gebhart/patrepeval huggingface dataset:
Surface interpolation with radial basis functions for medical imaging (1997)

Radial basis functions are presented as a practical solution to the problem of interpolating incomplete surfaces derived from three-dimensional (3-D) medical graphics. The specific application considered is the design of cranial implants for the repair of defects, usually holes, in the skull. Radial basis functions impose few restrictions on the geometry of the interpolation centers and are suited to problems where the interpolation centers do not form a regular grid. However, their high computational requirements have previously limited their use to problems where the number of interpolation centers is small (< 300). Recently developed fast evaluation techniques have overcome these limitations and made radial basis interpolation a practical approach for larger data sets. In this paper radial basis functions are fitted to depth-maps of the skull's surface, obtained from X-ray computed tomography (CT) data using ray-tracing techniques. They are used to smoothly interpolate the surface of the skull across defect regions. The resulting mathematical description of the skull's surface can be evaluated at any desired resolution to be rendered on a graphics workstation or to generate instructions for operating a computer numerically controlled (CNC) mill.
Disease-modifying treatments for Alzheimer’s disease (2011)

The first drugs developed for Alzheimer's disease (AD), acetylcholinesterase inhibitors (AChEI), increase acetylcholine levels, previously demonstrated to be reduced in AD. To date, four AChEI are approved for the treatment of mild-to-moderate AD. A further therapeutic option available for moderate-to-severe AD is memantine. These treatments are symptomatic, whereas drugs under development are intended to modify the pathological steps leading to AD, thus acting on the evolution of the disease. For this reason they are have been termed 'disease-modifying' drugs. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid beta (Aβ) plaques and of intracellular neurofibrillary tangles, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review, new perspectives will be discussed. In particular, several approaches will be described, including interference with Aβ deposition by anti-Aβ aggregation agents, vaccination, γ-secretase inhibitors or selective Aβ-lowering agents; interference with tau deposition by methylthioninium chloride; and reduction of inflammation and oxidative damage.
Plasma concentrations and analgesic effect of EMLA (lidocaine/prilocaine) cream for the cleansing of leg ulcers. (1990)

Plasma concentrations of lidocaine and prilocaine were assessed in 8 patients after the application of 8-10 g EMLA 2% cream for 60 min to leg ulcers measuring 31-80 cm2. Maximum individual plasma concentrations were 205 ng/ml for lidocaine and 79 ng/ml for prilocaine, which is twenty times lower than those associated with toxicity. The analgesic effect of EMLA 2% and 5% cream for the surgical cleansing of leg ulcers was compared in a double-blind, four-period, cross-over study in 10 patients. The ulcer was covered with a thick layer of cream for 30 min before four consecutive debridements 1-4 days apart. While the 2% and 5% creams had similar analgesic effects post-cleansing pain tended to be more frequent with the 2% cream.
Doubly clamped Cope systems (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDoubly clamped Cope systemsFritz Voegtle, Norbert Eisen, Sybille Franken, Petra Buellesbach, and Heinrich PuffCite this: J. Org. Chem. 1987, 52, 25, 5560–5564Publication Date (Print):December 1, 1987Publication History Published online1 May 2002Published inissue 1 December 1987https://pubs.acs.org/doi/10.1021/jo00234a010https://doi.org/10.1021/jo00234a010research-articleACS PublicationsRequest reuse permissionsArticle Views376Altmetric-Citations16LEARN 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
CONSIDERATIONS IN THE PREPARATION AND USE OF POLIOMYELITIS VIRUS VACCINE (1955)

In assessing the state of knowledge of any subject at a particular point in time, it is as important to define what is not known as it is to appreciate what is known. It is for this reason that I would like to discuss some of the problems still before us, with respect to vaccination against poliomyelitis, as well as to review knowledge gained in the course of recent work. "Can durable immunity be induced by a noninfectious poliomyelitis vaccine?" is one of the principal questions still to be answered. Since the ultimate answer to this question cannot be obtained until time has passed, we must content ourselves only with an examination of facts now known, from which we can make some tentative interpretations from the trends observed. The hypothesis that the presence of neutralizing antibody in the circulating blood is an effective barrier in reducing the likelihood of paralysis
[Renal angiolipoma associated with bilateral double ureter. A clinical case]. (1997)

