gebhart/patrepeval huggingface dataset:
Covalently Binding of Bovine Serum Albumin to Unsaturated Poly(Globalide‐Co‐ε‐Caprolactone) Nanoparticles by Thiol‐Ene Reactions (2019)

When nanoparticles (NPs) are introduced to a biological fluid, different proteins (and other biomolecules) rapidly get adsorbed onto their surface, forming a protein corona capable of giving to the NPs a new "identity" and determine their biological fate. Protein-nanoparticle conjugation can be used in order to promote specific interactions between living systems and nanocarriers. Non-covalent conjugates are less stable and more susceptible to desorption in biological media, which makes the development of engineered nanoparticle surfaces by covalent attachment an interesting topic. In this work, the surface of poly(globalide-co-ε-caprolactone) (PGlCL) nanoparticles containing double bonds in the main polymer chain is covalently functionalized with bovine serum albumin (BSA) by thiol-ene chemistry, producing conjugates which are resistant to dissociation. The successful formation of the covalent conjugates is confirmed by flow cytometry (FC) and fluorescence correlation spectroscopy (FCS). Transmission electron microscopy (TEM) allows the visualization of the conjugate formation, and the presence of a protein layer surrounding the NPs can be observed. After conjugation with BSA, NPs present reduced cell uptake by HeLa and macrophage RAW264.7 cells, in comparison to uncoated NP. These results demonstrate that it is possible to produce stable conjugates by covalently binding BSA to PGlCL NP through thiol-ene reaction.
A 79dB SNDR, 10MHz BW, 675MS/s open-loop time-based ADC employing a 1.15ps SAR-TDC (2016)

This paper introduces a first-order noise-shaped time-domain ADC utilizing SAR-TDC as quantizer. The high resolution correlated double sampling SAR-TDC improves the quantization noise level of the ADC. The VCO non-linearity is resolved by employing a 1-bit folded VCO architecture. The ADC linearity is further improved using foreground digital calibration. Implemented in 65nm CMOS, the 675MS/s time-domain ADC achieves measured peak SNDR/SFDR of 79.5/86.4dB in 10MHz BW while consuming 11.65mW. The SAR-TDC achieves 1.15ps resolution with peak measured DNL/INL of 0.64/0.65LSB. The 1-bit folded VCO improves the VCO linearity from 12% to 0.17%.
Phase I study of infusion of HER2/neu (HER2) specific T cells in patients with advanced-stage HER2 overexpressing cancers who have received a HER2 vaccine (2009)

3000 Background: Adoptive T-cell therapy has shown promise in the treatment of advanced-stage melanoma. We have previously reported that expansion of HER2-specific T cells from peripheral blood mononuclear cells (PBMC) can be greatly facilitated by vaccine-priming. In this study, we evaluated the safety and clinical efficacy of infusion of HER2-specific T cells in patients with advanced HER2 overexpressing cancers. Methods: 10 patients with progressive HER2 + metastatic breast and ovarian cancer, not considered curable by conventional therapies, will be enrolled in this study. The patients must have been pre-immunized with a HER2-specific vaccine. Three escalating doses of T cells are given at 10-day intervals. Cyclophosphamide or denileukin diftitox is administrated before the first dose of T cells. Results: To date, 5 of 10 subjects have been enrolled. T cells were expanded with HER2-specific class II restricted peptides. After in vitro expansion cell products were &gt;95% CD3 + with an average of 35% CD4 + and 60% CD8 + T cells. The maximal doses infused were 1x10 9 -41x10 9 cells (median 10x10 9 ). Subjects tolerated the infusions well with the primary toxicity being related to the conditioning agent. Objective tumor regression has been observed in 2 of the 5 treated patients. One other patient has had stable disease after treatment. In patients with tumor regression, the magnitude of HER2-specific T cells in the infused product was 8-fold higher than that in patients without clinical responses. The total number of HER2-specific T cells infused was 43-fold higher in responding patients than in nonresponding patients. Moreover, HER2-specific CD4 + and CD8 + T cells persisted over a year and even augmented in magnitude post-infusion in responding patients. Conclusions: Adoptive transfer of autologous HER2 specific polyclonal T cells generated from PBMC after vaccine-priming is well tolerated and has shown evidence of some clinical efficacy in patients with advanced-stage HER2 + cancers. No significant financial relationships to disclose.
Beneficial effect of quetiapine monotherapy in patients with bipolar depression and comorbid obsessive-compulsive disorder (2020)

