gebhart/patrepeval huggingface dataset:
Ketoconazole Binds to the Human Androgen Receptor (1992)

Ketoconazole, an imidazole anti-fungal agent, has often produced features of androgen deficiency including decreased libido, gynecomastia, impotence, oligospermia, and decreased testosterone levels, in men being treated for chronic mycotic infections. Based on these potent effects on gonadal function in vivo as well as previous work in vitro demonstrating affinity of ketoconazole for receptor proteins for glucocorticoids and 1,25(OH)2 vitamin D3 and for sex steroid binding globulin (SSBG), the binding of ketoconazole to human androgen receptors (AR) in vitro was also examined. Ketoconazole competition with [3H]methyltrienolone (R1881) for androgen binding sites in dispersed, intact cultured human skin fibroblasts was determined at 22 degrees C. Fifty percent displacement of [3H]R1881 binding to AR was achieved by 6.4 +/- 1.8 (SE) x 10(-5) M ketoconazole. Additional binding studies performed with ketoconazole in the presence of increasing amounts of [3H]R1881 showed that the interaction of ketoconazole with AR was competitive when the data were analyzed by the Scatchard method. It should be noted, however, that the dose of ketoconazole required for 50% occupancy of the androgen receptor is not likely to be achieved in vivo, at least in plasma. Finally, androgen binding studies performed with other imidazoles, such as clotrimazole, miconazole, and fluconozole, revealed that in this class of compounds only ketoconazole appears to interact with the androgen receptor. Ketoconazole appears to be the first example of a non-steroidal compound which binds competitively to both SSBG and multiple steroid hormone receptors, suggesting that the ligand binding sites of these proteins share some features in common.
Speech and gestures for graphic image manipulation (1989)

An experiment was conducted with people using gestures and speech to manipulate graphic images on a computer screen. A human was substituted for the recognition devices. The analysis showed that people strongly prefer to use both gestures and speech for the graphics manipulation and that they intuitively use multiple hands and multiple fingers in all three dimensions. There was surprising uniformity and simplicity in the gestures and speech. The analysis of these results provides strong encouragement for future development of integrated multi-modal interaction systems.
Vagal regulation of acid secretion and gastrin release. (1996)

The vagus nerve plays a central role in the regulation of gastric acid secretion and gastrin release. The current understanding of the mechanisms involved in vagal regulation of acid secretion and gastrin release is reviewed. Thyrotropin-releasing hormone from the medullary raphe nuclei appears to be the central excitatory mediator of vagal action in the dorsal motor nucleus. Vagal stimulation of the parietal cell occurs through M3 cholinergic receptors and via the release of histamine and gastrin from enterochromaffin-like cells and G-cells, respectively. Somatostatin exerts a tonic basal inhibition of both the parietal cell and the G-cell. Vagal stimulation suppresses somatostatin release from delta cells, thereby "disinhibiting" these cells.
B7-1 expression by a non-antigen presenting cell-derived tumor. (1995)

The existence of a naturally occurring immunosurveillance against neoplastic cells is controversial. A difficulty with this concept is that tumor-specific antigen-reactive T cells would not be expected to become activated after encountering tumor cells, since T cells that bind to antigen in the absence of the costimulation provided by antigen-presenting cells may be inactivated. We studied a transgenic model of tumorigenesis where T cells reactive to a particular tumor-specific antigen are lost prior to the development of non-antigen-presenting cell-derived tumors; therefore, the tumors that develop are not subjected to immunosurveillance. We found that a tumor cell line derived from one such tumor expresses the T-cell costimulatory molecule B7-1, the expression of which is normally restricted to antigen-presenting cells. In addition, we found that several immortalized cell lines, which are nontumorigenic and thus have suffered only early genetic events in the tumorigenesis process, express B7. This suggests that a host cell can be induced to express surface B7-1 molecules after suffering an oncogenic insult, which might possibly be a primary mechanism of immunosurveillance against tumors.
Fifteen-Electrode Time-MAultiplex EEG Telemetry from Ambulatory Patients (1979)

