gebhart/patrepeval huggingface dataset:
Sustained and therapeutic delivery of factor IX in nude haemophilia B mice by encapsulated C2C12 myoblasts: concurrent tumourigenesis (2001)

This study reports the generation of an immunodeficient murine model for haemophilia B, obtained by breeding factor IX-deficient mice with an immunodeficient mouse strain, and use of this mouse model to evaluate the long-term efficacy and safety of a gene therapy strategy for treating haemophilia B. Nude haemophilic mice were implanted with biocompatible microcapsules enclosing recombinant myoblasts secreting human factor IX. The activated partial thromboplastin time (APTT) of plasma of mice thus treated was invariably shortened 3 weeks after microcapsule implantation, and remained shortened for at least 77 days. Shortening of the APTT of the haemophilia mice coincided with the appearance of human factor IX in mice plasmas (up to 600 ng mL(-1) on day 77), and normalization of the tail-bleeding time. Thus, the microencapsulated myoblasts reversed the clinical phenotype of haemophilia B. In contrast, plasmas of immunocompetent haemophilic mice similarly implanted with microcapsules only showed a transient shortening of APTT, and coincident transient delivery of human factor IX antigen. Rapid disappearance of human factor IX from plasmas of immunocompetent mice also coincided with production of antibodies to the human transgene. Significantly, 86% of the nude haemophilia mice developed tumours of myoblast origin. Thus, while this study revealed the feasibility of this gene therapy approach to treat severe haemophilia B, it also highlights the importance of using safer cell lines to prevent tumour development.
The effect of hemoglobin ligands on the kinetics of human hemoglobin A1c formation. (1985)

HbA1c is the most prevalent of the minor human hemoglobins. It is formed by the nonenzymatic addition of glucose to the alpha-amino group of the beta chain by an initial condensation reaction and a subsequent intermolecular Amadori rearrangement. We have developed a method of analysis which utilizes high performance liquid chromatography to follow the formation of HbA1c and greatly simplifies the determination of the kinetic parameters associated with this reaction. This has allowed us to study the effects of several Hb ligands, including the hydrogen ion, on the kinetics of this glycosylation reaction. Both the initial condensation reaction and the subsequent rearrangement are shown to exhibit acid catalysis, but the rate of the condensation step is limited by the extent of protonation of the alpha-amino group. The variation in kinetic parameters as a function of hydrogen ion concentration has allowed us to determine the probable reaction mechanism of HbA1c formation by comparison to previously reported model systems of Schiff base formation and Amadori rearrangement. The formation of pre-HbA1c from deoxy-Hb shows an increased forward rate when compared to oxy-Hb. The presence of physiologic concentrations of CO2 causes a proportional decrease in both k1 and k-1. 2,3-Diphosphoglycerate causes a significant increase in the keq of the formation reaction. The effects of CO and the substitution of L-glucose for D-glucose are not significant.
<title>Autostereoscopic display with real-image virtual screen and light filters</title> (2002)

A reality-enhanced autostereoscopic display system is presented. In this system, the viewers who do not wear any special glasses can perceive 3D images within their hands reach with little sense of incongruity. The feature of this system is combination of real image generation and parallax presentation. Real image of the display in the back is generated in the air by using Fresnel lenses, which has made it possible to narrow artificial parallax to display 3D objects in the workspace near the viewer without interfering the viewers' motion. Smaller artificial parallax leads to 3D perception with more reality and less eyestrain than the conventional 3D displays. For parallax presentation a mobile filter which plays the role of stereoscopic goggles is set between the display in the back and the Fresnel lenses and is controlled so that it follows the motion of the viewer to keep on presenting different images to each eye. To present undistorted 3D space the optical path including refraction by Fresnel lenses is calculated and the image on the screen is updated based on it. Real-time undistorted image presentation to unrestricted eye positions is realized by using texture mapping technique.
Zorba The Buddha: Capitalism, Charisma and the Cult of Bhagwan Shree Rajneesh (1996)

This essay suggests a new way of understanding the notorious Indian guru, Bhagwan Shree Rajneesh, by examining the intimate relationship between his religious teachings and his business practices. Rajneesh's ideal was in fact that of ‘Zorba the Buddha’, the perfect synthesis of the spiritual and material, the religious and capitalist impulses. After analysing and criticizing the classical Weberian concept of ‘charisma’, this paper argues that charismatic authority is by no means incompatible with bureaucratic organization or rational business practices. On the contrary, not only can charismatic authority be combined with a complex bureaucratic organization, but it can also be transformed into a kind of ‘commodity’ which is bought and sold on the consumer market. Rather than a ‘routinization of charisma’ what we find in the Rajneesh movement is a kind of ‘commodification’ and ‘commercialization’ of charisma. Bhagwan offered (and sold) his followers the promise of the same charismatic authority and divine freedom which he himself enjoyed (though, in practice, this authority could never actually be attained by any of his followers). Moreover, charismatic authority became the basis for a new kind of bureaucratic organization in Rajneesh's world-wide network of commercial enterprises—an organization characterized by a high degree of fluidity and flexibility, able to adapt itself rapidly to meet the changing demands of its consumer market.
Improved near-infrared transparency in sputtered In2O3-based transparent conductive oxide thin films by Zr-doping (2007)

