gebhart/patrepeval huggingface dataset:
Infant Immunization with Pneumococcal CRM $_{197}$ Vaccines: Effect of Saccharide Size on Immunogenicity and Interactions with Simultaneously Administered Vaccines (1997)

Six pentavalent pneumococcal conjugate vaccines (Pn-CRM197) were evaluated among 400 infants. The vaccines differed in saccharide chain length (oligosaccharide [OS] or polysaccharide [PS]) and saccharide quantity (0.5, 2, or 5 microg). Subjects were randomized into groups 1-6 (Pn-CRM197 recipients) or 7 (controls) for immunization at 2, 4, and 6 months of age. Pn-CRM197 were well tolerated and elicited mean antibody concentrations that exceeded those in controls for all 5 capsular serotypes. PS formulations were generally more immunogenic than their OS counterparts. For PS vaccines, a dose-response was documented (5 microg > 2 microg > 0.5 microg), but the differences between the 5- and 2-microg formulations were insignificant. The mean anti-PRP antibody concentration was significantly higher among Pn-CRM197 recipients. It is concluded that PS vaccines are more immunogenic than OS vaccines. The improved immunogenicity from Haemophilus type b oligosaccharide conjugate (HbOC) vaccine when given with Pn-CRM197 suggests that a decreased dose of HbOC vaccine may be sufficient to elicit protection.
A novel myogenic regulatory circuit controls slow/cardiac troponin C gene transcription in skeletal muscle. (1994)

The slow/cardiac troponin C (cTnC) gene is expressed in three distinct striated muscle lineages: cardiac myocytes, embryonic fast skeletal myotubes, and adult slow skeletal myocytes. We have reported previously that cTnC gene expression in cardiac muscle is regulated by a cardiac-specific promoter/enhancer located in the 5' flanking region of the gene (bp -124 to +1). In this report, we demonstrate that the cTnC gene contains a second distinct and independent transcriptional enhancer which is located in the first intron. This second enhancer is skeletal myotube specific and is developmentally up-regulated during the differentiation of myoblasts to myotubes. This enhancer contains three functionally important nuclear protein binding sites: a CACCC box, a MEF-2 binding site, and a previously undescribed nuclear protein binding site, designated MEF-3, which is also present in a large number of skeletal muscle-specific transcriptional enhancers. Unlike most skeletal muscle-specific transcriptional regulatory elements, the cTnC enhancer does not contain a consensus binding site (CANNTG) for the basic helix-loop-helix (bHLH) family of transcription factors and does not directly bind MyoD-E12 protein complexes. Despite these findings, the cTnC enhancer can be transactivated by overexpression of the myogenic bHLH proteins, MyoD and myogenin, in C3H10T1/2 (10T1/2) cells. Electrophoretic mobility shift assays demonstrated changes in the patterns of MEF-2, CACCC, and MEF-3 DNA binding activities following the conversion of 10T1/2 cells into myoblasts and myotubes by stable transfection with a MyoD expression vector. In particular, MEF-2 binding activity was up-regulated in 10T1/2 cells stably transfected with a MyoD expression vector only after these cells fused and differentiated into skeletal myotubes. Taken together, these results demonstrated that distinct lineage-specific transcriptional regulatory elements control the expression of a single myofibrillar protein gene in fast skeletal and cardiac muscle. In addition, they show that bHLH transcription factors can indirectly transactivate the expression of some muscle-specific genes.
Monte Carlo simulations of the hydration of substituted benzenes with OPLS potential functions (1993)

Abstract Intermolecular potential functions have been developed for use in computer simulations of substituted benzenes. Previously reported optimized potentials for liquid simulations (OPLS) for benzene and organic functional groups were merged and tested by computing free energies of hydration for toluene, p ‐xylene, phenol, anisole, benzonitrile, p ‐cresol, hydroquinone, and p ‐dicyanobenzene. The calculations featured Monte Carlo simulations at 25°C and 1 atm with statistical perturbation theory. The average difference between the computed results and experimental data for the absolute free energies of hydration is 0.5 kcal/mol. The AM1‐SM2 method is also found to perform well in predicting the free energies of hydration for the substituted benzenes. In addition, the Monte Carlo simulations provided details on the hydration of the substituted benzenes, in particular for the solute–water hydrogen bonding. © 1993 John Wiley &amp; Sons, Inc.
Effects of lovastatin and pravastatin on sleep efficiency and sleep stages (1991)

