gebhart/patrepeval huggingface dataset:
Ultradian Rhythm of Basal Corticosterone Release in the Female Rat: Dynamic Interaction with the Response to Acute Stress* (1998)

Abstract The present study investigated the dynamic regulation of the hypothalamo-pituitary-adrenal axis and its significance to acute stress responsiveness in the female rat. An automated, frequent blood-sampling technique allowed the circadian rhythm of corticosterone to be resolved into a series of pulses. These were equally distributed (mean interval, 50.9 ± 3.7 min) throughout the 24-h cycle, but their magnitude varied significantly, being higher between 1800–2200 h (137 ± 9 ng/ml) than between 0600–1000 h (75 ± 17 ng/ml). This pattern of release indicates continuous, but variable, activity of the axis throughout the day. The pulsatile ultradian rhythm suggested alternate periods of secretion and inhibition, which were found to have a profound effect on the corticosterone responses to acute stress. Noise stress (10 min, 114 decibels) evoked a transient increase in corticosterone, which reached a maximum (377 ± 87 ng/ml) 20 min after onset. However, within this group (n = 26) the response varied depending on the underlying basal activity. When stress coincided with a rising (secretory) phase of a pulse, corticosterone concentrations rose to 602 ± 150% of mean basal concentrations (P &amp;lt; 0.001). In contrast, when stress coincided with a falling (nonsecretory) phase of a pulse, a significantly smaller response, no greater than a basal pulse, was evoked. Thus, the alternate periods of secretion and inhibition generating basal hypothalamo-pituitary-adrenal activity are an important determinant of responses to acute stress.
Polymer Dispersed Palladium Catalysts for the Hydrogenation of p-Nitrophenol (1991)

Several commercial ion exchange resins dispersed palladium catalysts were prepared and used for the hydrogenation of p-nitrophenol.It has been found that the catalysts can all catalyze the hydrogenation of p-nitrophenol with relatively high activity.Among them, anion exchanger dispersed palladium catalysts possess higher activity.
4Pi confocal optical system with phase conjugation (1996)

We propose a 4Pi confocal system that incorporates a phase-conjugate mirror into the system to solve the alignment problem and automatically correct the spherical aberration associated with the conventional 4Pi confocal system when observing a thick sample. The proposed system is experimentally verified by use of cerium-doped barium titanate crystal as the phase-conjugate mirror. The full width of the central peak is ~0.15 microm. We also theoretically verify the advantage of automatic correction of the spherical aberration by calculating the intensity distribution at the focal spot.
The Structural Basis for the Specificity of Retinoid-X Receptor-selective Agonists: New Insights Into the Role of Helix H12 (2002)

Ligands that specifically target retinoid-X receptors (RXRs) are emerging as potentially powerful therapies for cancer, diabetes, and the lowering of circulatory cholesterol. To date, RXR has only been crystallized in the absence of ligand or with the promiscuous ligand 9-cis retinoic acid, which also activates retinoic acid receptors. Here we present the structure of hRXRbeta in complex with the RXR-specific agonist LG100268 (LG268). The structure clearly reveals why LG268 is specific for the RXR ligand binding pocket and will not activate retinoic acid receptors. Intriguingly, in the crystals, the C-terminal "activation" helix (AF-2/helix H12) is trapped in a novel position not seen in other nuclear receptor structures such that it does not cap the ligand binding cavity. Mammalian two-hybrid assays indicate that LG268 is unable to release co-repressors from RXR unless co-activators are also present. Together these findings suggest that RXR ligands may be inefficient at repositioning helix H12.
An immunochemical approach to the study of DNA damage and repair (1991)

The overall objective of this project is to produce antibodies to unique modified DNA bases and develop immunochemical assays to quantitate these lesions in damaged DNA. During this past year we have characterized antibodies to 8-oxopurines, produced novel antibodies to 5-hydroxyuracil and developed new methodologies to increase our level of sensitivity of detection. 7 refs., 5 figs.
Repetitive nanosecond all-solid-state pulsers based on SOS diodes (2002)

