Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Mechanisms Underlie Neurotoxin-Mediated Cell Death in Cultured Dopaminergic Neurons

Oxidative stress is thought to contribute to dopaminergic cell death in Parkinson’s disease (PD). The neurotoxin 6-hydroxydopamine (6-OHDA), which is easily oxidized to reactive oxygen species (ROS), appears to induce neuronal death by a free radical-mediated mechanism, whereas the involvement of free radicals inN-methyl-4-phenylpyridinium (MPP+) toxicity is less clear. Using free radical-sensitive fluorophores and vital dyes with post hoc identification of tyrosine hydroxylase-positive neurons, we monitored markers of apoptosis and the production of ROS in dopaminergic neurons treated with either 6-OHDA or MPP+. Annexin-V staining suggested that 6-OHDA but not MPP+-mediated cell death was apoptotic. In accordance with this assignment, the general caspase inhibitor Boc-(Asp)-fluoromethylketone only blocked 6-OHDA neurotoxicity. Both toxins exhibited an early, sustained rise in ROS, although only 6-OHDA induced a collapse in mitochondrial membrane potential temporally related to the increase in ROS. Recently, derivatives of buckminsterfullerene (C60) molecules have been shown to act as potent antioxidants in several models of oxidative stress (Dugan et al., 1997). Significant, dose-dependent levels of protection were also seen in these in vitro models of PD using the C3 carboxyfullerene derivative. Specifically, C3 was fully protective in the 6-OHDA paradigm, whereas it only partially rescued dopaminergic neurons from MPP+-induced cell death. In either model, it was more effective than glial-derived neurotrophic factor. These data suggest that cell death in response to 6-OHDA and MPP+ may progress through different mechanisms, which can be partially or entirely saved by carboxyfullerenes.
Novel measure of the weigh distribution balance on the brain network: Graph complexity applied to schizophrenia

The aim of this study was to assess brain complexity dynamics in schizophrenia (SCH) patients during an auditory oddball task. For this task, we applied a novel graph measure based on the balance of the node weights distribution. Previous studies applied complexity parameters that were strongly dependent on network topology. This could bias the results, as well as making correction techniques, such as surrogating process, necessary. In the present study, we applied a novel graph complexity measure derived from the information theory: Shannon Graph Complexity (SGC). Complexity patterns from electroencephalographic recordings of 20 healthy controls and 20 SCH patients during an auditory oddball task were analyzed. Results showed a significantly more pronounced decrease of SGC for controls than for SCH patients during the cognitive task. These findings suggest an important change in the brain configuration towards a more balanced network, mainly in the connections related to long-range interactions. Since these changes are significantly more pronounced in controls, a deficit in the neural network reorganization can be associated with SCH. In addition, an accuracy of 72.5% was obtained using a receiver operating characteristic curve with a leave-one-out cross-validation procedure. The independence of network topology has been demonstrated by the novel complexity measure proposed in this study, therefore, it complements traditional graph measures as a means to characterize brain networks.
Myocardial Dysfunction: A Primary Cause of Death Due To Severe Malaria in A Plasmodium falciparum-Infected Humanized Mouse Model

Background Our study aimed at substantiating the recent claim of myocardial complications in severe malaria by experimentally inducing severe Plasmodium falciparum infection in a humanized mouse model employed as human surrogate. Methods Twenty five humanized mice were inoculated with standard in vitro cultured P. falciparum and blood extracts collected from the inner cardiac muscles of infected mice that died were examined for the presence of the infectious cause of death. The therapeutic effect of quinine on 7 mice severely infected with P. falciparum was also evaluated. Results All the 25 humanized mice inoculated with the in vitro cultured P. falciparum revealed peripheral parasitemia with a total of 10 deaths recorded. Postmortem examination of the inner cardiac muscles of the dead mice also revealed massive sequestration of mature P. falciparum as well as significant infiltration of inflammatory cells such as lymphocytes and monocytes. Postmortem evaluation of the inner cardiac muscles of the P. falciparum-infected mice after quinine therapy showed significant decline in parasite density with no death of mice recorded. Conclusions Data obtained from our study significantly corroborated the findings of myocardial dysfunction as the primary cause of death in recent case reports of humans infected with P. falciparum.
Favorability potential for IOCG type deposits in the Riacho do Pontal Belt: new insights for identifying prospects of IOCG-type deposits in NE Brazil

