gebhart/patrepeval huggingface dataset:
Empathy: an essential skill for understanding the physician-patient relationship in clinical practice. (1993)

In clinical practice, empathy is the skill used by physicians to decipher and respond to thoughts and feelings in the physician-patient relationship. Empathetic understanding and empathetic response occur in three phases of every office visit: the negotiation phase, the clinical reasoning phase, and the establishment of therapeutic alliance. Masters of empathetic skills is difficult, and before teaching empathy to residents and students, teachers must first develop their own empathetic skills. Development of empathetic skills can occur in Balint training programs, through the use of audio- or videotaped patient encounters, or through one-on-one training with an experienced preceptor.
beditor : A Computational Workflow for Designing Libraries of Guide RNAs for CRISPR-Mediated Base Editing (2019)

CRISPR-mediated base editors have opened unique avenues for scar-free genome-wide mutagenesis. Here, we describe a comprehensive computational workflow called <i>beditor</i> that can be broadly adapted for designing guide RNA libraries with a range of CRISPR-mediated base editors, Protospacer Adjacent Motif (PAM) recognition sequences, and genomes of many species. Additionally, to assist users in selecting the best sets of guide RNAs for their experiments, <i>a priori</i> estimates of editing efficiency, called <i>beditor</i> scores, are calculated. These <i>beditor</i> scores are intended to select guide RNAs that conform to requirements for optimal base editing: the editable base falls within maximum activity window of the CRISPR-mediated base editor and produces nonconfounding mutational effects with minimal predicted off-target effects. We demonstrate the utility of the software by designing guide RNAs for base editing to model or correct thousands of clinically important human disease mutations.
Rapid Pediatric Cardiac Assessment of Flow and Ventricular Volume With Compressed Sensing Parallel Imaging Volumetric Cine Phase-Contrast MRI (2012)

Combined parallel imaging and compressed sensing can be applied to 4D phase contrast. With custom software, flow and ventricular volumes may be extracted with comparable accuracy to SSFP and 2D phase contrast. Furthermore, cardiac outputs were more consistent by 4D phase contrast.
On-Line Process Liquid Exclusion Chromatography Applied to the Production of Styrene-Butadiene Copolymers (1979)

Journal Article On-Line Process Liquid Exclusion Chromatography Applied to the Production of Styrene-Butadiene Copolymers Get access E.N. Fuller, E.N. Fuller Applied Automation, Inc., Research Development and Engineering Division, Pawhuska Road, Bartlesville, Oklahoma 74004 Search for other works by this author on: Oxford Academic PubMed Google Scholar G.T. Porter, G.T. Porter Applied Automation, Inc., Research Development and Engineering Division, Pawhuska Road, Bartlesville, Oklahoma 74004 Search for other works by this author on: Oxford Academic PubMed Google Scholar L.B. Roof L.B. Roof Applied Automation, Inc., Research Development and Engineering Division, Pawhuska Road, Bartlesville, Oklahoma 74004 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Chromatographic Science, Volume 17, Issue 12, December 1979, Pages 661–665, https://doi.org/10.1093/chromsci/17.12.661 Published: 01 December 1979
Use of a High Affinity DNA Ligand in Flow Cytometry (1996)

To investigate the feasibility of using oligonucleotides in flow cytometry we describe a model system consisting of human neutrophil elastase (HNE) coated on 3.3 micro beads and a high affinity DNA ligand for HNE isolated by in vitro selection (SELEX). In this system the fluoresceinated DNA ligand was equally effective as an anti- HNE antibody in detecting HNE on beads. The location on and the chemistry of attachment of fluorescein to the DNA ligand is critical for the sensitivity of detection. DNA constructs in which fluorescein was conjugated via an ethylene glycol tether to either the 5'-end or near the 3'-end gave much higher signals than did probes with fluorescein directly conjugated to either end. Second-step staining with strepavidin-conjugated phycoerythrin was accomplished using a biotinylated DNA ligand in the initial staining of HNE beads. These data suggest that instead of, or in addition to, antibodies high affinity oligonucleotide probes can be useful in diagnostic applications based on flow cytometry.
Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer’s Disease (2018)

