gebhart/patrepeval huggingface dataset:
Subcompartments of the G1 phase of cell cycle detected by flow cytometry. (1980)

Cellular DNA and RNA were simultaneously quantitated in individual cells of cycling and quiescent populations by flow cytometry. Based on differences in RNA content, two distinct subcompartments, G1A and G1B, were recognized in the G1 phase of exponentially growing cells. After mitosis, cells reside in the low-RNA, G1A compartment from which they cannot enter the S phase directly. An increase in RNA above a critical level is required for G1 cells to be able to initiate DNA replication; G1 cells with RNA values above this level are classified as G1B. Cell transition from G1A to G1B and from G1B to S was analyzed in a stathmokinetic experiment on L1210 cells with a doubling time of 10 hr. The half-time of cell residence in the indeterminate state of G1 was found to be 1 hr, and the duration of the deterministic portion of G1 phase was 2 hr. The indeterminate state, although not identical with G1A, is most likely located in G1A. Cell quiescence induced by serum deprivation (3T3 cells) or by addition of n-butyrate (L1210) results in cell arrest at a state which, judged by RNA content, is similar to that of G1A of exponentially growing cells. The exit from this state, however, is much slower after stimulation of these blocked cells than the transition of G1A to G1B in cells growing exponentially. Thymidine or hydroxyurea arrest cells in G1B or perhaps at the border between G1B and S. Prolonged incubation of 3T3 cells to confluence results in a marked loss of cellular RNA below the level of the G1A state. This deep quiescent state (G1Q) is distinctly different from the G1A state of cycling cells or cells blocked in G1A by serum deprivation.
Transport and metabolism of glucose in an insulin-secreting cell line, .beta.TC-1 (1991)

Kinetic characteristics of glucose transport and glucose phosphorylation were studied in the islet cell line beta TC-1 to explore the roles of these processes in determining the dependence of glucose metabolism and insulin secretion on external glucose. The predominant glucose transporter present was the rat brain/erythrocyte type (Glut1), as determined by RNA and immunoblot analysis. The liver/islet glucose transporter (Glut2) RNA was not detected. The functional parameters of zero-trans glucose entry were Km = 9.5 +/- 2 mM and Vmax = 15.2 +/- 2 nmol min-1 (microL of cell water)-1. Phosphorylation kinetics of two hexokinase activities were characterized in situ. A low-Km (0.036 mM) hexokinase with a Vmax of 0.40 nmol min-1 (microL of cell water)-1 was present along with a high-Km (10 mM) hexokinase, which appeared to conform to a cooperative model with a Hill coefficient of about 1.4 and a Vmax of 0.3 nmol min-1 (microL of cell water)-1. Intracellular glucose at steady state was about 80% of the extracellular glucose from 3 to 15 mM, and transport did not limit metabolism in this range. In this static (nonperifusion) system, 2-3 times more immunoreactive insulin was secreted into the medium at 15 mM glucose than at 3 mM. The dependence of insulin secretion on external glucose roughly paralleled the dependence of glucose metabolism on external glucose. Simulations with a model demonstrated the degree to which changes in transport activity would affect intracellular glucose levels and the rate of the high-Km hexokinase (with the potential to affect insulin release).
GENETICS OF HUMAN CELL LINES, IV. DNA-MEDIATED HERITABLE TRANSFORMATION OF A BIOCHEMICAL TRAIT (1962)

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.
Eosinophils, bronchial hyperreactivity and late‐phase asthmatic reactions (1985)

We have measured airways reactivity (methacholine PC20) and blood eosinophils in eleven asthmatics with allergen-induced late-phase reactions. Before challenge there was a significant (P less than 0.05) inverse correlation between blood eosinophils and the methacholine PC20. After allergen inhalation eosinophil counts were significantly (P less than 0.01) elevated at 24 hr. These increases in blood eosinophil counts were not observed in patients who developed single early responses. The magnitude of the changes in eosinophil counts (24 hr minus pre-challenge values) also correlated with the baseline methacholine PC20 (P less than 0.01) in the late-phase responders. These observations suggest that there may be a direct association between eosinophils and airway reactivity in subjects who develop late-phase asthmatic reactions.
Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation (2011)

Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of hepcidin, which negatively regulates iron bioavailability by inactivating ferroportin. Hepcidin is transcriptionally regulated by IL-6 and bone morphogenetic protein (BMP) signaling. We hypothesized that inhibiting BMP signaling can reduce hepcidin expression and ameliorate hypoferremia and anemia associated with inflammation. In human hepatoma cells, IL-6-induced hepcidin expression, an effect that was inhibited by treatment with a BMP type I receptor inhibitor, LDN-193189, or BMP ligand antagonists noggin and ALK3-Fc. In zebrafish, the induction of hepcidin expression by transgenic expression of IL-6 was also reduced by LDN-193189. In mice, treatment with IL-6 or turpentine increased hepcidin expression and reduced serum iron, effects that were inhibited by LDN-193189 or ALK3-Fc. Chronic turpentine treatment led to microcytic anemia, which was prevented by concurrent administration of LDN-193189 or attenuated when LDN-193189 was administered after anemia was established. Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation.
Radioimmunoassay for N-terminal probrain natriuretic peptide in human plasma (2001)

Measurement of plasma levels of natriuretic peptides has been used to assess left ventricular dysfunction and prognosis. Recently levels of the N-terminal peptide fragment of the precursor of brain natriuretic peptide have been reported to be present in peripheral plasma and to be increased in chronic heart failure patients. Our aim in this study was to develop a radioimmunoassay for N-terminal proBNP, to compare its plasma concentrations in control subjects and in patients with end-stage heart failure and to define its relation to brain natriuretic peptide (BNP). A polyclonal antibody was raised in rabbits against human N-terminal proBNP fragment (amino acid 1-21). The plasma N-terminal proBNP concentrations were assayed directly without extraction. No detectable cross-reactivity existed with other natriuretic peptides: BNP, ANP or N-terminal proANP. The assay had a detection limit (2 SD from zero) of 9.7 pmol/L. Plasma N-terminal proBNP was 29 (13-75) (median (range)) pmol/L in the control group. There were no gender difference, male: 28 (13-61) vs. female 33 (13-75) pmol/L, p= NS, but there was a positive correlation to age (r=0.52, p<0.0001). In patients with end-stage heart failure the median N-terminal proBNP levels were increased significantly 616 (114-2781) pmol/L (p<0.001) and in pooled data N-terminal proBNP showed a close correlation to BNP (r=0.96, p<0.0001). Size exclusion of plasma extracts indicated that proBNP (1-108) may circulate both as intact prohormone and as split products, N-terminal proBNP (1-76) and BNP (77-108). Our results support the concept that N-terminal proBNP measurement could be a valuable tool in the biochemical indication of increased cardiac wall stress.
Apoptosis signals in lymphoblasts induced by focused ultrasound (2004)

We investigated the effects of focused ultrasound (FUS) on specific molecular signaling and cellular response in three closely related human Tk6 lymphoblast cell lines that differed only in their p53 status. The applied ultrasound parameters fell between the physical dose range, which is safely used in medical diagnostics (peak pressure<0.1 MPa) and that used for high-energy FUS thermal ablation therapy (peak pressure>10 MPa). Based on cDNA microarrays and protein analysis, we found that FUS at the intermediate peak pressure of 1.5 MPa induced a complex signaling cascade with upregulation of proapoptotic genes [e.g., p53, p21, Thy1 (CD 90)]. Simultaneously, FUS downregulated cellular survival components (e.g., bcl-2, SOD). The p53 status was important for the reaction of the cells to ultrasound. Apoptosis and G1 arrest were induced primarily in p53+ cells, while p53- cells showed less apoptosis but exhibited G2 arrest. Likewise, the proliferation of lymphoblasts was much more strongly inhibited in p53+ than in p53- cells. Microarray analysis further demonstrated an upregulation of genes involved in oxidative stress (e.g., ferritin), suggesting that indirect sonochemical effects via reactive oxygen species play a causative role in the interaction of ultrasound with lymphoblasts. An important characteristic of FUS in therapeutic ultrasound applications is its ability to be administered to the human body in a targeted manner while sparing intermediate tissues. Therefore, our data indicate that this noninvasive, mechanical wave transmission, which is free of ionizing radiation, has the potential to specifically induce localized cell signals and apoptosis.
[Evidence-based medicine: treatment of chronic hepatitis C. Liege Study Group on Viral Hepatitis]. (2000)

