gebhart/patrepeval huggingface dataset:
Bacteria isolated from lung modulate asthma susceptibility in mice (2017)

Asthma is a chronic, non-curable, multifactorial disease with increasing incidence in industrial countries. This study evaluates the direct contribution of lung microbial components in allergic asthma in mice. Germ-Free and Specific-Pathogen-Free mice display similar susceptibilities to House Dust Mice-induced allergic asthma, indicating that the absence of bacteria confers no protection or increased risk to aeroallergens. In early life, allergic asthma changes the pattern of lung microbiota, and lung bacteria reciprocally modulate aeroallergen responsiveness. Primo-colonizing cultivable strains were screened for their immunoregulatory properties following their isolation from neonatal lungs. Intranasal inoculation of lung bacteria influenced the outcome of allergic asthma development: the strain CNCM I 4970 exacerbated some asthma features whereas the pro-Th1 strain CNCM I 4969 had protective effects. Thus, we confirm that appropriate bacterial lung stimuli during early life are critical for susceptibility to allergic asthma in young adults.
Prevalence of resistance and HIV-1 protease mutation patterns after failures with fosamprenavir-containing regimens (2010)

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK Fos-Amprenavir is one of the protease inhibitor that is recommended to treat protease inhibitor naïve of experienced patients. Amprenavir and darunavir share at least in part chemical structures and thus a possible selection of close protease gene mutations. Little is known about the frequency and the type of resistance mutations selected after virological failure to Fos-Amprenavir containing regimen. The aim of this study was to determine the genetic patterns and the prevalence of resistance mutations associated to virological failure to Fos-Amprenavir containing regimens in a cohort of naïve and experienced protease inhibitor patients. 172 PI experienced patients, treated by r/Fos-APV (100/700 mg BID) and 96 PI naïve patients treated by r/Fos-APV (100/700 mg BID n = 33 and 100/1400 mg OD n = 63) were analyzed. Reverse transcriptase (RT) and protease gene were sequenced and aminoacid changes analyzed before Fos-APV treatment and at time of virological failure. Mutations were analyzed with the ANRS algorithm V18. In PI experienced patients, there is a direct link between the number of PI resistance that were present at baseline and the probability of selection of resistance mutation at failure (p=0.01). The most common mutations selected were: V32I, L33F, M46L, I50V, I54L/V, I84V and L90M. In all cases when the protease gene at baseline harbored at least one PI resistance mutation, at least one resistance mutation was added at time of virological failure. Taking into account of the ANRS algorithm, 15% of patient developed a resistance to DRV. In PI naïve patients, only 6% of patients harbored a PI resistance mutation selected at time of virological failure. The most frequent selected mutations were V32I, I47V, I50V and I84V. There is a link between the duration of virological failure under r/Fos-APV and the rate of selected mutation (1% of cases at month 1, 3% at month 3 and 6% at month 6. Taking into account of the ANRS algorithm, only one patient developed a resistance to DRV. This study confirms that resistance mutations selected by Fos-APV occurs mainly in PI experienced patients. Except for patients with more than 6 months replication with Fos-APV, the risk to select cross resistance to DRV is very low.
Computer-Aided Ligand Discovery for Estrogen Receptor Alpha (2020)

Breast cancer (BCa) is one of the most predominantly diagnosed cancers in women. Notably, 70% of BCa diagnoses are Estrogen Receptor α positive (ERα+) making it a critical therapeutic target. With that, the two subtypes of ER, ERα and ERβ, have contrasting effects on BCa cells. While ERα promotes cancerous activities, ERβ isoform exhibits inhibitory effects on the same. ER-directed small molecule drug discovery for BCa has provided the FDA approved drugs tamoxifen, toremifene, raloxifene and fulvestrant that all bind to the estrogen binding site of the receptor. These ER-directed inhibitors are non-selective in nature and may eventually induce resistance in BCa cells as well as increase the risk of endometrial cancer development. Thus, there is an urgent need to develop novel drugs with alternative ERα targeting mechanisms that can overcome the limitations of conventional anti-ERα therapies. Several functional sites on ERα, such as Activation Function-2 (AF2), DNA binding domain (DBD), and F-domain, have been recently considered as potential targets in the context of drug research and discovery. In this review, we summarize methods of computer-aided drug design (CADD) that have been employed to analyze and explore potential targetable sites on ERα, discuss recent advancement of ERα inhibitor development, and highlight the potential opportunities and challenges of future ERα-directed drug discovery.
The Discovery of Manogepix/Fosmanogepix and Other Gwt1 Inhibitors for the Treatment of Invasive Fungal Infections (2019)

