gebhart/patrepeval huggingface dataset:
Towards a Frequentist Theory of Upper and Lower Probability (1982)

We present elements of a frequentist theory of statistics for concepts of upper and lower (interval-valued) probability (IVP), defined on finite event algebras. We consider IID models for unlinked repetitions of experiments described by IVP and suggest several generalizations of standard notions of independence, asymptotic certainty and estimability. Instability of relative freqencies is favoured under our IID models. Moreover, generalizations of Bernoulli's Theorem give some justification for the estimation of an underlying IVP mechanism from fluctuations of relative frequencies. Our results indicate that an objectivist, frequency- or propensity-oriented, view of probability does not necessitate an additive probability concept, and that IVP models can represent a type of indeterminacy not captured by additive probability.
Hydrodynamic metamaterials: Microfabricated arrays to steer, refract, and focus streams of biomaterials (2008)

We show that it is possible to direct particles entrained in a fluid along trajectories much like rays of light in classical optics. A microstructured, asymmetric post array forms the core hydrodynamic element and is used as a building block to construct microfluidic metamaterials and to demonstrate refractive, focusing, and dispersive pathways for flowing beads and cells. The core element is based on the concept of deterministic lateral displacement where particles choose different paths through the asymmetric array based on their size: Particles larger than a critical size are displaced laterally at each row by a post and move along the asymmetric axis at an angle to the flow, while smaller particles move along streamline paths. We create compound elements with complex particle handling modes by tiling this core element using multiple transformation operations; we show that particle trajectories can be bent at an interface between two elements and that particles can be focused into hydrodynamic jets by using a single inlet port. Although particles propagate through these elements in a way that strongly resembles light rays propagating through optical elements, there are unique differences in the paths of our particles as compared with photons. The unusual aspects of these modular, microfluidic metamaterials form a rich design toolkit for mixing, separating, and analyzing cells and functional beads on-chip.
Human Macrophage–derived Chemokine (MDC), a Novel Chemoattractant for Monocytes, Monocyte-derived Dendritic Cells, and Natural Killer Cells (1997)

A cDNA encoding a novel human chemokine was isolated by random sequencing of cDNA clones from human monocyte-derived macrophages. This protein has been termed macrophage-derived chemokine (MDC) because it appears to be synthesized specifically by cells of the macrophage lineage. MDC has the four-cysteine motif and other highly conserved residues characteristic of CC chemokines, but it shares <35% identity with any of the known chemokines. Recombinant MDC was expressed in Chinese hamster ovary cells and purified by heparin-Sepharose chromatography. NH2-terminal sequencing and mass spectrophotometry were used to verify the NH2 terminus and molecular mass of recombinant MDC (8,081 dalton). In microchamber migration assays, monocyte-derived dendritic cells and IL-2-activated natural killer cells migrated to MDC in a dose-dependent manner, with a maximal chemotactic response at 1 ng/ml. Freshly isolated monocytes also migrated toward MDC, but with a peak response at 100 ng/ml MDC. Northern analyses indicated MDC is highly expressed in macrophages and in monocyte-derived dendritic cells, but not in monocytes, natural killer cells, or several cell lines of epithelial, endothelial, or fibroblast origin. High expression was also detected in normal thymus and less expression in lung and spleen. Unlike most other CC chemokines, MDC is encoded on human chromosome 16. MDC is thus a unique member of the CC chemokine family that may play a fundamental role in the function of dendritic cells, natural killer cells, and monocytes.
Characterization and Binding Specificity of the Monomeric STAT3-SH2 Domain (1999)

