gebhart/patrepeval huggingface dataset:
Basic Concepts of Microarrays and Potential Applications in Clinical Microbiology (2009)

The introduction of in vitro nucleic acid amplification techniques, led by real-time PCR, into the clinical microbiology laboratory has transformed the laboratory detection of viruses and select bacterial pathogens. However, the progression of the molecular diagnostic revolution currently relies on the ability to efficiently and accurately offer multiplex detection and characterization for a variety of infectious disease pathogens. Microarray analysis has the capability to offer robust multiplex detection but has just started to enter the diagnostic microbiology laboratory. Multiple microarray platforms exist, including printed double-stranded DNA and oligonucleotide arrays, in situ-synthesized arrays, high-density bead arrays, electronic microarrays, and suspension bead arrays. One aim of this paper is to review microarray technology, highlighting technical differences between them and each platform's advantages and disadvantages. Although the use of microarrays to generate gene expression data has become routine, applications pertinent to clinical microbiology continue to rapidly expand. This review highlights uses of microarray technology that impact diagnostic microbiology, including the detection and identification of pathogens, determination of antimicrobial resistance, epidemiological strain typing, and analysis of microbial infections using host genomic expression and polymorphism profiles.
Activation of chromatin by acetylation of histone side chains. (1976)

The ability of calf thymus chromatin to support DNA-dependent RNA synthesis is markedly increased by modification of the histones with acetic anhydride. The extent of chemical acetylation of histones H2a, H2b, H3, and H4 required for the increase of template activity of the chromatin is within that which can be achieved enzymatically in the cell. The evidence suggests that the acetylation of histone side chains stimulates the rate of chain elongation during transcription of chromatin.
Self-phase-modulation in silica optical fibers (1978)

We report measurements of frequency broadening due to self-phase-modulation (SPM) in optical fibers. The use of single-mode silica-core fibers and mode-locked argon-laser pulses leads to the simplest and cleanest measurements yet made of SPM. The qualitative features of the frequency spectrum are in good agreement with theoretical expectations. The experiment provides an independent measurement of ${n}_{2}$, the self-focusing coefficient. The results also point to some simple and useful techniques based on fibers for the measurement and analysis of mode-locked laser pulses.
Al As ∕ Ga As micropillar cavities with quality factors exceeding 150.000 (2007)

The authors report on AlAs∕GaAs micropillar cavities with unprecedented quality factors based on high reflectivity distributed Bragg reflectors (DBRs). Due to an increased number of mirror pairs in the DBRs and an optimized etching process record quality (Q) factors up to 165.000 are observed for micropillars with diameters of 4μm. Optical studies reveal a very small ellipticity of 5×10−4 of the pillar cross section. Because of the high Q factors, strong coupling with a vacuum Rabi splitting of 23μeV is observed for micropillars with a diameter of 3μm.
The Less Harmful Cigarette:  A Controversial Issue. A Tribute to Ernst L. Wynder (2001)

The dose-response relationship between number of cigarettes smoked and risk for lung cancer was established in 1950 by epidemiological studies. Laboratory assays with tobacco tar on mouse skin and smoke inhalation experiments with hamsters provided further evidence for this relationship. In cigarette smoke, among 4800 identified compounds, 69 are carcinogens, and several are tumor promoters or cocarcinogens. The major toxic agents are nicotine, carbon monoxide, hydrogen cyanide, nitrogen oxides, some volatile aldehydes, some alkenes, and some aromatic hydrocarbons. Public health information and education have led to a reduction of cigarette smokers among U.S. adults from 40 to 25%. However, in high school students, smoking increased to 35% and in adults with less than a high school education it remains high at 33.3%. Intervention studies were augmented with attempts of risk reduction by changing the tobacco composition and makeup of cigarettes. This led to cigarettes that, according to the FTC, reduced the tar and nicotine yields from an average of 37 and 2.7 mg to 12 and 0.85 mg. The anticipated reduction of mortality rates from chronic diseases among cigarette smokers did not occur, primarily, because of a major adjustment in smoking intensity and depth of inhalation by the habitual smokers. It is, therefore, imperative that smoking control efforts are intensified and that, short of banning cigarette sales, cigarettes delivering smoke with the lowest potential for toxicity, addiction, and carcinogenicity are declared a matter of public health policy.
DNA Sequence Dependent Monomer−Dimer Binding Modulation of Asymmetric Benzimidazole Derivatives (2003)