Medicinal Chemistry Reviews is an outstanding 680 page volume providing timely and critical reviews of important topics in medicinal chemistry. It is provided free of charge to MEDI members in electronic format. Members can also order a print copy, for the cost of printing, shipping and handling
Evidence that the Arabidopsis Ubiquitin C-terminal Hydrolases 1 and 2 associate with the 26S proteasome and the TREX-2 complex (2012)

The 26S proteasome interacts with a number of different proteins, while the TREX-2 complex is an important component of the mRNA export machinery. In animals and yeast, members of the Ubiquitin C-terminal Hydrolase 37 (UCH37) family are found to associate with the 26S proteasome, but this has not been demonstrated in plants. The Arabidopsis UCH1 and UCH2 are orthologous to UCH37. Here, we show that UCH1 and UCH2 interact with the 26S proteasome lid subunits. In addition, the two UCHs also interact with TREX-2 components. Our data suggest that Arabidopsis UCHs may serve as a link between the 26S proteasome lid complex and the TREX-2 complex.
Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success (2016)

Photodynamic therapy (PDT) can be a highly complex treatment, with many parameters influencing treatment efficacy. The extent to which dosimetry is used to monitor and standardize treatment delivery varies widely, ranging from measurement of a single surrogate marker to comprehensive approaches that aim to measure or estimate as many relevant parameters as possible. Today, most clinical PDT treatments are still administered with little more than application of a prescribed drug dose and timed light delivery, and thus the role of patient-specific dosimetry has not reached widespread clinical adoption. This disconnect is at least partly due to the inherent conflict between the need to measure and understand multiple parameters in vivo in order to optimize treatment, and the need for expedience in the clinic and in the regulatory and commercialization process. Thus, a methodical approach to selecting primary dosimetry metrics is required at each stage of translation of a treatment procedure, moving from complex measurements to understand PDT mechanisms in pre-clinical and early phase I trials, towards the identification and application of essential dose-limiting and/or surrogate measurements in phase II/III trials. If successful, identifying the essential and/or reliable surrogate dosimetry measurements should help facilitate increased adoption of clinical PDT. In this paper, examples of essential dosimetry points and surrogate dosimetry tools that may be implemented in phase II/III trials are discussed. For example, the treatment efficacy as limited by light penetration in interstitial PDT may be predicted by the amount of contrast uptake in CT, and so this could be utilized as a surrogate dosimetry measurement to prescribe light doses based upon pre-treatment contrast. Success of clinical ALA-based skin lesion treatment is predicted almost uniquely by the explicit or implicit measurements of photosensitizer and photobleaching, yet the individualization of treatment based upon each patients measured bleaching needs to be attempted. In the case of ALA, lack of PpIX is more likely an indicator that alternative PpIX production methods must be implemented. Parsimonious dosimetry, using surrogate measurements that are clinically acceptable, might strategically help to advance PDT in a medical world that is increasingly cost and time sensitive. Careful attention to methodologies that can identify and advance the most critical dosimetric measurements, either direct or surrogate, are needed to ensure successful incorporation of PDT into niche clinical procedures.
Quantifying infection risks in incompatible living donor kidney transplant recipients (2020)