The paper describes design and technical specifications of nanosecond high-voltage pulsed generators that have an all-solid-state switching system. As a final power amplifier the semiconductor opening switch (SOS) and an inductive store are used. The devices present desktop hand-carried units that are capable of delivering to a load pulses with the following parameters: voltage 110 to 450 kV; current 0.4 to 1.5 kA; pulse width 20 to 40 ns; continuous pulse repetition rate 100 to 1000 pps; and burst mode up to 5000 pps.
The costs of asthma (1996)

At present, asthma represents a substantial burden on health care resources in all countries so far studied. The costs of asthma are largely due to uncontrolled disease, and are likely to rise as its prevalence and severity increase. Costs could be significantly reduced if disease control is improved. A large proportion of the total cost of illness is derived from treating the consequences of poor asthma control-direct costs, such as emergency room use and hospitalizations. Indirect costs, which include time off work or school and early retirement, are incurred when the disease is not fully controlled and becomes severe enough to have an effect on daily life. In addition, quality of life assessments show that asthma has a significant socioeconomic impact, not only on the patients themselves, but on the whole family. Underuse of prescribed therapy, which includes poor compliance, significantly contributes towards the poor control of asthma. The consequences of poor compliance in asthma include increased morbidity and sometimes mortality, and increased health care expenditure. To improve asthma management, international guidelines have been introduced which recommend an increase in the use of prophylactic therapy. The resulting improvements in the control of asthma will reduce the number of hospitalizations associated with asthma, and may ultimately produce a shift within direct costs, with subsequent reductions in indirect costs. In addition, costs may be reduced by improving therapeutic interventions and through effective patient education programmes. This paper reviews current literature on the costs of asthma to assess how effectively money is spent and, by estimating the proportion of the cost attributable to uncontrolled disease, will identify where financial savings might be made.
A Phase I/II Study of Herpes Simplex Virus Type 1 Thymidine Kinase “Suicide” Gene Therapy for Recurrent Glioblastoma (1998)

Despite extensive surgery for glioblastoma, residual tumor cells always lead to relapse. Gene therapy based on retrovirus-mediated gene transfer of herpes simplex virus type 1 thymidine kinase (HSV-1 TK), which specifically sensitizes dividing cells to ganciclovir (GCV) toxicity, may help eradicate such cells. During glioblastoma surgery, HSV-1 TK retroviral vector-producing cells (M11) were injected into the surgical cavity margins after tumor debulking. After a 7-day transduction period, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by MRI-based relapse-free survival at month 4 and by overall survival. Twelve patients with recurrent glioblastoma were treated without serious adverse events related to M11 cell administration or GCV. Quality of life was not negatively influenced by this treatment. Overall median survival was 206 days, with 25% of the patients surviving longer than 12 months. At 4 months after treatment, 4 of 12 patients had no recurrence; their median overall survival was 528 days, compared with 194 days for patients with recurrence (p=0.03 by the log rank test). One patient is still free of detectable recurrence, steroid free and independent, 2.8 years after treatment. Thus, brain injections of M11 retroviral vector-producing cells for glioblastoma HSV-1 TK gene therapy were well tolerated and associated with significant therapeutic responses. These results warrant further development of this therapeutic strategy in brain tumor, including recurrent glioblastoma.
Combined venetoclax and alvocidib in acute myeloid leukemia (2017)