Archean iron oxide-copper-gold (IOCG) deposits have been systematically described in the world class Carajas IOCG district, Amazonian region of Brazil. More recently, several Neoproterozoic (ca 1.13 to 0.96 Ga) IOCG deposits have been identified in the Riacho do Pontal mobile belt situated in the Borborema Province on the northern border of the Sao Francisco Craton. In these Neoproterozoic deposits, several copper occurrences have been mapped along shear zones. The primary hydrothermal mineral associations resulted in sodic, calcic-potassic and potassic-ferric alteration. The copper grades of the main prospects range between 0.5 and 0.8 wt% with an average of ~0.7 wt%. This study uses a fuzzy logic approach to create regional to district scale predictive exploration models. Specifically, multi-parameter geologic, geochemical, remote sensing, and airborne geophysical data incorporated into regional and local models predict known copper mineralization and, importantly, highlight prospective areas for new IOCG targets in the Borborema Province. At district scale, multiple higher resolution geological, soil geochemical, and airborne geophysical data that cover the Riacho do Pontal Belt, were analyzed. A drilling exploration program implemented on target RIA4 validated these model results. Drill hole RIA4-DH0001 crosscuts a mineralized zone with 32 m of 1.15 wt% copper.
Structural characteristics of shallowly buried accretionary prism: Rapidly uplifted Neogene accreted sediments on the Miura‐Boso Peninsula, central Japan

The upper Miocene Misaki and Nishizaki formations on the Miura and Boso peninsulas in central Japan preserve the deformation features of an off‐scraped accretionary prism. The spatial distribution, geometry, and style of accretion‐related deformation with paleotemperature and burial depth estimation are elucidated in this study. The deformation structures and textures are similar to those of modern accretionary prisms. The low maximum paleotemperature (<50°C) and high preserved porosity of the sediments (30–50%) imply a maximum burial depth of less than 1000 m. On the basis of the mode of deformation, this off‐scraped body is divided into an imbricate thrust, a thrust unit, and an upper coherent unit in ascending order. The imbricate thrust corresponds to a branch from the basal décollement zone and is subdivided into a brecciated zone, a main gouge zone, and a shear band zone. The thrust unit hosts a concentration of thrust systems that form various orders of duplex structures, while the upper coherent unit is characterized by gravitational instability‐ and earthquake‐induced deformation without thrust faulting. The duplex distribution, shear strain, and fluid migration associated with the off‐scraping processes are clearly localized within the imbricate thrust and thrust unit. This accretion‐related deformation occurred before lithification of the sediment and under high fluid pressure induced by shear deformation, thickening of the sedimentary sequence, and earthquake‐induced liquefaction. These processes are inferred to control the effect on the mode of deformation and the location of thrusting during early deformation of the accretionary prism.
Arabidopsis CURVATURE THYLAKOID1 Proteins Modify Thylakoid Architecture by Inducing Membrane Curvature[W]

