Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping of Eps15 Domains Involved in Its Targeting to Clathrin-coated Pits*

Clathrin-coated pit (CCP) formation occurs as a result of the targeting and assembly of cytosolic coat proteins, mainly the plasma membrane clathrin-associated protein complex (AP-2) and clathrin, to the intracellular face of the plasma membrane. In the present study, the mechanisms by which Eps15, an AP-2-binding protein, is targeted to CCPs was analyzed by following the intracellular localization of Eps15 mutants fused to the green fluorescent protein. Our previous results indicated that the N-terminal Eps15homology (EH) domains are required for CCP targeting. We now show that EH domains are, however, not sufficient for targeting to CCPs. Similarly, neither the central coiled-coil nor the C-terminal AP-2 binding domains were able to address green fluorescent protein to CCPs. Thus, targeting of Eps15 to CCPs likely results from the collaboration between EH domains and another domain of the protein. An Eps15 mutant lacking the coiled-coil domain localized to CCPs showing that Eps15 dimerization is not strictly required. In contrast, Eps15 mutants lacking all AP-2 binding sites showed a dramatic decrease in plasma membrane staining, showing that AP-2 binding sites, together with EH domains, play an important role in targeting Eps15 into CCPs. Finally, the effect of the Eps15 mutants on clathrin-dependent endocytosis was tested by both immunofluorescence and flow cytometry. The results obtained showed that inhibition of transferrin uptake was observed only with mutants able to interfere with CCP assembly.
Obstacle detection test in real-word traffic contexts for the purposes of motorcycle autonomous emergency braking (MAEB)

Research suggests that a Motorcycle Autonomous Emergency Braking system (MAEB) could influence 25% of the crashes involving powered two wheelers (PTWs). By automatically slowing down a host PTW of up to 10 km/h in inevitable collision scenarios, MAEB could potentially mitigate the crash severity for the riders. The feasibility of automatic decelerations of motorcycles was shown via field trials in controlled environment. However, the feasibility of correct MAEB triggering in the real traffic context is still unclear. In particular, MAEB requires an accurate obstacle detection, the feasibility of which from a single track vehicle has not been confirmed yet. To address this issue, our study presents obstacle detection tests in a real-world MAEB-sensitive crash scenario.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015 Dec; 159(4)

Aim. Polymyalgia rheumatica (PMR) is a disease presenting with pain and stiffness, mainly in shoulders, hip joints and neck. Laboratory markers of inflammation may bolster diagnosis. PMR afflicts patients over 50 years old, predominantly women, and may also accompany giant cell arteritis. Patients and Methods. 67 patients, who fullfiled Healey ́s criteria for PMR in the period between 2004 and 2013 and had positive FDG PET (PET/CT) findings were retrospectively evaluated. FDG uptake was assessed in large arteries, proximal joints (shoulders, hips and sternoclavicular joints), in extraarticular synovial structures (interspinous, ischiogluteal and praepubic bursae). Results. Articular/periarticular involvement (A) was detected in 59/67 (88.1%) patients and extrarticular synovial involvement (E) in 51/67 (76.1%) patients either individually or in combinations. Vascular involvement (V) was detected in 27/67 (40.3%) patients only in combination with articular (A) and/or extraarticular synovial (E) involvement. These combinations were: A+E involvement in 30/67 (44.8%) patients, A+V involvement in 8/67 (11.9%) patients, E+V involvement in 6/67 (9%) patients and A+E+V in 13/67 (19.4%) patients. Conclusions. PMR presents by articular/periarticular synovitis, extraarticular synovitis and can be accompanied by giant cell arteritis. All types of involvement have their distinct FDG PET (PET/CT) finding, which can be seen either individually or in any of their 4 combinations. FDG PET (PET/CT) examination seems to be an advantageous one-step examination for detecting different variants of PMR, for assessing extent and severity and also for excluding occult malignancy.
Central Administration of Minocycline and Riluzole Prevents Morphine-Induced Tolerance in Rats

