gebhart/patrepeval huggingface dataset:
Cross-linking Amine-Modified Silica Aerogels with Epoxies:  Mechanically Strong Lightweight Porous Materials (2005)

The mesoporous surfaces of TMOS-derived silica aerogels have been modified with amines by copolymerization of TMOS with APTES. The amine sites have become anchors for cross-linking the nanoparticles of the skeletal backbone of the aerogel by attachment of di-, tri-, and tetra-functional epoxies. The resulting conformal coatings increase the density of the native aerogels by a factor of 2−3 but the strength of the resulting materials may increase by more than 2 orders of magnitude. Processing variables such as the amount of APTES used to make the gels, the epoxy type and concentration used for cross-linking, and the cross-linking temperature and time were varied according to a multivariable design-of-experiments (DOE) model. It was found that while elastic modulus follows a similar trend with density, maximum strength is attained neither at the maximum density nor at the highest concentration of −NH2 groups, suggesting surface saturation effects. Aerogels cross-linked with the trifunctional epoxide always show improved strength compared with aerogels cross-linked with the other two epoxides under identical conditions. Solid 13C NMR studies show residual unreacted epoxides, which condense with one another by heating cross-linked aerogels at 150 °C.
Prokaryotic Regulation of Epithelial Responses by Inhibition of IκB-α Ubiquitination (2000)

Epithelia of the vertebrate intestinal tract characteristically maintain an inflammatory hyporesponsiveness toward the lumenal prokaryotic microflora. We report the identification of enteric organisms (nonvirulent Salmonella strains) whose direct interaction with model human epithelia attenuate synthesis of inflammatory effector molecules elicited by diverse proinflammatory stimuli. This immunosuppressive effect involves inhibition of the inhibitor kappaB/nuclear factor kappaB (IkappaB/NF-kappaB) pathway by blockade of IkappaB-alpha degradation, which prevents subsequent nuclear translocation of active NF-kappaB dimer. Although phosphorylation of IkappaB-alpha occurs, subsequent polyubiquitination necessary for regulated IkappaB-alpha degradation is completely abrogated. These data suggest that prokaryotic determinants could be responsible for the unique tolerance of the gastrointestinal mucosa to proinflammatory stimuli.
RIBONUCLEOSIDES AND RNA (1995)

Landmark discoveries such as the autocatalytic cleavage activity of certain RNA molecules, as well as small oligoribonucletide ribozymes and later the in vitro evolution of novel bioactive oligoribonucleotides (SELEX), have created entire new fields of biochemical research. The discovery of SELEX has provided a method for producing high-affinity nucleic acid ligands with high binding specificity to important medicinal targets. Including modified nucleotides into RNA ligands derived from SELEX may yield improved RNA therapeutics. The chemistry of oligoribonucleotides in comparison to oligodeoxyribonucleotides has led to resurgent attention on the role of modified nucleotides in RNA structure and function. Such modifications are also employed to impart stability towards endonuclease degradation on oligoribonucleotides.
Redirecting adaptive immunity against foreign antigens to tumors for cancer therapy (2007)

Immunotherapy for cancer is often limited by weak immunogenicity of tumor antigens. However, immune systems are usually strong and effective against foreign invading antigens. To test whether the destructive effect of adaptive immunity against foreign antigens can be redirected to tumors for cancer therapy, we immunized mice with adenovector expressing LacZ (Ad/CMV-LacZ). Subcutaneous syngeneic tumors were then established in the immunized animals or in naïve animals. The immune response against adenovirus or LacZ was redirected to tumors by intratumoral injection of Ad/CMV-LacZ. We found that immunization and treatment with the adenovector dramatically reduced the tumor growth rate compared with intratumoral administration of adenovector in naïve mice. Complete tumor regression was observed in about 50% of the immunized animals but not in the naïve animals. Similar effects were observed when oncolytic vaccinia virus was used to immunize and treat tumors. Lymphocyte infiltration in tumors was dramatically increased in the immunized group when compared with other groups. Moreover, immunity against parental tumor cells was induced in the animals cured with immunization and treatment with Ad/CMV-LacZ, as evidenced by the lack of tumor growth when the mice were challenged with parental tumor cells. Taken together, these results suggest that redirecting adaptive immunity against foreign antigens is a potential approach for anticancer therapy and that pre-existing immunity could enhance virotherapy against cancers.
Iterative simulation of elastic wave scattering in arbitrary dispersions of spherical particles (2006)