Although immunotherapies against the amyloid-β (Aβ) peptide tried so date failed to prove sufficient clinical benefit, Aβ still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aβ from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe the physiologic mechanisms of Aβ clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Aβ-immunotherapy and discuss the related hypothesis of the mechanism of action of "peripheral sink." We also present Aβ-immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Aβ including the "CSF-sink" therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Aβ oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a "CSF-sink" of Aβ will probably produce a steady clearance of Aβ in the ISF and therefore it may represent a new therapeutic strategy in AD.
A Bridge from Full-Function to Reduced-Function Workstations (1986)

This article describes a system that allows a reduced-function workstation, an Apple Macintosh, to perform as a low-end node in an Apollo Domain workstation network. Programs that run in the Apollo environment do not have to be modified to be accessed from the Macintosh; the appropriate system subroutines are intercepted and recast into a suitable form. Each Apollo workstation can support from two to three Macintosh PCs, making the average cost per console as little as $5000. A similar project is underway for the IBM PC family of computers.
MOS trench gate field-controlled thyristor (2003)

A novel device structure for a field-controlled thyristor (FCT) utilizing MOS trench gates (UMOS) to control the turn-off of the device is described. Two-dimensional computer modeling of static and dynamic characteristics was performed. This device exhibits a good forward conduction characteristic with a low forward voltage drop at high current densities. Simulation results on transient turn-off showed a turn-off capability of 500 A/cm/sup 2/ with the use of a reasonable gate bias. Experimental devices of the UMOS FCT were designed and fabricated. A turn-off current of 3.8 A with a very high turn-off current gain has been achieved.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Improved nerve cuff electrode recordings with subthreshold anodic currents (1998)

A method has been developed for improving the signal amplitudes of the recordings obtained with nerve cuff electrodes. The amplitude of the electroneurogram (ENG) has been shown to increase with increasing distance between the contacts when cuff electrodes are used to record peripheral nerve activity [9]. The effect is directly related to the propagation speed of the action potentials. Computer simulations have shown that the propagation velocity of action potentials in a length of a nerve axon can be decreased by subthreshold extracellular anodic currents. Slowing the action potentials is analogous to increasing the cuff length in that both result in longer intercontact delays, thus, larger signal outputs. This phenomenon is used to increase the amplitudes of whole nerve recordings obtained with a short cuff electrode. Computer simulations predicting the slowing effect of anodic currents as well as the experimental verification of this effect are presented. The increase in the amplitude of compound action potentials (CAP's) is demonstrated experimentally in an in vitro preparation. This method can be used to improve the signal-to-noise ratios when recording from short nerve segments where the cuff length is limited.
Abstract B168: ANG1005: Results of a phase I study in patients with advanced solid tumors and metastatic brain cancer (2009)

