gebhart/patrepeval huggingface dataset:
Optimizing the Cell Efficacy of Synthetic Ribozymes (1996)

Expression of the proto-oncogene c-myb is necessary for proliferation of vascular smooth muscle cells. We have developed synthetic hammerhead ribozymes that recognize and cleave c-myb RNA, thereby inhibiting cell proliferation. Herein, we describe a method for the selection of hammerhead ribozyme cleavage sites and optimization of chemical modifications that maximize cell efficacy. In vitro assays were used to determine the relative accessibility of the ribozyme target sites for binding and cleavage. Several ribozymes thus identified showed efficacy in inhibiting smooth muscle cell proliferation relative to catalytically inactive controls. A combination of modifications including several phosphorothioate linkages at the 5'-end of the ribozyme and an extensively modified catalytic core resulted in substantially increased cell efficacy. A variety of different 2'-modifications at positions U4 and U7 that confer nuclease resistance gave comparable levels of cell efficacy. The lengths of the ribozyme binding arms were varied; optimal cell efficacy was observed with relatively short sequences (13-15 total nucleotides). These synthetic ribozymes have potential as therapeutics for hyperproliferative disorders such as restenosis and cancer. The chemical motifs that give optimal ribozyme activity in smooth muscle cell assays may be applicable to other cell types and other molecular targets.
Sequence of MyD116 cDNA: a novel myeloid differentiation primary response gene induced by IL6 (1990)

Journal Article Sequence of MyD116 cDNA: a novel myeloid differentiation primary response gene induced by IL6 Get access Kenneth A. Lord, Kenneth A. Lord Department of Biochemistry and Biophysics, University of Pennsylvania School of MedicinePhiladelphia, PA 19104, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara Hoffman-Liebermann, Barbara Hoffman-Liebermann Department of Biochemistry and Biophysics, University of Pennsylvania School of MedicinePhiladelphia, PA 19104, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan A. Liebermann Dan A. Liebermann * Department of Biochemistry and Biophysics, University of Pennsylvania School of MedicinePhiladelphia, PA 19104, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 9, 11 May 1990, Page 2823, https://doi.org/10.1093/nar/18.9.2823 Published: 01 May 1990 Article history Received: 20 February 1990 Published: 01 May 1990
Site‐Specific Labeling of Proteins and Peptides with Trans‐cyclooctene Containing Handles Capable of Tetrazine Ligation (2014)

There is a growing library of functionalized non‐natural substrates for the enzyme protein farnesyltransferase ( PFT ase). PFT ase covalently attaches these functionalized non‐natural substrates to proteins ending in the sequence CAAX , where C is a cysteine that becomes alkylated, A represents an aliphatic amino acid, and X is Ser, Met, Ala, or Gln. Reported substrates include a variety of functionalities that allow modified proteins to undergo subsequent bioconjugation reactions. To date the most common strategy used in this approach has been copper catalyzed azide‐alkyne cycloaddition (Cu AAC ). While being fast and bioorthogonal Cu AAC has limited use in live cell experiments due to copper's toxicity. 1 Here, we report the synthesis of trans ‐cyclooctene geranyl diphosphate. This substrate can be synthesized from geraniol in six steps and be enzymatically transferred to peptides and proteins that end in a CAAX sequence. Proteins and peptides site‐specially modified with trans ‐cyclooctene geranyl diphosphate were subsequently targeted for further modification via tetrazine ligation. As tetrazine ligation is bioorthogonal, fast, and is contingent on ring strain rather than the addition of a copper catalyst, this labeling strategy should prove useful for labeling proteins where the presence of copper may hinder solubility or biological reactivity.
Understanding and Controlling Reactivity of Unsaturated Oxygenates and Polyols on Metal Catalysts (2011)

