gebhart/patrepeval huggingface dataset:
Alloantigen specific CD8+CD28− FOXP3+ T suppressor cells induce ILT3+ ILT4+ tolerogenic endothelial cells, inhibiting alloreactivity (2004)

Endothelial cells have been shown to activate T cell responses to alloantigens, triggering transplant rejection. However, they may also play a role in tolerance induction. Using RT-PCR we show here that alloantigen specific CD8(+)CD28(-) T suppressor cells generated in vitro are FOXP3 positive and interact with human endothelial cells. This interaction results in the induction of inhibitory receptors and down-regulation of costimulatory and adhesion molecules, thus rendering endothelial cells tolerogenic. In turn, tolerized endothelial cells elicit the differentiation of CD8(+)CD28(-) FOXP3(+) T suppressor cells. Taken together our data demonstrate a functional and phenotypic overlap between tolerogenic dendritic cells and endothelial cells. Furthermore, alloantigen specific CD8(+)CD28(-) FOXP3(+) T cells, which trigger the upregulation of inhibitory receptors in endothelial cells, are present in the circulation of heart allograft recipients in quiescence as demonstrated by flow cytometry, RT-PCR and luciferase transcription assays. Their detection facilitates the identification of patients who may benefit from partial or complete cessation of immunosuppressive therapy, a goal of obvious importance given the morbidity and mortality associated with chronic immunosuppression. Modulation of endothelial cells in favor of promoting tolerance may be important for long-term survival of organ allografts.
Optimal rate based flow control for ABR services in ATM networks (2003)

In this paper, we present an explicit rate-based flow control scheme for ABR services, which is based on the linear quadratic Gaussian (LQG) control-theoretic approach. The goal of our scheme is to share the available bandwidth capacity fairly among many sources while maintaining the queue length at a bottleneck node at a desired level.
Eukaryotic Translation Initiation Factor 4E Activity Is Modulated by HOXA9 at Multiple Levels (2005)

The eukaryotic translation initiation factor 4E (eIF4E) alters gene expression on multiple levels. In the cytoplasm, eIF4E acts in the rate-limiting step of translation initiation. In the nucleus, eIF4E facilitates nuclear export of a subset of mRNAs. Both of these functions contribute to eIF4E's ability to oncogenically transform cells. We report here that the homeodomain protein, HOXA9, is a positive regulator of eIF4E. HOXA9 stimulates eIF4E-dependent export of cyclin D1 and ornithine decarboxylase (ODC) mRNAs in the nucleus, as well as increases the translation efficiency of ODC mRNA in the cytoplasm. These activities depend on direct interactions of HOXA9 with eIF4E and are independent of the role of HOXA9 in transcription. At the biochemical level, HOXA9 mediates these effects by competing with factors that repress eIF4E function, in particular the proline-rich homeodomain PRH/Hex. This competitive mechanism of eIF4E regulation is disrupted in a subset of leukemias, where HOXA9 displaces PRH from eIF4E, thereby contributing to eIF4E's dysregulation. In regard to these results and our previous finding that approximately 200 homeodomain proteins contain eIF4E binding sites, we propose that homeodomain modulation of eIF4E activity is a novel means through which this family of proteins implements their effects on growth and development.
Resistance to Insulin Therapy Among Patients and Providers (2005)

Patient and provider resistance to insulin therapy is substantial, and for providers it is part of a larger pattern of reluctance to prescribe blood glucose-lowering medication. Interventions to facilitate timely initiation of insulin therapy will need to address factors associated with this resistance.
A Heptad Repeat in Herpes Simplex Virus 1 gH, Located Downstream of the α-Helix with Attributes of a Fusion Peptide, Is Critical for Virus Entry and Fusion (2005)