Obsessive-compulsive disorder (OCD) is a prevalent and clinically significant comorbid condition in patients with bipolar disorder. Treatment of bipolar disorder/OCD patients is challenging. We report the results of an open-label, short-term, prospective investigation of quetiapine monotherapy in 16 patients (three men and 13 women, aged 18-56 years) hospitalized for acute bipolar depression who in addition met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for OCD. The participants were treated with quetiapine in a dose range of 150-600 mg (mean 347 mg) for a mean duration of 4.3 ± 1.4 weeks (range 3-7 weeks). Eleven (68.8%) of the 16 study participants fulfilled the predefined criteria for response, namely a score of 'very much improved' (four patients) and 'much improved' (seven patients) on the Clinical Global Impression - Improvement scale. Treatment with quetiapine was associated with a statistically significant decrease from baseline in the relevant rating scales for the assessment of depressive, manic and OCD symptoms. Quetiapine was well tolerated. The most frequently reported side effects were sedation, orthostatic hypotension and constipation. Durability of the positive therapeutic effect of quetiapine monotherapy in patients with bipolar disorder/OCD comorbidity and the necessity for subsequent augmentation with anti-OCD agents need to be addressed in future controlled studies.
Static Polystyrene Gate Charge Density Modulation of Dinaphthothienothiophene with Tetrafluorotetracyanoquinodimethane Layer Doping: Evidence from Conductivity and Seebeck Coefficient Measurements and Correlations (2019)

We relate the static charging of organic field effect transistor (OFET) gate dielectric polymers, the resulting change in threshold voltage shift, and the modulation of thermoelectric properties of the transistor semiconductor. We utilize a bottom gate OFET structure with cross-linkable polystyrene and plain polystyrene (XLPS/PS) bilayer dielectrics and dinaphthothienothiophene (DNTT) organic molecular semiconductor with tetrafluorotetracyanoquinodimethane (F4TCNQ) doping layer. The conductivity and Seebeck coefficient are measured before and after charging. We find that the conductivity increases significantly, while the Seebeck coefficient decreases correspondingly in a trend of S ∝ ln(σ) after the dielectrics were negatively charged, resulting in an average of 5-fold increase in power factor at the maximum charging level. Additionally, temperature-dependent conductivity measurements show that the activation energy decreases with the increasing conductivity. We calculate the Seebeck coefficient based on the activation energy and find the result is consistent with the Mott mobility edge model. This work confirms the charging mechanism in our previous published work, including the location of static charges in the bulk of the dielectric, and demonstrates modulation and enhancement of the thermoelectric properties of organic thermoelectric materials by adjacent chargeable dielectrics without changing the molecular microstructure or applying external gate voltage during operation.
Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2) for tissue ablation (2017)

The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible electroporation with injection of drugs) and irreversible electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and electroporation, without the need to inject drugs as in reversible electroporation or use paralyzing anesthesia as in irreversible electroporation.
Generating Integration Tests Automatically Using Frequent Patterns of Method Execution Sequences (2019)

Integration testing is vitally important for ensuring software quality, since many serious software defects are not isolated in single components. Unfortunately, creating integration tests is often a manual and laborious effort. A fundamental problem of software testing is how to automatically create effective integration tests with oracles that find bugs efficiently.
Automated detection of critical findings in multi-parametric brain MRI using a system of 3D neural networks (2021)