Abstract ANG1005 is a new generation taxane created from Angiochem's Engineered Peptide Compound (EPiC) platform. Studies have shown that ANG1005 gains entry into the brain compartment by targeting the low-density lipoprotein receptor-related protein (LRP) which is one of the most highly expressed receptors on the surface of the BBB. Once inside the brain, ANG1005 enters tumor cells using the same receptor-mediated pathway through LRP, which is upregulated in various cancer cells including metastatic brain cancer cells. Metastatic brain cancer is the most common intracranial neoplasm in adults with an estimated incidence of 200 000 cases each year in the United States alone. To date, treatment options are limited and marginally effective. A multi-center, phase I, open-label, sequential cohort, dose escalation study of ANG1005 in patients with advanced solid tumors and brain metastases is ongoing in the US. Study objectives include characterization of safety and tolerability and identification of maximum tolerated dose (MTD). ANG1005 is administered by IV infusion once every 21 days (1 treatment cycle) without premedication. After evaluating doses of 30–700 mg/m2, 650 mg/m2 was identified as MTD. Data including adverse events and hematological parameters indicate that ANG1005 is safe and well tolerated. The most common events occurring at a severity ≥ Grade 2 according to CTCAE, version 3.0 at MTD (n=20) were neutropenia (95% of patients; Grade 4 in 75%), leucopenia (100%; Grade 4 in 40%), anemia (55%; no cases of Grade 4), thrombocytopenia (40%; no cases of Grade 4) and mucositis (25%; no cases of Grade 4); these events have been transient and manageable with standard treatments. Neurocognitive data have shown that ANG1005 does not cause cognitive impairment and tests for antibodies demonstrate that ANG1005 does not elicit antibody production even in patients who have received up to 6 cycles of treatment. Pharmacokinetic data indicate linear ANG1005 bioavailability. Disease control (≥ stable disease) assessed by CT/MRI in this heavily pre-treated group of patients was achieved in 70% at doses &amp;gt; 300 mg/m2 including 7 patients who had previously progressed on taxane therapy. Partial response was observed in 30% of patients dosed &amp;gt; 300 mg/m2. Tumor types that showed the best improvements were breast, non-small cell lung and ovarian cancers. Furthermore, partial and complete responses were achieved in metastatic locations including the brain (67% disease control), liver (70% disease control), lung (67% disease control) and lymph nodes (80% disease control). Clinical data gathered to date indicate that ANG1005 shows promise as a potential treatment option for patients with advanced solid tumors and brain metastases. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B168.
Learning to coordinate behaviors (1990)

We describe an algorithm which allows a behavior-based robot to learn on the basis of positive and negative feedback when to activate its behaviors. In accordance with the philosophy of behavior-based robots, the algorithm is completely distributed: each of the behaviors independently tries to find out (i) whether it is relevant (ie. whether it is at all correlated to positive feedback) and (ii) what the conditions are under which it becomes reliable (i.e. the conditions under which it maximizes the probability of receiving positive feedback and minimizes the probability of receiving negative feedback). The algorithm has been tested successfully on an autonomous 6-legged robot which had to learn how to coordinate its legs so as to walk forward. Situation of the Problem Since 1985, the MIT Mobile Robot group has advocated a radically different architecture for autonomous intelligent agents (Brooks, 1986). Instead of decomposing the architecture into functional modules, such as perception, modeling, and planning (figure 1), the architecture is decomposed into task-achieving modules, also called behaviors (figure 2). This novel approach has already demonstrated to be very successful and similar approaches have become more
High-level expression of a heterologous protein in the milk of transgenic swine using the cDNA encoding human protein C. (1992)

Transgenic pigs were generated that produced human protein C in their milk at up to 1 g/liter. The gene construct was a fusion gene consisting of the cDNA for human protein C inserted into the first exon of the mouse whey acidic protein gene. These results demonstrate that the mouse whey acidic protein gene contains regulatory elements that can direct cDNA expression at high levels in the pig mammary gland. Recombinant human protein C that was produced at about 380 micrograms/ml per hr in transgenic pig milk possessed anticoagulant activity that was equivalent to that of protein C derived from human plasma. These studies provide evidence that gamma-carboxylation can occur at high levels in the mammary gland of a pig.
Dynamic program slicing (1990)

Program slices are useful in debugging, testing, maintenance, and understanding of programs. The conventional notion of a program slice, the static slice , is the set of all statements that might affect the value of a given variable occurrence. In this paper, we investigate the concept of the dynamic slice consisting of all statements that actually affect the value of a variable occurrence for a given program input. The sensitivity of dynamic slicing to particular program inputs makes it more useful in program debugging and testing than static slicing. Several approaches for computing dynamic slices are examined. The notion of a Dynamic Dependence Graph and its use in computing dynamic slices is discussed. The Dynamic Dependence Graph may be unbounded in length; therefore, we introduce the economical concept of a Reduced Dynamic Dependence Graph, which is proportional in size to the number of dynamic slices arising during the program execution.
Role of the Liver and Kidney in the Desulphation of Heparin in vivo (1995)