Entry of herpes simplex virus 1 (HSV-1) into cells occurs by fusion with cell membranes; it requires gD as the receptor binding glycoprotein and the trigger of fusion, and the trio of the conserved glycoproteins gB, gH, and gL to execute fusion. Recently, we reported that the ectodomain of HSV-1 gH carries a hydrophobic alpha-helix (residues 377 to 397) with attributes of an internal fusion peptide (T. Gianni, P. L. Martelli, R. Casadio, and G. Campadelli-Fiume, J. Virol. 79:2931-2940, 2005). Downstream of this alpha-helix, a heptad repeat (HR) with a high propensity to form a coiled coil was predicted between residues 443 and 471 and was designated HR-1. The simultaneous substitution of two amino acids in HR-1 (E450G and L453A), predicted to abolish the coiled coil, abolished the ability of gH to complement the infectivity of a gH-null HSV mutant. When coexpressed with gB, gD, and gL, the mutant gH was unable to promote cell-cell fusion. These defects were not attributed to a defect in heterodimer formation with gL, the gH chaperone, or in trafficking to the plasma membrane. A 25-amino-acid synthetic peptide with the sequence of HR-1 (pep-gH(wt25)) inhibited HSV replication if present at the time of virus entry into the cell. A scrambled peptide had no effect. The effect was specific, as pep-gH(wt25) did not reduce HSV-2 and pseudorabies virus infection. The presence of a functional HR in the HSV-1 gH ectodomain strengthens the view that gH has attributes typical of a viral fusion glycoprotein.
Solvent-Induced Amphiphilic Molecular Baskets:  Unimolecular Reversed Micelles with Different Size, Shape, and Flexibility (2006)

Amphiphilic molecular baskets were obtained by attaching facially amphiphilic cholate groups to a covalent scaffold (calix[4]arene or 1,3,5-2,4,6-hexasubstituted benzene). In a solvent mixture consisting of mostly a nonpolar solvent (i.e., CCl4) and a polar solvent (i.e., DMSO), the hydrophilic faces of cholates turned inward to form a reversed-micelle-like conformer whose stability was strongly influenced by the number of the cholates and the topology of the scaffold. Preferential solvation of the hydrophilic faces of cholates within the molecule by the polar solvent was cooperative and gave the fundamental driving force to the conformational change. The reversed-micelle-like conformer was most stable in structures that allowed multiple cholates to form a microenvironment that could efficiently enrich the polar solvent molecules from the bulk solvent mixture.
A Dimeric Peptide That Binds Selectively to Prostate-Specific Membrane Antigen and Inhibits its Enzymatic Activity (2006)

Prostate-specific membrane antigen (PSMA) is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types; however, it is not expressed by normal endothelial cells or other normal tissues. PSMA, therefore, represents an attractive candidate for selectively targeted therapies for prostate and/or other solid tumors. As an alternative approach to antibody-based anti-PSMA therapies, small peptides that bind selectively to PSMA-producing cells can be used to deliver cytotoxic drugs, protein toxins, and viruses selectively to malignant sites while minimizing systemic toxicity to normal tissues. Small peptides are relatively inexpensive to produce, not immunogenic, and easily coupled to cytotoxic agents. In the present study, a random phage library consisting of linear 12 amino acid peptides was used to identify peptides that bound selectively to PSMA. From a series of monomeric peptides, one with the sequence WQPDTAHHWATL was used to show binding of soluble peptide to PSMA. A dimeric version of this peptide showed markedly enhanced binding to soluble PSMA and an IC50 of 2.2 micromol/L for inhibition of PSMA enzymatic activity. Fluorescently labeled dimeric peptide bound selectively to PSMA-producing prostate cancer cells in vitro with no significant binding to non-PSMA-producing cells. Molecular modeling of the dimeric peptide revealed that histidine residues in close vicinity can efficiently coordinate a divalent ion and hold the peptide in a favorable configuration for binding and subsequent inhibition. These dimeric peptides, therefore, represent putative PSMA-selective targeting agents that are currently being evaluated for selective binding in vivo.
Allelic Polymorphism Synergizes with Variable Gene Content to Individualize Human KIR Genotype (2002)

