gebhart/patrepeval huggingface dataset:
Adenovirus E1A makes two distinct contacts with the retinoblastoma protein (1992)

Two regions near the amino terminus of the adenovirus E1A protein, which were first identified by sequence conservation among various adenovirus serotypes, have been shown by genetic studies to be essential for E1A-mediated transformation. These same regions are also required for interaction with a number of cellular proteins, including the retinoblastoma protein (pRB). Using synthetic peptides corresponding to portions of these conserved regions, we show that each region can bind independently to pRB. These interactions were observed in both competition and binding assays. In both types of assay, region 2 peptides (E1A amino acids 115 to 132) bound pRB with higher affinity than did region 1 peptides (E1A amino acids 37 to 54), while a peptide combining region 1 and 2 sequences consistently provided the highest-affinity interaction. Cross-blocking experiments using region 1 peptides and region 2 peptides suggested that these two regions of E1A make distinct contacts with pRB. These data support the notion that the pRB-binding domain of E1A contains at least two functional elements.
Scene Graph Generation by Iterative Message Passing (2017)

Understanding a visual scene goes beyond recognizing individual objects in isolation. Relationships between objects also constitute rich semantic information about the scene. In this work, we explicitly model the objects and their relationships using scene graphs, a visually-grounded graphical structure of an image. We propose a novel end-to-end model that generates such structured scene representation from an input image. Our key insight is that the graph generation problem can be formulated as message passing between the primal node graph and its dual edge graph. Our joint inference model can take advantage of contextual cues to make better predictions on objects and their relationships. The experiments show that our model significantly outperforms previous methods on the Visual Genome dataset as well as support relation inference in NYU Depth V2 dataset.
The Glucose-Regulated Proteins (GRP78 and GRP94): Functions, Gene Regulation, and Applications (1994)

The knowledge of GRPs as molecular chaperones is rapidly evolving. It is anticipated that the GRPs will make special contributions in the areas of basic cell biology, biotechnology, and cancer biology. In particular, they may play a role as the prototype of a class of genes that are regulated by signal transduction pathways originating in the ER and traveling to the nucleus. GRP78 and GRP94 function as molecular chaperones and can bind to malfolded proteins and unassembled complexes. They are induced in response to stress, but once the stress is removed the GRPs are posttranscriptionally modified into biologically inactive forms. The promoters of the grp genes are highly conserved, with several CCAAT-like motifs and GC-rich regions. The high level of redundancy that exists in the mammalian grp promoters may act to ensure that the expression of the genes, both of which are single copy, is unlikely to be significantly lowered in the event of mutation. These genes are thought to be controlled by several transcription factors whose complex interactions with the grp promoters allow variable patterns of grp induction. The promoters of the grp genes constitutively express their gene products, and their promoter activities can be further enhanced in cellular environments of low glucose or oxygen. The grp78 promoter is known to retain its strong activity in differentiated and undifferentiated tissues. These features make it an attractive alternative to viral promoters for use in gene therapy. Gene therapy may also be useful in treating cancer in some cases, especially solid tumors. In these instances, GRP levels are already likely to be quite high. These high levels of GRPs may inhibit the efficacy of several anti-cancer treatments. Suppression of GRP induction, perhaps by anti-sense or ribozyme technology, may prove to be useful in conjunction with anti-cancer drugs to treat tumors.
Biofilms in device-related infections (1995)