Here, we characterize a protein family that forms a complex by oligomerization, which is required for bending of the thylakoid membrane. Without this complex, the typical thylakoid ultrastructure of land plant chloroplasts, composed of grana stacks and stroma lamellae, cannot develop. Strikingly, the loss of this active compartmentalization within thylakoids affects photosynthesis only moderately. Chloroplasts of land plants characteristically contain grana, cylindrical stacks of thylakoid membranes. A granum consists of a core of appressed membranes, two stroma-exposed end membranes, and margins, which connect pairs of grana membranes at their lumenal sides. Multiple forces contribute to grana stacking, but it is not known how the extreme curvature at margins is generated and maintained. We report the identification of the CURVATURE THYLAKOID1 (CURT1) protein family, conserved in plants and cyanobacteria. The four Arabidopsis thaliana CURT1 proteins (CURT1A, B, C, and D) oligomerize and are highly enriched at grana margins. Grana architecture is correlated with the CURT1 protein level, ranging from flat lobe-like thylakoids with considerably fewer grana margins in plants without CURT1 proteins to an increased number of membrane layers (and margins) in grana at the expense of grana diameter in overexpressors of CURT1A. The endogenous CURT1 protein in the cyanobacterium Synechocystis sp PCC6803 can be partially replaced by its Arabidopsis counterpart, indicating that the function of CURT1 proteins is evolutionary conserved. In vitro, Arabidopsis CURT1A proteins oligomerize and induce tubulation of liposomes, implying that CURT1 proteins suffice to induce membrane curvature. We therefore propose that CURT1 proteins modify thylakoid architecture by inducing membrane curvature at grana margins.
Smart Emission - Building a Spatial Data Infrastructure for an Environmental Citizen Sensor Network

Smart Emission is a citizen sensor network using low-cost sensors that enables citizens to gather data about environmental quality, like air quality, noise load, vibrations, light intensities and heat stress. This paper introduces the design and development of the data infrastructure for the Smart Emission initiative and discusses challenges for the future. The Spatial Data Infrastructure (SDI) is open and accessible on the Internet using open geospatial standards and (Web-) client applications. Smart Emission as a citizen sensor network offers several possibilities for heterogonous applications, from health determination to spatial planning purposes, environmental monitoring for sustainable traffic management, climate adaptation in cities and city planning.
Exploiting Core Working Sets to Filter the L1 Cache with Random Sampling

Locality is often characterized by working sets, defined by Denning as the set of distinct addresses referenced within a certain window of time. This definition ignores the fact that dramatic differences exist between the usage patterns of frequently used data and transient data. We therefore propose to extend Denning's definition with that of core working sets, which identify blocks that are used most frequently and for the longest time. The concept of a core motivates the design of dual-cache structures that provide special treatment for the core. In particular, we present a probabilistic locality predictor for L1 caches that leverages the skewed popularity of blocks to distinguish transient cache insertions from more persistent ones. We further present a dual L1 design that inserts only frequently used blocks into a low-latency, low-power, direct-mapped main cache, while serving others from a small fully associative filter. To reduce the prohibitive cost of such a filter, we present a content addressable memory design that eliminates most of the costly lookups using a small auxiliary lookup table. The proposed design enables a 16K direct-mapped L1 cache, augmented with a small 2K filter, to outperform a 32K 4-way cache, while at the same time consumes 70-80 percent less dynamic power and 40 percent less static power.
Modeling of a Buck Converter With a SiC JFET to Predict EMC Conducted Emissions

The reduced switching times of silicon carbide (SiC) components compared to Si components in similar conditions are a great advantage from the point of view of efficiency, but, due to the high dv/dt and di/dt, conducted electromagnetic emissions are increased. Therefore, the availability of a method which can predict these emissions is increasingly necessary. To the best of the authors' knowledge, a model that can predict differential mode as well as common mode for a converter including sic devices has not yet been published. the novelty of the work presented here is the integration of different modeling approaches to form a circuit model of a SiC-based buck dc-dc converter working in frequency range from 40 Hz to 30 MHz. A modeling approach of the passive parts of the converter is presented. Then, the model obtained is used in simulations to predict the drain-to-source voltage and the drain current for the JFET. Conducted emissions received by the line impedance stabilization network are also computed. Simulation results are compared to measurements for different duty cycles and different gate resistors in the time and frequency domains. A good agreement is obtained. In the frequency domain, in all cases, differences are less than 5 dBμV up to 30 MHz excepted in the JFET source current.
Multiple sclerosis: reduced proportion of circulating plasmacytoid dendritic cells expressing BDCA-2 and BDCA-4 and reduced production of IL-6 and IL-10 in response to herpes simplex virus type 1

