gebhart/patrepeval huggingface dataset:
Ki‐67 labeling in postmitotic cells defines different Ki‐67 pathways within the 2c compartment (1991)

Simultaneous quantification of DNA and Ki-67 proliferation-associated antigen was performed using fluorescence image cytometry. In the MCF-7 cell line, the Ki-67 antigen content increases during the cell cycle, and its intranuclear distribution pattern varies. Quantitative evolution of Ki-67 content as a function of nuclear area makes it possible to define several pathways followed by cells going through the 2c compartment. 1) In some cells, the amount of Ki-67 antigen remains constant during G1 (Ki-67 stable pathway), and a characteristic speckled pattern can be observed. 2) In the larger fraction of cells analyzed, there is a postmitotic decrease in the Ki-67 (Ki-67 decrease pathway) content. In this pathway, labeling is located in the nucleoplasm in small nuclei, is located in nucleoli in intermediate-sized nuclei, and is absent from larger nuclei (G0). A progressive increase in Ki-67 content (Ki-67 increase pathway) was observed from intermediate-sized nuclei to S phase nuclei. From these results, we hypothesize that the Ki-67 stable pathway is the G1 phase of newly formed cells going directly to S phase in local optimal conditions of growth and that Ki-67 decrease pathway and Ki-67 increase pathway correspond to cells whose progression to S phase is regulated by extracellular factors.
Advances and challenges in the management of essential thrombocythemia (2015)

The new World Health Organization (WHO) diagnostic criteria for essential thrombocythemia (ET) issued in 2008 made an important distinction between true ET and early myelofibrosis (MF), which has helped to identify a more homogenous population for the diagnosis with longer survival and much less transformation to overt MF. The recent finding of a new mutation (CALR), which is mutually exclusive with JAK2 and MPL mutations, adds to the characterization of ET patients, since there are important phenotypic differences between the mutation types. CALR patients are younger, have lower white blood cell counts (WBC) and a lower thrombosis incidence. A growing field of interest is the state of hypercoagulation due to dysfunction of hemostatic systems, cell-cell interaction and hereditary prothrombotic traits. Activation of platelets, WBC and endothelial cells has been found, making the whole intravascular milieu prothrombotic. Several risk score models, based on retrospective studies, have been developed lately, distinguishing patient groups with graded risk for complications and death. Even if these may be helpful in evaluating patients, they have not been validated in prospective studies and there are not enough data to support their use as a basis for treatment algorithms. The traditional risk factors age, previous thrombosis and platelets >1500 × 10(9)/l are still recommended for the distinction between high risk and low risk ET and the decision to give cytoreductive therapy. However, cardiovascular (CV) risk factors add to thrombosis risk and should be considered both for specific treatment in any risk group and for upgrading low risk patients with high CV risk to an intermediary group where active therapy with aspirin and cytoreduction may be considered. First-line cytoreductive therapy differs with age; in younger patients interferon (IFN) or anagrelide are preferable, in older patients hydroxycarbamide (HC). Second-line therapy for younger patients is HC, for older patients IFN or anagrelide (ANA). JAK2 inhibitors may be suitable in rare cases with symptoms not responding to other therapy.
Catastrophe, chaos and Alzheimer's disease. The F E Williams Lecture. (1996)

A model can be developed for familial APP mutation Alzheimer's disease to explain why a patient who is cognitively normal until middle age experiences a catastrophic amyloid deposition, which is to some extent mirrored in the clinical deterioration due to a subtle shift in A beta metabolism. However, the analysis of young onset dementia hardly constitutes the study of 'the suffering and infirmities of old age' which F E Williams' bequest is intended to promote. It remains to be seen whether the models relevant to APP mutation FAD can be applied to Alzheimer's disease of old age, or indeed other degenerative diseases of later life. Such models, however, do provide an alternative to the view that Alzheimer's disease is an incremental process virtually indistinguishable from old age itself. With an incremental linear process, treatment is akin to a war of attention. By contrast, with a catastrophic process the difference between a normal elderly person and a patient with incipient Alzheimer's disease at the start may be minimal, perhaps only a few molecules of extended A beta peptide, but they diverge very rapidly. If treatment can be directed at the metabolic events at the onset then there is a real opportunity for optimism. If ultimately successful, prevention rather than delay becomes a realistic goal, echoing Duc de La Rochefoucauld's desire 'to die as young as possible as late as possible'.
A phase II trial of taxol in metastatic melanoma (1990)

