gebhart/patrepeval huggingface dataset:
New Era in Drug Interaction Evaluation: US Food and Drug Administration Update on CYP Enzymes, Transporters, and the Guidance Process (2008)

Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.
Influence of Geometry, Porosity, and Surface Characteristics of Silica Nanoparticles on Acute Toxicity: Their Vasculature Effect and Tolerance Threshold (2012)

Silica nanoparticles (SiO(2)) are widely used in biomedical applications such as drug delivery, cell tracking, and gene transfection. The capability to control the geometry, porosity, and surface characteristics of SiO(2) further provides new opportunities for their applications in nanomedicine. Concerns however remain about the potential toxic effects of SiO(2) upon exposure to biological systems. In the present study, the acute toxicity of SiO(2) of systematically varied geometry, porosity, and surface characteristics was evaluated in immune-competent mice when administered intravenously. Results suggest that in vivo toxicity of SiO(2) was mainly influenced by nanoparticle porosity and surface characteristics. The maximum tolerated dose (MTD) increased in the following order: mesoporous SiO(2) (aspect ratio 1, 2, 8) at 30-65 mg/kg < amine-modified mesoporous SiO(2) (aspect ratio 1, 2, 8) at 100-150 mg/kg < unmodified or amine-modified nonporous SiO(2) at 450 mg/kg. The adverse reactions above MTDs were primarily caused by the mechanical obstruction of SiO(2) in the vasculature that led to congestion in multiple vital organs and subsequent organ failure. It was revealed that hydrodynamic sizes of SiO(2) post-protein exposure had an important implication in relating SiO(2) physicochemical properties with their vasculature impact and resultant tolerance threshold, as the larger the hydrodynamic size in the presence of serum protein, the lower the MTD. This study sheds light on the rational design of SiO(2) to minimize in vivo toxicity and provides a critical guideline in selecting SiO(2) as the appropriate system for nanomedicine applications.
Thrombolysis and Reocclusion in Experimental Jugular Vein and Coronary Artery Thrombosis (1995)

Administration of the anti-PAI-1 antibody (CLB-2C8) results in increased endogenous thrombolysis and inhibition of thrombus growth in a venous thrombosis model in rabbits and facilitated reperfusion and reduction of reocclusion in a canine model of coronary artery thrombosis.
Plasma-enhanced chemical vapour deposition growth of carbon nanotubes on different metal underlayers (2005)

One important requirement for future applications of carbon nanotube electronic devices is the ability to controllably grow carbon nanotubes on metal electrodes. Here we show that it is possible to grow small diameter (
An Overview of Reasons for the Placement and Replacement of Restorations (2001)

The clinical diagnoses of caries may continue to be found to account for the placement and replacement of most intracoronal restorations. Surveys of the type reviewed provide valuable insight into patterns of provision of dental care and highlight research priorities in relation to direct restorations.
CompuCell, a multi-model framework for simulation of morphogenesis (2004)

Binaries and source code for Microsoft Windows, Linux and Solaris are available for download from http://sourceforge.net/projects/compucell/
Mining association rules with item constraints (1997)

The problem of discovering association rules has received considerable research attention and several fast algorithms for mining association rules have been developed. In practice, users are often interested in a subset of association rules. For example, they may only want rules that contain a specific item or rules that contain children of a specific item in a hierarchy. While such constraints can be applied as a postprocessing step, integrating them into the mining algorithm can dramatically reduce the execution time. We consider the problem of integrating constraints that are boolean expressions over the presence or absence of items into the association discovery algorithm. We present three integrated algorithms for mining association rules with item constraints and discuss their tradeoffs. 1. Introduction The problem of discovering association rules was introduced in (Agrawal, Imielinski, &amp;amp; Swami 1993). Given a set of transactions, where each transaction is a set of literals (call...
External dosimetry in the aftermath of a radiological terrorist event (2006)

This paper reviews external dosimetry in emergency preparedness planning for a potential terrorist release of radioactive material in a densely populated area. The radiation dose received by response workers and members of the public is needed to understand health risks. The existing framework for dosimetry of routinely occupationally exposed workers is not directly applicable to all emergency workers who would respond to a radiological terrorist event. Emergency preparedness plans incorporate various old and new dosimetry technologies, including quartz fibre electrets, electronic dosemeters, personnel badges and wallet cards. Environmental monitoring and dose calculations are the usual methods for determining public dose. However, during the late-phase response, after removable contamination has been eliminated, it may be easier and more straightforward to provide individual dosimetry for members of the public who may be moving through a city with varying contamination areas. Doing so could allow resumption of normal activities earlier and promote confidence in reusing the site.
Peroxynitrite-Mediated Mitochondrial Dysfunction (2001)

