gebhart/patrepeval huggingface dataset:
Design of Small-Molecule Peptidic and Nonpeptidic Smac Mimetics (2008)

Smac/DIABLO is a protein released from mitochondria into the cytosol in response to apoptotic stimuli. Smac promotes apoptosis at least in part through antagonizing inhibitor of apoptosis proteins (IAPs), including XIAP, cIAP-1, and cIAP-2. Smac interacts with these IAPs via its N-terminal AVPI binding motif. There has been an enormous interest in academic laboratories and pharmaceutical companies in the design of small-molecule Smac mimetics as potential anticancer agents. This task is particularly challenging because it involves targeting protein-protein interactions. Nevertheless, intense research has now generated potent, specific, cell-permeable small-molecule peptidomimetics and nonpeptidic mimetics. To date, two types of Smac mimetics have been reported, namely, monovalent and bivalent Smac mimetics. The monovalent compounds are designed to mimic the binding of a single AVPI binding motif to IAP proteins, whereas the bivalent compounds contain two AVPI binding motif mimetics tethered together through a linker. Studies from several groups have clearly demonstrated that both monovalent and bivalent Smac mimetics not only enhance the antitumor activity of other anticancer agents but also can induce apoptosis as single agents in a subset of human cancer cell lines in vitro and are capable of achieving tumor regression in animal models of human cancer. In general, bivalent Smac mimetics are 100-1000 times more potent than their corresponding monovalent Smac mimetics in induction of apoptosis in tumor cells. However, properly designed monovalent Smac mimetics can achieve oral bioavailability and may have major advantages over bivalent Smac mimetics as potential drug candidates. In-depth insights on the molecular mechanism of action of Smac mimetics have been provided by several independent studies. It was shown that Smac mimetics induce apoptosis in tumor cells by targeting cIAP-1/-2 for the rapid degradation of these proteins, which leads to activation of nuclear factor kappaB (NF-kappaB) and production and secretion of tumor necrosis factor alpha (TNFalpha). TNFalpha promotes formation of a receptor-interacting serine-threonine kinase 1 (RIPK1)-dependent caspase-8-activating complex, leading to activation of caspase-8 and -3/-7 and ultimately to apoptosis. For the most efficient apoptosis induction, Smac mimetics also need to remove the inhibition of XIAP to caspase-3/-7. Hence, Smac mimetics induce apoptosis in tumor cells by targeting not only cIAP-1/-2 but also XIAP. The employment of potent, cell-permeable, small-molecule Smac mimetics has yielded important insights into the regulation of apoptosis by IAP proteins. To date, at least one Smac mimetic has been advanced into clinical development. Several other Smac mimetics are in an advanced preclinical development stage and are expected to enter human clinical testing for the treatment of cancer in the near future.
Jones-matrix imaging of biological tissues with quadruple-channel optical coherence tomography (2002)

Two-dimensional depth-resolved Jones-matrix images of scattering biological tissues were measured with novel double-source double-detector polarization-sensitive optical coherence tomography (OCT). The Jones matrix can be determined in a single scan with this OCT system. The experimental results show that this system can be effectively applied to the measurement of soft tissues, which are less stable than hard tissues. Polarization parameters such as diattenuation, birefringence, and orientation of the fast axis can be extracted through decomposition of the measured Jones matrix. The Jones matrix of thermally treated porcine tendon showed a reduction of birefringence from thermal damage. The Jones matrices of porcine skin and bovine cartilage also revealed that the density and orientation of the collagen fibers in porcine skin and bovine cartilage are not distributed as uniformly as in porcine tendon. Birefringence is sensitive to changes in tissue because it is based on phase contrast.
Biochemical characterization of the phospholipase A2 purified from the venom of the Mexican beaded lizard (Heloderma horridum horridum Wiegmann) (1986)

