gebhart/patrepeval huggingface dataset:
Interleukin 1 beta is localized in the cytoplasmic ground substance but is largely absent from the Golgi apparatus and plasma membranes of stimulated human monocytes. (1988)

The subcellular location of IL-1 beta was determined using a postsectioning immunoelectron microscopic method on ultrathin frozen sections of human monocytes stimulated with LPS. This methodology permits access of antibody probes to all sectioned intracellular compartments, and their visualization at high resolution. Staining was performed with a rabbit antibody that specifically recognized amino acids 197-215 in the 33-kD IL-1 beta precursor molecule, followed by affinity-purified goat anti-rabbit IgG conjugated to 10 nm colloidal gold particles. Approximately 90% of the IL-1 beta antigens were localized in the ground substance of the cytoplasm at 4 or 20 h after activation, when both intracellular and extracellular accumulation of IL-1 beta was well underway. No significant IL-1 beta staining was observed on the outer cell membrane, nor within the lumens of the endoplasmic reticulum (ER), the Golgi apparatus, or secretory vesicles. In contrast, lysozyme was localized in the ER and dense secretory granules using these methods. Our results suggest that IL-1 beta is not anchored on the plasma membrane, and that its secretion occurs by a novel mechanism that does not use a secretory leader sequence, nor the classical secretory pathway involving the ER and Golgi apparatus.
Rapid diagnosis of maple syrup urine disease in blood spots from newborns by tandem mass spectrometry (1995)

We report a new method for the diagnosis of maple syrup urine disease (MSUD) from dried blood spots on newborn screening cards based on tandem mass spectrometry (MS-MS). The mean +/- SD concentration of Leu plus Ile in normal newborns was 151 +/- 47 mumol/L (n = 1096); for Val, 131 +/- 58 mumol/L (n = 791). SDs were lower when the concentrations of these amino acids were expressed relative to that of Phe. The mean ratio for Leu + Ile to Phe was 2.5 +/- 0.49; for Val to Phe, 2.18 +/- 0.51. These results compare well with values previously reported in the literature. With these criteria, samples from a collection categorized by a bacterial inhibition assay as normal or falsely positive for MSUD were normal by MS-MS [(Leu + Ile): Phe < 5.0]. Samples from confirmed MSUD patients were categorized as abnormal [(Leu+Ile): Phe > 9.0] by MS-MS.
Reversible and Chemically Programmable Micelle Assembly with DNA Block-Copolymer Amphiphiles (2004)

We report a general solid-phase synthesis strategy for a novel class of DNA block copolymer amphiphiles. The assembled spherical micelle structures exhibit recognition properties defined by their DNA sequences and can be used to build higher-ordered structures through hybridization with materials that possess complementary DNA. This work is an important step toward creating DNA modified structures that can act as phase transfer agents and carriers of nanovesicles.
3-D QSAR Investigations of the Inhibition ofLeishmaniamajorFarnesyl Pyrophosphate Synthase by Bisphosphonates (2003)