Renal angiomyolipoma is a rare renal tumor usually associated with tuberous sclerosis, a syndrome characterized by adenoma sebaceum, mental insufficiency and epilepsy. The authors present a rare case of renal angio-myolipoma associated with bilateral double ureter, in a young male patient not affected by tuberous sclerosis. Histologically, the angiomyolipoma is defined by the presence of smooth muscular cells, new formed vessels and fat. Clinical diagnosis requires the utilization of various imaging techniques, like intravenous pyelogram, ultrasonic scan, CT scan, and FNA (Fine Needle Aspiration). In the histopathologic diagnosis of angiomyolipoma the use of immunohistochemical techniques with different antibodies has been helpful, for the necessity to differentiate angiomyolipoma from other epithelial tumors, as renal cell carcinoma and sarcomatous neoplasms. As for as treatment is concerned, the indication for surgery is still maintained by two factors not affected by these diagnostic improvements: tumor size and presence of symptoms. Tumor size is an important predictive growth factor of the tumor. In the absence of symptoms a close follow-up with ultrasonographic scan may be indicated, keeping in mind the possible presence of a synchronous renal cell carcinoma. Hemorrhage can be a fatal complication of renal angiomyolipoma, requiring emergency surgery or embolization.
Biology of the Transition of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma (1998)

BACKGROUND: Approximately 25% of patients with monoclonal gammopathy of undetermined significance (MGUS) eventually develop multiple myeloma (MM) or a related plasma cell disorder that is universally fatal. In this report, we examine the changes that occur in the clonal plasma cell that are likely to be important in the progression of MGUS to active myeloma. METHODS: Studies that investigate the mechanisms involved in the multistep pathogenesis of monoclonal gammopathies are reviewed. Cytokines such as IL-6 and IL-1-beta, adhesion molecules, viruses, and oncogenes including ras, bcl-2, Rb, and p53 are discussed. RESULTS: IL-1-beta is produced by plasma cells from virtually all MM patients but is undetectable in most MGUS patients. IL-1-beta has potent osteoclast activating factor activity, can increase the expression of adhesion molecules, and can induce paracrine IL-6 production. The increased production of adhesion molecules could explain why myeloma cells are found predominantly in the bone marrow. Subsequently, these "fixed" monoclonal plasma cells could now stimulate osteoclasts through the production of IL-1-beta and paracrine generation of IL-6 resulting in osteolytic disease. With continued progression of the myeloma, the monoclonal plasma cells may later acquire the ability to produce IL-6 in an autocrine fashion that will be manifested clinically by an elevated labeling index. CONCLUSIONS: A better understanding of the progression of MGUS to myeloma may lead to novel therapeutic strategies to prevent the development of MM.
The discovery of S/GSK1265744: a carbamoyl pyridone HIV‐1 integrase inhibitor (2012)

Background HIV‐1 integrase is a virally encoded enzyme essential for lentiviral replication. Assiduous medicinal chemistry efforts culminated in the discovery of raltegravir, the first marketed HIV‐1 integrase inhibitor (INI). However, there is significant opportunity for improvement including overall dose burden, dosing interval and potency against resistant viruses. Our molecular design approach used a two‐metal binding pharmacophore strategy and succeeded in identification of carbamoyl pyridone HIV‐1 INIs. This enriched core scaffold has abundant structural features expanding the opportunity to control drug properties, leading to the discovery of S/GSK1265744. Methods The carbamoyl pyridone scaffold was derivatized and evaluated for antiviral activity against wild‐type virus (±HSA) along with key INI‐resistant mutants. Animal pharmacokinetic profiles including a key measure of the trough drug concentration over protein‐adjusted antiviral potency (C24/PAIC 50 ) along with in vitro DMPK properties, were used along with the virological data for compound selection. Results The carbamoyl pyridone series inhibitors exhibited potent antiviral profiles with promising DMPK properties. S/GSK1265744 demonstrated good coverage of C24 over PAIC 50 predicting low mg unboosted once daily dosing, now validated in phase 2 clinical studies. These preclinical data along with a long human T 1/2 of ~30 hours in oral tablet study supports S/GSK1265744 as a long acting parenteral agent for once‐monthly or less frequent dosing. Conclusions A medicinal chemistry approach utilizing key viral mutants in combination with C24/PAIC 50 has allowed for discovery of S/GSK1265744. This agent is currently in phase 2 development evaluating a novel, long‐acting parenteral route of administration and may enable new approaches to HIV therapy and prevention.
Quantum dot/peptide-MHC biosensors reveal strong CD8-dependent cooperation between self and viral antigens that augment the T cell response (2006)

