gebhart/patrepeval huggingface dataset:
Carotenoid composition, concentrations, and relationships in various human organs. (1990)

The carotenoid content of 10 different organs obtained at autopsy from 16 humans was determined using a high-performance liquid chromatography assay. The same qualitative pattern of carotenoids found in serum was found for all the tissues, although there were important quantitative differences in the different carotenoids between organs. The median levels of zeaxanthins, lycopene and beta-carotene varied disproportionately between organs; similar levels of one carotenoid for two organs would not predict similar levels of another carotenoid for the same organs. Similarly, there was not a consistent relationship between all the carotenoids for a given organ. The uneven but wide tissue distribution of most dietary carotenoids may indicate an active biological role for these compounds.
Sleep Research in Affective Illness: State of the Art Circa 1987 (1987)

Future sleep research in affective illness will probably continue the current evolution beyond cross-sectional to longitudinal studies, and beyond a largely descriptive emphasis to the testing of specific hypotheses and predictions derived from models of the pathophysiology of depression. These models are and will be variously neurochemical, chronobiological, genetic, and developmental in nature. Adequate testing of these models and predictions from them will require the use of pharmacologic and naturalistic probes and the use of sophisticated CNS imaging techniques. These probes will help further characterize the physiology of depression under conditions of disequilibrium or perturbation, such as following sleep deprivation, REM deprivation, phase advancement of the major sleep period, or the administration of antidepressant drugs with specific monoaminergic activity. Concurrently, if one is to understand further whether the sleep abnormalities of depression are part of a larger circadian rhythm disturbance, investigations will necessarily include 24-h measures of sleep-wake activity, psychomotor activity, and probably core body temperature rhythm under constant routine conditions. A complementary point of view would suggest that more intensive investigative efforts be focused on the first 100 min of sleep at night, since it is the first NREM-REM cycle that seems to show the greatest and most specific deviation in depressed patients from normal controls. Efforts to characterize further this part of the 24-h cycle, with respect to age- and gender-related variance as well as responses to physiologic, hormonal, pharmacologic, and naturalistic probes, are strongly warranted.
Protection Against Murine Cytomegalovirus Infection by Passive Transfer of Neutralizing and Non-Neutralizing Monoclonal Antibodies (1991)

The ability of eight neutralizing monoclonal antibodies (MAbs) specific for structural proteins of murine cytomegalovirus (MCMV) to protect mice passively against MCMV infection was examined to determine firstly whether a correlation existed between the neutralization titres of the MAbs in vitro and the protection afforded by the MAbs in vivo and, secondly, the contribution of the host towards neutralization by the MAbs in vivo. The reduction in MCMV titre in the livers of BALB/c and C57BL/10 mice by the MAbs closely correlated with their neutralization titres in vitro. However, in the spleens of BALB/c mice, in which MCMV replicates to high titre, almost all of the MAbs tested were ineffective in reducing MCMV replication. Indeed, a significant increase in splenic MCMV replication was observed in mice treated 24 h prior to MCMV replication with either neutralizing MAbs or polyclonal Ig. Each of six MAbs prophylactically protected between 66 and 100% of mice from an intraperitoneal challenge with 4 LD50 MCMV regardless of their neutralization titre in vitro. The persistence of MCMV replication in the salivary gland was not prevented by either polyclonal Ig or MAbs. Despite the absolute requirement for complement for the neutralization of MCMV in vitro, both polyclonal Ig and MAb 4F9 protected A/J mice, which are deficient in the fifth component of complement, as efficiently as they did complement competent BALB/c mice. These results demonstrate that MAbs specific for single MCMV polypeptides are protective in vivo. In addition, the extent to which the MAbs protected against MCMV could not be predicted from their immunoreactive or neutralizing titres in vitro or by their effect on splenic MCMV replication in vivo. Furthermore, these studies suggest that the mechanism(s) of neutralization of MCMV in vitro are different to those which act in vivo.
Photoacoustic Microscopy: Superdepth, superresolution, and superb contrast (2015)

Since its invention in the 17th century, optical microscopy has revolutionized biomedical studies by scrutinizing the biological realm on cellular levels, taking advantage of its excellent light-focusing capability. However, most biological tissues scatter light highly. As light travels in tissue, cumulative scattering events cause the photons to lose their original propagation direction and, thus, their ability to be focused, which has largely limited the penetration depth of optical microscopy. Conventional planar optical microscopy can provide penetration of only ~100 ?m before photons begin to be scattered. The penetration of modern optical microcopy, such as confocal microscopy and multiphoton microscopy, is still limited to approximately the optical diffusion limit (~1 mm in the skin as approximated by one optical transport mean free path), where scattered photons retain a strong memory of the original propagation direction. So far, it still remains a challenge for pure optical methods to achieve high-resolution in vivo imaging beyond the diffusion limit (i.e., superdepth imaging).
A Visual DNA Chip for Simultaneous Detection, Genotyping and Differentiation of Wild-type and Vaccine-type Classical Swine Fever Virus (2008)