Objective We hypothesized that autoaggressive immune responses observed in multiple sclerosis (MS) could be associated with an imbalance in proportion of immune cell subsets and in cytokine production in response to infection, including viruses. Methods We collected blood mononuclear cells (MNC) from 23 patients with MS and 23 sex- and age-matched healthy controls (HC) from the island of Sardinia, Italy, where the prevalence of MS is extraordinarily high. Using flow cytometry, we studied MNC for expression of blood dendritic cell antigens (BDCA)-2 and BDCA-4 surface markers reflecting the proportion of plasmacytoid dendritic cells (pDC) that produce type I interferons (IFNs) after virus challenge and promote Th2/anti-inflammtory cytokine production. In parallel, pro-inflammatory (interleukin [IL]-2, IL-12, IFN-γ), anti-inflammatory (IL-4, IL-10), and immuno-regulatory/pleiotropic cytokines (type I IFNs including IFN-α and β, IL-6) were measured before and after an in vitro exposure to herpes simplex virus type 1 (HSV-1). Results The subset of lineage negative (lin−), BDCA-2+ cells was lower in patients with MS compared with HC (0.08 ± 0.02% vs 0.24 ± 0.02%; P < 0.001). A similar pattern was observed for lin−BDCA-4+ cells (0.08 ± 0.02% vs 0.17% ± 0.03; P < 0.01). Spontaneous productions of IL-6 (45 ± 10 pg/mL vs 140 ± 26 pg/mL; P < 0.01) and IL-10 (17 ± 0.4 pg/mL vs 21 ± 1 pg/mL; P < 0.05) by MNC were lower in patients with MS compared with HC. Spontaneous production of IL-6 (6.5 ± 0.15 pg/mL vs 21 ± 5 pg/mL; P < 0.01 and IL-10 (11 ± 1 pg/mL vs 14 ± 3 pg/mL; P < 0.05) by pDC was also lower in patients with MS compared with HC. Exposure of MNC to HSV-1 showed, in both patients with MS and HC, increased production of IFN-α, IL-6, and IL-10 but decreased production of IL-4. In response to HSV-1 exposure, productions of IL-6 (165 ± 28 pg/mL vs 325 ± 35 pg/mL; P < 0.01) and IL-10 (27 ± 3 vs 33 ± 3 P < 0.05) by MNC as well as by pDC (IL-6: 28 ± 7 vs 39 ± 12 P < 0.05; IL-10: 14 ± 1 vs 16 ± 3 P < 0.05) were lower in patients with MS compared with HC. Conclusion The results implicate a new evidence for altered immune cells and reduced immune responses in response to viral challenge in MS.
Sandalwood Oil and Turmeric-Based Cream Prevents Ionizing Radiation-Induced Dermatitis in Breast Cancer Patients: Clinical Study

Background: The primary objective of this study was to ascertain the benefit of Vicco turmeric Ayurvedic cream (VTC; Vicco Laboratories, Mumbai, India) sandalwood oil and turmeric-based cream in preventing radiodermatitis in women undergoing curative radiotherapy for their breast cancer. Methods and Materials: The study was an investigator-blinded randomized study with Johnsons Baby Oil (JBO; Johnson & Johnson Ltd., Baddi, India) as a comparator, administered daily from the start of radiation therapy for 5 weeks in women receiving breast radiation therapy, 50 Gy in 2 Gy fractions daily for 5 weeks. The endpoints were to ascertain the delay in the appearance and the degree of severity of dermatitis throughout the study period in accordance to the Therapy Oncology Group (RTOG) score. Results: The results indicated that the topical application of VTC delayed and mitigated the radiodermatitis. When compared to the Johnson’s Baby Oil, a significant decrease (p = 0.025) in the incidence of grade 1 was seen at week two, and also in grade 2 and 3 at week 3 (p = 0.003) and week 4 (p = 0.02), respectively, in the VTC cohort. A concomitant decrease in the average severity was also observed at week 2 (p = 0.02), week 3 (p = 0.05) and week 4 (p = 0.03). Conclusions: The results indicate that VTC cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. The result of this study indicates the beneficial effects. Double blind randomized control studies are required to further confirm the beneficial effects of VTC in mitigating radiodermatitis is people undergoing radiation treatment for their cancer.
Clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in memantine therapy in Alzheimer’s disease with behavioral and psychological symptoms on dementia

