gebhart/patrepeval huggingface dataset:
Vaccinia locomotion in host cells: Evidence for the universal involvement of actin-based motility sequences ABM-1 and ABM-2 (1998)

Vaccinia uses actin-based motility for virion movement in host cells, but the specific protein components have yet to be defined. A cardinal feature of Listeria and Shigella actin-based motility is the involvement of vasodilator-stimulated phosphoprotein (VASP). This essential adapter recognizes and binds to actin-based motility 1 (ABM-1) consensus sequences [(D/E)FPPPPX(D/E), X = P or T] contained in Listeria ActA and in the p90 host-cell vinculin fragment generated by Shigella infection. VASP, in turn, provides the ABM-2 sequences [XPPPPP, X = G, P, L, S, A] for binding profilin, an actin-regulatory protein that stimulates actin filament assembly. Immunolocalization using rabbit anti-VASP antibody revealed that VASP concentrates behind motile virions in HeLa cells. Profilin was also present in these actin-rich rocket tails, and microinjection of 10 microM (intracellular) ABM-2 peptide (GPPPPP)3 blocked vaccinia actin-based motility. Vinculin did not colocalize with VASP on motile virions and remained in focal adhesion contacts; however, another ABM-1-containing host protein, zyxin, was concentrated at the rear of motile virions. We also examined time-dependent changes in the location of these cytoskeletal proteins during vaccinia infection. VASP and zyxin were redistributed dramatically several hours before the formation of actin rocket tails, concentrating in the viral factories of the perinuclear cytoplasm. Our findings underscore the universal involvement of ABM-1 and ABM-2 docking sites in actin-based motility of Listeria, Shigella, and now vaccinia.
Tuning TCP and UDP Demultiplexing (1998)

Large servers that handle many hundreds of simultaneous clients are&#13;\nbecoming more and more important to the Internetwork infrastructure,&#13;\nfrom Web servers and caches to DNS servers. As the number of clients&#13;\nsimultaneously served by a host increases, so may the cost of&#13;\ndemultiplexing incoming packets to the appropriate application endpoint.&#13;\nThis paper explores the effect of caching and hashing on demultiplexing&#13;\nefficiency in TCP/IP implementations using a trace-driven approach.&#13;\nWe compare several cache- and hash-based techniques using traffic traces&#13;\nthat include mixes of different types of applications. Our results show&#13;\nthat different techniques are effective for different types of server&#13;\n(e.g., UDP vs. TCP-based services, Web servers vs. NFS servers).&#13;\nIn addition, we show that an extremely simple hash function provides&#13;\nperformance comparable to more complex functions at a fraction of the&#13;\ncost and can also compare favorably with content addressable memory&#13;\n(CAM) search performance under certain conditions. Based on our results,&#13;\nwe recommend certain simple and transparent strategies for optimizing&#13;\nperformance.
4-Acetyl-N,N-dibenzoylphenylamine (2002)

In the title compound, C22H17NO3, the three aromatic rings are orthogonal. The crystal structure is stabilized by weak intermolecular C—H⋯O and C—H⋯π interactions.
Developmental biology of hematopoiesis (1995)

The cellular and environmental regulation of hematopoiesis has been generally conserved throughout vertebrate evolution, although subtle species differences exist. The factors that regulate hematopoietic stem cell homeostasis may closely resemble the inducers of embryonic patterning, rather than the factors that stimulate hematopoietic cell proliferation and differentiation. Comparative study of embryonic hematopoiesis in lower vertebrates can generate testable hypotheses that similar mechanisms occur during hematopoiesis in higher species.
Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders (2008)

Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases, are characterized pathognomonically by the presence of intra- and/or extracellular lesions containing proteinaceous aggregates, and by extensive neuronal loss in selective brain regions. Related non-neuropathic systemic diseases, e.g., light-chain and senile systemic amyloidoses, and other organ-specific diseases, such as dialysis-related amyloidosis and type-2 diabetes mellitus, also are characterized by deposition of aberrantly folded, insoluble proteins. It is debated whether the hallmark pathologic lesions are causative. Substantial evidence suggests that these aggregates are the end state of aberrant protein folding whereas the actual culprits likely are transient, pre-fibrillar assemblies preceding the aggregates. In the context of neurodegenerative amyloidoses, the proteinaceous aggregates may eventuate as potentially neuroprotective sinks for the neurotoxic, oligomeric protein assemblies. The pre-fibrillar, oligomeric assemblies are believed to initiate the pathogenic mechanisms that lead to synaptic dysfunction, neuronal loss, and disease-specific regional brain atrophy. The amyloid beta-protein (Abeta), which is believed to cause Alzheimer's disease (AD), is considered an archetypal amyloidogenic protein. Intense studies have led to nominal, functional, and structural descriptions of oligomeric Abeta assemblies. However, the dynamic and metastable nature of Abeta oligomers renders their study difficult. Different results generated using different methodologies under different experimental settings further complicate this complex area of research and identification of the exact pathogenic assemblies in vivo seems daunting. Here we review structural, functional, and biological experiments used to produce and study pre-fibrillar Abeta assemblies, and highlight similar studies of proteins involved in related diseases. We discuss challenges that contemporary researchers are facing and future research prospects in this demanding yet highly important field.
Interrelationship between Dendritic Cell Trafficking and Francisella tularensis Dissemination following Airway Infection (2008)

Francisella tularensis, the etiological agent of the inhalation tularemia, multiplies in a variety of cultured mammalian cells. Nevertheless, evidence for its in vivo intracellular residence is less conclusive. Dendritic cells (DC) that are adapted for engulfing bacteria and migration towards lymphatic organs could serve as potential targets for bacterial residence and trafficking. Here, we focus on the in vivo interactions of F. tularensis with DC following airway infection of mice. Lethal airway infection of mice with the live vaccine strain (LVS) results in trafficking of a CD11b(high)/CD11c(med)/autofluorescence(low) DC subset from the respiratory tract to the draining mediastinal lymph node (MdLN). Simultaneously, a rapid, massive bacterial colonization of the MdLN occurs, characterized by large bacterial foci formation. Analysis of bacteria in the MdLN revealed a major population of extracellular bacteria, which co-exists with a substantial fraction of intracellular bacteria. The intracellular bacteria are viable and reside in cells sorted for DC marker expression. Moreover, in vivo vital staining experiments indicate that most of these intracellular bacteria ( approximately 75%) reside in cells that have migrated from the airways to the MdLN after infection. The correlation between DC and bacteria accumulation in the MdLN was further demonstrated by manipulating DC migration to the MdLN through two independent pathways. Impairment of DC migration to the MdLN, either by a sphingosine-1-phosphate receptor agonist (FTY720) or by the D prostanoid receptor 1 agonist (BW245C), resulted in reduced bacterial colonization of MdLN. Moreover, BW245C treatment delayed the onset of morbidity and the time to death of the infected mice. Taken together, these results suggest that DC can serve as an inhabitation niche for F. tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment.
Transmission of <I>Xylella fastidiosa</I> to Grapevines by <I>Homalodisca coagulata</I> (Hemiptera: Cicadellidae) (2003)

Pierce's disease (PD) of grapevines is caused by a xylem-limited bacterium Xylella fastidiosa (Wells, Raju, Hung, Weisburg, Mandelco-Paul, and Brenner) that is transmitted to plants by xylem sap-feeding insects. The introduction of the sharpshooter leafhopper Homalodisca coagulata (Say) into California has initiated new PD epidemics in southern California. In laboratory experiments, the major characteristics of H. coagulata's transmission of X. fastidiosa to grapevines were the same as reported for other vectors: short or absent latent period; nymphs transmitted but lost infectivity after molting and regained infectivity after feeding on infected plants; and infectivity persisted in adults. Adult H. coagulata acquired and inoculated X. fastidiosa in <1 h of access time on a plant. Inoculation rates increased with access time, but acquisition efficiency (20% per individual) did not increase significantly beyond 6-h access. Estimated inoculation efficiency per individual per day was 19.6, 17.9, and 10.3% for experiments where plant access was 1, 2, and 4 d, respectively. Freshly molted adults and nymphs acquired and transmitted X. fastidiosa more efficiently than did older, field-collected insects. H. coagulata transmitted X. fastidiosa to 2-yr-old woody tissues of grapevines as efficiently as to green shoots. H. coagulata transmitted X. fastidiosa 3.5 mo after acquisition, demonstrating persistence of infectivity in adults. About half (14/29) of the H. coagulata from which we failed to culture X. fostidiosa from homogenized heads (with a detection threshold of 265 CFU/head) transmitted the pathogen to grape, and 17 of 24 from which we cultured X. fastidiosa transmitted.
Supramolecular Biomaterials. A Modular Approach towards Tissue Engineering (2007)