Transparent conductive Zr-doped In2O3 (In2−2xZr2xO3) films were deposited on glasses by sputtering method. High mobility of over 80 cm2∕V s was achieved under a carrier density of 1.3−2.9×1020 cm−3 at Zr concentrations (x) of 0.014–0.022, and the film at x=0.022 showed the lowest resistivity of 2.6×10−4 Ω cm. Reflecting the high mobility and the low carrier density, the transparency extended from the visible to the near-infrared (NIR) wavelength region with reduced magnitude of the free-carrier absorption. The results indicate that Zr-doped In2O3 films have a performance advantage for applications that require high conductivity and transparency in NIR wavelength region.
Fine‐Line Applications of Ormet® Transient Liquid Phase Sintered Conductive Ink (1997)

In recent years, electronic devices have increasingly employed printed circuits produced using electrically conductive adhesives, commonly known as polymer thick films. This method is much more cost‐effective and efficient than other methods of wiring, including those using chemical etching or plating. In the past, the use of metal‐filled polymers as conductors in printed circuit fabrication has suffered from several limitations such as poor solderability, conductivity and adhesion. A new electrically conductive metal‐filled polymer formulation has been developed which overcomes these problems inherent in typical polymer thick film inks. This new product is based on transient liquid‐phase sintering wherein the metallic components of the formulation sinter at a relatively low temperature, resulting in a highly conductive continuous metal network. The sintering is achieved through the interaction of several metallic components with an adhesive‐flux component. The final product is highly conductive, solderable and exhibits excellent adhesion to a wide range of substrate materials. A new process for manufacturing fine‐line printed circuit boards using this ink technology is under investigation. It promises potentially simpler processing and lower cost than plating. In this new process, traces (in the form of troughs in the dielectric) are imaged using conventional photoimageable dielectrics. Exposure and developing conditions depend upon the polymer system used. The transient liquid phase sinterable conductive ink is applied to fill the photo‐exposed conductor pattern. Next, another layer of photoimageable dielectric is applied over the traces and imaged with vias for interconnections with subsequent layers. The dielectric is then cured and the ink applied to fill the vias. These steps may be repeated several times to produce low‐profile fine‐line multilayer printed circuits. This process for producing multilayer circuits using conductive inks simplifies the manufacturing of printed circuits, reduces profile, eliminates most waste in manufacturing, and reduces cost compared with plating.
Breakthrough Zygomycosis after Voriconazole Treatment in Recipients of Hematopoietic Stem-Cell Transplants (2004)

To the Editor: The Food and Drug Administration (FDA) approved voriconazole for the treatment of invasive aspergillosis partly on the basis of data published in a report in the Journal, 1 which sho...
Anaerobes and Bacterial Vaginosis in Pregnancy: Virulence Factors Contributing to Vaginal Colonisation (2014)

The aetiology and pathogenesis of bacterial vaginosis (BV) is unclear but it appears to be associated with factors that disrupt the normal acidity of the vagina thus altering the equilibrium between the normal vaginal microbiota. BV has serious implications for female morbidity, including reports of pelvic inflammatory disease, adverse pregnancy outcomes, increased susceptibility to sexually transmitted infections and infertility. This paper reviewed new available information regarding possible factors contributing to the establishment of the BV vaginal biofilm, examined the proposed role of anaerobic microbial species recently detected by new culture-independent methods and discusses developments related to the effects of BV on human pregnancy. The literature search included Pubmed (NLM), LISTA (EBSCO), and Web of Science. Because of the complexity and diversity of population groups, diagnosis and methodology used, no meta-analysis was performed. Several anaerobic microbial species previously missed in the laboratory diagnosis of BV have been revealed while taking cognisance of newly proposed theories of infection, thereby improving our understanding and knowledge of the complex aetiology and pathogenesis of BV and its perceived role in adverse pregnancy outcomes.
A 1.8–V, 6–bit, 1.3–GHz CMOS flash ADC in 0.25 µm CMOS (2002)