Peroxynitrite anion (ONOO(-)) is a potent biological oxidant produced by the near diffusion-limited reaction of superoxide and nitric oxide. Peroxynitrite has been implicated in diverse forms of free radical-induced tissue injury. Experimental evidence showed that exogenous and endogenous peroxynitrite causes alterations of the structure and function of mitochondrial proteins, leading to mitochondrial dysfunction and cellular or organ injury. These data are discussed along with its physiopathological implications.
Human melanoma cells express a novel integrin receptor for laminin (1989)

This study sought to determine whether human melanoma cells express integrin-related receptors that mediate their adhesion to laminin. We found that antibodies against the integrin beta 1 chain blocked cell attachment to laminin-coated surfaces. Furthermore, immunofluorescence staining demonstrated beta 1 complexes in vinculin-positive focal adhesion plaques on the basal surface of cells attached to laminin substrates. Chromatography of detergent extracts of 125I-surface-labeled cells on laminin-Sepharose columns recovered two major laminin-binding proteins (100 and 130 kDa, reduced) that bound with high affinity to the columns and were eluted with EDTA. Both proteins were specifically immunoprecipitated from column fractions with monoclonal and polyclonal antibodies to the integrin beta 1 subunit, indicating that they form a noncovalent heterodimer complex. The alpha-like subunit is composed of a 30-kDa light chain that is joined by a disulfide bond to the 100-kDa heavy chain. This complex was not recovered from columns of fibronectin- or collagen type I- or IV-Sepharose. Laminin-binding by the alpha beta 1 complex was independent of Arg-Gly-Asp or Tyr-Ile-Gly-Ser-Arg-like sequences, but required the presence of divalent cations. The 100-kDa alpha-like subunit was electrophoretically and immunochemically distinct from the other known alpha subunits, alpha 1-alpha 6. The results indicate that human melanoma cells express a novel laminin-specific integrin beta 1 complex which may mediate the cells' interactions with this ligand.
Performance data for a six-sample look-ahead (1993)

The authors present a modification to the five-sample
On the nature of simultaneous colour contrast (2006)

Our journey from the psychophysics of simple displays toward the perception of natural scenes may call to mind the following well-known story that appears in many guises.Benighted space traveller in impenetrable rain forest on unknown planet, on meeting small person with long ears: "Sir, can you tell me the way to Alderon?" Person with ears: "If to Alderon going were I, not from here start would I." -
Inactivation of Viruses by Benzalkonium Chloride (1964)

Benzalkonium chloride (as Roccal or Zephiran) was found to inactivate influenza, measles, canine distemper, rabies, fowl laryngotracheitis, vaccinia, Semliki Forest, feline pneumonitis, meningopneumonitis, and herpes simplex viruses after 10 min of exposure at 30 C or at room temperature. Poliovirus and encephalomyocarditis virus were not inactivated under the same conditions. It was concluded that all viruses tested were sensitive except members of the picorna group. The literature was reviewed.
Opportunistic controls (2008)

We present Opportunistic Controls, a class of user interaction techniques for augmented reality (AR) applications that support gesturing on, and receiving feedback from, otherwise unused affordances already present in the domain environment. Opportunistic Controls leverage characteristics of these affordances to provide passive haptics that ease gesture input, simplify gesture recognition, and provide tangible feedback to the user. 3D widgets are tightly coupled with affordances to provide visual feedback and hints about the functionality of the control. For example, a set of buttons is mapped to existing tactile features on domain objects. We describe examples of Opportunistic Controls that we have designed and implemented using optical marker tracking, combined with appearance-based gesture recognition. We present the results of a user study in which participants performed a simulated maintenance inspection of an aircraft engine using a set of virtual buttons implemented both as Opportunistic Controls and using simpler passive haptics. Opportunistic Controls allowed participants to complete their tasks significantly faster and were preferred over the baseline technique.
The use of culture redox potential and oxygen uptake rate for assessing glucose and glutamine depletion in hybridoma cultures (1997)

