gebhart/patrepeval huggingface dataset:
The mRNA 5' cap-binding protein, eIF-4E, cooperates with v-myc or E1A in the transformation of primary rodent fibroblasts. (1992)

We present evidence that eIF-4E, the mRNA 5' cap-binding protein, cooperates with two immortalizing oncogenes, v-myc and E1A, to cause transformation of rat embryo fibroblasts. eIF-4E alone can transform rat embryo fibroblasts when selection is applied. The pattern of transformation by eIF-4E is similar to that of p21 Ras, raising the possibility that eIF-4E shares a common signal transduction pathway with p21 Ras.
Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection (2006)

To date there is insufficient data to determine whether PGS is an effective intervention in IVF/ICSI for improving live birth rates. Available data on PGS for advanced maternal age showed no difference in live birth rate and ongoing pregnancy rate. However, only two randomised trials were found, of which one included only 39 patients. For both studies comments on their methodological quality can be made. Therefore more properly conducted randomised controlled trials are needed. Until such trials have been performed PGS should not be used in routine patient care.
Evidence for the use of intramuscular injections in outpatient practice. (2009)

There are few studies comparing the outcomes of patients who are treated with oral versus intramuscular antibiotics, corticosteroids, nonsteroidal anti-inflammatory drugs, or vitamin B12. This may lead to confusion about when the intramuscular route is indicated. For example, intramuscular ceftriaxone for Neisseria gonorrhoeae infection and intramuscular penicillin G benzathine for Treponema pallidum infection are the treatments of choice. However, oral antibiotics are the treatment of choice for the outpatient treatment of pneumonia and most other outpatient bacterial infections. Oral corticosteroids are as effective as intramuscular corticosteroids and are well-tolerated by most patients. High daily doses of oral vitamin B12 with ongoing clinical surveillance appear to be as effective as intramuscular treatment. Few data support choosing intramuscular ketorolac over an oral nonsteroidal anti-inflammatory drug unless the patient is unable to tolerate an oral medication. For other indications, the intramuscular route should be considered only when the delivery of a medication must be confirmed, such as when a patient cannot tolerate an oral medication, or when compliance is uncertain.
In vitro generation of an HTLV-III variant by neutralizing antibody. (1986)

Transmission and culture of "parental" virus (HTLV-III) from H9 cells transfected with the cloned isolate (lambda HXB-2D) in human serum possessing HTLV-III neutralizing antibody selected for a "variant" that was not neutralized by the selecting serum but was neutralized by another antibody-positive serum "Control" virus, selected in serum lacking neutralizing antibody, and the variant showed highly similar tryptic peptide maps of the major envelope glycoprotein, and no changes in restriction enzyme patterns of viral DNA. These findings show that HTLV-III type-specific neutralizing antibodies occur, can influence the propagation of variant viruses that may arise, and presumably result from minor changes in the eliciting antigen. The extent to which such type-specific neutralizing antibodies influence immune surveillance against HTLV-III infection in vivo, a question with relevance to future vaccination attempts, remains to be determined. Nucleotide sequencing of the control and variant envelope genes may elucidate a region important for virus neutralization and vaccine development.
Learning to Explore using Active Neural SLAM (2020)

This work presents a modular and hierarchical approach to learn policies for exploring 3D environments, called `Active Neural SLAM'. Our approach leverages the strengths of both classical and learning-based methods, by using analytical path planners with learned SLAM module, and global and local policies. The use of learning provides flexibility with respect to input modalities (in the SLAM module), leverages structural regularities of the world (in global policies), and provides robustness to errors in state estimation (in local policies). Such use of learning within each module retains its benefits, while at the same time, hierarchical decomposition and modular training allow us to sidestep the high sample complexities associated with training end-to-end policies. Our experiments in visually and physically realistic simulated 3D environments demonstrate the effectiveness of our approach over past learning and geometry-based approaches. The proposed model can also be easily transferred to the PointGoal task and was the winning entry of the CVPR 2019 Habitat PointGoal Navigation Challenge.
Mechanisms, models and biomarkers in amyotrophic lateral sclerosis (2013)