The production of fuels and chemicals from biomass requires heterogeneous catalysts that facilitate selective reactions of highly functional oxygenates. Although designing catalysts for high selectivity is a universal challenge in heterogeneous catalysis research, the problem is particularly acute for highly functional molecules, which contain two or more functional groups that may react over metal surfaces. This perspective article focuses on recent efforts to develop structure–property relations on metal surfaces and catalysts for two classes of highly functional molecules: multifunctional oxygenates such as α,β-unsaturated aldehydes and furanic compounds, and polyfunctional oxygenates such as glycerol and other polyols. Recent results from comparative reaction studies over a variety of catalysts, surface science experiments, and computational investigations suggest an array of approaches for producing more selective catalysts, many relying on the addition of multiple metals or other surface modifiers. General strategies that appear to show promise in the selective reactions of unsaturated oxygenates and of polyols are discussed in detail.
<title>Method for registration of 3-D shapes</title> (1992)

This paper describes a general purpose, representation independent method for the accurate and computationally efficient registration of 3-D shapes including free-form curves and surfaces. The method handles the full six-degrees of freedom and is based on the iterative closest point (ICP) algorithm, which requires only a procedure to find the closest point on a geometric entity to a given point. The ICP algorithm always converges monotonically to the nearest local minimum of a mean-square distance metric, and experience shows that the rate of convergence is rapid during the first few iterations. Therefore, given an adequate set of initial rotations and translations for a particular class of objects with a certain level of 'shape complexity', one can globally minimize the mean-square distance metric over all six degrees of freedom by testing each initial registration. For examples, a given 'model' shape and a sensed 'data' shape that represents a major portion of the model shape can be registered in minutes by testing one initial translation and a relatively small set of rotations to allow for the given level of model complexity. One important application of this method is to register sensed data from unfixtured rigid objects with an ideal geometric model prior to shape inspection. The described method is also useful for deciding fundamental issues such as the congruence (shape equivalence) of different geometric representations as well as for estimating the motion between point sets where the correspondences are not known. Experimental results show the capabilities of the registration algorithm on point sets, curves, and surfaces.
[Identification of tumor-associated proteins in laryngeal squamous cell carcinoma by proteomics]. (2007)

Thirteen proteins which are associated with the tumorigenesis of the laryngeal squamous cell carcinoma were characterized. These extensive protein variations indicate that multiple protein molecules should be simultaneously targeted as an effective strategy to counter the disease. It is better for understanding of the oncogenesis and pathogenesis in a global way, which in turn is a basis-for the rational designs of diagnostic and therapeutic methods.
Genotypic variation in water-soluble carbohydrate accumulation in wheat (2006)

The water-soluble carbohydrate (WSC) that accumulates in the stems of wheat during growth can be an important contributor to grain filling, particularly under conditions when assimilation is limited, such as during end-of-season drought. WSC concentration was measured at anthesis across a diverse set of wheat genotypes over multiple environments. Environmental differences in WSC concentration were large (means for the set ranging between 108 and 203 mg g<sup>-1</sup> dry weight), and there were significant and repeatable differences in WSC accumulation among genotypes (means ranging from 112 to 213 mg g<sup>-1</sup> dry weight averaged across environments), associated with large broad-sense heritability (H = 0.90 ± 0.12). These results suggest that breeding for high WSC should be possible in wheat. The composition of the WSC, examined in selected genotypes, indicated that the variation in total WSC was attributed mainly to variation in the fructan component, with the other major soluble carbohydrates, sucrose and hexose, varying less. The degree of polymerisation (DP) of fructo-oligosaccharides was up to ~13 in samples where higher levels of WSC were accumulated, owing either to genotype or environment, but the higher DP components (DP > 6) were decreased in samples of lower total WSC. The results are consistent with fructan biosynthesis occurring via a sequential mechanism that is dependent on the availability of sucrose, and differences in WSC contents of genotypes are unlikely to be due to major mechanistic differences.
LATEST DEVELOPMENTS IN PROTON THERAPY (2000)