Abstract Supramolecular chemistry is an exciting area of science that plays a central role in bringing different disciplines together, ranging from molecular medicine to nanotechnology. Materials science based on supramolecular interactions is an emerging field, which has made important steps forward in the past ten years. The self-assembly of small synthetic molecules into long-chain architectures gives rise to the careful design of supramolecular polymers or fibers based on highly directional, reversible, non-covalent interactions. Much afford is put into the development of supramolecular (polymeric) materials with true materials properties, both in solution and in the solid state. These supramolecular materials are beginning to reach the market in all kind of applications. The field of regenerative medicine in general and that of tissue engineering in particular is one of the most challenging areas in which supramolecular materials might have a high potential. In tissue engineering, the biological environment and the interactions of cells with the artificial biomaterial is of utmost importance for the functioning of the implant, i.e. the engineered tissue. Ideal biomaterials do not only have to fulfil the biomaterials trinity of tuneable mechanical properties, regulation of the degradability and the ease for bioactivity incorporation, but also have to mimic the natural environment where the materials are brought into. Therefore, a modular, self-assembly approach using several supramolecular building blocks is an exquisite way to produce such “responsive” biomaterials. It is proposed that the artificial materials described in this account have the same type of dynamic ability to adapt its biofunctionality as is so well known for the living cells in the host tissue. This account will highlight two systems, i.e. self-assembling oligopeptide fibers as pioneered by Stupp et al. and Zhang et al., and our hydrogen-bonded supramolecular polymers, to show the potential of a modular approach to dynamic biomaterials for tissue engineering.
Smooth Muscle Differentiation Marker Gene Expression Is Regulated by RhoA-mediated Actin Polymerization (2001)

Smooth muscle cell (SMC) differentiation is regulated by a complex array of local environmental cues, but the intracellular signaling pathways and the transcription mechanisms that regulate this process are largely unknown. We and others have shown that serum response factor (SRF) contributes to SMC-specific gene transcription, and because the small GTPase RhoA has been shown to regulate SRF, the goal of the present study was to test the hypothesis that RhoA signaling is a critical mechanism for regulating SMC differentiation. Coexpression of constitutively active RhoA in rat aortic SMC cultures significantly increased the activity of the SMC-specific promoters, SM22 and SM alpha-actin, whereas coexpression of C3 transferase abolished the activity of these promoters. Inhibition of either stress fiber formation with the Rho kinase inhibitor Y-27632 (10 microm) or actin polymerization with latrunculin B (0.5 microm) significantly decreased the activity of SM22 and SM alpha-actin promoters. In contrast, increasing actin polymerization with jasplakinolide (0.5 microm) increased SM22 and SM alpha-actin promoter activity by 22-fold and 13-fold, respectively. The above interventions had little or no effect on the transcription of an SRF-dependent c-fos promoter or on a minimal thymidine kinase promoter that is not SRF-dependent. Taken together, the results of these studies indicate that in SMC, RhoA-dependent regulation of the actin cytoskeleton selectively regulates SMC differentiation marker gene expression by modulating SRF-dependent transcription. The results also suggest that RhoA signaling may serve as a convergence point for the multiple signaling pathways that regulate SMC differentiation.
Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice # (2008)

These findings establish a crucial role of hepatic ACL in lipid and glucose metabolism; therefore, hepatic ACL may serve as a potential target to treat NAFLD and type 2 diabetes.
Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants (1999)