Signal transducers and activators of transcription (STATs) are important mediators of cytokine signal transduction. STAT factors are recruited to phosphotyrosine-containing motifs of activated receptor chains via their SH2 domains. The subsequent tyrosine phosphorylation of the STATs leads to their dissociation from the receptor, dimerization, and translocation to the nucleus. Here we describe the expression, purification, and refolding of the STAT3-SH2 domain. Proper folding of the isolated protein was proven by circular dichroism and fluorescence spectroscopy. The STAT3-SH2 domain undergoes a conformational change upon dimerization. Using an enzyme-linked immunosorbent assay we demonstrate that the monomeric domain binds to specific phosphotyrosine peptides. The specificity of binding to phosphotyrosine peptides was assayed with the tyrosine motif encompassing Tyr705 of STAT3 and with all tyrosine motifs present in the cytoplasmic tail of the signal transducer gp130.
Surface phospholipids in gastric injury and protection when a selective cyclooxygenase‐2 inhibitor (Coxib) is used in combination with aspirin (2007)

Aspirin's gastric toxicity in combination with a coxib can be dissociated from its ability to inhibit COX-1 and appears to be dependent, in part, on its ability to attenuate the stomach's surface hydrophobic barrier. This adverse drug interaction between aspirin and coxibs, which impacts the treatment of osteoarthritic and cardiac patients requiring cardiovascular prophylaxis, can be circumvented by the administration of phosphatidylcholine (PC)-associated aspirin, to maintain the stomach's hydrophobic properties.
[n]Staffanes with Terminal Nitrile and Isonitrile Functionalities and Their Metal Complexes (1993)

The synthesis of several bridgehead nitrile and isonitrile derivatives of the first two [n]staffanes, n = 1 and 2, is reported. Both isonitriles were converted into pentacarbonylmolybdenum complexes. [2]Staffane-3-carbonitrile was converted to a complex with rhodium(II) acetate, which was characterized by a single crystal X-ray analysis.
[Physiopathology of intestinal Salmonella infection]. (1992)

Following a long period during which studies on the pathogenesis of salmonellosis and typhoid fever have been exclusively based on careful evaluation of clinicopathological data in infected patients and experimental infection in mice, the new tools that are now offered by molecular genetics and cell biology allow more systematic and analytical approaches. Numerous mutants have been obtained that can be assayed in selected cell assay systems such as in vitro-cultivated epithelial cells or macrophages, thus allowing to identify and characterize key virulence bacterial products as well as their eucaryotic receptors and effectors. Significant contributions have recently been made in the analysis of the mechanisms allowing invasion of the intestinal epithelium and survival and multiplication of bacteria within macrophages. However, many unsolved questions remain. It is still unclear what produces diarrhea during salmonellosis and studies on the pathogenesis of typhoid fever are still impaired by the lack of a proper animal model.
New Perspectives in the Treatment of Cushing's Syndrome (2004)

Regardless of etiology, all cases of endogenous Cushing's syndrome are due to increased production of cortisol by the adrenal gland. Most are caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas. Alternatively, the glucocorticoid excess may be due to adrenal neoplasia or to ectopic ACTH-secreting tumors. Cushing's syndrome is characterized by endocrine and metabolic alterations such as truncal obesity, hypertension, weakness, amenorrhea, hyperglycemia, osteoporosis and depression. Unless treated, the disease is associated with high morbidity, and ultimately, mortality. Depending on the etiology of Cushing's syndrome two different treatment modalities are possible: reduction of pituitary ACTH production or reduction of adrenocortical cortisol secretion. In the absence of efficient drug therapy, transsphenoidal resection of the pituitary adenoma is the primary treatment of choice for the reduction of ACTH secretion. In the last years there was much progress in understanding the molecular mechanisms that control the function of the hypothalamic-pituitary-adrenal axis. Thus, new insights made it possible to identify potential drug targets for the treatment of Cushing's syndrome. The present article reviews different drug targets and therapeutic options including drugs that control the central ACTH regulation, e.g. by modulating signaling pathways and transcriptional regulation of ACTH biosynthesis, corticotrophin releasing hormone (CRH) or glucocorticoid receptor antagonists, inhibitors of glucocorticoid synthesis, ketoconazole, somatostatin and dopamine analogs. Some of these substances might be useful for the treatment of Cushing's syndrome.
Identification of Diagnostic Proteins in <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> by a Whole Genome Analysis Approach (2006)

Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is an economically significant veterinary pathogen that causes Johne's disease in cattle and sheep. There is a critical need for improved diagnostic tests to detect M. paratuberculosis infection in these animals. As with many other animal diseases, efforts need to be concentrated on the development of simple, rapid, noninvasive tests that can be performed by veterinarians or animal producers without expensive laboratory equipment. With the genome sequence of M. paratuberculosis now complete, we have taken a different strategy to identify novel proteins that are present uniquely in M. paratuberculosis and are antigenic in the context of infected cattle. Through a whole genome comparison of M. paratuberculosis with other sequenced mycobacterial genomes, we identified a collection of more than 90 genes that are present uniquely in M. paratuberculosis. This list has been further trimmed to 39 after amplification using polymerase chain reaction of unique genes using the genomic deoxyribonucleic acid template from several mycobacterial species and isolates. A selection of the remaining genes has been cloned and expressed in Escherichia coli and purified by affinity chromatography. Successfully purified proteins were analyzed using sera from rabbits immunized with M. paratuberculosis. Furthermore, to identify antigens in the context of disease, sera from cattle with Johne's disease as well as healthy control cattle are used in immunoassays. Using this methodology, we identified the first protein antigens specific to M. paratuberculosis.
Differential regulation of glial cell line‐derived neurotrophic factor (GDNF) mRNA expression during hypoxia and reoxygenation in astrocytes isolated from stroke‐prone spontaneously hypertensive rats (2001)

Glial cell line-derived neurotrophic factor (GDNF) plays several important roles in the survival and recovery of mature neurons during ischemia. We examined the possibility that the expression of GDNF mRNA and the release of GDNF protein are regulated differentially in cultured astrocytes from the stroke-prone spontaneously hypertensive rat (SHRSP) compared with those from Wistar Kyoto rats (WKY) during hypoxia and reoxygenation (H/R) and after exposure to glutamate and hydrogen peroxide (H(2)O(2)). The mRNA expression was quantitated by reverse transcription-polymerase chain reaction (RT-PCR) based on the fluorescent TaqMan methodology. A new instrument capable of measuring fluorescence in real-time was used to quantify gene amplification in astrocytes. GDNF protein was investigated by enzyme-linked immunosorbent assay (ELISA). GDNF mRNA expression and GDNF protein release at normoxia were greater in SHRSP than in WKY astrocytes. During H/R, however, the mRNA expression and protein release tended to be reduced in SHRSP compared with WKY. Glutamate and H(2)O(2) induced the expression of GDNF mRNA and the release of GDNF protein in both WKY and SHRSP in a dose-dependent manner. Levels of GDNF mRNA and protein in SHRSP were significantly lower than in WKY. These findings indicate that GDNF production in SHRSP astrocytes was low in response to H/R, glutamate, and H(2)O(2), compared with that observed in WKY. We conclude that the attenuated production of GDNF in astrocytes is involved in neuronal vulnerability in SHRSP during H/R, as GDNF production, which is stimulated by glutamate and H(2)O(2), is closely related to the protective effect against H/R-mediated neurotoxicity.
Role of Lefty in the anti tumor activity of human adult liver stem cells (2012)