Taxol is an investigational new drug which is currently undergoing Phase II evaluation in various tumors. It is a plant alkaloid extracted from the western Yew, Taxus brevifolia. In this study, patients with metastatic melanoma who were previously untreated, received Taxol at a starting dose of 250 mg/m2 delivered as a continuous intravenous (IV) infusion over 24 hours, at 3-week intervals. All patients were premedicated with oral dexamethasone and IV diphenhydramine hydrochloride as prophylaxis against allergic reactions. Three of 25 patients had a partial response (PR) for a response rate of 12% (CI, 3%-31%). In addition four patients had objective regression of tumor that failed to qualify for a PR but these responses were as durable, lasting 6 to 17 months. No patient experienced acute allergic reactions. The major toxicity of Taxol was neutropenia requiring dose reduction to 200 mg/m2 in a majority of the patients. Our data confirm that Taxol has definite although limited activity against metastatic melanoma.
UV--Visible Absorption Derivatization in Liquid Chromatography (1979)

Journal Article UV—Visible Absorption Derivatization in Liquid Chromatography Get access Thomas Jupille Thomas Jupille Bio-Rad Laboratories, 2200 Wright Avenue, Richmond, California 94804 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Chromatographic Science, Volume 17, Issue 3, March 1979, Pages 160–167, https://doi.org/10.1093/chromsci/17.3.160 Published: 01 March 1979
Round-Trip Packet Loss Metrics (2012)

Many user applications (and the transport protocols that make them
possible) require two-way communications. To assess this capability,
and to achieve test system simplicity, round-trip loss measurements
are frequently conducted in practice. The Two-Way Active Measurement
Protocol specified in RFC 5357 establishes a round-trip loss
measurement capability for the Internet. However, there is currently
no round-trip packet loss metric specified according to the RFC 2330
framework. This memo adds round-trip loss to the set of IP
Performance Metrics (IPPM). [STANDARDS-TRACK]
HLA‐DR/Dw MATCHING BY PCR FINGERPRINTING: THE ORIGIN OF PCR FINGERPRINTS AND FURTHER APPLICATIONS (1991)

Polymerase chain reaction (PCR) fingerprinting, a new method for the rapid matching of HLA-Dr/Dw allotypes, involves the visual comparison of polymorphic HLA-DRB gene second exon PCR products, resolved in non-denaturing polyacrylamide gels (Bidwell & Hui, 1990). We show here that the satellite DNA bands within PCR fingerprints originate by heteroduplex formation between heterologous DNAs co-amplified by a common PCR primer set. We also present two further applications of the technique which permit discrimination between unrelated HLA-DR/Dw allotypes with similar PCR fingerprints.
Cloning and expression of a human kinesin heavy chain gene: interaction of the COOH-terminal domain with cytoplasmic microtubules in transfected CV-1 cells (1992)

