gebhart/patrepeval huggingface dataset:
Pharmacokinetics of the Novel Echinocandin CD101 in Multiple Animal Species (2017)

CD101 is a novel semisynthetic echinocandin with antifungal activity against <i>Candida</i> and <i>Aspergillus</i> spp. The pharmacokinetics (PK) of CD101 administered intravenously to mice, rats, dogs, cynomolgus monkeys, and chimpanzees are presented. CD101 consistently exhibited very low clearance, a modest volume of distribution at steady state (<i>V</i><sub>ss</sub>), and a long half-life (<i>t</i><sub>1/2</sub>) across all species tested. In mouse, rat, dog, cynomolgus monkey, and chimpanzee, CD101 clearance was 0.10, 0.47, 0.30, 0.41, and 0.06 ml/min/kg, respectively; <i>V</i><sub>ss</sub> was 206, 1,390, not determined, 597, and 400 ml/kg, respectively; and <i>t</i><sub>1/2</sub> was 25, 39, 53, 40, and 81 h, respectively. CD101 demonstrated a lower clearance and correspondingly longer half-life than those of anidulafungin, with more pronounced differences in higher species (anidulafungin <i>t</i><sub>1/2</sub>, 8 h in cynomolgus monkey and 30 h in chimpanzee). In the rat, tissue/plasma area under the concentration-time curve (AUC) ratios, in descending order, were 4.62 (kidney), 4.33 (lung), 4.14 (liver), 3.87 (spleen), 1.09 (heart), and 0.609 (brain), indicating that CD101 exposure relative to plasma levels was comparable for major organs (approximately 4-fold higher in tissue than in plasma), with the exception of the heart and brain. Biliary elimination of intact CD101 was the predominant route of excretion; the mean cumulative amount of CD101 excreted into the bile and feces over the course of 5 days accounted for 22.6% and 27.7% of the total dose administered, respectively. There were no sex differences in the pharmacokinetics of CD101. Given its low clearance, long half-life, and wide tissue distribution, CD101 once weekly is expected to provide appropriate systemic levels for treatment and prevention of invasive fungal infections.
Differential Emotional Responses of Varsity Athletes to Concussion and Musculoskeletal Injuries (2009)

The results revealed that both injured groups experienced emotional disturbance after injury. More importantly, the findings strongly suggest that the emotional reaction after concussion is different from that of musculoskeletal injury. Therefore, we concluded that assessing emotional reactions to concussion is particularly important and recommend that sports medicine professionals assess and monitor emotional functioning as well as somatic complaints and neurocognitive changes during recovery.
A content-based image authentication system with lossless data hiding (2003)

In this paper, we present a novel content-based image authentication framework which embeds the authentication information into the host image using a lossless data hiding approach. In this framework the features of a target image are first extracted and signed using the digital signature algorithm (DSA). The authentication information is generated from the signature and the features are then inserted into the target image using a lossless data hiding algorithm. In this way, the unperturbed version of the original image can be obtained after the embedded data are extracted. An important advantage of our approach is that it can tolerate JPEG compression to a certain extent while rejecting common tampering to the image. The experimental results show that our framework works well with JPEG quality factors greater than or equal to 80 which are acceptable for most authentication applications.
Women's attitudes to withdrawal bleeding and their knowledge and beliefs about the oral contraceptive pill (1988)

One hundred and fifty-eight attenders at general practices and family-planning clinics, and 20 young female doctors volunteered to complete a questionnaire about how women take the oral contraceptive pill, their knowledge of the Pill and their attitudes to withdrawal bleeding. Forty-three per cent of female patients has used the Pill to alter the time of withdrawal bleeding. Twenty-two per cent of female patients had taken the Pill daily for more than six weeks on at least one occasion and all reported positive experiences. However, 83% of female patients believed that it was necessary to bleed monthly when taking the Pill and 69% of the female patients believed that continuous use of active medication is undesirable. The over-all knowledge of the Pill was poor and 43% of female patients did not know what to do if they missed two consecutive Pills. Female doctors were better informed but had similar attitudes about the Pill to those of other women. Forty-six per cent of the female patients and 55% of young female doctors would chose to bleed at intervals of three months or greater if they could determine their own Pill regimen.
Rapid Evolution of RNA Genomes (1982)

RNA viruses show high mutation frequencies partly because of a lack of the proofreading enzymes that assure fidelity of DNA replication. This high mutation frequency is coupled with high rates of replication reflected in rates of RNA genome evolution which can be more than a millionfold greater than the rates of the DNA chromosome evolution of their hosts. There are some disease implications for the DNA-based biosphere of this rapidly evolving RNA biosphere.
Adeno-associated virus 2-mediated gene transfer in murine hematopoietic progenitor cells. (1993)