The effects on sleep of two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (40 mg lovastatin and 40 mg pravastatin) were evaluated in 12 normal subjects in a double-blind placebo-controlled sleep laboratory study. Subjects were randomly assigned to each of two parallel groups (lovastatin and pravastatin). Each parallel-group protocol consisted of 22 consecutive nights including 4 placebo-baseline nights, 2 weeks of drug administration, and 4 placebo-withdrawal nights. Lovastatin did not disturb sleep initially (nights 5 through 7) but, with continued administration (nights 16 through 18), it significantly and markedly increased wake time after sleep onset and stage 1 sleep compared with baseline. By contrast, pravastatin was not associated with sleep disturbance either initially or with continued use. Neither drug caused any sleep disturbance after withdrawal. Lovastatin's sleep disturbing effects with continued administration are attributed to its high degree of lipophilicity in contrast with the hydrophilicity of pravastatin.
Innervation of "Painful" Lumbar Discs (1997)

Findings indicate a more extensive disc innervation in the severely degenerated human lumbar disc compared with normal discs. The nociceptive properties of at least some of these nerves are highly suggested by their substance P immunoreactivity, which provides further evidence for the existence of a morphologic substrate of discogenic pain.
p53 Mutations and Survival in Stage I Non-Small-Cell Lung Cancer: Results of a Prospective Study (2003)

Tumor p53 mutations are a statistically significant predictor of poor outcome in patients with stage I NSCLC.
Antibody–drug conjugates – a perfect synergy (2012)

Introduction: There is a great unmet need for effective new treatments in cancer, which continues to be a major cause of death. Antibody–drug conjugates (ADCs) are emerging, after a long gestation, as a class of biopharmaceuticals with the potential to address this need by directing highly potent cytotoxic drugs to their point of action. There is increasing interest in ADCs by major pharmaceutical companies and a growing pipeline of candidates for clinical use. This review summarises progress with development of this new class of drugs. Areas covered: The authors describe separately the antibody and drug elements of ADCs and then examine the technology and consequences of linkage. The work is presented in the light of recent developments in the design, using clinical examples where possible. Expert opinion: Since their emergence as independent drugs, antibodies and chemotherapy are being brought together in effective synergy. The conjunction is timely: many of the technical challenges in preparing antibodies have been addressed; potent new drugs are available and linker technology is advancing apace. ADCs however are not just a sum of their individual parts. The current challenge is in understanding the holistic nature of this exciting class of drugs that promise a new avenue for cancer treatment. Target selection, the interaction of ADC with tumour and off-tumour targets and the internalisation of ADCs, are critical to the effective maturation of ADC technology. Ongoing recent developments in attachment sites and linker chemistry can provide fine-tuning of drug loading, elements of ADC PK and off-target ADC toxicity.
The requirement for the association of two adjacent rabbit gamma-G-antibody molecules in the fixation of complement by immune complexes. (1968)

An amidinated and benzylated rabbit γG-antibody preparation has been used to study the mechanism of complement fixation. This doubly conjugated antibody retained only 8% of the complement-fixing ability of untreated antibody, but had not lost the ability to combine and precipitate with antigen. It partially suppressed the ability of untreated, complement-fixing rabbit γG-antibody to fix complement, when the two were reacted together with antigen. This effect could be explained if two or more active (untreated) antibody molecules were required to be in close juxtaposition for complement fixation to occur. Under these circumstances, the presence of inactive (treated) molecules would result in a failure of some of the active ones to associate, since there is random co-precipitation of the two types of antibody in the immune lattice. A quantitative study of this suppressive effect led to the conclusion that there is a requirement for two adjacent active γG-antibody molecules acting together in the fixation of complement.
Efficient DNA Click Reaction Replaces Enzymatic Ligation (2019)

We report a chemical DNA-DNA ligation method based on copper-catalyzed azide-alkyne cycloaddition (CuAAC). We demonstrate that ion addition dramatically influences the efficiency of the so-called click reaction. Even without any further additions, such as typically splint oligonucleotides for preorganization, the "click ligation" yields up to ∼83% product without any byproducts. Additionally, purification of the desired product is straightforward. In comparison to enzymatic ligation methods used to introduce adapters into, e.g., mRNA library preparation, this targeted chemical ligation method exhibits several advantages: increased ligated product and no adapter or cDNA oligomers byproducts. The advantages of the click ligation method were demonstrated by incorporation of azide modified nucleotides by several enzymes as well as broad polymerase acceptance of the obtained triazole linkage in PCR.
Highly diastereoselective synthesis of 11β,17β-diaryl-18a-homo-19-nor steroids (1997)

In a highly diastereoselective fashion novel 11β, 17β-diaryl steroids 17 and 18 were synthesized via Birch-type reduction [1] of styrylic precursors 11 and 15. Both precursors were readily available by Suzuki-type coupling reactions [2] of aromatic boronic acids [3] and the corresoponding enol triflates 6, 10, and 14. Regioselective 17-enol triflate formation in presence of a 11-keto function could be demonstrated in case of steroid 5. The remarkably high degree of stereo-selectivity observed parallels results from the natural series [4] and demonstrated a broader applicability of such single electron transfer reductions in stereoselective transformations on the steroid skeleton.
Specification of the Zebrafish Nervous System by Nonaxial Signals (1997)