The last 30 years have seen a major advance in the understanding of the clinical and pathological heterogeneity of amyotrophic lateral sclerosis (ALS), and its overlap with frontotemporal dementia. Multiple, seemingly disparate biochemical pathways converge on a common clinical syndrome characterized by progressive loss of upper and lower motor neurons. Pathogenic themes in ALS include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, altered energy metabolism, and most recently RNA mis-processing. The transgenic rodent, overexpressing mutant superoxide dismutase-1, is now only one of several models of ALS pathogenesis. The nematode, fruit fly and zebrafish all offer fresh insight, and the development of induced pluripotent stem cell-derived motor neurons holds promise for the screening of candidate therapeutics. The lack of useful biomarkers in ALS contributes to diagnostic delay, and the inability to stratify patients by prognosis may be an important factor in the failure of therapeutic trials. Biomarkers sensitive to disease activity might lessen reliance on clinical measures and survival as trial endpoints and reduce study length. Emerging proteomic markers of neuronal loss and glial activity in cerebrospinal fluid, a cortical signature derived from advanced structural and functional MRI, and the development of more sensitive measurements of lower motor neuron physiology are leading a new phase of biomarker-driven therapeutic discovery.
Stencil mask ion implantation technology (2002)

The ion implantation process is important for the development or manufacturing of semiconductor devices, because ion implantation conditions directly influence some characteristics of semiconductor devices. Recently, we developed a new implantation technology, stencil mask ion implantation technology (SMIT). In the SMIT system, the stencil mask acts like a resist mask, and ions passing through the mask holes are implanted into selected regions of the Si substrate chip by chip. Use of SMIT has several advantages, notably lower manufacturing cost and shorter process time than in the case of conventional processing, because no photolithography process (including deposition and stripping of resist) is required. We have already demonstrated an application of SMIT to transistor fabrication, using various implanted dose conditions for the same wafer. Threshold voltage values can be controlled as effectively by implanted doses as they can by conventional implantation, and the dose dependence of the threshold voltage could be obtained from one wafer to which various implantation conditions are applied. Using SMIT, implantation conditions can be changed chip by chip without additional processes. This flexibility of implantation conditions is another advantage of SMIT. In this paper, we propose stencil mask ion implantation technology and show some fundamental results obtained by applying SMIT.
Intoxication of high affinity IL-2 receptor positive thymocytes blocks early stages of T cell maturation (1992)

Early murine fetal thymocytes express functional, high affinity IL-2 receptors as determined by: (i) the presence of IL-2R beta chain (p75) mRNA; (ii) IL-2 (10 U/ml) induced cell proliferation/cellular maturation in lobe submersion cultures (LSC). Under the influence of IL-2, early thymocytes differentiate in vitro into more mature, early single positive CD4-CD8+ followed in vivo by double positive CD4+CD8+ and single positive CD4+CD8-T and CD4-CD8+ thymocytes. Specific intoxication of high affinity IL-2R positive thymocytes by recombinant interleukin-2-diphtheria toxin-related fusion protein (DAB486-IL-2) results in transient, dose dependent blockade of in vivo and in vitro thymocyte maturation. DAB486-IL-2 induced effects upon in vivo maturation are reversible within 2 weeks after cessation of drug administration. Taken together, these results demonstrate the expression of functional, high affinity IL-2 receptors on early thymocytes. Elimination of high affinity IL-2 receptor positive thymocytes with DAB486-IL-2 results in transient blockade of T cell maturation. Since DAB486-IL-2 is now in clinical trial, it is reassuring to note that it does not permanently disrupt thymic maturation.
Transient nuclear envelope rupturing during interphase in human cancer cells (2012)

