gebhart/patrepeval huggingface dataset:
The future of vitamin D analogs (2014)

The active form of vitamin D3, 1,25-dihydroxyvitamin D3, is a major regulator of bone and calcium homeostasis. In addition, this hormone also inhibits the proliferation and stimulates the differentiation of normal as well as malignant cells. Supraphysiological doses of 1,25-dihydroxyvitamin D3 are required to reduce cancer cell proliferation. However, these doses will lead in vivo to calcemic side effects such as hypercalcemia and hypercalciuria. During the last 25 years, many structural analogs of 1,25-dihydroxyvitamin D3 have been synthesized by the introduction of chemical modifications in the A-ring, central CD-ring region or side chain of 1,25-dihydroxyvitamin D3 in the hope to find molecules with a clear dissociation between the beneficial antiproliferative effects and adverse calcemic side effects. One example of such an analog with a good dissociation ratio is calcipotriol (Daivonex®), which is clinically used to treat the hyperproliferative skin disease psoriasis. Other vitamin D analogs were clinically approved for the treatment of osteoporosis or secondary hyperparathyroidism. No vitamin D analog is currently used in the clinic for the treatment of cancer although several analogs have been shown to be potent drugs in animal models of cancer. Transcriptomics studies as well as in vitro cell biological experiments unraveled basic mechanisms involved in the antineoplastic effects of vitamin D and its analogs. 1,25-dihydroxyvitamin D3 and analogs act in a cell type- and tissue-specific manner. Moreover, a blockade in the transition of the G0/1 toward S phase of the cell cycle, induction of apoptosis, inhibition of migration and invasion of tumor cells together with effects on angiogenesis and inflammation have been implicated in the pleiotropic effects of 1,25-dihydroxyvitamin D3 and its analogs. In this review we will give an overview of the action of vitamin D analogs in tumor cells and look forward how these compounds could be introduced in the clinical practice.
Active Memory Cube: A processing-in-memory architecture for exascale systems (2015)

Many studies point to the difficulty of scaling existing computer architectures to meet the needs of an exascale system (i.e., capable of executing <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="TeX">$10^{18} $</tex-math></inline-formula> floating-point operations per second), consuming no more than 20 MW in power, by around the year 2020. This paper outlines a new architecture, the Active Memory Cube, which reduces the energy of computation significantly by performing computation in the memory module, rather than moving data through large memory hierarchies to the processor core. The architecture leverages a commercially demonstrated 3D memory stack called the Hybrid Memory Cube, placing sophisticated computational elements on the logic layer below its stack of dynamic random-access memory (DRAM) dies. The paper also describes an Active Memory Cube tuned to the requirements of a scientific exascale system. The computational elements have a vector architecture and are capable of performing a comprehensive set of floating-point and integer instructions, predicated operations, and gather-scatter accesses across memory in the Cube. The paper outlines the software infrastructure used to develop applications and to evaluate the architecture, and describes results of experiments on application kernels, along with performance and power projections.
Nickel-Catalyzed Direct Electrochemical Cross-Coupling between Aryl Halides and Activated Alkyl Halides (1996)

The electrochemical reduction of a mixture of aryl halides and activated alkyl halides in DMF in the presence of catalytic amount of NiBr(2)bipy leads to cross-coupling products in good to high yields. The method applies to the synthesis of alpha-aryl ketones, alpha-aryl esters, and allylated compounds from readily available organic halides. Optimization of the process has been obtained by slowly adding the most reactive organic halide (usually the activated alkyl halide) during the electrolysis which is best conducted at 70 degrees C when aryl bromides are involved.
Sequence similarities among kappa IIIb chains of monoclonal human IgM kappa autoantibodies. (1984)

