gebhart/patrepeval huggingface dataset:
Parent meetings (2008)

Evening sessions also give working parents the chance to explore the setting and meet all the members of staff. Try the following suggestions to help you make the most of the sessions:
Efficient gene targeting by TAL effector nucleases coinjected with exonucleases in zygotes (2013)

TAL Effector Nucleases (TALENs) are versatile tools for targeted gene editing in various species. However, their efficiency is still insufficient, especially in mammalian embryos. Here, we showed that combined expression of Exonuclease 1 (Exo1) with engineered site-specific TALENs provided highly efficient disruption of the endogenous gene in rat fibroblast cells. A similar increased efficiency of up to ~30% with Exo1 was also observed in fertilized rat eggs, and in the production of knockout rats for the albino (Tyr) gene. These findings demonstrate TALENs with Exo1 is an easy and efficient method of generating gene knockouts using zygotes, which increases the range of gene targeting technologies available to various species.
The Myeloid-specific Sialic Acid-binding Receptor, CD33, Associates with the Protein-tyrosine Phosphatases, SHP-1 and SHP-2 (1999)

The myeloid restricted membrane glycoprotein, CD33, is a member of the recently characterized "sialic acid-binding immunoglobulin-related lectin" family. Although CD33 can mediate sialic acid-dependent cell interactions as a recombinant protein, its function in myeloid cells has yet to be determined. Since CD33 contains two potential immunoreceptor tyrosine-based inhibition motifs in its cytoplasmic tail, we investigated whether it might act as a signaling receptor in myeloid cells. Tyrosine phosphorylation of CD33 in myeloid cell lines was stimulated by cell surface cross-linking or by pervanadate, and inhibited by PP2, a specific inhibitor of Src family tyrosine kinases. Phosphorylated CD33 recruited both the protein-tyrosine phosphatases, SHP-1 and SHP-2. CD33 was dephosphorylated in vitro by the co-immunoprecipitated tyrosine phosphatases, suggesting that it might also be an in vivo substrate. The first CD33 phosphotyrosine motif is dominant in CD33-SHP-1/SHP-2 interactions, since mutating tyrosine 340 in a CD33-cytoplasmic tail fusion protein significantly reduced binding to SHP-1 and SHP-2 in THP-1 lysates, while mutation of tyrosine 358 had no effect. Furthermore, the NH2-terminal Src homology 2 domain of SHP-1 and SHP-2, believed to be essential for phosphatase activation, selectively bound a CD33 phosphopeptide containing tyrosine 340 but not one containing tyrosine 358. Finally, mutation of tyrosine 340 increased red blood cell binding by CD33 expressed in COS cells. Hence, CD33 signaling through selective recruitment of SHP-1/SHP-2 may modulate its ligand(s) binding activity.
B7‐H1 restricts neuroantigen‐specific T cell responses and confines inflammatory CNS damage: Implications for the lesion pathogenesis of multiple sclerosis (2008)

The co-inhibitory B7-homologue 1 (B7-H1/PD-L1) influences adaptive immune responses and has been proposed to contribute to the mechanisms maintaining peripheral tolerance and limiting inflammatory damage in parenchymal organs. To understand the B7-H1/PD1 pathway in CNS inflammation, we analyzed adaptive immune responses in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced EAE and assessed the expression of B7-H1 in human CNS tissue. B7-H1(-/-) mice exhibited an accelerated disease onset and significantly exacerbated EAE severity, although absence of B7-H1 had no influence on MOG antibody production. Peripheral MOG-specific IFN-gamma/IL-17 T cell responses occurred earlier and enhanced in B7-H1(-/-) mice, but ceased more rapidly. In the CNS, however, significantly higher numbers of activated neuroantigen-specific T cells persisted during all stages of EAE. Experiments showing a direct inhibitory role of APC-derived B7-H1 on the activation of MOG-specific effector cells support the assumption that parenchymal B7-H1 is pivotal for delineating T cell fate in the target organ. Compatible with this concept, our data investigating human brain tissue specimens show a strong up-regulation of B7-H1 in lesions of multiple sclerosis. Our findings demonstrate the critical importance of B7-H1 as an immune-inhibitory molecule capable of down-regulating T cell responses thus contributing to the confinement of immunopathological damage.
The Effect of Medical Therapy and Islet Cell Transplantation on Diabetic Nephropathy: An Interim Report (2007)

