gebhart/patrepeval huggingface dataset:
Adsorbed Protein Secondary and Tertiary Structures by Circular Dichroism and Infrared Spectroscopy with Refractive Index Matched Emulsions (2001)

The secondary structure of protein adsorbed at the emulsion interface has been studied in refractive index matched emulsions using the techniques of circular dichroism (CD) and Fourier transform infrared spectroscopy. Bovine serum albumin (BSA) and bovine beta-lactoglobulin (betalg) stabilized emulsions were studied, and the refractive index was altered by the addition of glycerol or polyethylene glycol. The effect of additive on the solution and adsorbed protein structure in addition to the effect of adsorption time was considered. Both adsorption and glycerol addition alter protein secondary structure; however, the majority of secondary structure remains. Small changes are observed in the secondary structure of adsorbed protein with time. Near-ultraviolet CD studies showed the effect of glycerol and adsorption on the aromatic groups. BSA showed small changes both upon the addition of glycerol to protein in solution and upon adsorption. betalg showed slightly larger changes upon the addition of glycerol to protein in solution and a larger change upon adsorption.
Tempering the wrath of RAGE: An emerging therapeutic strategy against diabetic complications, neurodegeneration, and inflammation (2009)

The multiligand receptor RAGE (receptor for advanced glycation end-products) is emerging as a central mediator in the immune/inflammatory response. Epidemiological evidence accruing in the human suggests upregulation of RAGE's ligands (AGEs, S100/calgranulins, high mobility group box-1 (HMGB1), and amyloid beta-peptide and beta-sheet fibrils) and the receptor itself at sites of inflammation and in chronic diseases such as diabetes and neurodegeneration. The consequences of ligand-RAGE interaction include upregulation of molecules implicated in inflammatory responses and tissue damage, such as cytokines, adhesion molecules, and matrix metalloproteinases. In this review, we discuss the localization of RAGE and its ligand families and the biological impact of this axis in multiple cell types implicated in chronic diseases. Lastly, we consider findings from animal model studies suggesting that although tissue-damaging effects ensue from recruitment of the ligand-RAGE interaction, in distinct settings, adaptive and repair/regeneration outcomes appear to override detrimental effects of RAGE. As RAGE blockade moves further into clinical development, clarifying the biology of RAGE garners ever-increasing importance.
The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy (2014)

The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.
BART is essential for nuclear retention of STAT3 (2008)

Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation and survival in immune responses, hematopoiesis, neurogenesis and other biological processes. STAT3, for example, is involved in the epithelial-mesenchymal transition during gastrulation, organogenesis, wound healing and cancer progression. STAT activity is regulated by a variety of mechanisms, including nuclear translocation. To clarify the molecular mechanisms underlying the regulation of STAT activity, we performed yeast two-hybrid screening. Here, we identified binder of ADP-ribosylation factor-like two (BART) as a novel STAT-binding partner. Importantly, we showed that BART is essential for the transcriptional activity and nuclear retention of STAT3. Furthermore, an effector of BART, ADP-ribosylation factor-like 2 (ARL2) was also involved in nuclear retention of STAT3. These results indicate that BART plays an essential role in the nuclear retention of STAT3 through interaction with ARL2.
The Preparation and Properties of 6-Halomethylpurines1 (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation and Properties of 6-Halomethylpurines1Sasson Cohen, Edna Thom, and Aaron BendichCite this: J. Org. Chem. 1962, 27, 10, 3545–3549Publication Date (Print):October 1, 1962Publication History Published online1 May 2002Published inissue 1 October 1962https://pubs.acs.org/doi/10.1021/jo01057a033https://doi.org/10.1021/jo01057a033research-articleACS PublicationsRequest reuse permissionsArticle Views141Altmetric-Citations33LEARN 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 Get e-Alerts
The Primary Structure of a Human Lambda II Chain (1975)

The human myeloma protein Boh (gamma 2, lambda) was isolated and completely reduced and aminoethylated. The light chain was obtained by chromatography on Sephadex G-100 in 4 M guanidine HC1. The amino-terminal sequence on the blocked light chain could be determined by automatic sequence degradation after PCAase treatment. Twenty-one peptides were isolated from a tryptic digest and 12 peptides from a chymotryptic digest. The sequence determination on these peptides was performed by automatic sequencing methods. The light chain of Boh protein belongs to the lambda II subgroup. Unique substitutions have been found at position 8 (Arg) and position 62 (Tyr). Furthermore, the Boh light chain has six cysteine residues, the additional (sixth) cysteine being adjacent to the invariable intrachain-S-S linking cysteine at position 91. Sequence comparison of lambda II proteins reveals a high degree of homology emphasizing the biologic significance of the hypervariable region sequences;
Extension of Multiple Range Tests to Group Means with Unequal Numbers of Replications (1956)