A 15-electrode time-multiplex EEG telemetry unit is described that fits on the patient's head. A continuous 24-hour transmission is possible. RF-to-AF feedback is prevented by mode switching at the basic cycle rate, 400 Hz, so that the RF transmission is cut off while the AF amplifiers are on, and vice versa. The channel rate is 12,800 Hz. The channel 16 input consists of a 200-Hz reference signal. The unit weighs 200 grams, and draws 10 mA at 5 V. Each channel bandwidth extends from 0.36 to 59 Hz. The output is FM with a peak deviation of 75 kHz of a 20 MHz carrier. The decoder locks on a 400 Hz AM sync signal. RF carrier shift due to motion artifact is fed back to the 15 data channels so as to cancel out their shift components.
Virtual colonoscopy for colorectal cancer screening: current status (2005)

Computed tomography colonography (CTC) (also known as 'virtual colonoscopy') is a noninvasive method of imaging the colon using helical CT. Although CTC has been shown to be useful for certain clinical indications, it has not yet been endorsed as a colorectal cancer screening test. The purpose of this article is to review the current status of CTC for colorectal cancer screening. CTC is an accurate method to detect colonic polyps and to select patients who would benefit from colonoscopy. The major advantages of CTC over conventional colonography include its relatively low risk and greater tolerance by patients. In this article, the CTC procedure and results of clinical trials are reviewed, as well as potential pitfalls related to CTC performance and interpretation. Finally, radiation dose, the discovery of incidental extracolonic findings with CTC, bowel preparation methods, and computer-aided diagnosis are addressed.
Amnesia in layered insulator FET memory devices (1973)

A retention time theory is developed for layered insulator FET (LIFET) memory devices in which the dominant cause of amnesia is attributed to tunnelling of charge back to the silicon. The theory incorporates the effect of surface states and the time dependence of the electric fields in the insulators. An equation for the threshold voltage correct to first order in the electric field is derived and solved exactly. To facilitate comparison with other theories, the solution is given in expressions valid over several decades of time. The solution predicts in agreement with experimental results that after a delay time which is exponentially dependent on the initial threshold voltage, the oxide thickness and the surface state density, the threshold voltage decays logarithmically eventually tailing off exponentially. In the logarithmic regime the decay rate varies as the inverse square of the oxide thickness, the square root of the trap depth and inversely as the rate at which the density of surface states increases. The calculated decay rate is found consistently to be lower for alumina devices than for nitride devices. The effect on the decay rate of trap depth, density of surface states, thickness of each of the two insulators, the dielectric constant of the thicker insulator and the initial threshold voltage are carefully examined and the results presented in the form of graphs and tables to provide guidance for memory product design.
Upregulation of Bcl-2 and Elevation of Ceramide in Batten Disease (1997)

The late infantile and juvenile variants of Batten disease are genetically distinct neurodegenerative disorders. Hallmarks of Batten disease include cognitive and motor decline, seizures and blindness due to retinitis pigmentosa. Recently, the CLN3 gene responsible for the juvenile variant has been cloned. Also, apoptosis was proven to be the mechanism by which neurons and photoreceptors die. This paper provides mechanistic support for the occurrence of apoptosis in this disease: There was marked upregulation of Bcl-2 in brain from the late infantile and juvenile types at the protein and RNA levels both by immunocytochemistry and by Northern blot analysis; there were also a 42% to 197% increase in brain ceramide determinations in brains from three patients with the juvenile type and three patients with the late infantile type. Double immunolabeling of brain sections for apoptosis and Bcl-2 supported a protective role for Bcl-2 in the juvenile form of Batten disease. These results raise the possibility that the intact CLN3 gene is normally antiapoptotic, and that it could be an upstream regulator of ceramide.
Conjugation reactions in drug metabolism : an integrated approach : substrates, co-substrates, enzymes and their interactions in vivo and in vitro (1990)

Introduction, G.J.Mulder kinetics of conjugation reactions in eliminating organs, K.S.Pang competition between conjugations for the same substate, G.J.Mulder glucuronidation, G.J.Mulder et al sulfation, G.J.Mulder and W.B.Jakoby acetylation, W.W.Weber et al O-methylation, D.R.Thakker and C.R.Greveling N-methylation, S.S.Ansher and W.B.Jakoby S-methylation, J.L.Stevens and J.E.Bakke amino acid conjugation, A.J.Hutt and J.Caldwell glutathione conjugation, B.Ketterer and G.J.Mulder epoxide hydrolase, T.M.Guenthner.
A New Two-Phase Flow Map and Transition Boundary Accounting for Surface Tension Effects in Horizontal Miniature and Micro Tubes (2001)