We do not find evidence of worsening of renal function after islet transplantation compared with medically treated patients.
New prodigiosin-like pigment from Alteromonas rubra (1979)

The red prodigiosin-like pigment from Alteromonas rubra was shown to be a mixture of prodigiosin (pigment 1) and a new cyclic isomer (pigment 2). The new structure was elucidated by mass and nuclear magnetic resonance spectra. Careful examinations of the prodigiosins produced by Serratia marcescens, Vibrio psychoerythrus, and an unidentified red bacterium (LL-100-6) failed to disclose any of the new pigment, pigment 2.
Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones. (1987)

Type beta transforming growth factor (TGF-beta) activity was found in conditioned medium harvested from fetal rat and neonatal mouse calvariae by using the anchorage-independent growth of normal rat kidney fibroblasts as an indicator system. Calvariae incubated with parathyroid hormone, 1,25-dihydroxyvitamin D3, and interleukin 1, all factors that stimulate bone resorption showed a concentration-dependent increase in TGF-beta activity in the culture medium. Increases in TGF-beta activity persisted undiminished for 48 hr after removal of these factors. The increases in TGF-beta activity from the resorbing bone cultures were relatively greater than the increases in bone resorption. Calcitonin inhibition of bone resorption correlated with a decrease in TGF-beta activity. Thus, agents that modulate bone resorption also affect TGF-beta activity in the bone culture medium. Changes in local concentrations of TGF-beta activity by osteotropic hormones may be important in the regulation of normal bone remodeling.
Structure of the Brain-Derived Neurotrophic Factor/Neurotrophin 3 Heterodimer (1995)

The development and sustenance of specific neuronal populations in the peripheral and central nervous systems are controlled through the binding of neurotrophic factors to high-affinity cell surface receptors. The neurotrophins (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT3; and neurotrophin 4, NT4) are dimeric molecules which share approximately 50% sequence identity. The crystal structure of the murine NGF homodimer [McDonald et al. (1991) Nature 354, 411-414] indicated that the dimer interface corresponds to regions of high sequence conservation throughout the neurotrophin family. This potential compatibility was duly exploited for the production in vitro of noncovalent heterodimers between the different neurotrophins [Radziejewski, C., & Robinson, R.C. (1993) Biochemistry 32, 13350-13356; Jungbluth et al. (1994) Eur. J. Biochem. 221, 677-685]. Here, we report the X-ray structure at 2.3 A resolution of one such heterodimer, between human BDNF, and human NT3. The NGF, BDNF, and NT3 protomers share the same topology and are structurally equivalent in regions which contribute to the dimer interface in line with the propensity of the neurotrophins to form heterodimers. Analysis of the structure of regions of the BDNF/NT3 heterodimer involved in receptor specificity led us to conclude that heterodimer binding to p75 involves distant binding sites separately located on each protomer of the heterodimer. In contrast, heterodimer interactions with the trk receptors probably utilize hybrid binding sites comprised of residues contributed by both protomers in the heterodimer. The existence of such hybrid binding sites for the trk receptor provides an explanation for the lower activity of the BDNF/NT3 heterodimer in comparison to the homodimers.(ABSTRACT TRUNCATED AT 250 WORDS)
How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology (2007)

Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) <97 mL/m(2). Diagnostic evidence of diastolic LV dysfunction can be obtained invasively (LV end-diastolic pressure >16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF.
Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the mobilization of peripheral blood cells that engraft lethally irradiated dogs (1994)