Cytotoxic T lymphocytes (CTL) can respond to a few viral peptide-MHC-I (pMHC-I) complexes among a myriad of virus-unrelated endogenous self pMHC-I complexes displayed on virus-infected cells. To elucidate the molecular recognition events on live CTL, we have utilized a self-assembled biosensor composed of semiconductor nanocrystals, quantum dots, carrying a controlled number of virus-derived (cognate) and other (noncognate) pMHC-I complexes and examined their recognition by antigen-specific T cell receptor (TCR) on anti-virus CD8(+) T cells. The unique architecture of nanoscale quantum dot/pMHC-I conjugates revealed that unexpectedly strong multivalent CD8-MHC-I interactions underlie the cooperative contribution of noncognate pMHC-I to the recognition of cognate pMHC-I by TCR to augment T cell responses. The cooperative, CD8-dependent spread of signal from a few productively engaged TCR to many other TCR can explain the remarkable ability of CTL to respond to virus-infected cells that present few cognate pMHC-I complexes.
Prevention of Allogeneic Bone Marrow Graft Rejection by H-2 Transgene in Donor Mice (1989)

Rejection of bone marrow grafts in irradiated mice is mediated by natural killer (NK) cells and is controlled by genes linked to the major histocompatibility complex (MHC). It has, however, not been possible to identify the genes or their products. An MHC class I (Dd) transgene introduced in C57BL donors prevented the rejection of their bone marrow by NK cells in irradiated allogeneic and F1 hybrid mice expressing the Dd gene. Conversely, H-2Dd transgenic C57BL recipients acquired the ability to reject bone marrow from C57BL donors but not from H-2Dd transgenic C57BL donors. These results provide formal evidence that NK cells are part of a system capable of rejecting cells because they lack normal genes of the host type, in contrast to T cells, which recognize cells that contain abnormal or novel sequences of non-host type.
Detection of and Discrimination between Gram-Positive and Gram-Negative Bacteria in Intraocular Samples by Using Nested PCR (2000)

A nested PCR protocol has been developed for the detection of and discrimination between 14 species of gram-positive and -negative bacteria in samples of ocular fluids. First-round PCR with pan-bacterial oligonucleotide primers, based on conserved sequences of the 16S ribosomal gene, was followed by a gram-negative-organism-specific PCR, which resulted in a single 985-bp amplification product, and a multiplex PCR which resulted in two PCR products: a 1,025 bp amplicon (all bacteria) and a 355 bp amplicon (gram-positive bacteria only). All products were detected by gel electrophoresis. The sensitivity of the assay was between 10 fg and 1 pg of bacterial DNA, depending on the species tested, equivalent to between 24 and 4 live bacteria spiked in water. The identification was complete in 3.5 h. The molecular techniques were subsequently applied to four samples of intraocular fluid, (three vitreous and one aqueous) from three patients with clinical signs of bacterial endophthalmitis (test samples) and two samples of vitreous from a patient with chronic intraocular inflammation (control samples). In all culture-positive samples (two of three vitreous and one of one aqueous), a complete concordance was observed between molecular methods and culture results. PCR correctly identified the gram stain classification of the organisms. The bacterial etiology was also identified in a culture-negative patient with clinical history and signs highly suggestive of bacterial endophthalmitis. Furthermore, control samples from a patient with chronic intraocular inflammation remained PCR negative. In summary, this protocol has demonstrated potential as a rapid diagnostic test in confirming the diagnosis of infection and also determining the Gram status of bacteria with high specificity and sensitivity.
Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis (2010)