The intent of this review is to give insight in the present status and on the prospective future of proton therapy. The major point of reference is conventional therapy with photons. Traditional radiotherapy is showing nowadays a very rapid progress using advanced dynamic beam delivery techniques and sophisticated computer algorithms for treatment planning. The new fashionable concepts in medical physics are &amp;quot;Inverse planning &amp;quot; and &amp;quot;Intensity modulated therapy&amp;quot;. Proton therapy compared to photon therapy has the advantage of the localisation of dose in depth, but implies higher costs for the accelerator and beam lines. Within the field of proton therapy the competition is between the established traditional beam delivery techniques using passive scattering and the new methods based on magnetic beam scanning. The innovative developments are compact gantries dedicated to beam scanning capable of delivering &amp;quot;intensity modulated proton therapy&amp;quot;. Despite many uncertainties, proton therapy is steadily gaining in socio-economical importance. About 10 hospital-based proton or heavy ion therapy facilities are now under construction or already available in the U.S.A. and Japan. Europe is waiting. 1
Effects of flow and diffusion on chemotaxis studies in a microfabricated gradient generator (2005)

An understanding of chemotaxis at the level of cell-molecule interactions is important because of its relevance in cancer, immunology, and microbiology, just to name a few. This study quantifies the effects of flow on cell migration during chemotaxis in a microfluidic device. The chemotaxis gradient within the device was modeled and compared to experimental results. Chemotaxis experiments were performed using the chemokine CXCL8 under different flow rates with human HL60 promyelocytic leukemia cells expressing a transfected CXCR2 chemokine receptor. Cell trajectories were separated into x and y axis components. When the microchannel flow rates were increased, cell trajectories along the x axis were found to be significantly affected (p < 0.05). Total migration distances were not affected. These results should be considered when using similar microfluidic devices for chemotaxis studies so that flow bias can be minimized. It may be possible to use this effect to estimate the total tractile force exerted by a cell during chemotaxis, which would be particularly valuable for cells whose tractile forces are below the level of detection with standard techniques of traction-force microscopy.
The Simple Near-Optimal Pairing Scheme of Superposition Coding in Downlink DS-CDMA Multi-path Channel (2007)

The paring scheme of superposition coding (SC) is developed to increase the user capacity in downlink DS-CDMA on multi-path channel. Unlike the previous work on frequency flat fading channel, the inter-user interference in the same SC and interference from other orthogonal codes are considered in selecting a pair of users for SC and evaluating their power allocation. We first examine the maximum supportable signal to interference and noise power ratio (SINR) and introduce the simple pairing scheme which offers nearly the same capacity with the same transmit power as the optimum pairing but requires far less computational complexity.
T Cell Cross-Reactivity and Conformational Changes during TCR Engagement (2004)

All thymically selected T cells are inherently cross-reactive, yet many data indicate a fine specificity in antigen recognition, which enables virus escape from immune control by mutation in infections such as the human immunodeficiency virus (HIV). To address this paradox, we analyzed the fine specificity of T cells recognizing a human histocompatibility leukocyte antigen (HLA)-A2-restricted, strongly immunodominant, HIV gag epitope (SLFNTVATL). The majority of 171 variant peptides tested bound HLA-A2, but only one third were recognized. Surprisingly, one recognized variant (SLYNTVATL) showed marked differences in structure when bound to HLA-A2. T cell receptor (TCR) recognition of variants of these two peptides implied that they adopted the same conformation in the TCR-peptide-major histocompatibility complex (MHC) complex. However, the on-rate kinetics of TCR binding were identical, implying that conformational changes at the TCR-peptide-MHC binding interface occur after an initial permissive antigen contact. These findings have implications for the rational design of vaccines targeting viruses with unstable genomes.
Botulinum toxin‐induced focal paresis in mice is unaffected by muscle activity (2011)

This in vivo paradigm quantifies the degree of otherwise clinically inapparent botulinum toxin-induced focal calf muscle paresis. Increased muscle activity after low-dose injections does not influence the efficacy of botulinum toxin in normal muscles.
BONE FORMATION IN VIVO: COMPARISON OF OSTEOGENESIS BY TRANSPLANTED MOUSE AND HUMAN MARROW STROMAL FIBROBLASTS (1997)