Self-renewing, totipotent embryonic stem (ES) cells may provide a virtually unlimited donor source for transplantation. A protocol that permits the in vitro generation of precursors for oligodendrocytes and astrocytes from ES cells was devised. Transplantation in a rat model of a human myelin disease shows that these ES cell-derived precursors interact with host neurons and efficiently myelinate axons in brain and spinal cord. Thus, ES cells can serve as a valuable source of cell type-specific somatic precursors for neural transplantation.
Gene Transfer to Intact Mesenteric Arteries by Electroporation (2000)

The purpose of the present study was to develop a rapid, reproducible method of nonviral gene transfer to the intact vasculature. Male Sprague-Dawley rats were anesthetized, a midline abdominal incision was made and segmental branches of the superior mesenteric artery were dissected free of surrounding mesentery. A specially designed electroporation probe was placed around the neurovascular bundle and the electroporation chamber filled with a solution containing the firefly luciferase expressing plasmid (pCMV-Lux-DTS) or the green fluorescent protein expressing plasmid (pEGFP-N1). Vessels were electroporated with eight 10-ms pulses of 200 V/cm. Sixty seconds after electroporation, the DNA solution was removed, the intestine returned to the abdomen and the abdominal wall closed with suture and metal wound clips. Six hours to 5 days later, rats were sacrificed and electroporated vessels were recovered. Luciferase activity of the blood vessels was monitored. Gene expression was detected as early as 6 h postelectroporation, peaked at 1-3 days with levels up to 1 ng of reporter gene product per vessel segment and returned towards baseline by day 5. Histological analysis of blood vessel segments revealed green fluorescent protein-positive cells throughout the thickness of the vessel wall (endothelial cells to adventitia). Responses of electroporated vessels to vasoconstricting stimuli were indistinguishable from those of control vessels at either 2 or 40 days posttreatment. The results of this study provide evidence that electroporation is an effective means for introducing naked DNA into the blood vessel wall and form the basis for future studies on targeted gene therapy to the intact vasculature.
Peripheral Blood Progenitor Cell Transplantation: A Replacement for Marrow Auto‐ or Allografts (1996)

Circulating hematopoietic progenitor cells include pluripotent stem cells expressing indefinite self-renewal capacity and, therefore, can be used for restoring hematopoiesis following myeloablative treatment. A transient shifting of progenitor cells from extravascular sites into the circulation by chemopriming and/or cytokine treatment enables the collection by apheresis of a sufficient number of progenitor cells to guarantee engraftment. The addition of new cytokines (e.g., thrombopoietin) and large volume apheresis will increase peripheral blood progenitor cell (PBPC) procurement efficiency, whereas the risk of concurrently mobilizing clonogenic tumor cells in patients with solid tumors and hematologic malignancies remains to be carefully evaluated. As compared with bone marrow (BM) progenitor cells, the use of PBPCs significantly shortens the recovery of WBC and platelets following transplantation. Most recently, successful allogeneic transplantation of PBPCs has been reported without increasing the incidence and severity of acute graft-versus-host-disease. Due to the more than one log higher number of lymphoid subsets contained in a PBPC allograft, one might expect a more pronounced graft-versus-leukemia effect in the transplant patient. Similar to BM cells, ex vivo manipulation of mobilized apheresis products is used or being developed (ultralight density percoll gradient, CD8 depletion, selection of graft facilitating cells, CD34 + cell purification and others). The transduction and long-term expression of marker genes and, most recently, therapeutic genes (e.g., MDR-1) in PBPCs have been successfully demonstrated by several groups in patients with hematologic malignancies and selected solid tumors. It is expected that, based on the easier procurement of hematopoietic stem cells and advantageous engraftment characteristics, PBPCs in both autologous and allogeneic transplant situations will eventually replace BM-derived progenitor cells.
Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease (2009)