A numerical modeling approach was developed to simulate the propagation of shear and longitudinal waves in arbitrary, dense dispersions of spherical particles. The scattering interactions were modeled with vector multipole functions and boundary condition solutions for each particle. Multiple scattering was simulated by translating the scattered wave fields from one particle to another with the use of translational addition theorems, summing the multiple-scattering contributions, and recalculating the scattering using an iterative method. The approach can simulate 3D dispersions with a variety of particle sizes, compositions, and volume fractions. To test the model, spectra and wave field images were generated from ordered and disordered microstructures containing up to several thousand particles. The model predicted wave propagation phenomena such as refractive focusing and mode conversion. The iterations converged for many particle configurations, but did not converge or only partially converged for certain conditions, specifically large particle dispersions (&amp;gt;100 particles) at short wavelengths (λ∼particle diameter). Incorporating viscoelastic damping into the matrix properties reduced these numerical instabilities. The model is currently constrained by these convergence limitations and by the computation of sufficiently high multipole order for large numbers of particles. The theory and initial results for the model are presented.
An investigation of fragmentation mechanisms of doubly protonated tryptic peptides (1992)

Peptides formed as reaction products, of specific hydrolysis of proteins by trypsin, are characterized by a basic residue (Arg or Lys) at the C-terminus, which facilitates formation of abundant [M + 2H]2+ ions under electrospray or ionspray conditions. These doubly charged ions readily dissociate upon collisional activation to y" and b fragment ions which are mass complements of one another. The suggestion that these fragments are formed by direct charge-separation dissociations must contend with the observation that the y" intensities are generally appreciably larger than those of their b counterparts. However, it is shown that this can be accounted for by a greater susceptibility of the b ions to undergo further dissociation to smaller fragments such as immonium ions. In addition no evidence could be found to support alternative mechanisms, including dissociative electron capture, for which equal intensities of the two fragment ion series are not obligatory. Initial protonation at the N-terminus was shown to be required for formation of these [M + 2H]2+ ions via its suppression by mono-acetylation at the N-terminus. These findings, and others concerning formation of [y"']2+ fragments, are consistent with extensions of published mechanisms for formation of b and of y" fragments from singly protonated peptides, via charge-site-induced cleavages and intramolecular proton transfers between nitrogen atoms, respectively.
High Glucose-Induced Tyrosine Nitration in Endothelial Cells: Role of eNOS Uncoupling and Aldose Reductase Activation (2003)

Increases in glucose levels and osmotic stress similar to those in diabetic patients increase the formation of nitrotyrosine in retinal endothelial cells because of their actions increasing NOS activity and causing superoxide formation due to eNOS uncoupling and AR activation.
A mild and efficient procedure for α-bromination of ketones using N-bromosuccinimide catalysed by ammonium acetate (2004)

Cyclic ketones reacted with N-bromosuccinimide (NBS) catalysed by NH(4)OAc in Et(2)O at 25 degrees C to give the corresponding alpha-brominated ketones in good yields, while acyclic ketones were efficiently brominated in CCl(4) at 80 degrees C.
Urinary excretion of RAS, BMP, and WNT pathway components in diabetic kidney disease (2014)