Light chains of the serologically and chemically defined V region sub-subgroup kappa IIIb are preferentially associated with several types of human IgM kappa (monoclonal) autoantibodies and are remarkably homologous in primary structure, as evidenced by partial amino acid sequence data. To establish the extent of homology among such proteins, we have determined the complete variable region (V) sequence of the light chains of four monoclonal IgM kappa autoantibodies, of which two (GAR and GOT) are rheumatoid factors (RFs), the third (SON) has anti-apo beta lipoprotein specificity, and the fourth (PIE) binds specifically to intermediate filaments. The region encoded by the V kappa segment gene (positions 1-95) in all four light (L) chains is virtually identical in sequence, differing by only one residue in the FR3 of protein SON and in the first CDR of protein GOT. Further, the CDR3 of kappa chain SON contains an additional residue (prolyl) located at the carboxyl-terminus of the V segment. The region encoded by the J gene (positions 96-108) is identical after position 96 for the two RFs GAR and GOT (J kappa 2), but different in proteins SON (J kappa 4) and PIE (J kappa 1). The amino acid residue at position 96, located in CDR3 at the site of combinatoriaL joining of the V kappa and J kappa gene segments and involved as a contacting residue in the hapten binding site, is different in all four light chains. These results demonstrate the extensive homology in sequence among light chains of IgM kappa autoantibodies and indicate that a particular V kappa germ line gene, kappa IIIb, is expressed as a phylogenetic response to certain self antigens or as part of a selection process by which these autoimmune responses are regulated.
DOWNSTREAM PROCESSING OF MONOCLONAL ANTIBODIES: CURRENT PRACTICES AND FUTURE OPPORTUNITIES (2017)

Monoclonal antibodies (mAbs) are established as the most prevalent class of recombinant protein therapeutics. This introductory chapter attempts to set the context for the following chapters, which cover many aspects of mAb purification in detail. A typical mAb purification process flowsheet is described and used to illustrate the impact of purification platforms on mAb production. Factors to consider with respect to the various process alternatives or new technologies are addressed, emphasizing the integration of unit operations and process design principles into an optimized, holistic process. Both current practices and controversial topics are introduced, among them the challenges of very large- scale (VLS) production, issues related to facility fit, the maturation of separation technology for mAb processing, the need for innovations in purification technology, and the impact of the evolving regulatory environment. The processes used for production of intravenous immunoglobulin (IVIG) from human plasma differ from those used for recombinant mAbs.
Perceiving auditory distance using level and direct-to-reverberant ratio cues (2011)

The study investigated how level and reverberation cues contribute to distance discrimination, and how accuracy is affected by reverberation cue strength. Sentence pairs were presented at distances between 1 and 8 m in a virtual room simulated using an image-source model and two reverberation settings (lower and higher). Listeners performed discrimination judgments in three conditions: level cue only (Level-Only), reverberation only (Equalized), and both cues available (Normal). Percentage correct judgment of which sentence was closer was measured. Optimal distance discrimination was obtained in the Normal condition. Perception of the difference in distance between sentences had a lower threshold (i.e., performance was significantly better, p&amp;lt;0.05) for closer than further targets in Normal and Level-Only conditions. On the contrary, in the Equalized condition, these thresholds were lower for further than closer targets. Thresholds were lower at higher reverberation in the Equalized condition, and for further targets in the Normal condition. Data indicate that level generally provided more accurate discrimination information than direct-to-reverberant ratio. Direct-to-reverberant ratio provided better information for sounds further from the listener than for nearer sounds, and listeners were able to use direct-to-reverberant ratio as effectively as level in highly reverberant rooms when discriminating far sound sources.
THEORY AND PRACTICE OF PARENTERAL FLUID ADMINISTRATION (1934)

In the early stages of undue loss of water from the body, regardless of the cause of such loss, the composition of the blood in respect to its water content and electrolyte pattern tends to remain unaltered because of the stabilizing or buffering effect of the intercellular fluid of the body. This portion of the body may be looked on as a reservoir which may shrink appreciably in order that changes in the blood and perhaps also in the fixed tissue cells may be kept at a minimum. When, however, the intercellular fluid becomes exhausted, changes do appear in the blood indicative of this exhaustion, and probably also in the fixed tissues themselves. The nature of the changes is largely dependent on the manner in which fluid is lost; sometimes acidosis may accompany dehydration, at other times alkalosis, while occasionally a tendency toward one such change may be almost exactly
Removal of Perchlorate Anion from an Aqueous Solution by Encapsulation in an Anion-templated Self-assembled Molecular Capsule (2009)

