gebhart/patrepeval huggingface dataset:
Technosphere ™ /Insulin—A New Approach for Effective Delivery of Human Insulin Via the Pulmonary Route (2002)

The development of pulmonary insulin formulation offers an attractive alternative to the current requirement of repeated subcutaneous (s.c.) injections for insulin administration. Technosphere/Insulin is a formulation of regular human insulin that was designed to produce an efficient transport of insulin across the respiratory epithelium into the systemic circulation. Several studies using the euglycemic clamp technique were performed in healthy volunteers and patients with Type 2 diabetes to assess the pharmacokinetic and pharmacodynamic properties of Technosphere/Insulin. The investigations revealed a very rapid systemic insulin uptake (insulin T(max) approximately 12-14 min), a fast onset of action (maximum activity approximately 20-30 min), and a short duration of action (approximately 2-3 h) in healthy volunteers and in patients with Type 2 diabetes. In the first study, employing a commercially available inhaler, the relative bioavailability (compared with s.c. injections) was initially reported to be 26% for the first 3 h and 16% for the entire observation period of 6 h. With the development of a specific inhaler adapted to the physical properties of Technosphere/Insulin, the MedTone Inhaler, relative bioavailability was 50% for the first 3 h and 30% over the entire 6-h period. A clear linearity of systemic insulin uptake was observed in a study employing 12 healthy volunteers inhaling doses of 25, 50, and 100 IU. Repeated inhalation of 100 IU of Technosphere/Insulin by 12 patients with Type 2 diabetes revealed a lower variability in comparison with published s.c. injection data from healthy volunteers. This new Technosphere/Insulin formulation was well tolerated, and no serious adverse events were reported in any of the investigations. Given its attractive time-action profile, Technosphere/Insulin may become a suitable alternative to s.c. injection for prandial insulin delivery, especially in patients with Type 2 diabetes, if the long-term safety, tolerability, and efficacy of this pulmonary insulin are established and confirmed in future studies.
Fluorescent and Photochemical Probes of Dynamic Biochemical Signals inside Living Cells (1993)

A particularly popular and powerful use of fluorescent indicators is nondestructive monitoring of the activity or free concentration of important ions or messengers such as Ca2+, H+, Na+, Mg2+, Cl-, or cyclic adenosine 3′,5′-monophosphate (cAMP) inside living cells and tissues. Successful indicators and chelators must fulfill many biological criteria in addition to the chemically obvious ones of sensitivity and specificity. Four examples will be discussed here. A family of Ca2+ indicators is derived from the versatile Ca2+-chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid by extension into rigidized stilbenes or linkage to xanthene fluorophores. To show whether complex Ca2+ signals are sufficient or necessary for biological functions, photolabile chelators are valuable because flash photolysis can suddenly and cleanly release or sequester the analyte. The only fluorescent indicator for Na+ so far demonstrated to work intracellularly is "SBFI", a diaza-15-crown-5 with additional liganding methoxyls attached to fluorophores on the nitrogens. An indicator for cAMP is prepared by labeling the regulatory and catalytic subunits of cAMP-dependent protein kinase such that binding of cAMP and dissociation of the subunits is sensed by loss of fluorescence energy transfer. This protein-based indicator shows that fluorescence chemosensors can measure analytes larger and more complex than simple inorganic ions and that techniques of molecular biology and protein engineering may offer exciting new possibilities in this field.
On-state distortion in high electron mobility transistor microwave and RF switch control circuits (2000)

The origin of the distortion generating mechanism in microwave and RF control circuits using high electron-mobility transistors (HEMTs) is presented in this paper. A model is presented for predicting the distortion in series-connected HEMT switches. The theoretical discussion shows that turn-off voltages in the range of 1.0-1.5 V provide the lowest distortion in series switch configurations. A comparison of the HEMT snitch with MESFET switches shows that the HEMT switch generates more distortion than its MESFET counterpart. In addition, the frequency response of HEMT switches is the opposite of the MESFET switch, with less distortion at low frequencies. The model is validated with experimental data taken on a AlGaAs/GaAs HEMT in the series switch configuration.
Fluorescent Protein Based FRET Pairs with Improved Dynamic Range for Fluorescence Lifetime Measurements (2015)

