO(x)) and carbon monoxide (CO) (measured at single background station) and hospital admissions for stroke in Copenhagen (2003-2006). Of 7485 stroke admissions, 6798 were ischaemic and 687 haemorrhagic, 3485 mild, and 2248 severe. Of the ischaemic stroke cases, 1204 had AF and 5273 did not. We found significant positive association with exposure to UFPs, NO(x) and CO, and ischaemic strokes, and UFPs and NO(x) and mild strokes, 4 days before admission. The strongest associations were with UFPs. Exposure to UFPs lead to a 21% increase in hospital admissions (per interquartile range of 5-day averages; 95% confidence interval 4-41%) for mild ischaemic stroke of without AF (likely thrombotic origin). CONCLUSION Our results indicate possible effects of traffic-related air pollution, mainly UFPs, on hospital admissions for ischaemic stroke, especially for mild ischaemic stroke of likely thrombotic origin (without AF). These are novel findings regarding the relevance of UFPs and the heterogeneous effect of air pollution on the severity and origin of stroke, and need confirmation by other data.
Plastin 3 Is a Protective Modifier of Autosomal Recessive Spinal Muscular Atrophy

Homozygous deletion of the survival motor neuron 1 gene (SMN1) causes spinal muscular atrophy (SMA), the most frequent genetic cause of early childhood lethality. In rare instances, however, individuals are asymptomatic despite carrying the same SMN1 mutations as their affected siblings, thereby suggesting the influence of modifier genes. We discovered that unaffected SMN1-deleted females exhibit significantly higher expression of plastin 3 (PLS3) than their SMA-affected counterparts. We demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN down-regulation in motor neurons of SMA mouse embryos and in zebrafish. Our study suggests that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases.
Ring of Negative Charge in BK Channels Facilitates Block by Intracellular Mg2+ and Polyamines through Electrostatics

Intracellular Mg2+ and natural polyamines block outward currents in BK channels in a highly voltage-dependent manner. Here we investigate the contribution of the ring of eight negatively charged residues (4 x E321/E324) at the entrance to the inner vestibule of BK channels to this block. Channels with or without (E321N/E324N) the ring of negative charge were expressed in oocytes and unitary currents were recorded from inside-out patches over a range of intracellular Mg2+ and polyamine concentrations. Removing the ring of charge greatly decreased the block, increasing K B ap (0 mV) for Mg2+ block from 48.3 ± 3.0 to 143 ± 8 mM, and for spermine block from 8.0 ± 1.0 to 721 ± 9 mM (150 mM symmetrical KCl). Polyamines with fewer amine groups blocked less: putrescine < spermidine < spermine. An equation that combined an empirical Hill function for block together with a Boltzmann function for the voltage dependence of K B ap described the voltage and concentration dependence of the block for channels with and without the ring of charge. The Hill coefficients for these descriptions were <1 for both Mg2+ and spermine block, and were unchanged by removing the ring of charge. When KCli was increased from 150 mM to 3 M, the ring of charge no longer facilitated block, Mg2+ block was reduced, spermine block became negligible, and the Hill coefficients became ∼1.0. BK channels in cell-attached oocyte patches displayed inward rectification, which was reduced for channels without the ring of charge. Taken together, these observations suggest that the ring of negative charge facilitates block through a preferential electrostatic attraction of Mg2+ and polyamine over K+. This preferential attraction of multivalent blockers over monovalent K+ would decrease the K+ available at the inner vestibule to carry outward current in the presence of Mg2+ or polyamines, while increasing the concentration of blocker available to enter and block the conduction pathway.
From Boolean to probabilistic Boolean networks as models of genetic regulatory networks

Mathematical and computational modeling of genetic regulatory networks promises to uncover the fundamental principles governing biological systems in an integrative and holistic manner. It also paves the way toward the development of systematic approaches for effective therapeutic intervention in disease. The central theme in this paper is the Boolean formalism as a building block for modeling complex, large-scale, and dynamical networks of genetic interactions. We discuss the goals of modeling genetic networks as well as the data requirements. The Boolean formalism is justified from several points of view. We then introduce Boolean networks and discuss their relationships to nonlinear digital filters. The role of Boolean networks in understanding cell differentiation and cellular functional states is discussed. The inference of Boolean networks from real gene expression data is considered from the viewpoints of computational learning theory and nonlinear signal processing, touching on computational complexity of learning and robustness. Then, a discussion of the need to handle uncertainty in a probabilistic framework is presented, leading to an introduction of probabilistic Boolean networks and their relationships to Markov chains. Methods for quantifying the influence of genes on other genes are presented. The general question of the potential effect of individual genes on the global dynamical network behavior is considered using stochastic perturbation analysis. This discussion then leads into the problem of target identification for therapeutic intervention via the development of several computational tools based on first-passage times in Markov chains. Examples from biology are presented throughout the paper.
An information theoretic approach for tracker performance evaluation

