gebhart/patrepeval huggingface dataset:
Modulators of STAT Transcription Factors for the Targeted Therapy of Cancer (STAT3 Inhibitors) (2011)

The transcription factor STAT3 (signal transducer and activator of transcription 3) mediates the effects of growth factors and cytokines by regulating gene expression. In many human cancers, including breast and prostate, STAT3 is constitutively active. This leads to increased expression of genes regulating survival and proliferation, and drives the malignant behavior of these cells. As a result, the identification of novel compounds that selectively inhibit STAT3 activity may lead to useful tools to reduce cancer-associated cell proliferation, inflammation, and chemotherapeutic resistance. In this report we describe the identification of a potent and selective STAT3 inhibitor through the use of high throughput screening, synthetic medicinal chemistry, and molecular assays. The novel inhibitor (PubChem CID-2100018) belongs to the thienopyrimidine scaffold and is assigned probe number ML116 within the NIH Molecular Libraries Probe Production Center Network. Probe ML116 exhibits a STAT3 IC50 value of approximately 4 micromolar and does not inhibit the STAT1, STAT5, or NFkB signaling pathways (IC50 values greater than 56 micromolar), as determined using cell-based luciferase reporter assays. Quantitative PCR experiments demonstrated that probe ML116 inhibits transcription of the STAT3-regulated gene BCL3. In contrast, the gene A20 which is regulated by the unrelated transcription factor NF-kB, was not inhibited, further supporting the STAT3 selectivity of this probe. Whereas this compound can induce loss of viability of breast cancer cell lines such as MDA-MB-468 cells that are dependent on STAT3 activity, it displays essentially no toxicity to STAT3-independent SKBR3 breast cancer cells. Similar results were found in ovarian cancer cell lines and multiple myeloma cell lines. Due to the central role of aberrant STAT3 signaling in cancer pathogenesis, this compound may provide a useful starting point for the development of chemical scaffolds to block STAT3 signaling for cancer therapy.
A rapid and efficient method to purify proteins at replication forks under native conditions (2013)

Tools for studying replication fork dynamics are critical for dissecting the mechanisms of DNA replication, DNA repair, histone deposition, and epigenetic memory. Isolation of protein on nascent DNA (iPOND) is an elegant method for purifying replication fork proteins. Here, we present accelerated native iPOND (aniPOND), a simplification of the iPOND procedure with improved protein yield. Cell membrane lysis and nuclei harvesting are combined in one step to reduce washes and minimize sample loss. A mild nuclei lysis protocol is then used to better preserve DNA-protein complexes. aniPOND is faster than iPOND, avoids formaldehyde cross-linking, and improves protein yield 5- and 20-fold for the CAF1-complex or PCNA respectively. Moreover, using aniPOND, but not iPOND, we could detect the polycomb repressive complex 2 (PRC2) components SUZ12, EZH2, and RBBP4 at replication forks. This faster, higher-yield method will facilitate MS analysis of replication fork complexes.
Significant Parameters in Elastoplastic Analysis of Underground Openings (1993)

In this paper we show how it is possible to reduce the number of significant parameters appearing in typical rock mechanics boundary value problems of rock engineering and tunneling. Further, we present methods to gain information concerning the solutions to these problems, presuming the rock mass obeys the well‐known, and in geomechanics widely used, Mohr‐Coulomb yield criterion. The system of differential equations that governs boundary value problems with a Mohr‐Coulomb elastoplastic material can be reformulated by means of simple substitutions in such a way that cohesion and Young's modulus do not explicitly appear. This makes substantial savings of computational effort possible, and contributes to a better understanding of the structure of the solution. Computational results obtained for some values of Young's modulus, cohesion, initial stresses, and boundary tractions can easily be transformed to the results for other values. The transformed equations suggest very clearly the influence of cohesion, i.e., as compared to the effect of a support pressure.
Electrochemical stability properties of titanium-doped WO3 electrochromic thin films (2016)

Pure, 5% Ti-doped and 10% Ti-doped WO 3 thin films were prepared by the radio frequency magnetron sputtering and characterised by a SEM, an electrochemical workstation and an UV–VIS–NIR spectrophotometer. Research results showed that Ti doping had no apparent influence on the surface morphology and optical band gap. It could also be found that the addition of Ti has little interference with the electrochromic property of WO 3 in both bleached and coloured states at initial cycles from electrochemical and optical test results, while there were apparent differences in the optical transmittance and inserted and extracted charge with increasing cycles. This is attributed that Ti-doped WO 3 thin films allow facile ion interaction/extraction and have less ion residues, which can stabilise the electrochemical cycling performance. Furthermore, the data we have obtained indicate that 5% Ti-doped WO 3 film has the best electrochromic property.
Layout 'hot spots' for advancing optical technologies (2006)