We report the activities of 62 bisphosphonates as inhibitors of the Leishmania major mevalonate/isoprene biosynthesis pathway enzyme, farnesyl pyrophosphate synthase. The compounds investigated exhibit activities (IC(50) values) ranging from approximately 100 nM to approximately 80 microM (corresponding to K(i) values as low as 10 nM). The most active compounds were found to be zoledronate (whose single-crystal X-ray structure is reported), pyridinyl-ethane-1-hydroxy-1,1-bisphosphonates or picolyl aminomethylene bisphosphonates. However, N-alicyclic aminomethylene bisphosphonates, such as incadronate (N-cycloheptyl aminomethylene bisphosphonate), as well as aliphatic aminomethylene bisphosphonates containing short (n = 4, 5) alkyl chains, were also active, with IC(50) values in the 200-1700 nM range (corresponding to K(i) values of approximately 20-170 nM). Bisphosphonates containing longer or multiple (N,N-) alkyl substitutions were inactive, as were aromatic species lacking an o- or m-nitrogen atom in the ring, or possessing multiple halogen substitutions or a p-amino group. To put these observations on a more quantitative structural basis, we used three-dimensional quantitative structure-activity relationship techniques: comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA), to investigate which structural features correlated with high activity. Training set results (N = 62 compounds) yielded good correlations with each technique (R(2) = 0.87 and 0.88, respectively), and were further validated by using a training/test set approach. Test set results (N = 24 compounds) indicated that IC(50) values could be predicted within factors of 2.9 and 2.7 for the CoMFA and CoMSIA methods, respectively. The CoMSIA fields indicated that a positive charge in the bisphosphonate side chain and a hydrophobic feature contributed significantly to activity. Overall, these results are of general interest since they represent the first detailed quantitative structure-activity relationship study of the inhibition of an expressed farnesyl pyrophosphate synthase enzyme by bisphosphonate inhibitors and that the activity of these inhibitors can be predicted within about a factor of 3 by using 3D-QSAR techniques.
Update on Taxanes in the First-Line Treatment of Advanced Non-Small-Cell Lung Cancer (2014)

Based on demonstrated favourable risk-benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability compared with solvent-based paclitaxel-carboplatin in a phase iii trial. This review focuses on the evolution of first-line taxane therapy for advanced nsclc and the new options and advances in taxane therapy that might address unmet needs in advanced nsclc.
Antibacterial 15-kDa protein isoforms (p15s) are members of a novel family of leukocyte proteins. (1993)

We have previously described the isolation and initial characterization of functionally distinct 15-kDa protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind with high affinity to Escherichia coli and modulate the antibacterial actions of other leukocyte proteins on this Gram-negative bacterium. We now report the cloning and sequencing of two distinct cDNAs from a rabbit bone marrow library that encode p15s differing at only 2 residues (His-3, Arg-88 versus Arg-3, Trp-88). Tryptophan-directed chemical cleavage of two isoforms purified from a single rabbit confirms the existence of multiple isoforms with distinct function and primary structure in a single rabbit. The p15 cDNAs encode putative signal sequences and studies of cellular and subcellular localization indicate that the p15s are granule-associated proteins of PMN. Both purified isoforms bind avidly to lipopolysaccharide (LPS), the major component of the Gram-negative bacterial outer membrane. Analysis of the deduced primary structures of the p15s reveals homology to three other leukocyte proteins: CAP-18, an 18-kDa LPS-binding protein from rabbit PMN, pro-indolicidin, a 16-kDa precursor of an antibacterial peptide of bovine PMN, and cathelin, an 11-kDa cysteine protease inhibitor from porcine leukocytes, suggesting the existence of a novel family of leukocyte proteins with LPS-binding, antimicrobial, and protease-inhibitory activities.
High-resolution image reconstruction from a sequence of rotated and translated frames and its application to an infrared imaging system (1998)

Some imaging systems employ detector arrays which are not su‐ciently dense so as to meet the Nyquist criteria during image acquisition. This is particularly true for many staring infrared imagers. Thus, the full resolution afiorded by the optics is not being realized in such a system. This paper presents a technique for estimating a high resolution image, with reduced aliasing, from a sequence of undersampled rotated and translationally shifted frames. Such an image sequence can be obtained if an imager is mounted on a moving platform, such as an aircraft. Several approaches to this type of problem have been proposed in the literature. Here we extend some of this previous work. In particular, we deflne an observation model which incorporates knowledge of the optical system and detector array. The high resolution image estimate is formed by minimizing a new regularized cost function which is based on the observation model. We show that with the proper choice of a tuning parameter, our algorithm exhibits robustness in the presence of noise. We consider both gradient descent and conjugate gradient optimization procedures to minimize the cost function. Detailed experimental results are provided to illustrate the performance of the proposed algorithm using digital video from an infrared imager.
The enzymatic repair of DNA. I. Formation of circular lambda-DNA. (1967)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Fluorophores at the N Terminus of Nascent Chloramphenicol Acetyltransferase Peptides Affect Translation and Movement through the Ribosome (2000)

