gebhart/patrepeval huggingface dataset:
SF3B1 mutations in chronic lymphocytic leukemia (2013)

SF3B1 is a critical component of the splicing machinery, which catalyzes the removal of introns from precursor messenger RNA (mRNA). Next-generation sequencing studies have identified mutations in SF3B1 in chronic lymphocytic leukemia (CLL) at high frequency. In CLL, SF3B1 mutation is associated with more aggressive disease and shorter survival, and recent studies suggest that it can be incorporated into prognostic schema to improve the prediction of disease progression. Mutations in SF3B1 are predominantly subclonal genetic events in CLL, and hence are likely later events in the progression of CLL. Evidence of altered pre-mRNA splicing has been detected in CLL cases with SF3B1 mutations. Although the causative link between SF3B1 mutation and CLL pathogenesis remains unclear, several lines of evidence suggest SF3B1 mutation might be linked to genomic stability and epigenetic modification.
ChemInform Abstract: Multiple Bonds Between Main Group Elements and Transition Metals. (1986)

Abstract 0 Connection by [3 + 2! Cycloaddition of Dipheuylketen to a Dioxometal Unit.
Using Fluid Velocity in Lieu of Impeller Speed for Dimensional Analysis and a Method for Estimating Fluidborne Noise Due to Flow Turbulence Within Centrifugal Pumps (2007)

An empirical method for estimating fluidborne broadband noise associated with flow turbulence within centrifugal pumps is considered in this paper. Given the flow rate, developed head and the operating speed, an estimate of the pump’s fluidborne broadband noise can be made using the method. The method is developed by correlating the noise performance of centrifugal pumps with different specific speeds to the pump parameters (i.e. impeller dimensions and hydraulic performance). The correlation is achieved by using dimensional analysis, where the Buckingham Pi theorem is applied to relate the acoustic signature of the pump to the characteristics of the pump. Similar analysis had previously been performed on centrifugal pumps using air as a medium. The studies evaluated pumps at different flow coefficients of the same pump speed. To some extent, aerodynamic noise was correlated to the impeller tip speed. However, simply using the impeller tip speed may not be accurate. This paper offers an alternate method in relating noise, where instead of the impeller speed, the actual fluid velocity is calculated and used in the analysis.
Clinical Outcome in Chordoma (2002)

Study Design. A retrospective review of 100 patients with chordoma of the lumbar spine and sacrum. Twenty-three patients had flow cytometry data available and a minimum follow-up period of 5 years. Objectives. To determine whether DNA content and cell cycle analysis were associated with patient outcome. Summary of Background Data. DNA flow cytometry has been shown to be predictive for biologic behavior of various tumors. Chordoma has been evaluated in very small numbers of patients using DNA flow cytometric analysis, and the utility of DNA patterns in predicting outcome has not been clearly demonstrated. Methods. Between January 1979 and December 1995, 100 patients underwent surgical resection for chordoma, and 23 had a minimum follow-up period of 5 years with flow cytometry data. DNA content and cell cycle analysis were determined by enzymatically staining cells with propidium iodide dye and passing them through a flow cytometer. DNA histograms were generated. Survivorship and freedom from local recurrence curves were constructed by the Kaplan-Meier method and compared by the log-rank test. Results. The mean follow-up period was 7.3 years. For this group of 23 patients, mortality was 61% (14 patients) and local recurrence was 78% (18 patients). Eleven patients had tumors with diploid DNA content, and 12 patients had tumors with aneuploid DNA content. Metastases occurred in 4 of the 11 patients with a diploid pattern and 6 of the 12 with an aneuploid pattern. Six of the 11 patients with the diploid pattern died, in comparison with 8 of 12 patients with the aneuploid pattern. The Kaplan-Meier estimated survivorship (95% confidence interval) was 78% (66–90%) at a follow-up period of 5 years and 36% at a follow-up period of 10 years (22–50%), and no significant differences were found between patients with diploid and aneuploid patterns. Conclusions. Patients in whom metastases did not develop had a more favorable clinical outcome. DNA pattern was not associated with local recurrence or survival.
Abstract IA11: Targeting enhancers in CNS tumors (2015)