A pattern matching technique for quickly scanning layouts to find 'worst case' printing problems has been extended to and tested for accuracy on a progressive sequence of advances in optical lithography, including off-axis illumination, attenuated masks, optical-proximity correction and double exposure treatments. These extensions required including phase-variations from off-axis sources with the usual method for production of Maximum Lateral Test Patterns, and utilizing a composite match factor computer from McIntyre et al. to give a vulnerability score. Direct aerial image simulation of the projection printing of the local pattern shows that the basic trends are correctly extracted at high-speed with pattern matching. Pattern matching is found to be a useful tool under these technologies for prescreening layouts to find the most sensitive areas to residual effects, and also for quick comparison of worst case issues among different lithography treatments.
Crystallization and preliminary X-ray crystallographic analysis of the EGF receptor ectodomain (1998)

Crystallization of the hydrophilic ectodomain of the epidermal growth factor (EGF) receptor has been accomplished in the presence of the ligand EGF. Two different crystal forms have been obtained, one of which was suitable for X-ray analysis. The space group of this form has been assigned to P21212 with unit-cell dimensions of a = 207.4, b = 113.3 and c = 120.4 A. A native data set has been recorded and a heavy-atom search is currently under way. Diffraction from these crystals, however, is limited to low resolution and extensive trials to improve crystal quality further have all failed. To analyse the molecular shape and aggregation of the receptor protein in solution, small-angle X-ray diffraction and dynamic light-scattering techniques have been applied. Synchrotron radiation in combination with cryo-techniques is essential for data collection because of the high solvent content and radiation sensitivity.
Modeling the behavior of complex media by jointly using discrete and continuum approaches (2004)

We propose a new approach to modeling the behavior of heterogeneous media, according to which such objects are represented as composed of regions of two types, one being described within the framework of a discrete, and the other, a continuum approach. This joint approach is promising for the numerical modeling of complex media with strongly different properties of components. Possibilities of the proposed method were verified by studying the propagation of elastic waves in a two-component medium with a discrete component, modeled by the method of movable cellular automata, and a continuum component described by a system of equations of motion of continuum solved by the finite difference method. The results of calculations show that this approach provides adequate description of the propagation of elastic waves in complex media and does not introduce nonphysical distortions at the boundaries where the two models are matched.
Surgeons call for identity of knife crime victims to be shared with police (2010)

The Association of Surgeons of Great Britain and Ireland is calling for all hospital accident and emergency departments to share information about knife crime with the police as “standard practice”—including non-anonymised data such as the victim’s identity.

At the moment about 100 A&E departments in the United Kingdom, around two thirds of the total, have started logging details of violent injuries and sharing this information with the police, although only 50 are sharing their data fully.

But in a consensus statement this week from the first joint surgical and police conference on knife crime, the association and the …
The Florida Pancreas Collaborative Next-Generation Biobank: State-wide Infrastructure to Reduce Disparities and Improve Survival for a Racially and Ethnically Diverse Cohort of Patients with Pancreatic Cancer (2020)

Abstract Background Well-annotated, high-quality biorepositories provide a valuable platform to support translational research and discovery. However, most biorepositories have poor representation of minority groups, limiting the ability to address cancer health disparities and improve disease outcomes. This report describes the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective longitudinal cohort study and biorepository specifically designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). Methods We describe rationale for establishing the FPC and provide an overview of key stakeholders; study eligibility and design; ascertainment and recruitment strategies; and standard operating procedures (SOPs) developed to collect, process, store, and transfer biospecimens, medical images, and data. We also describe the customized cloud-based, secure data management platform built to facilitate recruitment, track study-related workflow, house data, and perform queries. We also present progress to date regarding recruitment and biobanking. Results The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for study eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and baseline questionnaire data (62%). Conclusions This biorepository addresses a critical gap in PaCa research with the potential to advance basic, clinical, population-based, and translational studies intended to minimize disparities, increase quality of life, and reduce PaCa-related morbidity and mortality. Impact This multi-institutional infrastructure can serve as a prototype for development of similar resources across the country and disease sites.
Technology-dependent pedagogical process redesign: leveraging lean methods (2021)