A new flow map is proposed to emphasize the importance of surface tension in two-phase flow in horizontal miniature and micro tubes. A transition boundary based on a force balance including shear, buoyancy and surface tension forces is also proposed. The flow map is compared against a number of existing experimental data sets totaling 1589 data points. Comparison of the proposed map and model with previous models shows substantial improvement and accuracy in determining surface tension dominated regimes. Furthermore, the proposed flow map shows how each regime transition boundary is affected by surface tension.
Changes to AIDS dementia complex in the era of highly active antiretroviral therapy (1999)

Objectives: To determine the protective efficacy of highly active antiretroviral therapy (HAART) against AIDS dementia complex (ADC) relative to other initial AIDS-defining illnesses (ADIs), Australian AIDS notification data over recent years were examined. Methods: All initial ADIs in Australia over the period 1992-1997 were included. Three initial ADI groups were established: ADC; other predominantly central nervous system (CNS) ADIs (toxoplasmosis and cryptococcosis); and non-CNS ADIs. For each ADI grouping, the proportion of total ADIs, and median CD4 cell count in the pre-HAART era (1992-1995) were compared with the HAART era (1996 and 1997). Results: Initial ADIs peaked in Australia in 1994 (n=1049), with a gradual decline to 1996 (n=722), and a marked decline in 1997 (n=367). ADC constituted 4.4% of initial ADIs over the period 1992-1995, but increased after the introduction of HAART to 6.0% in 1996 and 6.5% in 1997 (P=0.02). In contrast, the proportion of other CNS ADIs (1992-1995, 8.1%; 1996, 6.0%; 1997, 8.2%; P=0.41) was stable over the period 1992-1997. The median CD4 cell count at ADC diagnosis increased from 70/mm3 in 1992-1995 to 120/mm3 in 1996 and 170/mm3 in 1997 (P=0.04). Although the median CD4 cell count also increased significantly over this period for both other CNS ADIs (40-60/mm3; P=0.02), and non-CNS ADIs (60-70/mm3; P=0.02), the increase was small. Conclusion: A proportional increase in ADC compared with other ADIs and a marked increase in the median CD4 cell count at ADC diagnosis have occurred since the introduction of HAART in Australia. These changes suggest that HAART has a lesser impact on ADC than on other ADIs, with the poor CNS penetration of many antiretroviral agents a possible explanation.
Cellular Targets of Gefitinib (2005)

Targeted inhibition of protein kinases with small molecule drugs has evolved into a viable approach for anticancer therapy. However, the true selectivity of these therapeutic agents has remained unclear. Here, we used a proteomic method to profile the cellular targets of the clinical epidermal growth factor receptor kinase inhibitor gefitinib. Our data suggest alternative cellular modes of action for gefitinib and provide rationales for the development of related drugs.
Gene Therapy — A Novel Form of Drug Delivery (1995)

Gene therapy is a novel form of drug delivery that enlists the synthetic machinery of the patient's cells to produce a therapeutic agent. Using the body to treat its own disease overcomes the need to manufacture highly purified proteins. It also eliminates the need for repeated parenteral administration of proteins (as in hemophilia) or drugs (as in hereditary hypercholesterolemia) and reduces the difficulties of complying with exogenous-drug regimens. Applications of gene therapy are not limited to rare inherited diseases but extend potentially to common acquired disorders, including cancer, heart disease, and the acquired immunodeficiency syndrome. Gene therapy is thus likely . . .
Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes (1992)

