gebhart/patrepeval huggingface dataset:
Segment velocities in normal and transtibial amputees: prosthetic design implications (1998)

Dynamic elastic response foot and ankle prostheses (Seattle-Lite, Flex Foot, etc.) used by transtibial amputees feature substantial design improvements over conventional designs (SACH, Single Axis, etc.). Despite this progress, transtibial amputees continue to expend greater energy than normals. Increased residual limb EMG data and altered gait patterns suggest that impaired mobility may be the cause of overactive muscles in early stance. Prosthetic mobility was therefore quantified by measuring foot, shank and thigh velocities in nine transtibial amputees, wearing three different foot designs: Single Axis (SA), Seattle Lite (SL) and Flex Foot (FF). The magnitude, timing and rate of segment velocities for each prosthetic design, characterizing early stance mobility, were compared with corresponding measures in normal, nonamputee (NA) controls using Dunnett's test. Regardless of foot type, transtibial (TT) amputees walked slower than non amputee controls (63.3-65.8 m/min versus 78.5 m/min, p < 0.05) and their stride length was shorter (1.21-1.26 m versus 1.41 m, p < 0.01). In early stance, peak foot and shank velocities were lower (p < 0.01) for both the SL and FF while only shank velocity was lower (p < 0.01) with the SA compared to NA controls. Significant delays in the timing of early stance events such as peak shank velocity, peak ankle plantarflexion and peak knee flexion compromised shank and knee stability in TT amputees. Foot and shank mobility was uncontrolled with the SA design while ankle mobility was restricted by the FF and SL feet. In NA controls on the other hand, appropriate timing and rate of segment velocity changes preserved dynamic stability and forward progression in early stance. This was evidenced by rapid decreases in foot and shank velocity as the thigh velocity increased during weight acceptance. Future prosthetic designs should provide TT amputees with improved ankle mobility that attempt to capture the dynamic characteristics of a normal articulation between the foot and shank segments during the early stance weight acceptance period.
[A case of 'hallucination of soliloquy' with hypothyroidism induced Hashimoto disease. Meaning of psychopathological research about symptomatic psychosis]. (2001)

We describe the first reported case of symptomatic psychosis with the 'hallucination of soliloquy.' A 48[correction of 40]-year-old woman with Hashimoto disease exhibited of compulsive checking, mysophobia, and excessive hand washing. When these obsessive-compulsive symptoms diminished, she began to suffer from the 'hallucination of soliloquy', the automatic flow of meaningless words inside her mind. As the 'soliloquy' increased, her mood became unstable and she attempted suicide by analgesic ingestion. After this, she was admitted to the psychiatric ward of a general hospital. The administration of clomipramine (150 mg daily) decreased the 'soliloquy' symptoms, but they did not resolve. When hypothyroidism became available, thyroid hormone treatment (levothyroxine at 50 mg daily) was started. Four weeks later, her 'soliloquy' symptoms had almost resolved and after three months in a stable state, thyroid hormone treatment was stopped and her 'soliloquy' symptoms soon reappeared. After thyroid hormone treatment was resumed, her 'soliloquy' symptoms disappeared immediately. Typical auditory hallucinations and delusions of reference were not observed throughout the clinical course. We speculate that the symptoms were symptomatic psychosis induced by hypothyroidism secondary to Hashimoto disease, because the changes of her hallucinations were related to free T3 values and the symptoms disappeared soon after starting thyroid hormone treatment. The main features of this case were 'soliloquy' alternating with obsessive-compulsive symptoms, but her 'soliloquy' symptoms were thought to be autochthonous ideas rather than obsessive thoughts. Furthermore, the symptoms in this case were different from schizophrenia, since there was no disturbance of communication, and she had the sensation of both speaking and hearing her own voice. The psychopathology of this 'hallucination of soliloquy' may be related to the theory of 'vocalization of background thinking' (N. Nakayasu). Detailed observation of patients with symptomatic psychosis and a psychopathological description of their symptoms may help to contribute to the etiologic elucidation and treatment of psychosis.
Familial Risk of Lung Carcinoma in the Icelandic Population (2004)

These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.
EXCHANGE AND CORRELATION EFFECTS IN AN INHOMOGENEOUS ELECTRON GAS (1965)

