gebhart/patrepeval huggingface dataset:
Induction of Immunological Tolerance in Bone Marrow-Derived Lymphocytes of the IgE Antibody Class (1973)

Administration of the 2,4-dinitrophenyl (Dnp) determinant conjugated to the "nonimmunogenic" copolymer of D-glutamic acid and D-lysine (D-GL) induces Dnp-specific immunological tolerance which is essentially restricted to bone marrow-derived (B) lymphocytes. Previous studies have demonstrated tolerance induction by Dnp-D-GL in predominantly B lymphocytes of the IgG class. The present studies establish and analyze conditions for tolerance induction in Dnp-specific B lymphocytes of the IgE antibody class by taking advantage of: (i) the relatively easy capacity to induce tolerance with Dnp-D-GL in an animal or cell population previously primed to the Dnp determinant; (ii) previously established parameters for the successful adoptive transfer of Dnp-specific IgE antibody responses; and (iii) the capacity to induce, and maintain a state of Dnp-specific tolerance with Dnp-D-GL in adoptive transfer responses. Using these approaches, we have successfully rendered Dnp-specific B cells of the IgE class profoundly and apparently irreversibly tolerant after exposure of such cells to Dnp-D-GL. These observations represent a starting point of wide potential for solving many therapeutic problems concerned with clinical allergies.
Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects (2017)

Our results contribute to the development of CRISPR-Cas9 system for agriculture applications.
Metallo/clusto hybridized supramolecular polymers (2014)

The introduction of metal centers to a supramolecular polymer system is an important approach to fabricate hybrid supramolecular polymers with synergistic properties between their inorganic and organic components, which is mainly realized through two strategies: one is the embedment of metal ions through metal-ligand coordination to form metallo-supramolecular polymers (MSPs); the other is using metal-containing clusters as hybrid building blocks to prepare clusto-supramolecular polymers (CSPs). The available paradigms of MSPs and CSPs not only exhibit the unique functions of metal centers but also hold the good processing ability and the stimuli-responsibility of dynamically bonded polymeric structures, thus representing a new class of hybrid soft materials. In this review, the development and recent progress of MSPs and CSPs are discussed in detail, including their structure design, synthetic procedures and related properties. Finally, challenges and potential areas in metal-containing supramolecular polymers are outlooked.
EM49, a new peptide antibiotic. IV. The structure of EM49. (1975)

EM49 is a family of similar peptide antibiotics, each an octapeptide acylated with a beta-hydroxy fatty acid. This paper described the determination of the structure of the fatty acyl residue, the selective removal of this residue from the peptide portion of the molecule, and the sequential analysis of the peptide by the EDMAN method. The structure of EM49, 1, is derived by this degradation.
Germ line manipulation: applications in agriculture and biotechnology. (1992)

Little is known about the association of sleep duration with hyperuricemia. Especially lacking is evidence from longitudinal studies. Based on the MJ Health Examination Database in Beijing, China, a prospective study was designed. Participants were classed into short, normal, and long groups by sleep duration. The Cox regression model was used to estimate the hazard risk of hyperuricemia for short or long sleep duration compared with the normal group after adjusting for potential confounders. During a median 3.08 years follow-up, 4868 (14.31%) incident hyperuricemia events were documented among 34,025 participants with a crude incidence rate of 39.49 per 1000 persons. Years after adjusting for potential confounders, a 7% higher risk of hyperuricemia in the short sleep duration group (<7 h, 95% confidence interval: 1.01−1.14) and a 15% lower risk in the long sleep duration group (≥8 h, 95%CI: 0.74−0.97) were found compared with the normal group (7−8 h) (p for trend < 0.001). Nevertheless, the association of the short sleep duration group was marginally significant after further adjustment of the count of white blood cells (hazard ratio: 1.07, 95%CI: 1.00−1.13). Sleep duration was inversely associated with hyperuricemia, which highlights the public health significance of sufficient sleep duration for preventing hyperuricemia.
Molecular Biology of Alzheimer’s Dementia and Its Clinical Relevance to Early Diagnosis and New Therapeutic Strategies (2001)

