gebhart/patrepeval huggingface dataset:
A new modified DNA enzyme that targets influenza virus A mRNA inhibits viral infection in cultured cells (2004)

DNA enzymes are RNA-cleaving single-stranded DNA molecules. We designed DNA enzymes targeting the PB2 mRNA translation initiation (AUG) region of the influenza A virus (A/PR/8/34). The modified DNA enzymes have one or two N3'-P5' phosphoramidate bonds at both the 3'- and 5'-termini of the oligonucleotides, which significantly enhanced their nuclease resistance. These modified DNA enzymes had the same cleavage activity as the unmodified DNA enzymes, determined by kinetic analyses, and reduced influenza A virus replication by more than 99%, determined by plaque formation. These DNA enzymes are highly specific; their protective effect was not observed in influenza B virus (B/Ibaraki)-infected Madin-Darby canine kidney cells.
Experimental respiratory syncytial virus infection of adults. Possible mechanisms of resistance to infection and illness. (1971)

Volunteers were inoculated with a low (102.7 pfu), or 200-fold higher dose (105.0 pfu) of respiratory syncytial virus (RSV). The low dose infected 100% of the men but did not produce illness; the level of virus replication and the magnitude of the subsequent antibody response were inversely correlated with the level of nasal secretory neutralizing antibody prior to infection. The high dose infected only 53% of the men (9 of 17); five of the infected men became ill. Two of the men who excreted virus apparently resisted experimental inoculation and acquired infection secondarily by contact with infected men. The differences in rates of infection between the two studies were minimized if only those men who had extensive infection (virus excretion τ; 102.5 pfu or significant antibody responses) were considered. Resistance to extensive infection in both studies, and resistance to illness in the second study, appeared to be correlated with high levels of nasal wash antibody, but not with the level of serum antibody.
Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment? (2006)

Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.
Molecular diversity of thermophilic cellulolytic and hemicellulolytic bacteria (1999)

Many thermophilic bacteria belong to groups with deep phylogenetic lineages and ancestral forms were established before the occurrence of eucaryotes that produced cellulose and hemicellulose.Thus they may have acquired their L-glycanase genes from more recent mesophilic bacteria.Most research has focussed on extremely thermophilic eubacteria growing above 65C under anaerobic conditions.Only recently have aerobic cellulolytic thermophiles been described from widely separated lineages (for example, Rhodothermus marinus, Caldibacillus cellulovorans).Many thermophilic bacteria produce cellulases and xylanases that have novel structures, with additional protein domains not identified with their catalytic activity.Many of these enzymes are multifunctional and code for more than one catalytic activity.This type of enzyme structure was first identified in the extreme thermophile Caldicellulosiruptor saccharolyticus.There is a general relatedness evident between catalytic domains, cellulose binding domains and other ancillary domains, which suggests that there may have been significant lateral gene transfer in the evolution of these microorganisms.Detailed molecular studies show that there is variation in the sequences of these related but not identical genes from taxonomically widely-separated organisms.
Exogenous glycosyl phosphatidylinositol-anchored CD59 associates with kinases in membrane clusters on U937 cells and becomes Ca(2+)-signaling competent. (1995)

CD59, an 18-20-kD complement inhibitor anchored to the membrane via glycosyl phosphatidylinositol (GPI), can induce activation of T cells and neutrophils upon cross-linking with antibody. GPI-anchored molecules cocluster in high mol wt detergent-resistant complexes containing tyrosine kinases that are implicated in the signaling pathway. Exogenous, incorporated GPI-anchored molecules are initially unable to induce activation, presumably because they are not associated with kinases. Here we demonstrate that erythrocyte-derived CD59 incorporated in a CD59-negative cell line acquires signaling capacity in a time-dependent manner. Confocal microscopy revealed an initial diffuse distribution of CD59 that became clustered within 2 h to give a pattern similar to endogenous GPI-anchored molecules. Gel filtration of detergent-solubilized cells immediately after incorporation revealed that CD59 was mainly monomeric, but after 3 h incubation all was in high mol wt complexes and had become associated with protein kinases. Newly incorporated CD59 did not deliver a Ca2+ signal upon cross-linking, but at a time when it had become clustered and associated with kinase activity, cross-linking induced a large calcium transient, indicating that CD59 had incorporated in a specialized microenvironment that allowed it to function fully as a signal-transducing molecule.
Trastuzumab-Auristatin immunoconjugates inhibit growth and induce apoptosis in human breast cancer cells in vitro (2005)

