gebhart/patrepeval huggingface dataset:
Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. (1989)

Thirty-seven men with symptomatic bone metastases from prostate cancer that had progressed following earlier treatment with estrogens and/or orchidectomy were treated with low-dose prednisone (7.5 to 10 mg daily). The rationale for this treatment was that some patients might still have hormone-sensitive disease that was stimulated by weak androgens of adrenal origin, and that these androgens could be suppressed by prednisone through its negative feedback on secretion of adrenocorticotrophic hormone (ACTH). Response to treatment was assessed by requirement for analgesics, by the McGill-Melzack pain questionnaire, and by a series of 17 linear analog self-assessment (LASA) scales relating to pain and to various aspects of quality of life. Fourteen patients (38%) had improvement in indices used to assess pain at 1 month after starting prednisone, and seven patients (19%) maintained this improvement for 3 to 30 months (median, 4 months). Reduction in pain was associated with improvement in other dimensions of quality of life, and in the scale for overall well-being. Prednisone treatment led to a decrease in the concentration of serum testosterone in seven of nine patients where it was not initially suppressed below 2 nmol/L, and caused a decrease in serum levels of androstenedione and dehydroepiandrosterone sulfate in more than 50% of patients. Symptomatic response was associated with a decrease in serum concentration of adrenal androgens. We conclude that (1) low-dose prednisone may cause useful relief of pain in some patients with advanced prostatic cancer; (2) relief of pain was associated with suppression of adrenal androgens; and (3) measures of pain and quality of life can be used to assess possible benefits of systemic therapy in patients with metastatic prostate cancer.
The Ultraviolet-induced Isomerization of Tiglic Acid to Angelic Acid (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Ultraviolet-induced Isomerization of Tiglic Acid to Angelic AcidS. W. Pelletier and William L. McLeishCite this: J. Am. Chem. Soc. 1952, 74, 24, 6292–6293Publication Date (Print):December 1, 1952Publication History Published online1 May 2002Published inissue 1 December 1952https://doi.org/10.1021/ja01144a518RIGHTS & PERMISSIONSArticle Views102Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (293 KB) Get e-Alerts Get e-Alerts
Microdroplets in Microfluidics: An Evolving Platform for Discoveries in Chemistry and Biology (2010)

Microdroplets in microfluidics offer a great number of opportunities in chemical and biological research. They provide a compartment in which species or reactions can be isolated, they are monodisperse and therefore suitable for quantitative studies, they offer the possibility to work with extremely small volumes, single cells, or single molecules, and are suitable for high-throughput experiments. The aim of this Review is to show the importance of these features in enabling new experiments in biology and chemistry. The recent advances in device fabrication are highlighted as are the remaining technological challenges. Examples are presented to show how compartmentalization, monodispersity, single-molecule sensitivity, and high throughput have been exploited in experiments that would have been extremely difficult outside the microfluidics platform.
ARMMs as a versatile platform for intracellular delivery of macromolecules (2018)

Majority of disease-modifying therapeutic targets are restricted to the intracellular space and are therefore not druggable using existing biologic modalities. The ability to efficiently deliver macromolecules inside target cells or tissues would greatly expand the current landscape of therapeutic targets for future generations of biologic drugs, but remains challenging. Here we report the use of extracellular vesicles, known as arrestin domain containing protein 1 [ARRDC1]-mediated microvesicles (ARMMs), for packaging and intracellular delivery of a myriad of macromolecules, including the tumor suppressor p53 protein, RNAs, and the genome-editing CRISPR-Cas9/guide RNA complex. We demonstrate selective recruitment of these macromolecules into ARMMs. When delivered intracellularly via ARMMs, these macromolecules are biologically active in recipient cells. P53 delivered via ARMMs induces DNA damage-dependent apoptosis in multiple tissues in mice. Together, our results provide proof-of-principle demonstration that ARMMs represent a highly versatile platform for packaging and intracellular delivery of therapeutic macromolecules.
Mixing in the shear superposition micromixer: three-dimensional analysis (2004)

In this paper, we analyse mixing in an active chaotic advection micromixer. The micromixer consists of a main rectangular channel and three cross-stream secondary channels that provide ability for time-dependent actuation of the flow stream in the direction orthogonal to the main stream. Three-dimensional motion in the mixer is studied. Numerical simulations and modelling of the flow are pursued in order to understand the experiments. It is shown that for some values of parameters a simple model can be derived that clearly represents the flow nature. Particle image velocimetry measurements of the flow are compared with numerical simulations and the analytical model. A measure for mixing, the mixing variance coefficient (MVC), is analysed. It is shown that mixing is substantially improved with multiple side channels with oscillatory flows, whose frequencies are increasing downstream. The optimization of MVC results for single side-channel mixing is presented. It is shown that dependence of MVC on frequency is not monotone, and a local minimum is found. Residence time distributions derived from the analytical model are analysed. It is shown that, while the average Lagrangian velocity profile is flattened over the steady flow, Taylor-dispersion effects are still present for the current micromixer configuration.
Total Synthesis of Epothilone A: The Olefin Metathesis Approach (1997)