Abstract : From a theory of Hohenberg and Kohn, approximation methods for treating an inhomogeneous system of interacting electrons are developed. They lead to selfconsistent equations analagous to the Hartree and HartreeFock equations, respectively. In these equations the exchange and correlation portions of the chemical potential of a uniform electron gas appear as corrections to the electrostatic potential.
Ultrahigh efficient spin-orbit torque magnetization switching in all-sputtered topological insulator - ferromagnet multilayers (2020)

Spin-orbit torque (SOT) magnetization switching of ferromagnets with large perpendicular magnetic anisotropy has a great potential for the next-generation non-volatile magnetoresistive random-access memory (MRAM). It requires a high-performance pure spin current source with a large spin Hall angle and high electrical conductivity, which can be fabricated by a mass production technique. In this work, we demonstrate ultrahigh efficient and robust SOT magnetization switching in all-sputtered BiSb topological insulator - perpendicularly magnetized Co/Pt multilayers. Despite fabricated by the industry-friendly magnetron sputtering instead of the laboratory molecular beam epitaxy, the topological insulator layer, BiSb, shows a large spin Hall angle of $θ$$_{SH}$ = 12.3 and high electrical conductivity of $σ$ = 1.5x$10^5$ $Ω^{-1}$m$^{-1}$. Our results demonstrate the mass production capability of BiSb topological insulator for implementation of ultralow power SOT-MRAM and other SOT-based spintronic devices.
Preliminary Clinical Activity in a Phase I Trial of the BCR-ABL/IGF- 1R/Aurora Kinase Inhibitor XL228 in Patients with Ph++ Leukemias with Either Failure to Multiple TKI Therapies or with T315I Mutation (2008)

Abstract XL228 is a protein kinase inhibitor with potent activity against wild-type and T315I isoforms of BCR-ABL (wild-type ABL kinase, IC50 = 5 nM; ABL T315I, 1.4 nM), Aurora A (3.1 nM), IGF-1R (1.6 nM), SRC (6.1 nM), and LYN (2 nM). A Phase 1 dose escalation clinical trial in patients (pts) with CML or Ph++-ALL who are resistant or intolerant to at least two prior standard therapies (including imatinib, dasatinib, and nilotinib) or have a known BCR-ABL T315I mutation is ongoing. XL228 is administered as a 1-hour IV infusion either once weekly or twice weekly. Twenty-seven pts have been enrolled into six cohorts with the once-weekly dosing schedule (dose range from 0.45 mg/kg to 10.8 mg/kg). All pts have failed prior imatinib therapy, and received nilotinib, dasatinib, and other therapies The majority of pts harbor mutations in BCR-ABL, with the most common mutations being T315I (n=10), F317L (n=7), and V299L (n=3). The maximum administered dose (MAD) of once-weekly IV dosing of XL228 is 10.8 mg/kg. Dose escalation of pts in the twice-weekly dosing schedule at an initial XL228 dose of 3.6 mg/kg on Days 1 and 4 of each week is ongoing. XL228 has been generally well-tolerated. Dose limiting toxicities observed with once-weekly dosing included Grade 3 syncope and hyperglycemia in two pts dosed at 10.8 mg/kg. Grade 2 adverse events reported to be possibly related to XL228 in the once-weekly dosing schedule were usually transient and manageable, and included hyperglycemia, fatigue, nausea, vomiting, and bradycardia. Pharmacokinetic analysis across five cohorts treated with once-weekly dosing of XL228 demonstrated an approximately dose-proportional exposure, with a mean terminal half life of 15 to 38 hours. In the 7.2 mg/kg cohort, the Cmax of approximately 13 μM exceeds the IC50 for modulation of phospho-CrkL levels determined in mouse K562 xenograft pharmacodynamic studies. Peak exposures of XL228 in the 7.2- and 10.8-mg/kg cohorts were associated with inhibition of peripheral blood leukocyte CrkL phosphorylation in several patients, including three harboring the T315I mutation. Transient increases in mean plasma glucose levels (up to three fold) and mean insulin levels (up to 40 fold) postinfusion are coupled, dose-related, and imply inhibition of the IGF1R and IR pathways by XL228. Preliminary evidence of clinical activity has been observed in pts treated at doses of 3.6 mg/kg and higher, including stable or decreasing white blood cell count and/or platelet count within 2 months (14 pts, 5 with T315I), and/or &amp;gt;1 log reduction in BCR-ABL levels by QPCR within 3 months (3 pts, 2 with T315I). Pts in the 7.2 mg/kg and higher cohorts have been followed a minimum of 1 month to a maximum of 4 months at the time of abstract submission. XL228 shows potential for treating drug-resistant CML and Ph+-ALL, including pts harboring the T315I gatekeeper mutation.
Isolation of differentially expressed sequence tags from human breast cancer. (1994)

