gebhart/patrepeval huggingface dataset:
Radioprotection of DNA by Polyamines (1995)

Putrescine, spermidine and spermine are natural polyamines bearing at neutral pH the net electrical charges +2, +3 and +4 respectively. We report here the radioprotective effect of these polyamines on the radiolysis of pBR322 plasmid DNA. We observe a very efficient protection against fast neutron-induced single and double-strand breakage in the presence of spermine and spermidine, and a significantly less efficient protection in the presence of putrescine. An ionic strength dependence is observed for spermidine and spermine, but not for putrescine. Circular dichroism measurements show spermidine- and spermine-induced structural modifications of DNA, i.e. the formation of tightly packaged condensates in the concentration range corresponding to radioprotection. No structural change is observed for concentrations of putrescine affording radioprotection. We explain the radioprotection by: (1) the scavenging of OH radicals in the bulk, essentially observed in the case of putrescine; (2) a local scavenging at the sites of binding of polyamines; and (3) the reduced accessibility of the attack sites in the condensed structures induced by spermine or spermidine.
Development of new radiopharmaceuticals based on N-substitution of iminodiacetic acid. (1976)

A new approach to radiopharmaceutical design is demonstrated, in which small chelating groups capable of binding gamma-emitting radiometals are attached to biologically active molecules, thus producing radiopharmaceuticals based on bifunctional drug and biochemical analogs. The chelating group iminodiacetic acid has been evaluated for this role by examining two N-substituted iminodiacetic acids: methyliminodiacetic acid (MIDA) and N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (HIDA). Radiochemical and biologic studies showed that both agents were obtained in high radiochemical purity, were stable in vitro and in vivo, and possessed biologic distributions governed almost exclusively by the N-substituted group. These characteristics of 99mTc-labeled N-substituted iminodiacetic acids, prepared using an "instant kit" method, provide the basis for a valuable new class of radiopharmaceuticals based on bifunctional drug and biochemical analogs.
Filling the Gap Between Morality and Jurisprudence: The Use of Binding Arbitration to Resolve Claims of Restitution Regarding Nazi-Stolen Art (2003)

Recognizing the gaps in existing legislation, this article will argue that disputes arising between claimants and museums regarding the repatriation of Nazi-looted artwork should be decided by binding arbitration rather than litigation. To facilitate such arbitration, international law should support the creation of an arbitration commission, which would provide the most efficient and consistent way to resolve claims. Moreover, a neutral forum with clear rules of law and procedure capable of resolving claims would not only be more fair to claimants, but also to museums and personal collectors. This article will first discuss the severity and magnitude of Nazi looting during the Holocaust. Next, the article will examine post-war efforts to retrieve stolen artwork, focusing upon international laws regarding the disposition of looted assets. Further, this article will analyze particular lawsuits that illustrate the ineffective nature of litigation as a means to facilitate the resolution of these disputes. Finally, this article will argue for the creation of international law or a treaty designating arbitration as the forum to resolve claims of stolen art resulting from the Holocaust, presenting the arguments for and against the use of arbitration to resolve looted artwork claims.
Recent advances in the design of polymeric microneedles for transdermal drug delivery and biosensing (2017)

Microneedles are an efficient and minimally invasive approach to transdermal drug delivery and extraction of skin interstitial fluid. Compared to solid microneedles made of silicon, metals and ceramics, polymeric microneedles have attracted extensive attention due to their excellent biocompatibility, biodegradability and nontoxicity. They are easy to fabricate in large scale and can load drugs in high amounts. More importantly, polymers with different degradation profiles, swelling properties, and responses to biological/physical stimuli can be employed to fabricate polymeric microneedles with different mechanical properties and performance. This review provides a guideline for the selection of polymers and the corresponding fabrication methods for polymeric microneedles while summarizing their recent application in drug delivery and fluid extraction. It should be noted that although polymeric microneedles can achieve efficient transdermal delivery of drugs, their wide applications were limited by their unsatisfactory transdermal therapeutic efficiency. Delivery of nanomedicines that incorporate drugs into functional nanoparticles/capsules can address this problem and thus may be an interesting direction in the future.
Identification of a small molecule that primes the type I interferon response to cytosolic DNA (2017)