Over the past few years, molecular biological research has considerably deepened our understanding of the pathophysiological basis of Alzheimer's dementia (AD). Although different genetic origins of the disease have been identified, all of the findings point to a common terminal sequence in familial AD. This consists of an increased production of beta-amyloid peptides from beta-amyloid precursor protein. For the cases of sporadic AD, which far outweigh the number of cases of familial AD, an impaired catabolism of the beta-amyloid peptides may also be pathophysiologically decisive according to the latest findings. Research into the molecular level of AD makes it possible to identify points of attack for rational drug treatment of the disease, while molecular markers of AD are increasingly being used as a part of early and differential neurochemical diagnostics.
Melancholic symptom features and DSM-IV (1994)

The available evidence suggests some clinical utility and some (albeit not entirely consistent) validity for the concept of melancholic features. Consequently, DSM-IV will retain the designation "with melancholic features," return to the shorter DSM-III feature listing, and broaden the designation by requiring either unreactive mood or pervasive anhedonia but not both. Further research on this subgroup is indicated.
Theoretical and practical advances in genome halving (2004)

In this paper, we derive a new upper bound on the genome halving distance that is tighter than the best known, and a new lower bound that is almost always tighter than the best known. We also define the notion of genome halving diameter, and obtain both upper and lower bounds for it. Our tighter bounds on genome halving distance yield a new algorithm for reconstructing an ancestral duplicated genome. We create a software package GenomeHalving based on this new algorithm and test it on the yeast genome, identifying a sequence of translocations for halving the yeast genome that is shorter than previously conjectured possible.
Increased gut cholinergic activity and antagonism of 5‐hydroxytryptamine M‐receptors by BRL 24924: potential clinical importance of BRL 24924 (1987)

The mechanisms by which BRL 24924 ([(+/-)- (endo)])-4-amino-5-chloro-2-methoxy-N-(1-azabicyclo-[3.3.1]-non- 4-yl) benzamide hydrochloride stimulates gut motility and the relationships between BRL 24924 and 5-hydroxytryptamine (5-HT) receptors have been studied. In guinea-pig isolated ileum, BRL 24924 (10(-14)-10(-6) M) increased electrically-evoked, cholinergically-mediated contractions, probably by increasing acetylcholine (ACh) release. This action of BRL 24924 was prevented by the presence of high concentrations of 5-HT, but not by hexamethonium, phentolamine and propranolol, methysergide or ICS 205-930. The mechanism by which BRL 24924 can increase gut ACh release is not certain, but most likely involves activation of an enteric 5-HT receptor which differs from those 5-HT M-receptors antagonized by ICS 205-930 or by higher concentrations of BRL 24924 in other test systems. BRL 24924 antagonized 5-HT-evoked, cholinergically-mediated contractions of guinea-pig isolated ileum (pA2 = 7.56 +/- 0.12). Similar and higher concentrations of BRL 24924 did not antagonize contractions evoked by nicotinic receptor stimulation. In rabbit isolated heart, BRL 24924 1-10 nM reduced the tachycardia evoked by 5-HT. In anaesthetized rats, BRL 24924 0.3-83 nmol kg-1 i.v. antagonized the Bezold-Jarisch reflex evoked by 5-HT; the ID50 for BRL 24924 was 10.2 +/- 3.0 nmol kg-1 (3.7 +/- 1.1 microgram kg-1). A direct action of BRL 24924 on nerve function was excluded. In rat cortex, BRL 24924 10(-6) M did not displace [3H]-5-HT or [3H]-ketanserin binding to 5-HT1 and 5-HT2 receptors. The actions of BRL 24924 are discussed in terms of its potential clinical use as a stimulant of gastric motility and as a 5-HT M-receptor antagonist.
In vitro and in vivo activities of the nitroimidazole CGI 17341 against Mycobacterium tuberculosis (1993)