Fluorescence Resonance Energy Transfer (FRET) using fluorescent protein variants is widely used to study biochemical processes in living cells. FRET detection by fluorescence lifetime measurements is the most direct and robust method to measure FRET. The traditional cyan-yellow fluorescent protein based FRET pairs are getting replaced by green-red fluorescent protein variants. The green-red pair enables excitation at a longer wavelength which reduces cellular autofluorescence and phototoxicity while monitoring FRET. Despite the advances in FRET based sensors, the low FRET efficiency and dynamic range still complicates their use in cell biology and high throughput screening. In this paper, we utilized the higher lifetime of NowGFP and screened red fluorescent protein variants to develop FRET pairs with high dynamic range and FRET efficiency. The FRET variations were analyzed by proteolytic activity and detected by steady-state and time-resolved measurements. Based on the results, NowGFP-tdTomato and NowGFP-mRuby2 have shown high potentials as FRET pairs with large fluorescence lifetime dynamic range. The in vitro measurements revealed that the NowGFP-tdTomato has the highest Förster radius for any fluorescent protein based FRET pairs yet used in biological studies. The developed FRET pairs will be useful for designing FRET based sensors and studies employing Fluorescence Lifetime Imaging Microscopy (FLIM).
Temperature‐Enhanced Solvent Vapor Annealing of a C3 Symmetric Hexa‐peri‐Hexabenzocoronene: Controlling the Self‐Assembly from Nano‐ to Macroscale (2009)

Temperature-enhanced solvent vapor annealing (TESVA) is used to self-assemble functionalized polycyclic aromatic hydrocarbon molecules into ordered macroscopic layers and crystals on solid surfaces. A novel C3 symmetric hexa-peri-hexabenzocoronene functionalized with alternating hydrophilic and hydrophobic side chains is used as a model system since its multivalent character can be expected to offer unique self-assembly properties and behavior in different solvents. TESVA promotes the molecule's long-range mobility, as proven by their diffusion on a Si/SiO(x) surface on a scale of hundreds of micrometers. This leads to self-assembly into large, ordered crystals featuring an edge-on columnar type of arrangement, which differs from the morphologies obtained using conventional solution-processing methods such as spin-coating or drop-casting. The temperature modulation in the TESVA makes it possible to achieve an additional control over the role of hydrodynamic forces in the self-assembly at surfaces, leading to a macroscopic self-healing within the adsorbed film notably improved as compared to conventional solvent vapor annealing. This surface re-organization can be monitored in real time by optical and atomic force microscopy.
An Integrated Cloud-based Healthcare Infrastructure (2011)

We present a cloud-based healthcare system that integrates a formal care system (DACAR) with an informal care system (Microsoft Health Vault). The system provides high levels of security and privacy within a cloud environment, enabling sharing of both health records and the access rights, along the patient pathway. We also define a case study that can help in evaluating and in demonstrating the usefulness of a cloud-based integrated health care system.
Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis (2014)

Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator-related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator-related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25-30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of 'occult' mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow-up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.
Lightweight People Counting and Localizing for Easily Deployable Indoors WSNs (2008)

We describe a lightweight method for counting and localizing people using camera sensor networks. The algorithm makes use of a motion histogram to detect people based on motion and size criteria. The motion histogram is an averaged shifted histogram that estimates the distribution of people in a room given the above-threshold pixels in a frame-differenced ldquomotionrdquo image. The algorithm provides good detection rates at low computational complexity. In this paper, we describe the details of our design and experimentally determine suitable parameters for the proposed histogram. The resulting histogram and counting algorithm are implemented and tested on a network of iMote2 sensor nodes. Our implementation on sensor nodes uses a custom sensor board with a commercial off-the-shelf camera, but the motion histogram is designed to easily adapt to ultralow-power address-event motion imagers.
Single copies of HIV proviral DNA detected by fluorescent in situ hybridization. (1990)

A fluorescent in situ DNA hybridization assay employing a biotinylated DNA probe was used to visualize single copies of human immunodeficiency virus (HIV) proviral DNA in the nuclei and metaphase chromosomes of infected cells. In clonal cell lines that contain either one or two copies of proviral DNA, the efficiency of detection of individual loci of proviral DNA was 57% to 78%. Only 1% of uninfected control cells exhibited a false-positive signal. HIV proviral DNA could be accurately identified in mixed populations comprised of only 5% infected cells. Thus, this assay could be used to identify cells that harbor HIV proviral DNA and to monitor the status of proviral DNA throughout the course of HIV infection.
The BioC O-Methyltransferase Catalyzes Methyl Esterification of Malonyl-Acyl Carrier Protein, an Essential Step in Biotin Synthesis (2012)