Killer Ig-like receptor (KIR) genes are a multigene family on human chromosome 19. KIR genes occur in various combinations on different haplotypes. Additionally, KIR genes are polymorphic. To examine how allelic polymorphism diversifies KIR haplotypes with similar or identical combinations of KIR genes, we devised methods for discriminating alleles of KIR2DL1, -2DL3, -3DL1, and -3DL2. These methods were applied to 143 individuals from 34 families to define 98 independent KIR haplotypes at the allele level. Three novel 3DL2 alleles and a chimeric 3DL1/3DL2 sequence were also identified. Among the A group haplotypes were 22 different combinations of 2DL1, 2DL3, 3DL1, and 3DL2 alleles. Among the B group haplotypes that were unambiguously determined were 15 distinct haplotypes involving 9 different combinations of KIR genes. A and B haplotypes both exhibit strong linkage disequilibrium (LD) between 2DL1 and 2DL3 alleles, and between 3DL1 and 3DL2 alleles. In contrast, there was little LD between the 2DL1/2DL3 and 3DL1/3DL2 pairs that define the two halves of the KIR gene complex. The synergistic combination of allelic polymorphism and variable gene content individualize KIR genotype to an extent where unrelated individuals almost always have different KIR types. This level of diversity likely reflects strong pressure from pathogens on the human NK cell response.
Prolonged cholestasis triggered by hepatitis A virus infection and variants of the hepatocanalicular phospholipid and bile salt transporters (2012)

Hepatitis A virus (HAV) infection resolves in most patients uneventfully within weeks from the onset of the disease. In rare cases, however, it may relapse or cause prolonged cholestasis. Here we present a case of a 36-year-old female patient who developed severe pruritus and jaundice three weeks after initially uncomplicated hepatitis A. A relapse of the infection was excluded. Since therapy with colestyramin, antihistaminics, naloxon and ursodeoxycholic acid (UDCA) did not improve symptoms, we decided to perform plasma absorption and to start rifampicin therapy. Under these measures, pruritus and jaundice, as well as serum bilirubin levels improved gradually and after four plasmapheresis sessions we were able to discharge the patient. Genetic testing showed the presence of two procholestatic polymorphisms, the c.3084 [GG] variant within the gene encoding the hepatocanalicular bile salt transporter ABCB11 and the c.711 [AT] variant of the phosphatidylcholine floppase ABCB4. We speculate that this compound ABCB4-ABCB11 genotype led to a severe intrahepatic cholestasis in the setting of HAV infection. In conclusion, our case suggests that polymorphisms within the hepatocanalicular transporters may contribute to a more pronounced course of HAV infection. Although dedicated studies in large cohorts of patients are needed to confirm this observation, we speculate that patients carrying procholestatic hepatobiliary transporter variants may benefit from vaccination against hepatitis A.
Loss of heterozygosity on the X chromosome in human breast cancer (1995)

The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.
A Comparison of High- Versus Low-Linear Energy Transfer Somatostatin Receptor Targeted Radionuclide Therapy In Vitro (2005)

(213)Bi-DOTATOC is significantly more potent than (177)Lu-DOTATOC in vitro because of its high-LET alpha-emission.(213)Bi-DOTATOC shows enhanced effects on mitotic and apoptotic cell deaths.
Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain (2000)

In a complementary DNA (cDNA) screening of murine Th2-skewed lymphocytes with our recently developed signal sequence trap method termed SST-REX, a novel type 1 cytokine receptor, Delta1 (delta1), was identified. Although delta1 is ubiquitously expressed in multiple tissues, the expression level is higher in Th2-skewed lymphocytes than in Th1-skewed ones. The delta1 cDNA encodes a 359-amino acid type 1 membrane protein. The extracellular domain of 206 amino acids showed 24% identity with the murine common gamma receptor that is shared among the receptors for interleukin(IL)-2, IL-4, IL-7, IL-9, and IL-15. The membrane-proximal region of delta1 includes a box1 motif, which is important for association with Janus kinases (JAKs), and showed a significant homology with that of the mouse erythropoietin receptor (EPOR). A box2 motif was also found in close proximity to the box1 region. Dimerization of the cytoplasmic region of delta1 alone did not transduce proliferative signals in IL-3-dependent cell lines. However, the membrane-proximal region of delta1 could substitute for that of human EPOR in transmitting proliferative signals and activating JAK2. These results suggest that delta1 is a subunit of cytokine receptor that may be involved in multiple receptor systems and play a regulatory role in the immune system and hematopoiesis.
Refined crystal structure and mutagenesis of human granulocyte-macrophage colony-stimulating factor (1996)

