gebhart/patrepeval huggingface dataset:
Enzyme action at 3' termini of ionizing radiation-induced DNA strand breaks. (1983)

gamma-Irradiation of DNA in vitro produces two types of single strand breaks. Both types of strand breaks contain 5'-phosphate DNA termini. Some strand breaks contain 3'-phosphate termini, some contain 3'-phosphoglycolate termini (Henner, W.D., Rodriguez, L.O., Hecht, S. M., and Haseltine, W. A. (1983) J. Biol. Chem. 258, 711-713). We have studied the ability of prokaryotic enzymes of DNA metabolism to act at each of these types of gamma-ray-induced 3' termini in DNA. Neither strand breaks that terminate with 3'-phosphate nor 3'-phosphoglycolate are substrates for direct ligation by T4 DNA ligase. Neither type of gamma-ray-induced 3' terminus can be used as a primer for DNA synthesis by either Escherichia coli DNA polymerase or T4 DNA polymerase. The 3'-phosphatase activity of T4 polynucleotide kinase can convert gamma-ray-induced 3'-phosphate but not 3'-phosphoglycolate termini to 3'-hydroxyl termini that can then serve as primers for DNA polymerase. E. coli alkaline phosphatase is also unable to hydrolyze 3'-phosphoglycolate groups. The 3'-5' exonuclease actions of E. coli DNA polymerase I and T4 DNA polymerase do not degrade DNA strands that have either type of gamma-ray-induced 3' terminus. E. coli exonuclease III can hydrolyze DNA with gamma-ray-induced 3'-phosphate or 3'-phosphoglycolate termini or with DNase I-induced 3'-hydroxyl termini. The initial action of exonuclease III at 3' termini of ionizing radiation-induced DNA fragments is to remove the 3' terminal phosphate or phosphoglycolate to yield a fragment of the same nucleotide length that has a 3'-hydroxyl terminus. These results suggest that repair of ionizing radiation-induced strand breaks may proceed via the sequential action of exonuclease, DNA polymerase, and DNA ligase. The possible role of exonuclease III in repair of gamma-radiation-induced strand breaks is discussed.
Sliding interleaved KY (SLINKY) acquisition: A novel 3D MRA technique with suppressed slab boundary artifact (1998)

This work addresses the elimination of the slab boundary artifact (SBA) or venetian blind artifact in three-dimensional multiple overlapped thin slab acquisition (3D MOTSA) for magnetic resonance angiography (MRA). Our method uses a sliding-slab, interleaved kY (SLINKY) data acquisition strategy, equalizing flow-related signal intensity weighting across the entire slab dimension. This technique demodulates signal intensity changes along the slab direction and can essentially eliminate the SBA while retaining the same or better imaging time efficiency than that of conventional MOTSA, providing robustness to complicated flow patterns and thereby resulting in more accurate depiction of vascular morphology. In addition, this technique does not need specialized reconstruction and extra computation. The unique penalty of this technique is the sensitivity to phase inconsistency in the data. Both phantom and in vivo experiments verify the clinical significance of the technique. The new MRA images acquired with this imaging technique show highly reliable mapping of vascular morphology without the SBA and reduction of signal voids in complex/slow flow regions.
Minireview: Lipid Metabolism, Metabolic Diseases, and Peroxisome Proliferator-Activated Receptors (2003)

Lipid and carbohydrate homeostasis in higher organisms is under the control of an integrated system that has the capacity to rapidly respond to metabolic changes. The peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors that have been implicated to play an important role in obesity-related metabolic diseases such as hyperlipidemia, insulin resistance, and coronary artery disease. The three PPAR subtypes, alpha, gamma, and delta, have distinct expression patterns and evolved to sense components of different lipoproteins and regulate lipid homeostasis based on the need of a specific tissue. Recent advances in identifying selective ligands in conjunction with microarray analyses and gene targeting studies have helped delineate the subtype-specific functions and the therapeutic potential of these receptors. PPARalpha potentiates fatty acid catabolism in the liver and is the molecular target of the lipid-lowering fibrates (e.g. fenofibrate and gemfibrozil), whereas PPARgamma is essential for adipocyte differentiation and mediates the activity of the insulin-sensitizing thiazolidinediones (e.g. rosiglitazone and pioglitazone). Recent evidence suggests that PPARdelta may be important in controlling triglyceride levels by sensing very low-density lipoprotein. Thus, uncovering the regulatory mechanisms and transcriptional targets of the PPARs will continue to provide insight into the pathogenesis of metabolic diseases and, at the same time, offer valuable information for rational drug design.
25th Anniversary Article: Engineering Hydrogels for Biofabrication (2013)

