gebhart/patrepeval huggingface dataset:
Transcriptomics and Transposon Mutagenesis Identify Multiple Mechanisms of Resistance to the FGFR Inhibitor AZD4547 (2018)

In human cancers, FGFR signaling is frequently hyperactivated by deregulation of FGF ligands or by activating mutations in the FGFR receptors such as gene amplifications, point mutations, and gene fusions. As such, FGFR inhibitors are considered an attractive therapeutic strategy for patients with mutations in FGFR family members. We previously identified <i>Fgfr2</i> as a key driver of invasive lobular carcinoma (ILC) in an <i>in vivo</i> insertional mutagenesis screen using the <i>Sleeping Beauty</i> transposon system. Here we explore whether these FGFR-driven ILCs are sensitive to the FGFR inhibitor AZD4547 and use transposon mutagenesis in these tumors to identify potential mechanisms of resistance to therapy. Combined with RNA sequencing-based analyses of AZD4547-resistant tumors, our <i>in vivo</i> approach identified several known and novel potential resistance mechanisms to FGFR inhibition, most of which converged on reactivation of the canonical MAPK-ERK signaling cascade. Observed resistance mechanisms included mutations in the tyrosine kinase domain of FGFR2, overexpression of MET, inactivation of RASA1, and activation of the drug-efflux transporter ABCG2. ABCG2 and RASA1 were identified only from <i>de novo</i> transposon insertions acquired during AZD4547 treatment, demonstrating that insertional mutagenesis in mice is an effective tool for identifying potential mechanisms of resistance to targeted cancer therapies.<b>Significance:</b> These findings demonstrate that a combined approach of transcriptomics and insertional mutagenesis <i>in vivo</i> is an effective method for identifying potential targets to overcome resistance to therapy in the clinic. <i>Cancer Res; 78(19); 5668-79. ©2018 AACR</i>.
2-(4-Fluorophenyl)-2-oxoethyl 2-methoxybenzoate (2012)

In the title compound, C(16)H(13)FO(4), the aromatic rings enclose an angle of 73.68 (6)°. In the crystal, C-H⋯O and C-H⋯F contacts connect the mol-ecules into a three-dimensional network. The shortest inter-centroid distance between two aromatic π-systems is 3.6679 (7) Å and is apparent between the fluorinated phenyl groups.
Transcriptional profile and response to neoadjuvant chemotherapy in breast cancer (2011)

Identifying patients responsive to chemotherapy is of essential interest and despite major steps have been taken, the issue warrants further studies in view of its complexity.
Cirolanidae (Crustacea: Isopoda) of Australia (1986)

An account is given of the cirolanid fauna of Australia. The total number of species recorded is 102, of which 51 are new. Two new species not yet recorded from Australian coastal waters are also included. Full descriptions of all genera are given, and detailed descriptions and figures are given for all species not previously recorded from Australia or in need of redescription. The following genera and species are recorded from Australian waters: Anopsilana (2 species), Bathynomus (3 species), Cartetolana (1 species), Orolana (30 species), Eurydice (8 species), Eurylana (1 species), Excirolana (1 species), Hansenolana (1 species), Metacirolana (7 species), Natatolana (31 species), Neocirolana (5 species), Orphelana (1 species), Pseudolana (7 species), and three new genera-Booralana (2 species), Dolicholana (1 species) and Limicolana (1 species).
Alcohol hyper‐responsiveness in chronic rhinosinusitis with nasal polyps (2016)

Nasal hyper-responsiveness to alcohol is significantly more prevalent in severe eosinophilic upper airway disease.
BLR-D (2011)