Recent work implicated the Escherichia coli BioC protein as the initiator of the synthetic pathway that forms the pimeloyl moiety of biotin (Lin, S., Hanson, R. E., and Cronan, J. E. (2010) Nat. Chem. Biol. 6, 682-688). BioC was believed to be an O-methyltransferase that methylated the free carboxyl of either malonyl-CoA or malonyl-acyl carrier protein based on the ability of O-methylated (but not unmethylated) precursors to bypass the BioC requirement for biotin synthesis both in vivo and in vitro. However, only indirect proof of the hypothesized enzymatic activity was obtained because the activities of the available BioC preparations were too low for direct enzymatic assay. Because E. coli BioC protein was extremely recalcitrant to purification in an active form, BioC homologues of other bacteria were tested. We report that the native form of Bacillus cereus ATCC10987 BioC functionally replaced E. coli BioC in vivo, and the protein could be expressed in soluble form and purified to homogeneity. In disagreement with prior scenarios that favored malonyl-CoA as the methyl acceptor, malonyl-acyl carrier protein was a far better acceptor of methyl groups from S-adenosyl-L-methionine than was malonyl-CoA. BioC was specific for the malonyl moiety and was inhibited by S-adenosyl-L-homocysteine and sinefungin. High level expression of B. cereus BioC in E. coli blocked cell growth and fatty acid synthesis.
A Simple Mesh Generator in MATLAB (2004)

Creating a mesh is the first step in a wide range of applications, including scientific computing and computer graphics. An unstructured simplex mesh requires a choice of meshpoints (vertex nodes) and a triangulation. We want to offer a short and simple MATLAB code, described in more detail than usual, so the reader can experiment (and add to the code) knowing the underlying principles. We find the node locations by solving for equilibrium in a truss structure (using piecewise linear force-displacement relations) and reset the topology by the Delaunay algorithm. The geometry is described implicitly by its distance function. In addition to being much shorter and simpler than other meshing techniques, our algorithm typically produces meshes of very high quality. We discuss ways to improve the robustness and the performance, but our aim here is simplicity. Readers can download (and edit) the codes from http://math.mit.edu/~persson/mesh.
AbsCN-seq: a statistical method to estimate tumor purity, ploidy and absolute copy numbers from next-generation sequencing data (2014)

The R package absCNseq is available from http://biostats.mcc.ucsd.edu/files/absCNseq_1.0.tar.gz CONTACT: kmesser@ucsd.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Toward a breast cancer vaccine: work in progress. (2003)

Advances in biotechnology and basic immunology have converged to create an unprecedented opportunity to use vaccines to harness the power of the immune system in the fight against breast cancer. Cancer vaccines have several therapeutic advantages over more traditional breast cancer treatment modalities. First, targeting the antitumor immune response to critical tumor-specific antigens defines a therapy with exquisite specificity and minimal toxicity. Second, immune-mediated tumor destruction occurs by mechanisms distinct from those underlying the efficacy of chemotherapy and hormone therapy. Thus, immunotherapy offers an approach to circumventing the intrinsic drug resistance that currently underlies therapeutic failure. Third, the phenomenon of immunologic memory endows immunotherapy with the potential for creating a durable therapeutic effect that is reactivated at the onset of disease relapse. Moreover, immunologic memory also underlies the potential future use of vaccines for the prevention of breast cancer. Early clinical trials have highlighted the promise of breast cancer vaccines, and have further defined the challenges facing translational scientists and clinical investigators. The judicious application of laboratory advances to clinical trial design should facilitate the development of immunotherapy as an additional major therapeutic modality for breast cancer, with the potential for breast cancer prevention as well as treatment.
Expression of the rat growth hormone-releasing hormone gene in placenta is directed by an alternative promoter. (1991)

Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that plays a critical role in controlling the synthesis and secretion of growth hormone by the anterior pituitary. GHRH has also been detected in other nonneural extrahypothalamic tissues, including rat placenta, although its role in the hormonal control of pregnancy and/or fetal development has not yet been defined. Here we present the isolation and characterization of cDNA clones corresponding to rat placental GHRH. The placental GHRH mRNA codes for a pre-pro-GHRH identical to that found in the hypothalamus, suggesting that the mature placental GHRH is identical to its hypothalamic counterpart. Nevertheless, the placental and the hypothalamic GHRH mRNAs differ in the region corresponding to the untranslated exon 1 because of the use of an alternative promoter in the placenta located 10 kilobases upstream from the hypothalamic promoter. A combined mechanism involving the use of tissue-specific alternative promoters and the differential splicing of exon 1 generates the mature GHRH transcript in placenta and hypothalamus. Multiple transcription initiation sites have been found in the placental GHRH mRNA, which correlates to the lack of a consensus TATA box in the promoter region.
A benchmark for comparison of cell tracking algorithms (2014)

The challenge Web site (http://www.codesolorzano.com/celltrackingchallenge) provides access to the training and competition datasets, along with the ground truth of the training videos. It also provides access to Windows and Linux executable files of the evaluation software and most of the algorithms that competed in the challenge.
Application of a laser heterodyne technique to characterize surface acoustic waves generated via a pulsed laser excitation (2014)

