gebhart/patrepeval huggingface dataset:
Synthesis of 3-(2-Amino)benzylidene-2,5-piperazinedione and Its Conversion to 1-Azanaphthalenone and Spiro[indolinepiperazine]dione Derivtives (1992)

Synthesis of 3-(2-amin0)benzylidene-2.5-pipe- razinedione and its conversions by photolysis and by treatment with NBS gave 3-amino-1-azanaphthalen-2(g- one and spiro [indoline-2 (3H) ,2 -~i~erazine] -3 , 6 ' -dione derivatives, respectively.In connection with the synthesis of aspirochlorin,' previously, we reported briefly that two kinds of intramolecular cyclization of 3-salicylidene-2,5-piperazinedione (2.5-piperazinedione=PDO), which was derived by the condensation of 1,4-diacetyl-PDO (1) with salicylaldehyde, gave 3-(acetylglycylamino) coumarin and spiro [benzofuran-2 (3g), 2'-piperazine] -3 ' ,6'-dione derivatives, respectively.2From these results, it is very interesting to explore the similar conversion of 3-arylidene-PDO derivatives possessing a protic functional group, such as -NH2 at ortho position of phenyl group.In this paper, we wish to report on the synthesis of ( Z ) -and (E)-3-(2-amin0)benzylidene-PDO derivatives and their conversions to l-azanaphthalen-2-(HI --one and spiro [indoline-2 (3H) ,2 ' -piperazine]-3, , 6 derivatives.' H Nmr (DMSO-d6) : 6 7.96 (br s, lH, -NH-) , 6.04 (s, lH, -CHBr-) , 4.40 IABq, J=18.0 Hz, 2H, -CH2-).Anal.Calcd for C15H15N304Br: C, 47.79; H, 3.98; N, 11.05.Found: C, 47.58; H, 4.11; N, 11.35.The similar concentration of the second fraction gave 6b as colorless powder.Yield, 120 mg (36%), mp 106-107 OC.Ir (KBr): 3230 (NH), 1780, 1695 (C=O) cm-l.' H Nmr (DMSO-d6): 8 8.24 (br s, lH, -NH-), 5.57 (s, 1H.-CHBr-), 4.34 (ABq, J=18.0 Hz, 2H, -CH2-).Anal.Calcd for C15H15N304Br: C, 47.
A Mechanism-Based Approach to Prevention of and Therapy for Fibromyalgia (2011)

Fibromyalgia syndrome (FMS) is characterized by pain referred to deep tissues. Diagnosis and treatment of FMS are complicated by a variable coexistence with regional pain, fatigue, sleep disruption, difficulty with mentation, and depression. The widespread, deep pain of FMS can be a consequence of chronic psychological stress with autonomic dysregulation. Stress acts centrally to facilitate pain and acts peripherally, via sympathetic vasoconstriction, to establish painful muscular ischemia. FMS pain, with or without a coexistent regional pain condition, is stressful, setting up a vicious circle of reciprocal interaction. Also, stress interacts reciprocally with systems of control over depression, mentation, and sleep, establishing FMS as a multiple-system disorder. Thus, stress and the ischemic pain it generates are fundamental to the multiple disorders of FMS, and a therapeutic procedure that attenuates stress and peripheral vasoconstriction should be highly beneficial for FMS. Physical exercise has been shown to counteract peripheral vasoconstriction and to attenuate stress, depression, and fatigue and improve mentation and sleep quality. Thus, exercise can interrupt the reciprocal interactions between psychological stress and each of the multiple-system disorders of FMS. The large literature supporting these conclusions indicates that exercise should be considered strongly as a first-line approach to FMS therapy.
Deep Conservation of MicroRNA-target Relationships and 3'UTR Motifs in Vertebrates, Flies, and Nematodes (2006)