The crystal structure of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) has been refined against data extending to a resolution of approximately 2.4 A along a* and approximately 1.9 A along b* and c*. Anisotropic scale factors of B11 = -20.8 A2, B22 = 7.4 A2, B33 = 13.3 A2 corrected for the more rapid fall of diffraction in the a* direction. The anisotropy correlates with the weak crystal packing interactions along the a axis. In addition to apolar side chains in the protein core, there are 10 buried hydrogen bonding residues. Those residues involved in intramolecular hydrogen bonding to main chain atoms are better conserved than those hydrogen bonding to other side chain atoms; 24 solvation sites are observed at equivalent positions in the two molecules in the asymmetric unit, and the strongest among these are located in clefts between secondary structural elements. No buried water sites are seen. Two surface clusters of hydrophobic side chains are located near the expected receptor binding regions. Mutagenesis of 11 residues on the helix A/helix C face confirms the importance of Glu-21 and shows that Gly-75 and Gln-86, located on helix C, each cause a greater than fourfold drop in activity. Glu-21 and Gly-75, but not Gln-86, are structurally equivalent to residues involved in the growth hormone binding to its receptor.
Tumor Targets and Biomarkers in Renal Cell Carcinoma (2007)

Renal cell carcinoma (RCC) is the most common malignancy of the kidney. Unfortunately, 50% off all patients diagnosed with this disease will develop metastasized disease for which no adequate treatment can be offered currently. Therefore, the identification of prognostic factors and biomarkers is of the greatest importance. They might show additional prognostic value over classical prognostic factors like stage and grade. Also, these markers can be used for a better patient selection, development of specific gene immunotherapy strategies, and a better follow-up. In this chapter, we review current and future biomarkers of interest in the diagnosis, treatment, and follow-up of patients with RCC.
Pneumococcal immunization in patients with systemic lupus erythematosus treated with immunosuppressives. (1985)

Immunogenicity of 14 valent pneumococcal vaccine was evaluated in a placebo controlled, double blind, randomized study involving 77 patients with systemic lupus erythematosus (SLE). Antibodies to 12 type specific capsular antigens were measured prior to and one and 6 months post injection. In 17 patients treated with prednisone plus cyclophosphamide and/or azathioprine, mean body concentrations (ng antibody nitrogen/ml serum) increased from 528 to 1328 and 852, respectively, in vaccinated patients compared to 307, 308 and 344 following placebo. In 60 patients not receiving immunosuppressives, mean antibody concentrations were 355, 1361 and 920 post vaccine and 401, 473 and 377 post placebo. Our study demonstrates that antibody responses to pneumococcal vaccine in SLE patients is unaffected by these immunosuppressive agents.
Optimizing statistical queries by exploiting orthogonality and interval properties of grouping relations (2002)

A statistical query first manipulates source category data to build a target category in the form of a grouping relation and then performs statistical functions on the associated measurement data. In this paper, the attributes in a grouping relation are partitioned into pair-wise disjoint sets, each called a dimension. A grouping relation is said to be orthogonal if it is equal to the cross product of the projections of itself on all the dimensions. Orthogonality is useful in searching for and using pre-computed summaries on other categories. However, a grouping relation is sometimes not orthogonal, but rather k-partially orthogonal (i.e., the union of k orthogonal ones). It is shown that it is NP-complete to decide if a grouping relation is k-partially orthogonal. The paper then gives an algorithm to derive partial orthogonality. Also investigated in this paper are interval properties of grouping relations useful for optimizing statistical queries. An algorithm is described to derive interval properties.
The Effect of Lateral Stabilization on Walking in Young and Old Adults (2007)