The organizer of the amphibian gastrula provides the neurectoderm with both neuralizing and posteriorizing (transforming) signals. In zebrafish, transplantations show that a spatially distinct transformer signal emanates from tissues other than the organizer. Cells of the germring (nonaxial mesendoderm) posteriorized forebrain progenitors when grafted nearby, resulting in an ectopic hindbrain-like structure; in contrast, cells of the organizer (axial mesendoderm) caused no posterior transformation. Local application of basic fibroblast growth factor, a candidate transformer in Xenopus, caused malformation but not hindbrain transformation in the forebrain. Thus, the zebrafish gastrula may integrate spatially distinct signals from the organizer and the germring to pattern the neural axis.
RANTES chemokine expression in transplant-associated accelerated atherosclerosis. (1996)

The pathogenesis of transplantation-associated accelerated atherosclerosis is poorly understood, but it is likely to be an alloimmune response involving infiltration of the vessel wall by T lymphocytes and monocytes leading to smooth muscle cell proliferation and extracellular matrix deposition. RANTES is a chemokine that selectively chemoattracts T lymphocytes, NK cells, monocytes, and eosinophils. The expression of RANTES in accelerated atherosclerosis was investigated by in situ hybridization and immunohistochemistry.Coronary arteries from six patients undergoing accelerated atherosclerosis were obtained at the time of retransplantation. Normal coronary arteries from two patients with idiopathic dilated cardiomyopathy were used as controls. Messenger RNA for RANTES was localized with digoxigenin-labeled complementary DNA probes. RANTES protein was detected by use of a monoclonal antibody and a three-step horseradish peroxidase method.RANTES mRNA and protein were detected in the lymphocytes, macrophages, myofibroblasts, and endothelial cells of arteries undergoing accelerated atherosclerosis but not in normal coronary arteries.In view of its in vitro biologic activity and in vivo expression pattern, RANTES may be a pivotal mediator of the cellular infiltrate seen in graft atherosclerosis. This information may help in the design of novel diagnostic and therapeutic approaches to this increasingly important disease process.
Signaling Functions of Reactive Oxygen Species (2010)

We review signaling by reactive oxygen species, which is emerging as a major physiological process. However, among the reactive oxygen species, H(2)O(2) best fulfills the requirements of being a second messenger. Its enzymatic production and degradation, along with the requirements for the oxidation of thiols by H(2)O(2), provide the specificity for time and place that are required in signaling. Both thermodynamic and kinetic considerations suggest that among possible oxidation states of cysteine, formation of sulfenic acid derivatives or disulfides can be relevant as thiol redox switches in signaling. In this work, the general constraints that are required for protein thiol oxidation by H(2)O(2) to be fast enough to be relevant for signaling are discussed in light of the mechanism of oxidation of the catalytic cysteine or selenocysteine in thiol peroxidases. While the nonenzymatic reaction between thiol and H(2)O(2) is, in most cases, too slow to be relevant in signaling, the enzymatic catalysis of thiol oxidation by these peroxidases provides a potential mechanism for redox signaling.
Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology (2014)

We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed "luminal" and "basal-like," which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtype-specific therapies, will be of interest.
Sequencing and characterization of a gene cluster encoding the enzymes for L-rhamnose metabolism in Escherichia coli (1993)

The sequencing of the EcoRI-HindIII fragment complementing mutations in the structural genes of the L-rhamnose regulon of Escherichia coli has permitted identification of the open reading frames corresponding to rhaB, rhaA, and rhaD. The deduced amino acid sequences gave a 425-amino-acid polypeptide corresponding to rhamnulose kinase for rhaB, a 400-amino-acid polypeptide corresponding to rhamnose isomerase for rhaA, and a 274-amino-acid polypeptide corresponding to rhamnulose-1-phosphate aldolase for rhaD. Transcriptional fusions of the three putative promoter regions to lacZ showed that only the rhaB leader region acted as a promoter, as indicated by the high beta-galactosidase activity induced by rhamnose, while no significant activity from the rhaA and rhaD constructions was detected. The rhaB transcription start site was mapped to -24 relative to the start of translation. Mutations in the catabolic genes were used to show that L-rhamnose may directly induce rhaBAD transcription.
Protein Kinase G from Pathogenic Mycobacteria Promotes Survival Within Macrophages (2004)