Abstract Master regulatory transcription factors instruct cell specification and dynamically modulate cell state via interactions with cis-regulatory elements, or enhancers, that together coordinate transcriptional programs. With an interest in understanding chromatin-dependent signal transduction to RNA polymerase in developmental and disease biology, we have undertaken to discover and optimize small molecule modulators of chromatin regulatory factors that function at enhancers. This research has produced informative chemical probes, with which we have validated hypotheses regarding BRD4 in chromatin-dependent signal transduction from MYC to promote cell growth, and the influence of EZH2 on silencing developmental programs. The mechanistic study of protoypical inhibitors of BRD4 and EZH2 led to the development of genome-wide measurements of drug localization, leading to insights into how small molecules modulate chromatin structure and function as well as fundamental insights into the organization of the regulatory landscape of the human genome. Here, mechanistic insights into the role of enhancers and enhancer factors in CNS tumors will be discussed, as well as translational opportunities for the development of epigenome-directed drugs in adult and pediatric tumors. Citation Format: James Bradner. Targeting enhancers in CNS tumors. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA11.
Personalised patient monitoring in haemodialysis using hierarchical Gaussian processes (2017)

The prevalence of end-stage renal failure is 861 per million population in the UK, and these patients undergo three haemodialysis sessions per week, each lasting 4 hours. In addition, patients are at risk of intra-dialytic hypotension, which leads to chronic heart disease and a high incidence of mortality. Through continuous monitoring of blood pressure during dialysis, we describe the use of Gaussian process regression to model changes of systolic blood pressure over time for each patient. We use Hierarchical Gaussian processes to infer the assumed latent structure of the systolic blood pressure trajectory for each individual patient, to describe their personalised “normal” and “abnormal” physiological patterns.
ChemInform Abstract: One‐Pot Combination of the Wittig Olefination with Bromination and Oxidation Reactions. (2013)

Abstract Z‐Configured‐bromo‐unsaturated esters (III) are obtained in a stereoselective one‐pot reaction.
Relating multi-sequence longitudinal intensity profiles and clinical covariates in new multiple sclerosis lesions (2015)

Structural magnetic resonance imaging (MRI) can be used to detect lesions in the brains of multiple sclerosis (MS) patients. The formation of these lesions is a complex process involving inflammation, tissue damage, and tissue repair, all of which are visible on MRI. Here we characterize the lesion formation process on longitudinal, multi-sequence structural MRI from 34 MS patients and relate the longitudinal changes we observe within lesions to therapeutic interventions. In this article, we first outline a pipeline to extract voxel level, multi-sequence longitudinal profiles from four MRI sequences within lesion tissue. We then propose two models to relate clinical covariates to the longitudinal profiles. The first model is a principal component analysis (PCA) regression model, which collapses the information from all four profiles into a scalar value. We find that the score on the first PC identifies areas of slow, long-term intensity changes within the lesion at a voxel level, as validated by two experienced clinicians, a neuroradiologist and a neurologist. On a quality scale of 1 to 4 (4 being the highest) the neuroradiologist gave the score on the first PC a median rating of 4 (95% CI: [4,4]), and the neurologist gave it a median rating of 3 (95% CI: [3,3]). In the PCA regression model, we find that treatment with disease modifying therapies (p-value &lt; 0.01), steroids (p-value &lt; 0.01), and being closer to the boundary of abnormal signal intensity (p-value &lt; 0.01) are associated with a return of a voxel to intensity values closer to that of normal-appearing tissue. The second model is a function-on-scalar regression, which allows for assessment of the individual time points at which the covariates are associated with the profiles. In the function-on-scalar regression both age and distance to the boundary were found to have a statistically significant association with the profiles.
Board level solder joint reliability modeling of Embedded Wafer Level BGA (eWLB) packages under temperature cycling test conditions (2011)