More effective treatment options for elderly acute myeloid leukemia (AML) patients are needed as only 25-50% of patients respond to standard-of-care therapies, response duration is typically short, and disease progression is inevitable even with some novel therapies and ongoing clinical trials. Anti-apoptotic BCL-2 family inhibitors, such as venetoclax, are promising therapies for AML. Nonetheless, resistance is emerging. We demonstrate that venetoclax combined with cyclin-dependent kinase (CDK) inhibitor alvocidib is potently synergistic in venetoclax-sensitive and -resistant AML models <i>in vitro</i>, <i>ex vivo</i> and <i>in vivo</i>. Alvocidib decreased MCL-1, and/or increased pro-apoptotic proteins such as BIM or NOXA, often synergistically with venetoclax. Over-expression of BCL-XL diminished synergy, while knock-down of BIM almost entirely abrogated synergy, demonstrating that the synergistic interaction between alvocidib and venetoclax is primarily dependent on intrinsic apoptosis. CDK9 inhibition predominantly mediated venetoclax sensitization, while CDK4/6 inhibition with palbociclib did not potentiate venetoclax activity. Combined, venetoclax and alvocidib modulate the balance of BCL-2 family proteins through complementary, yet variable mechanisms favoring apoptosis, highlighting this combination as a promising therapy for AML or high-risk MDS with the capacity to overcome intrinsic apoptosis mechanisms of resistance. These results support clinical testing of combined venetoclax and alvocidib for the treatment of AML and advanced MDS.
In vitro phosphorylation of AlgR, a regulator of mucoidy in Pseudomonas aeruginosa, by a histidine protein kinase and effects of small phospho‐donor molecules (1992)

AlgR is a transcriptional regulator of mucoidy in Pseudomonas aeruginosa, a critical virulence factor expressed in cystic fibrosis. AlgR belongs to the superfamily of bacterial signal transduction systems, and has been shown to bind to the algD promoter, a critical point in the regulation of mucoidy. This protein, like other typical response regulators, contains highly conserved residues known to be critical for the phosphorylation and signal transduction processes. However, a typical second component interacting with AlgR has not been identified. Here we demonstrate that AlgR undergoes phosphorylation in vitro when interacting with the well-characterized histidine protein kinase CheA. These results indicate that AlgR is capable of undergoing phosphorylation typical of other two-component signal transduction systems. Moreover, the phosphotransfer reaction between CheA and AlgR was found to be affected by the presence of carbamoyl phosphate, acetyl phosphate, and salts of phosphoramidic acid, recently shown to act as small-molecular-weight phospho-donors in the process of phosphorylation of several response regulators. These findings suggest that AlgR may react with intermediary metabolites such as carbamoyl phosphate and acetyl phosphate, and that these processes may play a role in the control of mucoidy in P. aeruginosa.
The Briefing Associate: easing authors into the Semantic Web (2002)

The Semantic Web has clear benefits for information consumers, but for authors it typically means added work with no immediate payoff. This article describes Briefing Associate (BA), a tool that eases the effort by automating markup within a popular commercial off-the-shelf (COTS) application. The BA is a descendent of the Design Editor, an application for producing visual, domain-specific design environments. Both tools are implemented as extensions of Microsoft's PowerPoint, which, as this paper describes, is a key factor in our research.
Switching energy limits of waveguide-coupled graphene-on-graphene optical modulators (2012)

The fundamental switching energy limitations for waveguide coupled graphene-on-graphene optical modulators are described. The minimum energy is calculated under the constraints of fixed insertion loss and extinction ratio. Analytical relations for the switching energy both for realistic structures and in the quantum capacitance limit are derived and compared with numerical simulations. The results show that sub-femtojoule per bit switching energies and peak-to-peak voltages less than 0.1 V are achievable in graphene-on-graphene optical modulators using the constraint of 3 dB extinction ratio and 3 dB insertion loss. The quantum-capacitance limited switching energy for a single TE-mode modulator geometry is found to be < 0.5 fJ/bit at λ = 1.55 μm, and the dependences of the minimum energy on the waveguide geometry, wavelength, and graphene location are investigated. The low switching energy is a result of the very strong optical absorption in graphene, and the extremely-small operating voltages needed as the device approaches the quantum capacitance regime.
Solid Phase Microextraction (SPME) (1997)