The type I interferon response plays a pivotal role in host defense against infectious agents and tumors, and promising therapeutic approaches rely on small molecules designed to boost this system. To identify such compounds, we developed a high-throughput screening assay based on HEK-293 cells expressing luciferase under the control of Interferon-Stimulated Response Elements (ISRE). An original library of 10,000 synthetic compounds was screened, and we identified a series of 1H-benzimidazole-4-carboxamide compounds inducing the ISRE promoter sequence, specific cellular Interferon-Stimulated Genes (ISGs), and the phosphorylation of Interferon Regulatory Factor (IRF) 3. ISRE induction by ChX710, a prototypical member of this chemical series, was dependent on the adaptor MAVS and IRF1, but was IRF3 independent. Although it was unable to trigger type I IFN secretion per se, ChX710 efficiently primed cellular response to transfected plasmid DNA as assessed by potent synergistic effects on IFN-β secretion and ISG expression levels. This cellular response was dependent on STING, a key adaptor involved in the sensing of cytosolic DNA and immune activation by various pathogens, stress signals and tumorigenesis. Our results demonstrate that cellular response to cytosolic DNA can be boosted with a small molecule, and potential applications in antimicrobial and cancer therapies are discussed.
Exogenous retinoic acid rapidly induces anterior ectopic expression of murine <i>Hox-2</i> genes in vivo (1992)

Exogenous retinoic acid (RA) has teratogenic effects on vertebrate embryos and alters Hox-C gene expression in vivo and in vitro. We wish to examine whether RA has a role in the normal regulation of Hox-C genes, and whether altered Hox-C gene expression in response to RA leads to abnormal morphology. The expression of 3' Hox-2 genes (Hox-2.9, Hox-2.8, Hox-2.6 and Hox-2.1) and a 5' gene (Hox-2.5) were examined by whole-mount in situ hybridization on embryos 4 hours after maternal administration of teratogenic doses of RA on embryonic day 7 to 9. The expression of the 3' Hox-2 genes was found to be ectopically induced in anterior regions in a stage-specific manner. The Hox-2.9 and Hox-2.8 genes were induced anteriorly in the neurectoderm in response to RA on day 7 but not at later stages. Expression of Hox-2.6 and Hox-2.1 was ectopically induced anteriorly in neurectoderm in response to RA on day 8. Hox-2.1 remained responsive on day 9, whereas Hox-2.6 was no longer responsive at this stage. The expression of the 5' gene Hox-2.5 was not detectably altered at any of these stages by RA treatments. We also examined the response of other genes whose expression is spatially regulated in early embryos. The expression of En-2 and Wnt-7b was not detectably altered by RA, whereas RAR beta expression was induced anteriorly by RA on day 7 and 8. Krox-20 expression was reduced in a stage- and region-specific manner by RA. The ectopic anterior expression of Hox-2.8 and Hox-2.9 induced by RA on day 7 was persistent to day 8, as was the altered expression of Krox-20. The altered pattern of expression of these genes in response to RA treatment on day 7 may be indicative of a transformation of anterior hindbrain to posterior hindbrain, specifically, a transformation of rhombomeres 1 to 3 towards rhombomere 4 identity with an anterior expansion of rhombomere 5. The ectopic expression of the 3' Hox-2 genes in response to RA is consistent with a role for these genes in mediating the teratogenic effects of RA; the rapid response of the Hox-C genes to RA is consistent with a role for endogenous RA in refining 3' Hox-C gene expression boundaries early in development.
Novel non-basic bioisostere of histidine synthesized from L-aspartic acid (1987)

H. L. Sham, H. Stein and J. Cohen, J. Chem. Soc., Chem. Commun., 1987, 1792 DOI: 10.1039/C39870001792
Systemic Inflammation Induced by microRNAs: Endometriosis-Derived Alterations in Circulating microRNA 125b-5p and Let-7b-5p Regulate Macrophage Cytokine Production (2017)