Abstract A new M2L4-type molecular capsule was prepared and characterized. It is shown that the anion-templated self-assembled construction is useful for selective removal of perchlorate anion from aqueous solution.
Synthesis, properties, functionalisation and applications of carbon nanotube: a state of the art review (2010)

Abstr act. The investigation of fullerenes and especially of carbon nanotubes (CNTs) has opened a new window for the development of polymer matrix composites with novel properties and applications. CNTs, which have a number of unexpected properties, both mechanical and electrical, seem to have a large potential as a filler, i.e. as a reinforcement in nanocomposites. With the discovery of carbon nanotubes, the research efforts have been initially concentrated on the better understanding of their processing conditions, modification, and properties.
Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex (2001)

Cardiomyopathy is a multifactorial disease, and the dystrophin-glycoprotein complex has been implicated in the pathogenesis of both hereditary and acquired forms of the disease. Using mouse models of cardiomyopathy made by ablating genes for components of the sarcoglycan complex, we show that long-term treatment with verapamil, a calcium channel blocker with vasodilator properties, can alleviate the severe cardiomyopathic phenotype, restoring normal serum levels for cardiac troponin I and normal cardiac muscle morphology. Interruption of verapamil treatment leads again to vascular dysfunction and acute myocardial necrosis, indicating that predilection for cardiomyopathy is a continuing process. In contrast, verapamil did not prevent cardiac muscle pathology in dystrophin-deficient mdx mice, which neither show a disruption of the sarcoglycan complex in vascular smooth muscle nor vascular dysfunction. Hence, our data strongly suggest that pharmacological intervention with verapamil merits investigation as a potential therapeutic option not only for patients with sarcoglycan mutations, but also for patients with idiopathic cardiomyopathy associated with myocardial ischemia not related to atherosclerotic coronary artery disease.
The maize transcription factor Sn alters proanthocyanidin synthesis in transgenic Lotus corniculatus plants (1999)

Lotus corniculatus L. plants were transformed with Agrobacterium rhizogenes binary vector carrying the maize Sn regulatory gene driven by the 35S promoter. These plants showed modifications in the pattern of accumulation of proanthocyanidin (PA). All the transformed plants but one showed an increase in PA content in the root relative to control untransformed and control gus gene transformed plants (C). With respect to the PAaccumulation in leaves, Sn transgenic plants were grouped in two classes: suppressed (S), that showed a consistent reduction of foliar PAcontent, and unsuppressed (U) that did not differ significantly from controls. Dihydroflavanol reductase (DFR) and leucocyanidin reductase (LAR) enzyme activities in S and U plant leaves mirrored the changes seen with foliar PA accumulation. LAR activity in the roots was consistent with the root PA levels. Mature Sn mRNA accumulated in the leaves of U plants, but not in leaves of S plants; however, leaves of both S and U plants were able to initiate Sn transcription. All Sn -transformed plants accumulated Sn message in root tissue. A possible negative interaction of Sn and an unidentified homologous endogene is proposed for explaining the behaviour of S plants.
Performance of unlicensed devices with a spectrum etiquette (2002)

There are growing opportunities for the wireless industry to deploy products in the unlicensed spectrum, where no licensing is required and devices share the spectrum. The unlicensed spectrum (PCS band at 2 GHz, the National Information Infrastructure (NII) band at 5 GHz, and the millimeter wave band at 59-64 GHz) offers several benefits, but there are serious challenges to overcome before these benefits can be fully realized. Foremost among these is the risk of inefficient utilization, resulting from a lack of incentive to conserve the shared spectrum. This phenomenon is demonstrated in one scenario, and some techniques to deal with this problem are presented.
T lymphocytes derived from skin lesions of patients with psoriasis vulgaris express a novel cytokine pattern that is distinct from that of T helper type 1 and T helper type 2 cells (1994)