A number of studies indicate that DNA sequences such as AATT and TTAA have significantly different physical and interaction properties. To probe these interaction differences in detail and determine the influence of charge, we have synthesized three bisbenzimidazole derivatives, a diamidine, DB185, and monoamidines, DB183 and DB210, that are related to the well-known minor groove agent, Hoechst 33258. Footprinting studies with several natural and designed DNA fragments indicate that the synthetic compounds bind at AT sequences in the minor groove and interact more weakly at sites with TpA steps relative to sites without such steps. Circular dichroism spectroscopy also indicates that the compounds bind in the DNA minor groove. Surprisingly, Tm studies as a function of ratio indicate that the monoamidines bind to TTAA sequences as dimers, whereas the diamidine binds as a monomer. Biosensor-surface plasmon resonance (SPR) studies allowed us to quantitate the interaction differences in more detail. SPR results clearly show that the monoamidine compounds bind to the TTAA sequence in a cooperative 2:1 complex but bind as monomers to AATT. The dication binds to both sequences in monomer complexes but the binding to AATT is significantly stronger than binding to TTAA. Molecular dynamics simulations indicate that the AATT sequence has a narrow time-average minor groove width that is a very good receptor site for the bisbenzimidazole compounds. The groove in TTAA sequences is wider and the width must be reduced to form a favorable monomer complex. The monocations thus form cooperative dimers that stack in an antiparallel orientation and closely fit the structure of the TTAA minor groove. The amidine groups in the dimer are oriented in the 5' direction of the strand to which they are closest. Charge repulsion in the dication apparently keeps it from forming the dimer. It instead reduces the TTAA groove width, in an induced fit process, sufficiently to form a minor groove complex. The dimer-binding mode of DB183 and DB210 is a new DNA recognition motif and offers novel design concepts for selective targeting of DNA sequences with a wider minor groove, including those with TpA steps.
Electrooptic mapping and finite-element modeling of the near-field pattern of a microstrip patch antenna (2000)

A comprehensive electrooptic field-mapping technique is applied to the characterization of near-field radiation patterns above a microstrip patch antenna. The amplitude and phase maps of three orthogonal electric-field components, measured using electrooptic crystals above the patch, also have revealed the transition from the near field to the far field of the radiation pattern. In addition, experimental results have been compared with a finite-element method (FEM) simulation. The measurememts show superior results to the FEM simulation, especially in terms of spatial resolution and data acquisition times. Furthermore, the scattering parameter S/sub 11/ for the patch antenna has been calculated from the electrooptic measurement results of standing waves on the feeding line and compared with results from a conventional network analyzer.
On the low-temperature mobility of holes in gated oxide Si/SiGe heterostructures (1997)

A detailed comparison is made between theory and experiment for the low-temperature mobility of holes in gated oxide, coherently strained Si/SiGe heterostructures. We conclude that the mobility is mainly limited by interface impurities, conventional surface roughness and strain fluctuations; by contrast, we argue that alloy scattering is comparatively weak. Comments regarding possible mobility degradation due to oxide formation are also made.
An Adhesive Patch-Based Skin Biopsy Device for Molecular Diagnostics and Skin Microbiome Studies. (2017)

The adhesive patch skin sampling procedure is well tolerated and provides robust means to obtain skin tissue, RNA, DNA, and microbiome samples without involving surgical biopsies. The non-invasively obtained skin samples can be shipped cost effectively at ambient temperature by mail or standard courier service, and are suitable for a variety of molecular analyses of the skin microbiome as well as of keratinocytes, T cells, dendritic cells, melanocytes, and other skin cells involved in the pathology of various skin conditions and conditions where the skin can serve as a surrogate target organ. <em>J Drugs Dermatol. 2017;16(10):979-986.</em> .
Molecular cloning and characterization of the glucoamylase gene of Aspergillus awamori. (1984)