Objective: We investigated the clinical efficacy and changes in the dosages of concomitantly used psychotropic drugs in memantine therapy in Alzheimer’s disease (AD) with behavioral and psychological symptoms on dementia (BPSD). Methods: The subjects were 38 inpatients who had been diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the neuropsychiatric inventory (NPI) and cognitive function was assessed using the mini-mental examination (MMSE). The changes in the dosages of concomitant psychotropic drugs were also assessed. Results: Significant decreases were found in the memantine therapy group in the following NPI total score and five NPI subscales: delusions, hallucinations, agitation, irritability, and aberrant motor behavior, but no significant differences were seen between the memantine therapy group and the control group. Furthermore, the memantine therapy group allowed the dosage of the psychotropic drugs to be significantly reduced compared with the control group. Conclusion: The results of this study suggest that the administration of memantine to patients with AD with BPSD may afford superior efficacy and may also make it possible to reduce the risperidone equivalent dose, the diazepam equivalent dose and the dosage of the psychotropic drugs.
Recovery from sports concussion in high school and collegiate athletes

Introduction: Neuropsychological testing is a valuable tool in concussion diagnosis and management. ImPACT, a computerized neuropsychological testing program, consists of eight cognitive tasks and a 21-item symptom inventory. Method: ImPACT was used to examine the cognitive performance of 104 concussed athletes at baseline, 2, 7 and 14 days post-injury. Dependent measures included composite scores from the ImPACT computerized test battery, as well as a total symptom score from the Post-Concussion Symptom Scale. Results: Differences between baseline and day 2 post-injury scores were observed for all ImPACT composites (Verbal memory-VERM, visual memory-VISM, processing speed-PROC and reaction time-RT) as well as in total symptom score (SX). At day 7, concussed athletes continued to perform significantly poorer on VERM, VISM, RT and SX. At day 14, only VERM scores were significantly different from baseline. Conclusions: Cognitive performance deficits in concussed athletes may persist to 7 and even to 14 days in some cases. In addition to symptom status, the athlete's post-concussion cognitive functioning should be considered when making return-to-play decisions.
Inhibition of the Herpes Simplex Virus Type 1 DNA Polymerase Induces Hyperphosphorylation of Replication Protein A and Its Accumulation at S-Phase-Specific Sites of DNA Damage during Infection

ABSTRACT The treatment of mammalian cells with genotoxic substances can trigger DNA damage responses that include the hyperphosphorylation of replication protein A (RPA), a protein that plays key roles in the recognition, signaling, and repair of damaged DNA. We have previously reported that in the presence of a viral polymerase inhibitor, herpes simplex virus type 1 (HSV-1) infection induces the hyperphosphorylation of RPA (D. E. Wilkinson and S. K. Weller, J. Virol. 78:4783-4796, 2004). We initiated the present study to further characterize this genotoxic response to HSV-1 infection. Here we report that infection in the presence of polymerase inhibitors triggers an S-phase-specific response to DNA damage, as demonstrated by induction of the hyperphosphorylation of RPA and its accumulation within viral foci specific to the S phase of the cell cycle. This DNA damage response occurred in the presence of viral polymerase inhibitors and required the HSV-1 polymerase holoenzyme as well as the viral single-stranded-DNA binding protein. Treatment with an inhibitor of the viral helicase-primase did not induce the hyperphosphorylation of RPA or its accumulation in infected cells. Taken together, these results suggest that the S-phase-specific DNA damage response to infection is dependent on the specific inhibition of the polymerase. Finally, RPA hyperphosphorylation was not induced during productive infection, indicating that active viral replication does not trigger this potentially detrimental stress response.