CGI 17341 (2-ethyl-5-nitro-2,3-dihydro[2-1b]imidazo-oxazole) is a novel orally active representative of the 5-nitroimidazole series of antimicrobial agents. At concentrations ranging from 0.1 to 0.3 micrograms/ml, CGI 17341 inhibited the drug-susceptible and multi-drug-resistant strains of Mycobacterium tuberculosis. CGI 17341 had no cross-resistance with isoniazid, rifampin, streptomycin, or ethambutol. While the in vitro activity of CGI 17341 against M. tuberculosis was comparable to those of isoniazid and rifampin, it was superior to those of streptomycin, ciprofloxacin or norfloxacin, and oxazolidinone DuP 721. The MIC of CGI 17341 was not affected when the pH of the medium was decreased from 6.8 to 5.6, while four- to sixfold increases in the MICs of ciprofloxacin and isoniazid were observed. In mice infected with M. tuberculosis, the 50% effective dose for CGI 17341 was 7.7 mg/kg of body weight (95% confidence limits, 3.5 and 10.27) when administered on days 11 and 12 postinfection. CGI 17341 gave a dose-dependent (r = 0.995) and significant increase in the survival time. Our data indicate that the 5-nitroimidazole CGI 17341 is a promising and novel antituberculosis compound with potent in vitro and in vivo activities. Further investigations on this compound are warranted.
Voltage-gated sodium channels and the molecular pathogenesis of pain: a review. (2001)

Pain pathways begin with spinal sensory (dorsal root ganglion, DRG) neurons that produce nociceptive signals and convey them centrally. Following injury to the nervous system, DRG neurons can become hyperexcitable, generating spontaneous action potentials or abnormal high-frequency activity that contributes to chronic pain. Because the generation of action potentials in DRG neurons depends on voltage-gated sodium channels, an understanding of the expression and function of these channels in DRG neurons is important for an understanding of pain. Molecular studies have indicated that at least eight distinct voltage-gated sodium channels, sharing a common overall motif but encoded by different genes that endow them with different amino acid sequences, are present within the nervous system. The DRG neurons express six different sodium channels, including several sensory-neuron-specific sodium channels that are not present at significant levels within other parts of the nervous system. Following injury to their axons within peripheral nerve, DRG neurons down-regulate some sodium channel genes, and up-regulate others. As a result, a different repertoire of sodium channels is inserted into the DRG neuron cell membrane following injury, which is a molecular change that is accompanied by changes in physiological properties that contribute to hyperexcitability in these cells. Sodium channel expression is also altered in experimental models of inflammatory pain. The multiplicity of sodium channels, and the dynamic nature of their expression, makes them important targets for pharmacologic manipulation in the search for new therapies for pain.
An O(n1.5logn) 1-d compaction algorithm (1990)

In this paper, we bound the complexity of the major algorithms of 1-d compaction in graph solution and module assembly to be Ο(n15logn). An 1-d hierarchical module assembly method is shown to be free from the x-y interlock problem and achieves significant improvement in space and time requirements by exploiting hierarchy.
A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies (2013)

NCT00687934.
CCDC26,CDKN2BAS,RTEL1andTERTPolymorphisms in pediatric brain tumor susceptibility (2015)

The role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is poorly understood. We hypothesized that single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) on adult glioma would also be associated with PBT risk. The study is based on the Cefalo study, a population-based multicenter case-control study. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was extracted and genotyped for 29 SNPs reported by GWAS to be significantly associated with risk of adult glioma. Data were analyzed using unconditional logistic regression. Stratified analyses were performed for two histological subtypes: astrocytoma alone and the other tumor types combined. The results indicated that four SNPs, CDKN2BAS rs4977756 (p = 0.036), rs1412829 (p = 0.037), rs2157719 (p = 0.018) and rs1063192 (p = 0.021), were associated with an increased susceptibility to PBTs, whereas the TERT rs2736100 was associated with a decreased risk (p = 0.018). Moreover, the stratified analyses showed a decreased risk of astrocytoma associated with RTEL1 rs6089953, rs6010620 and rs2297440 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). Our findings indicate that SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26 may be associated with the risk of PBTs. Therefore, we suggest that pediatric and adult brain tumors might share common genetic risk factors and similar etiological pathways.
Diffusion Controlled and Temperature Stable Microcapsule Reaction Compartments for High‐Throughput Microcapsule‐PCR (2008)