microRNAs (miRNAs) are a class of small noncoding RNAs that posttranscriptionally regulate a large fraction of genes in animal genomes. We have previously published computational miRNA target predictions in five vertebrates, six flies, and three nematodes. Here, we report a comprehensive study of the "deep" conservation of miRNA targets and conserved 3'UTR (untranslated region) motifs in general across vertebrates, flies, and nematodes. Our data indicate that although many miRNA genes and 3'UTR motifs are well-conserved, miRNA-target relationships have diverged more rapidly, and we explicitly assign each gained or lost miRNA-target relationship to one of the three clades. However, we also identify a small but significant number of deeply conserved miRNA targets and show that these are enriched for essential processes related to development. Finally, we provide lists of 3'UTR motifs that are significantly conserved, and thus likely functional, classified by their distribution in the three clades. We find hundreds of such motifs specific to each clade, dozens specific to each pair of clades, and ten shared by vertebrates, flies, and nematodes. These findings suggest that posttranscriptional control has undergone extensive rewiring during metazoan evolution and that many deeply conserved miRNA-target relationships may be vital subunits of metazoan gene regulatory networks.
GAS6 Induces Axl-mediated Chemotaxis of Vascular Smooth Muscle Cells (1998)

Atherosclerosis and arterial restenosis are disease processes involving the accumulation of vascular smooth muscle cells following vascular injury. Key events leading to these processes are migration and proliferation of these cells. Here, we demonstrate that GAS6, encoded by the growth arrest-specific gene 6, induces a directed migration (chemotaxis) of both rat and human primary vascular smooth muscle cells while showing only marginal mitogenic potential in human vascular smooth muscle cells. GAS6 stimulation induces Axl autophosphorylation in human vascular smooth muscle cells, indicating that specific GAS6-Axl interactions may be associated with GAS6-directed chemotaxis. To test this hypothesis, vascular smooth muscle cells overexpressing Axl were generated by gene transfer and assessed for their ability to migrate along a GAS6 gradient. These Axl overexpressors exhibited 2-5-fold increased sensitivity to GAS6-induced chemotaxis. Furthermore, vascular smooth muscle cells expressing the kinase dead mutant of Axl or exposure to the soluble Axl extracellular domain showed attenuated GAS6-induced migration. Taken together, these results suggest that GAS6 is a novel chemoattractant that induces Axl-mediated migration of vascular smooth muscle cells. The separation of mitogenesis from migration provided by this study may enhance the molecular dissection of cell migration in vascular damage.
Magnetic behavior and structure of the halogen-doped fullerene C60 (1992)

We simultaneously doped bromine and iodine (electron acceptors) into C60 (fullerene) which is known to become superconductive by doping alkali metals (electron donors). The simultaneous doping of bromine and iodine into C60 brought about a hysteresis in the magnetic moment versus magnetic field curves as well as a structural change when the molar ratio of IBr (the 1:1 compound of iodine and bromine) to C60 is over about 2.5.
Voyage inside the cell: Microsystems and nanoengineering for intracellular measurement and manipulation (2015)

Abstract Properties of organelles and intracellular structures play important roles in regulating cellular functions, such as gene expression, cell motility and metabolism. The ability to directly interrogate intracellular structures inside a single cell for measurement and manipulation has significant implications in the understanding of subcellular and suborganelle activities, diagnosing diseases, and potentially developing new therapeutic approaches. In the past few decades, a number of technologies have been developed to study single-cell properties. However, methods of measuring intracellular properties and manipulating subcellular structures have been largely underexplored. Due to the even smaller size of intracellular targets and lower signal-to-noise ratio than that in whole-cell studies, the development of tools for intracellular measurement and manipulation is challenging. This paper reviews emerging microsystems and nanoengineered technologies for sensing and quantitative measurement of intracellular properties and for manipulating structures inside a single cell. Recent progress and limitations of these new technologies as well as new discoveries and prospects are discussed.
Fuzzy systems as universal approximators (1994)