Embedded Wafer-Level Ball Grid Array (eWLB) technology was developed to provide a wafer-level packaging solution for semiconductor devices requiring a higher integration level and a greater number of external contacts. Essentially, eWLB is a fan-out wafer-level packaging in which silicon die is embedded in the mold compound and the redistributed layer can be carried out over both silicon die and mold compound areas. Although many solder joint thermal fatigue models have been published for BGA and WLCSP packages, they may not be applicable for the eWLB packages. In this paper, the board level solder fatigue life modeling for lead-free solder Sn96.5Ag3.0Cu0.5 (SAC305) used in embedded Wafer Level Ball Grid Array (eWLB) packages under temperature cycling test conditions will be presented. Thermal fatigue life models, associated with Anand viscoplastic constitutive model used for the solder material, are first established by curve-fitting the equivalent creep strain and creep strain energy density data, respectively, with temperature cycling test data. A series of numerical parameter studies is then carried out on various design parameters such as material properties, configurations of packages and test boards, and temperature cycling test conditions. The effects of coefficient of thermal expansion (CTE) mismatch and bending stiffness of the eWLB package assemblies on the solder joint lifetime and the shift of critical solder joint locations will be discussed.
Synthetic studies towards isomeric pyrazolopyrimidines as potential ATP synthesis inhibitors of Mycobacterium tuberculosis. Structural correction of reported N-(6-(2-(dimethylamino)ethoxy)-5-fluoropyridin-3-yl)-2-(4-fluorophenyl)-5-(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-7-amine (2021)

During our studies into preparing analogues of pyrazolopyrimidine as ATP synthesis inhibitors of <i>Mycobacterium tuberculosis</i>, a regiospecific condensation reaction between ethyl 4,4,4-trifluoroacetoacetate and 3-(4-fluorophenyl)-1<i>H</i>-pyrazol-5-amine was observed which was dependent on the specific reaction conditions employed. This work identifies optimized reaction conditions to access either the pyrazolo[3,4-<i>β</i>]pyridine or the pyrazolo[1,5-<i>α</i>]pyrimidine scaffold. This has led to the structural confirmation of the previously reported pyrazolopyrimidine <b>17b</b> which was reported as pyrazolo[1,5-<i>α</i>]pyrimidine structure <b>2</b> which was corrected to pyrazolo[3,4-<i>β</i>]-pyrimidine <b>19</b>.
ChemInform Abstract: Enantioselective Conjugate Radical Addition Reactions Mediated by Chiral Lewis Acid Complexes of (R,R)‐4,6‐Dibenzofurandiyl‐2,2′‐bis(4‐phenyloxazoline) (DBFOX/Ph). (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A Flexible Photoactive Titanium Metal–Organic Framework Based on a [TiIV3(μ3‐O)(O)2(COO)6] Cluster (2015)

The synthesis of titanium-carboxylate metal-organic frameworks (MOFs) is hampered by the high reactivity of the commonly employed alkoxide precursors. Herein, we present an innovative approach to titanium-based MOFs by the use of titanocene dichloride to synthesize COK-69, the first breathing Ti MOF, which is built up from trans-1,4-cyclohexanedicarboxylate linkers and an unprecedented [Ti(IV)3(μ3-O)(O)2(COO)6] cluster. The photoactive properties of COK-69 were investigated in depth by proton-coupled electron-transfer experiments, which revealed that up to one Ti(IV) center per cluster can be photoreduced to Ti(III) while preserving the structural integrity of the framework. The electronic structure of COK-69 was determined by molecular modeling, and a band gap of 3.77 eV was found.
Analysis of the complete nucleotide sequence of theAgrobacterium tumefaciens virB operon (1988)

The complete nucleotide sequence of the virB locus, from the octopine Ti plasmid of Agrobacterium tumefaciens strain 15955, has been determined. In the large virB-operon (9600 nucleotides) we have identified eleven open reading frames, designated virB1 to virB11. From DNA sequence analysis it is proposed that nearly all VirB products, i.e. VirB1 to VirB9, are secreted or membrane associated proteins. Interestingly, both a membrane protein (VirB4) and a potential cytoplasmic protein (VirB11) contain the consensus amino acid sequence of ATP-binding proteins. In view of the conjugative T-DNA transfer model, the VirB proteins are suggested to act at the bacterial surface and there play an important role in directing T-DNA transfer to plant cells.
Learning to Suggest Phrases. (2017)

