gebhart/patrepeval huggingface dataset:
Reversion of B Cell Commitment upon Loss of Pax5 Expression (2002)

The transcription factor Pax5 is essential for initiating B cell lineage commitment, but its role in maintaining commitment is unknown. Using conditional Pax5 inactivation in committed pro-B cells, we demonstrate that Pax5 is required not only to initiate its B lymphoid transcription program, but also to maintain it in early B cell development. As a consequence of Pax5 inactivation, previously committed pro-B cells regained the capacity to differentiate into macrophages in vitro and to reconstitute T cell development in vivo in RAG2-/- mice. Hence, Pax5 expression is continuously required to maintain B cell lineage commitment, because its loss converts committed pro-B cells into hematopoietic progenitors with multilineage potential.
Biochemical and biologic characterization of murine monocyte chemoattractant protein-1. Identification of two functional domains. (1994)

Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine-beta (or C-C) family of cytokines. Murine MCP-1, first identified as the JE gene, differs from human MCP-1 in molecular size and extent of glycosylation. We have used Chinese hamster ovary cells to express recombinant murine MCP-1 and find that its predominant form is a microheterogeneous protein of M(r) approximately 25,000. Most of MCP-1's microheterogeneity is due to variable amounts of sialic acid that are terminally attached to a constant number of O-linked oligosaccharide chains per molecule. This carbohydrate, along with a small amount of N-linked carbohydrate, accounts for 50% of the apparent molecular size of murine MCP-1 and is not required for in vitro monocyte chemoattractant activity. Mutational analysis shows that most of the carbohydrate is added to a 49-amino acid C-terminal domain that is not present in human MCP-1 and is not required for in vitro biologic activity, suggesting that murine MCP-1 consists of an N-terminal domain containing monocyte chemoattractant activity and a heavily glycosylated C-terminal domain of as yet unknown function. MCP-1 produced in COS cells contains a small amount of sulfate, but Chinese hamster ovary-produced MCP-1 does not. The absence of sulfate does not alter MCP-1's in vitro chemoattractant properties. In vitro, highly purified murine MCP-1 attracts monocytes, but not neutrophils, with a specific activity similar to human MCP-1 (EC50 approximately 0.5 nM). Equilibrium binding experiments with human monocytes reveal the presence of approximately 3000 binding sites per cell with a Kd of 0.77 nM. In vivo, injection of up to 1 micrograms murine MCP-1 in a variety of murine strains induces the appearance of a sparse mixed inflammatory infiltrate. The disparity between MCP-1's in vitro and in vivo effects suggests that other factors may be required to elicit a full-blown monocyte chemotactic response to MCP-1 in vivo.
An improved, non-isotopic method of screening cells from patients with abnormalities of sexual differentiation for Y chromosomal DNA content. (1993)

The detection of 45,X/46,XY mosaicism in patients with abnormalities of sexual differentiation is of crucial diagnostic importance. Here we present application of a PCR based method of detection of alphoid repeats of Y chromosomal origin. The method detects 0.01% of male DNA on a female DNA background. Out of 28 patients studied, in all cases where the Y chromosome or a part of it containing centromeric sequences was present, a positive amplification signal of Y chromosomal alphoid repeats was detected. In five cases the Y origin of marker chromosomes was diagnosed. The pattern of amplification signal distribution of the SRY gene was identical to that of Y specific alphoid primers, which confirms applicability of this method in the molecular diagnostic laboratory. The other diagnostic advantage is the ability to use dried blood specimens as an easy to handle and efficient source of DNA.
Example-Based Machine Translation in the Pangloss system (1996)

The Pangloss Example-Based Machine Translation engine (PanEBMT) is a translation system requiring essentially no knowledge of the structure of a language, merely a large parallel corpus of example sentences and a bilingual dictionary. Input texts are segmented into sequences of words occurring in the corpus, for which translations are determined by subsentential alignment of the sentence pairs containing those sequences. These partial translations are then combined with the results of other translation engines to form the final translation produced by the Pangloss system. In an internal evaluation, PanEBMT achieved 70.2% coverage of unrestricted Spanish news-wire text, despite a simplistic subsentential alignment algorithm, a suboptimal dictionary, and a corpus from a different domain than the evaluation texts.
Lower Airway Inflammation in Infants and Young Children with Cystic Fibrosis (1997)

