gebhart/patrepeval huggingface dataset:
Protein kinase Cα actively downregulates through caveolae-dependent traffic to an endosomal compartment (2000)

Receptor desensitization occurs through receptor internalization and targeting to endosomes, a prerequisite for sorting and degradation. Such trafficking processes may not be restricted to membrane associated receptors but may also play an important role in the downregulation of cytoplasmic transducers such as protein kinase C (PKC). It is demonstrated here that acute TPA exposure induces the transport of activated PKC(alpha) from the plasma membrane to endosomes. This process requires PKC activity and catalytically competent PKC can even promote a similar process for a truncated regulatory domain PKC(&agr;) protein. It is established that PKC(&agr;) is targeted to the endosome compartment as an active kinase, where it colocalizes with annexin I, a substrate of PKC. Thus, PKC(alpha) downregulation shares features with plasma membrane associated receptor sorting and degradation. However, it is shown that PKC(&agr;) delivery to the endosome compartment is not a Rab5 mediated process in contrast to the well characterised internalisation of the transferrin receptor. An alternative route for PKC(alpha) is evidenced by the finding that the cholesterol binding drugs nystatin and filipin, known to inhibit caveolae mediated trafficking, are able to block PKC(alpha) traffic and down regulation. Consistent with this, the endosomes where PKC(alpha) is found also contain caveolin. It is concluded that the initial step in desensitisation of PKC(alpha) involves active delivery to endosomes via a caveolae mediated process.
CD34+ Progenitor Cell Selection: Clinical Transplantation, Tumor Cell Purging, Gene Therapy, Ex Vivo Expansion, and Cord Blood Processing (1996)

A unique avidin-biotin immunoadsorption system (CellPro CEPRATE SC) has been developed for the rapid clinical scale purification of CD34+ cells from bone marrow, mobilized peripheral blood (PBSC), or cord blood. This system has been used to treat more than 2500 patients worldwide in a variety of clinical studies. In the autologous transplantation setting, selection for CD34+ cells results in significant reduction (2- > 5 logs) of contaminating tumor cells in the enriched fractions, as documented using sensitive immunocytochemistry staining techniques or quantitative PCR analyses. In the allogeneic bone marrow or PBSC transplant setting, using the CEPRATE SC system as a method for T cell depletion has shown a 3-log reduction in overall T cell content, with more rapid hematopoietic recovery after PBSC reinfusion as compared with bone marrow. CD34+ enrichment is required for efficient ex vivo expansion of progenitor cells as well as for gene therapy applications involving the genetic modification of stem cells.
Mammographic densities and breast cancer risk. (1998)

The radiological appearance of the female breast varies among individuals because of differences in the relative amounts and X-ray attenuation characteristics of fat and epithelial and stromal tissues. Fat is radiolucent and appears dark on a mammogram, and epithelium and stroma are radiodense and appear light. We review here the evidence that these variations, known as mammographic parenchymal patterns, are related to risk of breast cancer. Studies that used quantitative measurement to classify mammographic patterns have consistently found that women with dense tissue in more than 60-75% of the breast are at four to six times greater risk of breast cancer than those with no densities. These risk estimates are independent of the effects of other risk factors and have been shown to persist over at least 10 years of follow up. Estimates of attributable risk suggest that this risk factor may account for as many as 30% of breast cancer cases. Mammographically dense breast tissue is associated both with epithelial proliferation and with stromal fibrosis. The relationship between these histological features and risk of breast cancer may by explained by the known actions of growth factors that are thought to play important roles in breast development and carcinogenesis. Mammographically dense tissue differs from most other breast cancer risk factors in the strength of the associated relative and attributable risks for breast cancer, and because it can be changed by hormonal and dietary interventions. This risk factor may be most useful as a means of investigating the etiology of breast cancer and of testing hypotheses about potential preventive strategies.
Applying Winnow to Context-Sensitive Spelling Correction (1996)

Multiplicative weight-updating algorithms such as Winnow have been studied extensively in the COLT literature, but only recently have people started to use them in applications. In this paper, we apply a Winnow-based algorithm to a task in natural language: context-sensitive spelling correction. This is the task of fixing spelling errors that happen to result in valid words, such as substituting {\it to\/} for {\it too}, {\it casual\/} for {\it causal}, and so on. Previous approaches to this problem have been statistics-based; we compare Winnow to one of the more successful such approaches, which uses Bayesian classifiers. We find that: (1)~When the standard (heavily-pruned) set of features is used to describe problem instances, Winnow performs comparably to the Bayesian method; (2)~When the full (unpruned) set of features is used, Winnow is able to exploit the new features and convincingly outperform Bayes; and (3)~When a test set is encountered that is dissimilar to the training set, Winnow is better than Bayes at adapting to the unfamiliar test set, using a strategy we will present for combining learning on the training set with unsupervised learning on the (noisy) test set.
Of Madness and machines: Names in Ken Kesey's One Flew Over the Cuckoo's Nest (1989)

