gebhart/patrepeval huggingface dataset:
TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice (2006)

Defects in purine nucleoside phosphorylase (PNP) enzyme activity result in abnormal nucleoside homeostasis, severe T cell immunodeficiency, neurological dysfunction, and early death. Protein transduction domain (PTD) can transfer molecules into cells and may help restore PNP activity in cases of PNP deficiency. However, long-term use of PTD to replace enzymes in animal models or patients has not previously been described. We fused human PNP to the HIV-TAT PTD and found that the fusion with TAT changed the retention and distribution of PNP in PNP-deficient mice. TAT induced rapid intracellular delivery of PNP into tissues, including the brain, prevented urinary excretion of PNP, and protected PNP from neutralizing antibodies, resulting in significant extension of the enzyme's biological activity in vivo. Frequent TAT-PNP injections in PNP-deficient mice corrected the metabolic disorder and immune defects with no apparent toxicity. TAT-PNP remained effective over 24 weeks of treatment, resulting in continued improvement in immune function and extended survival. Our data demonstrate that TAT changes the properties of PNP in vivo and that long-term intracellular delivery of PNP by TAT corrects PNP deficiency in mice. We provide evidence to promote further use of PTD to treat diseases that require repeated intracellular enzyme or protein delivery.
Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells (2019)

Abstract: Background: β-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs). These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling. Results: We classified human HCC cell lines into "well-differentiated" and "poorly differentiated" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant β-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant β-catenin in HCC cell lines. Conclusion: Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt signaling in well-differentiated, and its repression in poorly differentiated cell lines. One potential mechanism of repression involved Wnt5a, acting as an antagonist of canonical Wnt signaling. Our observations support the hypothesis that Wnt pathway is selectively activated or repressed depending on differentiation status of HCC cells. We propose that canonical and noncanonical Wnt pathways have complementary roles in HCC, where the canonical signaling contributes to tumor initiation, and noncanonical signaling to tumor progression.
International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: Rationale and protocol (2011)

Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators. The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naive or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm. First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide. International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849 URL:
 http://clinicaltrials.gov/ct2/show/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1
POSIDONIA 6000: a new long range highly accurate ultra short base line positioning system (2002)

FREMER (French Research Institute for the Exploitation of the Sea) is currently operating manned submersibles, towed sonars and ROVs up to 6000 m. In most cases, long base lines are to be replaced by a new ultra short base line positioning system called POSIDONIA 6000. This system was developed by Thomson Marconi Sonar and Mors Environment. It reduces the operation time and overall costs by improving accuracy, reliability in noisy environments and reducing multipath effects. After a complete description of the system, the paper presents results of sea operations with SAR (deep water side scan sonar), VICTOR 6000 (IFREMER ROV) and NAUTILE (deep manned submersible). These vehicles have been operated at depths reaching up to 5,400 m in various combinations. A precision better than 1% of water depth was obtained, even in very bad weather conditions.
Teneurins: Role in Cancer and Potential Role as Diagnostic Biomarkers and Targets for Therapy (2021)

Teneurins have been identified in vertebrates as four different genes (TENM1-4), coding for membrane proteins that are mainly involved in embryonic and neuronal development. Genetic studies have correlated them with various diseases, including developmental problems, neurological disorders and congenital general anosmia. There is some evidence to suggest their possible involvement in cancer initiation and progression, and drug resistance. Indeed, mutations, chromosomal alterations and the deregulation of teneurins expression have been associated with several tumor types and patient survival. However, the role of teneurins in cancer-related regulatory networks is not fully understood, as both a tumor-suppressor role and pro-tumoral functions have been proposed, depending on tumor histotype. Here, we summarize and discuss the literature data on teneurins expression and their potential role in different tumor types, while highlighting the possibility of using teneurins as novel molecular diagnostic and prognostic biomarkers and as targets for cancer treatments, such as immunotherapy, in some tumors.
Developmental Programming: Impact of Gestational Steroid and Metabolic Milieus on Adiposity and Insulin Sensitivity in Prenatal Testosterone-Treated Female Sheep (2015)

