3,506 research outputs found
Characterisation of the natural attenuation of chromium contamination in the presence of nitrate using isotopic methods. A case study from the Matanza-Riachuelo river basin, Argentina
The groundwater contamination by hexavalent chromium (Cr(VI)) in a site of the Matanza-Riachuelo River basin (MRB), Argentina, has been evaluated by determining the processes that control the natural mobility and attenuation of Cr(VI) in the presence of high nitrate (NO3−) contents. The groundwater Cr(VI) concentrations ranged between 1.9E-5 mM and 0.04 mM, while the NO3− concentrations ranged between 0.5 mM and 3.9 mM
Immediate effects of a telerehabilitation program based on aerobic exercise in women with fibromyalgia
Background: We analyzed the immediate effects of a Telerehabilitation Program (TP) based on aerobic exercise in women with fibromyalgia (FM) syndrome during the lockdown declared in Spain due to the COVID-19 pandemic.
Methods: A single-blind randomized controlled trial was designed. Thirty-four women with FM were randomized into two groups: TP group and Control group. The intervention lasted 15 weeks, with 2 sessions per week. The TP based on aerobic exercise was guided by video and the intensity of each session was monitored using the Borg scale. Pain intensity (Visual Analogue Scale), mechanical pain sensitivity (algometer), number of tender points, FM impact (Revised Fibromyalgia Impact Questionnaire), pain catastrophizing (Pain Catastrophizing Scale), physiological distress (Hospital Anxiety and Depression Scale), upper (Arm Curl Test) and lower-limb physical function (6-min Walk Test) were measured at baseline and after the intervention.
Results: The TP group improved pain intensity (p = 0.022), mechanical pain sensitivity (p 0.05).
Conclusion: A TP based on aerobic exercise achieved improvements on pain intensity, mechanical pain sensitivity, and psychological distress compared to a Control group during the lockdown declared in Spain due to COVID-19 pandemic
Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents
New treatments are needed for neglected tropical diseases (NTDs) such as Human African
trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism
high-throughput screening campaign, we previously identified 797 human kinase inhibitors
that grouped into 59 structural clusters and showed activity against T. brucei, the causative
agent of HAT. We herein report the results of further investigation of one of these clusters
consisting of substituted isatin derivatives, focusing on establishing structure-activity and
-property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best
activity-property profile, pharmacokinetic parameters were measured in mice
Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis
Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments
Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis.
Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.The authors acknowledge funding from the National Institute of Allergy and Infectious Diseases (M.P.P. and M.N., R01AI114685; M.P.P., 1R21AI127594, R01AI124046; C.R.C., R21AI126296; https://www.niaid.nih.gov/), the Spanish Ministerio de Economí a, Industria y Competitividad (M.N., SAF2015-71444-P; D.G.-P., SAF2016-79957-R; http://www.mineco.gob.es), Subdireccion General de Redes ́ y Centros de Investigacion Cooperativa (RICET, https://www.ricet.es/) (M.N., RD16/0027/0019; D.G.P., RD16/ 0027/0014), and RTI2018-097210-B-I00 (MINCIU-FEDER) to F.G. An ACS MEDI Predoctoral Fellowship for D.M.K. is gratefully acknowledged, as is support from the National Science Foundation for K.F. (CHE-1262734). We thank AstraZeneca, Charles River Laboratories, and GlaxoSmithKline for the provision of the in vitro ADME and physicochemical properties data. The use of JChem/ChemAxon software is acknowledged
Hidden Sylvatic Foci of the Main Vector of Chagas Disease Triatoma infestans: Threats to the Vector Elimination Campaign?