BACKGROUND:Long-term exposure to opiates induces tolerance to the analgesic effect. The neurobiological mechanism of this phenomenon is not completely clear. In this study, we evaluated the effects of central administration of minocycline (a tetracycline derivative) and riluzole (an antiglutamatergic drug) on morphine-induced tolerance in rats. METHODS:Groups of rats received daily morphine (10 mg/kg, IP) in combination with saline (10 &mgr;L/rat, intracerebroventricular [ICV]) or 1% Tween 80 (10 &mgr;L/rat, ICV) or minocycline (60, 120, and 240 &mgr;g/10 &mgr;L per rat, ICV) or riluzole (20, 40, 80 &mgr;g/10 &mgr;L per rat, ICV). Nociception was assessed using hotplate apparatus (55°C ± 0.5°C). Hotplate latency was recorded when the rat licked its hindpaw. Baseline latencies were determined once per day for each rat, then morphine (10 mg/kg) was injected. After 20 min, the above-mentioned drugs were administered and postdrug latency was measured 10 min after the injection of drugs or vehicles. RESULTS:Results showed that ICV administration of minocycline and riluzole delayed morphine-induced tolerance. Morphine tolerance was complete after 8 days in the control groups but was complete in the groups treated with minocycline (120 &mgr;g/10 &mgr;L per rat) and riluzole (80 &mgr;g/10 &mgr;L per rat) on the 13th day. In addition, our results showed that minocycline and riluzole increased the total analgesic effect of morphine (area under the curve of the percentage of maximal possible effect values). CONCLUSION:The effects of minocycline on nitric oxide and the glutamatergic system and the effect of riluzole on the glutamate system are potentially important mechanisms in delaying morphine-induced tolerance.
Traceability of Laser Frequency Calibrations at MIKES

We describe the traceability chain of length measurements at Centre for Metrology and Accreditation (MIKES) from atomic clocks to the lasers of primary interferometers. Crucial part of the traceability chain, an optical frequency comb generator linking optical frequencies to atomic clocks, is described in detail. The frequency comb generator is used in frequency calibrations of iodine-stabilized lasers, which are operated in compliance with the recommendations of the Practical Realization of the Definition of the Meter. Measured absolute frequencies of iodine-stabilized lasers, time records of the measurements, and the respective Allan deviations demonstrate the solid performance of the MIKES laser frequency standards. The results are in good agreement with the recommended values, as well as with the independent characterizations of the measured lasers.
A Spatio-Temporal Analysis of Mobile Internet Traffic in Public Transportation Systems: A View of Web Browsing from The Bus

Mobile devices are ubiquitous, and mobile-generated traffic is arguably a major component of today's web traffic. In particular, the use of smart-phones whilst commuting using public transport is a very popular and common practice in many countries. Mobile commuters however, often suffer from poor performance due to limited bandwidth and/or intermittent network coverage. This paper provides insights into the characteristics of web traffic generated by mobile commuters in these challenged conditions of public transportation systems. We use a dataset collected from 22 Inter-city Buses running on 6 different routes over 5 weeks in Sweden. By analyzing content similarity in time and across different routes, we discover a number of findings that reveal the existence of a spatio-temporal correlation of content popularity and that shed light on diurnal patterns of behavior of mobile commuters. We study popular content accessed by commuters and show that Social Networking and News content are predominant and are mutually exclusive. One of the salient findings is that mobile users' interest on buses is very concentrated, with 35% of the popular content solely accessed on a single day during the 5 weeks, and more than 70% of the popular content from a given day is accessed during one single hour of the day. We also observe high content similarity between specific routes which suggests that content caching within the bus can significantly improve user web experience. Our results indicate that based on the observed strong spatio-temporal correlation of content requests of mobile commuters, caching content inside the buses leads to a daily hit rate ranging from 10 to 20%, with a 20% savings of the daily bandwidth usage.
skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration

Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC−/− adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC−/− mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice.
Implications of shear heating and fracture zones for ridge formation on Europa

We present 2D and 3D numerical simulations of convection to test the role of shear heating and fracture zones on Europan ridge formation. Our simulations show that a pre‐existing fracture zone promotes upwelling and lithospheric thinning, leading to topographic uplift of 50 m. Shear heating also promotes lithospheric thinning and buoyant ascent, producing a ridge‐like feature with topography up to 120 m. Topography remains linear along strike even under the influence of heterogeneous 3D convection within the ice shell. Although the central trough is not reproduced in the simulations, our results support the idea that shear heating can produce ridge‐like structures on Europa.
Prevalence of metabolic syndrome among newly diagnosed hypertensive patients in the hills of Himachal Pradesh, India

To study the prevalence of metabolic syndrome (MS) among newly diagnosed hypertensive patients in a tertiary care hospital in the northern hilly state of Himachal Pradesh, India, located in western Himalayas at a moderate altitude of 2200 m above mean sea level. One hundred and eighteen newly diagnosed hypertensive patients above the age of 20 years were studied in a hospital-based cross-sectional study. MS prevalence was estimated by International Diabetes Federation (IDF) criteria and modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Student's t-test was used to compare the mean of the continuous variables. Chi-square test was used to compare discrete variables. The prevalence of MS in hypertensive patients was 68.6% (modified NCEP-ATP III) and 63.6% (IDF criteria). The most common phenotype of MS with the component of hypertension was the coexistence of waist circumference (90.1%), low high-density lipoprotein (HDL; 70.4%), and high triglycerides (67.9%) as per the modified NCEP-ATP III criteria, and low HDL (76.2%) and high triglycerides (66.4%) as per the IDF criteria. Fasting blood glucose (33.2% as per the modified NCEP-ATP III criteria and 32.6% as per the IDF criteria) was the least significant factor having an association with MS. The prevalence of MS among hypertensive patients was high and indicates the need for metabolic screening in all hypertensive patients at the first diagnosis.
Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 pathway in human Tenon's fibroblasts.