A phospholipase A2 was isolated from the venom of the mexican beaded lizard (Heloderma horridum horridum) by phenyl-Sepharose chromatography followed by Sephadex G-75 gel filtration and two additional steps on ion exchange resins (DE-32 cellulose). The affinity chromatographic method (PC-Sepharose 4B) reported for the isolation of other phospholipases [Rock, Ch. O., & Snyder, F. (1975) J. Biol. Chem. 250, 2564-2566; King, T. P., Alagon, A. C., Kwan, J., Sobotka, A. K., & Lichteinstein, L. M. (1983) Mol. Immunol. 20, 297-308; King, T. P., Kochoumian, L., & Joslyn, A. (1984) Arch. Biochem. Biophys. 230, 1-12] was uneffective for the separation of this enzyme. The monomeric form of the Heloderma phospholipase has an apparent Mr of 18 000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 19 060 as calculated from amino acid analysis. It also contains on the order of 7% carbohydrates per mole of enzyme. The N-terminal amino acid sequence was shown to be very different from that of phospholipases isolated from mammalian pancreas and crotalids and elapids snake venoms. The first 39 amino acid residues at the N-terminal region have 56% homology with bee venom phospholipase but differ from the bee phospholipase in that its isoelectric point is acidic (pI = 4.5), instead of basic, and it has approximately 50 amino acid residues more in the molecule. The specificity of the enzyme is mainly A2 type with possible residual B-type activity. The enzymatic activity is Ca2+-dependent. Half-cystine alignment of the Heloderma phospholipase sequence with those of other known phospholipases shows the lack of an octadecapeptide at the N-terminal region, the existence of an extra hexapeptide at positions 42-47, and an exact correspondence of Heloderma Gly-12, Gly-14, His-36, and Asp-37 with Gly-30, Gly-32, His-48, and Asp-49 from other phospholipases shown to be important for Ca2+ binding (( Dijkstra, B. W., Drenth, J., Kalk, K. H., & Vandermaalen, P. J. (1978) J. Mol. Biol. 124, 53-60 )).(ABSTRACT TRUNCATED AT 250 WORDS)
The Adipose Tissue Phenotype of Hormone‐Sensitive Lipase Deficiency in Mice (2001)

In isolated fat cells, the lipolytic rate after beta-adrenergic stimulation is mainly dependent on HSL. However, the observation of a normal rate of lipolysis in unstimulated HSL-/- adipocytes suggests that HSL-independent lipolytic pathway(s) exist in fat. Physiologically, HSL deficiency in mice has a modest effect under normal fed conditions and is compatible with normal maintenance of core body temperature during cold stress. However, the lipolytic response to overnight fasting is subnormal.
The ALOHA System-Another Alternative for Computer Communications (1970)

In September 1968 the University of Hawaii began work on a research program to investigate the use of radio communications for computer-computer and console-computer links. In this report we describe a remote-access computer system---THE ALOHA SYSTEM---under development as part of that research program and discuss some advantages of radio communications over conventional wire communications for interactive users of a large computer system. Although THE ALOHA SYSTEM research program is composed of a large number of research projects, in this report we shall be concerned primarily with a novel form of random-access radio communications developed for use within THE ALOHA SYSTEM.
Pharmacological Characterization of Postjunctional α-Adrenoceptors in Human Nasal Mucosa (2005)

Our results indicate that functional alpha1- and alpha2-adrenoceptors are present and functional in human nasal mucosa. The alpha2-adrenoceptors display a predominant role in contracting the veins and the alpha1-adrenoceptors appear to preferentially constrict the human nasal arteries.
Intra-articular Injection of Tenoxicam in Osteoarthritic Knee Joints With Effusion (2007)

Thirty patients who had grade II to III osteoarthritis according to Kellgren-Lawrence system and presenting with acute effusion of the knee joint were randomly assigned to 2 groups. All patients were treated with aspiration of the synovial fluid, cold application, and rest. Fifteen patients received an intra-articular injection of tenoxicam 20 mg following aspiration. The other group was administered oral tenoxicam 20 mg a day for 10 days. Patients were examined at 2, 4, and 8 weeks and then in 3-month intervals. At followup visits, pain was assessed using visual analog scale: range of motion, and effusion of the knee joint were recorded. A repeated measure test was used to determine the significance of changes in pain and mobility between the groups. Student's Neyman Keuls test was used to determine the significance of differences within the groups. Chi-square test was used for the number of episodes. The intra-articular injection group had more rapid pain relief than the oral treatment group (P < .01). At the end of 1 year, the number of effusions was significantly lower in the intra-articular treatment group (P < .01). These results indicate that intra-articular injection of tenoxicam provides rapid pain relief in the patients with acute flare-up of knee osteoarthritis and helps to prevent effusion.
A Survey of Methods for the Preparation of Pyrrolopyrimidines (1974)