Airway inflammation is an important component of cystic fibrosis (CF) lung disease. To determine whether this begins early in the illness, before the onset of infection, we examined bronchoalveolar lavage (BAL) fluid from 46 newly diagnosed infants with CF under the age of 6 mo identified by a neonatal screening program. These infants were divided into three groups: 10 had not experienced respiratory symptoms or received antibiotics and pathogens were absent in their BAL fluid; 18 had clear evidence of lower respiratory viral or bacterial (> or = 10(5) CFU/ml) infection; and the remaining 18 had either respiratory symptoms, taken antibiotics, or had < 10(5) CFU/ml of respiratory pathogens. Their BAL cytology, interleukin-8, and elastolytic activity were compared with those from 13 control subjects. In a longitudinal study to assess if inflammation develops or persists in the absence of infection, the results of 56 paired annual BAL specimens from 44 CF infants were grouped according to whether they showed absence, development, clearance, or persistence of infection. In newly diagnosed infants with CF, those without infection had BAL profiles comparable with control subjects while those with a lower respiratory infection had evidence of airway inflammation. In older children, the development and persistence of infection was accompanied by increased inflammatory markers, whereas these were decreased in the absence, or with the clearance, of infection. We conclude that airway inflammation follows respiratory infection and, in young children, improves when pathogens are eradicated from the airways.
Differentiation Status of Human Renal Proximal and Distal Tubular Epithelial Cells in vitro<i>: </i>Differential Expression of Characteristic Markers (2006)

We demonstrate differential expression of E-cadherin, intercellular adhesion molecule 1 and aquaporin 1 in cultured PTC and DTC as described for the renal tubule in vivo. We could show the in vitro differentiation of the cells, and thus, their usefulness as an in vitro model of the human proximal and early distal tubule.
Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy (2016)

The application of CTCs and ctDNA for the early detection of cancer is of high public interest, but it faces serious challenges regarding specificity and sensitivity of the current assays. Prediction of prognosis in patients with curable disease can already be achieved in several tumor entities, particularly in breast cancer. Monitoring the success or failure of systemic therapies (i.e., chemotherapy, hormonal therapy, or other targeted therapies) by sequential measurements of CTCs or ctDNA is also feasible. Interventional studies on treatment stratification based on the analysis of CTCs and ctDNA are needed to implement liquid biopsy into personalized medicine. Cancer Discov; 6(5); 479-91. ©2016 AACR.
Advances in gene delivery through molecular design of cationic lipids (2009)

This feature article describes the recent developments in the design of cationic lipids and their applications in gene delivery. Various structure-activity investigations explaining the variations in gene transfection efficacies with respect to different molecular structures of the cationic lipids have been discussed. Gene transfer abilities are presented in relation to aggregation properties of different aqueous formulations such as cationic liposomes and surfactant aggregates from various amphiphiles and cationic lipids, as a function of their hydrophobic parts, linkers and head groups.
Isolation of a novel KIR2DL3-specific mAb: comparative analysis of the surface distribution and function of KIR2DL2, KIR2DL3 and KIR2DS2 (2004)

In recent years an increasing number of sequences coding for new KIRs have been described. However, the limited availability of mAbs with unique KIR specificities has hindered an exhaustive assessment of their actual function, HLA-specificity, expression at the cell surface and distribution in different cell populations. In this study we report the generation of a novel mAb (ECM41) specific for KIR2DL3 molecules. By the use of cell transfectants expressing one or other KIR we show that this reagent allows discrimination of KIR2DL3 from other GL183 mAb-reactive molecules such as KIR2DL2 and KIR2DS2. Moreover we show that this novel mAb can be used to assess the surface expression and distribution of KIR2DL3 in different polyclonal NK populations and in NK cell clones. Along this line, we were able to analyze the HLA class I specificity of NK clones expressing either KIR2DL3 or KIR2DL2, two inhibitory receptors that were so far serologically undistinguishable. Finally, the combined use of GL183 and ECM41 mAbs in redirected killing assays allowed us to investigate the functional outcome of the simultaneous engagement of KIR2DL3 and KIR2DS2 in NK cell clones co-expressing KIRs that display opposite (inhibitory vs activating) function.
Synthesis of thyrotropin-releasing hormone analogs. 1. Complete dissociation of central nervous system effects from thyrotropin-releasing activity (1984)