Neoplastic cells are often characterized by specific morphological abnormalities of the nuclear envelope (NE), which have been used for cancer diagnosis for more than a century. The NE is a double phospholipid bilayer that encapsulates the nuclear genome, regulates all nuclear trafficking of RNAs and proteins and prevents the passive diffusion of macromolecules between the nucleoplasm and the cytoplasm. Whether there is a consequence to the proper functioning of the cell and loss of structural integrity of the nucleus remains unclear. Using live cell imaging, we characterize a phenomenon wherein nuclei of several proliferating human cancer cell lines become temporarily ruptured during interphase. Strikingly, NE rupturing was associated with the mislocalization of nucleoplasmic and cytoplasmic proteins and, in the most extreme cases, the entrapment of cytoplasmic organelles in the nuclear interior. In addition, we observed the formation of micronuclei-like structures during interphase and the movement of chromatin out of the nuclear space. The frequency of these NE rupturing events was higher in cells in which the nuclear lamina, a network of intermediate filaments providing mechanical support to the NE, was not properly formed. Our data uncover the existence of a NE instability that has the potential to change the genomic landscape of cancer cells.
CD4 + CD25 + Foxp3 + regulatory T cells induce alternative activation of human monocytes/macrophages (2007)

CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are potent suppressors of the adaptive immune system, but their effects on innate immune cells are less well known. Here we demonstrate a previously uncharacterized function of Tregs, namely their ability to steer monocyte differentiation toward alternatively activated macrophages (AAM). AAM are cells with strong antiinflammatory potential involved in immune regulation, tissue remodeling, parasite killing, and tumor promotion. We show that, after coculture with Tregs, monocytes/macrophages display typical features of AAM, including up-regulated expression of CD206 (macrophage mannose receptor) and CD163 (hemoglobin scavenger receptor), an increased production of CCL18, and an enhanced phagocytic capacity. In addition, the monocytes/macrophages have reduced expression of HLA-DR and a strongly reduced capacity to respond to LPS in terms of proinflammatory mediator production (IL-1beta, IL-6, IL-8, MIP-1alpha, TNF-alpha), NFkappaB activation, and tyrosine phosphorylation. Mechanistic studies reveal that CD4(+)CD25(+)CD127(low)Foxp3(+) Tregs produce IL-10, IL-4, and IL-13 and that these cytokines are the critical factors involved in the suppression of the proinflammatory cytokine response. In contrast, the Treg-mediated induction of CD206 is entirely cytokine-independent, whereas the up-regulation of CD163, CCL18, and phagocytosis are (partly) dependent on IL-10 but not on IL-4/IL-13. Together these data demonstrate a previously unrecognized function of CD4(+)CD25(+)Foxp3(+) Tregs, namely their ability to induce alternative activation of monocytes/macrophages. Moreover, the data suggest that the Treg-mediated induction of AAM partly involves a novel, cytokine-independent pathway.
Optical Studies on KBr:Tl and KCl‐Br:Tl Mixed Crystals (2009)

Optical absorption spectra of KBr:Tl + (0.0125 mol%) single crystals shows A, B and C bands around 258, 220 and 210 nm respectively. In KCl 0.1 Br 0.9 :Tl + (0.0125 mol%) mixed crystals exhibit slightly broadening of the A‐band towards lower wavelength side. The broadening of the absorption spectra are suggested to be due to some complex Tl + centers involving Br - and Cl - ions formed in the mixed crystals. When excited at A, B and C‐bands of Tl + ions, PL of KBr:Tl + showed emission band around 320 with a prominent shoulder around 365 nm. In KCl 0.1 Br 0.9 mixed crystals the shoulder around 365 nm is not prominent due to the perturbing influence of Cl - ions. Addition bands in the excitation spectra are attributed to the presence of Tl + dimmers. PSL observed in X‐ray irradiated crystals resembled their respective PL emissions indicating that PSL in them is due to Tl + ions.
Uncoupling of sustained MAMP receptor signaling from early outputs in an Arabidopsis endoplasmic reticulum glucosidase II allele (2009)