Heparin radiolabelled with 125I was given intravenously to intact, bilaterally nephrectomised or completely hepatectomised rats in the presence and absence of 1 mg unlabelled heparin/kg. Plasma samples were collected and analysed by gel filtration chromatography and affinity chromatography on Polybrene-Sepharose, which binds sulphated glycosaminoglycans. Radiolabel in the plasma was associated with both intact heparin and fully desulphated macromolecular carbohydrate chains. Levels of intact heparin in plasma from control rats decreased with time at both doses with a concomitant increase in desulphated material. Livers accumulated the greatest amounts of radiolabel on a per organ basis. Hepatectomy both increased levels of radiolabel in plasma and decreased amounts of desulphated heparin produced, indicating that the liver was the major site of desulphation. Even after removal of the liver, the desulphated metabolite comprised approximately 15% of radiolabelled material at all times and doses, suggesting an additional site of GAG desulphation which may be the vascular endothelium. The kidneys contributed significantly to in vivo desulphation of heparin only at the high dose.
Insulin peptides. Part XXIII. The synthesis of a hexadecapeptide derivative related to the B chain of human insulin (1973)

A protected hexadecapeptide with the amino-acid sequence found at the C-terminal region of the human insulin B chain has been prepared by condensation of N-terminal hexapeptide and C-terminal decapeptide fragments, which were prepared stepwise. All the protecting groups employed are labile to hydrogen fluoride.
Antiinflammatory and antiallergic effects of a novel metabolite of Nocardiopsis sp. as a potent protein kinase C inhibitor from microbial origin. (1988)

The antiallergic and antiinflammatory effects of the new protein kinase C and calmodulin inhibitor K-252a (8R, 9S, 11S)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11- epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]cycl oocta [cde] trinden-1-one) were investigated in animal models, and the following results were obtained: 1. Oral administration of K-252a, ketotifen or oxatomide showed a dose-dependent inhibition on 48 h homologous passive cutaneous anaphylaxis in rats and anaphylactic bronchoconstriction in passively sensitized guinea pigs. 2. K-252a (1-100 mg/kg p.o.) exerted a dose-dependent protection against platelet-activating factor (PAF)-induced mortality in mice. This protective effect of K-252a was sustained for 7 h. 3. K-252a (1-100 mg/kg p.o.), as well as dexamethasone (1 mg/kg s.c.), showed remarkable inhibitory effects on rat paw edema induced by carrageenin, zymosan, PAF, and antigen-antibody reaction (passive Arthus reaction) and on the croton oil-induced rat ear edema. On the other hand, indomethacin (10 mg/kg p.o.) significantly inhibited carrageenin-induced edema, but did not inhibit edema induced by other phlogistic agents. Based on these results it is suggested that K-252a, by oral administration, has antiallergic and antiinflammatory effects.
Min-cut based segmentation of point clouds (2009)

We present a min-cut based method of segmenting objects in point clouds. Given an object location, our method builds a k-nearest neighbors graph, assumes a background prior, adds hard foreground (and optionally background) constraints, and finds the min-cut to compute a foreground-background segmentation. Our method can be run fully automatically, or interactively with a user interface. We test our system on an outdoor urban scan, quantitatively evaluate our algorithm on a test set of about 1000 objects, and compare to several alternative approaches.
First-in-human study of AMG 655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors (2007)