An additive fuzzy system can uniformly approximate any real continuous function on a compact domain to any degree of accuracy. An additive fuzzy system approximates the function by covering its graph with fuzzy patches in the input-output state space and averaging patches that overlap. The fuzzy system computes a conditional expectation E|Y|X| if we view the fuzzy sets as random sets. Each fuzzy rule defines a fuzzy patch and connects commonsense knowledge with state-space geometry. Neural or statistical clustering systems can approximate the unknown fuzzy patches from training data. These adaptive fuzzy systems approximate a function at two levels. At the local level the neural system approximates and tunes the fuzzy rules. At the global level the rules or patches approximate the function.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dietary polyphenols can modulate the intestinal inflammatory response (2009)

Inflammatory bowel diseases (IBD) arise from multiple causes, including environmental factors, gut microflora, immunity, and genetic predispositions. In the course of IBD, immune homeostasis and intestinal mucosa barrier integrity are impaired. Among natural preventive treatments that have been identified to date, polyphenols appear as promising candidates. They have been shown to protect against several diseases, including cardiovascular diseases and cancers, and they have anti-inflammatory properties in non-intestinal models. This paper will review the literature that has described to date some effects of polyphenols on intestinal inflammation. Studies, conducted using in vivo and in vitro models, provide evidence that pure polyphenolic compounds and natural polyphenolic plant extracts can modulate intestinal inflammation.
Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells (1993)

The human FLT3 cDNA was cloned from a pre-B cell line and characterized. The deduced amino acid sequence shows that FLT3 codes for a receptor-type tyrosine kinase of 993 residues, presenting a strong similarity with the corresponding mouse FLT3/FLK2 protein as well as with the receptors for colony-stimulating factor 1 (CSF1R/FMS) and steel locus factor (SLFR/KIT). An analysis of the expression of the gene using amplification of reverse transcribed FLT3 mRNA by polymerase chain reaction shows that FLT3 is expressed in various lymphohematopoietic cells and tissues, including a series of immature cell lines and leukemias of lymphocytic origin.
The Role of Irreversible EGFR Inhibitors in the Treatment of Non-Small Cell Lung Cancer: Overcoming Resistance to Reversible EGFR Inhibitors (2010)

Reversible epidermal growth factor receptor tyrosine kinase inhibitors are often used for the treatment of non-small cell lung cancer following failure of cytotoxic chemotherapy. While these agents are active in a subset of patients, most develop resistance and progress within the course of 1 year. In nearly half of the cases, acquired resistance is caused by a secondary epidermal growth factor receptor T790M mutation. Irreversible epidermal growth factor receptor tyrosine kinase inhibitors are an emerging class of agents that may have the potential to overcome and prevent the emergence of such mutation-related resistance.
Defining the therapeutic window in a severe animal model of spinal muscular atrophy (2014)

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of a single gene, Survival Motor Neuron-1 (SMN1). Administration of a self-complementary Adeno-Associated Virus vector expressing full-length SMN cDNA (scAAV-SMN) has proven an effective means to rescue the SMA phenotype in SMA mice, either by intravenous (IV) or intracerebroventricular (ICV) administration at very early time points. We have recently shown that ICV delivery of scAAV9-SMN is more effective than a similar dose of vector administered via an IV injection, thereby providing an important mechanism to examine a timeline for rescuing the disease and determining the therapeutic window in a severe model of SMA. In this report, we utilized a relatively severe mouse model of SMA, SMNΔ7. Animals were injected with scAAV9-SMN vector via ICV injection on a single day, from P2 through P8. At each delivery point from P2 through P8, scAAV9-SMN decreased disease severity. A near complete rescue was obtained following P2 injection while a P8 injection produced a ∼ 40% extension in survival. Analysis of the underlying neuromuscular junction (NMJ) pathology revealed that late-stage delivery of the vector failed to provide protection from NMJ defects despite robust SMN expression in the central nervous system. While our study demonstrates that a maximal benefit is obtained when treatment is delivered during pre-symptomatic stages, significant therapeutic benefit can still be achieved after the onset of disease symptoms.
Bistability in coupled cavity semiconductor lasers (1984)