Structurally different fluorescent probes were covalently attached to methionyl-tRNA(f) and tested for their incorporation into nascent peptides and full-length protein using an Escherichia coli cell-free coupled transcription/translation system. Bovine rhodanese and bacterial chloramphenicol acetyltransferase (CAT) were synthesized using derivatives of cascade yellow, eosin, pyrene, or coumarin attached to [(35)S]Met-tRNA(f). All of the probes tested were incorporated into polypeptides, although less efficiently when compared with formyl-methionine. Eosin, the largest of the fluorophores used with estimated dimensions of 20 x 11 A, caused the largest reduction in product formed. The rate of initiation was reduced with the fluorophore-Met-tRNA(f) compared with fMet-tRNA(f) with pyrene having the least and eosin the biggest effect. Analysis of the nascent polypeptides showed that the modifications at the N terminus affected the rate at which nascent CAT peptides were elongated causing accumulation of peptides of about 4 kDa, possibly by steric hindrance inside the tunnel within the 50 S ribosomal subunit. Fluorescence measurements indicate that the probe at the N terminus of nascent pyrene-CAT peptides is in a relatively hydrophilic environment. This finding is in agreement with recent data showing cross-linking of the N terminus of nascent peptides to nucleotides of the 23 S ribosomal RNA.
Application of a New Mathematical Method for the Estimation of the Mean Surface Area to Calculate the Percolation Threshold of Lobenzarit Dissodium Salt in Controlled Release Matrices (2004)

One of the practical handicaps for the application of the percolation theory to estimate the percolation threshold of drugs in controlled release systems is the fact that the dissolution studies must be carried out so that only one surface of the tablet is exposed to the dissolution medium. The aim of this work is to estimate the percolation threshold of the antiarthritic drug lobenzarit dissodium (LBD) in inert matrices prepared with the excipients Ethocel((R)) 100 and Eudragit((R)) RS-PO (10-75% w/w). Release assays were performed using the paddle method. The whole surface of the tablets was exposed to the dissolution medium. For the first time, a new mathematical method is developed to transform the amount of drug released in amount released per surface area in order to calculate the percolation thershold of LBD. The mathematical method proposed allows to calculate, using a new equation, the evolution of the mean surface area (O((t))). The new method was validated and three novel results were achieved: A constant value of (O((t))) at critical time (theta) in the matrices (O((theta))=1.272 cm(2)); a linear relationship between initial surface area (O((0))) and critical time; and a linear relationship between O((t)) and time. Employing the values of O((t)), it was possible to calculate for the first time, the percolation threshold (p(c1)) for LBD in Ethocel((R)) 100 (p(c1)=0.280+/-0.102) and Eudragit((R)) RS-PO (p(c1)=0.344+/-0.07) matrices.
Optical coherence tomography of porcine coronary arteries in vivo (2000)

A catheter-based OCT system was developed and tested for feasibility of coronary artery imaging in five living swine. In this study, OCT provided high-resolution imaging of coronary vessel wall structure, dissections, and stent deployment.
A low-jitter PLL clock generator for microprocessors with lock range of 340-612 MHz (1999)

A fully integrated, phase-locked loop (PLL) clock generator/phase aligner for the POWER3 microprocessor has been designed using a 2.5-V, 0.40-/spl mu/m digital CMOS6S process. The PLL design supports multiple integer and noninteger frequency multiplication factors for both the processor clock and an L2 cache clock. The fully differential delay-interpolating voltage-controlled oscillator (VCO) is tunable over a frequency range determined by programmable frequency limit settings, enhancing yield and application flexibility. PLL lock range for the maximum VCO frequency range settings is 340-612 MHz. The charge-pump current is programmable for additional control of the PLL loop dynamics. A differential on-chip loop filter with common-mode correction improves noise rejection. Cycle-cycle jitter measurements with the microprocessor actively executing instructions were 10.0 ps rms, 80 ps peak to peak (P-P) measured from the clock tree. Cycle-cycle jitter measured for the processor in a reset state with the clock tree active was 8.4 ps rms, 62 ps P-P. PLL area is 1040/spl times/640 /spl mu/m/sup 2/. Power dissipation is <100 mW.
Circulating lymphocyte populations in Hodgkin's disease after mantle and paraaortic irradiation (1983)