Routinely, RT-PCR followed by DNA sequencing has been the method used to detect classical swine fever virus (CSFV) and exclude the interference of vaccine viruses for the field cases. Here, a DNA chip assay was developed to enable simultaneous detection, genotyping and differentiation between wild and vaccine-type CSFV. Specific oligonucleotide primers and probes were designed in the 3'non-translated region of the CSFV genome. One-step RT-PCR amplification was performed with biotin-labeled primers, followed by hybridization to the DNA probe immobilized on the plastic chip. The DNA chip can not only accurately differentiate between the three major genotypes of CSFV, but can also discriminate between wild-type and vaccine-type CSFV. The limit of detection for wild-type virus was 10 TCID50/mL for RT-PCR and 1 TCID50/mL for the DNA chip. The sensitivity of the visual DNA Chip was 10 times higher than that of the RT-PCR confirmed by agarose gel. We conclude that RT-PCR coupled with DNA probe hybridization provides a highly sensitive diagnostic tool for genotyping CSFV and discriminating between wild-type and vaccine-type CSFV in clinical samples.
Pharmacologic treatment of Alzheimer's disease: an update. (2003)

Alzheimer's disease is characterized by the development of senile plaques and neurofibrillary tangles, which are associated with neuronal destruction, particularly in cholinergic neurons. Drugs that inhibit the degradation of acetylcholine within synapses are the mainstay of therapy. Donepezil, rivastigmine, and galantamine are safe but have potentially troublesome cholinergic side effects, including nausea, anorexia, diarrhea, vomiting, and weight loss. These adverse reactions are often self-limited and can be minimized by slow drug titration. Acetylcholinesterase inhibitors appear to be effective, but the magnitude of benefit may be greater in clinical trials than in practice. The drugs clearly improve cognition, but evidence is less robust for benefits in delaying nursing home placement and improving functional ability and behaviors. Benefit for vitamin E or selegiline has been suggested, but supporting evidence is not strong. Most guidelines for monitoring drug therapy in patients with Alzheimer's disease recommend periodic measurements of cognition and functional ability. The guidelines generally advise discontinuing therapy with acetylcholinesterase inhibitors when dementia becomes severe.
The 289-amino acid E1A protein of adenovirus binds zinc in a region that is important for trans-activation. (1988)

The E1A gene of adenovirus type 5 encodes two major proteins of 289 and 243 amino acid residues, which are identical except that the larger protein has an internal stretch of 46 amino acids required for efficient trans-activation of early viral promoters. This domain contains a consensus zinc finger motif (Cys-Xaa2-Cys-Xaa13-Cys-Xaa2-Cys) in which the cysteine residues serve as postulated ligands. Atomic absorption spectrophotometry applied to bacterially expressed E1A proteins revealed that the 289-amino acid protein binds one zinc ion, whereas the 243-amino acid protein binds no zinc. Replacing individual cysteine residues of the finger with other amino acids destroyed the trans-activating ability of the 289-amino acid protein, even when structurally or functionally conserved amino acids were substituted. These results strongly suggest that the zinc finger of the 46-amino acid domain is intimately linked to the ability of the large E1A protein to stimulate transcription of E1A-inducible promoters. Furthermore, zinc binding to one of the mutant finger proteins suggests either that only a precise finger structure formed by the tetrahedral coordination of zinc to the four consensus ligands is required for trans-activation or, possibly, that one of several neighboring histidine residues in various combinations with three of the consensus cysteine residues normally coordinates zinc. How the zinc finger in E1A might interact with DNA or protein to bring about trans-activation is discussed.
Pathogenicity ofFusobacterium necrophorumstrains from man and animals (1993)

Necrobacillosis occurs in man and animals. The typical forms of the disease in animals are caused by Fusobacterium necrophorum biovar A; biovar B strains are much less pathogenic. In this study the pathogenicity for mice of eight human isolates of F. necrophorum was compared with that of animal biovar A and B strains. By subcutaneous inoculation seven of the human strains differed from biovar A but resembled biovar B in (1) producing, at the most, mild local lesions that rapidly healed, and (2) showing no enhancement of infectivity when suspended in sub-lethal doses of Staphylococcus aureus broth culture. The eighth human strain (A2433) resembled biovar A but differed from biovar B in (1) producing severe lesions, and (2) showing greatly enhanced infectivity in the presence of S. aureus. Nonetheless, strain A2433 differed from biovar A, both in the nature of the lesions produced and in its failure to cause severe general signs of illness and rapidly fatal infection. By intravenous inoculation one of two biovar B strains and all except one of the eight human strains produced purulent lesions, often severe, in the liver and elsewhere, but infection was not usually associated with general signs of illness. In contrast, intravenous injection of a biovar A strain gave rise to a rapidly fatal infection, with severe lesions in the liver or elsewhere. The results suggest that the term 'necrobacillosis' as used in human and veterinary medicine refers to diseases that differ in important respects.
Block-level 3D IC design with through-silicon-via planning (2012)

