gebhart/patrepeval huggingface dataset:
Dual Wavelength Parametric Test of Two-State Models for Circular Dichroism Spectra of Helical Polypeptides:  Anomalous Dichroic Properties of Alanine-Rich Peptides (2003)

A two-state helix-coil model underlies all calculations of fractional helicities FH from CD spectra of helical polypeptides. The presence of an isodichroic point near 203 nm is widely assumed to validate this model, but is shown here to provide inadequate validation for alanine-rich peptides. A parametric correlation with constant slope B between CD ellipticities at a pair of wavelengths is introduced as a more rigorous two-state test. Correlations of temperature-dependent [theta](222) vs [theta](208) values are reported for a variety of peptides. Constant slopes B are observed for literature CD data obtained from fragments of helical proteins and dimeric helical coiled coils, but parametric correlations of CD data for alanine-rich peptides consistently exhibit anomalous concave upward curvature, characterized by local slopes that are linearly temperature dependent. Low-temperature CD studies together with parametric correlations at a series of wavelengths demonstrate that the curvature anomaly is maximal at 222 nm and localized in the 215-230 nm wavelength region. Precedented structural variation of the phi, psi dihedral angles of the alpha-helix is suggested as a possible explanation. For the important case of alanine-rich peptides, experiments are proposed that may yield temperature corrections for [theta](222) and permit reliable calculations of FH from [theta](222) values.
A NEW SYNTHESIS OF CYCLOPROPANES FROM OLEFINS (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA NEW SYNTHESIS OF CYCLOPROPANES FROM OLEFINSHoward E. Simmons and Ronald D. SmithCite this: J. Am. Chem. Soc. 1958, 80, 19, 5323–5324Publication Date (Print):October 1, 1958Publication History Published online1 May 2002Published inissue 1 October 1958https://pubs.acs.org/doi/10.1021/ja01552a080https://doi.org/10.1021/ja01552a080research-articleACS PublicationsRequest reuse permissionsArticle Views4738Altmetric-Citations551LEARN 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
Prevention of Selenite-Induced Cataratogenesis byGinkgo bilobaExtract (Egb761) in Wistar Rats (2014)

The treatment with G. biloba extract is effective against oxidative stress - a crucial factor of cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and by inhibiting lipid peroxidation.
A New Class of Arabidopsis Constitutive Photomorphogenic Genes Involved in Regulating Cotyledon Development (1993)

Yongmin Hou, Albrecht G. von Arnim, Xing-Wang Deng, A New Class of Arabidopsis Constitutive Photomorphogenic Genes Involved in Regulating Cotyledon Development, The Plant Cell, Vol. 5, No. 3 (Mar., 1993), pp. 329-339
Phase Transfer-Catalyzed Preparation of Oxiranes (1985)

Oxiranes 3 are prepared in 70 -85% yields by treating 1.2-diols 1 with one molar equivalent of p-toluenesulfonyl (2) or methanesulfonyl chloride (2′) under phase transfer conditions.
Radical Cyclization Approach to Spirocyclohexadienones (2004)

Cyclization of an aryl radical at the ipso position of a p-O-aryl-substituted acetamide or benzamide generates oxindoles or quinolones bearing spirocyclohexadienone rings. This versatile reaction is applied to formal syntheses of the vasopressin inhibitor SR121463A and aza-galanthamine.
Historical Comparisons of Morbidity and Mortality for Vaccine-Preventable Diseases in the United States (2007)

The number of cases of most vaccine-preventable diseases is at an all-time low; hospitalizations and deaths have also shown striking decreases.
A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. (1995)

A group of human cytochrome P450 genes encompassing the CYP2A, CYP2B, and CYP2F subfamilies were cloned and assembled into a 350-kb contig localized on the long arm of chromosome 19. Three complete CYP2A genes--CYP2A6, CYP2A7, and CYP2A13--plus two pseudogenes truncated after exon 5, were identified and sequenced. A variant CYP2A6 allele that differed from the corresponding CYP2A6 and CYP2A7 cDNAs previously sequenced was found and was designated CYP2A6v2. Sequence differences in the CYP2A6v2 gene are restricted to regions encompassing exons 3, 6, and 8, which bear sequence relatedness with the corresponding exons of the CYP2A7 gene, located downstream and centromeric of CYP2A6v2, suggesting recent gene-conversion events. The sequencing of all the CYP2A genes allowed the design of a PCR diagnostic test for the normal CYP2A6 allele, the CYP2A6v2 allele, and a variant--designated CYP2A6v1--that encodes an enzyme with a single inactivating amino acid change. These variant alleles were found in individuals who were deficient in their ability to metabolize the CYP2A6 probe drug coumarin. The allelic frequencies of CYP2A6v1 and CYP2A6v2 differed significantly between Caucasian, Asian, and African-American populations. These studies establish the existence of a new cytochrome P450 genetic polymorphism.
Specific Sequence Motif of 8-Cys Repeats of TGF-β Binding Proteins, LTBPs, Creates a Hydrophobic Interaction Surface for Binding of Small Latent TGF-β (2000)