In this paper, we address a pattern of diagnosis problems in which each of J entities produces the same K features, yet we are only informed of overall faults from the ensemble. Furthermore, we suspect that only certain entities and certain features are leading to the problem. The task, then, is to reliably identify which entities and which features are at fault. Such problems are particularly prevalent in the world of computer systems, in which a datacenter with hundreds of machines, each with the same performance counters, occasionally produces overall faults. In this paper, we present a means of using a constrained form of bilinear logistic regression for diagnosis in such problems. The bilinear treatment allows us to represent the scenarios with J+K instead of JK parameters, resulting in more easily interpretable results and far fewer false positives compared to treating the parameters independently. We develop statistical tests to determine which features and entities, if any, may be responsible for the labeled faults, and use false discovery rate (FDR) analysis to ensure that our values are meaningful. We show results in comparison to ordinary logistic regression (with L1 regularization) on two scenarios: a synthetic dataset based on a model of faults in a datacenter, and a real problem of finding problematic processes/features based on user-reported hangs.
Amphiphilic silane modified multifunctional nanoparticles for ratiometric oxygen sensing (2017)

Precise detection of dissolved oxygen (DO) at the cellular level plays a pivotal role in the diagnosis of many diseases and intraoperative observation.
Insights into novel antimicrobial compounds and antibiotic resistance genes from soil metagenomes (2014)

In recent years a major worldwide problem has arisen with regard to infectious diseases caused by resistant bacteria. Resistant pathogens are related to high mortality and also to enormous healthcare costs. In this field, cultured microorganisms have been commonly focused in attempts to isolate antibiotic resistance genes or to identify antimicrobial compounds. Although this strategy has been successful in many cases, most of the microbial diversity and related antimicrobial molecules have been completely lost. As an alternative, metagenomics has been used as a reliable approach to reveal the prospective reservoir of antimicrobial compounds and antibiotic resistance genes in the uncultured microbial community that inhabits a number of environments. In this context, this review will focus on resistance genes as well as on novel antibiotics revealed by a metagenomics approach from the soil environment. Biotechnology prospects are also discussed, opening new frontiers for antibiotic development.
Relative Binding Affinity Prediction of Charge-Changing Sequence Mutations with FEP in Protein–Protein Interfaces (2019)

Building on the substantial progress that has been made in using free energy perturbation (FEP) methods to predict the relative binding affinities of small molecule ligands to proteins, we have previously shown that results of similar quality can be obtained in predicting the effect of mutations on the binding affinity of protein-protein complexes. However, these results were restricted to mutations which did not change the net charge of the side chains due to known difficulties with modeling perturbations involving a change in charge in FEP. Various methods have been proposed to address this problem. Here we apply the co-alchemical water approach to study the efficacy of FEP calculations of charge changing mutations at the protein-protein interface for the antibody-gp120 system investigated previously and three additional complexes. We achieve an overall root mean square error of 1.2 kcal/mol on a set of 106 cases involving a change in net charge selected by a simple suitability filter using side-chain predictions and solvent accessible surface area to be relevant to a biologic optimization project. Reasonable, although less precise, results are also obtained for the 44 more challenging mutations that involve buried residues, which may in some cases require substantial reorganization of the local protein structure, which can extend beyond the scope of a typical FEP simulation. We believe that the proposed prediction protocol will be of sufficient efficiency and accuracy to guide protein engineering projects for which optimization and/or maintenance of a high degree of binding affinity is a key objective.
Extension of strain–life equation for low‐cycle fatigue of sheet metals using anisotropic yield criteria and distortional hardening model (2014)

ABSTRACT The fatigue strain–life equation is in general applicable to isotropic materials. It was recently attempted to account for material anisotropy because of crystallographic texture in fatigue modelling. The proposed modification was limited to isotropic hardening. The present work is an extension of the previous work, wherein a general framework to model anisotropy using phenomenological yield criterion and anisotropic hardening is provided. Yld2004‐18p yield criterion and the so‐called homogenous anisotropic hardening model are used to demonstrate the anisotropic cyclic behaviour of low carbon steel. The proposed methodology can be utilized in applications including multiaxial fatigue modelling.
Unexpected structural complexity of supernumerary marker chromosomes characterized by microarray comparative genomic hybridization (2008)