Twenty-four thyrotropin-releasing hormone (TRH) analogues containing mainly aliphatic amino acids in position 2 were synthesized and tested for central nervous system (CNS) and hormonal (TSH) activity. Application of the pentafluorophenyl ester method in the syntheses resulted in optimal yields and high purity of the products. The neutral tripeptides pGlu- Nva -Pro-NH2 (9), pGlu-Nle-Pro-NH2 (10), and pGlu-Leu-Pro-NH2 (3) with a three- or four-membered straight or branched alkyl side chain in the position of the central amino acid had 2.5 to 10 times stronger anticataleptic effect than TRH, demonstrating that the presence of histidine is not essential for the CNS activity. Analogue 9 exhibited tenfold anticataleptic activity as compared to TRH, and it was found to be fully inactive in the release of TSH.
Synthesis and Secretion of Insulin-like Growth Factor II by a Leiomyosarcoma with Associated Hypoglycemia (1988)

We describe a case of recurrent hypoglycemia apparently caused by secretion of insulin-like growth factor II (IGF-II) by a leiomyosarcoma. A 67-year-old woman presented with recurrent severe hypoglycemia and a large mass in the thorax. During hypoglycemia, plasma cortisol was elevated, but insulin and growth hormone levels were low. After resection of a large leiomyosarcoma, the hypoglycemia resolved. After an eight-year remission, both the tumor and symptomatic hypoglycemia recurred. During a second operation a second large tumor was removed, with relief of the patient's hypoglycemia. The tumor contained high concentrations of IGF-II mRNA and 2100 ng of IGF-II immunoreactive peptide per gram. Filtration through a BioGel P-60 gel column established that 77 percent of the IGF-II was present as a larger molecule, demonstrating incomplete processing of the pro-IGF-II peptides. A similar fraction of high-molecular-weight IGF-II was present in the serum, indicating that the tumor was the chief source of IGF-II. The high-molecular-weight IGF-II found in both the tumor and serum was fully reactive with the IGF-II receptor. Radioimmunoassay showed that the concentrations of insulin-like growth factor I (IGF-I) in tumor and serum were low, suggesting feedback inhibition of growth hormone secretion by IGF-II. Eight months after reoperation, plasma concentrations of IGF-I and IGF-II were normal, and high-molecular-weight IGF-II was virtually undetectable. We conclude that the most likely cause of this patient's recurrent hypoglycemia was IGF-II produced by the leiomyosarcoma.
The Efficacy of Periosteal Cells Compared to Chondrocytes in the Tissue Engineered Repair of Bone Defects (1995)

We studied the efficacy of tissue generated from polymers seeded with periosteal cells and compared it to that of polymers seeded with chondrocytes, for its ability to repair surgically created cranial bone defects in rats. Large (approximately 40 mm2) bilateral defects were created in the parietal and temporal bones of 20 nude rats. One defect in each mouse was filled with synthetic biocompatible and biodegradable polymer templates seeded in vitro with either bovine periosteal cells (experimental group I) or chondrocytes (experimental group II). Contralateral defects were filled with either polymer not seeded with cells (control group I), or nothing at all (control group II). There was gross evidence of new bone formation repairing the defect in 7 of the 10 defects filled with polymers seeded with periosteal cells, while 8 of the 10 defects filled with polymers containing chondrocytes showed gross evidence of new cartilage formation covering the defect. Control defects showed no gross evidence of repair with either bone or cartilage.
New Polymers from Natural Phenols Using Horseradish or Soybean Peroxidase (2002)

The flavonol quercetin, its glycoside rutin, the flavanol catechin, the isoflavone daidzein and 5,6,4′-trihydroxyisoflavone can be oxidatively polymerized via a radical polyrecombination mechanism catalyzed by horseradish or soybean peroxidase in a mixture of phosphate buffer (pH 7) and 1,4-dioxane. The average molecular weights of the polymers were found to be in the range 4 000–12 000 g/mol. Daidzein derivatives with a methoxy (formononetin) or nitro group or a hydrogen atom at C-4′ could not be polymerized under these conditions. These results and molecular modeling studies suggest that polymerization preferentially occurs via the electron-rich ring B of the isoflavonoids. The polymers were characterized by means of FT-IR and UV spectroscopy, and their redox behavior was analyzed using cyclic voltammetry.
Arginine transport in human monocytic leukemia THP-1 cells during macrophage differentiation (2011)