Recombinant human adeno-associated virus 2 (AAV) virions were constructed containing a gene for resistance to neomycin (neoR), under the control of either the herpesvirus thymidine kinase (TK) promoter (vTK-Neo), the murine colony-stimulating factor-1 (CSF-1) promoter (vCSF1-Neo) or the CSF-1 promoter plus an upstream human erythroid cell-specific enhancer, HS-2 (vHS2-CSF1-Neo). Recombinant virions were used to infect low-density murine primary bone marrow cells. In hematopoietic progenitor cell assays initiated with cells infected with these recombinant virions, myeloid as well as erythroid cell colonies resistant to the drug G418, a neomycin analogue, were readily obtained, indicating that the murine hematopoietic progenitor cells were susceptible to infection by the recombinant AAV virions and that the transduced neo gene was functionally active in these cells. Whereas only approximately 10% of the colony-forming unit-granulocyte/macrophage (CFU-GM) colonies cloned from mock-infected cells survived the G418-selection at a final active concentration of 250 micrograms/mL of the drug, the extent of the CFU-GM colony formation initiated with the recombinant AAV-Neo virions was as follows: 15% with vTK-Neo, 22% with vCSF1-Neo and 49% with vHS2-CSF1-Neo. In addition, only 14% of the burst-forming unit-erythroid (BFU-E) colonies from mock-infected cells were resistant to G418, whereas 82% of the BFU-E colonies initiated with cells infected with vHS2-CSF1-Neo virions survived the drug selection, suggesting that a human erythroid cell-specific enhancer was able to potentiate expression of the transduced neoR gene from a murine promoter. Individual CFU-GM and BFU-E colonies from mock-infected or recombinant AAV-Neo virus-infected cultures were subjected to polymerase chain reaction (PCR) analysis using a neo-specific synthetic oligonucleotide primer-pair. A 276 bp DNA fragment that hybridized with a neo-specific DNA probe on Southern blots was detected only in colonies cloned from the recombinant virus-infected cells, indicating stable integration of the transduced neo gene. These studies suggest the feasibility of using the AAV-based vector system in an animal model as a prelude to evaluating its safety and efficacy in human gene therapy.
A Rapid Modified Method for Compositional Carbohydrate Analysis of Lignocellulosics by High pH Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC/PAD) (1998)

Abstract During the last decade, high pH anion exchange chromatography with pulsed amperometric detection (HPAEC/PAC) has gained increasing acceptance as the method of choice for analysis of neutral sugars commonly occurring in woods, pulps, and other lignocellulosics. This paper describes modified chromatographic conditions and discusses other critical factors that improve the precision and efficiency of this application. The method involves a controlled loading of acetate onto the column prior to equilibration with water and injection of sample. In-line solid-phase extraction is used to remove hydrophobic substances that have the potential to foul the analytical column. Critical operational parameters for the successful application of the method include a metal-free flowpath and a consistent application of anions with sample. Resolution of rhamnose is achieved while maintaining the resolution of xylose and mannose. Simplified sample pretreatment allows a ca. five-fold increase in sample through-put compared with gas chromatography of derivatized sugars or to partition chromatography. Run times are less than half those of the widely used hydroxide reverse gradient method for HPAEC/PAD analysis of wood sugars. Long-term system performance data indicate that the method is highly precise and robust. The acetate loading method affords better precision than those of other HPAEC/PAD methods and of gas chromatographic analysis of alditol acetate derivatives by Tappi Method T249 cm−85.
Signal transducer and activator of transcription proteins in leukemias (2003)

Signal transducer and activator of transcription (STAT) proteins are a 7-member family of cytoplasmic transcription factors that contribute to signal transduction by cytokines, hormones, and growth factors. STAT proteins control fundamental cellular processes, including survival, proliferation, and differentiation. Given the critical roles of STAT proteins, it was hypothesized that inappropriate or aberrant activation of STATs might contribute to cellular transformation and, in particular, leukemogenesis. Constitutive activation of mutated STAT3 has in fact been demonstrated to result in transformation. STAT activation has been extensively studied in leukemias, and mechanisms of STAT activation and the potential role of STAT signaling in leukemogenesis are the focus of this review. A better understanding of mechanisms of dysregulation of STAT signaling pathways may serve as a basis for designing novel therapeutic strategies that target these pathways in leukemia cells.
Screening for Sources of Interindividual Pharmacokinetic Variability in Anticancer Drug Therapy: Utility of Population Analysis (2001)

Most cytotoxic drugs are characterized by a narrow therapeutic index, such that clinically effective doses are associated with some degree of acute or delayed toxicity. In cancer chemotherapy, the ...
Broad-band guided-wave electrooptic modulators (1984)

