Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphological, immunophenotypical and isoenzymatic profiles of human leukemia cells and derived T‐cell lines

Six monoclonal leukemia cell lines (MOLT 12‐17) were established from three patients with acute leukemia. Two of the patients' samples were of the T‐ALL type, the third had morphological, isoenzymatic and immunological features of AMoL. The cell lines resulting from these original cells displayed distinct, but stable marker profiles. A comparison between primary cells and resulting cell lines showed that the cell lines established from patients with T‐ALL (MOLT 12, 13, 14 and MOLT 16, 17) expressed similar phenotypes and isoenzyme patterns, but were different in a few specific aspects. The changes suggest a modulation of marker expression in vitro or an arrest at a more immature stage of differentiation than the original cells. The cell line MOLT 15 established from the case of AMoL exhibited a quite discordant profile when compared to the primary sample: the cells lacked all previously found myelomonocytic antigens and a monocyte‐specific esterase isoenzyme, but expressed the T‐cell associated CD7 antigen and had rearrangements and RNA transcripts of the T‐cell receptor β and γ chain genes. This striking discrepancy between the patient's malignant cells and the corresponding cell line suggests that subpopulation selection had occurred in culture.
Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium

Claudins are tight junction integral membrane proteins that are key regulators of the paracellular pathway. Defects in claudin-16 (CLDN16) and CLDN19 function result in the inherited human renal disorder familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Previous studies showed that siRNA knockdown of CLDN16 in mice results in a mouse model for FHHNC. Here, we show that CLDN19-siRNA mice also developed the FHHNC symptoms of chronic renal wasting of magnesium and calcium together with defective renal salt handling. siRNA knockdown of CLDN19 caused a loss of CLDN16 from tight junctions in the thick ascending limb (TAL) without a decrease in CLDN16 expression level, whereas siRNA knockdown of CLDN16 produced a similar effect on CLDN19. In both mouse lines, CLDN10, CLDN18, occludin, and ZO-1, normal constituents of TAL tight junctions, remained correctly localized. CLDN16- and CLDN19-depleted tight junctions had normal barrier function but defective ion selectivity. These data, together with yeast two-hybrid binding studies, indicate that a heteromeric CLDN16 and CLDN19 interaction was required for assembling them into the tight junction structure and generating cation-selective paracellular channels.
Effect of diagnostic threshold on the validity and reliability of epidemiological caries diagnosis using the Dundee Selectable Threshold Method for caries diagnosis (DSTM).

OBJECTIVES To develop a method for recording dental caries at the D1 (enamel and dentine) diagnostic threshold (without loss of D3 information) and assess its reliability, 'benchmark' validity and potential effects on reported caries prevalence and needs assessment. METHODS Multi-examiner training, calibration and validation trial. Two groups of 10 dental examiners were trained to diagnose dental caries at the D1 (enamel and dentine) diagnostic threshold under the conditions of a caries prevalence survey, prior to a calibration trial being undertaken. RESULTS Where 'experienced examiners' were trained to examine at the D1 (enamel and dentine) diagnostic threshold, under the conditions of a cross-sectional epidemiological survey, there was no significant deterioration in inter-examiner agreement on the assessment of teeth and a significant difference in one of two comparisons on the assessment of surfaces using the kappa statistic. Assessed against a benchmark examiner, there was no significant loss of sensitivity at the D1 diagnostic threshold compared with the D3 threshold and, although there was a significant loss of specificity at the D1 threshold, all specificity values could be considered to be high. CONCLUSIONS Modifying the diagnostic criteria typically used in surveys of caries prevalence (to allow assessment of the levels of enamel caries which could benefit from preventive care as well as dentinal caries requiring restorative care) in adolescents does not adversely affect the reliability or benchmark validity of experienced examiners to a significant degree.
Inducing self-motion sensations in driving simulators using force-feedback and haptic motion