Solid phase microextraction (SPME) was developed to address the need for a fast, solvent-free and field compatible sample preparation method. It has been applied to a range of applications including environmental, industrial hygiene, process monitoring, clinical, forensic, food and drug analysis. In SPME, coated fibers are used to isolate and concentrate analytes into a range of coating materials. After extraction, the fibers are transferred, with the help of the syringe-like handling device, to analytical instruments for separation and quantification of the target analytes.
Nanomolar Affinity Small Molecule Correctors of Defective ΔF508-CFTR Chloride Channel Gating (2003)

Deletion of Phe-508 (Delta F508) is the most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) causing cystic fibrosis. Delta F508-CFTR has defects in both channel gating and endoplasmic reticulum-to-plasma membrane processing. We identified six novel classes of high affinity potentiators of defective Delta F508-CFTR Cl- channel gating by screening 100,000 diverse small molecules. Compounds were added 15 min prior to assay of iodide uptake in epithelial cells co-expressing Delta F508-CFTR and a high sensitivity halide indicator (YFP-H148Q/I152L) in which Delta F508-CFTR was targeted to the plasma membrane by culture at 27 degrees C for 24 h. Thirty-two compounds with submicromolar activating potency were identified; most had tetrahydrobenzothiophene, benzofuran, pyramidinetrione, dihydropyridine, and anthraquinone core structures (360-480 daltons). Further screening of >1000 structural analogs revealed tetrahydrobenzothiophenes that activated DeltaF508-CFTR Cl- conductance reversibly with Kd < 100 nm. Single-cell voltage clamp analysis showed characteristic CFTR currents after Delta F508-CFTR activation. Activation required low concentrations of a cAMP agonist, thus mimicking the normal physiological response. A Bayesian computational model was developed using tetrahydrobenzothiophene structure-activity data, yielding insight into the physical character and structural features of active and inactive potentiators and successfully predicting the activity of structural analogs. Efficient potentiation of defective Delta F508-CFTR gating was also demonstrated in human bronchial epithelial cells from a Delta F508 cystic fibrosis subject after 27 degrees C temperature rescue. In conjunction with correctors of defective Delta F508-CFTR processing, small molecule potentiators of defective Delta F508-CFTR gating may be useful for therapy of cystic fibrosis caused by the Delta F508 mutation.
DOTA-Functionalized Polylysine: A High Number of DOTA Chelates Positively Influences the Biodistribution of Enzymatic Conjugated Anti-Tumor Antibody chCE7agl (2013)

Site-specific enzymatic reactions with microbial transglutaminase (mTGase) lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA) chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA)1-decalysine, (DOTA)3-decalysine or (DOTA)5-decalysine to the antibody heavy chain (via Gln295/297) gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with (177)Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA)-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA)3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA)5-decalysine)]2. The rapid elimination from the blood of chCE7agl-[(DOTA)-decalysine]2 (1.0±0.1% ID/g at 24 h) is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h). This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA)3 versus 11.7±1.4% ID/g (DOTA)5, p<0.005 at 24 h) and lower radioactivity levels in the liver (21.4±3.4 (DOTA)3 versus 5.8±0.7 (DOTA)5, p<0.005 at 24 h). We conclude that the site-specific and stoichiometric uniform conjugation of the highly DOTA-substituted decalysine ((DOTA)5-decalysine) to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for radioimmunotherapy and potentially antibody-drug conjugates (ADCs).
A Highly Active and Easily Accessible Cobalt Catalyst for Selective Hydrogenation of C═O Bonds (2015)