Lumped-element Mach-Zehnder interferometric modulators have been designed, fabricated in LiNbO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> , tested and analyzed. These modulators had 3 dB bandwidths from 280 MHz to 2.75 GHz and V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">π</inf> 's from 1 V to 4 V, respectively. A simple <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RLC</tex> equivalent circuit is utilized to model the packaged modulator performance and results are compared with those measured using a swept-frequency technique. The model is seen to break down at the higher frequencies due to a frequency-dependent resistance and the electrode and parasitic inductances are seen to limit the overall modulator performance. The effects of varying the electrode capacitance, resistance, or inductance on modulator performance are demonstrated.
AP-1 (Fos/Jun) transcription factors in hematopoietic differentiation and apoptosis. (1998)

A combination of in vitro and in vivo molecular genetic approaches have provided evidence to suggest that AP-1 (Fos/Jun) transcription factors play multiple roles in functional development of hematopoietic precursor cells into mature blood cells along most, if not all, of the hematopoietic cell lineages. This includes the monocyte/macrophage, granulocyte, megakaryocyte, mastocyte and erythroid lineages. In addition, studies using c-fos knockout mice have established a unique role for Fos, as a member of the AP-1 transcription factor complex, in determining the differentiation and activity of progenitors of the osteoclast lineage, a population of bone-forming cells which are of hematopoietic origin as well. Evidence has also accumulated to implicate AP-1 (Fos/Jun) transcription factor complexes as both positive and negative modulators of distinct apoptotic pathways in many cell types, including cells of hematopoietic origin. Fos/Jun have been implicated as positive modulators of apoptosis induced in hematopoietic progenitor cells of the myeloid lineage, a function that may relate to the control of blood cell homeostasis, as well as in programmed cell death associated with terminal differentiation of many other cell types, and apoptosis associated with withdrawal of growth/survival factors. On the other hand, the study of apoptosis induced in mammalian cells has implicated AP-1 in the protection against apoptosis induced by DNA-damaging agents. However, evidence to the contrary has been obtained as well, suggesting that AP-1 may function to modulate stress-induced apoptosis either positively or negatively, depending on the microenvironment and the cell type in which the stress stimulus is induced.
Theoretical Elucidation of the Origins of Substituent and Strain Effects on the Rates of Diels–Alder Reactions of 1,2,4,5-Tetrazines (2014)

The Diels-Alder reactions of seven 1,2,4,5-tetrazines with unstrained and strained alkenes and alkynes were studied with quantum mechanical calculations (M06-2X density functional theory) and analyzed with the distortion/interaction model. The higher reactivities of alkenes compared to alkynes in the Diels-Alder reactions with tetrazines arise from the differences in both interaction and distortion energies. Alkenes have HOMO energies higher than those of alkynes and therefore stronger interaction energies in inverse-electron-demand Diels-Alder reactions with tetrazines. We have also found that the energies to distort alkenes into the Diels-Alder transition-state geometries are smaller than for alkynes in these reactions. The strained dienophiles, trans-cyclooctene and cyclooctyne, are much more reactive than unstrained trans-2-butene and 2-butyne, because they are predistorted toward the Diels-Alder transition structures. The reactivities of substituted tetrazines correlate with the electron-withdrawing abilities of the substituents. Electron-withdrawing groups lower the LUMO+1 of tetrazines, resulting in stronger interactions with the HOMO of dienophiles. Moreover, electron-withdrawing substituents destabilize the tetrazines, and this leads to smaller distortion energies in the Diels-Alder transition states.
A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein‐2: A potential treatment for infected bone defects (2006)

To produce an osteogenic and bacteriocidal biomaterial for the treatment of infected nonunions or bone defects, a synthetic degradable block copolymer of poly-D,L-lactic acid segments with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) segments was mixed with recombinant human BMP-2 (rhBMP-2) and antibiotics at high concentration. We then examined the in vitro elution profile of an antibiotic (teicoplanin) from the polymer, the effects of antibiotics on the bone-inducing capacity of rhBMP-2 or on ectopic new bone formation induced by the rhBMP, and the ability of the polymer to repair bone in a rat cranial defect model. Approximately 40% of teicoplanin was released within the first 24 h, with the remaining amount released steadily over 21 days with no loss of antibacterial activity. The polymer had disappeared by degradation in the phosphate buffered saline (pH 7.4) at the end of the incubation period. The in vivo performance of pellets with antibiotics and rhBMP-2 revealed no significant change in bone yield within the ossicles after 3 weeks. Also, antibiotics had no inhibitory effect on the ability of rhBMP2 to repair cranial defects. Indeed, when the defect was filled by a polymer disc loaded with rhBMP-2 with or without teicoplanin, the defect was repaired by new bone, and normal anatomy was restored within 6 weeks. In conclusion, the PLA/DX/PEG polymer appears to work as effectively for antibiotics as it does for rhBMP-2. Additionally, the biological activity of rhBMP-2 was retained irrespective of the presence of antibiotics.
Mycoflora and fungal vector capacity of the parasitic miteVarroa destructor(Mesostigmata: Varroidae) in honey bee (Hymenoptera: Apidae) colonies (2004)