Since re-designing and re-optimizing existing logic, memory, and IP blocks in a 3D fashion significantly increases design cost, near-term three-dimensional integrated circuit (3D IC) design will focus on reusing existing 2D blocks. One way to reuse 2D blocks in the 3D IC design is to first perform 3D floorplanning, insert signal through-silicon vias (TSVs) for 3D inter-block connections, and then route the blocks. In this paper, we propose algorithms (finding signal TSV locations, assigning TSVs to whitespace blocks, and manipulating whitespace blocks) for post-floorplanning signal TSV planning in the block-level 3D IC design. Experimental results show that our signal TSV planner outperforms the state-of-the-art TSV-aware 3D floorplanner by 7% to 38% with respect to wirelength. In addition, our multiple TSV insertion algorithm outperforms a single TSV insertion algorithm by 27% to 37%.
The spectrum of SCN1A-related infantile epileptic encephalopathies (2007)

The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.
Enzymatic Synthesis of Neoglycopeptide Building Blocks (2000)

A transglutaminase-catalyzed transacylation is the major step in a practical, regioselective synthesis of N-linked spacer-modified glycopeptide analogues. The process requires minimal modification of the saccharide during the N-glycosylation, photoinduced coupling of cysteamine, and final enzymatic reaction (see scheme).
Bildung von Estern und Lactonen durch Silberionen‐Katalyse (1974)

A mild and efficient method for the preparation of esters has been found in the silver ion induced reaction of alcohols with 2‐pyridyl esters of thiocarboxylic S‐acids. Examples are given to show the utility of this push button activation for the rapid formation of macrocyclic lactones and esters at room temperature under non‐basic conditions.
Hepatoprotective Effect of Hovenia dulcis THUNB. on Experimental Liver Injuries Induced by Carbon Tetrachloride or D-Galactosamine/Lipopolysaccharide. (1997)

The hepatoprotective effects of the fruits of Hovenia dulcis THUNB. on chemically or immunologically induced experimental liver injury models were examined. The methanol extract showed significant hepatoprotective activity against CCl4-toxicity in rats and D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. The methanol extract also significantly protected against CCl4-toxicity in primary cultured rat hepatocytes. Hepatoprotective activity-guided fractionation and chemical analysis led to the isolation of an active constituent, (+)-ampelopsin (1) from the methanol extract.
Mechanism of polyethylene glycol interaction with proteins (1985)

Poly(ethylene glycol) (PEG) is one of the most useful protein salting-out agents. In this study, it has been shown that the salting-out effectiveness of PEG can be explained by the large unfavorable free energy of its interaction with proteins. Preferential interaction measurements of beta-lactoglobulin with poly(ethylene glycols) with molecular weights between 200 and 1000 showed preferential hydration of the protein for those with Mr greater than or equal to 400, the degree of hydration increasing with the increase in poly(ethylene glycol) molecular weight. The preferential interaction parameter had a strong cosolvent concentration dependence, with poly(ethylene glycol) 1000 having the sharpest decrease with an increase in concentration. The preferential hydration extrapolated to zero cosolvent concentration increased almost linearly with increasing size of the additive, suggesting steric exclusion as the major factor responsible for the preferential hydration. The poly(ethylene glycol) concentration dependence of the preferential interactions could be explained in terms of the nonideality of poly(ethylene glycol) solutions. All the poly(ethylene glycols) studied, when used at levels of 10-30%, decreased the thermal stability of beta-lactoglobulin, suggesting that caution must be exercised in the use of this additive at extreme conditions such as high temperature.
Observational retrospective evaluation of treatment with liposomal irinotecan plus fluorouracil/leucovorin for metastatic pancreatic cancer patients: An Italian large real-world analysis. (2020)