Purpose This research compared the efficacy of process outcomes leveraging lean methods versus traditional pedagogy applied to dental education dependent on emerging technology. The pedagogical objective was to improve system efficiency without compromising traditional outcomes of effectiveness (quality). Design/methodology/approach The research team tested the efficacy of a lean A3 framework to identify, remove waste and redesign a technology-dependent simulation laboratory course (CAD/CAM/IR Restorative Dentistry). Students were also sensitized to time-in-chair to introduce a stronger patient focus. Baseline data collected from a control group were statistically compared to the research group's data after the course redesign. In addition, course time allocations were measured and then compared. Findings The results showed the interventions significantly reduced procedure cycle times without compromising quality. Additionally, the course was more efficiently conducted as measured by course time allocations. Practical implications This research demonstrated that the use of the A3 framework enhanced learning through process documentation, reengineering and systems optimization resolving issues of inefficiency associated with the CAD/CAM/IR pedagogy. This work is significant because it demonstrates the practice of using lean interventions to redesign and improve a technology-based healthcare course to maximize benefits. Originality/value This research is the first to examine how to leverage lean methods in a healthcare simulation laboratory, dependent on innovative technology, to educate and train future practitioners. This research applied statistical rigor in a controlled experiment to maximize its applicability and generalizability.
Einleitung (1978)

Primäres Ziel dieser Untersuchung ist es, einen Beitrag zur Weiterentwicklung der Erlösrechnung zu leisten und die gewonnenen Erkenntnisse anhand von Beispielen aus dem Bereich der Eisen — und Stahlindustrie zu konkretisieren.
Structure - property Relationships in High - strength High - modulus Polyethyelene Fibres (2005)

Six commercially available high-strength, high-modulus polyethylene fibres have been studied with the aim of developing a deeper understanding of their structure-property relationships. Structural studies have been carried out on the measurement of crystallite size and orientation parameters using a wide range of techniques including optical microscopy, thermal analysis and wide-angle X-ray diffraction techniques, together with polarised IR spectroscopy. Birefringence, melting temperatures, melting enthalpies and crystallinity values are found to increase with increasing tensile strength and modulus as a direct result of the increased chain alignment induced during the fibre-drawing stages. Careful examination of the results show that improving the chain alignment encourages the alignment and lateral perfection of unoriented non-crystalline chains. Analysis of wide-angle X-ray diffraction, polarised IR spectroscopy and thermal analysis confirms the presence of a three-phase structure consisting of polymorphic crystalline (i.e. orthorhombic and monoclinic), highly oriented non-crystalline (i.e. paracrystalline) and unoriented non-crystalline (i.e. amorphous) structures, as opposed to the classical two-phase (crystalline and amorphous) structures. Analysis of polarised IR data shows the existence of a polymorphic structure consisting of highly oriented orthorhombic and monoclinic crystallites, together with highly oriented non-crystalline structure containing pseudohexagonally packed chains. Analysis of second order orientation parameter, , shows that the monoclinic crystallites are more oriented than the orthorhombic crystallites. The analysis of the X-ray diffraction data suggests that increasing crystallinity and lateral perfection leads to a consistent reduction in the proportion of the oriented non-crystalline structure. A scanning electron microscopy (SEM) examination of the longitudinal views showed fibrillar striations along the fibre axis direction, together with relatively smooth surfaces with increasing tensile moduli. The samples showed excellent bending behaviour advantageous for the formation of fabrics. The cross-sectional images appeared to vary from deformed triangular to deformed circular shapes.
High-Precision Measurement of Sine and Pulse Reference Signals Using Software-Defined Radio (2018)

This paper addresses simultaneous high-precision measurement and analysis of generic reference signals by using inexpensive commercial off-the-shelf software-defined radio hardware. Sine reference signals are digitally downconverted to baseband for the analysis of phase deviations. Hereby, we compare the precision of the fixed-point hardware digital signal processing chain with a custom single instruction multiple data x86 floating-point implementation. Pulse reference signals are analyzed by a software trigger that precisely locates the time where the slope passes a certain threshold. The measurement system is implemented and verified using the Universal Software Radio Peripheral (USRP) N210 by Ettus Research LLC. Applying standard 10 MHz and 1 PPS reference signals for testing, a measurement precision (standard deviation) of 0.36 and 16.6 ps is obtained, respectively. In connection with standard PC hardware, the system allows long-term acquisition and storage of measurement data over several weeks. A comparison is given to the dual-mixer time difference and time interval counter, which are state-of-the-art measurement methods for sine and pulse signal analysis, respectively. Furthermore, we show that our proposed USRP-based approach outperforms measurements with a high-grade digital sampling oscilloscope.
Analysis of individual differences in radiosensitivity using genome editing (2016)