Producing sensations of motion in driving simulators often requires using cumbersome and expensive motion platforms. In this article we present a novel and alternative approach for producing self-motion sensations in driving simulations by relying on haptic-feedback. The method consists in applying a force-feedback proportional to the acceleration of the virtual vehicle directly to the hands of the driver, by means of a haptic device attached to the manipulated controller (or a steering wheel). We designed a proof-of-concept based on a standard gamepad physically attached at the extremity of a standard 3DOF haptic display. Haptic effects were designed to match notably the acceleration/braking (longitudinal forces) and left/right turns (lateral forces) of the virtual vehicle. A preliminary study conducted with 23 participants, engaged in gamepad-based active VR navigations in a straight line, showed that haptic motion effects globally improved the involvement and realism of motion sensation for participants with prior experience with haptic devices. Taken together, our results suggest that our approach could be further tested and used in driving simulators in entertainment and/or professional contexts.
VCSEL-Based Light Sources—Scalability Challenges for VCSEL-Based Multi-100- Gb/s Systems

Future high-performance computers require optical interconnects with aggregated Exa-Byte/s data transport. Densely packed arrays of vertical-cavity surface-emitting lasers (VCSELs) might present the only feasible technical solution. The high-speed properties of semiconductor lasers, however, are strongly affected by their operating temperature. Thermal crosstalk becomes dominant when densely packed arrays of high-speed VCSELs are required. In this paper, we derive the maximum bandwidth of future VCSEL-based optical interconnects from the influence of device heating occurring in high-speed VCSEL arrays. Furthermore, we estimate the scalability of this technology and address the challenges. From our calculations we obtain, that VCSEL arrays are scalable from a bandwidth density of 100 Gbps/mm2 with today's devices up to a technological limit of 15 Tbps/mm2.
The assembly factor Erb1 functions in multiple remodeling events during 60S ribosomal subunit assembly in S. cerevisiae

Abstract A major gap in our understanding of ribosome assembly is knowing the precise function of each of the ∼200 assembly factors. The steps in subunit assembly in which these factors participate have been examined for the most part by depleting each protein from cells. Depletion of the assembly factor Erb1 prevents stable assembly of seven other interdependent assembly factors with pre-60S subunits, resulting in turnover of early preribosomes, before the ITS1 spacer can be removed from 27SA3 pre-rRNA. To investigate more specific functions of Erb1, we constructed eight internal deletions of 40–60 amino acid residues each, spanning the amino-terminal half of Erb1. The erb1Δ161–200 and erb1Δ201–245 deletion mutations block a later step than depletion of Erb1, namely cleavage of the C2 site that initiates removal of the ITS2 spacer. Two other remodeling events fail to occur in these erb1 mutants: association of twelve different assembly factors with domain V of 25S rRNA, including the neighborhood surrounding the peptidyl transferase center, and stable association of ribosomal proteins with rRNA surrounding the polypeptide exit tunnel. This suggests that successful initiation of construction of these functional centers is a checkpoint for committing to spacer removal.
Improving the accuracy of recombinant protein production through integration of bioinformatics, statistical and mass spectrometry methodologies

Heterologous protein production is a key technology for biotechnological, health sciences and many other research fields. Various approaches have been developed for its optimization, but the research emphasis has been on optimization of protein yield rather than protein quality. In this study, we have established a workflow for synthetic gene optimization for heterologous protein expression that combines bioinformatics, laboratory experiments, mass spectrometry and statistical analysis. Two gene primary structure analysis platforms, Anaconda and EuGene, and multivariate optimization methods were employed to re‐design the Plasmodium falciparum lysyl‐tRNA synthetase gene for optimal expression in Escherichia coli. Synthetic genes were expressed from common vectors, and amino acid mis‐incorporations in the expressed proteins were detected and quantified using mass spectrometry. The association between the identified amino acid mis‐incorporations and 23 gene variables was then analysed. The synthetic genes yielded significantly higher levels of protein relative to the wild‐type gene, but 71 amino acid mis‐incorporation sites were observed along the whole protein and across the synthetic genes that were statistically associated with specific codons and protein secondary structures. The optimization method that led to production of the most accurate protein was based on a multivariate approach that combined variables that are known to influence mRNA translation.
A Broadly Neutralizing Human Monoclonal Antibody Directed against a Novel Conserved Epitope on the Influenza Virus H3 Hemagglutinin Globular Head