The design and optimization of a high-speed, low-voltage CMOS flash analog to digital converter (ADC) is presented. The optimization procedures used during the design give the needed specifications of the different building blocks. The used analog power supply is only 1.8V. The maximum sampling speed is 1.3GHz, SNDR@133kHz is 33,2dB. SNDR@500MHz is 32dB. The total power consumption of the converter at full speed is 600µW and the total active area is only 0.13 mm2. The ADC is implemented in a 0.25 µm pure digital CMOS technology.
Electrophysiology of the olfactory nerve of the pike, Esox lucius: a pilot study on optimal experimental conditions (2022)

Electrophysiological recordings in the olfactory nerve of the European pike Esox lucius were done as early as at the beginning of the 20th century, but since then, the nerve has not been extensively studied. It contains 4 to 6 millions unmyelinated sensory axons, with a relatively homogenous population of sizes, more than 95% have diameters of about 0.2 µm. The aim of our work concerned the keeping conditions under which reproducible electrophysiological responses can be obtained, and some of the electrophysiological properties of these unmyelinated sensory axons. Particular attention has been given to the dissection of the pike olfactory nerve. We have adapted the technique described by von Muralt et al. (1976) to obtain the nerves more quickly and to prolong their survival. For the latter aim, we have found that a medium, used to keep excised Xenopus oocytes for many days, kept 69% of the nerves functional for up to 3 days. The diphasic compound action potential (CAP) of the pike olfactory nerve propagated at a velocity of 12 ± 0.5 cm/s (n = 37) and was suppressed by tetrodotoxin (10 µM), known to block voltage-activated sodium channels. Nerve CAP kinetics were noticeably modified when tested after about 3 h in the medium at room temperature. However, the nerves produced consistent CAP during 30-60 min in the recording chamber in air. While preliminary, our results indicate that the olfactory nerve of the European pike, Esox lucius, by its survivability may be a suitable model for electrophysiological and pharmacological studies of unmyelinated sensory axons.
Chlorpheniramine inhibits the ornithine decarboxylase induction of Ehrlich carcinoma growing in vivo (1992)

The antihistaminic (+/-)-chlorpheniramine significantly reduced the progression of Ehrlich carcinoma when it was administered at 0.5 mg/mouse/day from the third day on, after tumour inoculation. The ODC activity of tumour cells was diminished by 70% on day 7 after tumour transplantation, when maximum ODC activity is detected in non-treated tumour growing 'in vivo'. Northern blot analyses indicated that the inhibitory effect of this 1,4-diamine takes place at a post-transcriptional level. Results obtained from serum-free cultured cells indicated that chlorpheniramine inhibits the ODC synthesis rate.
Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update (2020)

The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines.
Peptide Conjugated Phosphorodiamidate Morpholino Oligomers Increase Survival of Mice Challenged with Ames <i>Bacillus anthracis</i> (2012)

Targeting bacterial essential genes using antisense phosphorodiamidate morpholino oligomers (PMOs) represents an important strategy in the development of novel antibacterial therapeutics. PMOs are neutral DNA analogues that inhibit gene expression in a sequence-specific manner. In this study, several cationic, membrane-penetrating peptides were conjugated to PMOs (PPMOs) that target 2 bacterial essential genes: acyl carrier protein ( acpP ) and gyrase A ( gyrA ). These were tested for their ability to inhibit growth of Bacillus anthracis , a gram-positive spore-forming bacterium and causative agent of anthrax. PPMOs targeted upstream of both target gene start codons and conjugated with the bacterium-permeating peptide (RFF) 3 R were found to be most effective in inhibiting bacterial growth in vitro . Both of the gene-targeted PPMOs protected macrophages from B. anthracis induced cell death. Subsequent, in vivo testing of the PPMOs resulted in increased survival of mice challenged with the virulent Ames strain of B. anthracis . Together, these studies suggest that PPMOs targeting essential genes have the potential of being used as antisense antibiotics to treat B. anthracis infections.
Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice (2018)

Archaeosomes are liposomes traditionally comprised of total polar lipids (TPL) or semi-synthetic glycerolipids of ether-linked isoprenoid phytanyl cores with varied glyco- and amino-head groups. As adjuvants, they induce robust, long-lasting humoral and cell-mediated immune responses and enhance protection in murine models of infectious disease and cancer. Traditional total polar lipid (TPL) archaeosome formulations are relatively complex and first generation semi-synthetic archaeosomes involve many synthetic steps to arrive at the final desired glycolipid composition. We have developed a novel archaeosome formulation comprising a sulfated disaccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA) that can be more readily synthesized yet retains strong immunostimulatory activity for induction of cell-mediated immunity following systemic immunization. Herein, we have evaluated the immunostimulatory effects of SLA archaeosomes when used as adjuvant with ovalbumin (OVA) and hepatitis B surface antigen (HBsAg) and compared this to various other adjuvants including TLR3/4/9 agonists, oil-in-water and water-in-oil emulsions and aluminum hydroxide. Overall, we found that semi-synthetic sulfated glycolipid archaeosomes induce strong Ag-specific IgG titers and CD8 T cells to both antigens. In addition, they induce the expression of a number of cytokines/chemokines including IL-6, G-CSF, KC & MIP-2. SLA archaeosome formulations demonstrated strong adjuvant activity, superior to many of the other tested adjuvants.
Double exponential smoothing (2003)