Identification of quantitative changes in gene expression that occur in the malignant mammary gland, if sufficiently characterized, may yield novel molecular markers which may be useful in the diagnosis and treatment of human breast cancer. Using modifications of a previously documented technique, the differential display polymerase chain reaction, we describe the isolation of differentially expressed sequence tags, short complementary DNA fragments corresponding to mRNAs that are differentially expressed in breast cancer biopsies, as compared to normal breast tissue controls. Direct sequencing and expression analysis of two sequence tags demonstrate that they represent sequences which are overexpressed in a number of breast carcinoma cell lines. A paradigm for generating a catalogue of these sequence tags is discussed.
Rhodium-Catalyzed Regioselective Olefination Directed by a Carboxylic Group (2011)

The ortho-olefination of benzoic acids can be achieved effectively through rhodium-catalyzed oxidative coupling with alkenes. The carboxylic group is readily removable to allow ortho-olefination/decarboxylation in one pot. α,β-Unsaturated carboxylic acids such as methacrylic acid also undergo the olefination at the β-position. Under the rhodium catalysis, the cine-olefination of heteroarene carboxylic acids such as thiophene-2-carboxylic acid proceeds smoothly accompanied by decarboxylation to selectively produce the corresponding vinylheteroarene derivatives.
In vitro cytostatic activity of 8-substituted and tricyclic analogues of acyclovir. (2002)

Out of a series of twenty 8-substituted or/and 1,N-2-bridged (tricyclic) derivatives of acyclovir (a selective antiherpetic drug), known to be nontoxic to normal cells, seven compounds were found to exhibit moderate cytostatic activity in KB human tumor tissue culture system with ED50 activity values ranging from 0.052-0.094 x 10(-3) mole/l. The structure-activity relationship analysis indicated that the primary factors determining their cytotoxicity were: 1) bromine atom at the C-8 position of the bicyclic derivatives and 2) unsubstituted appended ring in the tricyclic derivatives. Combination of two structural elements carrying the cytotoxicity gave diverse effects, enhancement or decrease in activity depending on particular cases. Two compounds (of four selected), 8-bromoacyclovir and 1,N-2-etheno-acyclovir, having unsubstituted 9-[(2-hydroxyethoxy)methyl] chain, showed approximately 2-fold increase in their cytotoxicity against HeLa tumor cells in the presence of the induced microsomal generating system suggesting that their cytotoxicity depends on the drug metabolic transformation into their active metabolites (intermediates) via MFO-system, and that structural unit of this chain is essential for abovementioned activation. Presently found remarkable cytotoxic selectivity of acyclovir analogues against KB and HeLa tumor cells together with previously reported in the literature specific cytotoxic activity of acyclovir against murine leukemia L 1210 cells seem to be encouraging for further investigation of this class of compounds in other tumor systems.
Interferon-gamma improves splicing efficiency of CYBB gene transcripts in an interferon-responsive variant of chronic granulomatous disease due to a splice site consensus region mutation (2000)