6184 Trastuzumab (Herceptin ®) is a humanized anti-HER2 antibody approved for use in the treatment of women with HER2-overexpressing metastatic breast cancer. There is great interest in using MAbs as vehicles for the selective delivery of cytotoxic agents to tumor cells. Linking a cytotoxic agent to an antibody that recognizes a tumor-associated antigen may improve the therapeutic index of the drug. We demonstrate in vitro activity of antibody-drug conjugates consisting of a potent antimitotic agent monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF, an acidic MMAE analogue) linked to trastuzumab. The conjugate trastuzumab-vc-MMAE or trastuzumab-vc-MMAF is internalized and trafficked to lysosomes in HER2-overexpressing cells, where drug is released after hydrolysis of the valine-citrulline (vc) peptide linker. Trastuzumab-vc-MMAE or trastuzumab-vc-MMAF selectively and potently inhibited the growth of SK-BR-3 and BT-474 cells that overexpress HER2. In contrast, the conjugates did not affect MCF-7 cells, which express normal/low amounts of HER2, or MDA-MB-468 cells, which lack HER2 expression. Short (10 min) exposure to the conjugates produced long-lasting (at least 72 h) inhibition of SK-BR-3 and BT-474 cell proliferation in culture. Treatment of SK-BR-3 or BT-474 cells with the conjugates resulted in a dose-dependent growth arrest at the G2/M phase of the cell cycle after 48 hours. Exposure to the conjugates induced apoptosis as demonstrated by activation of caspase 3/7 and processing of caspases 8 and 9. Apoptosis induction was confirmed by release of cytochrome c from the mitochondria into the cytosol, and degradation of poly (ADP-ribose) polymerase (PARP). In addition, trastuzumab conjugates induced bcl-2 hyperphosphorylation in MCF-7/HER2-18 cells (engineered to overexpress HER2) in a dose dependent manner. These data suggest that trastuzumab-auristatin immunoconjugates may be a highly effective and selective therapy for the treatment of HER2-overexpressing breast cancer.
Detecting disruptive routers: a distributed network monitoring approach (1998)

An attractive target for a computer system attacker is the router. An attacker in control of a router can disrupt communication by dropping or misrouting packets passing through the router. We present a protocol called WATCHERS which detects and reacts to routers that drop or misroute packets. WATCHERS is based on the principle of conservation of flow in a network: all data bytes sent into a node, and not destined for that node, are expected to exit the node. WATCHERS tracks this flow, and detects routers that violate the conservation principle. We show that WATCHERS has several advantages over existing network monitoring techniques. We discuss WATCHERS response to several different types of bad router behavior. We demonstrate that in ideal conditions WATCHERS makes no false positive diagnoses, and we describe how WATCHERS can be tuned to perform nearly as well in realistic conditions. Also, we argue that WATCHERS impact on router performance and WATCHERS memory requirements are reasonable for many environments.
Anatomy and Function of the Eye (2007)

This text is not a generic book on the immunology of the eye, but instead is based on the theme of ocular immune privilege. In subsequent chapters it is apparent that the immunologic privilege within the eye is dependent upon novel anatomic and physiologic properties of the organ. The focus of this chapter is to provide a concise description of both the function and anatomy of the normal eye.
Case Report: Vacuum-assisted closure of a sacral pressure sore (1997)

This case study illustrates the use of a vacuum suction technique to stimulate the granulation response in a chronic wound in a patient with morbid obesity
Analysis of the transcriptional activity of the hut promoter in Bacillus subtilis and identification of a cis‐acting regulatory region associated with catabolite repression downstream from the site of transcription (1992)

Levels of transcripts initiated at a hut promoter in Bacillus subtilis were analysed. The addition of histidine to the culture medium increased the level of the transcript sixfold. In the presence of histidine and glucose together, the level of the transcript was reduced to the level in the absence of induction. Furthermore, addition of a mixture of 16 amino acids to cultures of induced cells and of catabolite-repressed cells decreased levels of the transcript 16-fold and 2.6-fold, respectively. Thus, it appears that at least three regulatory mechanisms associated with induction, catabolite repression, and amino acid repression, control the transcriptional activity of the hut promoter. Expression of the hut promoter-lacZ fusions that contained various regions of the hutP gene and deletion analysis of the hutP region revealed a cis-acting sequence associated with catabolite repression that was located between positions +204 and +231 or around position +203.
Fibrinogen Substrate Recognition by Staphylocoagulase·(Pro)thrombin Complexes (2005)