ABSTRACT Most neutralizing antibodies elicited during influenza virus infection or vaccination target immunodominant, variable epitopes on the globular head region of hemagglutinin (HA), which leads to narrow strain protection. In this report, we describe the properties of a unique anti-HA monoclonal antibody (MAb), D1-8, that was derived from human B cells and exhibits potent, broad neutralizing activity across antigenically diverse influenza H3 subtype viruses. Based on selection of escape variants, we show that D1-8 targets a novel epitope on the globular head region of the influenza virus HA protein. The HA residues implicated in D1-8 binding are highly conserved among H3N2 viruses and are located proximal to antigenic site D. We demonstrate that the potent in vitro antiviral activity of D1-8 translates into protective activity in mouse models of influenza virus infection. Furthermore, D1-8 exhibits superior therapeutic survival benefit in influenza virus-infected mice compared to the neuraminidase inhibitor oseltamivir when treatment is started late in infection. The present study suggests the potential application of this monoclonal antibody for the therapeutic treatment of H3N2 influenza virus infection. IMPORTANCE Recently, a few globular head-targeting MAbs have been discovered that exhibit activity against different subtypes of influenza subtypes, such as H1; however, none of the previously described MAbs showed broadly neutralizing activity against diverse H3 viruses. In this report, we describe a human MAb, D1-8, that exhibits potent, broadly neutralizing activity against antigenically diverse H3 subtype viruses. The genotypic analysis of escape mutants revealed a unique putative epitope region in the globular head of H3 HA that is comprised of highly conserved residues and is distinct from the receptor binding site. Furthermore, we demonstrate that D1-8 exhibits superior therapeutic efficacy in influenza virus-infected mice compared to the neuraminidase inhibitor oseltamivir when treatment is started late in infection. In addition to describing a novel anti-globular head of H3 HA MAb with potent broadly neutralizing activity, our report suggests the potential of D1-8 for therapeutic treatment of seasonal influenza virus H3 infection.
A Novel Plant-Specific Family Gene, ROOT PRIMORDIUM DEFECTIVE 1, Is Required for the Maintenance of Active Cell Proliferation1

Hypocotyl segments of Arabidopsis (Arabidopsis thaliana) produce adventitious roots in response to exogenously supplied auxin. root primordium defective 1 (rpd1) is a temperature-sensitive mutant isolated on the basis of impairment in this phenomenon. This study describes further phenotypic analysis of the rpd1 mutant and isolation of the RPD1 gene. When adventitious root formation was induced from the rpd1 explants at the restrictive temperature, cell proliferation leading to root promordia formation was initiated at the same time as in wild-type explants. However, development of the root primordia was arrested thereafter in the mutant. Temperature-shift experiments indicated that RPD1 exerts its function before any visible sign of root primordium formation. The expression patterns of the auxin-responsive gene DR5:β-glucuronidase and the cytodifferentiation marker gene SCARECROW suggest that the rpd1 mutation interferes with neither axis formation nor cellular patterning at the initial stage of root primordium development. Taken together with the effect of the rpd1 mutation on callus cell proliferation, these data imply a role for RPD1 in prearranging the maintenance of the active cell proliferation during root primordium development. Positional cloning of the RPD1 gene revealed that it encodes a member of a novel protein family specific to the plant kingdom. Disruption of the RPD1 gene by a T-DNA insertion caused embryogenesis arrest at the globular to transition stages. This phenotype is consistent with the hypothesized function of RPD1 in the maintenance of active cell proliferation.
Virulence of endemic nonpigmented northern Australian Staphylococcus aureus clone (clonal complex 75, S. argenteus) is not augmented by staphyloxanthin.