Recent studies demonstrated that factors derived from embryonic stem cells inhibit the tumorigenicity of a variety of cancer cell lines. Embryonic stem cell-secreted Lefty, an inhibitor of Nodal-signalling pathway, was implicated in reprogramming cancer cells. Whether adult stem cells exhibited similar properties has not been explored. The aim of the present study was to investigate whether the conditioned medium (CM) derived from adult stem cells influence in vitro and in vivo tumor growth by a Nodal-dependent pathway. In particular we compared the anti-tumor effect of CM from human liver stem cells (HLSC) with that of bone marrow-derived mesenchymal stem cells (MSC). We found that HLSC-CM inhibited the in vitro growth and promoted apoptosis in HepG2 cells that expressed a deregulated Nodal pathway. The effect of HLSC-CM was related to the presence of Lefty A in the CM of HLSC. Silencing Lefty A in HLSC or Lefty A blockade with a blocking peptide abrogated the anti-proliferative and pro-apoptotic effect of HLSC-CM. Moreover, the administration of human recombinant Lefty A protein mimicked the effect of HLSC-CM indicating that Nodal pathway is critical for the growth of HepG2. At variance of HLSC, bone marrow-derived MSC did not express and release Lefty A and the MSC-CM did not exhibited an anti-tumor activity in vitro, but rather stimulated proliferation of HepG2. In addition, the intra-tumor administration of HLSC-CM was able to inhibit the in vivo growth of HepG2 hepatoma cells implanted subcutaneously in SCID mice. At variance, HLSC-CM derived from Lefty A silenced HLSC was unable to inhibit tumor growth. In conclusion, the results of present study suggest that Lefty A may account for the tumor suppressive activity of HLSC as a result of an inhibition of the Nodal-signalling pathway by a mechanism similar to that described for embryonic stem cells.
BIOS Instant Notes in Organic Chemistry (2004)

Instant Notes in Organic Chemistry, Second Edition, is the perfect text for undergraduates looking for a concise introduction to the subject, or a study guide to use before examinations. Each topic begins with a summary of essential facts−an ideal revision checklist−followed by a description of the subject that focuses on core information, with clear, simple diagrams that are easy for students to understand and recall in essays and exams.
A Small-Molecule-Inducible Nrf2-Mediated Antioxidant Response Provides Effective Prophylaxis against Cerebral IschemiaIn Vivo (2005)

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates expression of genes required for free radical scavenging, detoxification of xenobiotics, and maintenance of redox potential. Previously, activation of this pleiotropic response was neuroprotective in cell culture models that simulate components of stroke damage. However, the role of Nrf2 in limiting stroke damage in vivo remained unclear. We report that Nrf2 activation protects the brain from cerebral ischemia in vivo. Acute (1-3 d) intracerebroventricular or intraperitoneal pretreatment with tert-butylhydroquinone (tBHQ), an Nrf2 activity inducer, reduced cortical damage and sensorimotor deficit at 24 h and even 1 month after ischemia-reperfusion in rats. Cortical glutathione levels robustly increased with tBHQ administration to rats and Nrf2-expressing mice, but not Nrf2(-/-) mice. Basal and inducible activities of antioxidant/detoxification enzymes in Nrf2(-/-) mice were reduced when compared with Nrf2(+/+) controls. Interestingly, larger infarcts were observed in Nrf2(-/-) mice at 7 d after stroke, but not at 24 h, suggesting that Nrf2 may play a role in shaping the penumbra well after the onset of ischemia. Neuronal death caused by a "penumbral" model of stroke, using intracortical endothelin-1 microinjection, was attenuated by tBHQ administration to Nrf2(+/+), but not to Nrf2(-/-) mice, confirming the Nrf2-specific action of tBHQ in vivo. We conclude that Nrf2 plays a role in modulating ischemic injury in vivo. Accordingly, Nrf2 activation by small molecule inducers may be a practical preventative treatment for stroke-prone patients.
A varactor tuned 16-element MESFET grid oscillator (2002)

Much of the recent research in millimeter-wave quasi-optical systems has been directed at developing reliable solid-state power combiners. The grid oscillator developed by Popovic et al. (1991), is based on integrating active devices directly into a planar grid and has been used to generate powers as high as 10 Watts at 10 GHz. Essentially, the grid structure is a frequency selective surface whose period is only a fraction of a wavelength. Because the grid structure is a frequency selective surface, the impedance presented to devices is a strong function of frequency. This means the frequency tuning bandwidths of these arrays can be quite narrow, a distinct disadvantage for systems that require a broad tuning bandwidth. We present a new grid oscillator configuration in which varactor diodes are integrated directly into a planar array of FETs. The varactors are used to electronically tune the embedding impedance presented to the devices and, thus, the oscillation frequency. We investigate the frequency tuning of an X-band common gate grid oscillator using packaged varactor diodes. Simulations with the grid equivalent circuit model show good agreement with measurement and indicate that the tuning bandwidth can be increased considerably by reducing the minimum capacitance of the varactors. Such a reduction in capacitance can be realized through the use of chip devices and by using a single varactor tuner for each FET. In addition, the varactors could potentially be used to control the relative phase distribution across the grid, resulting in a beam-steerable quasi-optical source.
Recent Advances in the Design and Synthesis of Carbon-14 Labelled Pharmaceuticals from Small Molecule Precursors (2000)