To understand the interactions between the microtubule-based motor protein kinesin and intracellular components, we have expressed the kinesin heavy chain and its different domains in CV-1 monkey kidney epithelial cells and examined their distributions by immunofluorescence microscopy. For this study, we cloned and sequenced cDNAs encoding a kinesin heavy chain from a human placental library. The human kinesin heavy chain exhibits a high level of sequence identity to the previously cloned invertebrate kinesin heavy chains; homologies between the COOH-terminal domain of human and invertebrate kinesins and the nonmotor domain of the Aspergillus kinesin-like protein bimC were also found. The gene encoding the human kinesin heavy chain also contains a small upstream open reading frame in a G-C rich 5' untranslated region, features that are associated with translational regulation in certain mRNAs. After transient expression in CV-1 cells, the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules but not vimentin intermediate filaments. Altering the number and distribution of microtubules with taxol or nocodazole produced corresponding changes in the localization of the expressed kinesin heavy chain. The expressed NH2-terminal motor and the COOH-terminal tail domains, but not the alpha-helical coiled coil rod domain, also colocalized with microtubules. The finding that both the kinesin motor and tail domains can interact with cytoplasmic microtubules raises the possibility that kinesin could crossbridge and induce sliding between microtubules under certain circumstances.
Binding of Ribosomes to Linear and Circular Forms of the 5′‐Terminal Leader Fragment of Tobacco‐Mosaic‐Virus RNA (1981)

The sequence of the 5'-terminal leader fragment preceding the AUG codon in the RNA of tobacco mosaic virus (TMV), tomato strain, SPS isolate, has been determined. This RNA, similarly to the RNAs of the U1 and Dahlemense strains of TMV [Kukla et al. (1979) Eur. J. Biochem. 98, 61--66] has the 7-methylguanosine(5')triphospho(5')guanosine cap separated from the initiation codon by a long stretch of nucleotides devoid of guanosine residues. The RNase-T1-resistant 73-nucleotide-long leader fragment of TMV RNA from the SPS isolate was assayed for its ability to interact with eukaryotic and prokaryotic ribosomes. The linear fragment, labelled either at its 5' or 3' end, efficiently formed disome initiation complexes when incubated with wheat-germ protein-synthesis extract. In contrast to its linear counterpart, the circular covalently closed RNA leader fragment, obtained in a reaction catalysed by T4 RNA ligase, was unable to interact with wheat germ ribosomes. Both kinds of leader fragment bound equally well to Escherichia coli 70-S ribosomes. The results offer further support to the notion that in eukaryotic initiation the free 5' end (either capped or uncapped) is required for mRNA interaction with ribosomes. Furthermore, they suggest that both ribosomes found in disome initiation complexes with the TMV RNA leader fragment enter the mRNA sequentially via the free 5' terminus.
Staphylococcus aureus Bacteriophages Mediating the Simultaneous Lysogenic Conversion of  -Lysin, Staphylokinase and Enterotoxin A: Molecular Mechanism of Triple Conversion (1989)

A new group of serotype F bacteriophages of Staphylococcus aureus has been found which mediates the simultaneous triple-lysogenic conversion of enterotoxin A, staphylokinase and beta-lysin. The phages were recovered fro methicillin-resistant strains of S. aureus isolated in Irish hospitals between 1971 and 1988 and from strain PS42-D, which has been used as the propagating strain for the S. aureus typing phage 42D since before 1965. The molecular mechanism of triple conversion mediated by three of these phages was determined by molecular cloning, restriction endonuclease site mapping and hybridization analysis, and compared with the mechanism of beta-lysin and staphylokinase conversion mediated by the serotype F, double-converting phase phi 13. THe genetic determinants mediating expression of enterotoxin A (entA) and staphylokinase (sak) were cloned from the DNA of the triple-converting phage and expression of the cloned determinants detected in Escherichia coli and S. aureus. The entA and sak determinants were closely linked in the phage DNA adjacent to the phage attachment site (attP) in each case and furthermore, the sak determinant of phage phi 13 was also located near its attP. The restriction maps of the entA-, sak- and attP-containing DNA regions of the three triple-converting phages were very similar to each other and to the corresponding sak- and attP- containing DNA region of phage phi 13. Hybridization analysis using a cloned beta-lysin determinant (hlb) and cloned attP-containing DNA fragments as probes demonstrated that beta-lysin conversion mediated by the triple-converting phages and phage phi 13 was caused by insertional inactivation of the chromosomally encoded hlb determinant by orientation-specific integration of phage DNA following lysogenization.
Sleep‐stage sequencing of sleep‐onset REM periods in MSLT predicts treatment response in patients with narcolepsy (2015)

Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first-line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep-stage sequencing of sleep-onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5-year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep-stage sequencing of sleep-onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy-five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow-up of 2.37 ± 1.35 years. Ninety-seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow-up. Twenty-nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep-onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep-stage sequence in all sleep-onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep-stage sequence analysis of sleep-onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2.
Internalization and recycling of the C5a anaphylatoxin receptor: evidence that the agonist-mediated internalization is modulated by phosphorylation of the C-terminal domain (1997)

The C5a anaphylatoxin receptor is a member of the G protein-coupled receptor family involved in chemoattraction and activation of myeloid cells, as well as in host defence against infection by Pseudomonas aeruginosa. Upon challenge by C5a, the C5a receptor undergoes a rapid phosphorylation on serine residues in the carboxyl-terminal region. In this study, we used cells stably transfected with either the wild-type C5a receptor, or mutants affected in their capacity to be phosphorylated, to examine the role played by phosphorylation in the intracellular trafficking of the C5a receptor. Upon agonist binding, the wild-type receptor was rapidly internalized into endosomes that cluster near the nucleus after 10 minutes. Internalization of a non-phosphorylable mutant was severely impaired relative to wild-type receptor, whereas a mutant phos-phorylated on serine 327 and/or serine 338, showed a rate of internalization intermediate between that of wild-type receptor and that of the non-phosphorylable mutant. Under continuous exposure to C5a and in the absence of protein synthesis, the C5a receptor was maintained in a highly phosphorylated state but was not degraded. Confocal microscopy and ligand-binding studies indicated that internalized receptors were recycled to the plasma membrane. During this process, receptors were dephosphorylated with kinetics that correlated with the kinetics of receptor recovery on the cell surface. Altogether, our data suggest that phosphorylation plays a key role in the intracellular trafficking of the C5a receptor. Phosphoryl-ated receptors might be recognized by an adaptor protein that interacts with the endocytic machinery.
Efficient techniques for the capacitance extraction of chip-scale VLSI interconnects using floating random walk algorithm (2014)

To enable the capacitance extraction of chip-scale large VLSI layout using the floating random walk (FRW) algorithm, two techniques are proposed. The first one is a virtual Gaussian surface sampling technique. It makes efficient random sampling on the Gaussian surface for complex nets with vias, and optimizes the sampling scheme to reduce the time of random walk. The other one is a parallelized, improved construction approach for Octree based space management structure. It can be over 5000X faster than the existing approach and provides same convenience to the FRW procedure. Numerical experiments on large cases with up to half million conductors validate the proposed techniques, and demonstrate a fast FRW solver for chip-scale extraction task.
Overcoming the Insolubility of Carbon Nanotubes Through High Degrees of Sidewall Functionalization (2004)

The use of carbon nanotubes in materials applications has been slowed due to nanotube insolubility and their incompatibility with polymers. We recently developed two protocols to overcome the insoluble nature of carbon nanotubes by affixing large amounts of addends to the nanotube sidewalls. Both processes involve reactions with aryl diazonium species. First, solvent-free functionalization techniques remove the need for any solvent during the functionalization step. This delivers functionalized carbon nanotubes with increased solubility in organic solvents and processibility in polymeric blends. Additionally, the solvent-free functionalization process can be done on large scales, thereby paving the way for use in bulk applications such as in structural materials development. The second methodology involves the functionalization of carbon nanotubes that are first dispersed as individual tubes in surfactants within aqueous media. The functionalization then ensues to afford heavily functionalized nanotubes that do not re-rope. They remain as individuals in organic solvents giving enormous increases in solubility. This protocol yields the highest degree of functionalization we have obtained thus far-up to one in nine carbon atoms on the nanotube has an organic addend. The proper characterization and solubility determinations on nanotubes are critical; therefore, this topic is discussed in detail.
Polymer-based microfluidic chip for rapid and efficient immunomagnetic capture and release of Listeria monocytogenes (2015)