In various immunological disorders the pathomechanisms of tissue damage are causally associated with specific patterns of locally produced cytokines. To study the molecular and cellular mechanisms involved in the manifestation of psoriasis vulgaris we have assessed the cytokine mRNA profile expressed in lesional psoriatic skin and in T cell clones (TCC) that were established from skin lesions of patients with psoriasis. As demonstrated by use of the polymerase chain reaction (PCR), psoriasis lesions consistently exhibit transcription of a complex pattern of cytokines. It includes mediators selectively produced by T lymphocytes [interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, interleukin (IL)-2, IL-3 and IL-5] as well as cytokines secreted by various cell types [transforming growth factor (TGF)-alpha/-beta, TNF-alpha, IL-6/-8 and granulocyte-macrophage-colony stimulating factor], while IL-4 is missing. With the exception of TGF-alpha, this cytokine profile was also observed in lesional psoriatic T cell clones yielding supernatants mitogenic for keratinocytes in vitro (MTCC), but not in T cell clones yielding supernatants that inhibited keratinocyte proliferation (STCC). The congruent cytokine expression of psoriatic skin lesions and MTCC emphasizes that inflammation in psoriasis is driven by a sofar unrecognized regulatory T cell subset that may serve to control epidermal regeneration and convey immunosurveillance over epithelial surfaces. It is characterized by the combined expression of IFN-gamma, TGF-beta, IL-2 and IL-5 in the absence of IL-4 and by its selective capacity to enhance keratinocyte proliferation. This newly defined combination of regulatory properties of a distinct T cell population cannot be reconciled with an immune response of the T helper cells (TH)0, TH1 or TH2 type.
ChemInform Abstract: CHEMISTRY OF HETEROCYCLIC COMPOUNDS PART 12, PREPARATION AND REACTIONS OF 2‐PYRIDYLACETYLENES (1974)

Abstract Durch Kondensation zwischen dem Pyridinaldehyd (Ia) und Picolin (IIa) entsteht ‐ ′das Olefin (IIIa), aus 6‐Methykpyridin‐2‐aidehyd (Ib) und Lutidin (IIb) entsteht das Olefin (IIIb) neben einem 2: l‐Kondensat (IV).
Role of the single disulphide bond of β2‐microglobulin in amyloidosis in vitro (2001)

The aggregation of beta(2)-microglobulin (beta(2)m) into amyloid fibrils occurs in the condition known as dialysis-related amyloidosis (DRA). The protein has a beta-sandwich fold typical of the immunoglobulin family, which is stabilized by a highly conserved disulphide bond linking Cys25 and Cys80. Oxidized beta(2)m forms amyloid fibrils rapidly in vitro at acidic pH and high ionic strength. Here we investigate the role of the single disulphide bond of beta(2)m in amyloidosis in vitro. We show that reduction of the disulphide bond destabilizes the native protein such that non-native molecules are populated at neutral pH. These species are prone to oligomerization but do not form amyloid fibrils when incubated for up to 8 mo at pH 7.0 in 0.4 M NaCl. Over the pH range 4.0-1.5 in the presence of 0.4 M NaCl, however, amyloid fibrils of reduced beta(2)m are formed. These fibrils are approximately 10 nm wide, but are shorter and assemble more rapidly than those produced from the oxidized protein. These data show that population of non-native conformers of beta(2)m at neutral pH by reduction of its single disulphide bond is not sufficient for amyloid formation. Instead, association of one or more specific partially unfolded molecules formed at acid pH are necessary for the formation of beta(2)m amyloid in vitro. Further experiments will now be needed to determine the role of different oligomeric species of beta(2)m in the toxicity of the protein in vivo.
Magnetically soft higher order harmonic stress and temperature sensors (2003)

A stress and temperature sensor based on changes in the higher order harmonics of a magnetically soft magnetoelastic sensor is reported. When excited by a low-frequency ac magnetic field, the nonlinear permeability of the ferromagnetic sensor causes the emission of higher order magnetic induction that can be detected by a coil. The sensor can be used for temperature monitoring since temperature affects the permeability and magnetic hardness of the sensor material, causing a change in the higher order harmonic amplitudes. The higher order harmonics also respond to stress since the sensor material is magnetoelastic. A theoretical model is presented to explain the effects of temperature and stress on the higher order harmonics. Experimental results are presented illustrating application of this sensor technology to monitoring of stress and temperature from within solid structures such as wooden and concrete beams.
Transcriptional regulation of secretin gene expression. (1995)