Expression of vascular cell adhesion molecule-1 (VCAM-1) in synovial tissue was determined using the immunoperoxidase technique. Normal, rheumatoid arthritis (RA), and osteoarthritis (OA) synovia bound VCAM-1 antibodies in the intimal lining as well as blood vessels. The amount of VCAM-1 was significantly greater in the synovial lining of RA and OA tissues compared with normal synovium (p less than 0.002). There was also a trend toward greater levels of VCAM-1 staining in blood vessels of arthritic tissue (RA greater than OA greater than normal). Because VCAM-1 staining was especially intense in the synovial lining, VCAM-1 expression and regulation was studied on cultured fibroblast-like synoviocytes (FLS) derived from this region. Both VCAM-1 and intercellular adhesion molecule 1 were constitutively expressed on FLS. VCAM-1 expression was further increased by exposure to IL-1 beta, TNF-alpha, IL-4, and IFN-gamma. These cytokines (except for IL-4) also induced intercellular adhesion molecule 1 expression on FLS. ELAM was not detected on resting or cytokine-stimulated FLS. The specificity of VCAM-1 for FLS was demonstrated by the fact that only trace amounts were detected on normal and RA dermal fibroblasts. Cytokines induced intercellular adhesion molecule 1 display on dermal fibroblasts but had minimal effect on VCAM-1 expression. Finally, in adherence assays, Jurkat cell binding to resting FLS monolayers was inhibited by antibody to alpha 4/beta 1 integrin (VLA-4), CS-1 peptide from alternatively spliced fibronectin (which is another VLA-4 ligand), and, to a lesser extent, anti-VCAM-1 antibody. After cytokine stimulation of FLS, Jurkat-binding significantly increased, and this increase was blocked by anti-VCAM-1 antibody. Therefore, both CS-1 and VCAM-1 participate in VLA-4-mediated adherence to resting FLS in vitro, and VCAM-1 is responsible for the increase in Jurkat binding mediated by cytokines.
Beyond lysis: how complement influences cell fate (2003)

Complement is a central component of the innate immune system involved in protection against pathogens. For many years, complement has been known to cause death of targets, either indirectly by attracting and activating phagocytes or directly by formation of a membrane pore, the membrane attack complex. More recently, it has been recognized that complement may cause other 'non-classical' effects that may not directly be aimed at killing of pathogens. Products of complement activation collaborate with the adaptive immune system to enhance responses to antigens. The membrane attack complex of complement, apart from lysing cells, can also trigger diverse events in target cells that include cell activation, proliferation, resistance to subsequent complement attack and either resistance to, or induction of, apoptosis. Various complement products play important roles in signalling for clearance by phagocytes of apoptotic self cells. Here we review some of these non-classical activities of complement and stress the roles that they may play in maintaining the integrity of the organism.
Expression of a cellular gene cloned in herpes simplex virus: rabbit beta-globin is regulated as an early viral gene in infected fibroblasts (1987)

We constructed nondefective herpes simplex virus type 1 recombinants bearing the intact rabbit beta-globin gene inserted into the viral gene for thymidine kinase to study the expression of a cellular gene when it is present in the viral genome during lytic viral infections. The globin promoter was activated to high levels during productive infection of Vero cells, giving rise to properly spliced and processed cytoplasmic globin transcripts. Expression of globin RNA occurred with early kinetics, was not affected by blocking viral DNA replication, and was strongly inhibited by preventing viral immediate-early protein synthesis with cycloheximide. These results support the hypothesis that temporal control of herpes simplex virus early gene expression is accomplished by mechanisms that are not restricted to viral promoters. In addition, these data show that a cellular transcript can be correctly processed and can accumulate to high levels during viral infection; this indicates that the mechanisms of virally induced shutoff of host RNA accumulation and degradation of host mRNAs do not depend on sequence-specific differentiation between host and viral RNAs. These findings also suggest that herpesviruses have considerable potential as high-capacity gene transfer vectors for a variety of applications.
Transdermal Measurement of Glomerular Filtration Rate in Mice (2018)

Transdermal analysis of glomerular filtration rate (GFR) is an established technique that is used to assess renal function in mouse and rat models of acute kidney injury and chronic kidney disease. The measurement system consists of a miniaturized fluorescence detector that is directly attached to the skin on the back of conscious, freely moving animals, and measures the excretion kinetics of the exogenous GFR tracer, fluorescein-isothiocyanate (FITC) conjugated sinistrin (an inulin analog). This system has been described in detail in rats. However, because of their smaller size, measurement of transcutaneous GFR in mice presents additional technical challenges. In this paper we therefore provide the first detailed practical guide to the use of transdermal GFR monitors in mice based on the combined experience of three different investigators who have been performing this assay in mice over a number of years.
PCR Detection of Bacteria in Seven Minutes (1999)