Abstract A novel approach to perform a high number of individual polymerase chain reactions (PCR) in microcapsule reaction compartments, termed “Microcapsule‐PCR” was developed. Temperature stable microcapsules with a selective permeable capsule wall were constructed by matrix‐assisted layer‐by‐layer (LbL) Encapsulation technique. During the PCR, small molecular weight building blocks – nucleotides (dNTPs) were supplied externally and diffuse through the permeable capsule wall into the interior, while the resulted high molecular weight PCR products were accumulated within the microcapsule. Microcapsules (∼110.8 µm average diameter) filled with a PCR reaction mixture were constructed by an emulsion technique having a 2% agarose core and a capsule formed by LbL coating with poly(allylamine‐hydrochloride) and poly(4‐styrene‐sulfonate). An encapsulation efficiency of 47% (measured for primer‐FITC (22 bases)) and 98% PCR efficiency was achieved. Microcapsules formed by eight layers of polyelectrolyte and subjected to PCR cycling (up to 95 °C) demonstrated good temperature stability without any significantly changes in DNA retention yield and microcapsule morphology. A multiplex Microcapsule‐PCR experiment demonstrated that microcapsules are individual compartment and do not exchange templates or primers between microcapsules during PCR cycling.
Two-Layer Flow with One Viscous Layer in Inclined Channels (2008)

We study pressure-driven, two-layer flow in inclined channels with high density and viscosity contrasts. We use a combination of asymptotic reduction, boundary-layer theory and the Karman-Polhausen approximation to derive evolution equations that describe the interfacial dynamics. Two distinguished limits are considered: where the viscosity ratio is small with density ratios of order unity, and where both density and viscosity ratios are small. The evolution equations account for the presence of inertia, gravity, capillarity and viscous retardation; attention is restricted to situations in which the flow is laminar. The results of our linear stability analysis and numerical simulations indicate that the flow is destabilised by positive channel inclination in the stably stratified case. The dependence of the nonlinear wave dynamics on system parameters is also explored.
Recent advances in IL-22 biology (2011)

Several cell types, in particular epithelial cells, express the receptor for the cytokine IL-22 and upon its recognition produce molecules that are active both locally and systemically. Many different types of lymphocyte secrete IL-22. T(h)17 cells produce IL-22 although the optimal conditions for secretion of IL-17 or IL-22 by T(h)17 cells differ, as do the transcription factors involved. Aryl hydrocarbon receptor is required for IL-22 production by T(h)17, T(h)22 and γδ T cells. T(h)22 cells produce IL-22 in response to IL-6 and tumor necrosis factor α (TNF-α), particularly in the skin, whereas γδ T cells produce IL-22 in response to IL-23, particularly in the lung. NK cells produce IL-22 in response to IL-12 and IL-18 or IL-23. Retinoic acid-related orphan receptorγt-positive innate lymphoid cells, including lymphoid tissue inducer (LTi) and LTi-like cells express IL-22 with IL-23 again enhancing expression. IL-22 is known to be expressed in many chronic inflammatory conditions, including psoriasis and rheumatoid arthritis, and its up-regulation often correlates with disease activity. IL-22 is known to be protective in the gastrointestinal tract in inflammatory bowel disease but may mediate either harmful or helpful inflammatory responses in different models of intestinal infection. Finally, IL-22 may also play an important role in tissue repair.
Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase (2008)

Destruction of skeletal muscle extracellular matrix is an important pathological consequence of many diseases involving muscle wasting. However, the underlying mechanisms leading to extracellular matrix breakdown in skeletal muscle tissues remain unknown. Using a microarray approach, we investigated the effect of tumor necrosis factor-related weak inducer of apoptosis (TWEAK), a recently identified muscle-wasting cytokine, on the expression of extracellular proteases in skeletal muscle. Among several other matrix metalloproteinases (MMPs), we found that the expression of MMP-9, a type IV collagenase, was drastically increased in myotubes in response to TWEAK. The level of MMP-9 was also higher in myofibers of TWEAK transgenic mice. TWEAK increased the activation of both classical and alternative nuclear factor-kappaB (NF-kappaB) signaling pathways. Inhibition of NF-kappaB activity blocked the TWEAK-induced production of MMP-9 in myotubes. TWEAK also increased the activation of AP-1, and its inhibition attenuated the TWEAK-induced MMP-9 production. Overexpression of a kinase-dead mutant of NF-kappaB-inducing kinase or IkappaB kinase-beta but not IkappaB kinase-alpha significantly inhibited the TWEAK-induced activation of MMP-9 promoter. The activation of MMP-9 also involved upstream recruitment of TRAF2 and cIAP2 proteins. TWEAK increased the activity of ERK1/2, JNK1, and p38 MAPK. However, the inhibition of only p38 MAPK blocked the TWEAK-induced expression of MMP-9 in myotubes. Furthermore the loss of body and skeletal muscle weights, inflammation, fiber necrosis, and degradation of basement membrane around muscle fibers were significantly attenuated in Mmp9 knock-out mice on chronic administration of TWEAK protein. The study unveils a novel mechanism of skeletal muscle tissue destruction in pathological conditions.
Time-resolved coherent anti-Stokes Raman scattering microscopy: Imaging based on Raman free induction decay (2002)