The increasing use of array CGH in clinical cytogenetic laboratories will provide an efficient method for more comprehensive characterization of SMCs. Improved SMC characterization, facilitated by array CGH, will allow for more accurate SMC/phenotype correlation.
Development of an Autoflow Cruise Control System for a Centrifugal Pump (1995)

To improve the ease of driving a centrifugal pump that is afterload dependent, we have developed an automatic flow control system for the Terumo Capiox centrifugal pump system. This system consists of an autoflow cruise control system with a safety cutoff. The Capiox Pump Console 3000 was controlled by a personal computer through a serial communication line. In the usual manual mode, the motor speed knob works as a pump speed control, and in the autoflow mode, the same knob works as a blood flow rate control. After selecting and obtaining the desired flow rate, the mode was changed from manual to autoflow mode. In the autoflow mode, the computer compares the desired flow rate with the actual flow measured by an ultrasonic Doppler flowmeter and adjusts the motor rotational speed accordingly. During both in vivo and in vitro testing, this autoflow mode was able to return the changed flow that was disrupted by either clamping and declamping of the tubing or by the bolus injection of a vasomotor drug to the selected flow rate within 10 s without any significant fluctuation. In conclusion, the newly developed computer controlled autoflow system was able to produce a reliable and effective flow regulation for a centrifugal pump.
Some Like it Hot! (2022)

What are extremophiles? What can we learn from them that is relevant in our warming climate? Carols Goller, Ph.D. introduces you to these resilient microbes, and discusses how we can apply what we learn from them as we face current challenges. (VersiÃ³n en EspaÃ±ol del Video de Carlos Goller <https://youtu.be/YD7TgXO0ak8> )
Syntheses and applications of nanocatalysts based on nanoporous materials (2006)

Heterogeneous catalysis has always been an inherently nanoscopic phenomenon with important technological and societal consequences for energy conversion and the production of chemicals. In fact, catalysts have been reported to represent the oldest commercial application of nanotechnology. Nanocatalysts are generally defined as nanoscale materials that have at least one nanoscale dimension, or have been subjected to nanoscale structural modification in order to enhance their catalytic activity. They could be classified into four distinct types of catalysts: nanoparticulate, nanoporous, nanocrystalline, and supramolecular catalysts. Most catalysts have consisted of nanometre-sized particles dispersed on a high-surface-area support, but recent advances in synthetic methods are leading to increasingly precise control of the variables affecting catalyst activity and selectivity in the nanoporous catalyst. Widespread applications of nanoporous materials in the fields of catalysis, adsorption and separation have emphasised the need to search for new structures with new framework compositions. This contribution summarises recent results on the synthesis, characterisation, and catalytic performance of new nanoporous catalysts performed by the present authors.
Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus (2008)

rs7951 T allele of the C3 gene was significantly associated with SLE, and decreased serum level of C3 seems to be correlated with this allele.
Cover Image (2020)

COVER ILLUSTRATION Handwriting, a unique form of language and motor processing, has been found to show robust sex differences. Using fMRI, the neural evidence for the sex differences in handwriting was revealed. Specifically, males and females showed significant differences in brain activation and functional connectivity in Exner's area (illustrated as green circle), a writing-specific brain region.
Cryogenic laser performance of Yb:YAG diode-pumped at 940 nm and 969 nm for high power lasers (2014)

We demonstrated the laser performance of Yb:YAG for different cryogenic tempertures pumped by fibre coupled diode laser emitting at 940 nm and 969 nm. Laser diode bandwidth, absorption bandwidth of laser material plays a crucial role.
Profile of patients treated with intravitreal anti-vascular endothelial growth factor injections in Bhutan: a 3-year national survey (2022)