Included here is the introductory paragraph of the article. Ken Kesey's first novel, One Flew Over the Cuckoo's Nest, reflects his experiences as a young attendant in two California mental hospitals in which he was employed. Book reviewers spoke highly of One Flew Over the Cuckoo's Nest, and recognized the authority with which Kesey captured the day-to-day routines and events in mental wards. Irving Malin observed that One Flew Over the Cuckoo's Nest is a gothic novel, for it employs imprisonment, madness, violence and distorted reflections, but it does so in a new way which Malin calls new American gothic. 1 Joseph J. Waldmeir, in a long review-essay, considers One Flew Over the Cuckoo's Nest a novel of the absurd, ((the first truly successful American novel of the absurd since World War II." 2
Different tissue-specific expression of the amylase gene Amy-1 in mice and rats. (1986)

We cloned the rat alpha-amylase gene Amy-1 and compared its structure and expression with its mouse counterpart. The results showed that the general organization of the transcriptionally active rat Amy-1 gene was similar to that of its mouse counterpart; i.e., the rat gene also contained two independent transcriptional promoters. The distance between the two promoters in the rat gene was, however, more than double (6 kilobases) that measured in the mouse gene (2.8 kilobases). In addition, the rat genome also contained an independent, orphonlike version of the weaker Amy-1 promoter, which was transcriptionally silent. In spite of the similar overall organization of the Amy-1 genes in mouse and rat cells, an interesting difference was observed in the expression of the weak promoter in these two closely related rodents. In rats this promoter was significantly active only in liver cells, while in mice it was utilized with similar efficiencies in parotid, liver, and pancrease cells. Moreover, the transcripts produced in rat liver had a very heterogeneous population of 5' ends, located between 180 and 220 nucleotides upstream of the two homologous start sites observed for this promoter in mouse liver, even though the sequences around this region were strongly conserved between the two species.
Blood Eicosapentaenoic and Docosahexaenoic Acids Predict All-Cause Mortality in Patients With Stable Coronary Heart Disease (2010)

In these outpatients with stable coronary heart disease, blood n-3 FA levels were inversely associated with total mortality independent of standard and emerging risk factors, suggesting that reduced tissue n-3 FA levels may adversely impact metabolism.
Bone Marrow Transplants from HLA-Identical Siblings as Compared with Chemotherapy for Children with Acute Lymphoblastic Leukemia in a Second Remission (1994)

For children with acute lymphoblastic leukemia in a second remission, bone marrow transplants from HLA-identical siblings result in fewer relapses and longer leukemia-free survival than does chemotherapy.
Electron and Oxygen Transfer in Polyoxometalate, H5PV2Mo10O40, Catalyzed Oxidation of Aromatic and Alkyl Aromatic Compounds:  Evidence for Aerobic Mars−van Krevelen-Type Reactions in the Liquid Homogeneous Phase (2001)

The mechanism of aerobic oxidation of aromatic and alkyl aromatic compounds using anthracene and xanthene, respectively, as a model compound was investigated using a phosphovanadomolybdate polyoxometalate, H(5)PV(2)Mo(10)O(40), as catalyst under mild, liquid-phase conditions. The polyoxometalate is a soluble analogue of insoluble mixed-metal oxides often used for high-temperature gas-phase heterogeneous oxidation which proceed by a Mars-van Krevelen mechanism. The general purpose of the present investigation was to prove that a Mars-van Krevelen mechanism is possible also in liquid-phase, homogeneous oxidation reactions. First, the oxygen transfer from H(5)PV(2)Mo(10)O(40) to the hydrocarbons was studied using various techniques to show that commonly observed liquid-phase oxidation mechanisms, autoxidation, and oxidative nucleophilic substitution were not occurring in this case. Techniques used included (a) use of (18)O-labeled molecular oxygen, polyoxometalate, and water; (b) carrying out reactions under anaerobic conditions; (c) performing the reaction with an alternative nucleophile (acetate) or under anhydrous conditions; and (d) determination of the reaction stoichiometry. All of the experiments pointed against autoxidation and oxidative nucleophilic substitution and toward a Mars-van Krevelen mechanism. Second, the mode of activation of the hydrocarbon was determined to be by electron transfer, as opposed to hydrogen atom transfer from the hydrocarbon to the polyoxometalate. Kinetic studies showed that an outer-sphere electron transfer was probable with formation of a donor-acceptor complex. Further studies enabled the isolation and observation of intermediates by ESR and NMR spectroscopy. For anthracene, the immediate result of electron transfer, that is formation of an anthracene radical cation and reduced polyoxometalate, was observed by ESR spectroscopy. The ESR spectrum, together with kinetics experiments, including kinetic isotope experiments and (1)H NMR, support a Mars-van Krevelen mechanism in which the rate-determining step is the oxygen-transfer reaction between the polyoxometalate and the intermediate radical cation. Anthraquinone is the only observable reaction product. For xanthene, the radical cation could not be observed. Instead, the initial radical cation undergoes fast additional proton and electron transfer (or hydrogen atom transfer) to yield a stable benzylic cation observable by (1)H NMR. Again, kinetics experiments support the notion of an oxygen-transfer rate-determining step between the xanthenyl cation and the polyoxometalate, with formation of xanthen-9-one as the only product. Schemes summarizing the proposed reaction mechanisms are presented.
Balloon Angioplasty for Arteriovenous Graft Stenosis (2001)