The filamentous ascomycete Aspergillus awamori secretes large amounts of glucoamylase upon growth in medium containing starch, glucose, or a variety of hexose sugars and sugar polymers. We examined the mechanism of this carbon source-dependent regulation of glucoamylase accumulation and found a several hundredfold increase in glucoamylase mRNA in cells grown on an inducing substrate, starch, relative to cells grown on a noninducing substrate, xylose. We postulate that induction of glucoamylase synthesis is regulated transcriptionally. Comparing total mRNA from cells grown on starch and xylose, we were able to identify an inducible 2.3-kilobase mRNA-encoding glucoamylase. The glucoamylase mRNA was purified and used to identify a molecularly cloned 3.4-kilobase EcoRI fragment containing the A. awamori glucoamylase gene. Comparison of the nucleotide sequence of the 3.4-kilobase EcoRI fragment with that of the glucoamylase I mRNA (as determined from molecularly cloned cDNA) revealed the existence of four intervening sequences within the glucoamylase gene. The 5' end of the glucoamylase mRNA was mapped to several locations within a region -52 to -73 nucleotides from the translational start. Sequence and structural features of the glucoamylase gene of the filamentous ascomycete A. awamori were examined and compared with those reported in genes of other eucaryotes.
Needle-free epidermal powder immunization (2002)

Due to the presence of a network of antigen-presenting cells and other cells with innate and adaptive immune functions, the skin is both a sensitive immune organ and a practical target site for vaccine administration. A handful of needle-free immunization technologies have emerged in recent years that aim to take advantage of these characteristics. Skin delivery technologies provide potentially safer alternatives to needle injection and promises increased efficacy in the prevention and/or therapy of infectious diseases, allergic disorders and cancer. In this review, we will cover advances in needle-free skin vaccination technologies and their potential applications to disease prevention and therapy. Emphasis will be placed on epidermal powder immunization and particle-mediated ('gene gun') DNA immunization, which use similar mechanical devices to deliver protein and DNA vaccines, respectively, into the viable epidermis.
Matrix metalloproteinase 10 contributes to hepatocarcinogenesis in a novel crosstalk with the stromal derived factor 1/C‐X‐C chemokine receptor 4 axis (2015)

MMP10 contributes to HCC development, participating in tumor angiogenesis, growth, and dissemination. We identified a new reciprocal crosstalk between MMP10 and the CXCR4/SDF1 axis contributing to HCC progression and metastasis. To our knowledge, this is the first report addressing the role of a MMP in hepatocarcinogenesis in the corresponding genetic mouse model.
Visualization and quantitative analysis of nanoparticles in the respiratory tract by transmission electron microscopy (2007)

Nanotechnology in its widest sense seeks to exploit the special biophysical and chemical properties of materials at the nanoscale. While the potential technological, diagnostic or therapeutic applications are promising there is a growing body of evidence that the special technological features of nanoparticulate material are associated with biological effects formerly not attributed to the same materials at a larger particle scale. Therefore, studies that address the potential hazards of nanoparticles on biological systems including human health are required. Due to its large surface area the lung is one of the major sites of interaction with inhaled nanoparticles. One of the great challenges of studying particle-lung interactions is the microscopic visualization of nanoparticles within tissues or single cells both in vivo and in vitro. Once a certain type of nanoparticle can be identified unambiguously using microscopic methods it is desirable to quantify the particle distribution within a cell, an organ or the whole organism. Transmission electron microscopy provides an ideal tool to perform qualitative and quantitative analyses of particle-related structural changes of the respiratory tract, to reveal the localization of nanoparticles within tissues and cells and to investigate the 3D nature of nanoparticle-lung interactions.This article provides information on the applicability, advantages and disadvantages of electron microscopic preparation techniques and several advanced transmission electron microscopic methods including conventional, immuno and energy-filtered electron microscopy as well as electron tomography for the visualization of both model nanoparticles (e.g. polystyrene) and technologically relevant nanoparticles (e.g. titanium dioxide). Furthermore, we highlight possibilities to combine light and electron microscopic techniques in a correlative approach. Finally, we demonstrate a formal quantitative, i.e. stereological approach to analyze the distributions of nanoparticles in tissues and cells.This comprehensive article aims to provide a basis for scientists in nanoparticle research to integrate electron microscopic analyses into their study design and to select the appropriate microscopic strategy.
Multicolumn Infusion of Gene Therapy Cells into Human Brain Tumors: Technical Report (2000)