The Hepatitis C virus (HCV) infects nearly 170 million people in the world. The major characteristic of virus C is its tendency to chronicity in more than 85% of cases. Generally asymptomatic, HCV infection may also evolve with time to cirrhosis and hepatocellular carcinoma. During the last few years, HCV-related end-stage cirrhosis has become the first cause of liver transplantation. In 10 years only, very significant progress has been made in the knowledge of the virus, not only in the field of diagnosis but also in therapy. Several consensus conferences taking last discoveries into account have been organized in order to promote recommendations useful for the management of hepatitis C patients. The aim of this short overview is to summarize practical recommendations that emerged recently from consensus meetings.
Electromigration in thin aluminum films on titanium nitride (1976)

The aluminum electromigration drift velocity was measured at the temperature range 250–400 °C. A threshold current density was found inversely proportional to the stripe length. An activation energy of 0.65 eV was found for the drift velocity. The occurrence of the threshold is explained by opposing chemical gradients created by the atom pile-up and depletion at the stripe ends. The threshold may explain several observations reported previously. The threshold is increased by decreasing the temperature or by enclosing the aluminum in silicon nitride. Virtually no electromigration is seen for very short aluminum stripes even at current densities above 106 A/cm2.
Isolation and Characterization of Single Anti‐U1A‐specific B Cells from Autoimmune Patients (1997)

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A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity (2005)

Nicotine is the principal addictive component in tobacco, and following uptake acts in the central nervous system. The smoking-cessation efforts of most smokers fail because a single slip often delivers sufficient nicotine to the brain to reinstate the drug-seeking behaviour. Blocking nicotine from entering the brain by induction of specific antibodies may be an effective means to prevent such relapses. The hapten nicotine was coupled to virus-like particles (VLP) formed by the coat protein of the bacteriophage Qb. In preclinical experiments, this Nicotine-Qb VLP (NicQb) vaccine induced strong antibody responses. After intravenous nicotine challenge, vaccinated mice exhibited strongly reduced nicotine levels in the brain compared with control mice. In a phase I study, 32 healthy non-smokers were immunized with NicQb. The vaccine was safe and well-tolerated. All volunteers who received NicQb showed nicotine-specific IgM antibodies at day 7 and nicotine-specific IgG antibodies at day 14. Antibody levels could be boosted by a second injection or the addition of Alum as an adjuvant and the antibodies had a high affinity for nicotine. These data suggest that antibodies induced by NicQb may prevent relapses by sequestering nicotine in the blood of immunized smokers.
Mutational analysis of the human immunodeficiency virus type 1 env gene product proteolytic cleavage site (1990)