Staphylococcus aureus clonal complex 75 (herein referred to as S. argenteus) lacks the carotenoid pigment operon, crtOPQMN, responsible for production of the putative virulence factor, staphyloxanthin. Although a common cause of community-onset skin infections among Indigenous populations in northern Australia, this clone is infrequently isolated from hospital-based patients with either bacteremic or nonbacteremic infections. We hypothesized that S. argenteus would have attenuated virulence compared to other S. aureus strains due to its staphyloxanthin "deficiency. " Compared to prototypical S. aureus strains, S. argenteus was more susceptible to oxidative stress and neutrophil killing in vitro and had reduced virulence in murine sepsis and skin infection models. Transformation with pTX-crtOPQMN resulted in staphyloxanthin expression and increased resistance to oxidative stress in vitro. However, neither resistance to neutrophil killing nor in vivo virulence was increased. Thus, reduced virulence of S. argenteus in these models is due to mechanisms unrelated to lack of staphyloxanthin production.
Protection from Systemic Candida albicans Infection by Inactivation of the Sts Phosphatases

ABSTRACT The human fungal pathogen Candida albicans causes invasive candidiasis, characterized by fatal organ failure due to disseminated fungal growth and inflammatory damage. The suppressor of TCR signaling 1 (Sts-1) and Sts-2 are two homologous phosphatases that negatively regulate signaling pathways in a number of hematopoietic cell lineages, including T lymphocytes, mast cells, and platelets. Functional inactivation of both Sts enzymes leads to profound resistance to systemic infection by C. albicans, such that greater than 80% of mice lacking Sts-1 and -2 survive a dose of C. albicans (2.5 × 105 CFU/mouse) that is uniformly lethal to wild-type mice within 10 days. Restriction of fungal growth within the kidney occurs by 24 h postinfection in the mutant mice. This occurs without induction of a hyperinflammatory response, as evidenced by the decreased presence of leukocytes and inflammatory cytokines that normally accompany the antifungal immune response. Instead, the absence of the Sts phosphatases leads to the rapid induction of a unique immunological environment within the kidney, as indicated by the early induction of a proinflammatory cytokine (CXL10). Mice lacking either Sts enzyme individually display an intermediate lethality phenotype. These observations identify an opportunity to optimize host immune responses toward a deadly fungal pathogen.
Amino Acid Substitutions in the Melanoma Antigen Recognized by T Cell 1 Peptide Modulate Cytokine Responses in Melanoma-Specific T Cells

Single amino acid substitutions in melanoma-associated peptides dramatically enhance T-cell cytotoxicity against target cells presenting the modified peptides (often referred to as heteroclitic peptides). The authors tried to determine whether peptide modifications influence other aspects of T-cell immunity toward malignant melanoma. A heteroclitic peptide, E26F, with an E to F substitution in melanoma antigen recognized by T cell 1 (MART-1)26-35, triggers an enhanced tyrosine phosphorylation response when compared with the native-and other-modified MART-1 peptides. Similarly, the E26F peptide enhances the production of mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-&ggr; and significantly enhances release of IL-13 and IL-10 from anti–MART-1 cytotoxic T cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-127-35, also enhances the tyrosine phosphorylation response in anti–MART-1 cytotoxic CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2–like cytokines (IL-10 and IL-13). Together these data show that minor amino acid modifications of immunodominant melanoma peptides profoundly influence the cytokine response in melanoma-specific T cells.
Psychotherapy: A Meta-analysis Effectiveness of Long-term Psychodynamic

Correction Contact me if this article is corrected. Citations Contact me when this article is cited. This article has been cited 4 times. Topic collections Contact me when new articles are published in these topic areas. Evidence-Based Medicine; Review; Prognosis/ Outcomes Disorders; Depression; Psychotherapy; Psychiatry, Other; Quality of Care; Patient-Physician Relationship/ Care; Psychosocial Issues; Psychiatry; Anxiety
High levels of population subdivision in a morphologically conserved Mediterranean toad (Alytes cisternasii) result from recent, multiple refugia: evidence from mtDNA, microsatellites and nuclear genealogies