Taken together, our results showed a novel and efficient strategy to control experimental tuberculosis, besides opening novel perspectives for the use of mRNA in vaccines against infectious diseases and clarifying the mechanisms involved in the disease protection we noticed as well.
A Randomized Phase II Trial of the Antiangiogenic Agent SU5416 in Hormone-Refractory Prostate Cancer (2004)

No disease modifying effects of SU5416 were detectable in this small study. Modest toxicity, an inconvenient administration schedule, and availability of other VEGFR-targeted agents support the decision to halt further evaluation of SU5416 in prostate cancer.
An osmotic model for the fusion of biological membranes (1986)

A molecular model for fusion-fission reactions in membranes is proposed that is based on data from studies on artificially induced cell fusion and on the behaviour of phospholipid bilayers: it is put forward as a framework for further investigations into this fundamental property of biological systems.
Alterations in Lipoxygenase and Cyclooxygenase-2 Catalytic Activity and mRNA Expression in Prostate Carcinoma (2001)

Recent studies in prostate tissues and especially cell lines have suggested roles for arachidonic acid (AA) metabolizing enzymes in prostate adenocarcinoma (Pca) development or progression. The goal of this study was to more fully characterize lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) gene expression and AA metabolism in benign and malignant prostate using snap-frozen tissues obtained intraoperatively and mRNA analyses and enzyme assays. Formation of 15-hydroxyeicosatetraenoic acid (15-HETE) was detected in 23/29 benign samples and 15-LOX-2 mRNA was detected in 21/25 benign samples. In pairs of pure benign and Pca from the same patients, 15-HETE production and 15-LOX-2 mRNA were reduced in Pca versus benign in 9/14 (P=.04) and 14/17 (P=.002), respectively. Under the same conditions, neither 5-HETE nor 12-HETE formation was detectable in 29 benign and 24 tumor samples; with a more sensitive assay, traces were detected in some samples, but there was no clear association with tumor tissue. COX-2 mRNA was detected by nuclease protection assay in 7/16 benign samples and 5/16 tumors. In benign and tumor pairs from 10 patients, COX-2 was higher in tumor versus benign in only 2, with similar results by in situ hybridization. Paraffin immunoperoxidase for COX-2 was performed in whole mount sections from 87 additional radical prostatectomy specimens, with strong expression in ejaculatory duct as a positive control and corroboration with in situ hybridization. No immunostaining was detected in benign prostate or tumor in 45% of cases. Greater immunostaining in tumor versus benign was present in only 17% of cases, and correlated with high tumor grade (Gleason score 8 and 9 vs. 5 to 7). In conclusion, reduced 15-LOX-2 expression and 15-HETE formation is the most characteristic alteration of AA metabolism in Pca. Increased 12-HETE and 5-HETE formation in Pca were not discernible. Increased COX-2 expression is not a typical abnormality in Pca in general, but occurs in high-grade tumors.
Meniscal repair using engineered tissue (2001)

In this study, devitalized meniscal tissue pre-seeded with viable cultured chondrocytes was used to repair a bucket-handle incision in meniscal tissue transplanted to nude mice. Lamb knee menisci were devitalized by cyclic freezing and thawing. Chips measuring four by two by one-half millimeters were cut from this devitalized tissue to serve as scaffolds. These chips were then cultured either with or without viable allogeneic lamb chondrocytes. From the inner third of the devitalized meniscal tissue, rectangles were also cut approximately 8 x 6 mm. A 4 mm bucket-handle type incision was made in these blocks. The previously prepared chips either with (experimental group) or without viable chondrocytes (control group) were positioned into the incisions and secured with suture. Further control groups included blocks of devitalized menisci with incisions into which no chips were positioned and either closed with suture or left open with no suture. Specimens were transplanted to subcutaneous pouches of nude mice for 14 weeks. After 14 weeks, seven of eight experimental specimens (chips with viable chondrocytes) demonstrated bridging of the incision assessed by gross inspection and manual distraction. All the control groups were markedly different from the experimental group in that the incision remained grossly visible. Histological analysis was consistent with the differences apparent at the gross level. Only the experimental specimens (chips with viable chondrocytes) with gross bridging demonstrated obliteration of the interface between incision and scaffold. None of the control specimens revealed any cells or tissue filling the incision. Tissue engineering using scaffolds and viable cells may have an application in meniscal repair in vivo.
Differential Tyrosine Phosphorylation of N-Methyl-D-aspartate Receptor Subunits (1995)