A time-resolved coherent anti-Stokes Raman scattering (CARS) microscope allows three-dimensional imaging based on Raman free induction decay of molecular vibration with no requirement for labeling of the sample with natural or artificial fluorophores. A major benefit of the technique is the capability to completely remove nonresonant coherent background signal from the sample and the solvent, and thus increasing the detection sensitivity of CARS microscopy significantly.
Genetic and Biochemical Studies on Mannose-Negative Mutants That Are Deficient in Phosphomannose Isomerase in Escherichia coli K-12 (1967)

Two mannose-negative mutants of Escherichia coli K-12 have been isolated. These mutants are deficient in the ability to synthesize phosphomannose isomerase and capsular polysaccharide when grown on glucose-containing media. Interrupted mating experiments to determine the kinetics of genetic transfer show that the two mannose-negative mutations map together between the histidine and tryptophan regions of the E. coli chromosome.
Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis (2013)

Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).
A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity (2001)

GM1-ganglioside receptor binding by the B subunit of cholera toxin (CtxB) is widely accepted to initiate toxin action by triggering uptake and delivery of the toxin A subunit into cells. More recently, GM1 binding by isolated CtxB, or the related B subunit of Escherichia coli heat-labile enterotoxin (EtxB), has been found to modulate leukocyte function, resulting in the down-regulation of proinflammatory immune responses that cause autoimmune disorders such as rheumatoid arthritis and diabetes. Here, we demonstrate that GM1 binding, contrary to expectation, is not sufficient to initiate toxin action. We report the engineering and crystallographic structure of a mutant cholera toxin, with a His to Ala substitution in the B subunit at position 57. Whereas the mutant retained pentameric stability and high affinity binding to GM1-ganglioside, it had lost its immunomodulatory activity and, when part of the holotoxin complex, exhibited ablated toxicity. The implications of these findings on the mode of action of cholera toxin are discussed.
Metal pattern fabrication using the local electric field of a conducting atomic force microscope probe (1997)

Two approaches were developed using an ambient atomic force microscope (AFM) to pattern metal in either positive or negative tone. The difference in surface chemical reactivity between exposed and unexposed regions was used to selectively attach colloidal Pd(II) nanoparticles capable of initiating the deposition of electroless (EL) Ni. In one case, EL Ni was selectively deposited in the unexposed regions of an organosilane film. In the second case, EL Ni was selectively deposited directly on an AFM oxide pattern. Based on the different binding selectivities of the Pd(II) catalysts, selective deposition on AFM patterns was attributed to the presence of a carbon residue in AFM oxide patterns formed under ambient conditions. The patterned Ni films were used as a mask for pattern transfer into the underlying substrate by reactive ion etching.
The mannitol repressor (MtlR) of Escherichia coli (1994)

The mannitol operon of Escherichia coli, encoding the mannitol-specific enzyme II of the phosphotransferase system (Mt1A) and mannitol phosphate dehydrogenase (Mt1D), is here shown to contain a single additional downstream open reading frame which encodes the mannitol repressor (Mt1R). Mt1R contains 195 amino acids and has a calculated molecular weight of 21,990 and a calculated pI of 4.5. It is homologous to the product of an open reading frame (URF2D) upstream of the E. coli gapB gene but represents a novel type of transcriptional regulatory protein.