660 Background: In the NAPOLI I phase III trial, Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed better outcome compared to 5FU/LV in patients with metastatic Pancreatic Cancer (MPC) progressed to 1st- line gemcitabine-based therapy. Aim of this study is to explore the real-world efficacy and safety of 5FU/LV-nal-IRI by a compassionate use programme and to identify potential prognostic factors that could affect survival in this setting. Methods: This is a retrospective multi-center analysis including patients with MPC who received 5FU/LV-nal-IRI after failure of a gemcitabine-based therapy. Survival analyses were carried out by the Kaplan-Meier method. Univariate and multivariate analyses were performed by using the log-rank test and the Cox regression. Results: A total of 296 pts (median age, 69 years, range 30-82; 50% male; ECOG PS 0, 44%) were treated at 11 Italian institutions from June 2016 and November 2018. 34% of the pts have been previously resected on their primary tumor, and 76% received gemcitabine-nabpaclitaxel as 1st - line treatment. 5FU/LV-nal-IRI has been administered as 2nd - line in 72% of the pts, while in 23% of the cases as 3rd - line or more. The median OS was 7.1 months [95% confidence interval (CI) 6.1 - 8.1] and the median PFS was 3.3 months (95% CI 2.9 - 3.6). At six months, OS and PFS rate were 53.4% and 31.4% respectively. ORR was 12% and DCR was 40%. 52% of pts received more than 4 cycle with dose reduction in 148 pts (50%). Most common grade 3 toxicities were neutropenia (14%), diarrhea (11%), anemia (3%), nausea (3%), fatigue (3%), mucositis (2%) and vomiting (1%). Baseline characteristics associated with better OS were ECOG PS 0, normal CEA, neutrophil-to-lymphocyte ratio ≤5 and haemoglobin ≥11 g/dL. Conclusions: These real-world data confirm the efficacy and safety of 5FU/LV-nal-IRI in patients with MPC progressed to a gemcitabine-based therapy, with outcome comparable to NAPOLI-1 even in a less selected population and with more active 1st - line combination therapy. In this cohort, well known prognostic markers has been confirmed, as expected.
Fourier-domain holographic optical coherence imaging of tumor spheroids and mouse eye (2005)

Fourier-domain holography (FDH) has several advantages over image-domain holography for optical coherence imaging of tissue. Writing the hologram in the Fourier plane significantly reduces background arising from reference light scattered from the photorefractive holographic film. The ability to use FDH is enhanced by the use of a diffuse target, such as scattering tissue, rather than specular targets, because the broader angular distribution from diffuse targets is transformed into a relatively uniform distribution in the Fourier plane. We demonstrate significantly improved performance for Fourier-domain optical coherence imaging on rat osteogenic sarcoma tumor spheroids and mouse eye. The sensitivity is documented at -95 dB.
Biosynthetic Pathway and Gene Cluster Analysis of Curacin A, an Antitubulin Natural Product from the Tropical Marine Cyanobacterium Lyngbya majuscula (2004)

Curacin A (1) is a potent cancer cell toxin obtained from strains of the tropical marine cyanobacterium Lyngbya majuscula found in Curaçao. Its structure is unique in that it contains the sequential positioning of a thiazoline and cyclopropyl ring, and it exerts its potent cell toxicity through interaction with the colchicine drug binding site on microtubules. A series of stable isotope-labeled precursors were fed to cultures of curacin A-producing strains and, following NMR analysis, allowed determination of the metabolic origin of all atoms in the natural product (one cysteine, 10 acetate units, two S-adenosyl methionine-derived methyl groups) as well as several unique mechanistic insights. Moreover, these incorporation experiments facilitated an effective gene cloning strategy that allowed identification and sequencing of the approximately 64 kb putative curacin A gene cluster. The metabolic system is comprised of a nonribosomal peptide synthetase (NRPS) and multiple polyketide synthases (PKSs) and shows a very high level of collinearity between genes in the cluster and the predicted biochemical steps required for curacin biosynthesis. Unique features of the cluster include (1) all but one of the PKSs are monomodular multifunctional proteins, (2) a unique gene cassette that contains an HMG-CoA synthase likely responsible for formation of the cyclopropyl ring, and (3) a terminating motif that is predicted to function in both product release and terminal dehydrative decarboxylation.
In-vivo transfection of pcDNA3.1-IGFBP7 inhibits melanoma growth in mice through apoptosis induction and VEGF downexpression (2010)

These results suggest a potential new clinical strategy for MM gene treatment.
Synthetic Polypeptide Mimics of Marine Adhesives (1998)

Water soluble copolypeptides containing l-dihydroxyphenylalanine (DOPA) and l-lysine were prepared by ring-opening polymerization of alpha-amino acid N-carboxyanhydride (NCA) monomers. We have prepared a range of different copolymers to probe the effects of functional group composition on adhesive and cross-linking behavior. Aqueous solutions of these copolymers, when mixed with a suitable oxidizing agent (e.g., O2, mushroom tyrosinase, Fe3+, H2O2, or IO4-), formed cross-linked networks that were found to form moisture-resistant adhesive bonds to a variety of substrates (e.g., aluminum, steel, glass, and plastics). It was found that successful adhesive formation was dependent on oxidation conditions, with chemical oxidants giving the best results. Optimized systems were found to form adhesive bonds that rival in strength those formed by natural marine adhesive proteins. Our synthetic systems are readily prepared in large quantities and require no enzymes or other biological components.