Automated tracking of vehicles and people is essential for the effective utilization of imagery in wide area surveillance applications. In order to determine the best tracking algorithm and parameters for a given application, a comprehensive evaluation procedure is required. However, despite half a century of research in multi-target tracking, there is no consensus on how to score the overall performance of these trackers. Existing evaluation approaches assess tracker performance through measures of correspondence between ground truth tracks and system tracks using metrics such as track detection rate, track completeness, track fragmentation rate, and track ID change rate. However, each of these only provides a partial measure of performance and no good method exists to combine them into a holistic metric. Towards this end, this paper presents a pair of information theoretic metrics with similar behavior to the Receiver Operating Characteristic (ROC) curves of signal detection theory. Overall performance is evaluated with the percentage of truth information that a tracker captured and the total amount of false information that it reported. Information content is quantified through conditional entropy and mutual information computations using numerical estimates of the probability of association between the truth and the system tracks. This paper demonstrates how these information quality metrics provide a comprehensive evaluation of overall tracker performance and how they can be used to perform tracker comparisons and parameter tuning on wide-area surveillance imagery and other applications. 1 This work was sponsored by the Department of Defense under Air Force Contract FA8721-05-C-0002. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense or the United States Air Force.
Proinflammatory Cytokines Activate the Intrinsic Apoptotic Pathway in β-Cells

OBJECTIVE Proinflammatory cytokines are cytotoxic to β-cells and have been implicated in the pathogenesis of type 1 diabetes and islet graft failure. The importance of the intrinsic mitochondrial apoptotic pathway in cytokine-induced β-cell death is unclear. Here, cytokine activation of the intrinsic apoptotic pathway and the role of the two proapoptotic Bcl-2 proteins, Bad and Bax, were examined in β-cells. RESEARCH DESIGN AND METHODS Human and rat islets and INS-1 cells were exposed to a combination of proinflammatory cytokines (interleukin-1β, interferon-γ, and/or tumor necrosis factor-α). Activation of Bad was determined by Ser136 dephosphorylation, mitochondrial stress by changes in mitochondrial metabolic activity and cytochrome c release, downstream apoptotic signaling by activation of caspase-9 and -3, and DNA fragmentation. The inhibitors FK506 and V5 were used to investigate the role of Bad and Bax activation, respectively. RESULTS We found that proinflammatory cytokines induced calcineurin-dependent dephosphorylation of Bad Ser136, mitochondrial stress, cytochrome c release, activation of caspase-9 and -3, and DNA fragmentation. Inhibition of Bad Ser136 dephosphorylation or Bax was found to inhibit cytokine-induced intrinsic proapoptotic signaling. CONCLUSIONS Our findings demonstrate that the intrinsic mitochondrial apoptotic pathway contributes significantly to cytokine-induced β-cell death and suggest a functional role of calcineurin-mediated Bad Ser136 dephosphorylation and Bax activity in cytokine-induced apoptosis.
Mechanical Principles of Natural Crimp of Fiber

A mathematical model for natural fiber crimp is proposed which assumes that the analogy with Timoshenko's theory of bimetal thermostats is valid. Formulas for crimp parameters are derived accordingly. They correctly account for the inverse relation ship between crimp and denier which has been shown to exist for wool fibers. Experi mental data obtained with fibers related to "Orlon Sayelle" 2 Type 21 fibers support the validity of the assumed model. The crimp model hypothesis leads logically to a helical coil spring model for the spatial configuration of natural crimp of fibers. The actual spatial path of crimp is shown to depend in part on fiber bending and torsion rigidities and environmental constraints. The equations derived by Holdaway, based on the helical coil model, for the force-extension characteristic of natural crimp are shown to be valid for the elastic behavior of crimped fibers in the unerimping regions of the load-elongation curve. A technique is described for direct measurement of the ratio of bending to torsion rigidity of naturally crimped fibers. For a number of fibers, of the type that includes Orlon Sayelle Type 21, the ratio has been measured and found to vary between about 1.0 and 3.5.
Inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) Attenuates Interleukin-6 (IL-6)-induced Collagen Synthesis and Resultant Hypertrophy in Rat Heart