Endometriosis-derived miRNAs regulate macrophage cytokine production that contributes to inflammation associated with this condition.
Spatial distribution of the internal and near-field intensities of large cylindrical and spherical scatterers (1987)

Spatial distributions of the near-field and internal electromagnetic intensities have been calculated and experimentally observed for dielectric cylinders and spheres which are large relative to the incident wavelength. Two prominent features of the calculated results are the high intensity peaks which exist in both the internal and near fields of these objects, even for nonresonant conditions, and the well-defined shadow behind the objects. Such intensity distributions were confirmed by using the fluorescence from iodine vapor to image the near-field intensity distribution and the fluorescence from ethanol droplets impregnated with rhodamine 590 to image the internal-intensity distribution.
Formulation of <i>Bacillus</i> spp. for Biological Control of Plant Diseases (2004)

ABSTRACT Maximizing the potential for successfully developing and deploying a biocontrol product begins with a carefully crafted microbial screening procedure, proceeds with developing mass production protocols that optimize product quantity and quality, and ends with devising a product formulation that preserves shelf-life, aids product delivery, and enhances bioactivity. Microbial selection procedures that require prospective bio-control agents to possess both efficacy and amenability to production in liquid culture increase the likelihood of selecting agents with enhanced commercial development potential. Scale-up of biomass production procedures must optimize product quantity without compromise of product efficacy or amenability to stabilization and formulation. Formulation of Bacillus spp. for use against plant pathogens is an enormous topic in general terms but limited in published specifics regarding formulations used in commercially available products. Types of formulations include dry products such as wettable powders, dusts, and granules, and liquid products including cell suspensions in water, oils, and emulsions. Cells can also be microencapsulated. Considerations critical to designing successful formulations of microbial biomass are many fold and include preserving biomass viability during stabilization, drying, and rehydration; aiding biomass delivery, target coverage, and target adhesion; and enhancing biomass survival and efficacy after delivery to the target. Solutions to these formulation considerations will not necessarily be compatible. Data from several biocontrol systems including the use of B. subtilis OH 131.1 (NRRL B-30212) to reduce Fusarium head blight of wheat are used to illustrate many of these issues. Using our recently described assay for efficiently evaluating biomass production and formulation protocols, we demonstrate the effectiveness, in vitro, of UV protectant compounds lignin (PC 1307) and Blankophor BBH in reducing OH 131.1 morbidity when cells were exposed to UV light from artificial sunlight.
Newly designed computer controlled knee-ankle-foot orthosis (Intelligent Orthosis) (1998)

The authors have developed a knee-ankle-foot orthosis with a joint unit that controls knee movements using a microcomputer (Intelligent Orthosis). The Intelligent Orthosis was applied to normal subjects and patients, and gait analysis was performed. In the gait cycle, the ratio of the stance phase to the swing phase was less in gait with the knee locked using a knee-ankle-foot orthosis than in gait without an orthosis or gait with the knee controlled by a microcomputer. The ratio of the stance phase to the swing phase between controlled gait and normal gait was similar. For normal subjects the activity of the tibialis anterior was markedly increased from the heel-off phase to the swing phase in locked gait. The muscle activities of the lower limb were lower in controlled gait than in locked gait. The ground reaction force in locked gait showed spikes immediately after heel-contact in the vertical component, and unusual patterns were observed at heel-contact in the sagittal and lateral component. Therefore, compared to locked gait, gait with the Intelligent Orthosis is smooth and close to normal gait from the viewpoint of biomechanics. Even in patients with muscle weakness of the quadriceps, control of the knee joint using the Intelligent Orthosis resulted in a more smooth gait with low muscle discharge.
Pyrane, 100. 5,6‐Dihydro‐2<i>H</i>‐pyran‐3(4<i>H</i>)‐on als Baustein zur Synthese pyrananellierter Heterocyclen (1984)