PURPOSE To evaluate the expression profile of microRNAs (miRNAs) and their roles in human Tenon's fibroblasts (HTFs), and to establish an miRNA-based gene-silencing method for antifibrosis in vitro. METHODS The miRNA expression profile was analyzed by microarray using quiescent and transforming growth factor beta 1 (TGFβ1)-stimulated primary HTFs, respectively. Candidate miRNAs were identified by quantitative RT-PCR. miRNAs potentially targeting fibrosis-related genes were predicted using a published algorithm. Predicted fibrosis-related genes regulated by candidate miRNAs were confirmed by transfection of the miRNA into HTF culture (with or without TGFβ1 treatment), followed by quantitative RT-PCR and Western blot analysis. RESULTS In all, 38 miRNAs were identified to be upregulated and 31 downregulated, in TGFβ1-stimulated HTFs. Among those, the miR-29b, downregulated in TGFβ1-treated HTFs, targeted a cadre of mRNAs that encode proteins involved in fibrosis, including PI3Kp85α, Sp1, and collagen type I alpha1 (Col1A1). Treatment of HTFs with TGFβ1 activated the PI3K/Akt/Sp1 pathway and, consequently, induced an increase in the expression of type I collagen. Overexpression of miR-29b inhibited the PI3K/Akt/Sp1 pathway, and attenuated the expression of Col1A1. CONCLUSIONS. miR-29b acted as a suppressor of type I collagen gene by repressing the PI3K/Akt/Sp1 pathway in HTFs. Overexpression of miR-29b protected subconjunctival tissues against collagen production and fibrosis. These findings provided a novel rationale for the development of miRNA-based strategies for attenuating scar formation after glaucoma filtering surgery.
Decentralized multi-robot cooperation with auctioned POMDPs

Planning under uncertainty faces a scalability problem when considering multi-robot teams, as the information space scales exponentially with the number of robots. To address this issue, this paper proposes to decentralize multi-robot partially observable Markov decision processes (POMDPs) while maintaining cooperation between robots by using POMDP policy auctions. Auctions provide a flexible way of coordinating individual policies modeled by POMDPs and have low communication requirements. In addition, communication models in the multi-agent POMDP literature severely mismatch with real inter-robot communication. We address this issue by exploiting a decentralized data fusion method in order to efficiently maintain a joint belief state among the robots. The paper presents two different applications: environmental monitoring with unmanned aerial vehicles (UAVs); and cooperative tracking, in which several robots have to jointly track a moving target of interest. The first one is used as a proof of concept and illustrates the proposed ideas through different simulations. The second one adds real multi-robot experiments, showcasing the flexibility and robust coordination that our techniques can provide.
Heating rates for an atom in a far-detuned optical lattice

We calculate single-atom heating rates in a far-detuned optical lattice, in connection with recent experiments. We first derive a master equation, which includes a realistic atomic internal structure and a quantum treatment of the atomic motion in the lattice. The experimental feature that optical lattices are obtained by superimposing laser standing waves of different frequencies is also included, which leads to a micromotional correction to the light shift that we evaluate. We then calculate, and compare to experimental results, two heating rates, the total heating rate (which corresponds to the increase of the total mechanical energy of the atom in the lattice), and the ground-band heating rate (which corresponds to the increase of energy within the ground energy band of the lattice). The total heating rate remarkably is independent of the atomic state and of the sign of the laser detuning. In contrast, the ground-band heating rate in the deep lattice limit is strongly suppressed for blue-detuned lattices with respect to red-detuned lattices.
Targeting glutamine metabolism rescues mice from late-stage cerebral malaria

