Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration.
Size- and coating-dependent cytotoxicity and genotoxicity of silver nanoparticles evaluated using in vitro standard assays

Abstract The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having three different sizes and two different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA) and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronuclei from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materials also resulted in concentration-dependent cytotoxicity and significantly increased micronucleus frequency. With both the MLA and micronucleus assays, the smaller the AgNPs, the greater the cytotoxicity and genotoxicity. The coatings had less effect on the relative genotoxicity of AgNPs than the particle size. Loss of heterozygosity analysis of the induced Tk mutants indicated that the types of mutations induced by AgNPs were different from those of ionic silver. These results suggest that AgNPs induce cytotoxicity and genotoxicity in a size- and coating-dependent manner. Furthermore, while the MLA and in vitro micronucleus assay (in both types of cells) are useful to quantitatively measure the genotoxic potencies of AgNPs, the Ames test cannot.
Anti-oxidative aspect of inhaled anesthetic gases against acute brain injury

Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury.
Ischemic stroke subtypes: a population-based study of incidence and risk factors.

BACKGROUND AND PURPOSE There is scant population-based information on incidence and risk factors for ischemic stroke subtypes. METHODS We identified all 454 residents of Rochester, Minn, with a first ischemic stroke between 1985 and 1989 from the Rochester Epidemiology Project medical records linkage system. We used Stroke Data Bank criteria to assign infarct subtypes after reviewing medical records and brain imaging. We adjusted average annual incidence rates by age and sex to the US 1990 population and compared the age-adjusted frequency of stroke risk factors across ischemic stroke subtypes. RESULTS Age- and sex-adjusted incidence rates (per 100 000 population) were as follows: large-vessel cervical or intracranial atherosclerosis with >50% stenosis, 27; cardioembolic, 40; lacuna, 25; uncertain cause, 52; other or uncommon cause, 4. Sex differences in incidence rates were detected only for atherosclerosis with stenosis (47 [95% CI, 34 to 61] for men; 12 [95% CI, 7 to 17] for women). There was no difference in prior transient ischemic attack and hypertension among subtypes, and diabetes was not more common among patients with lacunar infarction than other common subtypes. CONCLUSIONS The age-adjusted incidence rate of stroke due to stenosis of the large cervicocephalic vessels is nearly 4 times higher for men than for women. There is no association between preceding transient ischemic attack and stroke mechanism. Diabetes and hypertension are not more common among patients with lacunae. Age- and sex-adjusted incidence rates for ischemic stroke subtypes in this population can be compared with similarly determined rates from other populations.
Vascularized composite tissue allotransplantation – state of the art

Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including – but not limited to – trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques.
Comparison of several short-term traffic speed forecasting models

The widespread adoption of smartphones in recent years has made it possible for us to collect large amounts of traffic data. Special software installed on the phones of drivers allow us to gather GPS trajectories of their vehicles on the road network. In this paper, we simulate the trajectories of multiple agents on a road network and use various models to forecast the short-term traffic speed of various links. Our results show that traditional techniques like multiple regression and artificial neural networks work well but simpler adaptive models that do not require prior training also perform comparatively well.
Using PrEP, losing condoms? PrEP promotion may undermine safe sex.

PrEP is a crucial new tool for the prevention of HIV. However, careful attention must be paid as to whether its widespread adoption could reduce condom usage, which may in turn increase STIs in the long-run. In this article we re-assess whether PrEP uptake may influence condom usage, and we call for vigilance by public health advocates to ensure that PrEP promotion does not lead to a drop-off in safe sex practices. Most of the evidence that PrEP does not change condom usage comes from double-blind clinical trials which are focused on the biological effect of PrEP on HIV incidence. However, subjects in these trials may not change their behavior because they do not actually know if they are taking PrEP. A number of focus group studies on individuals considering taking PrEP show that many see the drug as an opportunity for increasing unprotected sex. National survey data from the CDC show that condom rates are decreasing among MSM, which are a major target group for PrEP. Furthermore, data from public health records show that STIs are increasing among MSM in some areas with relatively high PrEP uptake. There is enough evidence that PrEP is contributing to rising STI infections to warrant concern. Public health advocates must ensure that PrEP uptake does not inadvertently threaten the public's health and that thirty years of condom promotion are not wasted.
Molecular biology of actin binding proteins: evidence for a common structural domain in the F-actin binding sites of gelsolin and α-actinin

Summary We review the impact of molecular biology on actin binding proteins, in particular on sequence relationships and expression of clones to dissect properties in vitro. Significant homologies exist between proteins in each class, but we propose, in addition, that common structural features exist between the F-actin binding sites of severing and cross-linking proteins.
Performance Analysis of Interference Alignment Under CSI Mismatch