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = <sub>0.77</sub> 1.40<sub>2.56</sub> ,P = .3) and moderately (wIRR = <sub>0.88</sub> 1.35<sub>2.06</sub> ,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = <sub>1.33</sub> 2.22<sub>3.72</sub> ,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = <sub>2.62</sub> 3.57<sub>4.88</sub> , P < .001) and death-censored graft loss (wHR = <sub>1.15</sub> 4.01<sub>13.95</sub> ,P = .03). Post-KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.
Numerical Investigation and Integrated Optimization of Solvent-SAGD Process (2014)

Abstract The hybrid process is a technique which involves the co-injection of liquid solvent with steam in a similar steam assisted gravity drainage (SAGD) pattern. The combined process can significantly reduce the limitation of the pure SAGD process. Numerous simulation studies have been previously conducted to understand the hybrid processes. However, most of the models suffer from the lack of an accurate equation-of-state (EOS)/viscosity models for the true estimation of the phase and volumetric behavior of solvent-bitumen-steam as well as the mixture viscosity at the edge oil-flow zone. The provided fluid model in this study is based on our extensive work done on the experimental analysis, and the modeling of viscosity and phase behavior of solvent and viscous oil mixtures for wide range of pressures and temperatures. In this study, hydrocarbon additives such as C5, C6, C7, C8and C12are used as medium solvents and C15is selected as the heavy solvent. First, the mechanism of the medium and heavy solvents and their impact at the oil-gas interface is discussed. It is found that the development of the edge oil-flow zone is significantly controlled by solvent type where different mechanisms based on K-values behavior exist for different solvents. Finally, we developed the integrated optimization model which includes the reservoir SAGD pattern and the surface facility process. Moreover, the pipeline used to transfer the mixture of heavy oil (or bitumen) and solvent from surface process to the market is integrated and optimized. The overall net present value (NPV) of the field is calculated and optimized by selecting the main regression variables. We found that for the specific solvent type; the solvent amount, the injection pressure of the solvent and steam are the main parameters which significantly determine the success of such processes. Our findings are significantly important for the future development of the solvent-SAGD pattern i.e. both reservoir and surface/pipe-line facilities. In addition, it can be implemented for any type of heavy oil field which still requires thermal methods to increase the oil recovery. Introduction From last decades, SAGD process has been proven to be a promising oil-recovery process in bitumen deposits. However, the economics of SAGD is mainly influenced by first the natural gas used to generate the steam and second the water treatment and recycling. This is due to the consumption of a large amount of water and natural gas, which results in costly post-production water treatment and a significant amount of CO2emission. The Hybrid process is another technique which involves the co-injection of liquid solvent with steam in a similar SAGD pattern. The combined process can significantly reduce the amount of energy, water and greenhouse gases compared to the SAGD process. Moreover, the main purpose of solvent additives to steam in an SAGD process is to take the advantage of steam for bringing heat to cold bitumen and also the solvent to dissolve into the bitumen and increase the economic efficiency of the process.
Activation of peripheral nerve fibers by electrical stimulation in the sole of the foot (2013)

The nerve staining and modeling results do not explain differences in NWR thresholds across the sole of the foot which may suggest that central mechanisms contribute to variation in NWR excitability across the sole of the foot.
LATE-BREAKING ABSTRACT: Inhibition of MAP3K19 - A novel therapeutic approach for treatment of IPF (2015)