With the rapid growth and increasing use of brain MRI, there is an interest in automated image classification to aid human interpretation and improve workflow. We aimed to train a deep convolutional neural network and assess its performance in identifying abnormal brain MRIs and critical intracranial findings including acute infarction, acute hemorrhage and mass effect. A total of 13,215 clinical brain MRI studies were categorized to training (74%), validation (9%), internal testing (8%) and external testing (8%) datasets. Up to eight contrasts were included from each brain MRI and each image volume was reformatted to common resolution to accommodate for differences between scanners. Following reviewing the radiology reports, three neuroradiologists assigned each study to abnormal vs normal, and identified three critical findings including acute infarction, acute hemorrhage, and mass effect. A deep convolutional neural network was constructed by a combination of localization feature extraction (LFE) modules and global classifiers to identify the presence of 4 variables in brain MRIs including abnormal, acute infarction, acute hemorrhage and mass effect. Training, validation and testing sets were randomly defined on a patient basis. Training was performed on 9845 studies using balanced sampling to address class imbalance. Receiver operating characteristic (ROC) analysis was performed. The ROC analysis of our models for 1050 studies within our internal test data showed AUC/sensitivity/specificity of 0.91/83%/86% for normal versus abnormal brain MRI, 0.95/92%/88% for acute infarction, 0.90/89%/81% for acute hemorrhage, and 0.93/93%/85% for mass effect. For 1072 studies within our external test data, it showed AUC/sensitivity/specificity of 0.88/80%/80% for normal versus abnormal brain MRI, 0.97/90%/97% for acute infarction, 0.83/72%/88% for acute hemorrhage, and 0.87/79%/81% for mass effect. Our proposed deep convolutional network can accurately identify abnormal and critical intracranial findings on individual brain MRIs, while addressing the fact that some MR contrasts might not be available in individual studies.
Dominant negatives p73 beim hepatozellulären Karzinom: Onkogen und Prädiktor für Prognose- und Therapieansprechen (2006)

Einl.: Mit der Identifikation der neuen p53 Familienmitglieder p63 und p73 und ihren dominant negativen Isoformen zeichnet sich ab, dass p53 nicht die alleinige Determinante für Prognose und Therapieansprechen maligner Tumore ist. Wir konnten für das hepatozelluläre Karzinom (HCC) zeigen, dass die Interaktion/das Netzwerk der p53 Familie und ihrer ΔN Formen über Tumorentstehung, Chemosensitivität und Prognose entscheidet. (EMBO J 24 (2005); Cell Death Differ Sep 30 2005). Wir haben die molekularen Mechanismen der onkogenen Wirkung von ΔNp73 beim HCC charakterisiert. Methoden: TAp53, TAp63, TAp73 und ΔNp73 wurden mittels adenoviraler Vektoren in Hep3B-Zellen transferiert. Zusätzlich wurden die Zellen mit Chemotherapeutika in klinisch relevanten Konzentrationen behandelt. Induzierte Apoptose-Signaltransduktionswege wurden unter dem inhibitorischen Einfluss von ΔNp73 untersucht. Die Charakterisierung der Apoptose-Signalwege erfolgt durch FACS Analyse (Nicoletti-, CD95-R, TNF-R, TRAIL-R1, TRAIL-R2 und JC–1-Färbung), Blockade- und Stimulationsexperimente (Todesrezeptoren, Caspasen), RNA Interferenz, Immunoblot, Luciferase-Reporter-Assays sowie mittels cDNA-Mikroarray-Analysen. Ergebnisse: 1) ΔNp73 hemmt die p53-, p63- und p73 vermittelte Todesrezeptor- und mitochondriale Apoptose und führt so zur Tumorprogression und Chemotherapieresistenz. 2) ΔNp73 hemmt die Expression pro-apoptotischer Gene wie CD95, TRAIL-R2, TNF-R1 und –R2, Caspasen sowie APAF–1. 3) ΔNp73 induziert die Expression antiapoptotischer Gene wie BNIP1 (BCL2/adenovirus E1B 19 kd-interacting protein (BNIP) family) und BCL2XL (Bcl–2-Familie). 4) ΔNp73 interferiert mit Signalwegen, die durch Chemotherapie getriggert werden; so wird die Expression proapoptotischer, durch Behandlung mit Bleomycin induzierter Gene, wie Caspasen, PIG11, PIG2, TNF, und TRAIL durch ΔNp73 herunterreguliert. 5) ΔNp73 aktiviert die Transkription von Onkogenen wie FosB und v-myc. Diskussion: ΔNp73 ist beim HCC aktiv onkogen. Die Expression von ΔNp73 führt zu einem Selektionsvorteil der Tumorzelle durch 1) Inhibition der zentralen Apoptose-Signalwege 2) Indukton anti-apoptotischer Gene. 3) Interferenz mit durch Chemotherapeutika getriggerten Signalwegen. 4) Aktivierung von Onkogenen. Wir sind überzeugt, dass die pharmakologische Beeinflussung des Gleichgewichtes von TAp53, TAp63 und TAp73 und ihrer ΔN Formen, zum Beispiel durch RNA Interferenz, wichtige therapeutische Optionen in der Therapie des HCC eröffnen wird.
Joint probability of shape and image similarities to retrieve 2D TRUS-MR slice correspondence for prostate biopsy (2012)