We tested how lateral stability affects gait as a function of age. A simple computational model suggests that walking is laterally unstable and that age-related decreases in motor and sensory function may be treated as noise-like perturbations to the body. Step width variability may be affected by active control of foot placement subject to noise. We hypothesized that age-related deficits may lead to increased step width variability. A possible compensation would be to walk with wider steps to reduce the lateral instability. The addition of external stabilization, through elastic cords acting laterally on the body during treadmill walking, would be expected to yield reduced step width variability and/or reduced average step width. We measured step width, its variability (defined as standard deviation), and metabolic energy expenditure in eight adult human subjects aged less than 30 years (Young) and ten subjects aged at least 65 years (Old). Subjects walked with and without external stabilization, each at a self-selected step width as well as a prescribed step width of zero. In normal walking, Old subjects preferred 41% wider steps than Young, and expended 26% more net energy (P < 0.05). External stabilization caused both groups to prefer 58% narrower steps. In the prescribed zero step width condition, Old subjects walked with 52% more step width variability and at 20% higher energetic cost. External stabilization resulted in reduced step width variability and 16% decreased energetic cost. Although there was no significant statistical interaction between age group and stabilization, Old and Young subjects walked with similar energetic costs in the stabilized, prescribed step width condition. Age-related changes appear to affect lateral balance, and the resulting compensations explain much of the increased energetic cost of walking in older adults.
Interleukin-8. A corneal factor that induces neovascularization. (1992)

A rabbit corneal pocket model was used to demonstrate that physiologic concentrations of human recombinant (r) IL-8 may induce corneal neovascularization. Computer-assisted analysis of sequential fluorescein angiograms showed that rIL-8 doses ranging from 2 to 40 ng/cornea (P = 0.01), but not high dose rIL-8 (400 ng/cornea), results in neovascularization within 14 days. Repeat fluorescein angiograms 6 weeks after placing angiogenic doses of rIL-8 demonstrated significant regression (P = 0.01) of the vascularity present at 2 weeks, suggesting that IL-8 angiogenesis undergoes dynamic modulation similar to that normally seen in wound healing. To our knowledge, this is the first study showing an angiogenic role for IL-8, a finding that emphasizes the interplay between inflammation and wound healing. Our results imply that corneal-derived IL-8 may be important in corneal neovascularization, in particular, and that IL-8 may modulate wound healing in general. Finally, these results raise the possibility that corneal-derived cytokines, such as IL-8, may obfuscate the effects of agents tested in experimental corneal pocket models.
Recovery and Characterization of a Chimeric Rinderpest Virus with the Glycoproteins of Peste-des-Petits-Ruminants Virus: Homologous F and H Proteins Are Required for Virus Viability (2000)

Rinderpest (RP) and peste-des-petits-ruminants (PPR) are two important diseases of domestic ruminants. To improve on currently available vaccines against PPR, we have created cDNA copies of the RP virus genome in which either the fusion (F) or hemagglutinin (H) gene, or both, was replaced with the corresponding gene from PPR virus. It was necessary to develop a modified rescue system in which the T7 RNA polymerase was provided by a recombinant fowlpox virus and the entire rescue procedure took place in Vero cells before we could obtain live virus from these chimeric constructs. No virus was recovered when only one of the glycoprotein genes was changed, but a chimeric virus containing both F and H genes from PPR virus was reproducibly rescued from cDNA, indicating that a virus-specific functional interaction takes place between the F and H proteins. The rescued virus expressing the PPR glycoproteins grew more slowly in tissue culture than either parental virus and formed abnormally large syncytia. Goats infected with the chimera showed no adverse reaction, as assessed by clinical signs, temperature, leukocyte count, virus isolation, and serology, and were protected from subsequent challenge with wild-type PPR virus.