Transforming growth factor (TGF)-betas are secreted in large latent complexes consisting of TGF-beta, its N-terminal latency-associated peptide (LAP) propeptide, and latent TGF-beta binding protein (LTBP). LTBPs are required for secretion and subsequent deposition of TGF-beta into the extracellular matrix. TGF-beta1 associates with the 3(rd) 8-Cys repeat of LTBP-1 by LAP. All LTBPs, as well as fibrillins, contain multiple 8-Cys repeats. We analyzed the abilities of fibrillins and LTBPs to bind latent TGF-beta by their 8-Cys repeats. 8-Cys repeat was found to interact with TGF-beta1*LAP by direct cysteine bridging. LTBP-1 and LTBP-3 bound efficiently all TGF-beta isoforms, LTBP-4 had a much weaker binding capacity, whereas LTBP-2 as well as fibrillins -1 and -2 were negative. A short, specific TGF-beta binding motif was identified in the TGF-beta binding 8-Cys repeats. Deletion of this motif in the 3(rd) 8-Cys repeat of LTBP-1 resulted in loss of TGF-beta*LAP binding ability, while its inclusion in non-TGF-beta binding 3(rd) 8-Cys repeat of LTBP-2 resulted in TGF-beta binding. Molecular modeling of the 8-Cys repeats revealed a hydrophobic interaction surface and lack of three stabilizing hydrogen bonds introduced by the TGF-beta binding motif necessary for the formation of the TGF-beta*LAP - 8-Cys repeat complex inside the cells.
Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell–suppressive activity (2008)

The induction of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) is an important immune-evading mechanism used by tumors. However, the exact nature and function of MDSCs remain elusive, especially because they constitute a heterogeneous population that has not yet been clearly defined. Here, we identified 2 distinct MDSC subfractions with clear morphologic, molecular, and functional differences. These fractions consisted of either mononuclear cells (MO-MDSCs), resembling inflammatory monocytes, or low-density polymorphonuclear cells (PMN-MDSCs), akin to immature neutrophils. Interestingly, both MO-MDSCs and PMN-MDSCs suppressed antigen-specific T-cell responses, albeit using distinct effector molecules and signaling pathways. Blocking IFN-gamma or disrupting STAT1 partially impaired suppression by MO-MDSCs, for which nitric oxide (NO) was one of the mediators. In contrast, while IFN-gamma was strictly required for the suppressor function of PMN-MDSCs, this did not rely on STAT1 signaling or NO production. Finally, MO-MDSCs were shown to be potential precursors of highly antiproliferative NO-producing mature macrophages. However, distinct tumors differentially regulated this inherent MO-MDSC differentiation program, indicating that this phenomenon was tumor driven. Overall, our data refine tumor-induced MDSC functions by uncovering mechanistically distinct MDSC subpopulations, potentially relevant for MDSC-targeted therapies.
COMPARISON OF TWO DOSES OF INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR TREATMENT OF MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION (2008)

There were no statistically significant differences between the two dose groups with regard to the number of injections and anatomical and functional outcomes. Intravitreal injection of bevacizumab at doses up to 2.5 mg appears to be effective in improving BCVA and reducing CMT in BRVO in the short term. Multiple injections are needed in a large number of eyes for continued control of macular edema and preservation of visual acuity in the short term. Longer studies are needed to determine what role if any intravitreal injection of bevacizumab may play in the long-term treatment of this condition.
Clinical and Experimental Applications of NIR-LED Photobiomodulation (2006)

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as "photobiomodulation," uses light in the far-red to near-infrared region of the spectrum (630-1000 nm) and modulates numerous cellular functions. Positive effects of NIR-light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction.
Nontoxic membrane translocation peptide from protamine, low molecular weight protamine (LMWP), for enhanced intracellular protein delivery: in vitro and in vivo study (2005)