The use of various medical devices including indwelling vascular catheters, cardiac pacemakers, prosthetic heart valves, chronic ambulatory peritoneal dialysis catheters and prosthetic joints has greatly facilitated the management of serious medical and surgical illness. However, the successful development of synthetic materials and introduction of these artificial devices into various body systems has been accompanied by the ability of microorganism to adhere to these devices in the environment of biofilms that protect them from the activity of antimicrobial agents and from host defense mechanisms. A number of host, biomaterial and microbial factors are unique to the initiation, persistence and treatment failures of device-related infections. Intravascular catheters are the most common devices used in clinical practice and interactions associated with these devices are the leading cause of nosocomial bacteremias. The infections associated with these devices include insertion site infection, septic thrombophlebitis, septicemia, endocarditis and metastatic abscesses. Other important device-related infections include infections of vascular prostheses, intracardiac prostheses, total artificial hearts, indwelling urinary catheters, orthopedic prostheses, endotracheal tubes and extended wear lenses. The diagnosis and management of biofilm-associated infections remain difficult but critical issues. Appropriate antimicrobial therapy is often not effective in eradicating these infections and the removal of the device becomes necessary. Several improved diagnostic and therapeutic modalities have been reported in recent experimental studies. The clinical usefulness of these strategies remains to be determined.
Electrical regulation of Schwann cells using conductive polypyrrole/chitosan polymers (2009)

Electrical stimulation (ES) can dramatically enhance neurite outgrowth through conductive polymers and accelerate peripheral nerve regeneration in animal models of nerve injury. Therefore, conductive tissue engineering graft in combination with ES is a potential treatment for neural injuries. Conductive tissue engineering graft can be obtained by seeding Schwann cells on conductive scaffold. However, when ES is applied through the conductive scaffold, the impact of ES on Schwann cells has never been investigated. In this study, a biodegradable conductive composite made of conductive polypyrrole (PPy, 2.5%) and biodegradable chitosan (97.5%) was prepared in order to electrically stimulate Schwann cells. The tolerance of Schwann cells to ES was examined by a cell apoptosis assay. The growth of the cells was characterized using DAPI staining and a MTT assay. mRNA and protein levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in Schwann cells were assayed by RT-PCR and Western blotting, and the amount of NGF and BDNF secreted was determined by an ELISA assay. The results showed that the PPy/chitosan membranes supported cell adhesion, spreading, and proliferation with or without ES. Interestingly, ES applied through the PPy/chitosan composite dramatically enhanced the expression and secretion of NGF and BDNF when compared with control cells without ES. These findings highlight for the first time the possibility of enhancing nerve regeneration in conductive scaffolds through ES-increased neurotrophin secretion.
Retroviral Expression in Embryonic Stem Cells and Hematopoietic Stem Cells (2000)

Achieving long-term retroviral expression in primary cells has been problematic. De novo DNA methylation of infecting proviruses has been proposed as a major cause of this transcriptional repression. Here we report the development of a mouse stem cell virus (MSCV) long terminal repeat-based retroviral vector that is expressed in both embryonic stem (ES) cells and hematopoietic stem (HS) cells. Infected HS cells and their differentiated descendants maintained long-term and stable retroviral expression after serial adoptive transfers. In addition, retrovirally infected ES cells showed detectable expression level of the green fluorescent protein (GFP). Moreover, GFP expression of integrated proviruses was maintained after in vitro differentiation of infected ES cells. Long-term passage of infected ES cells resulted in methylation-mediated silencing, while short-term expression was methylation independent. Tissues of transgenic animals, which we derived from ES cells carrying the MSCV-based provirus, did not express GFP. However, treatment with the demethylating agent 5-azadeoxycytidine reactivated the silent provirus, demonstrating that DNA methylation is involved in the maintenance of retroviral repression. Our results indicate that retroviral expression in ES cells is repressed by methylation-dependent as well as methylation-independent mechanisms.
The Use of Resin Coated Glass Beads in the Form of a Packed Bed for the Solid Phase Synthesis of Peptides (1971)

