The first measurement of heavy-flavor production by the LHCb experiment in its fixed-target mode is presented. The production of J/ψ and D^{0} mesons is studied with beams of protons of different ...energies colliding with gaseous targets of helium and argon with nucleon-nucleon center-of-mass energies of sqrts_{NN}=86.6 and 110.4 GeV, respectively. The J/ψ and D^{0} production cross sections in pHe collisions in the rapidity range 2, 4.6 are found to be σ_{J/ψ}=652±33(stat)±42(syst) nb/nucleon and σ_{D^{0}}=80.8±2.4(stat)±6.3(syst) μb/nucleon, where the first uncertainty is statistical and the second is systematic. No evidence for a substantial intrinsic charm content of the nucleon is observed in the large Bjorken-x region.
The difference in the angular distributions between beauty quarks and antiquarks, referred to as the charge asymmetry, is measured for the first time in bb pair production at a hadron collider. The ...data used correspond to an integrated luminosity of 1.0 fb(-1) collected at 7 TeV center-of-mass energy in proton-proton collisions with the LHCb detector. The measurement is performed in three regions of the invariant mass of the bb system. The results obtained are A(C)(bb))(40<M(bb))<75 GeV/c(2)) = 0.4 ± 0.4 ± 0.3%, A(C)(bb))(75<M(bb)) < 105 GeV/c(2)) = 2.0 ± 0.9 ± 0.6%, A(C)(bb)(M(bb)) > 105 GeV/c(2)) = 1.6 ± 1.7 ± 0.6%, where A(C)(bb)) is defined as the asymmetry in the difference in rapidity between jets formed from the beauty quark and antiquark, where in each case the first uncertainty is statistical and the second systematic. The beauty jets are required to satisfy 2 < η < 4, E(T) >20 GeV, and have an opening angle in the transverse plane Δ ϕ > 2.6 rad. These measurements are consistent with the predictions of the standard model.
Infection with the free-living amoeba
leads to life-threatening primary amoebic meningoencephalitis. Efficacious treatment options for these infections are limited, and the mortality rate is very ...high (∼98%). Parasite metabolism may provide suitable targets for therapeutic design. Like most other organisms, glucose metabolism is critical for parasite viability, being required for growth in culture. The first enzyme required for glucose metabolism is typically a hexokinase (HK), which transfers a phosphate from ATP to glucose. The products of this enzyme are required for both glycolysis and the pentose phosphate pathway. However, the
genome lacks an obvious HK homolog and instead harbors a glucokinase (Glck). The
Glck (NfGlck) shares limited (25%) amino acid identity with the mammalian host enzyme (
Glck), suggesting that parasite-specific inhibitors with anti-amoeba activity can be generated. Following heterologous expression, NfGlck was found to have a limited hexose substrate range, with the greatest activity observed with glucose. The enzyme had apparent
values of 42.5 ± 7.3 μM and 141.6 ± 9.9 μM for glucose and ATP, respectively. The NfGlck structure was determined and refined to 2.2-Å resolution, revealing that the enzyme shares greatest structural similarity with the
Glck. These similarities include binding modes and binding environments for substrates. To identify inhibitors of NfGlck, we screened a small collection of inhibitors of glucose-phosphorylating enzymes and identified several small molecules with 50% inhibitory concentration values of <1 μM that may prove useful as hit chemotypes for further leads and therapeutic development against
.
Infection with pathogenic free-living amoebae, including Naegleria fowleri,
spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central ...nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (
Glck) as a potential target for therapeutic intervention, as glucose metabolism is critical for
viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (
Glck) and
(
Glck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP,
Glck and
Glck have apparent
values of 472.5 and 41.0 μM, while Homo sapiens Glck (
Glck) has a value of 310 μM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent
values of 45.9 μM (
Glck) and 124 μM (
Glck) compared to ~8 mM for
Glck. Additionally,
Glck and
Glck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.