Thrombin generation and fibrinogen (Fbg) clotting are the ultimate proteolytic reactions in the blood coagulation pathway. Staphylocoagulase (SC), a protein secreted by the human pathogen Staphylococcus aureus, activates prothrombin (ProT) without proteolysis. The SC.(pro)thrombin complex recognizes Fbg as a specific substrate, converting it directly into fibrin. The crystal structure of a fully active SC fragment containing residues 1-325 (SC-(1-325)) bound to human prethrombin 2 showed previously that SC inserts its Ile(1)-Val(2) N terminus into the Ile(16) pocket of prethrombin 2, inducing a functional active site in the cognate zymogen conformationally. Exosite I of alpha-thrombin, the Fbg recognition site, and proexosite I on ProT are blocked by domain 2 of SC-(1-325). In the present studies, active site-labeled fluorescent ProT analogs were used to quantitate Fbg binding to the SC-(1-325).ProT complex. Fbg binding and cleavage are mediated by expression of a new Fbg-binding exosite on the SC-(1-325).ProT complex, resulting in formation of an (SC-(1-325).ProT)(2).Fbg pentameric complex with a dissociation constant of 8-34 nm. In both crystal structures, the SC-(1-325).(pre)thrombin complexes form dimers, with both proteinases/zymogens facing each other over a large U-shaped cleft, through which the Fbg substrate could thread. On this basis, a molecular model of the pentameric (SC-(1-325).thrombin)(2).Fbg encounter complex was generated, which explains the coagulant properties and efficient Fbg conversion. The results provide new insight into the mechanism that mediates high affinity Fbg binding and cleavage as a substrate of SC.(pro)thrombin complexes, a process that is central to the molecular pathology of S. aureus endocarditis.
Wnt signaling in adult intestinal stem cells and cancer (2013)

Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physiological range. In addition, the Wnt pathway involves various feedback loops that balance the opposing processes of cell proliferation and differentiation. Today, we have compelling evidence that mutations causing aberrant activation of the Wnt pathway promote expansion of undifferentiated progenitors and lead to cancer. The review summarizes recent advances in characterization of adult epithelial stem cells in the gut. We mainly focus on discoveries related to molecular mechanisms regulating the output of the Wnt pathway. Moreover, we present novel experimental approaches utilized to investigate the epithelial cell signaling circuitry in vivo and in vitro. Pivotal aspects of tissue homeostasis are often deduced from studies of tumor cells; therefore, we also discuss some latest results gleaned from the deep genome sequencing studies of human carcinomas of the colon and rectum.
Semi-Probabilistic Content-Based Publish-Subscribe (2005)

Mainstream approaches to content-based distributed publish-subscribe typically route events deterministically based on information collected from subscribers, and do so by relying on a tree-shaped overlay network. While this solution achieves scalability in fixed, large-scale settings, it is less appealing in scenarios characterized by high dynamicity, e.g., mobile ad hoc networks or peer-to-peer systems. At the other extreme, researchers in the related fields of multicast and group communication have successfully exploited probabilistic techniques that provide increased fault tolerance, resilience to changes, and yet are scalable. In this paper, we propose a novel approach where event routing relies on deterministic decisions driven by a limited view on the subscription information and, when this is not sufficient, resorts to probabilistic decisions performed by selecting links at random. Simulations show that the particular mix of deterministic and probabilistic decisions we put forth in this work is very effective at providing high event delivery and low overhead in highly dynamic scenarios, without sacrificing scalability
Subcellular, Time-Resolved Studies of Singlet Oxygen in Single Cells (2005)

In time-resolved and spatially resolved experiments, singlet molecular oxygen, O2(a1Deltag), was created in a single nerve cell upon irradiation of a sensitizer incorporated in the cell using a focused laser beam. The singlet oxygen thus produced was detected by its infrared phosphorescence. Data obtained indicate that in both the cytoplasm and the nucleus of the cell, this reactive species is approximately 1-2 orders of magnitude longer-lived than previously believed. The data demonstrate that deactivation of singlet oxygen in the cell is dominated by interactions with the solvent not cellular constituents such as proteins. These results provide a new perspective for mechanistic studies of the role of O2(a1Deltag) in photoinduced cell death and intracellular signaling.
Deep Brain Stimulation for Parkinson Disease (2010)

(1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients.
Clinical use of a frameless stereotactic arm: results of 325 cases (1995)