Abstract The renin-angiotensin system (RAS), bone morphogenetic protein (BMP), and WNT pathways are involved in pathogenesis of diabetic kidney disease (DKD). This study characterized assays for urinary angiotensinogen (AGT), gremlin-1, and matrix metalloproteinase 7 (MMP-7), components of the RAS, BMP, and WNT pathways and examined their excretion in DKD. We measured urine AGT, gremlin-1, and MMP-7 in individuals with type 1 diabetes and prevalent DKD (n = 20) or longstanding (n = 61) or new-onset (n = 10) type 1 diabetes without DKD. These urine proteins were also quantified in type 2 DKD (n = 11) before and after treatment with candesartan. The utilized immunoassays had comparable inter- and intra-assay and intraindividual variation to assays used for urine albumin. Median (IQR) urine AGT concentrations were 226.0 (82.1, 550.3) and 13.0 (7.8, 20.0) μg/g creatinine in type 1 diabetes with and without DKD, respectively (P < 0.001). Median (IQR) urine gremlin-1 concentrations were 48.6 (14.2, 254.1) and 3.6 (1.7, 5.5) μg/g, respectively (P < 0.001). Median (IQR) urine MMP-7 concentrations were 6.0 (3.8, 10.5) and 1.0 (0.4, 2.9) μg/g creatinine, respectively (P < 0.001). Treatment with candesartan was associated with a reduction in median (IQR) urine AGT/creatinine from 23.5 (1.6, 105.1) to 2.0 (1.4, 13.7) μg/g, which did not reach statistical significance. Urine gremlin-1 and MMP-7 excretion did not decrease with candesartan. In conclusion, DKD is characterized by markedly elevated urine AGT, MMP-7, and gremlin-1. AGT decreased in response to RAS inhibition, suggesting that this marker reflects therapeutic response. Urinary components of the RAS, BMP, and WNT pathways may identify risk of DKD and aid development of novel therapeutics.
Human mRNA polyadenylate binding protein: evolutionary conservation of a nucleic acid binding motif (1987)

We have isolated a full length cDNA (cDNA) coding for the human poly(A) binding protein. The cDNA derived 73 kd basic translation product has the same Mr, isoelectric point and peptidic map as the poly(A) binding protein. DNA sequence analysis reveals a 70,244 dalton protein. The N terminal part, highly homologous to the yeast poly(A) binding protein, is sufficient for poly(A) binding activity. This domain consists of a four-fold repeated unit of approximately 80 amino acids present in other nucleic acid binding proteins. In the C terminal part there is, as in the yeast protein, a sequence of approximately 150 amino acids, rich in proline, alanine and glutamine which together account for 48% of the residues. A 2,9 kb mRNA corresponding to this cDNA has been detected in several vertebrate cell types and in Drosophila melanogaster at every developmental stage including oogenesis.
Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement (2000)

Weight-losing patients with advanced cancer often fail to gain weight with conventional nutritional support. This suboptimal response might be explained, in part, by an increased metabolic response to feeding. It has been suggested that eicosapentaenoic acid (EPA) can modify beneficially the metabolic response to cancer. The aim of the present study was to examine the metabolic response to feeding in cancer and the effects of an EPA-enriched oral food supplement on this response. A total of 16 weight-losing, non-diabetic patients with unresectable pancreatic adenocarcinoma and six healthy, weight-stable controls were studied by indirect calorimetry in the fasting and fed states. Body composition was estimated by bioimpedence analysis. Cancer patients were then given a fish-oil-enriched nutritional supplement providing 2 g of EPA and 2550 kJ daily, and underwent repeat metabolic study after 3 weeks of such supplementation. At baseline, resting energy expenditure whether expressed per kg body weight, lean body mass or body cell mass was significantly greater in the cancer patients compared with controls. Fat oxidation was significantly higher in the fasting state in cancer patients [median 1.26 g.kg(-1).min(-1) (interquartile range 0.95-1.38)] than in controls [0.76 g.kg(-1). min(-1) (0.62-0.92); P<0.05]. Over the 4 h feeding period, changes in insulin and glucose concentrations in cancer patients suggested relative glucose intolerance. In response to oral meal feeding, the percentage change in the area under the curve of energy expenditure was significantly lower in the cancer patients [median 7.9% (interquartile range 3.4-9.0)] than in controls [12.6% (9.9-15.1); P<0.01]. After 3 weeks of the EPA-enriched supplement, the body weight of the cancer patients had increased and the energy expenditure in response to feeding had risen significantly [9.6% (6. 3-12.4)], such that it was no different from baseline healthy control values. Similarly, fasting fat oxidation fell to 1.02 g. kg(-1).min(-1) (0.8-1.18), again no longer significantly different from baseline healthy control values. While weight-losing patients with advanced pancreatic cancer have an increased resting energy expenditure and increased fat oxidation, the energy cost of feeding is, in fact, reduced. Provision of a fish-oil-enriched nutritional supplement results in some normalization of the metabolic response in both the fasted and fed states, in association with an improvement in nutritional status.
Expression of ED-B Fibronectin in Tissues from Human Hematologic Malignancies. (2006)