This paper presents a novel method to identify the 2D axial Magnetic Resonance (MR) slice from a pre-acquired MR prostate volume that closely corresponds to the 2D axial Transrectal Ultrasound (TRUS) slice obtained during prostate biopsy. The method combines both shape and image intensity information. The segmented prostate contours in both the imaging modalities are described by shape-context representations and matched using the Chi-square distance. Normalized mutual information and correlation coefficient between the TRUS and MR slices are computed to find image similarities. Finally, the joint probability values comprising shape and image similarities are used in a rule-based framework to provide the MR slice that closely resembles the TRUS slice acquired during the biopsy procedure. The method is evaluated for 20 patient datasets, of which 18 results match at least one of the two clinical expert choices.
An axisymmetric model for thread forming in polycarbonate and polypropylene screw and boss fasteners (2004)

Abstract Plastic boss and screw fasteners are an economical means of securing automotive components, such as instrument or body panels. However, new materials and/or suboptimal design present challenges to the boss/screw effectiveness. Failure of a boss/screw can result is loss of functional performance or increased squeak and rattle. Failure is often controlled by what occurs during the initial thread‐forming process. Thus, the goal of this paper is to develop an FEA model to elucidate the thread‐forming process so that we can facilitate subsequent design and/or process optimization, and understand potential failure modes. The FEA must accommodate nonlinear couplings, such as large strain and heat transfer. Heat generation is present in the forms of interfacial shear heating and plastic work associated with the large deformation of the interface between the boss and screw. Strain rate‐dependent materials are included using the Eyring theory for plastic flow of polymeric materials. Results of the model are presented and compared to experimentally determined torque curves and temperatures. Polym. Eng. Sci. 44:1498–1508, 2004. © 2004 Society of Plastics Engineers.
A power autonomous monopedal robot (2006)

We present the design and initial results of a power-autonomous planar monopedal robot. The robot is a gasoline powered, two degree of freedom robot that runs in a circle, constrained by a boom. The robot uses hydraulic Series Elastic Actuators, force-controllable actuators which provide high force fidelity, moderate bandwidth, and low impedance. The actuators are mounted in the body of the robot, with cable drives transmitting power to the hip and knee joints of the leg. A two-stroke, gasoline engine drives a constant displacement pump which pressurizes an accumulator. Absolute position and spring deflection of each of the Series Elastic Actuators are measured using linear encoders. The spring deflection is translated into force output and compared to desired force in a closed loop force-control algorithm implemented in software. The output signal of each force controller drives high performance servo valves which control flow to each of the pistons of the actuators. In designing the robot, we used a simulation-based iterative design approach. Preliminary estimates of the robot's physical parameters were based on past experience and used to create a physically realistic simulation model of the robot. Next, a control algorithm was implemented in simulation to produce planar hopping. Using the joint power requirements and range of motions from simulation, we worked backward specifying pulley diameter, piston diameter and stroke, hydraulic pressure and flow, servo valve flow and bandwidth, gear pump flow, and engine power requirements. Components that meet or exceed these specifications were chosen and integrated into the robot design. Using CAD software, we calculated the physical parameters of the robot design, replaced the original estimates with the CAD estimates, and produced new joint power requirements. We iterated on this process, resulting in a design which was prototyped and tested. The Monopod currently runs at approximately 1.2 m/s with the weight of all the power generating components, but powered from an off-board pump. On a test stand, the eventual on-board power system generates enough pressure and flow to meet the requirements of these runs and we are currently integrating the power system into the real robot. When operated from an off-board system without carrying the weight of the power generating components, the robot currently runs at approximately 2.25 m/s. Ongoing work is focused on integrating the power system into the robot, improving the control algorithm, and investigating methods for improving efficiency.
Reconfigurable Microfluidic System Architecture Based on Two-Dimensional Electrowetting Arrays (2005)