In this article, we describe the differences in the requirements for mouse and human MSFs to form bone, and report the development of a methodology for the consistent in vivo generation of extensive bone from human MSFs.
Controlling pathological pain by adenovirally driven spinal production of the anti‐inflammatory cytokine, interleukin‐10 (2005)

Gene therapy for the control of pain has, to date, targeted neurons. However, recent evidence supports that spinal cord glia are critical to the creation and maintenance of pain facilitation through the release of proinflammatory cytokines. Because of the ability of interleukin-10 (IL-10) to suppress proinflammatory cytokines, we tested whether an adenoviral vector encoding human IL-10 (AD-h-IL10) would block and reverse pain facilitation. Three pain models were examined, all of which are mediated by spinal pro-inflammatory cytokines. Acute intrathecal administration of rat IL-10 protein itself briefly reversed chronic constriction injury-induced mechanical allodynia and thermal hyperalgesia. The transient reversal caused by IL-10 protein paralleled the half-life of human IL-10 protein in the intrathecal space (t(1/2) approximately 2 h). IL-10 gene therapy both prevented and reversed thermal hyperalgesia and mechanical allodynia, without affecting basal responses to thermal or mechanical stimuli. Extra-territorial, as well as territorial, pain changes were reversed by this treatment. Intrathecal AD-h-IL10 injected over lumbosacral spinal cord led to elevated lumbosacral cerebrospinal fluid (CSF) levels of human IL-10, with far less human IL-10 observed in cervical CSF. In keeping with IL-10's known anti-inflammatory actions, AD-h-IL10 lowered CSF levels of IL-1, relative to control AD. These studies support that this gene therapy approach provides an alternative to neuronally focused drug and gene therapies for clinical pain control.
Targeting of Drugs to Cell Surface Receptors (1997)

The new approach to the treatment of cancer or to immunomodulation is drug targeting. The effort to achieve either an absolute or a relative amplification of the tumoricidal effect of anticancer drugs through increased generation or acquisition of reactive molecules at the tumor site or a reduction of the toxic molecules available to the periphery has led to a number of strategies. Among them are (1) targeting using antibodies to their fragments, hormones, carbohydrates, and growth factors; (2) retargeting using bispecific antibodies; (3) construction of chimeric genes; (4) streptavidin-biotin based immunotherapy; (5) prodrug activation strategies (ADEPT); (6) antibody-targeted superantigens; and (7) gene delivery for the purpose of gene therapy.
The TCP outcast problem: exposing unfairness in data center networks (2012)

In this paper, we observe that bandwidth sharing via TCP in commodity data center networks organized in multi-rooted tree topologies can lead to severe unfairness, which we term as the TCP Outcast problem, under many common traffic patterns. When many flows and a few flows arrive at two ports of a switch destined to one common output port, the small set of flows lose out on their throughput share significantly (almost by an order of magnitude sometimes). The Outcast problem occurs mainly in taildrop queues that commodity switches use. Using careful analysis, we discover that taildrop queues exhibit a phenomenon known as port blackout, where a series of packets from one port are dropped. Port blackout affects the fewer flows more significantly, as they lose more consecutive packets leading to TCP timeouts. In this paper, we show the existence of this TCP Outcast problem using a data center network testbed using real hardware under different scenarios. We then evaluate different solutions such as RED, SFQ, TCP pacing, and a new solution called equal-length routing to mitigate the Outcast problem. 1
Identification of a novel sesquiterpene biosynthetic machinery involved in astellolide biosynthesis (2016)