IL-6 has been shown to play a major role in collagen up-regulation process during cardiac hypertrophy, although the precise mechanism is still not known. In this study we have analyzed the mechanism by which IL-6 modulates cardiac hypertrophy. For the in vitro model, IL-6-treated cultured cardiac fibroblasts were used, whereas the in vivo cardiac hypertrophy model was generated by renal artery ligation in adult male Wistar rats (Rattus norvegicus). During induction of hypertrophy, increased phosphorylation of STAT1, STAT3, MAPK, and ERK proteins was observed both in vitro and in vivo. Treatment of fibroblasts with specific inhibitors for STAT1 (fludarabine, 50 μm), STAT3 (S31-201, 10 μm), p38 MAPK (SB203580, 10 μm), and ERK1/2 (U0126, 10 μm) resulted in down-regulation of IL-6-induced phosphorylation of specific proteins; however, only S31-201 and SB203580 inhibited collagen biosynthesis. In ligated rats in vivo, only STAT3 inhibitors resulted in significant decrease in collagen synthesis and hypertrophy markers such as atrial natriuretic factor and β-myosin heavy chain. In addition, decreased heart weight to body weight ratio and improved cardiac function as measured by echocardiography was evident in animals treated with STAT3 inhibitor or siRNA. Compared with IL-6 neutralization, more pronounced down-regulation of collagen synthesis and regression of hypertrophy was observed with STAT3 inhibition, suggesting that STAT3 is the major downstream signaling molecule and a potential therapeutic target for cardiac hypertrophy.
A comparative study of three adhesion tests (EN 582, similar to ASTM C633, LASAT (LASer Adhesion Test), and bulge and blister test) performed on plasma sprayed copper deposited on aluminium 2017 substrates

The aim of this study was to compare three adhesion tests carried out on plasma-sprayed copper coatings on aluminium substrates. The first test, the bond pull test, designated EN 582 or ASTM C633, involves a uniaxial static stress and is commonly used in the coating industry. The second test, the LASAT (LASer Adhesion Test), is a recently developed technique based on spallation phenomenon due to laser induced shock waves. In this test, the coating delamination results from spallation at the coating/substrate interface due to uniaxial tensile stress. The last test, the bulge and blister test, involves a quasi-static measurement of the crack propagation energy at the coating/substrate interface. These three techniques have been used to evaluate the influences of different process parameters involved in the coating adhesion such as aluminium surface roughness, substrate pre-heating and plasma spray conditions.
Far-Field Optical Nanoscopy

In 1873, Ernst Abbe discovered what was to become a well-known paradigm: the inability of a lens-based optical microscope to discern details that are closer together than half of the wavelength of light. However, for its most popular imaging mode, fluorescence microscopy, the diffraction barrier is crumbling. Here, I discuss the physical concepts that have pushed fluorescence microscopy to the nanoscale, once the prerogative of electron and scanning probe microscopes. Initial applications indicate that emergent far-field optical nanoscopy will have a strong impact in the life sciences and in other areas benefiting from nanoscale visualization.
Effect of near-UV light on Escherichia coli in the presence of 8-methoxypsoralen: wavelength dependency of killing, induction of prophage, and mutation

Wavelength dependency of photo-inactivation and photoinduced reverse mutation of Escherichia coli sensitized with 8-methoxypsoralen, and wavelength dependency of photoinduction of lambda prophage from the sensitized lysogen were measured in a range of 298 to 400 nm. The most efficient sensitization for these biological effects was observed between 320 and 340 nm. In the presence of 8-methyoxypsoralen, the induced mutation frequency per lethal hit was highest of 298 nm in the range examined and was gradually decreased with increasing wavelength to a minimum frequency at 345 nm. This finding may be a reflection of the production of more than one type of lesions which have different efficiencies for mutation compared with the killing efficiency.
Immunopathogenesis of HPV-Associated Cancers and Prospects for Immunotherapy

Human papillomavirus (HPV) infection is a causative factor for various cancers of the anogenital region and oropharynx, and is supposed to play an important cofactor role for skin carcinogenesis. Evasion from immunosurveillance favors viral persistence. However, there is evidence that the mere presence of oncogenic HPV is not sufficient for malignant progression and that additional tumor-promoting steps are required. Recent studies have demonstrated that HPV-transformed cells actively promote chronic stromal inflammation and conspire with cells in the local microenvironment to promote carcinogenesis. This review highlights the complex interplay between HPV-infected cells and the local immune microenvironment during oncogenic HPV infection, persistence, and malignant progression, and discusses new prospects for diagnosis and immunotherapy of HPV-associated cancers.
Optimum Resource Allocation for Amplify-and-Forward Relay Networks With Differential Modulation

The optimum resource allocation is an important method to improve the error performance and energy efficiency of wireless relay networks. In this paper, we consider the resource allocation as a two-dimensional optimization problem; that is, the energy optimization and the location optimization. Differential modulation which bypasses the channel estimation at the receiver is investigated using the amplify-and-forward protocol for a relay system with arbitrary number of relays. At high signal-to-noise ratio (SNR), we first derive the average symbol error rate for systems with and without a direct link. Then, the optimum resource allocation schemes which minimize the system error are developed. The comparisons based on analytical and simulated results confirm that the optimized systems provide considerable improvement over unoptimized ones, and that the minimum error can be achieved via the joint energy-location optimization.