Culture redox potential (CRP) and oxygen uptake rate (OUR) were monitored on-line during glucose- and glutamine-limited batch cultures of a murine hybridoma cell line that secretes a neutralizing monoclonal antibody specific to toxin 2 of the scorpion Centruroides noxius Hoffmann. It was found that OUR and CRP can be used for assessing the viable cell concentration and growth phases of the culture. Before nutrient depletion, OUR increased exponentially with viable cell concentration, whereas CRP decreased monotonically until cell viability started to decrease. During the death phase, CRP gradually increased. A sudden decrease in OUR occurred upon glucose or glutamine depletion. CRP traced the dissolved oxygen profile during a control action or an operational eventuality, however, during nutrient depletion it did not follow the expected behavior of a system composed mainly by the O(2)/H(2)O redox couple. Such a behavior was not due to the accumulated lactate or ammonia, nor to possible intracellular redox potential changes caused by nutrient depletion, as inferred from respiration inhibition by rotenone or uncoupled respiration by 2,4-dinitrophenol. As shown in this study, operational eventualities can be erroneously interpreted as changes in OUR when using algorithms based solely on oxygen balances. However, simultaneous measurements of CRP and OUR may be used to discriminate real metabolic events from operational failures. The results presented here can be used in advanced real-time algorithms for controling glucose and glutamine at low concentrations, avoiding under- or over-feeding them in hybridoma cultures, and consequently reducing the accumulation of metabolic wastes and improving monoclonal antibody production. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 555-563, 1997.
40-Gb/s tandem electroabsorption modulator (2002)

In this letter, we have developed a tandem electroabsorption modulator with an integrated semiconductor optical amplifier that is capable of both nonreturn-to-zero and return-to-zero (RZ) data transmission at 40 Gb/s. The tandem modulator consists of a broad-band data encoder and a narrow-band pulse carver. The pulse carver is able to produce 5-ps pulses with more than 20 dB of extinction. The on-chip semiconductor optical amplifier provides up to 8.5 dB of fiber-to-fiber gain and enables the modulator to be operated with zero insertion loss. Devices have been realized with greater than 40-GHz bandwidth, and 13-dB dynamic extinction for a 2.5-V swing. For optimized designs bandwidths of nearly 60 GHz: have been realized. Using these devices penalty free RZ data transmission over a 100-kin dispersion compensated fiber link has been demonstrated with a received power sensitivity of -29 dBm.
Is atherosclerosis caused by high cholesterol? (2002)

Is atherosclerosis caused by high cholesterol?
The neuroanatomy of autism – a developmental perspective (2016)

Autism Spectrum Disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that are diagnosed solely on the basis of behaviour. A large body of work has reported neuroanatomical differences between individuals with ASD and neurotypical controls. Despite the huge clinical and genetic heterogeneity that typifies autism, some of these anatomical features appear to be either present in most cases or so dramatically altered in some that their presence is now reasonably well replicated in a number of studies. One such finding is the tendency towards overgrowth of the frontal cortex during the early postnatal period. Although these reports have been focused primarily on the presumed pathological anatomy, they are providing us with important insights into normal brain anatomy and are stimulating new ideas and hypotheses about the normal trajectory of brain development and the function of specific anatomical brain structures. The use of model systems that include genetic model organisms such as the mouse and, more recently, human induced pluripotent stem cell-derived brain organoids to model normal and pathological human cortical development, is proving particularly informative. Here we review some of the neuroanatomical alterations reported in autism, with a particular focus on well-validated findings and recent advances in the field, and ask what these observations can tell us about normal and abnormal brain development.
Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis* (2007)

Transcutaneous vagus nerve stimulation is an efficacious treatment for mice with lethal endotoxemia or polymicrobial sepsis.
In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides. (1992)

The c-myb protooncogene encodes proteins that are critical for hematopoietic cell proliferation and development. Disrupting c-myb function might, therefore, prove an effective therapeutic strategy for controlling leukemic cell growth. Antisense oligodeoxynucleotides have been utilized for this purpose in vitro, but their in vivo efficacy has not been reported. We therefore established human leukemia-scid mouse chimeras with K562 cells and treated diseased animals with phosphorothioate-modified antisense oligodeoxynucleotides. K562 cells express the c-myb protooncogene, which served as the target for the antisense DNA. They also express the tumor-specific bcr-abl oncogene that was utilized to track the human cells in the mouse host. Once circulating leukemic blast cells had been detected, the survival of untreated control mice was 6 +/- 3 days (mean +/- SD). The survival of animals treated for 7 or 14 days with either sense or scrambled-sequence c-myb oligodeoxynucleotides was not statistically different from the control animals. In distinct contrast, animals treated for similar lengths of time with antisense c-myb oligodeoxynucleotides survived at least 3.5 times longer than the various control animals. In addition, animals receiving antisense c-myb DNA had significantly less disease at the two sites most frequently manifesting leukemic cell infiltration, the central nervous system and the ovary. These results suggest that phosphorothioate-modified antisense DNA may be efficacious for the treatment of human leukemia in vivo, and by analogy, for the treatment of other human neoplasias.
Thematic review series: Lipid Posttranslational Modifications. Farnesyl transferase inhibitors (2005)