The poor patency rate and high cost of TBA and SBA suggests that these procedures should not be routinely used for salvage of thrombosed arteriovenous grafts with outflow stenosis. Patch angioplasty or creation of simultaneous temporary and new permanent accesses may be a more cost-effective approach in these patients.
Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation (1999)

We have compared the efficiency of central nervous system and peripheral antigen-presenting cells (APC) in T cell priming and restimulation. OVA peptide 323 - 339-dependent activation of DO11.10 TCR-transgenic naive CD4+ and polarized Th1 or Th2 cells was assessed in the presence of microglia and astrocytes from the neonatal mouse brain as well as dendritic cells (DC) and B cells purified from adult mouse lymph nodes. DC were the most efficient in inducing naive T cell proliferation, IL-2 secretion and differentiation into Th1 cells, followed by IFN-gamma-preactivated microglia, large and small B cells. Astrocytes failed to activate naive T cells. IFN-gamma-pretreated microglia were as efficient as DC in the restimulation of Th1 cells, whereas IFN-gamma-pretreated astrocytes, large and small B cells were much less efficient. Conversely, Th2 cells were efficiently restimulated by all the APC types examined. During T cell priming, DC secreted more IL-12 than microglia but similar amounts of IL-12 were secreted by the two cell types upon interaction with Th1 cells. The hierarchy of APC established in this study indicates that DC and microglia are the most efficient in the stimulation of naive CD4(+) T cells and in the restimulation of Th1 cells, suggesting that activated microglia may effectively contribute to Th1 responses leading to central nervous system inflammation and tissue damage. These potentially pathogenic responses could be counteracted by the high efficiency of astrocytes as well as microglia in restimulating Th2 cells.
Stem cell therapy in pulmonary fibrosis (2011)

Adult MSCs may prove to be a valuable therapeutic option in lung tissue rescue and repair based on their ready availability, immunomodulatory effects and capacity for cell differentiation.
Antitumor, nephrotoxic and clastogenic effect of cis-DDP with DDTC or NAC. (1994)

Diethyldithiocarbamate (DDTC) and N-acetylcysteine (NAC) are nucleophile sulfur-containing compounds which can protect the platinum-induced nephrotoxicity. Combinations of cis-diamminedichloroplatinum(II) (cis-DDP) and DDTC or NAC were tested on the leukemia L1210 and melanoma B 16 tumor models. Nephrotoxicity of cis-DDP alone and in combination with DDTC or NAC was evaluated. On both of the investigated tumor models clastogenic effects in bone marrow cells were detected. DNA synthetic and mitotic activity of L1210 cells in vivo were evaluated by 3H-thymidine incorporation and cytogenetic analysis. Amelioration of the platinum induced nephrotoxicity and preservation of the antitumor activity of cis-DDP through combined application with DDTC or NAC were obtained at the L1210 model. Maximal inhibition of the DNA synthesis in L1210 cells was detected with the cis-DDP treatment. The sulfurcontaining nucleophiles DDTC or NAC could modulate the inhibitory effect of cis-DDP on the incorporation of 3H-thymidine into the nuclei of L1210 cells. Enhanced mitotic activity was detected during cytotoxic therapy with cis-DDP. Cis-DDP alone and in combination with DDTC or NAC caused a significant growth inhibition on the s.c. tumor of the melanoma B16 bearing mice. Two times better therapeutic results at this model were obtained with cis-DDP alone (T/C = 234.09%, T/C = 136.36% for cis-DDP+DDTC and T/C = 151.14% for cis-DDP+NAC). The usefulness of DDTC or NAC as adjuvants in the platinum based chemotherapy of human cancers have been discussed. Clastogenic effect and antitumor activity are probably connected and it is supposed that the reduction of the genotoxicity could lead to a decreased antitumor activity of the platinum complex.
On The Cellular and Network Bases of Epileptic Seizures (2001)