In many fields of research, one is faced with the task of comparing the effects of treatments which have been replicated unequally. This happens for a number of reasons. In an experiment on animals, some may get sick and have to be removed from the experiment. In some experiments, the amount of material available for certain treatments may not be as much as for other treatments. If the experimenter has specified orthogonal contrasts that he is interested in before he runs the experiment, one can test the various treatment effects by an F-test after the treatment sum of squares has been partitioned into individual degrees of freedom for each orthogonal contrast. If the experimenter has not specified orthogonal contrasts, one is faced with the problem of deciding which treatments are significantly different. Several writers, including Duncan, Keuls, Newman, and Tukey, have developed multiple range tests to show differences among treatments that have been replicated the same number of times and when nothing was specified concerning the treatments. Duncan [1] compares the above methods and gives citations. This extension to unequal numbers of replications will be exemplified with reference to Duncan's New Multiple Range Test, but is applicable to any of the above writers' tests; all one has to do is use their tabled ranges. In Duncan's test for an equal number of replications, the difference between any two ranked means is significant if the difference exceeds a shortest significant range. This shortest significant range is designated by R, and is obtained by multiplying the standard error of a mean, s,, by a given value, zn2, obtained from a table of significant studentized ranges which Duncan has tabled for both the 5% and 1% test. In Duncan's terminology, n2 is the degrees of freedom of the error mean square and p = 1, 2, * *, t is the number of means concerned. Consider an experiment with five treatments, A, B. C, D, and E, each replicated n times. Suppose on ranking the means from low to high one obtains
A high-throughput media design approach for high performance mammalian fed-batch cultures (2013)

An innovative high-throughput medium development method based on media blending was successfully used to improve the performance of a Chinese hamster ovary fed-batch medium in shaking 96-deepwell plates. Starting from a proprietary chemically-defined medium, 16 formulations testing 43 of 47 components at 3 different levels were designed. Media blending was performed following a custom-made mixture design of experiments considering binary blends, resulting in 376 different blends that were tested during both cell expansion and fed-batch production phases in one single experiment. Three approaches were chosen to provide the best output of the large amount of data obtained. A simple ranking of conditions was first used as a quick approach to select new formulations with promising features. Then, prediction of the best mixes was done to maximize both growth and titer using the Design Expert software. Finally, a multivariate analysis enabled identification of individual potential critical components for further optimization. Applying this high-throughput method on a fed-batch, rather than on a simple batch, process opens new perspectives for medium and feed development that enables identification of an optimized process in a short time frame.
Rationally Designed Tumor-Penetrating Nanocomplexes (2012)

Small interfering RNA (siRNA) therapeutics have broad potential uses in medicine but require safe and effective delivery vehicles to function. An ideal delivery system should encapsulate and protect the siRNA cargo from serum proteins, exhibit target tissue and cell specificity, penetrate the cell surface, and release its cargo in the desired intracellular compartment. One approach to the design of delivery vehicles that meets all of these requirements utilizes the systematic assembly of multiple components that can address each barrier. This rational approach was adopted by Ren et al., who designed novel myristoylated tandem peptides that consist of a tumor-targeting module and a cell-penetrating module, as described in this issue of ACS Nano. These tandem peptides were formulated with siRNAs into nanocomplexes for cell-specific delivery to a variety of tumor cell lines. The correlation of the structural properties of the nanocomplex to cell-type-specific activity via a computational approach identified the valence of the tumor-targeting ligand and overall nanocomplex charge as important parameters for the activity of the formulations. The in vivo gene silencing potency of these peptide-based nanocomplex formulations was demonstrated by Ren et al. in an ovarian cancer model. Tumor-penetrating nanocomplexes carrying a siRNA sequence against a novel oncogene (ID4) led to a significant reduction in tumor burden and an 80% increase in mouse survival. As such, the combination of a systematic approach with computational modeling can be advantageous for improving the delivery and potency of siRNA therapeutics.
Absolute Optical Frequency Measurement of the CesiumD1Line with a Mode-Locked Laser (1999)

We have measured the absolute optical frequency of the cesium ${D}_{1}$ line at 335 THz (895 nm). This frequency provides an important link for a new determination of the fine structure constant $\ensuremath{\alpha}$. The ${D}_{1}$ line has been compared with the fourth harmonic of a methane stabilized He-Ne laser at 88.4 THz ( $3.39\ensuremath{\mu}\mathrm{m}$). To measure the frequency mismatch of 18.39 THz between $4\ifmmode\times\else\texttimes\fi{}88.4\mathrm{THz}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}354\mathrm{THz}$ and the ${D}_{1}$ line a frequency comb spanning around 244 000 modes of a Kerr-lens mode-locked laser was used. We find 1 167 688 (81) kHz for the hyperfine splitting of the ${6P}_{1/2}$ state and 335 116 048 807 (41) kHz for the hyperfine centroid from which we derive ${\ensuremath{\alpha}}^{\ensuremath{-}1}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}137.0359924(41)$.
Targeting the Wnt pathways for therapies (2014)