Pleistocene glaciations often resulted in differentiation of taxa in southern European peninsulas, producing the high levels of endemism characteristic of these regions (e.g. the Iberian Peninsula). Despite their small ranges, endemic species often exhibit high levels of intraspecific differentiation as a result of a complex evolutionary history dominated by successive cycles of fragmentation, expansion and subsequent admixture of populations. Most evidence so far has come from the study of species with an Atlantic distribution in northwestern Iberia, and taxa restricted to Mediterranean‐type habitats remain poorly studied. The Iberian Midwife toad (Alytes cisternasii) is a morphologically conserved species endemic to southwestern and central Iberia and a typical inhabitant of Mediterranean habitats. Applying highly variable genetic markers from both mitochondrial and nuclear genomes to samples collected across the species’ range, we found evidence of high population subdivision within A. cisternasii. Mitochondrial haplotypes and microsatellites show geographically concordant patterns of genetic diversity, suggesting population fragmentation into several refugia during Pleistocene glaciations followed by subsequent events of geographical and demographic expansions with secondary contact. In addition, the absence of variation at the nuclear β‐fibint7 and Ppp3caint4 gene fragments suggests that populations of A. cisternasii have been recurrently affected by episodes of extinction and recolonization, and that documented patterns of population subdivision are the outcome of recent and multiple refugia. We discuss the evolutionary history of the species with particular interest in the increasing relevance of Mediterranean refugia for the survival of genetically differentiated populations during the Pleistocene glaciations as revealed by studies in co‐distributed taxa.
KNDy neuron as a gatekeeper of puberty onset

Hypothalamo–pituitary–gonadal axis has been recognized as a functional unit orchestrating reproductive performance in mammals. The mechanism governing puberty onset, however, is still one of the great mysteries of biology. The present article reviews previous studies over the last century, which gradually elucidated the brain mechanism controlling puberty onset in mammals along with the discovery of gonadotrophins and the gonadotrophin‐releasing hormone and the establishment of the concept for the hypothalamo–pituitary–gonadal axis. The discovery of kisspeptin and subsequent progress of neuroendocrinology in the last decade has resulted in much greater understanding of the way the brain governs puberty onset in mammals.
Validation of the English translation of the low anterior resection syndrome score

Many patients having anterior resection for rectal cancer suffer from severe long‐term bowel dysfunction, known as low anterior resection syndrome (LARS). The LARS score was developed in Denmark, and Swedish, Spanish and German versions have been validated. The aim of this study was to validate the English translation of the LARS score in British rectal cancer patients.
Cytosine deaminase MX cassettes as positive/negative selectable markers in Saccharomyces cerevisiae

We describe positive/negative selectable cytosine deaminase MX cassettes for use in Saccharomyces cerevisiae. The basis of positive selection for cytosine deaminase (Fcy1) activity is that (a) fcy1 strains are unable to grow on medium containing cytosine as a sole nitrogen source and (b) fcy1 ura3 strains are unable to grow on medium containing cytosine as the sole pyrimidine source. Conversely, as 5‐fluorocytosine (5FC) is toxic to cytosine deaminase‐producing cells, fcy1 strains are resistant to 5FC. FCY1MX and FCA1MX cassettes, containing open reading frames (ORFs) of S. cerevisiae FCY1 and Candida albicans FCA1, respectively, were constructed and used to disrupt targeted genes in S. cerevisiae fcy1 strains. In addition, new direct repeat cassettes, kanPR, FCA1PR, FCY1PR and CaURA3PR, were developed to allow efficient deletion of target genes in cells containing MX3 repeats. Finally, the FCY1‐ and FCA1MX3 or PR direct repeat cassettes can be readily recycled after 5FC counter‐selection on both synthetic and rich media. Copyright © 2005 John Wiley & Sons, Ltd.
Beyond Happiness: Building a Science of Discrete Positive Emotions

While trait positive emotionality and state positive-valence affect have long been the subject of intense study, the importance of differentiating among several “discrete” positive emotions has only recently begun to receive serious attention. In this article, we synthesize existing literature on positive emotion differentiation, proposing that the positive emotions are best described as branches of a “family tree” emerging from a common ancestor mediating adaptive management of fitness-critical resources (e.g., food). Examples are presented of research indicating the importance of differentiating several positive emotion constructs. We then offer a new theoretical framework, built upon a foundation of phylogenetic, neuroscience, and behavioral evidence, that accounts for core features as well as mechanisms for differentiation. We propose several directions for future research suggested by this framework and develop implications for the application of positive emotion research to translational issues in clinical psychology and the science of behavior change.