Experimental results on bistable operation of coupled cavity semiconductor lasers are presented. The light level at the upper and lower states can be controlled by varying the injection current. A model calculation of the coupled cavity laser system shows that the bistability is due to nonlinearities associated with above threshold gain saturation. Our results show that a coupled cavity laser can exhibit bistability at all temperatures and, in addition, the size of the ‘‘hysteresis loop’’ can be easily controlled by varying the injection current. These results are significant for a practical bistable optical device.
Flexible MIPS soft processor architecture (2008)

The flexible MIPS soft processor architecture borrows selected technologies from high-performance computing to deliver a modular, highly customizable CPU targeted towards FPGA implementations for embedded systems; the objective is to provide a more flexible architectural alternative to coprocessor-based solutions. The processor performs out-of-order execution on parallel functional units, it delivers in-order instruction commit and it is compatible with the MIPS-1 Instruction Set Architecture. Amongst many available options, the user can introduce custom instructions and matching functional units; modify existing units; change the pipelining depth within functional units to any fixed or variable value; customize instruction definitions in terms of operands, control signals and register file interaction; insert multiple redundant functional units for improved performance. The flexibility provided by the architecture allows the user to expand the processor functionality to implement instructions of coprocessor-level complexity through additional functional units. The processor design was implemented and simulated on two FPGA platforms, tested on multiple applications, and compared to three commercially available soft processor solutions in terms of features, area, clock frequency and benchmark performance.
Structure and Regulation of Voltage-Gated Ca2+ Channels (2000)

Voltage-gated Ca(2+) channels mediate Ca(2+) entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca(2+) currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca(2+) channels that have been characterized biochemically are complexes of a pore-forming alpha1 subunit of approximately 190-250 kDa; a transmembrane, disulfide-linked complex of alpha2 and delta subunits; an intracellular beta subunit; and in some cases a transmembrane gamma subunit. Ten alpha1 subunits, four alpha2delta complexes, four beta subunits, and two gamma subunits are known. The Cav1 family of alpha1 subunits conduct L-type Ca(2+) currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Cav2 family of alpha1 subunits conduct N-type, P/Q-type, and R-type Ca(2+) currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Cav3 family of alpha1 subunits conduct T-type Ca(2+) currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca(2+) current types. The distinct structures and patterns of regulation of these three families of Ca(2+) channels provide a flexible array of Ca(2+) entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca(2+) entry by second messenger pathways and interacting proteins.
Excitation of Coherent Phonon Polaritons with Femtosecond Optical Pulses (1985)

Coherent lattice vibrations in lithium tantalate have been observed directly in the time domain by use of femtosecond optical pulses and the electro-optic effect to coherently excite and detect phonon polaritons. The damping time of the lowest transverse optic phonon has been determined directly from the decay rate of these oscillations. This measurement establishes an intrinsic speed limit for the electro-optic response of this material.
The effect of units derived from diethylene glycol on crystallization kinetics of poly(ethylene terephthalate) (1986)

Abstract The effect of units derived from diethylene glycol (DEG) on the crystallization behaviour and linear growth rate of spherulites of poly(ethylene terephthalate) (PETP) free of metal catalyst residues, is studied by means of differential scanning calorimetry (DSC), small‐angle light scattering (SALS), polarized light microscopy (PLM), and transmission electron microscopy (TEM). The results show that the crystallization behaviour does not depend only on the temperature of crystallization, but also on a large scale on the content of DEG. In hot crystallization, the rate of PETP crystallization decreases with increasing DEG content; in cold crystallization, this effect is not so prominent. The higher the DEG content, the smaller is the number of nuclei and therefore the linear growth rate of PETP and, at the same time, the size of the spherulites becomes greater.
DNA Methylation Cancer Biomarkers: Translation to the Clinic (2019)