A flexible alterative route to the total synthesis of the antitumor agent epothilone A (1, see below) has been achieved by a highly convergent strategy involving olefin metathesis as a key step. The strategy may allow the chemical synthesis of a library of designed epothilones for biological screening.
CD4+FoxP3+ regulatory T cells confer infectious tolerance in a TGF-β–dependent manner (2008)

CD4+FoxP3+ regulatory T (T reg) cells comprise a separate lineage of T cells that are essential for maintaining immunological tolerance to self. The molecular mechanism(s) by which T reg cells mediate their suppressive effects remains poorly understood. One molecule that has been extensively studied in T reg cell suppression is transforming growth factor (TGF)-β, but its importance remains controversial. We found that TGF-β complexed to latency-associated peptide (LAP) is expressed on the cell surface of activated but not resting T reg cells. T reg cell LAP–TGF-β plays an important role in the suppression of the proliferation of activated T cells, but it is not required for the suppression of naive T cell activation. More importantly, T reg cell–derived TGF-β could generate de novo CD4+FoxP3+ T cells in vitro from naive precursors in a cell contact–dependent, antigen-presenting cell–independent and αV integrin–independent manner. The newly induced CD4+FoxP3+ T cells are suppressive both in vitro and in vivo. Transfer of activated antigen-specific T reg cells with naive antigen-specific responder T cells to normal recipients, followed by immunization, also results in induction of FoxP3 expression in the responder cells. T reg cell–mediated generation of functional CD4+FoxP3+ cells via this TGF-β–dependent pathway may represent a major mechanism as to how T reg cells maintain tolerance and expand their suppressive abilities.
Role of P-Glycoprotein and Cytochrome P450 3A in Limiting Oral Absorption of Peptides and Peptidomimetics† (1998)

Cytochrome P450 3A4 (CYP3A4), the major phase I drug metabolizing enzyme in humans, and the MDR1 gene product P-glycoprotein (P-gp) are present at high concentrations in villus tip enterocytes of the small intestine and share a significant overlap in substrate specificity. A large body of research both in vitro and in vivo has established metabolism by intestinal CYP3A4 as a major determinant of the systemic bioavailability of orally administered drugs. More recently it has been recognized that drug extrusion by intestinal P-gp can both reduce drug absorption and modulate the effects of inhibitors and inducers of CYP3A-mediated metabolism. There is relatively little data regarding the effects of CYP3A and P-gp on peptide drugs; however, studies with the cyclic peptide immunosuppresant cyclosporine as well as peptidomimetics such as the HIV-protease inhibitor saquinavir (Invirase) and a new cysteine protease inhibitor K02 (Morpholine-Urea-Phe-Hphe-Vinyl sulfone; Axys Pharmaceuticals) provide some insight into the impact of these systems on the oral absorption of peptides.
ART-EMAP: A neural network architecture for object recognition by evidence accumulation (1995)

A new neural network architecture is introduced for the recognition of pattern classes after supervised and unsupervised learning. Applications include spatio-temporal image understanding and prediction and 3D object recognition from a series of ambiguous 2D views. The architecture, called ART-EMAP, achieves a synthesis of adaptive resonance theory (ART) and spatial and temporal evidence integration for dynamic predictive mapping (EMAP). ART-EMAP extends the capabilities of fuzzy ARTMAP in four incremental stages. Stage 1 introduces distributed pattern representation at a view category field. Stage 2 adds a decision criterion to the mapping between view and object categories, delaying identification of ambiguous objects when faced with a low confidence prediction. Stage 3 augments the system with a field where evidence accumulates in medium-term memory. Stage 4 adds an unsupervised learning process to fine-tune performance after the limited initial period of supervised network training. Each ART-EMAP stage is illustrated with a benchmark simulation example, using both noisy and noise-free data.
Jet thrust vectoring using a miniature fluidic oscillator (2005)