Triatoma infestans, a highly domesticated species and historically the main vector of Trypanosoma cruzi, is the target of an insecticide-based elimination program in the southern cone countries of South America since 1991. Only limited success has been achieved in the Gran Chaco region due to repeated reinfestations. We conducted full-coverage spraying of pyrethroid insecticides of all houses in a well-defined rural area in northwestern Argentina, followed by intense monitoring of house reinfestation and searches for triatomine bugs in sylvatic habitats during the next two years, to establish the putative sources of new bug colonies. We found low-density sylvatic foci of T. infestans in trees located within the species' flight range from the nearest infested house detected before control interventions. Using multiple methods (fine-resolution satellite imagery, geographic information systems, spatial statistics, genetic markers and wing geometric morphometry), we corroborated the species identity of the sylvatic bugs as T. infestans and found they were indistinguishable from or closely related to local domestic or peridomestic bug populations. Two sylvatic foci were spatially associated to the nearest peridomestic bug populations found before interventions. Sylvatic habitats harbor hidden foci of T. infestans that may represent a threat to vector suppression attempts
Charge separation relative to the reaction plane in Pb-Pb collisions at TeV
Measurements of charge dependent azimuthal correlations with the ALICE
detector at the LHC are reported for Pb-Pb collisions at TeV. Two- and three-particle charge-dependent azimuthal correlations in
the pseudo-rapidity range are presented as a function of the
collision centrality, particle separation in pseudo-rapidity, and transverse
momentum. A clear signal compatible with a charge-dependent separation relative
to the reaction plane is observed, which shows little or no collision energy
dependence when compared to measurements at RHIC energies. This provides a new
insight for understanding the nature of the charge dependent azimuthal
correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286
A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE
In this small note we are concerned with the solution of Forward-Backward
Stochastic Differential Equations (FBSDE) with drivers that grow quadratically
in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem
is a comparison result that allows comparing componentwise the signs of the
control processes of two different qgFBSDE. As a byproduct one obtains
conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio
Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at = 5.02 TeV
Two-particle angular correlations between unidentified charged trigger and
associated particles are measured by the ALICE detector in p-Pb collisions at a
nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum
range 0.7 5.0 GeV/ is examined,
to include correlations induced by jets originating from low
momen\-tum-transfer scatterings (minijets). The correlations expressed as
associated yield per trigger particle are obtained in the pseudorapidity range
. The near-side long-range pseudorapidity correlations observed in
high-multiplicity p-Pb collisions are subtracted from both near-side
short-range and away-side correlations in order to remove the non-jet-like
components. The yields in the jet-like peaks are found to be invariant with
event multiplicity with the exception of events with low multiplicity. This
invariance is consistent with the particles being produced via the incoherent
fragmentation of multiple parton--parton scatterings, while the yield related
to the previously observed ridge structures is not jet-related. The number of
uncorrelated sources of particle production is found to increase linearly with
multiplicity, suggesting no saturation of the number of multi-parton
interactions even in the highest multiplicity p-Pb collisions. Further, the
number scales in the intermediate multiplicity region with the number of binary
nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/161
Transverse sphericity of primary charged particles in minimum bias proton-proton collisions at , 2.76 and 7 TeV
Measurements of the sphericity of primary charged particles in minimum bias
proton--proton collisions at , 2.76 and 7 TeV with the ALICE
detector at the LHC are presented. The observable is linearized to be collinear
safe and is measured in the plane perpendicular to the beam direction using
primary charged tracks with GeV/c in . The
mean sphericity as a function of the charged particle multiplicity at
mid-rapidity () is reported for events with different
scales ("soft" and "hard") defined by the transverse momentum of the leading
particle. In addition, the mean charged particle transverse momentum versus
multiplicity is presented for the different event classes, and the sphericity
distributions in bins of multiplicity are presented. The data are compared with
calculations of standard Monte Carlo event generators. The transverse
sphericity is found to grow with multiplicity at all collision energies, with a
steeper rise at low , whereas the event generators show the
opposite tendency. The combined study of the sphericity and the mean with multiplicity indicates that most of the tested event generators
produce events with higher multiplicity by generating more back-to-back jets
resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with
tune PERUGIA-2011 exhibits a noticeable improvement in describing the data,
compared to the other tested generators.Comment: 21 pages, 9 captioned figures, 3 tables, authors from page 16,
published version, figures from
http://aliceinfo.cern.ch/ArtSubmission/node/308
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