Abstract Female adults of the honey bee mite, Varroa destructor, have fungi on their surfaces, and have the potential to disperse fungal spores (conidia) throughout the bee colony. Fungi present are typical of those associated with bees, their combs and provisions, and are common filamentous, soil saprophytes (listed in order of relative abundance): Aspergillus, Penicillium, Fusarium, Trichoderma, Alternaria, Rhizopus and Mucor. These fungi have no biological control implications (i.e., entomopathogenic) because none were recovered internally within the mites; absence of fungi internally also implies that this mite is not a fungivore. Our isolation of Aspergillus flavus, agent of stonebrood disease in honey bees, implicates Varroa as a potential fungal vector of stonebrood disease.
Erythropoiesis in murine long-term marrow cultures following transfer of the erythropoietin cDNA into marrow stromal cells. (1990)

Long-term bone marrow cultures (LTMC) have provided a useful in vitro system to study stem cell self-renewal and myeloid differentiation. However, standard murine LTMC are devoid of erythroid differentiation within 2 weeks of establishment. In an attempt to develop a model system to study erythropoiesis in vitro, we have used a recombinant retrovirus vector to transfer the erythropoietin cDNA into stromal cells making up the hematopoietic microenvironment of murine LTMC. Three weeks after infection, erythroid differentiation was evident macroscopically, with clumps of hemoglobinized red blood cells present in the infected cultures. Hemoglobinization was confirmed by benzidine staining of nonadherent cells, which showed that up to 70% of nucleated cells were benzidine positive. In combination with LTMC, the use of recombinant retrovirus vectors to transfer growth factor genes may provide useful models to study the interactions of hematopoietic stem cells, hematopoietic microenvironment, and growth factors in vitro.
Improving direct-mapped cache performance by the addition of a small fully-associative cache prefetch buffers (1998)

Article Free Access Share on Improving direct-mapped cache performance by the addition of a small fully-associative cache prefetch buffers Author: Norman P. Jouppi Digital Equipment Corporation Western Research Lab, 100 Hamilton Ave., Palo Alto, CA Digital Equipment Corporation Western Research Lab, 100 Hamilton Ave., Palo Alto, CAView Profile Authors Info & Claims ISCA '98: 25 years of the international symposia on Computer architecture (selected papers)August 1998 Pages 388–397https://doi.org/10.1145/285930.285998Online:01 August 1998Publication History 16citation1,530DownloadsMetricsTotal Citations16Total Downloads1,530Last 12 Months26Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons (2003)

Opposing parasympathetic and sympathetic signals determine the autonomic output of the brain to the body and the change in balance over the sleep-wake cycle. The suprachiasmatic nucleus (SCN) organizes the activity/inactivity cycle and the behaviors that go along with it, but it is unclear how the hypothalamus, in particular the SCN, with its high daytime electrical activity, influences this differentiated autonomic balance. In a first series of experiments, we visualized hypothalamic pre-sympathetic neurons by injecting the retrograde tracer Fluoro-Gold into the thoracic sympathetic nuclei of the spinal cord. Pre-parasympathetic neurons were revealed by injection of the retrograde trans-synaptic tracer pseudorabies virus (PRV) into the liver and by sympathetic liver denervation, forcing the virus to infect via the vagus nerve only. This approach revealed separate pre-sympathetic and pre-parasympathetic neurons in the brainstem and hypothalamus. Next, selective retrograde tracing with two unique reporter PRV strains, one injected into the adrenal and the other into the sympathetic denervated liver, demonstrated that there are two separate populations of pre-sympathetic and pre-parasympathetic neurons within the paraventricular nucleus of the hypothalamus. Interestingly, this segregation persists into the SCN, where, as a result, the day-night balance in autonomic function of the organs is affected by specialized pre-sympathetic or pre-parasympathetic SCN neurons. These separate preautonomic SCN neurons provide the anatomical basis for the circadian-driven regulation of the parasympathetic and sympathetic autonomic output.
An ASIC implementation of digital front-end electronics for a high resolution PET scanner (1993)

An application specific integrated circuit (ASIC) is designed and fabricated. It implements many of the current functions found in the digital front-end electronics for a high resolution positron emission tomography scanner. The ASIC performs crystal selection, energy qualification, time correction, and event counting functions for block technology high resolution PET scanners. Digitized x and y position, event energy, and time information are used by the ASIC to determine block crystal number, qualify the event based on energy, and correct the event time. Event counting and block dead time calculations are performed for system dead time corrections. A loadable sequencer for controlling the analog front-end electronics is implemented. The ASIC is implemented in a 37000 gate, 1.0- mu m CMOS gate-array and is capable of handling four million events/second while reducing parts count, cost, and power consumption over current board-level designs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>