Over the past decade, the increased chemical complexity of new drug candidates has resulted in a parallel need to develop innovative syntheses of carbon-14 labelled pharmaceuticals. Faced with short time-lines and a limited number of labelled precursors, radiochemists have addressed this challenge by developing new reagents and adapting existing technology to labelled syntheses. Selected examples from the recent radiochemical literature illustrate some of the creative strategies used to rapidly solve these synthetic challenges. Examples describing the handling and use of common small molecule reagents, such as carbon-14 labelled carbon dioxide, methyl iodide, cyanide, acetic acids, sulfur and phosphorous stabilized ylides for the synthesis of labelled steroids, prostanoids, nucleosides, pyridines, quinolines, benzazepines and other heterocycles are presented. Several general strategies for radiolabelling are also discussed including the degradation strategy for accessing necessary intermediates and precursors, the radiolabelling of aromatic substrates, transition metal mediated cross-couplings, and the use of chiral auxiliaries for the enantioselective syntheses of radiolabelled pharmaceuticals.
Paresthesia thresholds in spinal cord stimulation: a comparison of theoretical results with clinical data (1993)

The potential distributions produced in the spinal cord and surrounding tissues by dorsal epidural stimulation at the midcervical, midthoracic, and low thoracic levels were calculated with the use of a volume conductor model. Stimulus thresholds of myelinated dorsal column fibers and dorsal root fibers were calculated at each level in models in which the thickness of the dorsal cerebrospinal fluid (CSF) layer was varied. Calculated stimulus thresholds were compared with paresthesia thresholds obtained from measurements at the corresponding spinal levels in patients. The influences of the CSF layer thickness, the contact separation in bipolar stimulation and the laterality of the electrodes on the calculated thresholds were in general agreement with the clinical data.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Path-length control in an interferometric QKD link (2003)

We describe a phase-encoded quantum key distribution system the uses continuous control of receiver-interferometer path length to maintain alignment with the transmitter. In this fiber-based system, a small number of training frames are sent over the quantum channel that allow the receiver to compensate for drift in the transmitter and receiver interferometers due to slow changes in temperature. The system is self-starting after disruption and can maintain a quantum bit error rate of less than 7% for phase drift rates of 0.5 deg/sec. The control system design is described and measured system data is compared with simulations.
A Bis(ferrocenyl)phenanthroline Iridium(III) Complex as a Lab-on-a-Molecule for Cyanide and Fluoride in Aqueous Solution (2012)

The bis(ferrocenyl)phenanthroline iridium(III) complex 1 is synthesized and elaborated as a lab-on-a-molecule for the competitive and quantitative determination of cyanide and fluoride in aqueous solution. 1 exhibits a strong OFF-ON photoluminescence (PL) response upon addition of cyanide with a good selectivity over other anions. The mechanism involves nucleophilic displacement of the phenanthroline ligand, which quenches PL, to furnish a strongly photoluminescent dicyano iridium complex. In contrast, in the electrochemiluminescence (ECL) channel, cyanide undergoes oxidation and a different selectivity is observed. The strong ferrocenium-fluoride interaction is exploited for the first time in ECL to selectively monitor fluoride by a >60-fold enhancement. In both PL and ECL channels, anion selectivity is further challenged by competitive assays in the presence of other anions. Quantitative determination of CN(-) and F(-) is achieved in both channels.