The viewing wand is a frameless stereotactic arm that can be used in conjunction with computerized tomography (CT) or magnetic resonance (MR) imaging to provide image-based intraoperative navigation. The authors report a series of 325 cases in which the viewing wand was used and evaluated for its utility, ease of integration into the standard surgical setup, reliability, and real-world accuracy. The use of the system was associated with minimal additional effort or time spent in setting up the procedure as long as a trained technician performed the data transfer and reconstruction. The viewing wand was used in 165 cases in conjunction with CT and 145 cases with MR imaging. The system was reliable, achieving a useful registration in 310 of 325 cases (95.4%). Fiducial-based registration was more accurate than an anatomical landmark-surface fit algorithm method of registration (mean 2.8 vs. 5.6 mm error, respectively, for CT; and mean 3.0 vs. 6.2 mm for MR imaging). The actual error of the system in estimating the position of the probe tip just after registration was judged by the operating surgeon to be less than 2 mm in 92% of MR imaging cases and in 82% of CT cases, between 2 and 5 mm in 7% of MR imaging and 17% of CT cases, and greater than 5 mm in less than 1% of MR imaging and 1.2% of CT cases. The accuracy of the system degraded during the operation, so that by the third evaluation the error was estimated to be less than 2 mm in 77% of MR imaging and 62% of CT cases. Overall, the viewing wand was found to be reliable and accurate. This real-world accuracy was sufficient for a broad range of applications including glioma resection, cerebrospinal fluid shunting procedures, resection of small subcortical masses, and temporal lobe resection. The system is a useful navigational aid that allows a direct approach to intracranial pathology without the drawbacks of application and the limitations of a stereotactic frame.
Cloning and characterization of a region of the Enterococcus faecalis conjugative plasmid, pCF10, encoding a sex pheromone-binding function (1993)

In order to investigate the mechanism by which peptide sex pheromones induce expression of the conjugation functions of certain Enterococcus faecalis plasmids, a biological assay was developed to measure the ability of cells carrying the conjugative plasmid pCF10 to bind the sex pheromone cCF10. The data indicated that pCF10 endows its host E. faecalis cell with the ability to specifically remove (apparently by irreversible binding) cCF10 activity from culture medium. The pCF10 DNA encoding this ability was localized to a 3.4-kb segment within a region involved in negative control of expression of conjugal transfer functions. This segment also encoded ability to bind the pheromone inhibitor peptide iCF10. DNA sequencing revealed three open reading frames, which have been denoted prgW (pheromone responsive gene W), prgZ, and prgY. The deduced product of prgW resembled regulatory proteins from other bacteria and eucaryotes, with a very high degree of identity within a putative DNA-binding domain. The prgY gene actually extended into an adjacent region of pCF10 and could encode a protein with significant similarity to a protein called TraB, believed to be involved in shutdown of pheromone cAD1 production by cells carrying the pheromone-inducible hemolysin plasmid pAD1, according to F.Y. An and D.B. Clewell (Abstr. Gen. Meet. Am. Soc. Microbiol. 1992, H70, 1992). The prgZ gene product showed significant relatedness to binding proteins encoded by oligopeptide permease (opp) operons in gram-positive and gram-negative bacteria and is highly similar to a pAD1-encoded protein, TraC, which is believed to mediate sex pheromone cAD1 binding (K. Tanimoto, F. Y. An, and D. B. Clewell, submitted for publication). A Tn5 insertion into prgZ abolished cCF10 binding ability.
Monomeric Fc Fusion Molecules (2009)

This chapter contains sections titled: Introduction Neonatal Fc Receptor FcRn for Delivery of Fc-Fusion Monomers and Dimers EpoFc Monomer and Dimer Prototype Molecules Other Monomeric Fc Fusion Proteins Summary Acknowledgments References
Charge analysis of N-Glycans from human recombinant coagulation factor VIII and human FVIII standards (2004)

Charge analysis of N-Glycans from human recombinant coagulation factor VIII and human FVIII standards -
Oral Administration of Tetrahydrobiopterin Prevents Endothelial Dysfunction and Vascular Oxidative Stress in the Aortas of Insulin-Resistant Rats (2000)

Abstract —We have reported that a deficiency of tetrahydrobiopterin (BH 4 ), an active cofactor of endothelial NO synthase (eNOS), contributes to the endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O 2 − ) generation in the insulin-resistant state. To further confirm this hypothesis, we investigated the effects of dietary treatment with BH 4 on endothelium-dependent arterial relaxation and vascular oxidative stress in the aortas of insulin-resistant rats. Oral supplementation of BH 4 (10 mg · kg −1 · d −1 ) for 8 weeks significantly increased the BH 4 content in cardiovascular tissues of rats fed high levels of fructose (fructose-fed rats). Impairment of endothelium-dependent arterial relaxation in the aortic strips of the fructose-fed rats was reversed with BH 4 treatment. The BH 4 treatment was associated with a 2-fold increase in eNOS activity as well as a 70% reduction in endothelial O 2 − production compared with those in fructose-fed rats. The BH 4 treatment also partially improved the insulin sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats. Moreover, BH 4 treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-κB and activating protein-1, which were increased in fructose-fed rats. The BH 4 treatment of control rats did not have any significant effects on these parameters. These results indicate that BH 4 augmentation is essential for the restoration of eNOS function and the reduction of vascular oxidative stress in insulin-resistant rats.