Abstract This paper presents a new approach to vectoring jet thrust using a miniature fluidic actuator that provided spatially distributed mass addition. The fluidic actuators used had no moving parts and produced oscillatory flow with a square wave form at frequencies up to 1·6kHz. A subsonic jet with an exit diameter of 3·81cm was controlled using single and dual fluidic actuators, each with an equivalent circular diameter of 1·06mm. The fluidic nozzle was operated at pressures between 20·68 and 165·47kPa. The objectives of the present work included documentation of the actuation characteristics of fluidic devices, assessment of the effectiveness of fluidic devices for jet thrust vectoring, and evaluation of mass flow requirements for vectoring under various conditions. Measurements were made in the flow field using a pitot probe for the vectored and unvectored cases. Some acoustic measurements were made using microphones in the near-field and for selected cases particle image velocimetry (PIV) measurements were made. Thrust vectoring was obtained in low speed jets by momentum effects with fluidic device mass flow rates of only 2 × 10 –4 kg/sec (0·6% of main jet mass flow per fluidic oscillator). Although a single fluidic device produced vectoring of the primary jet, the dual fluidic device configuration (with two fluidic devices on either side of the jet exit) produced mass flux enhancement of 28% with no vectoring. Our results indicate that fluidic actuators have the potential for use in thrust vectoring, flow mixing and industrial flow deflection applications.
Detection by monoclonal antibody of carbohydrate antigen CA 50 in serum of patients with carcinoma. (1984)

A solid phase radioimmunoassay was devised for measuring the value of the carcinoma associated carbohydrate antigen CA 50 in serum based on the use of a specific monoclonal antibody (C 50). Samples of serum from 259 patients with carcinoma, 114 patients with other malignancies or inflammatory diseases, and 150 healthy controls were examined. Serum values of CA 50 exceeding the mean plus three standard deviations for control samples from blood donors were found in a high proportion of patients with colorectal adenocarcinomas (50% of those with early, localised tumours and 75% of advanced cases), other gastrointestinal carcinomas (69%), uterine cancer (75% of those with corporeal and 88% of those with cervical cancer), prostatic cancer (90%), lung cancer (52%), and breast, ovarian, kidney, and urinary bladder carcinoma (26-67%). The CA 50 values in samples from patients with inflammatory diseases, including ulcerative colitis, with rare exceptions (0-7%) were within the normal range, as were those in patients with various sarcomas and malignant melanoma. Measuring serum values of CA 50, which is evidently a generalised carcinoma associated antigen, may be useful in clinical research studies of the diagnosis, management, and prognosis of patients with different types of carcinoma.
New control strategies for neuroprosthetic systems. (1996)

The availability of techniques to artificially excite paralyzed muscles opens enormous potential for restoring both upper and lower extremity movements with neuroprostheses. Neuroprostheses must stimulate muscle, and control and regulate the artificial movements produced. Control methods to accomplish these tasks include feedforward (open-loop), feedback, and adaptive control. Feedforward control requires a great deal of information about the biomechanical behavior of the limb. For the upper extremity, an artificial motor program was developed to provide such movement program input to a neuroprosthesis. In lower extremity control, one group achieved their best results by attempting to meet naturally perceived gait objectives rather than to follow an exact joint angle trajectory. Adaptive feedforward control, as implemented in the cycle-to-cycle controller, gave good compensation for the gradual decrease in performance observed with open-loop control. A neural network controller was able to control its system to customize stimulation parameters in order to generate a desired output trajectory in a given individual and to maintain tracking performance in the presence of muscle fatigue. The authors believe that practical FNS control systems must exhibit many of these features of neurophysiological systems.
Measures of emotion: A review (2009)

A consensual, componential model of emotions conceptualises them as experiential, physiological, and behavioural responses to personally meaningful stimuli. The present review examines this model in terms of whether different types of emotion-evocative stimuli are associated with discrete and invariant patterns of responding in each response system, how such responses are structured, and if such responses converge across different response systems. Across response systems, the bulk of the available evidence favours the idea that measures of emotional responding reflect dimensions rather than discrete states. In addition, experiential, physiological, and behavioural response systems are associated with unique sources of variance, which in turn limits the magnitude of convergence across measures. Accordingly, the authors suggest that there is no "gold standard" measure of emotional responding. Rather, experiential, physiological, and behavioural measures are all relevant to understanding emotion and cannot be assumed to be interchangeable.
OX40 Ligand Regulates Inflammation and Mortality in the Innate Immune Response to Sepsis (2010)