Expression of the gene encoding the hormone secretin is restricted to a specific enteroendocrine cell type and to beta-cells in developing pancreatic islets. To characterize regulatory elements in the secretin gene responsible for its expression in secretin-producing cells, we used a series of reporter genes for transient expression assays in transfection studies carried out in secretin-producing islet cell lines. Analysis of the transcriptional activity of deletion mutants identified a positive cis regulatory domain between 174 and 53 base pairs upstream from the transcriptional initiation site which was required for secretin gene expression in secretin-producing HIT insulinoma cells. Within this enhancer were sequences resembling two binding sites for the transcription factor Sp1, as well as a consensus sequence for binding to helix-loop-helix proteins. Analysis of these three elements by site-directed mutagenesis suggests that each is important for full transcriptional activity. The role of proximal enhancer sequences in directing secretin gene expression to appropriate tissues is further supported by studies in transgenic mice revealing that 1.6 kilobases of the secretin gene 5' flanking sequence were sufficient to direct the expression of either human growth hormone or simian virus 40 large T-antigen reporter genes to all major secretin-producing tissues.
Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. (1981)

Abstract The M7/14 monoclonal antibody (MAb) has previously been shown to block xenogeneic cytolytic T lymphocyte-(CTL) mediated killing by binding to the CTL rather than the target cell. It defines a novel surface antigen, termed LFA-1, with polypeptide chains of 180,000 and 95,000 M1 (1). The mechanism of this blockade and the effects of M7/14 on other T and B lymphocyte functional responses have been investigated here. Blockade of CTL-mediated killing is given by purified M7/14 MAb, and is not due to trivial mechanisms such as toxicity or agglutination. M7/14 blocks CTL directed to allogeneic and anti-modified self as well as xenogeneic determinants. Blockade occurs at the recognition-adhesion step, as shown by inhibition of CTL-target cell conjugate formation. M7/14 antibody was also shown to block a variety of other T cell functions: the mixed lymphocyte response (both in xenogeneic and allogeneic systems), antigen-specific T cell proliferation, and T cell-dependent plaque-forming cell responses, but not T cell-independent plaque-forming cell responses or LPS-induced B cell proliferation. Inhibition of both CTL and MLR function was extremely potent, occurring at MAb concentrations as low as 0.5 µg/ml. Inhibition of the MLR occurs in the 1st day of 6-day cultures. The data suggest that LFA-1 participates in or is closely associated with a number of different T lymphocyte functional pathways. LFA-1 appears crucial for the adhesive interaction between CTL and target cells, and it is possible that its importance in T helper and proliferative responses is also related to intercellular interactions.
Fluorination in Medicinal Chemistry: Methods, Strategies, and Recent Developments (2008)

Methods for introducing fluorine into organic molecules are reviewed, with an emphasis on preparation of compounds designed for biomedicinal applications. Electrophilic fluorination, nucleophilic fluorination, and enantioselective monofluorination procedures are discussed. This is followed by a review of the development of nucleophilic and electrophilic trifluoromethylation procedures. The final sections highlight recent applications of fluorine chemistry in drug development with selected examples.
Raman And Four Photon Mixing Amplification In Single Mode Fibers (1985)

In this paper, fibers and transmission system designs using nonlinear optical amplification and frequency conversion in single-mode fibers (SMF) are discussed. Optical amplification of signals issued from laser diodes in the first and second optical transmission windows is reported. Raman gains of 40 dB have been obtained for 1.32 um laser diode light at the rate of 11 dB/W in a 2.5 km long SMF. Parametric amplification of laser diode signals at 1.57µm in a 30 m long SMF pumped in the low dispersion region at 1.32 um is presented. Gain values in excess of 30 dB are measured. Up and down frequency conver-sions using stimulated four-photon mixing experiments are also demonstrated.