The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) and recombinant canine stem cell factor (rcSCF), a c-kit ligand, on the circulation of hematopoietic progenitor and stem cells were studied in a canine model. Administration of rcG-CSF (10 micrograms/kg) for 7 days led to a 5.4-fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 micrograms/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 micrograms/kg) had no effect on the level of peripheral blood progenitors, 7-day exposure to a combination of G-CSF plus low dose SCF led to a 21.6-fold increase (P = .03). To assess the ability of these factors to increase the circulation of cells capable of rescuing animals after lethal total body irradiation (TBI), 1 x 10(8) peripheral blood mononuclear cells (PBMC)/kg were collected and cryopreserved from animals after 7 days of treatment with G-CSF, SCF or a combination of the two. One month later, animals were exposed to 9.2 Gy TBI and transplanted with the previously collected cells. Control animals transplanted with 1 x 10(8) PBMC/kg collected without pretreatment died with marrow aplasia 11 to 29 days after TBI as did animals treated with only low-dose SCF before cell collection. In contrast, all animals given PBMC collected after G-CSF, high-dose SCF, or a combination of G-CSF plus low-dose SCF recovered granulocyte function. Recovery to 500 granulocytes/microL after transplant took 17, 18.8, and 13.6 days, respectively, (P = .056 for the difference between the combination G-CSF-SCF group and the other two groups). In both the G-CSF and SCF groups, 4 of 5 animals completely recovered while 1 of 5 in each group died with prolonged thrombocytopenia. In the combination group, all 5 animals became long- term survivors. These studies demonstrate that both G-CSF and SCF dramatically increase the level of peripheral blood hematopoietic progenitor and stem cells and support the view that these factors can act synergistically.
Intrapulmonary Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Survival and Attenuates Endotoxin-Induced Acute Lung Injury in Mice (2007)

Recent in vivo and in vitro work suggests that mesenchymal stem cells (MSC) have anti-inflammatory properties. In this study, we tested the effect of administering MSC directly into the airspaces of the lung 4 h after the intrapulmonary administration of Escherichia coli endotoxin (5 mg/kg). MSC increased survival compared with PBS-treated control mice at 48 h (80 vs 42%; p < 0.01). There was also a significant decrease in excess lung water, a measure of pulmonary edema (145 +/- 50 vs 87 +/- 20 microl; p < 0.01), and bronchoalveolar lavage protein, a measure of endothelial and alveolar epithelial permeability (3.1 +/- 0.4 vs 2.2 +/- 0.8 mg/ml; p < 0.01), in the MSC-treated mice. These protective effects were not replicated by the use of further controls including fibroblasts and apoptotic MSC. The beneficial effect of MSC was independent of the ability of the cells to engraft in the lung and was not related to clearance of the endotoxin by the MSC. MSC administration mediated a down-regulation of proinflammatory responses to endotoxin (reducing TNF-alpha and MIP-2 in the bronchoalveolar lavage and plasma) while increasing the anti-inflammatory cytokine IL-10. In vitro coculture studies of MSC with alveolar macrophages provided evidence that the anti-inflammatory effect was paracrine and was not cell contact dependent. In conclusion, treatment with intrapulmonary MSC markedly decreases the severity of endotoxin-induced acute lung injury and improves survival in mice.
T cells that help B cell responses to soluble antigen are distinguishable from those producing interleukin 2 on mitogenic or allogeneic stimulation. (1986)