The highly interconnected networks of the mammalian forebrain can generate a wide variety of synchronized activities, including those underlying epileptic seizures, which often appear as a transformation of otherwise normal brain rhythms. The cerebral cortex and hippocampus are particularly prone to the generation of the large, synchronized bursts of activity underlying many forms of seizures owing to strong recurrent excitatory connections, the presence of intrinsically burst-generating neurons, ephaptic interactions among closely spaced neurons, and synaptic plasticity. The simplest form of epileptiform activity in these structures is the interictal spike, a synchronized burst of action potentials generated by recurrent excitation, followed by a period of hyperpolarization, in a localized pool of pyramidal neurons. Seizures can also be generated in response to a loss of balance between excitatory and inhibitory influences and can take the form of either tonic depolarizations or repetitive, rhythmic burst discharges, either as clonic or spike-wave activity, again mediated both by intrinsic membrane properties and synaptic interactions. The interaction of the cerebral cortex and the thalamus, in conjunction with intrathalamic communication, can also generate spike waves similar to those occurring during human absence seizure discharges. Although epileptic syndromes and their causes are diverse, the cellular mechanisms of seizure generation appear to fall into only two categories: rhythmic or tonic "runaway" excitation or the synchronized and rhythmic interplay between excitatory and inhibitory neurons and membrane conductances.
THE APPLICATION OF NEURAL NETWORKS TO DRONE CONTROL (1990)

International Telemetering Conference Proceedings / October 29-November 02, 1990 / Riviera Hotel and Convention Center, Las Vegas, Nevada
Programming peptidomimetic syntheses by translating genetic codes designed de novo (2003)

Although the universal genetic code exhibits only minor variations in nature, Francis Crick proposed in 1955 that "the adaptor hypothesis allows one to construct, in theory, codes of bewildering variety." The existing code has been expanded to enable incorporation of a variety of unnatural amino acids at one or two nonadjacent sites within a protein by using nonsense or frameshift suppressor aminoacyl-tRNAs (aa-tRNAs) as adaptors. However, the suppressor strategy is inherently limited by compatibility with only a small subset of codons, by the ways such codons can be combined, and by variation in the efficiency of incorporation. Here, by preventing competing reactions with aa-tRNA synthetases, aa-tRNAs, and release factors during translation and by using nonsuppressor aa-tRNA substrates, we realize a potentially generalizable approach for template-encoded polymer synthesis that unmasks the substantially broader versatility of the core translation apparatus as a catalyst. We show that several adjacent, arbitrarily chosen sense codons can be completely reassigned to various unnatural amino acids according to de novo genetic codes by translating mRNAs into specific peptide analog polymers (peptidomimetics). Unnatural aa-tRNA substrates do not uniformly function as well as natural substrates, revealing important recognition elements for the translation apparatus. Genetic programming of peptidomimetic synthesis should facilitate mechanistic studies of translation and may ultimately enable the directed evolution of small molecules with desirable catalytic or pharmacological properties.
Biasing Brownian Motion in Different Directions in a 3-State Fluctuating Potential and an Application for the Separation of Small Particles (1996)

We consider diffusive motion on a periodic, anisotropic potential. Multiplicative three-state noise can bring about net flow. As the speed of this noise varies, the direction of the flux can change. We explain the flux reversals and discuss a possible application for the construction of a device for the separation of small particles.
Formate Dehydrogenase from Pseudomonas oxalaticus (1978)

Formate dehydrogenase (EC 1.2.1.2) from Pseudomonas oxalaticus has been isolated and characterized. The enzyme (molecular weight 315000) is a complex flavoprotein containing 2 FMN, 18--25 non-heme iron atoms and 15--20 acid-labile sulphides. In the last step of the purification, a sucrose gradient centrifugation, a second catalytically active species has been found apparently originating from a dissociation of the enzyme into two equal subunits. The enzyme is specific toward its natural substrate formate. It transfers electrons to NAD+, oxygen, ferricyanide, and a lot of nonphysiological acceptors (dyes). In addition electrons are transferred from NADH to these acceptors. The (reversible) removal of FMN requires a reduction step. Reincorporation has been followed by the reappearance of the reactivity against formate and by fluorescence titration. The deflavo enzyme also binds FAD and riboflavin. The resulting enzyme species show characteristic catalytic abilities. Activity against formate is peculiar to the FMN species.
Chemistry of the Podocarpaceae. XXX. Conversion of 8α,13-Epoxylabd-14-ene into a compound with an ambergris-type odour (1971)

Manoyl oxide (1) has been converted into the five-membered oxide (7), a compound with an ambergris-type odour which has been previously prepared from sclareol (13). The route involves the intermediates (14), (15), (17), (10), and (32), and gives an overall yield of 17% from manoyl oxide. The oxide (7) has also been prepared from manoyl oxide in two steps by oxidation with chromium trioxide followed by reduction of the lactone (10) with diborane.
Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria (2011)

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.