Current standards for radiological protection of the public have been uniformly established. However, individual differences in radiosensitivity are suggested to exist in human populations, which could be caused by nucleotide variants of DNA repair genes. In order to verify if such genetic variants are responsible for individual differences in radiosensitivity, they could be introduced into cultured human cells for evaluation. This strategy would make it possible to analyse the effect of candidate nucleotide variants on individual radiosensitivity, independent of the diverse genetic background. However, efficient gene targeting in cultured human cells is difficult due to the low frequency of homologous recombination (HR) repair. The development of artificial nucleases has enabled efficient HR-mediated genome editing to be performed in cultured human cells. A novel genome editing strategy, 'transcription activator-like effector nuclease (TALEN)-mediated two-step single base pair editing', has been developed, and this was used to introduce a nucleotide variant associated with a chromosomal instability syndrome bi-allelically into cultured human cells to demonstrate that it is the causative mutation. It is proposed that this editing technique will be useful to investigate individual radiosensitivity.
DNA Binding (Gel Retardation Assay) Analysis for Identification of Aryl Hydrocarbon (Ah) Receptor Agonists and Antagonists (2013)

The gel retardation assay (GRA), also referred as the electromobility shift assay (EMSA), is commonly used technique to examine DNA binding of transcription factors including activated nuclear receptors to their specific DNA recognition sites. GRA of the aryl hydrocarbon receptor (AhR) relies on the in vitro ability of the cytosolic AhR protein complex to convert into its high affinity DNA binding form following its interaction with and activation by an AhR agonist and, as such, the GRA can be used for detection of such ligands. In addition, examination of the ability of a chemical to block agonist-dependent DNA binding of the AhR provides an avenue to identify AhR antagonists. Accordingly, this assay allows relatively rapid screening and identification of both AhR agonists and/or antagonists and unlike cell-based or in vivo assays, it essentially eliminates the confounding effect of cellular metabolism of the test compounds. The GRA can also be used with nuclear extracts obtained from treated cells to further identify and/or characterize compounds capable of stimulating nuclear translocation and DNA binding of the AhR in intact cells. The methods described here can be applied to cytosolic, nuclear and/or whole cell extracts from various species and tissues.
FDA Considers Classification of ECT (2009)

With the increasing number of new brain stimulation techniques now available and on the horizon, does electroconvulsive therapy (ECT) still have a role? As clinicians and researchers we say most definitely “yes”. ECT is the most effective and rapidly acting treatment for severe forms of depression and other disorders. Transcranial magnetic stimulation has shown promise but mainly for less severely ill and less treatment resistant patients. Deep brain stimulation (DBS) has shown promise for the more resistant cases but its invasiveness limits its use. Results from only ∼50 patients treated worldwide are available and at present it is not approved by the United States Food and Drug Administration for depression. Vagus nerve stimulation, less invasive than DBS but still a surgical procedure, is presently FDA approved for acute treatment resistant depression but published efficacy rates fall short of those seen with ECT. Therefore, there continues to be an important role for ECT in the treatment of severe psychiatric disorders. But will ECT always be there when our patients need it? Somewhat unexpected recent developments at the FDA may impact the future availability of ECT to severely depressed patients. Here we provide background on the classification of ECT devices, the FDA reclassification process, and the process for providing FDA input in these critical deliberations.
Identification of three MADS-box genes expressed in sunflower capitulum (2003)

Three cDNA clones, HaPI, HaAG and HaAP3, were isolated from sunflower inflorescences at the R2 stage of development. The cDNAs share high sequence similarity with the PISTILLATA, AGAMOUS, and APETALA3 genes from Arabidopsis, respectively, which contain a MADS-box and are involved in floral organ development. Expression of the corresponding genes was analysed by northern blots and in situ hybridization. They are expressed preferentially in the R3 and R4 stages of capitulum development. HaAG accumulates in fertile flowers, mainly in stamens, while HaPI and HaAP3 are preferentially expressed in ray (sterile) flowers and more weakly in petals and stamens of fertile flowers.
A systems engineering design experience for the machine design curriculum (2002)

Traditional engineering education has tended to compartmentalize subject matter. This tendency can be viewed at a curriculum level where courses are established along subject lines such as Thermodynamics, Statics or Machine Design. There is also this tendency within the individual courses themselves. One purpose of a capstone senior design experience is to help students recognize the connectivity among the subjects throughout their curriculum as they apply their knowledge to a meaningful problem. Establishing projects that demonstrate the connectivity in a specific course is also beneficial, not only as it relates to the course material, but as a precursor to the more involved projects in the senior capstone experience. This paper describes a semester-long project for courses on machine design where the students are required to completely design a simple machine to demonstrate fundamental kinematic principles. The students are required to provide complete working drawings of the machine with all parts specified from vendor catalogs or drawn in sufficient detail for fabrication. From this system design project, the students gain experience with the activities required to specify the common machine elements that are discussed in a traditional classroom setting. They learn the importance and relevance of calculations required to support their decision making. They also recognize the influence imposed on the system design from individual component decisions. The scope of this project remains within the bounds of the course material with some application to the pre-requisite kinematics course.