An mAb MRC OX-22, reactive with the high molecular weight forms of the rat leukocyte-common antigen, has revealed a heterogeneity among CD4+ T cells in this species. Approximately two-thirds are CD4+, OX-22+, and one-third are CD4+, OX-22-. This phenotypic heterogeneity was found to be associated with a functional one. CD4+, OX-22+ cells proliferated well in mixed leukocyte culture, responded to the T cell mitogen Con A, and produced IL-2 on activation. In contrast, the CD4+, OX-22- cells performed poorly in these assays, but unlike CD4+, OX-22+ cells, did provide effective help for B cells. By sampling supernatants from cultures containing primed B cells and either of the two CD4+ T cell subsets, it was shown that, when specific antigen was included in the cultures, those containing the OX-22- subset of CD4+ cells produced high levels of antibody and some IL-2, whereas those containing the OX-22+ cells produced neither. In contrast, when specific antigen was replaced by Con A, the B cell cultures supplemented with CD4+, OX-22+ cells synthesized much higher levels of IL-2 than those containing CD4+, OX-22- cells, but only the latter cultures produced detectable levels of antibody. The data show that inducer/helper T cells comprise two functional subsets: one that, on appropriate stimulation, synthesizes high levels of IL-2, and may therefore be presumed to play an important role in cell-mediated immunity, and another that plays an essential role in humoral responses to soluble antigens. The significance of this functional heterogeneity, with regard to the possible independent regulation of cellular and humoral responses, is briefly considered.
Identification of mouse granulocyte chemotactic protein-2 from fibroblasts and epithelial cells. Functional comparison with natural KC and macrophage inflammatory protein-2 (1996)

Neutrophil and monocyte chemotactic factors were isolated from conditioned media of mouse fibroblasts and epithelial cells. Neutrophil chemotactic activities were purified to homogeneity using a four-step chromatographic procedure, and the corresponding proteins were identified by amino acid sequence analysis. Natural forms of the murine chemokines KC and macrophage inflammatory protein-2 were isolated from virus-infected fibroblasts. However, the major neutrophil chemotactic activity from fibroblasts stimulated with endotoxin plus double-stranded RNA and from PMA-treated epithelial cells resided in other 7- and 8-kDa proteins. Amino acid sequence analysis revealed a novel Cys-Xaa-Cys chemokine structure, characterized by the conservation of four cysteines and the Glu-Leu-Arg motif. Based on the completely identified primary structure of this natural protein, this chemokine must be considered to be the murine homologue of human and bovine granulocyte chemotactic protein-2 (GCP-2; 61 and 64% identical residues, respectively). Due to NH2-terminal cleavage, 11 different forms of mouse GCP-2 were discovered. In contrast to human and bovine GCP-2, functional comparison of long and short NH2-terminal forms of mouse GCP-2 demonstrated that truncated mouse GCP-2 (short form) has a higher specific activity in neutrophil activation (gelatinase B release) and chemotaxis assays. Furthermore, mouse GCP-2 was more potent than human GCP-2 on human neutrophils, and more active than murine KC and macrophage inflammatory protein-2 on mouse neutrophils. In view of the absence of a murine homologue for IL-8, NH2-terminally processed GCP-2 can be considered a major neutrophil chemoattractant in the mouse during the inflammatory response.
Functional size analysis of F-ATPase from Escherichia coli by radiation inactivation (1993)

A radiation inactivation technique was employed to determine the functional size of adenosine triphosphatase from Escherichia coli (EF0EF1-ATPase). Functional units of the membrane-bound and the soluble ATPases were estimated to be 300 +/- 39 and 295 +/- 32 kDa, respectively. The presence of the free radical scavenger dithiothreitol was crucial in measuring the radiation inactivation size of ATPase. When gramicidin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone were added, an increase in the functional mass of membrane-bound ATPase was observed. In contrast, valinomycin and KCl had hardly any effect on the functional size of ATPase. We also determined a functional unit of 355 +/- 33 kDa for proton translocation by a fluorescence quenching technique. A reconstitution study using irradiated coupling factor 1 (EF1)-depleted membrane revealed that the functional mass of the proton channel was 96 +/- 11 kDa. A similar functional size for ATP-Pi exchange and ATP hydrolysis implies that both reactions might utilize identical machinery. Furthermore, functional units of soluble EF1 for unisite (nonsteady state) and multisite (steady state) ATP hydrolysis were calculated as 200 +/- 32 and 298 +/- 32 kDa, respectively. A working hypothesis was proposed from radiation inactivation analysis to elucidate the structure and mechanism of F1-ATPase.
Salmonella typhi rpoS mutant is less cytotoxic than the parent strain but survives inside resting THP-1 macrophages (1998)