With advances in tissue engineering, the possibility of regenerating injured tissue or failing organs has become a realistic prospect for the first time in medical history. Tissue engineering - the combination of bioactive materials with cells to generate engineered constructs that functionally replace lost and/or damaged tissue - is a major strategy to achieve this goal. One facet of tissue engineering is biofabrication, where three-dimensional tissue-like structures composed of biomaterials and cells in a single manufacturing procedure are generated. Cell-laden hydrogels are commonly used in biofabrication and are termed "bioinks". Hydrogels are particularly attractive for biofabrication as they recapitulate several features of the natural extracellular matrix and allow cell encapsulation in a highly hydrated mechanically supportive three-dimensional environment. Additionally, they allow for efficient and homogeneous cell seeding, can provide biologically-relevant chemical and physical signals, and can be formed in various shapes and biomechanical characteristics. However, despite the progress made in modifying hydrogels for enhanced bioactivation, cell survival and tissue formation, little attention has so far been paid to optimize hydrogels for the physico-chemical demands of the biofabrication process. The resulting lack of hydrogel bioinks have been identified as one major hurdle for a more rapid progress of the field. In this review we summarize and focus on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions. We aim to highlight this current lack of effectual hydrogels within biofabrication and initiate new ideas and developments in the design and tailoring of hydrogels. The successful development of a "printable" hydrogel that supports cell adhesion, migration, and differentiation will significantly advance this exciting and promising approach for tissue engineering.
A comparison of three vaccines against respiratory syncytial virus in calves (1984)

An inactivated vaccine against respiratory syncytial virus (RSV) was compared with two live vaccines. The inactivated (GC) vaccine consisted of glutaraldehyde-fixed bovine nasal mucosa cells persistently infected with RSV and emulsified with oil adjuvant. The live vaccines were a modified virus (MV) derived from a bovine strain of RSV and a temperature-sensitive mutant (ts-1) derived from a human strain. The GC vaccine was inoculated subcutaneously into 12 calves and the live vaccines intramuscularly into eight calves each. Nine unvaccinated calves acted as controls. The vaccines were administered in two doses 3 weeks apart and all calves were challenged intranasally with 2 X 10(7) p.f.u. of bovine RSV 3 weeks after the second dose. At the time of challenge calves given GC, MV and ts-1 vaccines had mean serum neutralizing antibody titres of 25, 19 and 2 respectively; mean titres of IgG1 antibody by radioimmunoassay were log10 4.5, 1.3 and 2.6 respectively and mean zone areas by single radial haemolysis (SRH) were 107, 27 and 36 mm2 respectively. Eleven of 12 calves given GC vaccine were completely protected against challenge but all control animals and those given the two live vaccines were infected. The mean peak titre of virus in nasal swabs of control calves was 3.0 log10 p.f.u./ml and the mean duration of virus shedding was 6.8 days. Both these parameters were significantly reduced in animals given MV and ts-1 vaccines: mean peak titres were 2.1 and 2.4 log10 p.f.u./ml and mean duration of shedding was 3.4 and 3.3 days respectively. Thus, protection correlated better with RSV antibody detected by radioimmunoassay and SRH than with neutralizing antibody. These results are discussed in relation to the possible mechanism by which protection was mediated.
Development of Cancer Chemopreventive Agents: Oltipraz as a Paradigm (1999)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTDevelopment of Cancer Chemopreventive Agents: Oltipraz as a ParadigmThomas W. Kensler, John D. Groopman, Thomas R. Sutter, Thomas J. Curphey, and Bill D. RoebuckView Author Information Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, and Department of Pathology and Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755 Cite this: Chem. Res. Toxicol. 1999, 12, 2, 113–126Publication Date (Web):January 20, 1999Publication History Received7 August 1998Published online20 January 1999Published inissue 1 February 1999https://pubs.acs.org/doi/10.1021/tx980185bhttps://doi.org/10.1021/tx980185breview-articleACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views457Altmetric-Citations125LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Adducts,Peptides and proteins,Rodent models,Toxicology,Toxins Get e-Alerts
Near-minimum time open-loop slewing of flexible vehicles (1989)