Naturally derived, nontoxic peptides from protamine by the authors, termed low molecular weight protamines (LMWPs), possess high arginine content and carry significant sequence similarity to that of TAT, by far the most potent protein transduction domain peptide. Therefore, it was hypothesized that these LMWPs would also inherit the similar translocation activity across the cell membrane, which enables any impermeable species to be transduced into the cells. LMWPs were prepared by enzymatic digestion of protamine, examined their capability of transducing an impermeable protein toxin into the tumor cells by chemical conjugation, and determined cytotoxicity of transduced protein toxin (e.g., gelonin) against cancer cell lines and a tumor-bearing mouse. In vitro results showed that LMWPs could indeed translocate themselves into several mammalian cell lines as efficiently as TAT, thereby transducing impermeable gelonin into the cells by chemical conjugation. In vivo studies further confirmed that LMWP could carry an impermeable gelonin across the tumor mass and subsequently inhibit the tumor growth. In conclusion, the presence of equivalent cell translocation potency, absence of toxicity of peptide itself, and the suitability for low-cost production by simple enzymatic digestion could expand the range of clinical applications of LMWPs, including medical imaging and gene/protein therapies.
Biomaterials: Where We Have Been and Where We Are Going (2004)

Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
How Proteins Are Transported from Cytoplasm to the Nucleus (1997)

Nuclear proteins are transported actively through nuclear pores by a selective, mediated process. The process is mediated by a nuclear localization signal (NLS), and can be divided into at least two steps, (a) targeting to the pores and (b) translocation through the pores. The first step involves the formation of a stable complex containing a nuclear protein, termed nuclear pore-targeting complex (PTAC), in the cytoplasm. The second step, translocation, requires at least two soluble factors, a small GTPase Ran and its interacting protein p10/nuclear transport factor 2 (NTF2), along with nuclear pore complex components. These findings have been generally obtained by using the NLS of SV40 large T-antigen, and data concerning the detailed mechanism are now accumulating. Transport pathways other than for the SV40 T-antigen, for example, extracellular signal-dependent nuclear protein import pathway, have also recently been studied. Considering all these observations, one should be able to attain an understanding of the mechanism of intracellular information transduction between cytoplasm and the nucleus.
Sensing and actuating capabilities of a shape memory polymer composite integrated with hybrid filler (2010)

In this paper, hybrid fillers, including carbon black (CB) and chopped short carbon fibers (SCF), are integrated into a styrene-based shape memory polymer (SMP) with sensing and actuating capabilities. The hybrid filler is expected to transform insulating SMP into conducting. Static mechanical properties of the SMP composites containing various filler concentrations of hybrid filler reinforcement are studied first, and it is theoretically and experimentally confirmed that the mechanical properties are significantly improved by a factor of filler content of SCF. The excellent electrical properties of this novel type of SMP composite are determined by a four-point-probe method. As a consequence, the sensing properties of SMP composite filled with 5 wt% CB and 2 wt% SCF are characterized by functions of temperature and strain. These two experimental results both aid the use of SMP composites as sensors that respond to changes in temperature or mechanical loads. On the other hand, the actuating capability of SMP composites is also validated and demonstrated. The dynamic mechanical analysis result reveals that the output strength of SMP composites is improved with an increase in filler content of SCF. The actuating capability of SMP composites is subsequently demonstrated in a series of photographs.
Syntheses and applications of water‐soluble reactive polymers for purification and immobilization of biomolecules (1989)

Reactive polymers have been prepared by copolymeriz-ing N-isopropyl acrylamide (NIPAM) with N-acryloxy-succinimide (NASI) or glycidyl methacrylate (GMA). The amino groups of ligands could react with the residues of NASI or GMA and the polymers could be precipitated by temperature and/or salinity variation, since they contained the NIPAM residues. As a model, p-aminobenza-midine, a trypsin inhibitor, was attached to the polymers to form water-soluble macroligands, capable of selectively binding trypsin from a trypsin-chymotrypsin solution. After precipitation of the macroligand-trypsin complex, followed by dissociation, approximately 82% trypsin was isolated. The NIPAM-GMA copolymer was also reacted with immunogammaglobulin (IgG) and alkaline phosphatase (AP). It was demonstrated that the IgG bearing polymer was able to bind protein A and the whole complex was precipitable. The reactive polymer was also used for direct immobilization of AP which was active in repeated reactions.
Absence of Abundant Binding Sites for Anesthetics in Rabbit Brain (1990)