ABSTRACT Purpose Ocular vascular diseases are common causes of visual impairment and blindness, for which intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the first-line therapy. Current study describes the profile of patients receiving intravitreal anti-VEGF injections in Bhutan. This is the first study of its kind to inform the national health policy. Methods For this retrospective study, we reviewed the surgical registers of the vitreoretinal unit across Bhutan over three years. Patient demography, clinical findings, diagnostic tests performed, and diagnoses or indications for intravitreal anti-VEGF injections were logged. A descriptive analysis was performed. Results A total of 381 patients received intravitreal anti-VEGF injections in the operating theatres as mandated by the national guidelines. The majority of patients were males (230, 60.4%). The mean age was 65.2 ± 13.5 years, ranging from 13 to 90 years, and a median of 69 years. Majority of the treated eyes (117, 30.7%) had BCVA &lt;3/60 to light perception (PL), and another 51 eyes (13.4%) had &lt; 6/60 to 3/60. The most common indication for anti-VEGF injection was neovascular AMD (168 cases, 42.2%), followed by retinal vein occlusion (132 cases, 34.6%), diabetic macular oedema and retinopathy (50 cases, 13.1%), and myopic choroidal neovascular membrane (11 cases, 0.03%). Conclusions Bhutan faces both economic and geographic challenges, on top of limited human resources for managing vitreoretinal diseases. With an ever-increasing load of vitreoretinal diseases, and systemic diseases like diabetes and hypertension, there is a need to improve vitreoretinal services. Regular vitreoretinal services are provided only at the national referral hospital located in the north-west. For successful management, an effective community screening program, right referrals, and proper transport facilities must go hand-in-hand, and or extend regular vitreoretinal services to regional referral hospitals.
Computational Studies of Grain Boundary Behavior in Uranium Dioxide Nuclear Fuels (2017)

Nuclear power is responsible for the production of 380,000 Megawatts of energy worldwide, which results in over 11% of the world’s energy production [world-nuclear.org]. Pellet-cladding interactions (PCI) are a key nuclear fuel failure mechanism which presents formidable challenges to researchers due to extreme nuclear fission conditions. Although PCI interactions have been reduced due to fuel additives, understandings of PCI interactions remain elusive. We propose new approaches to increase understanding of nuclear fuel interactions; specifically, uranium dioxide and the effects of dopants. This study focuses on amorphous uranium dioxide and fission products, while benchmarking new methods with previous computational studies. Results will further research into modeling approaches and help guide future experimental design.
The STAT3 Transcription Factor Is a Target for the Myc and Riboblastoma Proteins on the Cdc25A Promoter (2005)

The STAT3 (signal transducer and activator of transcription) transcription factor functions as down-stream effector of growth factor signaling. Whereas STAT3 activation is transient in normal cells, constitutively activated forms of the transcription factor have been detected in several cancer cell lines and primary tumors. Through the up-regulation of cell cycle and survival genes, STAT3 plays important roles in cell growth, anti-apoptosis, and cell transformation yet the molecular basis for this behavior is poorly understood. In this study, we show that STAT3 and its transcriptional cofactors are recruited to the promoter of the Cdc25A gene to activate its expression. Using chromatin immunoprecipitations, we observed that Myc is recruited to this promoter following STAT3 DNA binding. Moreover, small interfering RNA-mediated knockdown of Myc specifically inhibits the STAT3-mediated activation of Cdc25A. Reduction in Myc protein level results in defective recruitment of the CREB-binding protein, Cdk9, and RNA polymerase complexes, indicating that Myc is necessary for STAT3 transcription. Surprisingly, the association of STAT3 with the Cdc25A promoter does not necessarily lead to transcriptional induction because this protein also functions as a transcriptional repressor of the Cdc25A gene. Following hydrogen peroxide stimulation, STAT3 forms a repressor complex with the retinoblastoma (Rb) tumor suppressor to occupy the Cdc25A promoter and block its induction. In coimmunoprecipitations and ChIP experiments, Rb was found to associate with STAT3 on DNA and we provide evidence that Rb binds directly to the transcription factor. Thus, we propose that Myc and STAT3 cooperate to induce the expression of Cdc25A and that their transcriptional activity is normally regulated by the Rb tumor suppressor gene.
Sintering and Grain Growth of Alumina (1954)