Pathogenic mycobacteria resist lysosomal delivery after uptake into macrophages, allowing them to survive intracellularly. We found that the eukaryotic-like serine/threonine protein kinase G from pathogenic mycobacteria was secreted within macrophage phagosomes, inhibiting phagosome-lysosome fusion and mediating intracellular survival of mycobacteria. Inactivation of protein kinase G by gene disruption or chemical inhibition resulted in lysosomal localization and mycobacterial cell death in infected macrophages. Besides identifying a target for the control of mycobacterial infections, these findings suggest that pathogenic mycobacteria have evolved eukaryotic-like signal transduction mechanisms capable of modulating host cell trafficking pathways.
Massive MIMO for next generation wireless systems (2014)

Multi-user MIMO offers big advantages over conventional point-to-point MIMO: it works with cheap single-antenna terminals, a rich scattering environment is not required, and resource allocation is simplified because every active terminal utilizes all of the time-frequency bins. However, multi-user MIMO, as originally envisioned, with roughly equal numbers of service antennas and terminals and frequency-division duplex operation, is not a scalable technology. Massive MIMO (also known as large-scale antenna systems, very large MIMO, hyper MIMO, full-dimension MIMO, and ARGOS) makes a clean break with current practice through the use of a large excess of service antennas over active terminals and time-division duplex operation. Extra antennas help by focusing energy into ever smaller regions of space to bring huge improvements in throughput and radiated energy efficiency. Other benefits of massive MIMO include extensive use of inexpensive low-power components, reduced latency, simplification of the MAC layer, and robustness against intentional jamming. The anticipated throughput depends on the propagation environment providing asymptotically orthogonal channels to the terminals, but so far experiments have not disclosed any limitations in this regard. While massive MIMO renders many traditional research problems irrelevant, it uncovers entirely new problems that urgently need attention: the challenge of making many low-cost low-precision components that work effectively together, acquisition and synchronization for newly joined terminals, the exploitation of extra degrees of freedom provided by the excess of service antennas, reducing internal power consumption to achieve total energy efficiency reductions, and finding new deployment scenarios. This article presents an overview of the massive MIMO concept and contemporary research on the topic.
Animal models of allergic and inflammatory conjunctivitis (2003)

Allergic eye diseases are complex inflammatory conditions of the conjunctiva with an increasing prevalence and incidence. The diseases are often concomitant with other allergic diseases such as allergic rhinitis, atopic dermatitis and allergic asthma. Despite the disabling and prominent symptoms of ocular allergies, they are less well studied and further insights into the molecular basics are still required. To establish new therapeutic approaches and assess immunological mechanisms, animal models of ocular allergies have been developed in the past years. The major forms of allergic ocular diseases, seasonal and perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis, each have different pathophysiological and immunological components. In contrast to these distinct entities, the current animal models are based on the sensitization against a small number of allergens such as ovalbumin, ragweed pollen or major cat allergens and consecutive challenge. Different animal species have been used so far. Starting with guinea-pig models of allergic conjunctivitis to assess pharmacological aspects, new models including rats and mice have been developed which mimic major features of ocular allergy. The presently preferred species for the investigation of the immunological basis of the disease is represented by murine models of allergic conjunctivitis. In the future, combined ocular, nasal and aerosolic challenges with allergens may provide a model of allergy that encompasses simultaneously the target organs eye, nose and airways with conjunctivitis, rhinitis and asthma.
Structural changes and metal binding by proalbumins and other amino-terminal genetic variants of human serum albumin. (1987)

Proalbumins are rare genetic variants of human serum albumin containing a basic propeptide that is not removed during post-transcriptional processing because of a mutation in the site of excision, an Arg-Arg sequence. We have identified the amino acid substitutions in three different types of proalbumins designated Gainesville, Taipei, and Takefu. The first two proalbumins are identical to previously described proalbumins of the Christchurch and Lille types, respectively, and exhibit the characteristic properties of susceptibility to tryptic cleavage and of lower metal-binding affinity. Takefu is a third type of proalbumin and resists tryptic cleavage because of the substitution Arg-1----Pro. Each of the first two types of proalbumins has been identified in geographically separate, ethnically diverse populations and therefore must have arisen by independent mutations. There is some tendency for mutations in albumin to cluster in the propeptide sequence. Although the substitution His3----Gln in the genetic variant albumin Nagasaki-3 decreases metal-binding affinity, mutations further down the polypeptide chain have no such effect, nor is there any reduction of copper-binding affinity in albumin from patients with Wilson disease.
Anti‐inflammatory Activity of Amine‐carboxyboranes in Rodents (1995)

Amine-carboxyboranes are potent anti-inflammatory agents reducing induced edema and pleural effusion at 8 mg/Kg, i.p. They protect against LPS (Salmonella) induced septic shock from 2-8 mg/Kg/day and are effective in blocking pain mediated both locally and centrally. The mode of action of these agents is by blocking release of cytokines from macrophages, thus reducing lysosomal hydrolytic and proteolytic enzyme activities of affected cells. The agents also reduce prostaglandin and leukotriene synthesis by blocking the activities of regulatory enzymes of the respective pathways.