Abstract Newly formed blood vessels in tissues infiltrated by hematologic malignancies or solid cancers are strikingly different from normal healthy counterparts. Notoriously, they are characterized by vascular shunts, uneven vessel diameters, and endothelial fenestrations. In addition, for the vast majority of solid cancers the extracellular matrix of such vessels was found to contain a type of fibronectin that has an extra-domain B (ED-B), which is expressed during embryonic development and during major tissue remodeling, but not in normal adult organs. The unique expression pattern attributed to ED-B suggests that it may be well suited for vascular targeting. Preliminary data has shown that ED-B expression may also be detected in hematologic malignancies. We have analyzed a large series of human samples of different hematological malignancies, non-malignant or reactive lymphatic conditions, and normal lymphatic and hematopoietic tissues for ED-B expression, using immunohistochemistry (IHC; mAbs BC1, L19, and the newly created MX1) on paraffin sections after steam pressure-based epitope recovery. Consistent with the data from solid tumors, ED-B expression was not detected in normal lymph nodes and lymphatic tissues. However, considerable but variable vessel-associated ED-B expression was detected in the following tissue samples of hematologic malignancies: 56/59 (95%) of Hodgkin lymphomas, 33/36 (91.7%) of DLBCLs, 32/33 (97%) of follicular lymphomas, 17/18 (94.4%) of mantle cell lymphomas, 14/15 (93.3%) of anaplastic large T cell lymphomas, 16/16 (100%) of multiple myelomas,13/14 (92.8%) of B-CLL samples, and in 5/6 (83.3%) samples from chronic myeloproliferative bone marrow, and in 3/3 (100%) from acute leukemia. Reactive lymph nodes (9/10; 90%) showed a faint ED-B expression in the vascular walls, whereas in hypertrophic tonsils (n=5) and healthy or reactive bone marrow (n=12) ED-B expression was rarely detected. Consistent with the literature, ED-B expression was not detected in tissue samples from normal lymph nodes (n=5). Immunofluorescence was used to identify co-localization of ED-B fibronectin and blood vessel-associated epitopes (eg CD34). Also, results will be presented from experiments in which lymphoma and leukemia animal models were treated with a novel IL2 immunocytokine specifically targeted to the ED-B fibronectin (L19-IL2). Preliminary results from these models suggest that hematopoietic malignancies contain ED-B+ vessels. Our study indicates the presence of vessel-associated ED-B in the vast majority of tissue samples from patients with varied hematologic malignancies, suggesting a potential approach for clinical investigation with targeted immunocytokines.
Characterization of the repertoire of hypervariable regions in the Protein II (opa) gene family of Neisseria gonorrhoeae (1990)

P.II outer membrane proteins of Neisseria gonorrhoeae are encoded by a family of closely related genes. Although the genes are highly conserved, major differences in sequence among them occur in two short regions, designated hypervariable regions 1 (HV1) and 2 (HV2). In this study, we determined the number and DNA sequence of the hypervariable regions in the P.II genes of strains FA1090. The FA1090 chromosome contained at least eleven P.II loci, having six different versions each of HV1 and HV2 among them. Southern blotting with HV-specific oligonucleotides showed that each version was present in one to three copies, and that there were nine unique combinations of HV1 and HV2 in the P.II genes. Although each of the versions of HV1 or HV2 had a unique DNA sequence, there were some similarities among them, particularly when certain ones were compared. Restriction fragments containing only the HV regions were cloned into an expression vector to demonstrate that the epitopes recognized by a set of monoclonal antibodies specific for different FA1090 P.II proteins were completely encoded by either HV1 or HV2.
Falls Risk Factors and a Compendium of Falls Risk Screening Instruments (2010)

Comparison of recently developed multidimensional and comprehensive screening algorithms for falls risk identification may aid in lowering the rates of false negatives associated with using very specific instruments that screen or assess in only 1 falls risk factor domain.
Superimposed Bragg gratings in high-birefringence fibre optics: three-parameter simultaneous measurements (2004)

We used a pair of Bragg gratings written in high birefringence fibre optics to measure, simultaneously, longitudinal and transverse strain and temperature. The Bragg gratings are superimposed in the same position of the fibre optic, so as to behave as a punctual sensor. The sensitivity of the spectral response of the device to longitudinal strain, transverse strain and temperature are all characterized, and the results of its application as a three-parameter sensor are also presented.
Acceleration of influenza virus clearance by Th1 cells in the nasal site of mice immunized intranasally with adjuvant-combined recombinant nucleoprotein (1996)