Minimum time, open-loop, optimal controls are calculated for single-axis maneuvers of a flexible structure. By shaping the control profiles with two independent parameters, a wide variety of control histories can be pro- duced. Based on the dynamics of the model, with a normalized time scale, the resulting Pontryagin's necessary conditions yield a nonlinear fixed final time, fixed final state, two-point boundary value problem with the maneuver time as a control parameter. Upon generating numerical solutions to the problem, the final maneuver time and residual flexural energy are compared to the bang-bang solution as a measure of the success of a given maneuver. Examples presented illustrate near-minimum time maneuvers with control of flexible modes in addi- tion to the rigid body modes, as well as the qualitative and quantitative effect of the torque shaping parameters. EAR-MINIMUM time attitude control of flexible spacecraft with active vibration suppression is a topic of current research. Although minimum time/fuel maneuvers have been previously examined,1 such bang-bang controls cause spillover effects that may induce high residual flexural energy. The source of the energy spillover into the flexural modes is the instantaneous switching that results from the bang-bang controls, a potential problem for the control hard- ware (reaction wheels, control moment gyros, etc.) as well. Consequently, minimum-time optimal control problems are often of academic interest only for producing theoretical lower bounds for the maneuver time. We have also found that near bang-bang controls are usually very sensitive to model er- rors; therefore, control shaping is an important issue in ob- taining robust controls. Upon modifying the control profile with a smoothing func- tion and transforming the independent variable (time), a near- minimum-time problem is generated with the mathematical form of a fixed-time nonlinear optimal control problem. The resulting boundary-value problem yields to a number of established methods of numerical solution. The controls are attenuated in such a way that the magnitude of the control rises smoothly from zero to the bounded maximum at the in- itiation of the maneuver and typically has an identically shaped reduction to zero at the final time. In addition, any in- stantaneous switch during the maneuver is shaped using a smooth, continuous function. The sharpness of the control trajectory is determined by a set of arbitrary parameters such that we can produce profiles with low control rates as well as controls that approach, to any desired degree, the bang-bang minimum time solution. The independent variable is transformed such that a linear free-final-time optimal control problem is converted to a nonlinear fixed-time problem, where the maneuver time is contained explicitly as a parameter in the transformed system. This augmented fixed-time problem can then be solved numerically for the controls and the corresponding minimum time required to complete the maneuver.
Maintaining a Reputation Against a Long-Lived Opponent (1996)

4 Celentani (1996) uses multiple types of short-run players to get around the problem of unobservable off-path behavior of the long-run player in repeated games with observable actions.His approach can be extended to short run players who live for more than one periodo
What Is Value-Based Management? (1994)

An excerpt from Valuation: Measuring and Managing the Value of Companies, Second Edition RECENT YEARS HAVE SEEN a plethora of new management approaches for improving organizational performance: total quality management, fiat organizations, empowerment, continuous improvement, reengineering, kaizen, team building, and so on. Many have succeeded -- but quite a few have failed. Often the cause of failure was performance targets that were unclear or not properly aligned with the ultimate goal of creating value. Value-based management (VBM) tackles this problem head on. It provides a precise and unambiguous metric -- value -- upon which an entire organization can be built. The thinking behind VBM is simple. The value of a company is determined by its discounted future cash flows. Value is created only when companies invest capital at returns that exceed the cost of that capital. VBM extends these concepts by focusing on how companies use them to make both major strategic and everyday operating decisions. Properly executed, it is an approach to management that aligns a company's overall aspirations, analytical techniques, and management processes to focus management decision making on the key drivers of value. Principles VBM is very different from 1960s-style planning systems. It is not a staff-driven exercise. It focuses on better decision making at all levels in an organization. It recognizes that top-down command-and-control structures cannot work well, especially in large multibusiness corporations. Instead, it calls on managers to use value-based performance metrics for making better decisions. It entails managing the balance sheet as well as the income statement, and balancing long- and short-term perspectives. When VBM is implemented well, it brings tremendous benefit. It is like restructuring to achieve maximum value on a continuing basis. It works. It has high impact, often realized in improved economic performance, as illustrated in Exhibit 1. Examples of VBM's impact Business Change in behavior Impact Retail Shifted from broad national 30-40% increase in household growth program to focus on potential value goods building regional scale first Insurance Repositioned product 25% increase in portfolio to emphasize potential value products most likely to create value Oil Used new planning and Multimillion dollar production control process to help drive reduction in planning major change program function through streamlining Prompted an acquisition Exposed nonperforming managers Banking Chose growth versus harvest 124% potential value strategy, even though increase five-year return on equity very similar Telecoms Generated ideas for value creation * New service 240% potential value increase in one unit * Premium pricing 246% potential value increase in one unit Around 40% of planned NA development projects in one business unit discontinued Salesforce expansion plans NA completely revised after discovering how much value they would destroy Pitfalls Yet value-based management is not without pitfalls. …
IL-33 reduces the development of atherosclerosis (2008)

Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which is a novel IL-1-like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE(-/-) mice on a high-fat diet. IL-33 and ST2 are present in the normal and atherosclerotic vasculature of mice and humans. Although control PBS-treated mice developed severe and inflamed atherosclerotic plaques in the aortic sinus, lesion development was profoundly reduced in IL-33-treated animals. IL-33 also markedly increased levels of IL-4, -5, and -13, but decreased levels of IFNgamma in serum and lymph node cells. IL-33 treatment also elevated levels of total serum IgA, IgE, and IgG(1), but decreased IgG(2a), which is consistent with a Th1-to-Th2 switch. IL-33-treated mice also produced significantly elevated antioxidized low-density lipoprotein (ox-LDL) antibodies. Conversely, mice treated with soluble ST2, a decoy receptor that neutralizes IL-33, developed significantly larger atherosclerotic plaques in the aortic sinus of the ApoE(-/-) mice compared with control IgG-treated mice. Furthermore, coadministration of an anti-IL-5 mAb with IL-33 prevented the reduction in plaque size and reduced the amount of ox-LDL antibodies induced by IL-33. In conclusion, IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5 and ox-LDL antibodies.
Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies (2016)

Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T). The switch redirects the activity of the bio-orthogonal sCAR-T cells through the selective formation of immunological synapses, in which the sCAR-T cell, switch, and target cell interact in a structurally defined and temporally controlled manner. Optimized switches specific for CD19 controlled the activity, tissue-homing, cytokine release, and phenotype of sCAR-T cells in a dose-titratable manner in a Nalm-6 xenograft rodent model of B-cell leukemia. The sCAR-T-cell dosing regimen could be tuned to provide efficacy comparable to the corresponding conventional CART-19, but with lower cytokine levels, thereby offering a method of mitigating cytokine release syndrome in clinical translation. Furthermore, we demonstrate that this methodology is readily adaptable to targeting CD20 on cancer cells using the same sCAR-T cell, suggesting that this approach may be broadly applicable to heterogeneous and resistant tumor populations, as well as other liquid and solid tumor antigens.
Stereoselective Synthesis of [l-Arg-l/d-3-(2-naphthyl)alanine]-Type (E)-Alkene Dipeptide Isosteres and Its Application to the Synthesis and Biological Evaluation of Pseudopeptide Analogues of the CXCR4 Antagonist FC131 (2004)

L,L-Type and L,D-type (E)-alkene dipeptide isosteres (EADIs) that have unnatural side chains at the alpha-position were synthesized by the combination of stereoselective aziridinyl ring-opening reactions and organozinc-copper-mediated anti-S(N)2' reactions toward a single substrate of gamma,delta-cis-gamma,delta-epimino (E)-alpha,beta-enoate. The utility of this methodology was demonstrated by the stereoselective synthesis of a set of diastereomeric EADIs of L-Arg-L/D-3-(2-naphthyl)alanine (Nal) that is contained in a small CXCR4 antagonist FC131 [cyclo(-D-Tyr-Arg-Arg-Nal-Gly-)]. Furthermore, a (Nal-Gly)-type EADI was synthesized by samarium diiodide (SmI(2))-induced reduction of a gamma-acetoxy-alpha,beta-enoate. Several FC131 analogues, in which these EADIs were inserted for reduction of their peptide character, were synthesized with analogues containing reduced amide-type dipeptide isosteres to investigate the importance of these amide bonds for anti-HIV and CXCR4-antagonistic activity.
An aminopeptidase nutritionally important to Fusobacterium nucleatum (1998)

The properties of an aminopeptidase (AP) from Fusobacterium nucleatum were studied in view of the fact that this organism, along with other Gram-negative anaerobes involved in periodontal diseases, survives in the subgingival environment by obtaining energy via the fermentation of a small number of peptide-derived amino acids. The AP was found to be cell-associated and was isolated from disrupted chemostat-grown cells. It was purified by (NH4)2SO4 fractionation, two column chromatographic steps and IEF. The enzyme was found to have a molecular mass of 54 kDa, a pI of 5.1, a pH optimum between 7.5 and 8.0 and, using Leu-Ala as substrate, it gave K(m) and Vmax values of 0.66 mM and 0.12 mumol min-1 mg-1, respectively. No complete homology was found between the N-terminal sequence of the first 20 amino acids (MDXKXYVDLKERFLRYVKFN...) and any other published sequence, but residues 8-20 gave a 62% match with residues 9-21 of an AP from Haemophilus influenzae. The enzyme was inactivated by chelating agents, bestatin, p-hydroxymercuribenzoate and some heavy metals. Cobalt ions restored EDTA-inactivated activity but did not reverse inhibition by 1,10-phenanthroline. In addition, bestatin and 1,10-phenanthroline had an inhibitory effect on the batch growth of F. nucleatum in a complex medium in which peptidase activities would be nutritionally essential. No such inhibition was observed in a chemically defined medium in which growth was not dependent upon peptidase activities. The peptidase described in this paper therefore appears to be a cobalt-activated metallo-AP which, together with other peptidases, is considered to be important in the survival of F. nucleatum in the subgingival environment of the mouth.