Some proteins undergo posttranslational modification by the addition of an isoprenyl lipid (farnesyl- or geranylgeranyl-isoprenoid) to a cysteine residue proximal to the C terminus. Protein isoprenylation promotes membrane association and contributes to protein-protein interactions. Farnesylated proteins include small GTPases, tyrosine phosphatases, nuclear lamina, cochaperones, and centromere-associated proteins. Prenylation is required for the transforming activity of Ras. Because of the high frequency of Ras mutations in cancer, farnesyl transferase inhibitors (FTIs) were investigated as a means to antagonize Ras function. Evaluation of FTIs led to the finding that both K- and N-Ras are alternatively modified by geranylgeranyl prenyltransferase-1 in FTI-treated cells. Geranylgeranylated forms of Ras retain the ability to associate with the plasma membrane and activate substrates. Despite this, FTIs are effective at inhibiting the growth of human tumor cells in vitro, suggesting that activity is dependent on blocking the farnesylation of other proteins. FTIs also inhibit the in vivo growth of human tumor xenografts and sensitize these models to chemotherapeutics, most notably taxanes. Several FTIs have entered clinical trials for various cancer indications. In some clinical settings, primarily hematologic malignancies, FTIs have displayed evidence of single-agent activity. Clinical studies in progress are exploring the antitumor activity of FTIs as single agents and in combination. This review will summarize the basic biology of FTIs, their antitumor activity in preclinical models, and the current status of clinical studies with these agents.
Preclinical Evaluation of a Tailor-Made DOTA-Conjugated PSMA Inhibitor with Optimized Linker Moiety for Imaging and Endoradiotherapy of Prostate Cancer (2015)

The tailor-made DOTA-conjugated PSMA inhibitor PSMA-617 presented here is sustainably refined and advanced with respect to its tumor-targeting and pharmacokinetic properties by systematic chemical modification of the linker region. Therefore, this radiotracer is suitable for a first-in-human theranostic application and may help to improve the clinical management of prostate cancer in the future.
Targets for asthma therapy. (2000)

Most asthma is allergic in origin, the disease involves four distinct phases of response: the sensitization phase and the activation phase, followed by the effector phase, initiated by the release of pharmacologically active agents, the growth and repair phase, characterized by proliferation of tissues as "remodeling" of the airway wall, altering structure and function.
The uptake of cholesterol at the small‐intestinal brush border membrane is inhibited by apolipoproteins (1997)

The uptake of free and esterified cholesterol at the brush border membrane is protein-mediated. Here we show that this sterol uptake is effectively inhibited by exchangeable serum apolipoproteins. Binding of the apolipoprotein to the brush border membrane mediates the inhibitory effect. Evidence is presented to show that the structural motif responsible for the inhibition is the amphipathic alpha-helix.
The bacterial spore: nature's survival package (2005)

Spores of Bacillus and Clostridium species are metabolically dormant and extremely resistant to acute environmental stresses such as heat, desiccation, UV and γ-radiation,
Human cytomegalovirus productively infects primary differentiated macrophages (1991)

Monocytes are one of the predominant cell types in the peripheral blood that are infected by human cytomegalovirus (HCMV). Although virus can be detected in these cells in vivo, HCMV replication in cultured monocytes has been unsuccessful. In this study, we demonstrate efficient HCMV replication in cultured monocytes. HCMV permissiveness in these cells was dependent on nonadherent cell-induced stimulation of the monocyte, with subsequent morphological differentiation into macrophages. Approximately 40% of the cells infected by virus were detected by immunofluorescent staining with both immediate-early and late antibodies. In addition, viral plaque assays demonstrated significant productive infection of macrophages. These observations are consistent with the suggestion that the monocyte/macrophage serves as a source of viral amplification and dissemination.
Different antibody response to a neutralizing epitope of human cytomegalovirus glycoprotein B among seropositive individuals (1994)

The amino-terminal portion of human cytomegalovirus glycoprotein B (HCMV-gB) was expressed as a fusion protein to analyze the neutralizing epitope recognized by human monoclonal antibody C23 and the humoral immune response to this epitope. The linear neutralizing epitope was further localized to the peptide within 17 amino acids (position 68-84) which were conserved between two HCMV laboratory strains. Ten out of 17 HCMV-seropositive human sera contained the antibody against this epitope. Although seven sera were negative for reacting with the fusion protein, the viruses isolated from the same patients retained the epitope. The immunogenicity of the epitope and the possible application of C23 human monoclonal antibody for passive immunization against HCMV infections are discussed.