This review covers various synthetic approaches to the pyrrolopyrimidine ring systems. The five main structural forms are discussed individually together with accounts of the syntheses, reactions, and transformations of some examples. A short account of the importance of these systems in pharmacology, biochemistry, chemistry, and industry is also given. 1. Scope 2. Pyrrolo[3,2-d]pyrimidines 2.1. Synthesis from Pyrimidine Derivatives 2.2. Transformations 3. Pyrrolo[3,4-d]pyrimidines 3.1. Synthesis from Pyrrole Derivatives 3.2. Synthesis from Pyrimidine Derivatives 3.3. Transformations 4. Pyrrolo[2,3-d]pyrimidines 4.1. Synthesis from Pyrimidine Derivatives 4.2. Synthesis from Pyrrole Derivatives 4.3. Transformations 5. Pyrrolo[1,2-a]pyrimidines 5.1. Synthesis from Pyrrole Derivatives 5.2. Synthesis from Open Chain Intermediates 5.3. Synthesis from Pyrimidine Derivatives 5.4. Synthesis from a Lactam 5.5. Transformations 6. Pyrrolo[1,2-c]pyrimidines 6.1. Synthesis from Pyrrole Derivatives 6.2. Synthesis from Pyrimidine Derivatives 6.3. Chemical Properties and Reactions 7. Applications 8. Addendum
Multichannel Quartz Crystal Microbalance (1999)

Arrays of quartz crystal resonators are fabricated on a single quartz wafer as a multichannel quartz crystal microbalance (MQCM). Three types of four-channel array of 10-MHz resonators are prepared and tested. Mechanical oscillation of each channel is entrapped within the channel almost completely, so that the interference between the channels via the quartz crystal plate is almost negligible. A mass change on each channel is quantitatively evaluated on the basis of Sauerbrey's law. Thus, each channel of a MQCM device can be used as an independent QCM. Influence from a longitudinal wave generated from another channel is also negligible compared to the influence from the wave from the monitored channel itself. The simultaneous oscillation of channels is also possible. The potential applicability of MQCM to the two-dimensional mapping of mass changes is demonstrated.
Degradation of atrial natriuretic factor by kidney cortex membranes. Isolation and characterization of the primary proteolytic product. (1987)

Synthetic rat atrial natriuretic factor (r-ANF, 1-28) was incubated with rat kidney cortex membranes, and a predominant degradation product was identified by reverse-phase high performance liquid chromatography. The degradation product was subjected to amino acid analyses and found to have a composition identical to r-ANF. Amino-terminal sequence analyses identified two distinct amino-terminal residues and suggested that cleavage had occurred between the cysteine-phenylalanine bond (residues 7 and 8) of r-ANF. This degradative process could be inhibited by 1,10-phenanthroline and EDTA, suggesting that the enzyme responsible for proteolysis is a metalloendoprotease. The enzyme exhibits a Michaelis-Menten constant of approximately 10 microM for the metabolism of r-ANF and has a broad pH optimum between 8.5 and 9.5. These findings suggest that ANF may be initially degraded in the kidney at a single cleavage site within the 17-residue ring structure.
Peptides as targeting probes against tumor vasculature for diagnosis and drug delivery (2012)

Tumor vasculature expresses a distinct set of molecule signatures on the endothelial cell surface different from the resting blood vessels of other organs and tissues in the body. This makes them an attractive target for cancer therapy and molecular imaging. The current technology using the in vivo phage display biopanning allows us to quickly isolate and identify peptides potentially homing to various tumor blood vessels. Tumor-homing peptides in conjugation with chemotherapeutic drugs or imaging contrast have been extensively tested in various preclinical and clinical studies. These tumor-homing peptides have valuable potential as targeting probes for tumor molecular imaging and drug delivery. In this review, we summarize the recent advances about the applications of tumor-homing peptides selected by in vivo phage display library screening against tumor vasculature. We also introduce the characteristics of the latest discovered tumor-penetrating peptides in their potential clinical applications.
Renewable Monomer Feedstocks via Olefin Metathesis:  Fundamental Mechanistic Studies of Methyl Oleate Ethenolysis with the First-Generation Grubbs Catalyst (2004)

The conversion of seed oil based feedstocks such as methyl oleate into useful commercial raw materials via olefin metathesis has been a research focus for decades, due to their low cost and renewable supply, but technical success has been limited due to poor catalyst activities and turnovers. We report here recent studies on the cross-metathesis of methyl oleate with ethylene (ethenolysis) catalyzed by bis(tricyclohexylphosphine)benzylideneruthenium dichloride (1). At 25 °C/60 psig of ethylene, catalysis by 1 results in the highly selective formation of 1-decene and methyl 9-decenoate. However, reactivity losses limit the catalyst turnovers well below commercial viability in batch reactor operation. In an attempt to address the limitations of this chemistry, a combination of an experimental evaluation of the impact of process parameters, a detailed analysis of the fundamental reaction steps, kinetic modeling, and molecular modeling has been applied to develop a more detailed understanding of this complex catalytic pathway. These fundamental studies have led to a more complete understanding of the factors impacting catalyst performance and the identification of approaches necessary to achieve an economically viable process.
Operating system issues for PDAs (2002)