Prenatal testosterone (T) excess in sheep leads to peripheral insulin resistance (IR), reduced adipocyte size, and tissue-specific changes, with liver and muscle but not adipose tissue being insulin resistant. To determine the basis for the tissue-specific differences in insulin sensitivity, we assessed changes in negative (inflammation, oxidative stress, and lipotoxicity) and positive mediators (adiponectin and antioxidants) of insulin sensitivity in the liver, muscle, and adipose tissues of control and prenatal T-treated sheep. Because T excess leads to maternal hyperinsulinemia, fetal hyperandrogenism, and functional hyperandrogenism and IR in their female offspring, prenatal and postnatal interventions with antiandrogen, flutamide, and the insulin sensitizer rosiglitazone were used to parse out the contribution of androgenic and metabolic pathways in programming and maintaining these defects. Results showed that (1) peripheral IR in prenatal T-treated female sheep is related to increases in triglycerides and 3-nitrotyrosine, which appear to override the increase in high-molecular-weight adiponectin; (2) liver IR is a function of the increase in oxidative stress (3-nitrotyrosine) and lipotoxicity; (3) muscle IR is related to lipotoxicity; and (4) the insulin-sensitive status of visceral adipose tissue appears to be a function of the increase in antioxidants that likely overrides the increase in proinflammatory cytokines, macrophages, and oxidative stress. Prenatal and postnatal intervention with either antiandrogen or insulin sensitizer had partial effects in preventing or ameliorating the prenatal T-induced changes in mediators of insulin sensitivity, suggesting that both pathways are critical for the programming and maintenance of the prenatal T-induced changes and point to potential involvement of estrogenic pathways.
FK506 and Nerve Regeneration: Past, Present, and Future (2013)

Promoting neurological recovery requires strategies that simultaneously provide protection to injured neurons and increase the numbers of neurons that extend axons while inducing more rapid and extensive axon regeneration across long nerve gaps. An agent that facilitates the speed and success of reinnervation will have direct applicability to the clinical management of severe peripheral nerve injuries. The immunosuppressive drug FK506 has been proven to have neuroprotective and neurotrophic actions in experimental models, increasing neurite elongation and accelerating the rate of nerve regeneration in vitro and in vivo. This review examines the role played by FK506, with primary focus on its role as a neurotrophic agent and its potential clinical use as a promoter of neurological recovery following peripheral nerve injuries.
Long pulse electron beam pumped molecular F*2 laser (1995)

An electron beam pumped molecular F*2 laser with optical pulse widths up to 160 ns, and an output energy of 1.7 J (optical flux of 4.6 MW/cm2) has been realized. The widths of the laser pulses seem only limited by the duration of the excitation pulse (160 ns). For specific output powers up to 100 kW/cm3 no signs of self-terminating laser pulses due to bottlenecking in the lower laser level have been observed.
Tetrahydropyranyl: A Non‐aromatic, Mild‐Acid‐Labile Group for Hydroxyl Protection in Solid‐Phase Peptide Synthesis (2017)

The use of the tetrahydropyranyl (Thp) group for the protection of serine and threonine side-chain hydroxyl groups in solid-phase peptide synthesis has not been widely investigated. Ser/Thr side-chain hydroxyl protection with this acid-labile and non-aromatic moiety is presented here. Although Thp reacts with free carboxylic acids, it can be concluded that to introduce Thp ethers at the hydroxyl groups of N-protected Ser and Thr, protection of the C-terminal carboxyl group is unnecessary due to the lability of Thp esters. Thp-protected Ser/Thr-containing tripeptides are synthesized and the removal of Thp studied in low concentrations of trifluoroacetic acid in the presence of cation scavengers. Given its general stability to most non-acidic reagents, improved solubility of its conjugates and ease with which it can be removed, Thp emerges as an effective protecting group for the hydroxyl groups of Ser and Thr in solid-phase peptide synthesis.
A polymorphic DNA sequence from the terminal part of chromosome 20q [D20S25] (1990)