We present novel algorithms for predictive tracking of user position and orientation based on double exponential smoothing. These algorithms, when compared against Kalman and extended Kalman filter-based predictors with derivative free measurement models, run approximately 135 times faster with equivalent prediction performance and simpler implementations. This paper describes these algorithms in detail along with the Kalman and extended Kalman Filter predictors tested against. In addition, we describe the details of a predictor experiment and present empirical results supporting the validity of our claims that these predictors are faster, easier to implement, and perform equivalently to the Kalman and extended Kalman filtering predictors.
Abstract 3485: Estrogen receptor ligands and their responses in de novo and tamoxifen resistant cell models (2016)

Abstract Approximately 75% of breast cancer incidences are Estrogen Receptor positive (ER+). Tamoxifen, a selective estrogen receptor modulator (SERM), is the standard of care for many of these ER+ breast cancer patients. Unfortunately, tamoxifen resistance occurs in almost 50% of patients within 5 years of treatment, and endocrine-independence accompanying resistance negates the effects of aromatase inhibitors. Paradoxically, estradiol (E2) has shown clinical efficacy in patients with resistant breast cancer. Understanding the antiproliferative role of E2 and ER signaling in resistant ER+ cell lines is essential to gain a better understanding of paradoxical clinical efficacy and for the appropriate biomarker-assisted selection of endocrine therapy for various stages of ER+ breast cancer. We have discovered ER ligands, based upon a single chemical scaffold with a diverse set of pharmacological responses, which can be used to better understand the role of ER signaling in resistance and therapy: selective ER modulators (SERMs), selective ER downregulators (SERDs), selective estrogen mimics (SEMs), and selective human ER partial agonists (ShERPAs). These compounds were initially classified using an ERE luciferase reporter assay and affinity for ER confirmed by biochemical assays. The effects of these novel ER-directed chemical probes on cell viability were further examined in multiple 2D and 3D spheroid models of tamoxifen resistance. Finally, ERα localization upon administration of these ligands in tamoxifen-sensitive and tamoxifen-resistant cells was studied. While SERDs and SEMs showed growth inhibition in tamoxifen resistant cell lines, both molecules had different responses and mechanisms of growth inhibition. ERα was localized to extranuclear sites upon administration of E2, SEMs, and ShERPAs, an observation specific to the resistant phenotype and mechanistically associated with spheroid disintegration. SERDs inhibited the antiproliferative actions of E2, but were antiproliferative in resistant cell lines. Further dissection of the role of ER in resistance and survival is needed to define the appropriate ER-directed, endocrine therapy in ER+ breast cancer. Citation Format: Lauren M. Gutgesell, Gregory R. J. Thatcher, Hitisha Patel, Rui Xiong. Estrogen receptor ligands and their responses in de novo and tamoxifen resistant cell models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3485.
Nonsteroidal Anti-Inflammatory Drugs: A Critical Review on Current Concepts Applied to Reduce Gastrointestinal Toxicity (2009)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide. Nevertheless, their intake is frequently associated with gastrointestinal side effects, representing still an important medical and socio-economic problem. In recent years efforts focused on the development of highly selective COX-2 inhibitors with an improved gastric tolerability profile. However, severe cardiovascular adverse reactions challenged the initial enthusiasm in this new class of anti-inflammatory drugs. In addition, the market withdrawals of some coxibs led to a relative reluctance in prescribing COX-2 inhibitors in clinical practice. As a consequence, the interest for alternative approaches to reduce gastrointestinal side effects associated with NSAIDs has re-emerged. There are two main components of gastric damaging properties of NSAIDs: (1) the acute toxicity associated with the short-term intake of NSAIDs, which is principally caused by local irritation of the gastric mucosa (2) the chronic toxicity resulting mainly from systemic effects associated with prolonged administration of NSAIDs. Based on that background two different approaches were pursued in the search for GI sparing NSAIDs: a) modification of classical NSAIDs by associating them with phospholipids, cyclodextrins, or chemical moieties that release gastroprotective mediators and b) defining novel targets as well as developing new compounds like dual COX/5-LO or mPGES-1 inhibitors. This review provides the first comprehensive overview of all currently applied approaches taken to improve the risk-benefit ratio of NSAIDs focusing on the structure activity relationships and the respective mechanism of action underlying the individual approaches. The insight gained in this review is useful for further research activity in this field.