With interference alignment (IA), the achievable degrees of freedom (DoFs) in wireless networks can be linearly scaled up with the number of users. However, to attain the full DoF, the availability of perfect network channel state information (CSI) is mandatory, which is not pragmatic in general. In this paper, we quantify the performance of IA under CSI mismatch where the variance of the CSI measurement error depends on the signal-to-noise ratio (SNR). We show that when this error variance is proportional to the inverse of the SNR, the full DoF is achievable, and an upper bound on asymptotic mean loss in sum rate compared with the perfect CSI case is derived. We also derive a bound on the achievable DoF when the CSI error variance is proportional to the inverse of the SNR to a power of a constant. Furthermore, we investigate the effect of CSI mismatch on the performance of the maximum signal-to-interference-plus-noise ratio (Max-SINR) algorithm. We show that with perfect CSI, the Max-SINR algorithm outperforms interference leakage minimization algorithms, but with the presence of imperfect CSI, its comparative improvement becomes negligible. We then propose an adaptive Max-SINR algorithm that can notably improve the performance of the original Max-SINR algorithm under CSI mismatch.
The influence of behavioural and psychological factors on medication adherence over time in rheumatoid arthritis patients: a study in the biologics era

Objectives. To investigate levels of self-reported adherence to biologic treatment and establish the contribution of demographic, physical and psychological factors to biologic medication adherence in an RA cohort. Methods. Adalimumab-treated patients were recruited through the British Society for Rheumatology Biologics Register for RA between May 2007 and April 2009. Demographic and baseline psychological measures including illness and medication beliefs were collected. Disease activity (28-item DAS), physical function (HAQ) and quality of life (36-item Short Form Health Survey) were also measured at baseline and at 6, 12 and 18 months. Adherence was assessed at each follow-up using the patient self-completed Compliance Questionnaire for Rheumatology (CQR). Multilevel mixed effects modelling analysis was performed to investigate predictors of adherence. Results. Of the 329 Adalimumab-treated patients included, low adherence (CQR score <65) was reported in 23%, with 41% reporting low adherence at at least one time point. After controlling for age and disease duration, factors independently predictive of increased adherence were increased belief in medication necessity, with baseline effect diminishing over time [β coefficient 1.68 (s.e. 0.19), P = 0.0001], lower medication concerns [0.50 (0.15), P = 0.001], with this effect remaining throughout follow-up, increased professional or family member support [0.81 (0.32), P = 0.01], strong views of illness being chronic [0.32 (0.14), P = 0.025] and increased treatment control [0.41 (0.19), P = 0.032]. Conclusion. Wider recognition of the importance of psychological factors, particularly medication beliefs, in driving medication adherence could have substantial clinical and health economic benefits in RA. The psychological factors we have identified are putative targets for strategies to improve adherence in RA.
Comparative study of spectrum sensing techniques base on techniques non-cooperative in cognitive radio networks

The growing demand of the wireless communications introduced the challenge of the efficient use of the spectrum. Cognitive radio is an emerging technology in the field of wireless access, in order to considerably improve the use of the radio spectrum by allowing access of opportunistic manner. The detection of the spectrum is the basic functionality in a cognitive radio that is why in this paper a particular emphasis is placed on the comparison of the different methods of detection of the spectrum in the case of detection non-cooperative. We note that the different techniques do not present the same performance. In this paper the CFD method presents a good performance by report to the MFD and ED. The result of the simulation was obtained through the Software Matlab.
Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem region, The Netherlands

Background: The frequency of clinical isolation of non-tuberculous mycobacteria (NTM) in the Netherlands is increasing, but its clinical relevance is often uncertain. Objective: To assess the frequency and clinical relevance of isolation of NTM in four associated hospitals in a single region in the Netherlands. Methods: Medical files of all patients from whom NTM were isolated between January 1999 and January 2005 were reviewed retrospectively. Diagnostic criteria for non-tuberculous mycobacterial disease published by the American Thoracic Society (ATS) were used to determine clinical relevance. Results: 232 patients were found, from whom NTM were isolated from the respiratory tract in 91% of cases. Patients were mostly white men, with an average age of 60 years and pre-existing pulmonary disease. Fifty-three of 212 patients (25%) with pulmonary isolates met the ATS diagnostic criteria for pulmonary NTM disease; this percentage differed by species. Most patients were treated with rifampicin, ethambutol and clarithromycin. Treatment outcome for pulmonary NTM disease was suboptimal but differed by species: overall, improvement was seen in 67% of treated patients, but in only 50% of those with pulmonary M avium disease. Lymphadenitis was the most common extrapulmonary disease type. Conclusions: Twenty-five per cent of all patients with pulmonary NTM isolates met the ATS criteria. Clinical relevance differs by species. NTM isolation increases over time. Species distribution differs from that of neighbouring countries and the M avium complex isolates have traits different from those reported in the USA. Adherence to diagnostic and treatment guidelines can be improved.
Monitoring of Hepatitis C Virus Quasispecies in Chronic Infection by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Mutation Detection