Esterified drimane-type sesquiterpene lactones such as astellolides display various biological activities and are widely produced by plants and fungi. Given their low homology to known sesquiterpene cyclases, the genes responsible for their biosynthesis have not been uncovered yet. Here, we identified the astellolide gene cluster from Aspergillus oryzae and discovered a novel sesquiterpene biosynthetic machinery consisting of AstC, AstI, and AstK. All these enzymes are annotated as haloacid dehalogenase-like hydrolases, whereas AstC also contains a DxDTT motif conserved in class II diterpene cyclases. Based on enzyme reaction analyses, we found that AstC catalysed the protonation-initiated cyclisation of farnesyl pyrophosphate into drimanyl pyrophosphate. This was successively dephosphorylated by AstI and AstK to produce drim-8-ene-11-ol. Moreover, we also identified and characterised a unique non-ribosomal peptide synthetase, AstA, responsible for esterifying aryl acids to drimane-type sesquiterpene lactones. In this study, we highlight a new biosynthetic route for producing sesquiterpene and its esterified derivative. Our findings shed light on the identification of novel sesquiterpenes via genome mining.
Acute Metformin Therapy Confers Cardioprotection Against Myocardial Infarction Via AMPK-eNOS–Mediated Signaling (2007)

These findings provide important information that myocardial AMPK activation by metformin following I/R sets into motion events, including eNOS activation, which ultimately lead to cardioprotection.
Insight into the Mechanism of Internalization of the Cell-Penetrating Carrier Peptide Pep-1 through Conformational Analysis (2004)

Recently, we described a new strategy for the delivery of proteins and peptides into mammalian cells, based on an amphipathic peptide of 21 residues, Pep-1, which was designed on the basis of a protein-interacting domain associated with a nuclear localization sequence and separated by a linker. This peptide carrier constitutes a powerful tool for the delivery of active proteins or peptides both in cultured cells and in vivo, without requiring any covalent coupling. We have examined the conformational states of Pep-1 in its free form and complexed with a cargo peptide and have investigated their ability to interact with phospholipids and the structural consequences of these interactions. From the conformational point of view, Pep-1 behaves significantly differently from other similarly designed cell-penetrating peptides. CD analysis revealed a transition from a nonstructured to a helical conformation upon increase of the concentration. Determination of the structure by NMR showed that in water, its α-helical domain extends from residues 4−13. CD and FTIR indicate that Pep-1 adopts a helical conformation in the presence of phospholipids. Adsorption measurements performed at the air−water interface are consistent with the helical form. Pep-1 does not undergo conformational changes upon formation of a particle with a cargo peptide. In contrast, we observe a partial conformational transition when the complex encounters phospholipids. We propose that the membrane crossing process involves formation of a transient transmembrane pore-like structure. Conformational change of Pep-1 is not associated with complexation with its cargo but is induced upon association with the cell membrane.
A Combined Top–Down/Bottom–Up Approach to the Microscopic Localization of Metallic Nanodots (2002)

Periodic and aperiodic two‐dimensional nanostructures with hierarchical order have been prepared by a combined top–down/bottom–up approach. This method allows 7 nm nanoparticles to be positioned with a accuracy of 10 nm or less, with a separation distance of several micrometers. The Figure is an optical dark field microscopy image of a square arrangement of Au dots on a Si wafer.
Comparison of different primer sets for detection of Chlamydia trachomatis by the polymerase chain reaction (1993)

The sensitivity and specificity of the polymerase chain reaction (PCR) method was studied in vitro with HeLa cells infected with Chlamydia trachomatis serovar L2. Three different primer sets were studied; they were derived from the endogenous plasmid, the nonvariable part of the MOMP gene and the 16S ribosomal RNA (rRNA) gene. The plasmid primers were the most sensitive in the PCR method and detected at least 0.1 infectious unit of C. trachomatis in the presence of a superfluous amount of human DNA. Application of this plasmid PCR to 13 C. trachomatis culture-positive cervical smears containing < 10- > 200 inclusion-forming units showed that it was the most sensitive of the three methods and detected C. trachomatis in all samples. This correlates with the observation that the plasmid PCR method could detect C. trachomatis in cervical smears of four symptomatic patients for up to 3 weeks after the start of treatment with doxycycline. In contrast, the MOMP gene- and rRNA gene-directed PCR, as well as culture and direct immunofluorescence, gave negative results within 1 week. Therefore, we conclude that the plasmid primers are the best candidates for use in the PCR method in C. trachomatis screening programmes and clinical follow-up studies.