This technique should facilitate saturation of tumors with tumoricidal doses of gene therapy vectors and should improve the results of gene therapy protocols that rely on intraparenchymal injection for delivery.
Specific activation of Gs by synthetic peptides corresponding to an intracellular loop of the β‐adrenergic receptor (1991)

Peptides corresponding to the amino acid sequence of the hamster beta 2-adrenergic receptor (beta 2AR) were synthesized and their ability to activate purified G-proteins determined. Two peptides, comprising the N- and C-terminal 15 amino acids of the putative third intracellular loop region of the beta 2AR were found to activate the G-protein Gs but not to activate a preparation of Gi/Go. Other peptides corresponding to the internal portions of this loop and the C-terminal tail region failed to activate either G-protein. The presence of phospholipid vesicles was required for this activation. The observation that peptides with sequences corresponding to the ends of the third intracellular loop of the beta AR can specifically activate Gs confirms the results of previous mutagenesis studies on the receptor and demonstrates that the secondary structure conferred by the amino acid sequences in these regions is sufficient for the activation of G-proteins.
Incidence and etiologies of complicated parapneumonic effusions in children, 1996 to 2001 (2003)

The incidence of complicated parapneumonic effusions in children with community-acquired pneumonia increased from 1996 to 1999 and then declined concomitant with the introduction of the pneumococcal conjugate vaccine. Although cases caused by S. pneumoniae have decreased, community onset methicillin-resistant Staphylococcus aureus has emerged as a cause of pneumonia with complicated effusions in children.
Engineering an IgG Scaffold Lacking Effector Function with Optimized Developability (2016)

IgG isotypes can differentially bind to Fcγ receptors and complement, making the selection of which isotype to pursue for development of a particular therapeutic antibody important in determining the safety and efficacy of the drug. IgG2 and IgG4 isotypes have significantly lower binding affinity to Fcγ receptors. Recent evidence suggests that the IgG2 isotype is not completely devoid of effector function, whereas the IgG4 isotype can undergo in vivo Fab arm exchange leading to bispecific antibody and off-target effects. Here an attempt was made to engineer an IgG1-based scaffold lacking effector function but with stability equivalent to that of the parent IgG1. Care was taken to ensure that both stability and lack of effector function was achieved with a minimum number of mutations. Among the Asn<sup>297</sup> mutants that result in lack of glycosylation and thus loss of effector function, we demonstrate that the N297G variant has better stability and developability compared with the N297Q or N297A variants. To further improve the stability of N297G, we introduced a novel engineered disulfide bond at a solvent inaccessible location in the CH2 domain. The resulting scaffold has stability greater than or equivalent to that of the parental IgG1 scaffold. Extensive biophysical analyses and pharmacokinetic (PK) studies in mouse, rat, and monkey further confirmed the developability of this unique scaffold, and suggest that it could be used for all Fc containing therapeutics (e.g. antibodies, bispecific antibodies, and Fc fusions) requiring lack of effector function or elimination of binding to Fcγ receptors.
Simultaneous Determination of Hydrolysis and Mutarotation Rates during the Enzymatic Hydrolysis of Lactose (2008)

An experiment is described in which a custom-made glucose electrode is used to directly monitor the enzymatic hydrolysis of lactose to glucose. The transient profile of beta- d-glucose can be used to simultaneously determine the rate constants for mutarotation and for enzymatic hydrolysis by applying a dynamic nonlinear regression routine. Due to differences in the mutarotation rate constants between lactose and glucose, the beta- d-glucose concentration "overshoots" equilibrium under certain conditions, which can be modeled mathematically. This overshoot can be observed reliably and used to quantify the differences in mutarotational equilibria between glucose and lactose. These observations may be important for the analysis of dairy products and commercial lactase preparations and illustrate an unusual kinetic phenomenon caused by intramolecular forces. This approach may also be important for the accurate determination of a variety of oligosaccharides such as glycogen, which tend to be composed primarily of one stereoisomer.
Pharmacokinetics and Pharmacodynamics of Biotech Drugs (2006)