Using magnetic resonance spectroscopy, the authors tested whether cerebral concentrations of inhaled anesthetics do not increase proportionately at inspired concentrations exceeding 3% 1) because anesthetics bind to and saturate specific sites in the brain or 2) because anesthetic-induced depression of ventilation limits the increase in alveolar anesthetic partial pressure. New Zealand White rabbits were anesthetized with methohexital, 70% nitrous oxide, and local infiltration of 1% lidocaine. Cerebral concentrations of anesthetic were determined from 19F spectra acquired with nuclear magnetic resonance (NMR). Inspired, end-tidal, and arterial anesthetic concentrations, and end-tidal and arterial partial pressure of carbon dioxide were measured. Blood/gas partition coefficients were determined and used to convert arterial anesthetic concentration to partial pressures. In seven spontaneously breathing animals, halothane (1%; n = 5) or isoflurane (0.8%; n = 2) was administered at a constant inspired concentration for 20 min; NMR spectra were acquired between 10 and 20 min. Thereafter, the inspired concentration was increased and the process repeated until apnea occurred. Two additional rabbits were anesthetized with isoflurane and studied similarly but with higher inspired concentrations during mechanical ventilation. In spontaneously breathing animals, ventilatory depression occurred, documented by marked increases in PaCO2, and cerebral concentrations of anesthetic did not increase proportionately at inspired concentrations exceeding 3%. In contrast to an absence of a correlation of inspired and cerebral concentrations during spontaneous ventilation, arterial and cerebral concentrations correlated linearly during both spontaneous and mechanical ventilation (R2 greater than 0.969). These results are consistent with depression of ventilation, rather than binding to specific cerebral sites as an explanation for the nonlinear relationship between cerebral and inspired anesthetic concentrations.
Interim Analysis of a Phase II study of epirubicin and paclitaxel as first-line therapy in patients with metastatic breast cancer. (1996)

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to be used routinely in clinical practice, has aroused considerable interest for its high single-agent activity in breast cancer and its novel mechanism of action. The 4' epimer of doxorubicin, epirubicin is an agent with high activity against breast cancer but a lower rate of toxic side effects, especially cardiotoxic events, than its parent compound. Although the paclitaxel/doxorubicin combination has yielded response rates between 63% and 94% in phase I/II studies, some severe cardiotoxic events were reported. The rationale for our study was to evaluate the paclitaxel/epirubicin combination, focusing mainly on cardiotoxicity. In all, 57 patients with metastatic breast cancer entered the study, 28% of whom had primary metastatic breast cancer with large tumors at the primary site. Half of the patients had received adjuvant chemotherapy. Study medication consisted of 60 mg/m2 epirubicin given intravenously over 1 hour, followed by paclitaxel 175 mg/m2 administered as a 3-hour intravenous infusion after premedication with steroids, antihistamines, and H2 antagonists. The main toxicity was neutropenia (World Health Organization toxicity index grade 3/4, 72%). Other hematologic side effects were rare and no febrile neutropenia was reported. Peripheral neuropathy, arthralgia, and myalgia were mild (only World Health Organization grade 1 and 2). All patients had alopecia. The paclitaxel dose was escalated to 200 mg/m2 in eight patients, four of whom received a further escalation to 225 mg/m2. Severe neutropenia necessitated dose reductions in eight patients. No cardiac adverse events were reported. Of 41 patients evaluable for response, seven had complete remissions and 21 had partial remissions (68%). An additional 12 patients (29%) had stable disease. The combination of paclitaxel 175 mg/m2 and epirubicin 60 mg/m2 can be administered safely to patients with metastatic breast cancer. Although response was not the primary end point of this trial, the response data are nonetheless encouraging and suggest that further evaluation of the role of this combination in the first-line treatment of metastatic breast cancer is warranted.
ProTide generated long-acting abacavir nanoformulations (2018)

Abacavir pronucleotide nanoformulations (NM3ABC) were prepared as a novel long acting slow effective release antiretroviral therapy. Single NM3ABC treatment of human monocyte-derived macrophages produced sustained intracellular carbovir-triphosphate and antiretroviral activities for up to 30 days.
Final Version of 2009 AJCC Melanoma Staging and Classification (2009)

Using an evidence-based approach, revisions to the AJCC melanoma staging system have been made that reflect our improved understanding of this disease. These revisions will be formally incorporated into the seventh edition (2009) of the AJCC Cancer Staging Manual and implemented by early 2010.