Resin coated glass beads can be used for the solid phase synthesis of peptides. Coated glass beads, as supplied by Northgate Laboratories* for the solid phase synthesis of peptides readily form a packed bed with a low impedance to liquid flow. For the solvents and reagents, used in Peptide synthesis, the resistance to mass transfer through the resin film on the beads is small and one to two orders less than the Merrifield resin beads. The ultimate rate of synthesis is shown to be controlled by reaction velocities and not the rates of reagent transfer. The attachment of the first amino acid to the resin can be achieved by the same procedure as that used with Merrifield beads. Peptides can be cleaved from the resin by passing hydrogen bromide gas saturated with trifluoroacetic acid vapor through the dry bed of beads. For the highest purity and maximum yield the beads should carry 0.4 to 0.7% w/w of 0.5% cross-linked polystyrene resin and the chlorine content should be about 25% of the resin. Under optimum conditions the addition of one amino acid to a peptide being synthesized can be achieved in 25 minutes compared with the 4½ hours required for Merrifield beads. The tetrapeptides produced using the beads had an average purity of 96 to 97% which also compares well with the purity of the same product made from the Merrifield beads. Under optimum conditions the Northgate beads can produce the tetrapeptide L-leucyl-L-alanyl-glycyl-L-valine (leu-ala-gly-val) at a rate of 170 micrograms per minute per unit volume of substrate.
Dual energy computed tomography for explosive detection (2006)

Single energy computed tomography (CT) scanners use measurements of densities to detect explosives in luggage. It is desirable to apply dual energy techniques to these CT scanners to obtain atomic number measurements to reduce false alarm rates. However, the direct application of existing dual energy techniques has practical problems, such as, approximation errors and lack of boundary constraints in dual energy decomposition, image artifacts, and x-ray spectral drifts. In this paper, we present methods to reduce these problems. The methods include constrained dual energy decomposition, adaptive scatter correction, nonlinear filtering of decomposed projections, and real-time image-based correction for x-ray spectral drifts. We demonstrate the effectiveness of the methods using simulated data and real data obtained from a commercial dual energy CT scanner.
Tk, a new colon tumor-associated antigen resulting from altered O-glycosylation. (2000)

Erythrocyte polyagglutination antigens T and Tn are truncated O-glycan chains that are also carcinoma-associated antigens. We investigated whether Tk polyagglutination antigen could similarly be a carcinoma-associated marker and a target of immunotherapy. Monoclonal antibody LM389 was raised against Tk erythrocytes and tested by immunohistochemistry. LM389 strongly reacted with 48% human colorectal carcinomas. Labeling of normal tissues was visible on epithelial cells, mainly digestive, but was confined at a supranuclear level. Expression of the antigen on cloned human carcinoma cells correlated with sialosyl-Tn expression. O-Sialoglycoprotein endopeptidase treatment revealed that on carcinomas and cell lines, the epitope was present on O-glycans. Antibody specificity was determined using synthetic carbohydrates. Direct binding and inhibition studies indicated that LM389 best ligands were terminated by two branched N-acetylglucosamine units. Screening of murine cellular cell lines with LM389 allowed development of an experimental model with Tk-positive and -negative cells in syngeneic BDIX rats. Vaccination of rats with Tk erythrocytes provided a protection against growth of rat Tk-positive, but not of Tk-negative, tumor cells in association with the development of antibodies. Taken together, the results indicate that Tk polyagglutination antigen is a new colorectal carcinoma-associated antigen, absent from the normal cell surface, resulting from alteration of O-glycans biosynthesis and with potential as a target of immunotherapy.
Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events (2006)

Circulating matrix markers have emerged as candidate biomarkers for predicting risk of subsequent atherosclerotic events. Future large longitudinal observational and intervention studies will determine the role of matrix biomarkers in diagnosis and prognostication, and as targets for intervention in cardiovascular diseases.
Cytokine regulation of immune tolerance (2014)

The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune tolerance, followed by discussing other cytokines that maintain immune tolerance through inducing CD4(+)Foxp3(+) regulatory T cells (Tregs), which negatively control immune cells. Interleukin (IL)-2 is the most potent cytokine in promoting the development and survival of Tregs, thereby mediating immune tolerance. IL-35 is mainly produced by Tregs, but its biology function remains to be defined. Finally, we discuss the actions of proinflammatory cytokines that breach immune tolerance and induce autoimmunity, which include IL-7, IL-12, IL-21, and IL-23. Recent genetic studies have revealed the role of these cytokines (or their cognate receptors) in susceptibility to autoimmune diseases. Taken together, we highlight in this review the cytokine regulation of immune tolerance, which will help in further understanding of human diseases that are caused by dysregulated immune system.
Insulin-Like Growth Factor I: A Possible Metabolic Signal Involved in the Regulation of Female Puberty (1991)