The initial phase of sepsis is characterized by massive inflammatory cytokine production that contributes to multisystem organ failure and death. Costimulatory molecules are a class of receptors capable of regulating cytokine production in adaptive immunity. Recent studies described their presence on neutrophils and monocytes, suggesting a potential role in the regulation of cytokine production in innate immunity. The purpose of this study was to determine the role for OX40-OX40 ligand (OX40L) interaction in the innate immune response to polymicrobial sepsis. Humans with sepsis demonstrated upregulation of OX40L on monocytes and neutrophils, with mortality and intensive care unit stay correlating with expression levels. In an animal model of polymicrobial sepsis, a direct role for OX40L in regulating inflammation was indicated by improved survival, decreased cytokine production, and a decrease in remote organ damage in OX40L(-/-) mice. The finding of similar results with an OX40L Ab suggests a potential therapeutic role for OX40L blockade in sepsis. The inability of anti-OX40L to provide significant protection in macrophage-depleted mice establishes macrophages as an indispensable cell type within the OX40/OX40L axis that helps to mediate the clinical signs of disease in sepsis. Conversely, the protective effect of anti-OX40L Ab in RAG1(-/-) mice further confirms a T cell-independent role for OX40L stimulation in sepsis. In conclusion, our data provide an in vivo role for the OX40/OX40L system in the innate immune response during polymicrobial sepsis and suggests a potential beneficial role for therapeutic blockade of OX40L in this devastating disorder.
Golden Angle Modulation: Approaching the AWGN Capacity (2018)

In this work, targeting, e.g., future generation cellular, microwave-links, or optical fiber systems, we propose a new geometric shaping design for golden angle modulation (GAM) based on a (double) truncated Gaussian input distribution. The design improves the mutual information (MI), and the peak-to-average power ratio, over the full signal-to-noise ratio (SNR) range relative to two key GAM schemes introduced in [1],[2]. Inspired by the proposed geometric shaping, a simpler, SNR-dependent, design is also suggested. The performance is numerically evaluated with respect to MI and compared with classical modulation schemes. With the proposed design, the SNR can be decreased relative to classical quadrature amplitude modulation, even for relatively modest target spectral efficiencies. As the GAM design can approach the Gaussian channel capacity, the power/energy efficiency is expected to improve.
Signal transduction by steroid hormones: nuclear localization is differentially regulated in estrogen and glucocorticoid receptors. (1990)

The glucocorticoid receptor accumulates in nuclei only in the presence of bound hormone, whereas the estrogen receptor has been reported to be constitutively nuclear. To investigate this distinction, we compared the nuclear localization domains of the two receptors and the capacity of their respective hormone-binding regions to regulate nuclear localization activity. As with the glucocorticoid receptor, we showed that the human estrogen receptor contained a nuclear localization signal between the DNA-binding and hormone-binding regions (amino acids 256-303); however, in contrast to the glucocorticoid receptor, the estrogen receptor lacked a second nuclear localization domain within the hormone-binding region. Moreover, the hormone-binding domain of the unliganded estrogen receptor failed to regulate nuclear localization signals, although it efficiently regulated other receptor functions. We conclude that the two receptors employ a common mechanism for signal transduction involving a novel "inactivation" function, but that they differ in their control of nuclear localization. Thus, despite the strong relatedness of the estrogen and glucocorticoid receptors in structure and activity, certain differences in their properties could have important functional implications.
Insulin-like growth factors (IGF-I, free IGF-I, and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, IGFBP-3, IGFBP-6, and ALS) in blood circulation (1999)

Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) play an important role in cell growth and differentiation. Clinical and epidemiological studies have indicated that measuring IGFs and IGFBPs in blood has potential implications in assessing growth-related abnormalities and risks of certain types of cancer. To facilitate the application, we reported a large collection of reference ranges of IGFs and IGFBPs in normal population and evaluations of these molecules in serum and plasma as well as the impact of freeze-thaw cycles on the measurement. IGF-I, IGFBP-3 andALS showed a similar pattern of change associated with age. Levels of these molecules were low at birth and increased with age through puberty. After puberty the levels declined slowly with age. Overall, IGF-I, IGFBP-3 and ALS were slightly higher in females than in males. Free IGF-I accounted for about 1% of the total IGF-I and its variation with age was similar to total IGF-I. IGF-II levels were also increased with age from birth to puberty, but became stable after puberty. There was little difference in IGF-II levels between genders. IGFBP-2 levels declined with age from birth to puberty. Levels of IGFBP-6 in contrast were increased with age. These IGF binding proteins were higher in males than in females. IGFs, IGFBP-3 and ALS were 5-10% higher in serum than in plasma. IGFBP-2 and IGFBP-6 differed substantially between serum and plasma. Freeze-thaw treatment up to five cycles had little impact on plasma levels of IGFs and IGFBP-3. Our observations suggest that levels of IGFs and their binding proteins are varied with age, gender, and types of specimen and that these variations need to be taken into consideration when IGFs and their binding proteins are utilized in clinic and research.