Intelligent keyboards can support writing by suggesting content.  Certain types of phrases, when offered as suggestions, may be systematically chosen more often than their frequency in a corpus of text would predict. In order to generate those types of suggestions, we collected a dataset of how human authors responded to suggestions offered to them during openended writing tasks. We present an offline strategy for evaluating suggestions that enables us to learn the parameters of an improved suggestion generation policy without the expense of collecting additional data under that policy. We validate the approach by simulation and on human data by demonstrating improvement in held-out suggestion acceptance rate. Our approach can be applied to other scenarios where what is typical is not necessarily what is desirable.
Championing Science: Communicating Your Ideas to Decision Makers (2019)

Championing Science shows scientists how to persuasively communicate complex scientific ideas to decision makers in government, industry, and education. This comprehensive guide provides real-world strategies to help scientists develop the essential communication, influence, and relationship-building skills needed to motivate nonexperts to understand and support their science. Instruction, interviews, and examples demonstrate how inspiring decision makers to act requires scientists to extract the essence of their work, craft clear messages, simplify visuals, bridge paradigm gaps, and tell compelling narratives. The authors bring these principles to life in the accounts of science champions such as Robert Millikan, Vannevar Bush, scientists at Caltech and MIT, and others. With Championing Science, scientists will learn how to use these vital skills to make an impact
Design and rationale of DISCOVER global registry in type 2 diabetes: Real-world insights of treatment patterns and its relationship with cardiovascular, renal, and metabolic multimorbidities (2021)

Establishment of this long-term, scalable, and sustainable global registry offers opportunities to enhance understanding of care gaps, establish quality benchmarks, and understand the role of various treatment strategies in addressing the multifactorial pathophysiology of T2DM and associated comorbidities- potentially enabling transformation of clinical data into actionable insights for improving patient outcomes.
Sub-Cellular Nanosurgery in Live Cells Using Ultrashort Laser Pulses (2005)

We performed sub-cellular ablation with resolution of 250nm by tightly focused femtosecond pulses and verified the ablated volume using electron microscopy. This ablation technique is successfully applied in live cells nanosurgery.
<title>DSP-based automatic color reduction using multiscale clustering</title> (2001)

This paper presents a modification of the multi-scale clustering algorithm in order to reduce the color content of an image in an automatic manner without requiring the specification of the number of colors. The clustering space is chosen to be the YCbCr color space as used in the JPEG compression standard. Although multi-scale clustering is capable of defining prominent data clusters in an automatic manner, it may not generate all perceptibly distinctive colors when applied to the YCbCr color space. In this work, we have modified the multi-scale clustering algorithm to overcome this limitation for color reduction purposes. Our color reduction algorithm consists of two parts. The first part is a modification of multi-scale clustering to obtain a set of primary color prototypes. The second part is a color sectoring method to obtain a set of secondary color prototypes. The developed color reduction algorithm has been implemented on a high performance DSP processor, namely TMS320C6201, due to the computational requirement associated with multi-scale clustering. The result show on average 50 percent more compression over that of the JPEG standard for the color portion of images with comparable levels of color distortion.
New imidazo[2,1-b]thiazole-based aryl hydrazones: unravelling their synthesis and antiproliferative and apoptosis-inducing potential (2020)

Herein, we have designed and synthesized new imidazo[2,1-<i>b</i>]thiazole-based aryl hydrazones (<b>9a-w</b>) and evaluated their anti-proliferative potential against a panel of human cancer cell lines. Among the synthesized compounds, <b>9i</b> and <b>9m</b> elicited promising cytotoxicity against the breast cancer cell line MDA-MB-231 with IC<sub>50</sub> values of 1.65 and 1.12 μM, respectively. Cell cycle analysis revealed that <b>9i</b> and <b>9m</b> significantly arrest MDA-MB-231 cells in the G0/G1 phase. In addition, detailed biological studies such as annexin V-FITC/propidium iodide, DCFH-DA, JC-1 and DAPI staining assays revealed that <b>9i</b> and <b>9m</b> triggered apoptosis in MDA-MB-213 cells. Overall, the current work demonstrated the cytotoxicity and apoptosis-inducing potential of <b>9i</b> and <b>9m</b> in breast cancer cells and suggested that they could be explored as promising antiproliferative leads in the future.
Rearrangement and expression of immunoglobulin genes and expression of Tac antigen in hairy cell leukemia. (1983)