Abstract Während 5,6‐Dihydro‐2 H ‐pyran‐3(4 H )‐on ( 3 ) sich mit ortho ‐substituierten Phenylcarbonylverbindungen nur in Einzelfällen regioselektiv zu pyrananellierten Heterocyclen umsetzt ‐ z. B. zum Pyrano[2,3‐ b ]chinolin 7c ‐, gelingt das besser mit dem aus 3 hergestellten Enamin 15d , dem Silylenolether 18 und dem daraus gewonnenen Lithiumenolat 14 . Diese Pyranderivate mit 2,3‐oder 3,4‐Doppelbindungen eignen sich zur gezielten Darstellung von 2‐ oder 4‐substituierten 3‐Pyranonen ‐ z.B. 2, 21a, 21b, 23a – c, 26a – c, 31a – c, 32 , sowie 35a – c – und von Pyrano[3,2‐ b ]‐ oder ‐[3,4‐ b ]chinolinen, ‐chinolonen, ‐chromonen und ‐thiochromonen 6a, 30a – c und 38a – d .
Strategies for Epicardial Mapping and Ablation of Ventricular Tachycardia (2009)

Catheter ablation for ventricular tachycardia (VT) is becoming an essential component of the successful management of patients with structural heart disease and refractory ventricular arrhythmias. Despite detailed mapping and ablation from the endocardium, nearly a third of VT circuits remain inaccessible. Pericardial access has improved our ability to address these resistant VTs. Adhesions after cardiac surgery can impede access, necessitating a direct surgical approach to the pericardial space. Potential risks include risk of injury to an epicardial coronary artery, the phrenic nerve, subdiaphragmatic vessels, and right ventricle. We describe the indications for and approach to catheter ablation of VT for the pericardial space.
Antiserum to a Synthetic Peptide Recognizes the HTLV-III Envelope Glycoprotein (1986)

In a study performed to determine which regions of the human T-cell lymphotrophic virus type III (HTLV-III) may represent vaccine candidates to prevent the acquired immune deficiency syndrome (AIDS), a synthetic peptide corresponding to amino acid sequence 735 to 752 of the precursor envelope glycoprotein of HTLV-III was used to immunize rabbits. The resulting rabbit antiserum to the synthetic peptide specifically recognized the precursor envelope glycoprotein (gp160) of HTLV-III. Human sera positive for antibody to HTLV-III reacted with this peptide. These findings indicate that synthetic peptides can be used to induce an immune response directed against a native envelope glycoprotein epitope of HTLV-III. The data are discussed in terms of using synthetic peptides to identify antigenic determinants involved in the induction of protective immunity and possibly as vaccine candidates against the etiologic agent of AIDS.
Clustering of cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null mice (2003)

A single gene defect, eNOS deficiency, causes a clustering of cardiovascular risk factors in young mice. We speculate that defective nitric oxide synthesis could trigger many of the abnormalities making up the metabolic syndrome in humans.
The cost of preterm birth: the low cost versus high value of tocolysis (2006)

The consequences of preterm birth (PTB), to the individual and society at large, remain a major financial and personal burden. Babies born at the limits of viability, who survive, often have major neurological impairments, such as cerebral palsy, developmental delay and blindness. The cost of initial hospitalisation is more than $200,000 for each birth but takes no account of future costs once they leave the hospital. The major morbidities associated with extreme prematurity are respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC). With advancing gestational age at birth, the financial costs and morbidity associated with these conditions decrease. The major morbidities (RDS, IVH and NEC) are rare by 34 weeks of gestation, with the exception of RDS, which complicates 7% of deliveries at this gestational age. While the vast majority of infants survive the first year of life, the infant mortality rate is markedly increased by three- to five-fold even for the mildly preterm infants, as compared with that of the term infants. Neonates born after 34 completed weeks of gestation rarely have mortality or major morbidity, but the financial costs remain significant ($7000 per case), and efforts to prevent delivery at this gestational age are probably indicated. Economic costs associated with PTB include the cost of initial hospitalisation, the cost of any chronic diseases resulting from the prematurity and social costs including loss of gainful employment by a family member taking care of the infant or child and loss of potential future earnings of the affected child. Antenatal steroids, if given to the mother at least 48 hours prior to a PTB, have shown significant reductions in RDS, IVH and NEC. Efforts to prevent, or avoid, PTB include the use of tocolytic agents which have been shown to prolong gestation for a minimum of 48 hours, or longer in some cases. The range of tocolytic agents used to delay or prevent PTB work through many different pathways, with varying degrees of success. Which tocolytic agent to use depends on many factors including underlying maternal status, gestational age of the fetus and documented efficacy of agent used.
The pathophysiology of superoxide: roles in inflammation and ischemia (1982)