The protective roles of influenza viral nucleoprotein (NP), together with the cellular mechanism of the protection in the nasal site, were examined in BALB/c mice immunized intranasally with an adjuvant (cholera toxin B subunit containing 0.2% of the whole toxin)-combined A or B virus recombinant NP. The NP-immune mice, when challenged intranasally with a sublethal dose of the virus 3 wk after immunization, had accelerated virus clearance from the nasal site in both an influenza type-specific and a nonspecific manner, as shown by the protection from high morbidity from the second day after challenge. Both type-specific and nonspecific acceleration of recovery was confirmed by the increased survival rate after challenge with a lethal dose of virus in mice immunized and boosted with adjuvant-combined NP. The acceleration of nasal virus clearance was accompanied with acceleration of type-specific systemic delayed-type hypersensitivity (DTH) and with IFN-gamma production by nasal lymphocytes. The nasal lymphocytes from the immunized and challenged mice generated a significantly high level of DTH when transferred locally, but no class I MHC-restricted CTL response. Moreover, nasal CD4+ T cells, induced by NP immunization and increased in number by the subsequent challenge, were involved in the accelerated IFN-gamma production. These results suggest that nasal Th1 cells, capable of producing IFN-gamma and mediating DTH, are involved in the type-specific acceleration of recovery from influenza after challenge in mice immunized intranasally with adjuvant-combined NP, although the nonspecific mechanism of accelerated recovery remains to be solved.
Metabotropic glutamate receptor agonists for schizophrenia (2008)

A drug acting at metabotropic glutamate receptors has recently been reported to be an effective antipsychotic, breaking the rule that only dopamine receptor-blocking drugs have this property. The finding complements accumulating evidence that glutamatergic abnormalities are important in the pathophysiology of schizophrenia.
How To Synthesize Macrocycles Efficiently by Using Virtual Combinatorial Libraries (2002)

The selection of different diimines 4 a-c by alkaline earth ions from a virtual combinatorial library (VCL) is described. The products were stabilized by reduction to the diamines 6 a-c; this allowed easy analysis. The library can be directed toward different target molecules 6 a-c upon addition of alkaline earth ions with different radii. Competition experiments show the possibility of synthesizing the macrocycles 6 a, 6 b, and 6 c simultaneously when using Mg(2+), Ca(2+), and Ba(2+) as template ions. The scope of this thermodynamically controlled, reversible approach for macrocycle syntheses is illustrated.
Palladium-Catalyzed Intermolecular Coupling of Aryl Chlorides and Sulfonamides under Microwave Irradiation (2003)

An efficient intermolecular N-arylation of sulfonamides with aryl chlorides is realized using palladium catalysis. The reaction proceeds under microwave irradiation at 180−200 °C for 10 min with 2−10 mol % of Pd catalyst in 32−85% isolated yields.
Immunogenicity of 2 Serogroup B Outer-Membrane Protein Meningococcal Vaccines (1999)

These data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain-specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.
CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells (2011)

Human ESCs provide a promising cell resource for the treatment of type I diabetes mellitus. Although PDX1-positive pancreatic progenitors can be efficiently generated from human ESCs by stepwise induction, further in vitro differentiation into functional, mature beta cells is not efficient or reproducible. Purification of pancreatic progenitor cells could facilitate the identification of signals that regulate beta cell differentiation and maturation. Here, we report the identification of a novel surface marker for PDX1-positive pancreatic progenitors based on an in vitro human ESC differentiation system. By costaining PDX1 and a panel of cell surface antigens at the pancreatic progenitor stage of human ESC differentiation, we discovered a positive marker, CD24. CD24-positive cells coexpressed most of the key transcription factors of pancreatic progenitors, and the expression of important pancreatic genes was greatly enriched in CD24-positive cells compared with the CD24-negative cells. In addition, CD24-positive cells could differentiate into insulin-producing cells but CD24-negative cells could not. These results indicate that CD24 could be a surface marker for PDX1-positive pancreatic progenitors derived from human ESCs. Enrichment of pancreatic progenitors with this marker will facilitate the investigation of beta cell maturation during the human ESC differentiation.