A portable, real-time polymerase chain reaction (PCR) instrument, consisting of an array of microfabricated silicon reaction chambers with integrated optical detectors, analyzed samples of 5 to 500 bacteria cells in as little as 7 minutes. The analysis included cell lysis, PCR, detection of the PCR product with a target-specific fluorescence energy transfer probe, and automated alerting of positive signals by the software. Thermal cycle times of only 17 seconds, the fastest that could be achieved on the instrument, yielded good productivity at each cycle and indicated that still faster analysis could potentially be performed. The short run times were achieved because of efficient heating and cooling of the reactions, precision in which the target temperatures were reached, and the sensitive, dedicated mini-optical detection systems.
Data replication in Mariposa (2002)

The Mariposa distributed data manager uses an economic model for managing the allocation of both storage objects and queries to servers. We present extensions to the economic model which support replica management, as well as our mechanisms for propagating updates among replicas. We show how our replica control mechanism can be used to provide consistent, although potentially stale, views of data across many machines without expensive per-transaction synchronization. We present a rule-based conflict resolution mechanism, which can be used to enhance traditional time-stamp serialization. We discuss the effects of our replica system on query processing for both read-only and read-write queries. We further demonstrate how the replication model and mechanisms naturally support name service in Mariposa.
A ‘mini‐microtome’ for preparing serial sections directly on a light microscope stage (1995)

SUMMARY A simple ‘mini‐microtome’ is described which can be attached to a standard compound microscope. The device enables small biological specimens, such as parasitic helminths, to be sectioned with precise orientation.
Differential Display Protocol With Selected Primers That Preferentially Isolates mRNAs of Moderate- to Low-Abundance in a Microscopic System (1996)

A modified reverse transcription polymerase chain reaction (RT-PCR)-based differential display procedure with selected primers (SPR) was developed to increase the bias toward isolating moderate- to low-abundance transcripts that are differentially expressed during synapse formation in a microscopic neuronal system, the embryonic chicken ciliary ganglion. Major modifications, in comparison with available arbitrarily primed RT-PCR protocols, include the use of (i) experimentally selected primer pairs (50% GC-rich 15-21-mers) that avoid the amplification of highly abundant ribosomal and mitochondrial transcripts; (ii) a higher PCR annealing temperature (50 degrees C instead of 40 degrees C); (iii) selection of sequencing gel bands that are dependent on the two primers for amplification; (iv) tests for reproducibility by SPR amplification of independent sets of RNA extractions and Southern blot analysis of the products with an isolated radiolabeled clone; and (v) quantitative RT-PCR, instead of Northern blot analysis, to confirm the differential expression of individual cDNAs. Thirty-six cDNAs were isolated and sequenced using SPR. None showed significant homology to highly abundant transcripts. In contrast, when no criterion for primer or band selection was applied, 22% of 55 cDNAs were identical to ribosomal and mitochondrial transcripts. Reproducible amplification of 9 out of 10 SPR-isolated cDNAs was established by Southern blot analysis. Differential expression was then confirmed for 4 selected sequences by quantitative RT-PCR. Thus, SPR is a reproducible and efficient procedure for identifying differentially regulated transcripts of moderate- to low-abundance in microscopic biological systems.
Fluid inking: augmenting the medium of free-form inking with gestures (2006)

We present Fluid Inking, a generally applicable approach to augmenting the fluid medium of free-form inking with gestural commands. Our approach is characterized by four design criteria, including: 1) pen-based hardware impartiality: all interactions can be performed with a button-free stylus, the minimal input hardware requirement for inking, and the least common denominator device for pen-based systems ranging from PDAs to whiteboards; 2) performability: gestures use short sequences of simple and familiar inking interactions that require minimal targeting; 3) extensibility: gestures are a regular pattern of optional shortcuts for commands in an arbitrarily scalable menu system; and 4) discoverability: gesture shortcuts (analogous to modifier keys) are displayed in the interactive menu and are suggested with dynamic feedback during inking. This paper presents the Fluid Inking techniques in the unified context of a prototype notetaking application and emphasizes how post-fix terminal punctuation and prefix flicks can disambiguate gestures from regular inking. We also discuss how user feedback influenced the Fluid Inking design.