We present an architectural design and optimization methodology for performing biochemical reactions using two-dimensional electrowetting arrays. We define a set of basic microfluidic operations and leverage electronic design automation principles for system partitioning, resource allocation, and operation scheduling. Fluidic operations are carried out by properly configuring a set of grid points. While concurrency is desirable to minimize processing time, the size of the two-dimensional array limits the number of concurrent operations of any type. Furthermore, functional dependencies between the operations also limit concurrency. We use integer linear programming to minimize the processing time by automatically extracting parallelism from a biochemical assay. As a case study, we apply our optimization method to the polymerase chain reaction.
Imaging Life at High Spatiotemporal Resolution (2015)

I will describe three different technologies that balance the inevitable tradeoffs of spatial resolution, speed, and non-invasiveness in fluorescence microscopy: 3D localization microscopy of cellular ultrastructure; nonlinear structured illumination microscopy of live cell dynamics in the sub-100 nm regime; and lattice light sheet microscopy of rapid 3D dynamic processes in vivo. Article not available.
Deposition of Au[sub x]Ag[sub 1−x]/Au[sub y]Ag[sub 1−y] Multilayers and Multisegment Nanowires (2003)

multilayers and multisegment nanowires were deposited from a single solution containing and (pH 13). Cyclic voltammograms for deposition from solutions containing and show the characteristic deposition peaks for gold and silver. The composition of the deposited alloys is dependent on the deposition potential (or current) and solution chemistry. Multisegment nanowires were prepared by sequential deposition at and from solutions containing and solution in porous templates. The different segments deposited at and are clearly distinguished by scanning electron microscopy and optical microscopy under blue light illumination. © 2003 The Electrochemical Society. All rights reserved.
ULK1 Phosphorylates and Regulates Mineralocorticoid Receptor (2018)

Mineralocorticoid receptor (MR) signaling regulates both renal Na-Cl reabsorption and K<sup>+</sup> excretion. We previously demonstrated that phosphorylation of S843 in the MR ligand-binding domain in renal intercalated cells is involved in the balance of these activities by regulating ligand binding and signaling. However, the kinase that phosphorylates MR<sup>S843</sup> is unknown. Using a high-throughput screen assay of 197 kinases, we found that ULK1 is the principal kinase that is responsible for the phosphorylation of MR<sup>S843</sup>. The results were confirmed by in vitro kinase assay, mass spectrometry, and siRNA knockdown experiments. Notably, phosphorylation at MR<sup>S843</sup> was markedly reduced in ULK1/2 double knockout mouse embryonic fibroblasts. Upstream, we show that ULK1 activity is inhibited by phosphorylation induced by angiotensin II via mTOR in cell culture and in vivo. These findings implicate mTOR and ULK1 as regulators of MR activity in intercalated cells, a pathway that is critical for maintaining electrolyte homeostasis.
Pharmacological Activation of Normal and Arrhythmia-Associated Mutant KCNQ1 Potassium Channels (2003)

KCNQ1 alpha-subunits coassemble with KCNE1 beta-subunits to form channels that conduct the slow delayed rectifier K+ current (IKs) important for repolarization of the cardiac action potential. Mutations in KCNQ1 reduce IKs and cause long-QT syndrome, a disorder of ventricular repolarization that predisposes affected individuals to arrhythmia and sudden death. Current therapy for long-QT syndrome is inadequate. R-L3 is a benzodiazepine that activates IKs and has the potential to provide gene-specific therapy. In the present study, we characterize the molecular determinants of R-L3 interaction with KCNQ1 channels, use computer modeling to propose a mechanism for drug-induced changes in channel gating, and determine its effect on several long-QT syndrome-associated mutant KCNQ1 channels heterologously expressed in Xenopus oocytes. Scanning mutagenesis combined with voltage-clamp analysis indicated that R-L3 interacts with specific residues located in the 5th and 6th transmembrane domains of KCNQ1 subunits. Most KCNQ1 mutant channels responded to R-L3 similarly to wild-type channels, but one mutant channel (G306R) was insensitive to R-L3 possibly because it disrupted a key component of the drug-binding site.