The Wnt/β-catenin signaling pathway is crucial in animal development from sponges to humans. Its activity in the adulthood is less general, with exceptions having huge medical importance. Namely, improper activation of this pathway is carcinogenic in many tissues, most notably in the colon, liver and the breast. On the other hand, the Wnt/β-catenin signaling must be re-activated in cases of tissue damage, and insufficient activation results in regeneration failure and degeneration. These both medically important implications are unified by the emerging importance of this signaling pathway in the control of proliferation of various types of stem cells, crucial for tissue regeneration and, in case of cancer stem cells - cancer progression and relapse. This article aims at briefly reviewing the current state of knowledge in the field of Wnt signaling, followed by a detailed discussion of current medical developments targeting distinct branches of the Wnt pathway for anti-cancer and pro-regeneration therapies.
Solution Structure of μ-Conotoxin PIIIA, a Preferential Inhibitor of Persistent Tetrodotoxin-sensitive Sodium Channels (2002)

Mu-conotoxins are peptide inhibitors of voltage-sensitive sodium channels (VSSCs). Synthetic forms of mu-conotoxins PIIIA and PIIIA-(2-22) were found to inhibit tetrodotoxin (TTX)-sensitive VSSC current but had little effect on TTX-resistant VSSC current in sensory ganglion neurons. In rat brain neurons, these peptides preferentially inhibited the persistent over the transient VSSC current. Radioligand binding assays revealed that PIIIA, PIIIA-(2-22), and mu-conotoxins GIIIB discriminated among TTX-sensitive VSSCs in rat brain, that these and GIIIC discriminated among the corresponding VSSCs in human brain, and GIIIA had low affinity for neuronal VSSCs. (1)H NMR studies found that PIIIA adopts two conformations in solution due to cis/trans isomerization at hydroxyproline 8. The major trans conformation results in a three-dimensional structure that is significantly different from the previously identified conformation of mu-conotoxins GIIIA and GIIIB that selectively target TTX-sensitive muscle VSSCs. Comparison of the structures and activity of PIIIA to muscle-selective mu-conotoxins provides an insight into the structural requirements for inhibition of different TTX-sensitive sodium channels by mu-conotoxins.
CE Update—Body Fluids I: Wright-Giemsa Cytology of Body Fluids (1997)

Body fluid analysis can provide important diagnostic information to the clinician. A key aspect of these analyses is the white blood cell differential and evaluation of cellular morphology on slides of specimens prepared with Wright-Giemsa stains. Despite the clinical imperative for providing consistently good slides, body fluid specimens pose special challenges. The cytocentrifuge provides one way to meet these challenges. We review several techniques for achieving optimal cytocentrifuge slide preparations.
Remnant Lipoproteins: Measurement and Clinical Significance (2002)

In this issue of the Journal, Chan et al. (1) make the significant observation, by three distinct measures, that the concentrations of remnant lipoproteins (RLPs) in plasma are increased in patients with obesity. This increase in RLPs could explain, in part, the increased cardiovascular risk associated with obesity (2). To date, although LDL- and HDL-cholesterol are clearly accepted as independent risk factors for premature atherosclerosis, the role of plasma triglycerides as a risk factor remains somewhat controversial.

Plasma triglycerides are clearly a measure of triglyceride-rich lipoproteins (TRLs), which derive from both the intestine and the liver. Measurement of plasma triglycerides, however, does not distinguish the various subspecies of TRLs, which clearly have various degrees of atherogenicity. Triglyceride-rich RLPs are formed in the circulation when chylomicrons of intestinal origin [with apolipoprotein B-48 (apo B-48)] and VLDL of hepatic origin (with apo B-100) are converted by lipoprotein lipase (and to a lesser extent by hepatic lipase) into smaller and more dense particles. Compared with their nascent precursors, RLPs are depleted of triglycerides, phospholipids, and apo C and are enriched in cholesteryl esters and apo E and are believed to be more atherogenic than the larger TRLs (3).