L-arginine metabolism in myeloid cells plays a central role in the processes of macrophage activation and in the regulation of immune responses. In this study, we investigated arginine transport activity and the expression of the related transporter genes during the differentiation of monocytes to macrophages. We show here that the induction of THP-1 monocyte differentiation by PMA markedly increases the expression of SLC7A7 mRNA and of y(+)LAT1 protein and consequently, the activity of system y(+)L-mediated arginine transport. Conversely, the activity of system y(+) decreases during macrophage differentiation as a result of a reduction in CAT1 protein expression. The PMA-induced, macrophage-differentiated phenotype and the increased activity of system y(+)L through the induction of SLC7A7 gene are mediated by the specific activation of PKCβ. SLC7A7 gene silencing causes a significant reduction of system y(+)L activity and a subsequent, marked increase of arginine and lysine cell content, thus suggesting that in macrophagic cells, system y(+)L activity is mainly directed outwardly. Differentiating agents other than PMA, i.e., VD3 and ATRA, are equally effective in the stimulation of system y(+)L transport activity through the increased expression of SLC7A7 mRNA and y(+)LAT1 protein. Moreover, we found that also during differentiation of human monocytes from peripheral blood SLC7A7 mRNA and system y(+)L activity are increased. These findings point to SLC7A7 gene as a marker of macrophage differentiation.
Cardiac monitoring in HER2-positive patients on trastuzumab treatment: A review and implications for clinical practice (2020)

Trastuzumab prolongs progression-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, trastuzumab treatment is hampered by cardiotoxicity, defined as a left ventricular ejection fraction (LVEF) decline with a reported incidence ranging from 3 to 27% depending on variable factors. Early identification of patients at increased risk of trastuzumab-induced myocardial damage is of great importance to prevent deterioration to irreversible cardiotoxicity. Although current cardiac monitoring with multi gated acquisition (MUGA) scanning and/or conventional 2D-echocardiography (2DE) have a high availability, their reproducibility are modest, and more sensitive and reliable techniques are needed such as 3D-echocardiography (3DE) and speckle tracking echocardiography (STE). But which other diagnostic imaging modalities are available for patients before and during trastuzumab treatment? In addition, what is the optimal frequency and duration of cardiac monitoring? At last, which biomarker monitoring strategies are currently available for the identification of cardiotoxicity in patients treated with trastuzumab?
Correlation of primate red nucleus discharge with muscle activity during free‐form arm movements. (1993)

1. We recorded from 239 neurons located in the magnocellular division of the red nucleus of four alert macaque monkeys. At the same time, we recorded electromyographic (EMG) signals from as many as twenty electrodes chronically implanted on muscles of the shoulder, arm, forearm and hand. We recorded EMG signals for periods ranging from several months to a year. 2. The monkeys were trained to perform three free-form food retrieval tasks, each of which activated all of the recorded muscles and most of the neurons. The 'prehension' task required simply that the monkey grasp a piece of food from a fixed point in space. The 'barrier' task required the monkey to reach around a small barrier to obtain the food, and the 'Kluver' task required that food be removed from small holes. During the prehension task, we found approximately equal numbers of neurons that were strongly active while the hand was being moved toward the target (70% of units), and while the food was being grasped (60%). Relatively few units were active as the hand was returned to the mouth (15%). 3. Data files of 1-2 min duration were collected while the monkey performed a single behavioural task. Whenever possible, we recorded files for all three tasks from each neuron. For each file we calculated long time-span analog cross-correlations (+/- 1.28 s) between instantaneous neuronal firing rate and each of the full-wave rectified, low-pass filtered EMG signals. We used the peak correlation and the time of the peak as two summary measures of the functional relation between modulation of neuronal activity and EMG. 4. The magnitude of the strongest correlations was between 0.4 and 0.5 (normalized to a perfect correlation of +/- 1.0). Distal muscles were the most frequently correlated, and extensors were more frequently correlated than flexors. For all monkeys, the lags for well correlated muscles were distributed broadly about a uni-modal value near 0 ms. Eighty five per cent of the correlations larger than or equal to 0.25 had peaks between -150 and 200 ms. 5. The activity of each neuron was represented in a muscle co-ordinate system by an n-dimensional 'functional linkage vector', each element of which was the peak correlation with one of n muscles. The vector for any given neuron points in a particular direction in muscle space, depending on the similarity between the activity of the neuron and the activity of each muscle.(ABSTRACT TRUNCATED AT 400 WORDS)
A Phase I Study of Escalating Doses of the Tyrosine Kinase Inhibitor Semaxanib (SU5416) in Combination with Irinotecan in Patients with Advanced Colorectal Carcinoma (2006)