International audience
Circulating DNA Demonstrates Convergent Evolution and Common Resistance Mechanisms during Treatment of Colorectal Cancer (2017)

<b>Purpose:</b> Liquid biopsies allow the tracking of clonal dynamics and detection of mutations during treatment.<b>Experimental Design:</b> We evaluated under blinded conditions the ability of cell-free DNA (cfDNA) to detect <i>RAS</i>/<i>BRAF</i> mutations in the plasma of 42 metastatic colorectal cancer patients treated on a phase Ib/II trial of FOLFOX and dasatinib, with or without cetuximab.<b>Results:</b> Prior to treatment, sequencing of archival tissue detected mutations in 25 of 42 patients (60%), while the cfDNA assay detected mutations in 37 of 42 patients (88%). Our cfDNA assay detected mutations with allele frequencies as low as 0.01%. After exposure to treatment, 41 of 42 patients (98%) had a cfDNA-detected <i>RAS</i>/<i>BRAF</i> mutation. Of 21 patients followed with serial measurements who were <i>RAS/BRAF</i> mutant at baseline, 11 (52%) showed additional point mutation following treatment and 3 (14%) no longer had detectable levels of another mutant allele. Of <i>RAS</i>/<i>BRAF</i> wild-type tumors at baseline, 4 of 5 (80%) showed additional point mutations. cfDNA quantitative measurements from this study closely mirrored changes in CEA and CT scan results, highlighting the importance of obtaining quantitative data beyond the mere presence of a mutation.<b>Conclusions:</b> Our findings demonstrate the development of new <i>RAS</i>/<i>BRAF</i> mutations in patients regardless of whether they had preexisting mutations in the pathway, demonstrating a convergent evolutionary pattern. <i>Clin Cancer Res; 23(16); 4578-91. ©2017 AACR</i>.
Electronic energy transfer from nitrogen molecules to metal atoms (1980)

The results of this research show that electronic excitation of metal atoms by N2(A) molecules is easily obtained in the metals studied. Moreover, EET is a fast and preferential process resulting in population inversion between some of the Cu states. Evidence is presented for the possible importance of the Franck-Condon principle in the collisional quenching of N2(A) by Cu. The similarity of the population distribution of the Cu states in the N2(A) + Cu and in the NF3 + Cu systems corroborates the suggestion that in the latter case the inverted population in copper originates from chemically produced N2(A). LIF studies of N2(B,v) have demonstrated a multiexponential decay which is interpreted as a fast collisional coupling of N2(B,v) to adjacent energy levels and a slower overall decay of these coupled levels. Our results may have bearing on existing interpretations of N2(B) chemistry. The 2N2(A) energy pooling rate constant could be estimated more accurately once the N2(B,v) quenching rate constant are found (13). This accuracy is needed since the energy pooling reaction is a competitive reaction to EET from N2(A). The information presented on the N2 Herman infrared system due to energy pooling may help in the identification of the upper and lower states of this unassigned band. (Author)
Synthesis of β-FeOOH and α-Fe2O3nanorods and electrochemical properties of β-FeOOH (2004)

β-FeOOH nanorods with a tunnel-type structure were synthesized via a hydrothermal method at low temperature and characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA) and galvanostatic tests. From TEM bright-field images, a rodlike morphology with an average diameter of 30 ± 5 nm and an average length of 400 nm (aspect ratio ≈ 13) is observed. Electrochemical tests show that thesew nanorods deliver a large discharge capacity of 275 mA h g−1vs. Li metal at 0.1 mA cm−2 (voltage window 1.5–4.2 V). α-Fe2O3 nanorods with a regular pore structure were obtained by calcining the as-synthesized FeOOH at 520 °C.
Plant active products and emerging interventions in water potabilisation: disinfection and multi-drug resistant pathogen treatment (2021)