Several lines of evidence have implicated RLPs in premature atherosclerosis. In fact, the prototypic disorder of remnant metabolism, type III dyslipidemia, is associated with accelerated atherosclerosis (4). Other evidence incriminating remnants as proatherogenic factors include the following: increased intermediate-density lipoprotein (IDL) concentrations have been associated with an increased incidence or recurrence of coronary artery disease (CAD) (3). Increased IDL is also found in diseases associated with accelerated atherosclerosis, such as type III dyslipidemia, type 2 diabetes mellitus, end stage renal disease (ESRD), and familial combined hyperlipidemia. Several previous reports have linked various measures of remnants to CAD in controlled angiographic follow-up trials (5). …
Characterization of Methylglyoxal Synthase from Clostridium acetobutylicum ATCC 824 and Its Use in the Formation of 1,2-Propanediol (1999)

A gene encoding a putative 150-amino-acid methylglyoxal synthase was identified in Clostridium acetobutylicum ATCC 824. The enzyme was overexpressed in Escherichia coli and purified. Methylglyoxal synthase has a native molecular mass of 60 kDa and an optimum pH of 7.5. The Km and Vmax values for the substrate dihydroxyacetone phosphate were 0.53 mM and 1.56 mmol min(-1) microgram(-1), respectively. When E. coli glycerol dehydrogenase was coexpressed with methylglyoxal synthase in E. coli BL21(DE3), 3.9 mM 1,2-propanediol was produced.
Culture of Adult Mouse Neurons (2005)

Primary neuronal cells used to model physiology are generally limited to embryonic tissue. However, embryonic tissue is not optimal as a model for age-related changes in physiology or late-onset disease. Successful culturing of neurons from adult animals, however, has been historically difficult, if not impossible. Here, we report methodology for routine and reliable cultivation of healthy striatal neurons from adult mice. The new methodology is cost-effective and improves the speed and simplicity of neuronal isolation.
Mechanical Integration of Actin and Adhesion Dynamics in Cell Migration (2010)

Directed cell migration is a physical process that requires dramatic changes in cell shape and adhesion to the extracellular matrix. For efficient movement, these processes must be spatiotemporally coordinated. To a large degree, the morphological changes and physical forces that occur during migration are generated by a dynamic filamentous actin (F-actin) cytoskeleton. Adhesion is regulated by dynamic assemblies of structural and signaling proteins that couple the F-actin cytoskeleton to the extracellular matrix. Here, we review current knowledge of the dynamic organization of the F-actin cytoskeleton in cell migration and the regulation of focal adhesion assembly and disassembly with an emphasis on how mechanical and biochemical signaling between these two systems regulate the coordination of physical processes in cell migration.
Plasmin Induces Local Thrombolysis without Causing Hemorrhage: A Comparison with Tissue Plasminogen Activator in the Rabbit (2001)

The direct fibrinolytic enzyme, plasmin, was compared with tissue plasminogen activator (TPA) in rabbit models of local thrombolysis and fibrinolytic hemorrhage. Plasmin was produced by solid-phase urokinase activation of plasminogen and purified on benzamidine Sepharose. Applied as an intra-arterial infusion into the thrombosed abdominal aorta under conditions of unimpeded blood flow, plasmin (4 mg/kg) and TPA (2 mg/kg) achieved equivalent clot dissolution and flow restoration. Using the model of restricted blood flow into the thrombosed aorta, which limits local plasminogen supply, plasmin was superior to TPA in clot lysis and vascular reperfusion. Using similar dosages of plasmin (2 or 4 mg/kg) and TPA (1 or 2 mg/kg) in the earpuncture rebleed model. TPA induced rebleeding in a dose-dependent manner from prior puncture sites in 9 of 10 animals, while none of the 10 animals exposed to plasmin rebled from these sites. These results suggest that plasmin is an effective, unique thrombolytic agent, distinguished from the plasminogen activators in current usage by its striking safety profile.
Synthesis of 2880-II, A Metabolite Related to Ferulic Acid (1991)

Abstract A synthesis of 2880-II (1), a co-metabolite of colabomycin A (2) from Streptomyces griseoflavus, is described.
Addition of a short peptide ligand to the adenovirus fiber protein. (1995)

A major concern associated with the use of recombinant adenoviral vectors is that viral receptors are found on the surface of many cell types and systemic in vivo delivery of the viral vector could result in uncontrolled and widespread expression of therapeutic molecules in many tissues. To construct a cell-type specific recombinant adenoviral vector, a new binding specificity must be added to the virus, and the endogenous binding specificity of the virus must be ablated. In order to introduce a new binding specificity to recombinant adenoviral vectors, the coding sequence of a physiological ligand, the terminal decapeptide of the gastrin releasing peptide (GRP), was placed at the 3' end of the coding sequence of the adenovirus type 5 fiber gene. The resulting fiber-GRP fusion protein was expressed using a T7 vaccinia expression system and has been shown to assemble protein trimers whose quaternary structure is indistinguishable from that of wild-type protein. The fiber-GRP fusion protein was correctly transported to the nucleus of HeLa cells immediately after synthesis. The added GRP ligand in the fiber-GRP fusion protein was accessible to binding by an anti-GRP antibody in both the monomeric and trimeric forms of the chimeric protein. These studies suggest that new cell type specificities for adenovirus binding might be introduced by genetic fusion of peptide ligands on to the carboxyl terminus of the adenovirus fiber protein.