A CW laser heterodyne spectrometer has been assembled with time resolved data acquisition for probing surface acoustic waves (SAWs) generated by the interaction of a pulsed laser and surface. Literature suggests that SAWs can enhance chemical catalysis, nucleation and surface chemical mobility. Pulsed lasers are known to induce SAWs with bandwidth that is inversely proportional to the pulse width. The goal of this experiment is to apply laser heterodyne spectroscopy to understand the photophysical interactions that promote the formation of laser induced SAWs. The experiment explores the effects produced by a 100 Hz repetition rate UV (355nm) laser with a 6 ns pulse width. Silicon (111) is used as the substrate material, making it is less likely for propagating non linear waves to experience anisotropy. The development of the time-resolved heterodyne spectrometer includes the development of specific data acquisition and software analysis tools to monitor sub-nanometer surface displacements. In addition, to insure that the pulsed laser irradiated material remains within the thermoelastic regime as opposed to ablation, a 2D laser thermal heating model is used to define the duty cycle of the repetitive pulsed laser. Results show that it is possible to measure and analyze laser induced SAWs many centimeters away from the source and substrate dispersion affects the spectral properties of the propagating SAWs. Under controlled conditions, we have measured surface vertical displacements approaching 0.1nm.
Midair Ultrasound Fragrance Rendering (2018)

We propose a system that controls the spatial distribution of odors in an environment by generating electronically steerable ultrasound-driven narrow air flows. The proposed system is designed not only to remotely present a preset fragrance to a user, but also to provide applications that would be conventionally inconceivable, such as: 1) fetching the odor of a generic object placed at a location remote from the user and guiding it to his or her nostrils, or 2) nullifying the odor of an object near a user by carrying it away before it reaches his or her nostrils (Fig. 1). These are all accomplished with an ultrasound-driven air stream serving as an airborne carrier of fragrant substances. The flow originates from a point in midair located away from the ultrasound source and travels while accelerating and maintaining its narrow cross-sectional area. These properties differentiate the flow from conventional jet- or fan-driven flows and contribute to achieving a midair flow. In our system, we employed a phased array of ultrasound transducers so that the traveling direction of the flow could be electronically and instantaneously controlled. In this paper, we describe the physical principle of odor control, the system construction, and experiments conducted to evaluate remote fragrance presentation and fragrance tracking.
Mechanism of enhancement of DNA expression consequent to cointernalization of a replication-deficient adenovirus and unmodified plasmid DNA (1994)

Given the knowledge that replication-deficient adenoviruses can mediate the delivery of unlinked plasmid DNA into eukaryotic cells (K. Yoshimura, M. A. Rosenfeld, P. Seth, and R. G. Crystal, J. Biol. Chem. 268:2300-2303, 1993), this study focuses on the role of receptor-mediated endocytosis in this process. AdCFTR (an E1- E3- adenovirus type 5-based replication-deficient adenovirus containing the 4.5-kb human cystic fibrosis transmembrane conductance regulator cDNA) was added to Cos-7 cells together with plasmid pRSVL (containing the Rous sarcoma virus long terminal repeat promoter followed by the luciferase cDNA), and luciferase activity was quantified as a measure of the expression of the plasmid DNA. When AdCFTR was bound to Cos-7 cells at 4 degrees C and the cells were subsequently incubated at 37 degrees C in the presence of pRSVL, the expression of luciferase activity was increased in proportion to the amount of AdCFTR added, reaching > 10(4)-fold at 3,000 PFU per cell. AdCFTR-mediated increase in pRSVL was inhibited by addition of purified adenovirus fiber but not hexon, suggesting cell surface adenovirus receptors were involved in the cointernalization process. Cell lines with a high number of adenovirus receptors (Cos-7 and HeLa) showed significant AdCFTR-dependent pRSVL expression, while cell lines with low numbers of adenovirus receptors (NIH 3T3 and U-937) showed little. AdCFTR-mediated increase in the expression of pRSVL was prevented when AdCFTR was heat treated and exposed to antibody against adenovirus or when the cointernalization process was evaluated in the presence of chloroquine, conditions all known to prevent adenovirus-mediated disruption of endocytic vesicles. In contrast, the uptake of AdCFTR into Cos-7 cells was not affected by any of these conditions. When AdCFTR was exposed to UV light, its ability to grow in 293 cells was obviated, but AdCFTR-dependent increase in pRSVL expression was minimally reduced. Finally, empty capsids of AdCFTR were able to enhance the delivery and expression of plasmid pRSVL into Cos-7 cells, suggesting that the adenovirus genome is not required for AdCFTR-mediated plasmid cointernalization. Together, these observations suggest that the ability of a replication-deficient recombinantly adenovirus to mediate the cointernalization and expression of plasmids is mediated by the receptor-mediated endocytosis pathway.