3534 Introduction: AMG 655 is a fully human monoclonal agonist antibody that binds human TRAIL receptor 2 (TR-2/DR5), activates caspases, and induces apoptosis in sensitive tumor cells. The primary objectives of this ongoing first-in-human study were to assess the safety, tolerability, and pharmacokinetics (PK) of AMG 655 in patients (pts) with advanced solid tumors. Methods: Three to 9 pts were enrolled into 1 of 5 sequential dose cohorts (0.3, 1, 3, 10, or 20 mg/kg) of AMG 655 administered intravenously Q2W. No AMG 655 was administered on day 43 to allow assessment of terminal PK parameters. RECIST and FDG-PET were analyzed by central radiology. Pts remained on study until tumor progression or unacceptable toxicities occurred. Results: As of October 19, 2006, 16 pts (4 in the 10 mg/kg cohort; 3 in each of the other cohorts) had received = 1 dose of AMG 655; 12 pts were men, mean (SD) age was 53 (±8.9) years. No DLTs or AMG 655-related serious AEs were reported. The MTD was not reached. Nine pts reported AMG 655-related AEs. Treatment-related AEs in 3 or more pts were: pyrexia (4 pts), fatigue (3 pts), and hypomagnesaemia (3 pts). Fatigue and elevated serum lipase were the only grade 3 or higher AMG 655-related AEs and both occurred in the same pt (0.3-mg/kg cohort). No anti-AMG 655 antibodies were detected. PK data were available from dose cohorts 1 to 3 (0.3, 1, and 3 mg/kg); AMG 655 demonstrated dose-linear kinetics with a half-life of ∼10 days. Tumor- response data were available for 13 pts. Partial response was observed in 1 pt with non-small cell lung cancer (NSCLC) who experienced a 46% reduction in tumor volume by RECIST and remains on study after 48 weeks. Stable disease was reported in 4 pts (range 6 to 35 weeks), and progressive disease in 8 pts. One pt with colorectal cancer and stable disease demonstrated a metabolic partial response with a 34% reduction in maximum standardized uptake value (SUV max ). Conclusions: AMG 655 administered up to 20 mg/kg Q2W appeared to be well tolerated in these pts. The anti-tumor activity of AMG 655 was confirmed with observation of a partial response in NSCLC and a metabolic partial response in colorectal cancer. Further studies evaluating AMG 655 in combination with chemotherapy and targeted agents are warranted. No significant financial relationships to disclose.
N-propionylated group B meningococcal polysaccharide mimics a unique epitope on group B Neisseria meningitidis. (1987)

Antibodies induced in mice by the N-propionyl (N-Pr)-group B meningococcal polysaccharide (GBMP)-tetanus toxoid (TT) conjugate were bactericidal for GBM organisms independent of protein serotype. The antisera contained two populations of N-Pr-GBMP-specific antibodies, only one of which crossreacted with the GBMP. Particularly significant was the fact that the bactericidal activity was mainly associated with the population of antibodies that did not crossreact with the GBMP. Therefore it can be inferred from the above evidence that the N-Pr-GBMP mimics a unique epitope on the surface of GBM organisms that is not present on the exogenous GBMP.
Site-Directed Mutagenesis of Surface-Exposed Lysine Residues Leads to Improved Transduction by AAV2, But Not AAV8, Vectors in Murine Hepatocytes In Vivo (2015)

The ubiquitin-proteasome pathway plays a critical role in the intracellular trafficking of recombinant adeno-associated virus 2 (AAV2) vectors, which negatively impacts the transduction efficiency of these vectors. Because ubiquitination occurs on lysine (K) residues, we performed site-directed mutagenesis where we replaced each of 10 surface-exposed K residues (K258, K490, K507, K527, K532, K544, K549, K556, K665, and K706) with glutamic acid (E) because of similarity of size and lack of recognition by modifying enzymes. The transduction efficiency of K490E, K544E, K549E, and K556E scAAV2 vectors increased in HeLa cells in vitro up to 5-fold compared with wild-type (WT) AAV2 vectors, with the K556E mutant being the most efficient. Intravenous delivery of WT and K-mutant ssAAV2 vectors further corroborated these results in murine hepatocytes in vivo. Because AAV8 vectors transduce murine hepatocytes exceedingly well, and because some of the surface-exposed K residues are conserved between these serotypes, we generated and tested two single mutants (K547E and K569E), and one double-mutant (K547 + 569E) AAV8 vector. However, no significant increase in the transduction efficiency of any of these mutant AAV8 vectors was observed in murine hepatocytes in vivo. These studies suggest that although targeting the surface-exposed K residues is yet another strategy to improve the transduction efficiency of AAV vectors, phenotypic outcome is serotype specific.