Recognition of microbe-associated molecular patterns (MAMPs), conserved structures typical of a microbial class, triggers immune responses in eukaryotes. This is accompanied by a diverse set of physiological responses that are thought to enhance defense activity in plants. However, the extent and mechanisms by which MAMP-induced events contribute to host immunity are poorly understood. Here we reveal Arabidopsis priority in sweet life4 (psl4) and psl5 mutants that are insensitive to the bacterial elongation factor (EF)-Tu epitope elf18 but responsive to flagellin epitope flg22. PSL4 and PSL5, respectively, identify beta- and alpha-subunits of endoplasmic reticulum-resident glucosidase II, which is essential for stable accumulation and quality control of the elf18 receptor EFR but not the flg22 receptor FLS2. We notice that EFR signaling is partially and differentially impaired without a significant decrease of the receptor steady-state levels in 2 weakly dysfunctional gIIalpha alleles, designated psl5-1 and rsw3. Remarkably, rsw3 plants exhibit marked supersusceptibility against a virulent bacterial phytopathogen despite nearly intact coactivation of MAPKs, reactive oxygen species, ethylene biosynthesis, and callose deposition in response to elf18, demonstrating that these signaling outputs alone are insufficient to mount effective immunity. However, rsw3 plants fail to maintain high transcript levels of defense-promoting WRKY, PR1, and PR2 genes at late time points (4 to 24 h) after elf18 elicitation. This points to an unexpected separation between initial and sustained activation of EFR-mediated signaling in the absence of proper glucosidase II-mediated endoplasmic reticulum quality control. Our findings strongly suggest the importance of sustained MAMP receptor signaling as a key step in the establishment of robust immunity.
Distinct regions in the 3′ untranslated region are responsible for targeting and stabilizing utrophin transcripts in skeletal muscle cells (2001)

In this study, we have sought to determine whether utrophin transcripts are targeted to a distinct subcellular compartment in skeletal muscle cells, and have examined the role of the 3' untranslated region (UTR) in regulating the stability and localization of utrophin transcripts. Our results show that utrophin transcripts associate preferentially with cytoskeleton-bound polysomes via actin microfilaments. Because this association is not evident in myoblasts, our findings also indicate that the localization of utrophin transcripts with cytoskeleton-bound polysomes is under developmental influences. Transfection of LacZ reporter constructs containing the utrophin 3'UTR showed that this region is critical for targeting chimeric mRNAs to cytoskeleton-bound polysomes and controlling transcript stability. Deletion studies resulted in the identification of distinct regions within the 3'UTR responsible for targeting and stabilizing utrophin mRNAs. Together, these results illustrate the contribution of posttranscriptional events in the regulation of utrophin in skeletal muscle. Accordingly, these findings provide novel targets, in addition to transcriptional events, for which pharmacological interventions may be envisaged to ultimately increase the endogenous levels of utrophin in skeletal muscle fibers from Duchenne muscular dystrophy (DMD) patients.
Transmembrane Peptides as Inhibitors of ErbB Receptor Signaling (2004)

Receptor tyrosine kinases have a single transmembrane (TM) segment that is usually assumed to play a passive role in ligand-induced dimerization and activation of the receptor. However, mutations within some of these receptors, and recent studies with the epidermal growth factor (EGF) and ErbB2 receptors have indicated that interactions between TM domains do contribute to stabilization of ligand-independent and/or ligand-induced receptor dimerization and activation. One consequence of the importance of these interactions is that short hydrophobic peptides corresponding to these domains should act as specific inhibitors. To test this hypothesis, we constructed expression vectors encoding short fusion peptides encompassing native or mutated TM domains of the EGF, ErbB2, and insulin receptors. In human cell lines overexpressing the wild-type EGF receptor or ErbB2, we observed that the peptides are expressed at the cell surface and that they inhibit specifically the autophosphorylation and signaling pathway of their cognate receptor. Identical results were obtained with peptides chemically synthesized. Mechanism of action involves inhibition of dimerization of the receptors as shown by the lack of effects of mutant nondimerizing sequences, completed by density centrifugation and covalent cross-linking experiments. Our findings stress the role of TM domain interactions in ErbB receptor function, and possibly for other single-spanning membrane proteins.
An Alphavirus Replicon-Based Human Metapneumovirus Vaccine Is Immunogenic and Protective in Mice and Cotton Rats (2008)

Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that causes upper and lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. Here, we developed Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and protective efficacy of these vaccine candidates in mice and cotton rats. VRPs encoding hMPV F protein, when administered intranasally, induced F-specific virus-neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. Challenge virus replication was reduced significantly in both the upper and lower respiratory tracts following intranasal hMPV challenge in these animals. However, vaccination with hMPV G protein VRPs did not induce neutralizing antibodies or protect animals from hMPV challenge. Close examination of the histopathology of the lungs of VRP-MPV F-vaccinated animals following hMPV challenge revealed no enhancement of inflammation or mucus production. Aberrant cytokine gene expression was not detected in these animals. Together, these results represent an important first step toward the use of VRPs encoding hMPV F proteins as a prophylactic vaccine for hMPV.
The role of immunostimulation in the development of postweaning multisystemic wasting syndrome in pigs under field conditions. (2006)

We evaluated the effects of immunostimulation in the development of postweaning multisystemic wasting syndrome (PMWS) in 930 pigs 53 to 54 d old in a grower/finisher barn with a history of PMWS. The pigs were allocated to 5 treatment groups: 4 groups received a single intramuscular injection of RespiSure-ONE (a commercial Mycoplasma hyopneumoniae vaccine; n = 197), Emulsigen (an oil-based adjuvant; n = 172), Alhydrogel (an aluminum-hydroxide-based adjuvant; n = 172), or physiologic saline (n = 218); 1 group received no treatment (n = 171). Pigs affected by PMWS were found in all the groups. Antigen to Porcine circovirus type 2 (PCV-2) was detected by immunohistochemical testing within lesions of mesenteric lymph node, spleen, Peyer's patch, and lung of affected pigs. There was no significant difference in the incidence of PMWS among the groups. The findings indicate that immunostimulation did not influence the expression of PMWS in this study. Thus, routine vaccination against swine diseases may not significantly contribute to the occurrence of PMWS under field conditions.
Disruption of a Sugar Transporter Gene Cluster in a Hyperthermophilic Archaeon Using a Host-Marker System Based on Antibiotic Resistance (2007)

We have developed a gene disruption system in the hyperthermophilic archaeon Thermococcus kodakaraensis using the antibiotic simvastatin and a fusion gene designed to overexpress the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene (hmg(Tk)) with the glutamate dehydrogenase promoter. With this system, we disrupted the T. kodakaraensis amylopullulanase gene (apu(Tk)) or a gene cluster which includes apu(Tk) and genes encoding components of a putative sugar transporter. Disruption plasmids were introduced into wild-type T. kodakaraensis KOD1 cells, and transformants exhibiting resistance to 4 microM simvastatin were isolated. The transformants exhibited growth in the presence of 20 microM simvastatin, and we observed a 30-fold increase in intracellular HMG-CoA reductase activity. The expected gene disruption via double-crossover recombination occurred at the target locus, but we also observed recombination events at the hmg(Tk) locus when the endogenous hmg(Tk) gene was used. This could be avoided by using the corresponding gene from Pyrococcus furiosus (hmg(Pf)) or by linearizing the plasmid prior to transformation. While both gene disruption strains displayed normal growth on amino acids or pyruvate, cells without the sugar transporter genes could not grow on maltooligosaccharides or polysaccharides, indicating that the gene cluster encodes the only sugar transporter involved in the uptake of these compounds. The Deltaapu(Tk) strain could not grow on pullulan and displayed only low levels of growth on amylose, suggesting that Apu(Tk) is a major polysaccharide-degrading enzyme in T. kodakaraensis.
Analysis of warfarin-albumin binding by HPLC with internal-surface reversed-phase silica column. (1988)

Protein binding of warfarin with bovine serum albumin (BSA) was analyzed by HPLC with an internal-surface reversed-phase (ISRP) silica column. When a relatively large volume (2100 μl) of the sample solution containing warfarin and BSA was applied directly to the ISRP column, two distinct peaks appeared separately from the protein peak. one of these had a short retention time and was ascribable to warfarin released from the strong-binding sites on BSA molecules during the process of chromatography. The other peak had a long retention time and was due to the sum of free warfarin and that released from weak-binding sites. The separation profiles of these peaks were investigated with varying injection volumes and mobile phase conditions. The binding constants for the strong site and the weak site were determined from the area of these warfarin peaks. The results were comparable to the reported values.