Transcription of the stationary-phase sigma factor RpoS of Salmonella typhi increased in the macrophage. A single rpoS mutant of S. typhi was constructed to analyze the role of RpoS in intracellular multiplication of the bacterium and host cell killing. This mutant was sensitive to starvation, low pH and hydrogen peroxide; however, it could still multiply inside resting macrophages and was less cytotoxic than the wild-type strain. Therefore, S. typhi might produce RpoS-dependent factors which could contribute to host cell death.
Fast Decoding in Sequence Models using Discrete Latent Variables (2018)

Autoregressive sequence models based on deep neural networks, such as RNNs, Wavenet and the Transformer attain state-of-the-art results on many tasks. However, they are difficult to parallelize and are thus slow at processing long sequences. RNNs lack parallelism both during training and decoding, while architectures like WaveNet and Transformer are much more parallelizable during training, yet still operate sequentially during decoding. Inspired by [arxiv:1711.00937], we present a method to extend sequence models using discrete latent variables that makes decoding much more parallelizable. We first auto-encode the target sequence into a shorter sequence of discrete latent variables, which at inference time is generated autoregressively, and finally decode the output sequence from this shorter latent sequence in parallel. To this end, we introduce a novel method for constructing a sequence of discrete latent variables and compare it with previously introduced methods. Finally, we evaluate our model end-to-end on the task of neural machine translation, where it is an order of magnitude faster at decoding than comparable autoregressive models. While lower in BLEU than purely autoregressive models, our model achieves higher scores than previously proposed non-autoregressive translation models.
Behavioral Recovery Induced by Applied Electric Fields After Spinal Cord Hemisection in Guinea Pig (1987)

Applied electric fields were used to promote axonal regeneration in spinal cords of adult guinea pigs. A propriospinal intersegmental reflex (the cutaneous trunci muscle reflex) was used to test lateral tract function after hemisection of the thoracic spinal cord. An electrical field (200 microvolts per millimeter, cathode rostral) applied across the lesion led to functional recovery of the cutaneous trunci muscle reflex in 25 percent of experimental animals, whereas the functional deficit remained in control animals, which were implanted with inactive stimulators.
Indirect activity recognition using a target-mounted camera (2011)

We present a new method to recognize activity patterns from video acquired by a camera mounted on the target (i.e., activity performer). Because of this unconventional camera setting, algorithms for activity recognition must be redesigned because the activity performer never appears in the video. We approach this recognition problem indirectly by observing background changes in the acquired image sequences. A motion histogram scheme is proposed to characterize activity patterns from the perspective of camera motion. This histogram is utilized as the input to our activity identification algorithm based on a hidden Markov model. Our experimental results show that our method successfully identifies complex activities even the motion profile of an activity involves a large variance. Our method is applied to the construction of a new wearable device that helps people lose weight and maintain a healthy lifestyle by automatically recognizing and monitoring physical activity.
Cell cycle and cell biology (1997)

The yeast cytoskeleton protein secretion, membrane biogenesis, and endocytosis biogenesis of yeast wall and surface components biogenesis and function of the yeast vacuole the nucleus and nucleocyttoplasmic transport in saccharomyces cerevisiae peroxisomes cell cycle control in saccharomyces cerevisiae cell cycle control in fission yeast mitosis and cytokinesis in the fission yeast schizosaccharomyces pombe the pathway of cell and nuclear fusion during mating in saccharomyces cerevisiae meiosis and sporulation in saccharomyces cerevisiae mating and sporulation in schizosaccharomyces pombe.