Protein-tyrosine phosphorylation has recently been suggested to play an important role in synaptic transmission at the neuromuscular junction. The role of tyrosine phosphorylation in the modulation of synaptic function in the central nervous system, however, is not clear. In this study, immunocytochemical staining with an anti-phosphotyrosine antibody demonstrates that there are high levels of phosphotyrosine, which co-localizes with glutamate receptors at excitatory synapses on cultured hippocampal neurons. In addition, the tyrosine phosphorylation of various subtypes of glutamate receptors were examined using subunit-specific antibodies. Glutamate receptors are the major excitatory neurotransmitter receptors in the central nervous system and are classified into three major classes: alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate, kainate, and N-methyl-D-aspartate (NMDA) receptors, based on their electrophysiological and pharmacological properties. NMDA receptors play a central role in synaptic plasticity, synaptogenesis, and excitotoxicity and are thought to be heteromeric complexes of the two types of subunits: NR1 and NR2(A-D) subunits. Immunoaffinity chromatography of detergent extracts of rat synaptic plasma membranes on anti-phosphotyrosine antibody-agarose showed that the NR2A and NR2B subunits but not the NR1 subunit are tyrosine-phosphorylated. Conversely, immunoprecipitation of the NR1, NR2A, and NR2B subunits with subunit specific antibodies followed by immunoblotting with anti-phosphotyrosine antibodies confirmed that the NR2A and NR2B subunits but not the NR1 subunit were phosphorylated on tyrosine residues. No tyrosine phosphorylation of the AMPA (GluR1-4) and kainate (GluR6/7, KA2) receptor subunits was detected. It was estimated that 2.1 +/- 1.3% of the NR2A subunits and 3.6 +/- 2.4% of the NR2B subunits were tyrosine-phosphorylated in vivo. In addition, endogenous protein-tyrosine kinases in synaptic plasma membranes phosphorylated the NR2A subunit in vitro, increasing its phosphorylation 6-8-fold but did not phosphorylate NR1 or NR2B. These studies demonstrate that NMDA receptor subunits are differentially tyrosine-phosphorylated and suggest that tyrosine phosphorylation of the NR2 subunits may be important for regulating NMDA receptor function.
Cognitive deficits in depression: Possible implications for functional neuropathology (2001)

Mnemonic and executive deficits do no appear to be epiphenomena of depressive disorder. A focus on the interactions between motivation, affect and cognitive function may allow greater understanding of the interplay between key aspects of the dorsal and ventral aspects of the prefrontal cortex in depression.
Tumor‐associated antigen synthesis synthesis of the gal‐α‐(1→3)‐gal‐β‐(1→4)‐GlcNAc epitope a specific determinant for metastatic progression? (1991)

Abstract A versatile synthesis of the Gal‐α‐(1→3)‐Gal‐β‐(1→4)‐GlcNAc epitope coupled to an alkyl spacer molecule could be developed. The important building block 3′‐allyl‐ D ‐lactal 6 was prepared in high yield by the action of dibutyltin oxide and allyl bromide on D ‐lactal and converted in several steps into the lactosamine derivative 13 with free 3′‐OH group. Stereoselective glycosidation with the β‐trichloroacetimidate of benzylated D ‐galactose 18 led to the trisaccharide in high yield. Activation of the protected Gal‐α‐(1→3)‐Gal‐β‐(1→4)‐GlcNAc derivative 21 by desilylation and trichloroacetimidate formation followed by glycosidation with ethyl 9‐hydroxynonanoate furnished the spacer‐bound trisaccharide hapten 24 in excellent yield after simple two‐step deprotection. The trisaccharide hapten 24 can easily be used as immunogen after coupling to an immunogenic carrier.