Abstract Background This review aims at establishing the emerging applications of phytobiotics in water treatment and disinfection. Results Statistical analysis of data obtained revealed that the use of plant product in water treatment needs more research attention. A major observation is that plants possess multifaceted components and can be sustainably developed into products for water treatment. The seed (24.53%), flower (20.75), leaf (16.98%) and fruit (11.32%) biomasses are preferred against bulb (3.77%), resin (1.89%), bark (1.89%) and tuber (1.89%). The observation suggests that novel applications of plant in water treatment need further exploration since vast and broader antimicrobial activities (63.63%) is reported than water treatment application (36.37%). Conclusions This review has revealed the existing knowledge gaps in exploration of plant resources for water treatment and product development. Chemical complexity of some plant extracts, lack of standardisation, slow working rate, poor water solubility, extraction and purification complexities are limitations that need to be overcome for industrial adoption of phytochemicals in water treatment. The field of phytobiotics should engage modern methodologies such as proteomics, genomics, and metabolomics to minimise challenges confronting phytobiotic standardisation. The knowledge disseminated awaits novel application for plant product development in water treatment.
Cyclic polyethers and their complexes with metal salts (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic polyethers and their complexes with metal saltsCharles J. PedersenCite this: J. Am. Chem. Soc. 1967, 89, 26, 7017–7036Publication Date (Print):December 1, 1967Publication History Published online1 May 2002Published inissue 1 December 1967https://pubs.acs.org/doi/10.1021/ja01002a035https://doi.org/10.1021/ja01002a035research-articleACS PublicationsRequest reuse permissionsArticle Views19180Altmetric-Citations3774LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Treatment of accumulative variables in data-driven prognostics of lead-acid batteries (2015)

Problems with starter batteries in heavy-duty trucks can cause costly unplanned stops along the road. Frequent battery changes can increase availability but is expensive and sometimes not necessary since battery degradation is highly dependent on the particular vehicle usage and ambient conditions. The main contribution of this work is case study where prognostic information on remaining useful life of lead-acid batteries in individual Scania heavy-duty trucks is computed. A data-driven approach using random survival forests is used where the prognostic algorithm has access to fleet operational data including 291 variables from 33603 vehicles from 5 different European markets. A main implementation aspect that is discussed is the treatment of accumulative variables such as vehicle age in the approach. Battery lifetime predictions are computed and evaluated on recorded data from Scania's fleet-management system and the effect of how accumulative variables are handled is analyzed.
Posterior Reversible Encephalopathy Syndrome After 90Y-Resin Microspheres Radioembolization (2019)

A 66-year-old man with colorectal carcinoma and liver-only metastases underwent radioembolization using Y-loaded, resin-based microspheres. One day after radioembolization, the patient experienced severe hypertension and multiple seizures. On MRI, symmetric edematous areas in the cerebellum and the parietal and occipital lobe were observed, a typical finding for posterior reversible encephalopathy syndrome (PRES). The PRES is associated with, for example, renal failure or blood pressure fluctuations leading to cerebral endothelial dysfunction. Antihypertensive and antiepileptic therapies led to normotensive blood pressure and neurological remission. Therefore, newly developed neurological symptoms accompanied by high blood pressure fluctuations after radioembolization should lead to PRES as differential diagnosis.
Effects of Proactivity and Expressivity on Collaboration with Interactive Robotic Drawers (2016)

In this study, we examined how participants (N=20) interacted and collaborated with a set of robotic drawers to accomplish an assembly task. Using Wizard of Oz techniques, the drawers' behavior varied along two dimensions -- proactivity and expressivity of motions. The results of our study indicate that participants consider an expressive robot to be more involved and interested in the interaction. We also observe that while proactive or expressive robots can dominate the interaction, proactivity may negatively affect the participants' perception of their social status relative to that of the robot's, while expressiveness does not. This shows the importance of utilizing expressive movements when designing socially appropriate robots that collaborate with human users.