The structural requirements for proteolytic cleavage of the human immunodeficiency virus type 1 env gene product, gp160, to gp120 and gp41 have been assessed by specific mutagenesis of the sequence Lys Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg located between amino acids 500 and 511, i.e., at the putative C terminus of gp120. The basic amino acids underlined have been mutated, individually and in combination, to neutral amino acids, and the cleavability of the mutated env gene products was examined after expression in CV-1 cells. The results show that the replacement of Arg-511 (cleavage presumably occurs C terminal to this amino acid) with Ser completely abolishes recognition and cleavage by the cellular protease(s), i.e., the remaining basic amino acids in the vicinity do not serve as alternative substrates. However, Arg-508 and Lys-510 are important features of the recognition site since, when they are individually changed to neutral amino acids, cleavage is severely impaired. The basic amino acids 500, 502, and 504 are, individually, not important for cleavage, since their individual replacement by neutral amino acids does not impair cleavage. However, when all four basic amino acids 500, 502, 503, and 504 are changed to neutral amino acids, cleavage is almost completely abolished. This shows that the sequence Arg Glu Lys Arg at the cleavage site is alone not sufficient for cleavage but that a contribution of other amino acids is required, whether the other amino acids provide a basic character or a certain structure in the vicinity of the cleavage site. When noncleavable or poorly cleavable mutant env genes are expressed from the infectious plasmid pNL4-3 in CD4+ human lymphoblastoid cells, noninfectious virus, incapable of spread throughout the culture, is produced.
Thinking Aloud and Reading Comprehension Research: Inquiry, Instruction, and Social Interaction (1997)

This is a review of research on thinking aloud in reading comprehension that considers thinking aloud as a method of inquiry, a mode of instruction, and a means for encouraging social interaction. As a method of inquiry, the analysis of verbal reports provided by readers thinking aloud revealed the flexible and goal-directed processing of expert readers. As a mode of instruction, thinking aloud was first employed by teachers who modeled their processing during reading, making overt the strategies they were using to comprehend text. Subsequently, instructional approaches were developed to engage students themselves in thinking aloud. Such endeavors revealed facilitation effects on text understanding. Current efforts to engage students in constructing meaning from text in collaborative discussions seem to indicate a new direction for thinking aloud research, one in which social interaction assumes increased importance.
Sampling and reconstruction of signals with finite rate of innovation in the presence of noise (2005)

Recently, it was shown that it is possible to develop exact sampling schemes for a large class of parametric nonbandlimited signals, namely certain signals of finite rate of innovation. A common feature of such signals is that they have a finite number of degrees of freedom per unit of time and can be reconstructed from a finite number of uniform samples. In order to prove sampling theorems, Vetterli et al. considered the case of deterministic, noiseless signals and developed algebraic methods that lead to perfect reconstruction. However, when noise is present, many of those schemes can become ill-conditioned. In this paper, we revisit the problem of sampling and reconstruction of signals with finite rate of innovation and propose improved, more robust methods that have better numerical conditioning in the presence of noise and yield more accurate reconstruction. We analyze, in detail, a signal made up of a stream of Diracs and develop algorithmic tools that will be used as a basis in all constructions. While some of the techniques have been already encountered in the spectral estimation framework, we further explore preconditioning methods that lead to improved resolution performance in the case when the signal contains closely spaced components. For classes of periodic signals, such as piecewise polynomials and nonuniform splines, we propose novel algebraic approaches that solve the sampling problem in the Laplace domain, after appropriate windowing. Building on the results for periodic signals, we extend our analysis to finite-length signals and develop schemes based on a Gaussian kernel, which avoid the problem of ill-conditioning by proper weighting of the data matrix. Our methods use structured linear systems and robust algorithmic solutions, which we show through simulation results.
Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure (2013)

This work reports a microfluidic device with deterministic lateral displacement (DLD) arrays allowing rapid and label-free cancer cell separation and enrichment from diluted peripheral whole blood, by exploiting the size-dependent hydrodynamic forces. Experiment data and theoretical simulation are presented to evaluate the isolation efficiency of various types of cancer cells in the microfluidic DLD structure. We also demonstrated the use of both circular and triangular post arrays for cancer cell separation in cell solution and blood samples. The device was able to achieve high cancer cell isolation efficiency and enrichment factor with our optimized design. Therefore, this platform with DLD structure shows great potential on fundamental and clinical studies of circulating tumor cells.
Development of Humanized Mouse models to Study Human Malaria Parasite Infection (2012)

Malaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria is primarily caused by Plasmodium falciparum. The burden of malaria on the developing world is enormous, and a fully protective vaccine is still elusive. One of the biggest challenges in the quest for the development of new antimalarial drugs and vaccines is the lack of accessible animal models to study P. falciparum infection because the parasite is restricted to the great apes and human hosts. Here, we review the current state of research in this field and provide an outlook of the development of humanized small animal models to study P. falciparum infection that will accelerate fundamental research into human parasite biology and could accelerate drug and vaccine design in the future.
Nuclear Import and Export of Viruses and Virus Genomes (1998)

Many viruses replicate in the nucleus of their animal and plant host cells. Nuclear import, export, and nucleo-cytoplasmic shuttling play a central role in their replication cycle. Although the trafficking of individual virus proteins into and out of the nucleus has been well studied for some virus systems, the nuclear transport of larger entities such as viral genomes and capsids has only recently become a subject of molecular analysis. In this review, the general concepts emerging are discussed and a survey is provided of current information on both plant and animal viruses. Summarizing the main findings in this emerging field, it is evident that most viruses that enter or exit the nucleus take advantage of the cell's nuclear import and export machinery. With a few exceptions, viruses seem to cross the nuclear envelope through the nuclear pore complexes, making use of cellular nuclear import and export signals, receptors, and transport factors. In many cases, they capitalize on subtle control systems such as phosphorylation that regulate traffic of cellular components into and out of the nucleus. The large size of viral capsids and their composition (they contain large RNA and DNA molecules for which there are few precedents in normal nuclear transport) make the processes unique and complicated. Prior capsid disassembly (or deformation) is required before entry of viral genomes and accessory proteins can occur through nuclear pores. Capsids of different virus families display diverse uncoating programs which culminate in genome transfer through the nuclear pores.
Macrophage-derived chemokine (MDC) (2000)

Macrophage-derived chemokine (MDC) is a CC chemokine paradigmatic of emerging aspects of chemokine immunobiology. It is constitutively expressed, yet microbial products and cytokines regulate its expression with divergent effects of type II (IL-4 and IL-13) and type I (interferon) cytokines. Processing of the mature protein by dipeptidyl peptidase IV/CD26 provides a further level of regulation. It acts on diverse cellular targets including dendritic cells (DC), NK cells, and T cell subsets. Among these, MDC is a potent attractant for CCR4 expressing polarized Th2 and Tc2 cells, and evidence is consistent with a role of this chemokine as an amplification loop of polarized type II responses. Emerging indications on the involvement of MDC in diverse pathologies, ranging from allergic reactions to HIV infection and neoplasia, are discussed.
Prevention of mucosally induced uveitis with a HSP60‐derived peptide linked to cholera toxin B subunit (2003)

Oral administration of the uveitogenic peptide (aa 336-351) derived from human HSP60 induced clinical and histological manifestations of uveitis in 65.8% (48/73) of Lewis rats. Uveitis was significantly decreased to 16.7% (11/66) in parallel experiments with the peptide linked to recombinant cholera toxin B subunit (rCTB), also given by mouth (chi(2)=34.2, p<0.0001). The protective efficacy between tolerized and immunized animals was 74.7%. Adoptive transfer of mesenteric lymph node cells from tolerized rats prevented the development of uveitis. A significantly higher proportion of regulatory CD4(+)CD45RC(low)RT6(+) subset of Th2 memory cells were found in the mesenteric lymph nodes (p<0.005) and spleens (p</=0.05) of tolerized rats without uveitis, as compared with immunized rats and uveitis. In situ hybridization studies of mesenteric lymph nodes and/or the uveal tract showed significant increases in IL-10 and TGF-beta mRNA but decreases in IFN-gamma and IL-12 mRNA in tolerized, as compared with immunized animals. Thus, the mechanism of tolerance, preventing the development of uveitis may involve a regulatory subset of memory cells and a shift from Th1 to Th2 and Th3 cytokines. We suggest that mucosally induced uveitis can be prevented by oral administration of the peptide-rCTB conjugate.