The origin and exact stage of differentiation of the neoplastic cells that comprise hairy cell leukemia have remained uncertain. As Ig heavy and light chain genes must both undergo a DNA rearrangement during B-cell development but rarely do so within other hematopoietic lineages, we examined these genes in this leukemia. The neoplastic cells of all eight cases demonstrated rearranged heavy and light chain genes and, in two cases examined, contained the corresponding mRNA for heavy and light chain Ig. Consistent with this B-cell genotype, all cases displayed cell surface HLA-DR and B-cell-associated antigens. Unexpectedly, all cases demonstrated cell surface Tac antigen, which previously had been restricted predominantly to select T-cell malignancies and activated T cells. Prior studies suggested that the anti-Tac monoclonal antibody recognized a peptide associated with the binding of interleukin 2 (T-cell growth factor) in such T cells. Immunoprecipitation with anti-Tac and NaDodSO4/polyacrylamide gel electrophoresis revealed an antigen on leukemic hairy cells with a Mr of 53,000-57,000, identical in size to the receptor on activated T cells. This apparent biphenotypic status might reflect a transformation-associated expression of the Tac antigen in this leukemia. Alternatively, hairy cell leukemia may be a malignancy of a unique stage of normal B-cell differentiation in which the Tac antigen is expressed.
A Cavopulmonary Assist Device for Long-Term Therapy of Fontan Patients (2021)

Treatment of univentricular hearts remains restricted to palliative surgical corrections (Fontan pathway). The established Fontan circulation lacks a subpulmonary pressure source and is commonly accompanied by progressively declining hemodynamics. A novel cavopulmonary assist device (CPAD) may hold the potential for improved therapeutic management of Fontan patients by chronic restoration of biventricular equivalency. This study aimed at translating clinical objectives toward a functional CPAD with preclinical proof regarding hydraulic performance, hemocompatibility and electric power consumption. A prototype composed of hemocompatible titanium components, ceramic bearings, electric motors, and corresponding drive unit was manufactured for preclinical benchtop analysis: hydraulic performance in general and hemocompatibility characteristics in particular were analyzed in-silico (computational fluid dynamics) and validated in-vitro. The CPAD's power consumption was recorded across the entire operational range. The CPAD delivered pressure step-ups across a comprehensive operational range (0-10 L/min, 0-50 mm Hg) with electric power consumption below 1.5 W within the main operating range. In-vitro hemolysis experiments (N = 3) indicated a normalized index of hemolysis of 3.8 ± 1.6 mg/100 L during design point operation (2500 rpm, 4 L/min). Preclinical investigations revealed the CPAD's potential for low traumatic and thrombogenic support of a heterogeneous Fontan population (pediatric and adult) with potentially accompanying secondary disorders (e.g., elevated pulmonary vascular resistance or systemic ventricular insufficiency) at distinct physical activities. The low power consumption implied adequate settings for a small, fully implantable system with transcutaneous energy transfer. The successful preclinical proof provides the rationale for acute and chronic in-vivo trials aiming at the confirmation of laboratory findings and verification of hemodynamic benefit.
Choosing the Device Generator and Leads: Matching the Device with the Patient (2012)

Several patient, device, and lead related characteristics should be considered prior to device implantation. Patient characteristics that determine the type of device implanted – single chamber, dual chamber or cardiac resynchronization therapy, include the underlying indication for pacing, presence of atrial arrhythmias, and indications for cardiac resynchronization. The implanting physician should also have a thorough understanding of lead design that affects lead performance, longevity, complications, and ease of extraction. Particular attention should be paid to the type of insulation, fixation mechanism, polarity, and compatibility of the generator and lead. Additional considerations for an implantable cardioverter-defibrillator (ICD) lead include sensing configuration (integrated vs. true bipolar) and defibrillation coil structure (single vs. dual). Coronary sinus leads should offer a low lead profile and flexibility to navigate the tortuous coronary venous system and stability to avoid dislodgement.