X-linked chronic granulomatous disease (CGD) derives from defects in the CYBB gene, which encodes the gp91-phox component of NADPH oxidase. We studied the molecular basis of the disease in a kindred with variant CGD, due to a single base substitution at the sixth position of CYBB first intron. The patients' phagocytes have been shown previously to greatly increase superoxide release in response to interferon-gamma (IFN-gamma) in vitro and in vivo. We examined CYBB gene expression in an Epstein-Barr virus (EBV)-transformed B-cell line from 1 patient in this kindred. These cells showed markedly decreased levels of CYBB transcripts in total RNA (5% of normal) and nuclear RNA (1.4% of normal), despite equal CYBB transcription rates in the CGD and control cells. Incubation with IFN-gamma produced a 3-fold increase in CYBB total messenger RNA (mRNA) levels in the patient's cells, and decreased nuclear transcripts to undetectable levels. Reverse transcriptase-polymerase chain reaction analysis of RNA splicing revealed a preponderance of unspliced CYBB transcripts in the patient's nuclear RNA. In vitro incubation with IFN-gamma increased by 40% the ratio of spliced relative to unspliced CYBB mRNA in nuclei from the CGD B-cell line. Total RNA harvested from the same patient's monocytes, on and off therapy with IFN-gamma, showed a similar improvement in splicing. We conclude that IFN-gamma partially corrects a nuclear processing defect due to the intronic mutation in the CYBB gene in this kindred, most likely by augmentation of nuclear export of normal transcripts, and improvement in the fidelity of splicing at the first intron.
Helicobacter pylori moves through mucus by reducing mucin viscoelasticity (2009)

The ulcer-causing gastric pathogen Helicobacter pylori is the only bacterium known to colonize the harsh acidic environment of the human stomach. H. pylori survives in acidic conditions by producing urease, which catalyzes hydrolysis of urea to yield ammonia thus elevating the pH of its environment. However, the manner in which H. pylori is able to swim through the viscoelastic mucus gel that coats the stomach wall remains poorly understood. Previous rheology studies on gastric mucin, the key viscoelastic component of gastric mucus, indicate that the rheology of this material is pH dependent, transitioning from a viscous solution at neutral pH to a gel in acidic conditions. Bulk rheology measurements on porcine gastric mucin (PGM) show that pH elevation by H. pylori induces a dramatic decrease in viscoelastic moduli. Microscopy studies of the motility of H. pylori in gastric mucin at acidic and neutral pH in the absence of urea show that the bacteria swim freely at high pH, and are strongly constrained at low pH. By using two-photon fluorescence microscopy to image the bacterial motility in an initially low pH mucin gel with urea present we show that the gain of translational motility by bacteria is directly correlated with a rise in pH indicated by 2',7'-Bis-(2-Carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), a pH sensitive fluorescent dye. This study indicates that the helicoidal-shaped H. pylori does not bore its way through the mucus gel like a screw through a cork as has previously been suggested, but instead achieves motility by altering the rheological properties of its environment.
Cloning and characterization of the maize An1 gene. (1995)

The Anther ear1 (An1) gene product is involved in the synthesis of ent-kaurene, the first tetracyclic intermediate in the gibberellin (GA) biosynthetic pathway. Mutations causing the loss of An1 function result in a GA-responsive phenotype that includes reduced plant height, delayed maturity, and development of perfect flowers on normally pistillate ears. The an1::Mu2-891339 allele was recovered from a Mutator (Mu) F2 family. Using Mu elements as molecular probes, an An1-containing restriction fragment was identified and cloned. The identity of the cloned gene as An1 was confirmed by using a reverse genetics screen for maize families that contain a Mu element inserted into the cloned gene and then by demonstrating that the insertion causes an an1 phenotype. The predicted amino acid sequence of the An1 cDNA shares homology with plant cyclases and contains a basic N-terminal sequence that may target the An1 gene product to the chloroplast. The sequence is consistent with the predicted subcellular localization of AN1 in the chloroplast and with its biochemical role in the cyclization of geranylgeranyl pyrophosphate, a 20-carbon isoprenoid, to ent-kaurene. The semidwarfed stature of an1 mutants is in contrast with the more severely dwarfed stature of GA-responsive mutants at other loci in maize and may be caused by redundancy in this step of the GA biosynthetic pathway. DNA gel blot analysis indicated that An1 is a single-copy gene that lies entirely within the deletion of the an1-bz2-6923 mutant. However, homozygous deletion mutants accumulated ent-kaurene to 20% of the wild-type level, suggesting that the function of An1 is supplemented by an additional activity.
Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer. (1998)

Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.
Reduced Endoglin Activity Limits Cardiac Fibrosis and Improves Survival in Heart Failure (2012)

Our results identify endoglin as a critical component of TGFβ1 signaling in the cardiac fibroblast and show that targeting endoglin attenuates cardiac fibrosis, thereby providing a potentially novel therapeutic approach for individuals with heart failure.
MODULAR PEPTIDE RECOGNITION DOMAINS IN EUKARYOTIC SIGNALING (1997)