Both irinotecan and semaxanib could be given at their full single-agent recommended doses without significant toxicity, and the combination showed signs of clinical activity. However, owing to discouraging results from Phase III trials, it is unlikely that this combination will be further explored.
Inactivation of Hepatitis B and Hutchinson Strain Non‐A, Non‐B Hepatitis Viruses by Exposure to Tween 80 and Ether1 (1984)

Titrated stocks of hepatitis B virus and Hutchinson strain non-A, non-B hepatitis virus were diluted in normal serum to contain, respectively, greater than or equal to 10(6) and greater than or equal to 10(4) chimpanzee infectious doses (CID50) per milliliter and exposed to 1% Tween 80 and 20% ether at 4 degrees C for 18 h. After evaporation of the ether, the treated sera were each inoculated into two chimpanzees. The animals remained free of serologic and biochemical evidence of hepatitis during a 6-month follow-up period, and were then shown to be susceptible to infection by challenge with the original untreated inocula. To assess the effect of exposure to Tween 80/ether on coagulation factors, four lots of antihemophilic factor (AHF) concentrate and 2 lots of commercial factor IX concentrate were treated as above. For the AHF concentrate there was an average of 70% recovery of factor VIII procoagulant activity, 93% recovery of factor VIII-related antigen, and 73% recovery of fibronectin opsonin activity and no detectable change in ristocetin cofactor activity or in fibronectin antigen. Crossed immunoelectrophoresis revealed no change in migration rate of fibrinogen, fibronectin, and von Willebrand factor (vWF), although the quantity of fibrinogen was reduced. Factor VIII procoagulant activity and vWF activity remained associated during chromatography on BioGel A15.
Electrospun fiber mats: Transport properties (1999)

Abstract No Abstrast.
Mask-induced polarization effects at high numerical aperture (2005)

Degradation in image contrast becomes a concern at higher numerical apertures (NAs) due to mask-induced polarization effects. We study how different photomask materials (binary and attenuated phase shift), feature sizes and shapes, pitch values, duty ratios (line to space), and wavelengths effect the polarization of transmitted radiation. Rigorous coupled-wave analysis (RCWA) is used to simulate the polarization of radiation by the photomask. The results show that higher NA leads to greater polarization effects in all cases. Off-axis illumination increases polarization in one of the first orders, decreasing it in the other. Nonvertical sidewall angles and rounded corners can also impact polarization, but the wavelength of incident radiation has no effect on polarization effects at the same NA values. In general, materials with higher refractive indices and lower extinction coefficients tend to pass more of the TM polarization state, whereas materials with lower refractive indices and a relatively wider range of extinction coefficients pass more TE polarized radiation. These properties can provide new design considerations for the development of next-generation masking materials.
Long term outcome of twin-twin transfusion syndrome (2000)

Twins with TTTS have high perinatal mortality and neonatal morbidity, and long term neurodevelopmental morbidity in survivors is high. Further investigation into the pathogenesis and management of TTTS is required.
Data center TCP (DCTCP) (2010)

Cloud data centers host diverse applications, mixing workloads that require small predictable latency with others requiring large sustained throughput. In this environment, today's state-of-the-art TCP protocol falls short. We present measurements of a 6000 server production cluster and reveal impairments that lead to high application latencies, rooted in TCP's demands on the limited buffer space available in data center switches. For example, bandwidth hungry "background" flows build up queues at the switches, and thus impact the performance of latency sensitive "foreground" traffic.