The effect of mantle and paraaortic radiation on peripheral blood lymphocytes was studied in 11 previously untreated patients with early stage Hodgkin's disease using a series of monoclonal antibodies defining immunoregulatory lymphoid cells. Immediately following the completion of radiotherapy, there was a significant reduction in the number of lymphocytes and the percent of circulating T cells. This acute decrease in T cells was due to a marked diminution in the number of inducer T cells, while the fraction of suppressor T cells remained constant. These changes persisted for up to 12 mo and were accompanied by a later increase in the fraction of circulating B lymphocytes and cells bearing surface Ia. It thus appears that mantle and paraaortic radiotherapy causes a relatively selective reduction in the inducer T- cell population. The implications of a change in the ratio of inducer to suppressor T cells is discussed.
Comparative Bioavailability of d-pseudoephedrine from a Conventional d-pseudoephedrine Sulfate Tablet and from a Repeat Action Tablet (1982)

The bioavailability of a single dose of d-pseudoephedrine sulfate administered to male volunteers in repeat action tablet form (60 mg d-pseudoephedrine sulfate in the coat and 60 mg d-pseudoephedrine sulfate in the core) was compared with the bioavailability of an equivalent quantity of the drug given as two 60 mg conventional tablets, one given at 0 hour and the second 6 hours later. There was no significant difference (P less than 0.10) between the conventional tablets and the repeat action tablet formulation in area under the plasma concentration-time curve and the maximum plasma concentration of d-pseudoephedrine. Based on the data, we conclude that the repeat action tablet formulation and the conventional tablet are bioequivalent.
Expression of cyclooxygenase 2 in human malignant melanoma. (2001)

Cyclooxygenase (COX)-2 is an inducible enzyme involved in production of prostaglandins in inflammatory processes. There is now increasing evidence that a constitutive expression of COX-2 plays a role in development and progression of malignant epithelial tumors. In the present study we investigated expression and function of COX-2 in malignant melanoma. Expression of COX-2 was determined by immunohistochemistry in 28 cases of primary skin melanoma and 4 benign nevi. We show that COX-2 was expressed in 26 cases (93%) of melanomas, with a moderate to strong expression in 19 cases (68%). Benign nevi as well as normal epithelium were negative in all cases. A constitutive expression of COX-2 mRNA and protein was found in five melanoma cell lines (A375, MeWo, SK-Mel-13, SK-Mel-28, and IGR-37) by using Northern blot as well as immunoblotting. All melanoma cell lines produced prostaglandin (PG) E2 between 468 and 3500 pg/ml as determined by ELISA. Treatment with NS-398 (50 microM), a specific inhibitor of COX-2, suppressed PGE2 production of all melanoma cell lines by 50-96%. The IC50 for inhibition of PGE2 production by NS-398 was determined as 4 microM, indicating that NS-398 acts via inhibition of the COX-2 isoenzyme. We could show that proliferation of melanoma cell lines was not influenced by treatment with NS-398 in concentrations up to 100 microM. However, NS-398 reduced Matrigel invasion of all five malignant melanoma cell lines by 50-68%. Our results indicate that COX-2 is expressed in malignant melanomas and may be involved in regulation of melanoma invasion. It remains to be investigated whether selective inhibitors of COX-2 might be useful for prevention or treatment of malignant melanoma.
Validity of activity-based devices to estimate sleep. (2010)

The results from this study suggest that a device designed for assessment of physical activity and truncal placement can be used to measure sleep duration as reliably as devices designed for wrist use and sleep wake inference.
Engineered single chain antibody fragments for radioimmunotherapy. (2004)