The sintering and grain growth of alumina as a function of the type of impurity (oxide) added was studied. One weight per cent of the impurity was added to a commercial Be‐grained alumina or was coprecipitated with iilcl 3 to form hydroxides. Fired shrinkage, bulk density, and apparent porosity measurements were used to correlate sintering with grain growth as observed by the petrographic and electron microscope. Some additives which increased grain growth were believed to enter into solid solution with alumina and to strain the lattice sufficiently to increase material transport greatly. Other additives were believed to produce a glassy phase which would greatly increase surface difusion and resulting grain growth. Some additives decreased grain growth because of the relatively large vapor phase produced by the impurity upon heating which may have been sorbed on the alumina; other additives may have Wed anion vacancies to reduce material transport or may have produced complex anions whose flow or diffusion may have been impeded.
Effect of the nitric oxide level in the medial preoptic area on male copulatory behavior in rats (1998)

We investigated the influence of the extracellular nitric oxide (NO) level on male copulatory behavior. We confirmed the changes of nitrite (NO2-) and nitrate (NO3-) in the medial preoptic area (MPOA) by administration of the NO precursor L-arginine (L-Arg, 10 mM) or the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mM) via a dialysis probe. NO2- and NO3- were measured simultaneously by an in vivo microdialysis method coupled with the Griess reaction. L-Arg induced significant elevations of extracellular NO2- and NO3-. L-NMMA significantly reduced NO2- and NO3- levels. We observed male copulatory behavior during infusion of L-Arg or L-NMMA. The mount rate of male rats significantly increased during infusion of L-Arg in the MPOA. Administration of L-NMMA reduced the mount rate. These findings suggested that the elevation of extracellular NO in the MPOA facilitates male copulatory behavior of rats, whereas the decrease of NO reduces their copulatory behavior.
Radioimmunoassay of creatine kinase isoenzymes in human serum: isoenzyme MM. (1978)

Abstract Measurement of the mass concentration of serum enzymes by radioimmunoassay provides direct quantitation of specific isoenzymes and may be less subject to some of the limitations of traditional assay procedures for enzymes. We describe the development of a sensitive and specific radioimmunoassay for the muscle isoenzyme of creatine kinase, CM-MM, in human serum. CK-MM, purified from human skeletal muscle, was used to raise high-titer antisera and for iodination by the Chloramine T method. The radioimmunoassay required 50 microliter of sample, utilized a double-antibody separation method, and was completed in 24 h. Cross reactivity with CK-BB was virtually zero, 3--17% with CK-MB. The mass concentration of CK-MM in the serum of healthy subjects ranged from 36 to 1668 microgram/liter and correlated closely with total CK enzymatic activity. Serum concentrations of CK-MM from casually selected patients correlated less well with total CK enzymatic activity, suggesting the existence of other CK isoenzymes or the presence of inactive forms.
Plant Virus Particles Carrying Tumour Antigen Activate TLR7 and Induce High Levels of Protective Antibody (2015)

Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the "gold standard" Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-α by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe "in-built" ssRNA adjuvant.
Study of muscular and ventricular function in dynamic cardiomyoplasty: a ten-year follow-up. (1997)

Our 10-year clinical experience demonstrates that cardiomyoplasty increases ejection fraction, improves functional class, and ameliorates quality of life. Ventricular volumes and diameters remain stable long term. LDM structure is maintained long term if electrostimulation is performed avoiding excessive myostimulation. Patient selection is the most important determinant for early and late outcome. Late death in patients undergoing cardiomyoplasty is principally due to sudden death. Our future aim is to incorporate a cardioverter-defibrillator in the cardiomyostimulator, thus improving long-term results. Cardiomyoplasty may delay or prevent end-stage heart failure and the need for heart transplantation.