In both rats and primates, including humans, serum levels of insulin-like growth factor I (IGF-I) increase during the onset of puberty, suggesting a role for IGF-I in this process. We examined the ability of IGF-I to affect the release of hypothalamic luteinizing hormone releasing hormone (LHRH) in prepubertal female rats. Our results indicate that IGF-I acts on the median eminence, which contains the highest density of type 1 IGF receptors in the brain, to elicit a dose-related increase in LHRH release. In this regard, a minimal effective dose of 10 ng/ml (p less than 0.05) and a maximal effective dose of 100 ng/ml (p less than 0.01) was observed. IGF-II and insulin were one order of magnitude less effective. The results demonstrate that IGF-I has the capability to act directly upon the median eminence to effect release of LHRH, thereby suggesting a role for IGF-I in facilitating peripubertal changes in LHRH release. Thus, IGF-I may represent one of the 'metabolic signals' thought to be involved in the initiation of puberty.
Reversible Addition Fragmentation Chain Transfer Polymerization of 4-Vinylbenzaldehyde (2007)

The direct reversible addition fragmentation chain transfer (RAFT) polymerization of 4-vinylbenzaldehyde (VBA) was established as a new synthetic method for the preparation of well-defined poly(vinylbenzaldehyde) (PVBA), a polymer having reactive aldehyde side chain substiuents. RAFT polymerization of VBA was investigated using S-1-dodecyl-S'-(α,α'-dimethyl-α"-acetic acid)trithiocarbonate (DDMAT) as chain transfer agent (CTA) and 2,2'-azobis(isobutyronitrile) (AIBN) as initiator in 1,4-dioxane or 2-butanone at 70-75 °C for 7.5-22.5 h. With 45-76% of monomer conversion, the resulting PVBA had well controlled number-average molecular weight (M(n)) and low polydispersity (PDI < 1.17). The living characteristic of the RAFT polymerization process was confirmed by the linearity between the M(n) values of PVBA and monomer conversions. Well-defined PVBA was further used as a macromolecular chain transfer agent (macro-CTA) in RAFT polymerization of styrene (St), and a block copolymer PVBA-b-PSt with relatively low polydispersity (PDI = 1.20) was successfully synthesized.
Retargeting of Adenovirus Vectors through Genetic Fusion of a Single-Chain or Single-Domain Antibody to Capsid Protein IX (2010)

Adenovirus (Ad) vectors are the most commonly used system for gene therapy applications, due in part to their ability to infect a wide array of cell types and tissues. However, many therapies would benefit from the ability to target the Ad vector only to specific cells, such as tumor cells for cancer gene therapy. In this study, we investigated the utility of capsid protein IX (pIX) as a platform for the presentation of single-chain variable-fragment antibodies (scFv) and single-domain antibodies (sdAb) for virus retargeting. We show that scFv can be displayed on the capsid through genetic fusion to native pIX but that these molecules fail to retarget the virus, due to improper folding of the scFv. Redirecting expression of the fusion protein to the endoplasmic reticulum (ER) results in correct folding of the scFv and allows it to recognize its epitope; however, ER-targeted pIX-scFv was incorporated into the Ad capsid at a very low level which was not sufficient to retarget virus infection. In contrast, a pIX-sdAb construct was efficiently incorporated into the Ad capsid and enhanced virus infection of cells expressing the targeted receptor. Taken together, our data indicate that pIX is an effective platform for presentation of large targeting polypeptides on the surface of the virus capsid, but the nature of the ligand can significantly affect its association with virions.
Evidence of flexibility in the nanoporous iron(iii) carboxylate MIL-89 (2008)