Infections caused by foodborne pathogens such as Listeria monocytogenes pose a threat to public health while timely detection is challenging due to pathogen low numbers. The development of robust and efficient sample preparation techniques is crucial to improve detection sensitivity and workflow. Immunomagnetic separation using magnetic nanoparticles (MNPs) is attractive, as it can efficiently capture target cells. For food safety applications, a platform is needed to rapidly process large sample volumes, allowing capture and release of target bacteria conjugated to immunomagnetic nanoparticles (IMNPs). Herein, we demonstrate a method for magnetic capture and release of bacteria-IMNPs complex based on a 3D magnetic trap integrated on a polymeric microfluidic device. The 3D magnetic capture region consist of a dense array of high-aspect ratio (3 : 1) cylindrical pillars embossed in thermoplastic polymer and coated with soft ferromagnetic nickel by an electroless deposition technique. This allows the generation of strong and switchable magnetic capture regions due to the very low remanence of the nickel shell. We propose and validate an optimized configuration of capture regions for efficient localized capture and rapid release of MNPs and IMNPs conjugated to L. monocytogenes. A maximum recovery rate for MNPs corresponded to 91% while a maximum capture efficiency of 30% was obtained for live bacteria, with a minimum detectable sample concentration of ~10 cfu ml(-1) in 1 ml volume using plate-culture method. We believe that the flexible design and low-cost fabrication process of the proposed system will allow rapid sample preparation for applications beyond food and water safety, including point-of-care diagnosis.
The Epidemiology and Genetics of Atopic Allergy (1981)

STUDIES of atopic allergy ("allergy") have provided new insight in defining the epidemiologic and genetic basis for the human immune response.1 , 2 Allergy is characterized by the development of antibody responses of a unique immunoglobulin — IgE3 — after exposure to inhaled, ingested, or injected antigens (usually termed "allergens"). Under conditions of natural exposure to extremely low doses (usually less than 1 μg per year),4 atopic persons have IgE-antibody responses toward an array of environmental allergens present in pollens, fungal spores, animal danders, and similar substances. Synthesis of IgE is favored by natural immunization through inhalation, since antigens come directly into . . .
The Pharmacological Basis of Therapeutics (1976)

Journal Article The Pharmacological Basis of Therapeutics Get access The Pharmacological Basis of Therapeutics, Fifth Edition, edited by Louis S. Goodman and Alfred Gilman. Published by Macmillan Publishing Co., Inc., 866 Third Avenue, New York, NY 10022, 1975. xvi + 1704 p. Price $30.00. American Journal of Hospital Pharmacy, Volume 33, Issue 4, 1 April 1976, Page 373, https://doi.org/10.1093/ajhp/33.4.373a Published: 01 April 1976
Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5-<i>a</i>]pyridine-3-carboxamides as Novel Antitubercular Agents (2015)

A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain and a panel of clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One of the representative compounds (5k) significantly reduces the bacterial burden in an autoluminescent H37Ra infected mouse model, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.
Real‐time imaging with a new ultrasonic camera: Part I, in vitro experimental studies on transmission imaging of biological structures (1975)

Results are described of in vitro biological experimentation using a new through-transmission ultrasonic camera system developed at the Stanford Research Institute. The camera system produces real-time focused, orthographic images of a 15 times 15 cm field. The in vitro studies, which demonstrate the diagnostic potential of the new technique, include transmission images of selected excised organs such as liver, kidney, spleen, and uterus. In addition, preliminary studies evaluating ultrasonic image quality and the effect of out-of-focus structures are discussed.