In recent years, biotechnologically derived peptide- and protein-based drugs have developed into mainstream therapeutic agents. Peptide and protein drugs, as well as oligonucleotides and DNA, now constitute a substantial portion of the compounds under preclinical and clinical development in the global pharmaceutical industry. The pharmacokinetic and pharmacodynamic properties of a biotech drug determine the relationship between administered dose, resulting systemic exposure, and subsequent pharmacologic response. Pharmacokinetics, and pharmacodynamics are, therefore, frequently crucial determinants of a drug's efficacy and safety, and their evaluation is an important component during the preclinical and clinical development of a drug candidate. However, pharmacokinetic and exposure/response evaluations for peptides and protein therapeutics are frequently complicated by their similarity to endogenous peptides and proteins as well as protein nutrients. In addition, pharmacokinetic/pharmacodynamic (PK/PD) correlations for biotech drugs are frequently convoluted by their close interaction with endogenous substances and physiologic regulatory feedback mechanisms. Extensive use of pharmacokinetic and exposure/response concepts in all phases of drug development has, in the past, been identified as a crucial factor for the success of a scientifically driven, evidence-based, and hence accelerated drug development process. Thus, PK/PD concepts are likely to continue and expand their role as a fundamental factor in the successful development of biotechnologically derived drug products in the future.


Keywords:

Biotech Drug;
Absorption;
Distribution;
Elimination;
Excretion;
Metabolism;
Clearance (CL);
Volume of Distribution (Vd );
Exposure /Response Correlation;
PK/PD Model
Ultrasonically Induced Cavitation in Water: A Step-by-Step Process (1953)

A 2.5-Mc, barium-titanate, spherically focusing radiator was used to produce cavitation in both degassed and aerated water entirely within the restricted, high intensity focal region, remote from the water boundaries. The sonic intensity rises to 1.8 kw/cm2, and the pressure amplitude to ±70 atmos at the focus. High-intensity illumination and an unusual high speed photographic technique permit observation and timing of the step-by-step process of cavitation development. Feather-shaped cavitation bursts are sporadically produced, being initiated in the insignificant quill portion nearest the radiator, then abruptly expanding to form the catastrophic plume portion. The plume is believed to be formed by myriads of micro-cavities, too small and close for individual observation. These two fundamental steps are identically produced, and with equal ease, both in degassed and aerated water. The whole action is over in several milliseconds, except that in the case of aerated water a third bubble step is produced. In aerated water, non-collapsing gas bubbles are generated by and concurrently with, the catastrophic step. These bubbles remain after collapse of the burst, to be blown off down stream by the sonically induced liquid streaming. The bubble step is not generated without the presence of the catastrophic step. The latter is generated only if the initiation step reaches a definite degree of development (not always attained). This requires sonic activation for increasing lengths of time for decreasingly smaller sonic intensities. Origination of the initiation step, and hence of the whole cavitation phenomena, is believed to occur whenever a stray nucleus (weak spot) streams into the high intensity sonic field.
Synergies between regulatory elements of the immunoglobulin heavy chain locus and its palindromic 3 ′ locus control region (1998)

Transcriptional enhancers of the IgH locus include E mu and four 3' elements (C alpha3', hs1-2, hs3 and hs4), some of which are by themselves weak. We show that these weak elements behave as strong "co-enhancers" when combined, and display a stage-dependent activity which differs from that obtained when they are alone. Combinations mimicking the palindromic structure of the 3' IgH region are particularly efficient. Noticeably in pre-B cells, hs4 is boosted by the addition of elements previously considered inactive at this stage, hs1-2 and hs3. Combinations of 3' elements also strongly boost E mu at all maturation stages, but inhibitory interactions occasionally occur between E mu and incomplete 3' combinations, indicating that full transcriptional activity is mainly achieved when all 5' and 3' partners play their respective roles.