The very large expansion upon adsorption of liquids, up to 160% in cell volume, has been observed in the iron(iii) trans,trans muconate MIL-89 [(MIL = Material Institut Lavoisier]. The structure of lutidine-containing MIL-89 (lutidine = 2,6-dimethylpyridine) has been determined using X-ray powder diffraction and computer simulations. Finally, the consequences of adsorption of various polar and apolar liquids have been evaluated using ex situ synchrotron X-ray powder diffraction data and reveals that the swelling behavior of MIL-89 is selective but slightly different from the MIL-88 analogues.
Ruthenium-Catalyzed Hydroxylation of Unactivated Tertiary C−H Bonds (2010)

The combination of catalytic RuCl(3) and pyridine with KBrO(3) as the stoichiometric oxidant is shown to efficiently promote the hydroxylation of unactivated tertiary C-H bonds. Substrates possessing different polar functional groups--ester, epoxide, sulfone, oxazolidinone, carbamate, and sulfamate--are found to engage in this reaction to give alcohol products in yields generally exceeding 50%. As judged based on efficiency, ease of operation, substrate scope, and selectivity toward tertiary C-H centers, the method appears competitive with other C-H hydroxylation processes.
<title>Step-and-scan and step-and-repeat: a technology comparison</title> (1996)

While the semiconductor manufacturing community is preparing for the transition from 0.35micrometers to 0.25micrometers technology, lithography equipment suppliers are preparing for the shift from step-and-repeat to step-and-scan systems. In addition, most wafer stepper users are planning to change from i-line to KrF laser wavelength technology. The question, however, is what are the advantages and disadvantages of scanners over steppers in a production environment. In this paper, we discuss the two different technologies using the following criteria: (1) throughput/cost of ownership, (2) CD control/depth of focus, (3) distortion and overlay. 248 nm lithography will be used for the 0.25micrometers process rule regime in combination with i-line systems being used for 50 to 70 percent of the lithography steps to reduce cost. Therefore, an ideal match is required between i-line systems and their DUV critical layer counterparts. For this reason, the economic equation of step-and-scan is determined by the total picture of matched DUV and i-line scanners. However, the comparisons between non-laser-based scanners and steppers and laser-based scanners and steppers are different. This paper discusses this subject using a combination of theoretical modeling and measured data. Imaging data from a new, DUV, double telecentric, 0.4 to 0.57 variable NA wafer stepper equipped with a variable coherence/annular illuminator is shown; thus proving that good imaging data at 0.25micrometers resolution at moderate cost is possible using wafer steppers.
Visualization of Epidermal Growth Factor (EGF) Receptor Aggregation in Plasma Membranes by Fluorescence Resonance Energy Transfer (1989)

Fluorescence resonance energy transfer between epidermal growth factor (EGF) molecules, labeled with fluorescent reporter groups, was used as a monitor for EGF receptor-receptor interactions in plasma membranes isolated from human epidermoid A431 cells. Epidermal growth factor molecules labeled at the amino terminus with fluorescein isothiocyanate served as donor molecules in these energy transfer measurements, while EGF molecules labeled with eosin isothiocyanate at the amino terminus served as the energy acceptors. Both of these derivatives were shown to be active in binding to membrane receptors and in the activation of the endogenous receptor/tyrosine kinase activity. We found that membranes in the absence of added metal ion activators showed relatively little energy transfer (approximately 10% donor quenching) between the labeled growth factors. However, divalent metal ion activators of the EGF receptor/tyrosine kinase caused a significant increase in the extent of energy transfer between the labeled EGF molecules. Specifically, in the presence of 20 mM MgCl2, the extent of quenching of the donor fluorescence increased to 25% (from 10% in the absence of metal), while in the presence of 4 mM MnCl2, the extent of energy transfer was increased still further to 40-50%. The addition of an excess of EDTA resulted in the reversal of the observed energy transfer to basal levels. The increased energy transfer in the presence of these divalent cations correlated well with the ability of these metals to stimulate the EGF receptor/tyrosine kinase activity. However, the extent of receptor-receptor interactions measured by energy transfer was independent of receptor autophosphorylation. Overall, these results suggest that conditions under which the EGF receptor is primed to be active as a tyrosine kinase, within a lipid milieu, result in an increased aggregation of the receptor.