MAP3K19 (RC Kinase) is a novel nuclear kinase that is expressed in healthy lung by macrophages and type II epithelial cells, upregulated in IPF lungs, and commonly found in atypical epithelium adjacent to fibroblastic foci. Consistent with this cellular distribution, late-stage pre-clinical small molecule inhibitors of MAP3K19 caused significant reductions in inflammatory infiltrate, extra-cellular matrix deposition and hydroxyproline production in a murine xenograft model of IPF. In the murine bleomycin model, prophylactic or therapeutic oral administration of a MAP3K19 antagonist compound significantly decreased inflammation, fibrosis and collagen content. In contrast, Pirfenidone only significantly affected lung collagen levels. To understand the mechanism of action of specific MAP3K19 inhibitors, we examined whether the TGF-β signaling pathway was impacted. An examination of IPF patient-derived myofibroblast cell lines, primary human macrophages, and numerous MAP3K19+ human cell lines showed that inhibition of MAP3K19 resulted in a significant decrease in the nuclear accumulation of P-Smad-2 and P-Smad-3 upon TGF-β stimulation. Pirfenidone had minimal effects. Inhibition of MAP3K19 did not affect Smad-4 levels, and cytoplasmic levels of Smad-2 and Smad-3 were also unaffected. Inhibition of MAP3K19 also blocked TGF-β-induced gene transcription of various EMT molecules. Surprisingly, inhibition of MAP3K19 also inhibited TGF-β-induced nuclear translocation of Notch. These results suggest that MAP3K19 may act as a regulator of nuclear translocation of various signaling molecules involved in transcription, and provides a mechanism to explain how MAP3K19 inhibition may provide therapeutic benefit in IPF.
MPC-LTV approach of a fuel cell/supercapacitor power supply system for electric vehicles (2016)

Seminar, Concordia University, Montréal, Canada
Lipo-chitooligosaccharides as regulatory signals of fungal growth and development (2020)

Lipo-chitooligosaccharides (LCOs) are signaling molecules produced by rhizobial bacteria that trigger the nodulation process in legumes, and by some fungi that also establish symbiotic relationships with plants, notably the arbuscular and ecto mycorrhizal fungi. Here, we show that many other fungi also produce LCOs. We tested 59 species representing most fungal phyla, and found that 53 species produce LCOs that can be detected by functional assays and/or by mass spectroscopy. LCO treatment affects spore germination, branching of hyphae, pseudohyphal growth, and transcription in non-symbiotic fungi from the Ascomycete and Basidiomycete phyla. Our findings suggest that LCO production is common among fungi, and LCOs may function as signals regulating fungal growth and development.
Cell transformation by c‐Ha‐rasVal12 oncogene is accompanied by a decrease in histone H1° and an increase in nucleosomal repeat length (1995)

The activated c-Ha-rasVal12 oncogene is often involved in the genesis of human malignancies. We show here that in c-Ha-rasVal12 oncogene-transformed mouse NIH 3T3 fibroblasts the copy number and expression level of the mutant ras oncogene correlates with the degree of chromatin decondensation, as assessed by micrococcal nuclease (MNase) and DNase I digestion. MNase and DNase I analyses further revealed that the nucleosomal repeat lengths were different in the normal and ras oncogene-transformed cells, 162.3 bp and 178.1 bp, respectively. These chromatin changes were accompanied by alterations in the content of histone H1 zero. Furthermore, using DNase I as a probe, we discovered that serum stimulation of normal and transformed cells, synchronized by serum starvation, induces rapid reversible changes in the structure of bulk chromatin that may be linked to transcriptional activation. Our data thus indicate that cell transformation by ras is associated with specific changes in chromatin structure that make it more vulnerable, and prone to additional mutations characteristic of cancer development in vivo.
Diagnostics and investigations of thermodynamic equilibrium in LIBS plasmas using Thomson Scattering (2010)

Présentation orale (G.Travaillé)
The rupe reaction applied to 3-(n-perfluorobutyl)alk-2-yn-1-ols: an unexpected route to 5-n-perfluoropropylfuran-3(2H)-ones (1985)

Under the conditions of the Rupe reaction hydration of the triple bond of the perfluorobutylalkynols n-C4F9CCCR(Me)OH occur yielding the ketone n-C4F9CH2COCR(Me)OH; this ketone undergoes intramolecular reaction providing an interesting route to 5-n-perfluoropropylfuran-3(2H)-ones.
Amblyopia: a tale of two approaches. (1995)