Personal digit assistants (PDAs) are small, mobile computing devices whose functionality ranges somewhere between that of an electronic organizer and that of a full-function portable computer. Since PDAs are too small in size to be used for extended work sessions they must justify their existence mostly by providing services that are tailored to people on the go. However, we observe that PDAs are also starting to acquire the ability to communicate and believe that in the long run much of their value will come from being able to interact with external services and devices. The goal of the paper is to relate a view of the ways in which operating systems for this new breed of small ubiquitous computing device will be different from the operating systems of today. The viewpoint is based partly on thoughts about what a ubiquitous computing world will look like and partly on experience with building and using various parts of a ubiquitous computing testbed. In particular, ParcTab computers and ParcPad notebook computers. Both are stylus-based and have onboard communications facilities.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Density Estimation for Statistics and Data Analysis (2018)

Although there has been a surge of interest in density estimation in recent years, much of the published research has been concerned with purely technical matters with insufficient emphasis given to the technique's practical value. Furthermore, the subject has been rather inaccessible to the general statistician.The account presented in this book places emphasis on topics of methodological importance, in the hope that this will facilitate broader practical application of density estimation and also encourage research into relevant theoretical work. The book also provides an introduction to the subject for those with general interests in statistics. The important role of density estimation as a graphical technique is reflected by the inclusion of more than 50 graphs and figures throughout the text.Several contexts in which density estimation can be used are discussed, including the exploration and presentation of data, nonparametric discriminant analysis, cluster analysis, simulation and the bootstrap, bump hunting, projection pursuit, and the estimation of hazard rates and other quantities that depend on the density. This book includes general survey of methods available for density estimation. The Kernel method, both for univariate and multivariate data, is discussed in detail, with particular emphasis on ways of deciding how much to smooth and on computation aspects. Attention is also given to adaptive methods, which smooth to a greater degree in the tails of the distribution, and to methods based on the idea of penalized likelihood.
Terretonin, a toxic compound from Aspergillus terreus (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTerretonin, a toxic compound from Aspergillus terreusJames P. Springer, Joe W. Dorner, Richard J. Cole, and Richard H. CoxCite this: J. Org. Chem. 1979, 44, 26, 4852–4854Publication Date (Print):December 1, 1979Publication History Published online1 May 2002Published inissue 1 December 1979https://pubs.acs.org/doi/10.1021/jo00394a023https://doi.org/10.1021/jo00394a023research-articleACS PublicationsRequest reuse permissionsArticle Views538Altmetric-Citations71LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Elastomer-supported cold welding for room temperature wafer-level bonding (2004)

This paper presents a method for room-temperature wafer-level bonding that is applicable for the MEMS and NEMS packaging and fabrication processes, but does not require an applied voltage, high pressure or vacuum. By applying a layer of elastomer between the wafer and gold overlayer, we successfully bonded two silicon wafers under limited load (/spl sim/3 KPa) at room temperature (25/spl deg/C). One of the important potential applications of this technique is to create a temporary cap wafer that would protect already released, bulk or surface-micromachined structures during the dicing process. The initial results of experiments on the detachment of the temporary cap wafers bonded using this method are presented.
Comparison of Combined Bupropion and Naltrexone Therapy for Obesity with Monotherapy and Placebo (2009)

NB caused gradual sustained weight loss over 48 wk; NB32 and NB16 demonstrated greater weight loss in the intent-to-treat population due to lower attrition rates. Further study is needed to demonstrate long-term efficacy and safety of NB.
Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6 (1989)

To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.
Clinical applications of monoclonal antibodies in gynecologic oncology (1987)

The advances of both murine and human monoclonal antibody (MoAb) technology have allowed the development of several antibodies against gynecologic tumors. The goals are to produce effective and specific reagents for both immunodiagnosis and therapy. However, despite an extensive research effort, a clear demonstration of specific cancer-associated antigens in gynecologic malignancies, or of specific immune responses to such antigens has been elusive. Currently, most antibodies found are cross reactive with either oncofetal antigens or some normal adult tissues. Clinical usefulness of these MoAbs as a screening test in radioimaging or in immunotherapy remains to be proven. However, the use of MoAb technology in defined antigens/tumor markers such as beta-human chorionic gonadotropin, and alpha fetal proteins has provided convenient, reproducible and highly specific reagents. More recently, promising antibodies have been shown to detect tumor antigens in serum of patients with ovarian cancer.