Objectives Current data do not provide enough information on how quality of life (QoL) evolves over time in cases of endoscopic thoracic sympathectomy (ETS). The purpose of this study was to ...ascertain whether the immediate improvement in QoL after the surgery was sustained until the fifth postoperative year. Methods This was a prospective, nonrandomized and uncontrolled study. From March 2001 to December 2003, 475 consecutive patients with hyperhidrosis submitted to ETS were included. A QoL questionnaire was applied at the preoperative day, around the 30th postoperative day, and after the fifth year. Results After excluding 22 patients who did not answer all the questions, we analyzed 453 patients. Their ages ranged from 11 to 57 years old, with a mean of 25.3 + 7.9 years, including 297 female patients (65.6%). All patients were assessed on three occasions: before surgery, around the 30th postoperative day, and after the fifth postoperative year. The QoL before surgery was considered to be poor or very poor for all patients. The QoL around 30 days after surgery was better in 412 patients (90.9%), the same in 27 patients (6.0%), and worse in 14 patients (3.1%). After 5 years, 409 patients (90.3%) were better, 27 (6.0%) were the same, and 14 (3.1%) were worse. There were no differences between these postoperative times according to the McNemar statistical test. Conclusion The patients had an immediate improvement in QoL after ETS, and this improvement was sustained until the fifth postoperative year.
The global lockdown to mitigate COVID-19 pandemic health risks has altered human interactions with nature. Here, we report immediate impacts of changes in human activities on wildlife and ...environmental threats during the early lockdown months of 2020, based on 877 qualitative reports and 332 quantitative assessments from 89 different studies. Hundreds of reports of unusual species observations from around the world suggest that animals quickly responded to the reductions in human presence. However, negative effects of lockdown on conservation also emerged, as confinement resulted in some park officials being unable to perform conservation, restoration and enforcement tasks, resulting in local increases in illegal activities such as hunting. Overall, there is a complex mixture of positive and negative effects of the pandemic lockdown on nature, all of which have the potential to lead to cascading responses which in turn impact wildlife and nature conservation. While the net effect of the lockdown will need to be assessed over years as data becomes available and persistent effects emerge, immediate responses were detected across the world. Thus, initial qualitative and quantitative data arising from this serendipitous global quasi-experimental perturbation highlights the dual role that humans play in threatening and protecting species and ecosystems. Pathways to favorably tilt this delicate balance include reducing impacts and increasing conservation effectiveness.
•The global COVID-19 lockdown has impacted nature and conservation programs.•Immediate effects are documented across the world and in all ecosystems.•Initial responses are biased towards established monitoring programs and networks.•Complex positive and negative effects were detected, some with cascading impacts.•Humans are important custodians of species and ecosystems.
Modern microscopy studies are capable of revealing ultra-fine particles (UFPs) and nanoparticles (NPs) that are produced in the processes related to traffic vehicular, industrial, metropolitan, and ...marine aerosol dry deposition in the coastal zones. Especially, secondary aerosol passages complexes categories of NPs and UFPs, which can be accumulated on construction compounds and by dry deposition, encourages multiples monuments deterioration routes. The advanced electron microscopies method is one of the most utilized in environmental studies. Between the different industrial areas in the world, the Caribbean area is the most relevant symbols of air quality due to climatic conditions with strong winds, but this study shows that regionally the most industrialized region does not have an adequate air quality. In the present work, electron microscopy analyses are used to describe of the extent of ultra-fine particle and nanoparticles in walls in contact to weathering. Numerous phases were recognized by advanced mineralogy methods. Thanks to the new analytical procedure it was feasible to understand NPs and UFPs; the occurrence of potential hazardous elements (PHEs), most of them as minerals but also combined in multiple accumulations with Al–Cr–Fe–K–Mg–Pb–Si–Ti–Zn amorphous; and carbonaceous phases.