Our understanding of the physiological basis for amblyopia in humans has undergone dramatic changes over the past two decades. The first such change occurred when we were first able to record from single neurones in different parts of the visual pathway and develop neural models of the anomaly. The second came from psychophysical investigations and evaluations of these animal models. Our understanding has progressed from one focused on the properties of single cortical cells to an appreciation of the anomalous behaviour of cellular networks.
Synthesis and Self-Assembly of RGD-Functionalized PEO-PB Amphiphiles (2009)

Amphiphilic block copolymer self-assembly provides a versatile means to prepare nanoscale micelles in solution. The utilization of these structures as targeted drug delivery vehicles has motivated efforts to prepare bioactive ligand-functionalized polymer micelles. The impact of ligand conjugation on micelle morphology was examined through use of well-characterized poly(ethylene oxide)-b-poly(butadiene) (OB) block copolymers functionalized to varying extents with a biologically relevant RGD-containing peptide sequence. Micelle morphology and dilute solution behavior of RGD-functionalized OB (RGD-OB) copolymers were examined using cryogenic transmission electron microscopy (cryo-TEM) and dynamic mechanical analysis. The direct dispersion of RGD-OB copolymers into deionized water yielded a variety of structures; the observed morphologies deviated from the canonical series predicted by the overall change in amphiphile composition due to peptide conjugation. RGD functionalized spherical micelles, cylindrical micelle networks, and annular multilayer vesicles were prepared. The morphological behavior was attributed to interactions between peptide moieties conjugated to the termini of coronal chains and has implications in the design of targeting micelles for drug delivery applications.
Faculty Opinions recommendation of Voltage sensor conformations in the open and closed states in ROSETTA structural models of K(+) channels. (2006)

Voltage-gated ion channels control generation and propagation of action potentials in excitable cells. Significant progress has been made in understanding structure and function of the voltage-gated ion channels, highlighted by the high-resolution open-state structure of the voltage-gated potassium channel, K(v)1.2. However, because the structure of the closed state is unknown, the gating mechanism remains controversial. We adapted the rosetta membrane method to model the structures of the K(v)1.2 and KvAP channels using homology, de novo, and domain assembly methods and selected the most plausible models using a limited number of experimental constraints. Our model of K(v)1.2 in the open state is very similar in overall topology to the x-ray structure of this channel. Modeling of KvAP in the open state suggests that orientation of the voltage-sensing domain relative to the pore-forming domain is considerably different from the orientation in the K(v)1.2 open state and that the magnitude of the vertical movement of S4 is significantly greater. Structural modeling of closed state of K(v)1.2 suggests gating movement that can be viewed as a sum of two previously suggested mechanisms: translation (2-4 A) plus rotation ( approximately 180 degrees ) of the S4 segment as proposed in the original "sliding helix" or "helical screw" models coupled with a rolling motion of the S1-S3 segments around S4, similar to recent "transporter" models of gating. We propose a unified mechanism of voltage-dependent gating for K(v)1.2 and KvAP in which this major conformational change moves the gating charge across the electric field in an analogous way for both channels. PMID: 16648251 Funding information This work was supported by: NIMH NIH HHS, United States Grant ID: K01 MH67625 NINDS NIH HHS, United States Grant ID: R01 NS15751 NINDS NIH HHS, United States Grant ID: R01 NS015751 NIMH NIH HHS, United States Grant ID: K01 MH067625
Multiplexing Gain of Amplify-Forward Relaying in Wireless Multi-Antenna Relay Networks (2009)

This paper studies the general multi-antenna multiple-relay network. Every two nodes of the network are either connected together through a Rayleigh fading channel or disconnected. We study the ergodic capacity of the network in the high SNR regime. We prove that the traditional amplify-forward relaying achieves the maximum multiplexing gain of the network. Furthermore, we show that the maximum multiplexing gain of the network is equal to the minimum vertex cut-set of the underlying graph of the network, which can be computed in polynomial time in terms of the number of network nodes. Finally, the argument is extended to the multicast and multi-access scenarios.