An ideal molecule to deliver radioimmunotherapy (RIT) would be target specific and have prolonged residence time at high concentrations in the tumour with rapid clearance from normal tissues. It would also be non-immunogenic. These features can be rationally introduced into recombinant antibody-based proteins using antibody engineering techniques. This review focuses on the use of antibody engineering in the design and development of RIT molecules which have single chain Fv (scFv) antibody fragments as building blocks.
Clinical Relevance of Microsatellite Instability in Colorectal Cancer (2010)

Microsatellite instability (MSI) is a clonal change in the number of repeated DNA nucleotide units in microsatellites. It arises in tumors with deficient mismatch repair due to the inactivation of one of the four mismatch repair genes: MSH2, MLH1, MSH6, and PMS2. In order to determine the MSI status of a tumor, microdissection and polymerase chain reaction-based detection strategies are required. For practical purposes, MSI is equivalent to the loss of staining by immunohistochemistry (IHC) of one of the mismatch repair genes since both signify an abnormality in mismatch repair. Of all colorectal cancers (CRCs), 15% to 20% display MSI or abnormal IHC (often referred to as microsatellite instability [MIN] pathway). The remaining 80% to 85% of CRCs are microsatellite stable but most are characterized by chromosomal instability (CIN pathway). Almost all Lynch syndrome tumors have MSI or abnormal IHC and they account for up to one third of all MIN CRCs (3% to 5% of all CRCs). The remaining MIN tumors are sporadic as a result of somatic inactivation of the MLH1 gene caused by methylation of its promoter. Thus, the presence of a MSI/IHC abnormality prompts further investigations to diagnose Lynch syndrome, whereas its absence excludes Lynch syndrome. We recommend screening all CRC tumors for IHC or MSI. MIN tumors have a more favorable outcome than CIN tumors, and fluorouracil-based adjuvant chemotherapy does not improve the outcome of stage II or stage III MIN tumors. More data are needed to determine how best to treat patients with stage II and stage III MIN CRCs.
Automation of micro‐preparation and enzymatic cleavage of gel electrophoretically separated proteins (1995)

To achieve high throughput, protein microcharacterization sample preparation must be automated. We describe a cartesian robot capable of processing 32 protein samples in parallel. The system is based on specially designed flow-through reactors for contamination-free reagent delivery and removal. Washing of excised gel pieces, reduction and alkylation, proteolytic cleavage and peptide extraction are performed in these reactors. Compatibility of the system with HPLC peptide separation and Edman degradation as well as with laser desorption mass spectrometry of the unseparated mixture is demonstrated. This is the first report describing automated preparation and processing of multiple protein samples.
Lymphoma of the Skin (2002)

This chapter describes the various ways in which the non-Hodgkin's lymphomas can involve the skin, how these diseases should be assessed, standard treatments available in 2002, and new directions in research. The goal of the session is to succinctly review recent developments in lymphoma classification and treatment as they apply to the unique aspects of lymphoma when manifest in the skin. In Section I, Dr. Eric Hsi reviews the special characteristics of the lymphomas seen when they proliferate in the skin and the application of the new World Health Organization classification system to the cutaneous lymphomas, emphasizing the unique challenges of recognizing and correctly classifying these diseases. He summarizes the evidence in favor of including the skin lymphomas in the overall lymphoma classification scheme and concludes with a practical description of the specific skin lymphoma entities. In Section II, Dr. Joseph Connors describes the current optimal treatment of the B-cell lymphomas when they present in or metastasize to the skin. Building on the classification scheme described by Dr. Hsi, Dr. Connors outlines a treatment approach based on current understanding of pathophysiology of these diseases and application of each of the effective modalities available for cutaneous lymphoma including radiation, chemotherapy, and immunotherapy. In Section III, Dr. Francine Foss concludes the session with a discussion of the different T-cell lymphomas that start in or spread to the skin concentrating on mycosis fungoides, cutaneous anaplastic large cell lymphoma and peripheral T-cell lymphoma. She includes comments on the newer anti-T-cell chemo- and immuno-therapeutics focusing on agents and techniques specific for cutaneous T-cell lymphomas.