Recent evidence suggests that some brain areas act as hubs interconnecting distinct, functionally specialized systems. These nexuses are intriguing because of their potential role in integration and also because they may augment metabolic cascades relevant to brain disease. To identify regions of high connectivity in the human cerebral cortex, we applied a computationally efficient approach to map the degree of intrinsic functional connectivity across the brain. Analysis of two separate functional magnetic resonance imaging datasets (each n = 24) demonstrated hubs throughout heteromodal areas of association cortex. Prominent hubs were located within posterior cingulate, lateral temporal, lateral parietal, and medial/lateral prefrontal cortices. Network analysis revealed that many, but not all, hubs were located within regions previously implicated as components of the default network. A third dataset (n = 12) demonstrated that the locations of hubs were present across passive and active task states, suggesting that they reflect a stable property of cortical network architecture. To obtain an accurate reference map, data were combined across 127 participants to yield a consensus estimate of cortical hubs. Using this consensus estimate, we explored whether the topography of hubs could explain the pattern of vulnerability in Alzheimer's disease (AD) because some models suggest that regions of high activity and metabolism accelerate pathology. Positron emission tomography amyloid imaging in AD (n = 10) compared with older controls (n = 29) showed high amyloid-beta deposition in the locations of cortical hubs consistent with the possibility that hubs, while acting as critical way stations for information processing, may also augment the underlying pathological cascade in AD.
Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis (2002)

These findings confirm that mutations in the NALP3/CIAS1/PYPAF1 gene are associated with FCU and MWS, and that disease severity and clinical features may differ substantially within and between families. Analysis of this gene will improve classification of patients with inherited or apparently sporadic periodic fever syndromes.
Differential effects of stress on the immune response to influenza A/PR8 virus infection in mice (2004)

The immune system can be viewed as a diffuse sensory organ that is responsible for detecting and eliminating infiltrating pathogens.However, the immune system must strike a balance between limiting microbial replication and immune-induced pathology.The immune system has various regulatory mechanisms that can do this; one such immunoregulatory pathway is the bidirectional communication among the nervous, endocrine and immune system.Extrinsic factors, e.g.infection, and intrinsic factors, e.g.psychogenic stress, can activate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS).Activation of these systems by either stress or infection leads to the secretion of glucocorticoids (GCs), catecholamines and opioids.Chronic elevation of GCs by restraint (RST) stress modulated the immune response to an experimental influenza A/PR8 viral infection.As demonstrated by experiments contained herein, RST altered cytokine gene expression, suppressed NK cell activity, and attenuated lymphocyte trafficking.Finally, RST enhanced viral replication (probably as a consequence of the RST mediated immunomodulation).Thus, alteration of normal immunoregulatory mechanisms by RST modulated the inflammatory, innate and adaptive response to an influenza A/PR8 viral infection.
New treatment for acute myelogenous leukemia (2014)

Advances in the scientific knowledge of the various genetic and epigenetic alterations in AML, in conjunction with more effective, rationally designed and/or novel targeted therapeutics, offers a real hope and expectation of improved AML outcomes in the future.
Modifying Lipophilicities of Zn(II) Coordination Species by Introduction of Ancillary Ligands: A Supramolecular Chemistry Approach (2010)

A homologous series of neutral Zn(II) coordination complexes including Zn(PNO)2 (1), Zn(PNO)2(3-Br-Py) (2), [Zn(PNO)2(1,10-phenanthroline)](H2O)5/3 (3), and Zn(PNO)2(2,2′-Bipy) (4), where PNO = deprotonated 2-hydroxypyridine N-oxide, have been synthesized and characterized. Complexes 2−4 were prepared by reacting ancillary ligands with complex 1. Ancillary ligands form coordinate bonds to transition metal center-Zn(II). Their solid-state crystal structures, solubilities, lipophilicities, and association−dissociation properties in aqueous phase have been investigated in the current work. Diffusion-ordered NMR data suggested that association−dissociation properties of mixed-ligand Zn(II) coordination complexes in the aqueous phase are greatly dependent upon the coordination mode of ancillary ligands to Zn(II). By introduction of ancillary ligands, we can rationally modify lipophilicities and solubilities of mixed-ligand Zn(II) coordination complexes on the basis of log P of the ancillary ligand. These in vitro data highlighted the approach of forming mixed-ligand coordination species in fine-tuning physical-chemical properties of Zn(II) species for medicinal applications.