Carcinogenesis is accompanied by widespread DNA methylation changes within the cell. These changes are characterized by a globally hypomethylated genome with focal hypermethylation of numerous 5'-cytosine-phosphate-guanine-3' (CpG) islands, often spanning gene promoters and first exons. Many of these epigenetic changes occur early in tumorigenesis and are highly pervasive across a tumor type. This allows DNA methylation cancer biomarkers to be suitable for early detection and also to have utility across a range of areas relevant to cancer detection and treatment. Such tests are also simple in construction, as only one or a few loci need to be targeted for good test coverage. These properties make cancer-associated DNA methylation changes very attractive for development of cancer biomarker tests with substantive clinical utility. Across the patient journey from initial detection, to treatment and then monitoring, there are several points where DNA methylation assays can inform clinical practice. Assays on surgically removed tumor tissue are useful to determine indicators of treatment resistance, prognostication of outcome, or to molecularly characterize, classify, and determine the tissue of origin of a tumor. Cancer-associated DNA methylation changes can also be detected with accuracy in the cell-free DNA present in blood, stool, urine, and other biosamples. Such tests hold great promise for the development of simple, economical, and highly specific cancer detection tests suitable for population-wide screening, with several successfully translated examples already. The ability of circulating tumor DNA liquid biopsy assays to monitor cancer <i>in situ</i> also allows for the ability to monitor response to therapy, to detect minimal residual disease and as an early biomarker for cancer recurrence. This review will summarize existing DNA methylation cancer biomarkers used in clinical practice across the application domains above, discuss what makes a suitable DNA methylation cancer biomarker, and identify barriers to translation. We discuss technical factors such as the analytical performance and product-market fit, factors that contribute to successful downstream investment, including geography, and how this impacts intellectual property, regulatory hurdles, and the future of the marketplace and healthcare system.
Characterisation of two differently processed forms of human recombinant factor IX synthesised in CHO cells transformed with a polycistronic vector (1988)

A stable transformed cell line constitutively expressing human factor IX has been established. Wild-type Chinese hamster ovary cells (CHO cells) were transformed using a polycistronic expression vector carrying a previously isolated factor IX cDNA and a selection gene encoding the Escherichia coli xanthine-guanine phosphoribosyl transferase. One clone, CHO 622.4, contains a high number of genomically integrated plasmids and secretes 1-3 mg factor IX l-1 day-1 into the culture medium with a biological activity ranging from 25% to 40%. The recombinant molecule was purified either by conventional chromatography or by immunoaffinity chromatography using antibodies specific to a calcium-induced factor IX conformer. The purified recombinant protein migrates as a single band with the same mobility as that of natural factor IX on SDS/polyacrylamide gels. N-terminal sequencing shows tow differently processed forms of recombinant factor IX: whereas the majority of the zymogen is correctly processed, approximately 20% of the purified recombinant molecule contains an 18-amino-acid NH2-extension corresponding to the precursor form of factor IX. Analysis of the 4-carboxyglutamic acid content indicates a high but incomplete carboxylation (70%) of the recombinant molecule as compared to natural factor IX. The carbohydrate composition of both the natural and recombinant molecules has been determined. Both molecules have a N-glycan structure of similar complexity, indicating that factor IX contains all the information to direct the same glycosylation pattern in human liver cells and in an unrelated cell line such as CHO-K1.
GUANOSINE PHOSPHATE BINDING PROTEIN COUPLED RECEPTORS IN PROSTATE CANCER: A REVIEW (2002)

GPCR stimulation induces proliferation and prevents apoptosis of hormone independent prostate cancer cells, indicating their important role in the progression of prostate cancer. While further confirmatory studies are required to verify the role of GPCRs in disease progression, the therapeutic implications of these studies may enhance the armamentarium in the fight against prostate cancer.