Significance Cerebral malaria (CM) is a deadly complication of Plasmodium falciparum infection in African children despite effective antimalarial treatment. Once signs of neurologic disease have commenced, there is no adjunctive treatment for CM, and overall mortality remains high. Thus, a treatment that arrests disease and promotes healing in the late stages is urgently needed. Here we report, in an animal model of CM, that the glutamine analog 6-diazo-5-oxo-L-norleucine (DON) is an effective therapy even when treatment is initiated after infected animals show neurological signs of disease. Within hours of DON treatment blood–brain barrier integrity was restored, and brain swelling was reduced. These results suggest DON as a strong candidate for an effective adjunctive therapy for CM in African children. The most deadly complication of Plasmodium falciparum infection is cerebral malaria (CM) with a case fatality rate of 15–25% in African children despite effective antimalarial chemotherapy. There are no adjunctive treatments for CM, so there is an urgent need to identify new targets for therapy. Here we show that the glutamine analog 6-diazo-5-oxo-l-norleucine (DON) rescues mice from CM when administered late in the infection a time at which mice already are suffering blood–brain barrier dysfunction, brain swelling, and hemorrhaging accompanied by accumulation of parasite-specific CD8+ effector T cells and infected red blood cells in the brain. Remarkably, within hours of DON treatment mice showed blood–brain barrier integrity, reduced brain swelling, decreased function of activated effector CD8+ T cells in the brain, and levels of brain metabolites that resembled those in uninfected mice. These results suggest DON as a strong candidate for an effective adjunctive therapy for CM in African children.
Positron Emission Tomographic Imaging in Stroke

Background and Purpose— Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction–driving amyloid deposition. We conducted a study to determine the presence of &bgr;-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger &bgr;-amyloid deposition, with deposition over time. Methods— Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup ⩽18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. Results— Forty-seven patients were imaged with 11C-PiB positron emission tomography. There was an increase in 11C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, −0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of 11C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, −0.02 to 0.10]; P=0.095). We repeated 11C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of 11C-PiB between regions of interest (median difference in standardized uptake value ratio, −0.08 [95% confidence interval, −0.23 to −0.03]; P=0.04). Conclusions— There was no significant increase in 11C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric 11C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased &bgr;-amyloid deposition ⩽18 months after stroke.
Simian Models of Acquired Immunodeficiency Syndrome (AIDS): A Review

Reports of the unprecedented occurrence of Kaposi’s sarcoma and fatal Pneumocystis carinii pneumonia in previously healthy homosexual men in New York and California in 198 1 heralded the onset of the current human epidemic known as the acquired immunodeficiency syndrome Since those initial reports, the incidence and spread of this disease have increased dramatically. Individuals affected with AIDS develop a prodrome of generalized lymphadenopathy, referred to as lymphadenopathy syndrome, frequently culminating in a selective and profound depression of cellmediated immunity that thus far appears irreversible. Typically, this immunodeficiency is characterized by a reversal of the ratio of T4 + (helper-inducer) to T8 + (suppressor-cytotoxic) subsets of lymphocytes in the peripheral circulation, impairment of delayed cutaneous hypersensitivity and decreased responsiveness of T-lymphocytes to in vitro mitogen stimulation. Patients with AIDS frequently develop life-threatening infections with one or more of the following opportunistic pathogens: Pneumocystis carinii, Cryptococcus neoformans, Toxoplasma gondii, Candida albicans, Mycobacterium tuberculosis, Mycobacterium aviumintracellulare, cytomegalovirus (CMV), Herpesvirus hominis (simplex), adenoviruses and papovaviruses. In addition, Kaposi’s sarcoma and Burkitt’s-like lymphoma occur with much greater frequency in AIDS patients than in the general population. Although initially confined to certain high-risk groups that included promiscuous male homosexuals, intravenous drug-abusers, Haitians, hemophiliacs, and blood transfusion receipients, AIDS is being increasingly recognized in patients that do not belong to any of these groups. It is now well established that the disease can be transmitted through both homosexual and heterosexual contact through use of contaminated hypodermic needles and blood products, and from infected mothers to their newborn children. Early epidemiologic evidence strongly suggested that AIDS was caused by a transmissible agent. In 1983, a retrovirus variously termed lymphadenopathy-associated virus (LAV), human T-lymphotropic virus type I11 (HTLV111) or AIDS-associated retrovirus (ARV) was isolated and shown to be the cause of AIDS.2,39,45 This agent will be referred to as HTLV-III/LAV in this review. Interestingly, HTLV-III/LAV has been shown to have a number of biological characteristics in common with several viruses of ungulates classified in the lentivirus subfamily of retroviruse~. ~~~ ~~ These agents include maedi-visna virus (MVV), caprine arthritis-encephalitis virus (CAEV) and equine infectious anemia virus (EIAV). Recently, HTLV-III/LAV has been shown to be neuropathic and associated with dementia and a characteristic granulomatous encephalitis in adult as well as pediatric patients.