The substitution of high-price noble metals such as Ir, Ru, Rh, Pd, and Pt by earth-abundant, inexpensive metals like Co is an attractive goal in (homogeneous) catalysis. Only two examples of Co catalysts, showing efficient C═O bond hydrogenation rates, are described. Here, we report on a novel, easy-to-synthesize Co catalyst family. Catalyst activation takes place via addition of 2 equiv of a metal base to the cobalt dichlorido precatalysts. Aldehydes and ketones of different types (dialkyl, aryl-alkyl, diaryl) are hydrogenated quantitatively under mild conditions partially with catalyst loadings as low as 0.25 mol%. A comparison of the most active Co catalyst with an Ir catalyst stabilized by the same ligand indicates the superiority of Co. Unique selectivity toward C═O bonds in the presence of C═C bonds has been observed. This selectivity is opposite to that of existing Co catalysts and surprising because of the directing influence of a hydroxyl group in C═C bond hydrogenation.
[Application of monoclonal antibody for drug delivery system--missile therapy for cancer]. (1998)

Clinical applications of monoclonal antibody for selective delivery of anticancer drug, toxin and radioisotope were reviewed. The difficulties in preparation and clinical application of chemoimmunoconjugate were pointed out. Also the difficulties of immunotoxin in clinical trial due to its high toxicity had been discussed and it is assumed that development of blocked ricin may overcome many problems related to toxicities. Clinically most advanced immunoconjugate seems to be radioimmunoconjugate. Among three types of immunoconjugates preparation of radioimmunoconjugate is easiest and some promising clinical trials were introduced in this review.
Graphical display of tactile sensing data with application in minimally invasive surgery (2007)

In this paper, the design of a hardware and software system for graphical representation of tactile sensing data is described in detail. The signal processing is developed using LabView 7 software. The signals from the sensors are processed, and then various tactile properties of the grasped material are extracted. The tactile information includes softness, stress distribution, and lumps. This information is displayed by means of a colour coding method. The technical specifications of the hardware and data acquisition system are described in detail. The system receives signals from the sensors, transforms them into digital signals, and then transmits them to a personal computer. The developed software is also presented, and its capabilities are discussed. Using the designed system, it is possible to determine the softness of objects that come into contact with it. To serve as sensing elements, two piezoelectric films made of polyvinylidene difluoride are incorporated into the sensing assembly, and the combination of the resulting output voltages is related to the object softness. As a practical application, the sensor assembly is integrated with a commercially available endoscopic grasper which has been modified for the purpose of this research.
Risk for Ischemic Heart Disease and All-Cause Mortality in Subclinical Hypothyroidism (2004)

We investigated possible associations between subclinical hypothyroidism and atherosclerotic diseases (ischemic heart disease and cerebrovascular disease) and mortality. Of 2856 participants (mean age 58.5 yr) in a thyroid disease screening between 1984 and 1987, 257 subjects with subclinical hypothyroidism (TSH > 5.0 mU/liter) and 2293 control subjects (TSH range 0.6-5.0 mU/liter) were analyzed. In the baseline cross-sectional analysis, subclinical hypothyroidism was associated with ischemic heart disease independent of age, systolic blood pressure, body mass index, cholesterol, smoking, erythrocyte sedimentation rate, or presence of diabetes mellitus [odds ratio (OR), 2.5; 95% confidence interval (95% CI), 1.1-5.4 in total subjects and OR, 4.0; 95% CI, 1.4-11.5 in men] but not in women. However, there was no association with cerebrovascular disease (OR, 0.9; 95% CI, 0.4-2.4). We were unable to detect an influence of thyroid antibody presence on the association between subclinical hypothyroidism and ischemic heart disease. In a 10-yr follow-up study until 1998, increased mortalities from all causes in yr 3-6 after baseline measurement were apparent in men with subclinical hypothyroidism (hazard ratio, 1.9-2.1) but not in women, although specific causes of death were not determined. Our results indicate that subclinical hypothyroidism is associated with ischemic heart disease and might affect all-cause mortality in men.
Patient Stratification Using Electronic Health Records from a Chronic Disease Management Program (2016)

The study shows that predictive modeling and clustering using EHR data can be beneficial for providing a systematic, generalized approach for care providers to tailor their management approach based upon patient-level factors.