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•Potential dangerous elements have been investigated in ultra-fine and nanoparticles from Marine Aerosol.•Self-made passive sampler (SMPS) was examined in a coastline atmosphere with diverse contamination.•Multi-analytical approach was utilized for the nondestructive investigation of sampled UFP and NPs.•Dry accumulation is an important influence on the preservation of human cultural heritage.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of malignant arrhythmia and sudden death particularly in young people. Although it is considered a desmosomal disease, ...mutations in non‐desmosomal genes have also been identified. We report on a family where a mutation in LDB3 is associated with this condition. The index case and first and second degree relatives underwent a complete clinical evaluation: physical examination, electrocardiography (ECG), signal‐averaged ECG, 2D echocardiogram, cardiac magnetic resonance and 24‐h monitoring. After ruling out mutations in the five desmosomal genes, genetic testing by means of Next Generation Sequencing was carried out on the proband. A heterozygous missense mutation in LDB3 c.1051A>G was identified. This result was confirmed by subsequent Sanger DNA sequencing. Another six carriers were identified amongst her relatives. Three subjects fulfilled the criteria for a definitive diagnosis of ARVC and one reached a borderline diagnosis. In conclusion, this is the first family with ARVC where a mutation in LDB3 is associated with ARVC. Next generation sequencing arises as a particular useful tool to point to new causative genes in ARVC.
Collision avoidance is one of the most difficult and challenging automatic driving operations in the domain of intelligent vehicles. In emergency situations, human drivers are more likely to brake ...than to steer, although the optimal maneuver would, more frequently, be steering alone. This statement suggests the use of automatic steering as a promising solution to avoid accidents in the future. The objective of this paper is to provide a collision avoidance system (CAS) for autonomous vehicles, focusing on pedestrian collision avoidance. The detection component involves a stereo-vision-based pedestrian detection system that provides suitable measurements of the time to collision. The collision avoidance maneuver is performed using fuzzy controllers for the actuators that mimic human behavior and reactions, along with a high-precision Global Positioning System (GPS), which provides the information needed for the autonomous navigation. The proposed system is evaluated in two steps. First, drivers' behavior and sensor accuracy are studied in experiments carried out by manual driving. This study will be used to define the parameters of the second step, in which automatic pedestrian collision avoidance is carried out at speeds of up to 30 km/h. The performed field tests provided encouraging results and proved the viability of the proposed approach.
Background and Purpose
Alterations in transcription factors that regulate the development and maintenance of dopamine (DA) neurons (such as Nurr1 and Pitx3) play an important role in the pathogenesis ...of addiction diseases. We have examined the effects of acute and chronic morphine and morphine withdrawal on TH expression and activity as well as expression of Nurr1, Pitx3 and Ago2 in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of the rat.
Experimental Approach
Rats were injected acutely with morphine and decapitated 1 or 2 h later. Another set of rats were made dependent on morphine by implantation of two morphine pellets. Precipitated withdrawal was induced by injection of naloxone. Ago2, Pitx3, Nurr1, total TH (tTH), TH phosphorylated at Ser31 and at Ser40, and 3,4‐Dihydroxyphenylacetic acid, and DA determination in the VTA and/or NAc were measured using immunoblotting, HPLC and immunofluorescence.
Key Results
Acute morphine produced a marked increase in TH activity and DA turnover in the NAc, concomitantly with increased Nurr1 and Pitx3 expression in the VTA. In contrast, precipitated morphine withdrawal decreased TH activation, TH expression and did not increase DA turnover in the NAc. These effects paralleled decreases in Ago2 expression, which was accompanied by increased Nurr1 and Pitx3, TH activity and normalized TH protein levels in the VTA.
Conclusions and Implications
The combined decrease in Ago2 and increases in Nurr1 and Pitx3 might represent some of the mechanisms that served to protect against accumbal TH regulation observed in morphine withdrawn rats, which may be critical for DA bioavailability to influence behaviour.
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