The superoxide radical plays major roles in the neutrophil-medicated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite different in these two pathological states. While neutrophils produce superoxide for the primary purpose of aiding in the killing of ingested microbes, a second useful function has evolved. The superoxide released from actively phagocytosing neutrophils serves to attract more neutrophils by reacting with, and activating, a latent chemotactic factor present in plasma. Superoxide dismutase, by preventing the activation of this superoxide-dependent chemotactic factor, exerts potent anti-inflammatory action. During ischemia, energy-starved tissues catabolize ATP to hypoxanthine. Calcium transients in these cells appear to activate a calmodulin regulated protease which attacks the enzyme xanthine dehydrogenase, converting it to a xanthine oxidase capable of superoxide generation. When the tissue is reperfused and reoxygenated, all the necessary components are present (xanthine oxidase, hypoxanthine, and oxygen) to produce a burst of superoxide which results in extensive tissue damage. Ischemic tissues are protected by superoxide dismutase or allupurinol, an inhibitor of xanthine oxidase.
The alpha 3 chain of type IV collagen induces autoimmune Goodpasture syndrome. (1994)

Human Goodpasture syndrome is a lethal form of autoimmune disease that is characterized by pulmonary hemorrhage and glomerulonephritis. The tissue injury is mediated by autoantibodies that bind to glomerular and alveolar basement membrane. The target autoantigen is alpha 3(IV) collagen, one of six genetically distinct chains that comprise type IV collagen, and the epitope is sublocalized to the noncollagenous domain (NC1) of the alpha 3 chain. The present study reports the unique capacity of alpha 3(IV)NC1 dimer from bovine kidney to aberrantly engage the immune system of rabbits to respond to self, mimicking the organ-specific form of the human disease, whereas the other chains of type IV collagen are nonpathogenic. However, alpha 3(IV)NC1 hexamer was nonpathogenic, suggesting the exposure of a pathogenic epitope upon dissociation of hexamer into dimers. Exposure of the pathogenic epitope by infection or organic solvents, events which are thought to precede Goodpasture syndrome, may be the principal factor in the etiology of the disease. The pathogenicity of alpha 3(IV) collagen brings full circle a decade of research that has identified four novel chains (alpha 3-alpha 6) of type IV collagen.
Inhibition of histone deacetylase activity by trichostatin A modulates gene expression during mouse embryogenesis without apparent toxicity. (2001)

Remodeling of the chromatin template by inhibition of histone deacetylase (HDAC) activities represents a major goal for transcriptional therapy in neoplastic diseases. Recently, a number of specific and potent HDAC-inhibitors that modulate in vitro cell growth and differentiation have been developed. In this study we analyzed the effect of trichostatin A (TSA), a specific and potent HDAC-inhibitor, on mouse embryos developing in vivo. When administered i.p. to pregnant mice (at a concentration of 0.5-1 mg/kg) at postimplantation stages (embryonic day 8 to embryonic day 10), TSA was not toxic for the mother and did not cause any obvious malformation during somitogenesis or at later stages of development. Treated embryos were born at similar frequency and were indistinguishable from control animals, developed normally, and were fertile. Interestingly, embryos from TSA-treated mice killed during somitogenesis were modestly but consistently larger than control embryos and presented an increased (+2 to +6) number of somites. This correlated with an increased acetylation of histone H4, the number of somites expressing the myogenic factor Myf-5, and the expression of Notch, RARalpha2, and RARbeta2 mRNAs. These data indicate that the effects of TSA on transcription: (a) are not toxic for the mother; (b) transiently accelerated growth in mouse embryos without perturbing embryogenesis; and (c) do not result in teratogenesis, at least in rodents. Thus, TSA might represent a nontoxic and effective agent for the transcriptional therapy of neoplasia.