ABSTRACT Using both a mass spectrometry-based method and the classical method of cloning and sequencing, we demonstrated weekly changes in the hypervariable region 1 quasispecies of a chimpanzee infected with an infectious clone, coinciding with neutralizing antibody emergence. We also used the mass spectrometry method in the clinical follow-up of a chronically infected patient over a 5-year period.
Unprecedented ichneumonid parasitoid wasp diversity in tropical forests

The megadiverse parasitoid wasp family Ichneumonidae (Hymenoptera) is classically considered an exception to the extensively studied latitudinal diversity gradient: the majority of ichneumonid species are described from temperate regions. The gradient has been hypothesized to be dependent on the biology of the wasps, but recently questions of sampling and description biases have been raised. Here, we show with primary data that the species richness of Ichneumonidae is markedly underestimated in tropical areas and that latitudinal diversity patterns in the family remain uncharacterized. We discovered a startling 177 likely undescribed orthocentrine species with relatively low sampling effort in the forests of Central America and Amazonian Ecuador, over three times the previously known orthocentrine diversity in the world's tropics. Species accumulation curves reveal that we are just beginning to unveil the true extent of tropical orthocentrine diversity. We also found evidence for cryptic species; our DNA analysis revealed additional species not easily distinguishable using morphological characteristics. The difficulty in establishing species richness patterns of Ichneumonidae probably follows from the relative lack of taxonomic expertise and the low density of ichneumonid species throughout the landscape.
Thermoregulatory behaviour affects prevalence of chytrid fungal infection in a wild population of Panamanian golden frogs

Predicting how climate change will affect disease dynamics requires an understanding of how the environment affects host–pathogen interactions. For amphibians, global declines and extinctions have been linked to a pathogenic chytrid fungus, Batrachochytrium dendrobatidis. Using a combination of body temperature measurements and disease assays conducted before and after the arrival of B. dendrobatidis, this study tested the hypothesis that body temperature affects the prevalence of infection in a wild population of Panamanian golden frogs (Atelopus zeteki). The timing of first detection of the fungus was consistent with that of a wave of epidemic infections spreading south and eastward through Central America. During the epidemic, many golden frogs modified their thermoregulatory behaviour, raising body temperatures above their normal set point. Odds of infection decreased with increasing body temperature, demonstrating that even slight environmental or behavioural changes have the potential to affect an individual's vulnerability to infection. The thermal dependency of the relationship between B. dendrobatidis and its amphibian hosts demonstrates how the progression of an epidemic can be influenced by complex interactions between host and pathogen phenotypes and the environments in which they are found.
Approximating the minimum weight triangulation

In <italic>O(n</italic> log <italic>n)</italic> time we compute a triangulation with <italic>O(n)</italic> new points, and no obtuse triangles, that has length within a constant factor of the minimum possible. We also approximate the minimum weight Steiner triangulation using triangulations with no sharp angles. No previous polyonomial time triangulation achieved an approximation factor better than <italic>O</italic>(log <italic>n</italic>).
Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index

Introduction Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer. Methods We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve. Results Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002). Conclusions Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.
Coevolution between a Family of Parasite Virulence Effectors and a Class of LINE-1 Retrotransposons

Parasites are able to evolve rapidly and overcome host defense mechanisms, but the molecular basis of this adaptation is poorly understood. Powdery mildew fungi (Erysiphales, Ascomycota) are obligate biotrophic parasites infecting nearly 10,000 plant genera. They obtain their nutrients from host plants through specialized feeding structures known as haustoria. We previously identified the AVR k1 powdery mildew-specific gene family encoding effectors that contribute to the successful establishment of haustoria. Here, we report the extensive proliferation of the AVR k1 gene family throughout the genome of B. graminis, with sequences diverging in formae speciales adapted to infect different hosts. Also, importantly, we have discovered that the effectors have coevolved with a particular family of LINE-1 retrotransposons, named TE1a. The coevolution of these two entities indicates a mutual benefit to the association, which could ultimately contribute to parasite adaptation and success. We propose that the association would benefit 1) the powdery mildew fungus, by providing a mechanism for amplifying and diversifying effectors and 2) the associated retrotransposons, by providing a basis for their maintenance through selection in the fungal genome.
Localized disjoint multipath routing protocol in irregular wireless sensor networks

Disjoint multipath routing is an attractive approach for improving the reliability of data delivery in wireless sensor networks. Recently, the issue for maintaining the robustness and efficiency of the disjoint multipath routing against network failures such as network holes are being studied. Several protocols have been proposed to handle the network failures. However, they cause the large performance degradation on data delivery ratio and delay due to its centralized manner for detouring the network holes in irregular network environments. Thus, we propose a Localized Disjoint Multipath Routing protocol called LDMR which can achieve reliable data delivery ratio and stable data delivery delay while handling network failures. LDMR constructs the fully disjoint multipath and manages them by using a localized management method with a path priority rule. Simulation results show that our protocol provides the more stable and reliable performance than the previous protocols in terms of packet delivery ratio and packet delivery delay.