A characteristic feature of cellular signal transduction pathways in eukaryotes is the separation of catalysis from target recognition. Several modular domains that recognize short peptide sequences and target signaling proteins to these sequences have been identified. The structural bases of the specificities of recognition by SH2, SH3, and PTB domains have been elucidated by X-ray crystallography and NMR, and these results are reviewed here. In addition, the mechanism of cooperative interactions between these domains is discussed.
Multidimensional Scaling by Optimizing Goodness of Fit to a Nonmetric Hypothesis (1964)

Multidimensional scaling is the problem of representing n objects geometrically by n points, so that the interpoint distances correspond in some sense to experimental dissimilarities between objects. In just what sense distances and dissimilarities should correspond has been left rather vague in most approaches, thus leaving these approaches logically incomplete. Our fundamental hypothesis is that dissimilarities and distances are monotonically related. We define a quantitative, intuitively satisfying measure of goodness of fit to this hypothesis. Our technique of multidimensional scaling is to compute that configuration of points which optimizes the goodness of fit. A practical computer program for doing the calculations is described in a companion paper.
Emerging cell and molecular strategies for the study and treatment of painful peripheral neuropathies (2000)

Pharmacologic treatment for the symptoms of painful neuropathy has been problematic, because there has been limited understanding of the underlying etiologies and systemic levels that an effective dose can have on multiple side effects. The use of molecular methods, such as gene deletion from knockout mice and cellular minipumps for delivery of biologic antinociceptive molecules, has led to a better understanding of the underlying mechanisms of the induction of intractable neuropathic pain. The initiation of an excitatory cascade after injury or disease leads to the induction of various second messenger systems, loss or down-regulation of the endogenous inhibitory spinal GABA system and central sensitization, causing such pain. The development and use of cellular minipumps, immortalized cell lines bioengineered to secrete various antinociceptive molecules for the reversal of neuropathic pain, makes cellular therapy a strategy for clinical use in the next few years. The development of molecular "disimmortalization" technologies will make the use of such engineered cell lines safe for human use. Direct somatic gene transfer for neuropathic pain will eventually overcome the problems associated with transplantation of non-autologous and xenogenic cells. These virus-mediated methods, although at the early stages of evolution and use, offer large-scale production of biologic agents that can be conveniently and confidently used for the long-term relief of chronic neuropathic pain in a clinical setting, without systemic effects or surgical interventions.
Functional Characterization of a Methionine -Lyase in Arabidopsis and its Implication in an Alternative to the Reverse Trans-sulfuration Pathway (2006)

Methionine gamma-lyase (MGL) catalyzes the degradation of L-methionine to alpha-ketobutyrate, methanethiol and ammonia. The Arabidopsis (Arabidopsis thaliana) genome includes a single gene (At1g64660) encoding a protein (AtMGL) with approximately 35% identity to bacterial and protozoan MGLs. When overexpressed in Escherichia coli, AtMGL allowed growth on L-methionine as sole nitrogen source and conferred a high rate of methanethiol emission. The purified recombinant protein exhibited a spectrum typical of pyridoxal 5'-phosphate enzymes, and had high activity toward l-methionine, L-ethionine, L-homocysteine and seleno-L-methionine, but not L-cysteine. Quantitation of mRNA showed that the AtMGL gene is expressed in aerial organs and roots, and that its expression in leaves was increased 2.5-fold by growth on low sulfate medium. Emission of methanethiol from Arabidopsis plants supplied with 10 mM L-methionine was undetectable (<0.5 nmol min(-1) g(-1) FW), suggesting that AtMGL is not an important source of volatile methanethiol. Knocking out the AtMGL gene significantly increased leaf methionine content (9.2-fold) and leaf and root S-methylmethionine content (4.7- and 7-fold, respectively) under conditions of sulfate starvation, indicating that AtMGL carries a significant flux in vivo. In Arabidopsis plantlets fed L-[(35)S]methionine on a low sulfate medium, label was incorporated into protein-bound cysteine as well as methionine, but incorporation into cysteine was significantly (30%) less in the knockout mutant. These data indicate that plants possess an alternative to the reverse trans-sulfuration pathway (methionine-->homocysteine-->cystathionine-->cysteine) in which methanethiol is an intermediate.