Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining the Ability of Cyclophosphamide Preconditioning to Enhance the Antigen-specific CD8+ T-cell Response to Peptide Vaccination: Creation of a Beneficial Host Microenvironment Involving Type I IFNs and Myeloid Cells

Although cyclophosphamide (CTX) has been clearly shown to enhance active specific and adoptive immunotherapies, the mechanism(s) underlying these beneficial effects have not been clearly defined. To define the impact of CTX preconditioning on the antigen-specific CD8 T-cell response to peptide vaccination, we used an adoptive transfer model based on the OT-1 T-cell receptor transgenic mouse. CTX preconditioning dramatically enhanced the antigen-specific CD8 T-cell response to peptide vaccination. Specifically, CTX significantly enhanced the expansion and function of responding CD8 T cells as demonstrated by flow cytometry and cytokine production. In parallel experiments, we attempted to define the mechanism(s) underlying these beneficial effects of CTX therapy. CTX therapy increased the relative number and activation status of myeloid dendritic cells, and was associated with the induction of significant levels of the inflammatory cytokines interferon-α, monocyte chemoattractant protein-1, and IL-6. Adoptive transfer experiments into type I IFNR−/− and CR3−/− mice confirmed that the beneficial effects of CTX were at least partially dependent on type I interferons and myeloid cells. Adoptive transfer of up to 150×106 naive spleen cells at the time of antigen-specific CD8 T-cell transfer did not abrogate the effects of CTX therapy, suggesting that the creation of a niche in the immune system may not be required. CTX decreased the absolute, but not relative number of CD4+CD25+ Treg cells, consistent with the possibility that regulatory T cells may be targeted by CTX therapy. Of note, combination therapy with CTX and a synthetic TLR3 agonist further enhanced the antigen-specific CD8+ T-cell response. Taken together, our data suggest that CTX modulates specific components of the innate immune system resulting in a beneficial host microenvironment. Specific targeting of these components may enhance the effectiveness of CTX preconditioning for adoptive immunotherapy.
A symmetrical theory of DNA sequences and its applications.

A unified symmetrical theory of DNA sequences has been established based on the basic symmetry of the DNA bases. It is shown that the symmetry of DNA sequences is inherently related to that of a cube and its inscribed regular tetrahedron. A DNA group is defined as a particular alternating group of order 4, in which the permuted objects are four bases. The symmetry of DNA sequences is described by the DNA group which is isomorphic to the tetrahedral group. The matrix representation for the DNA group has been obtained, and used to establish the relationships between the transforms of bases and the rotations of the tetrahedron. It is found that any DNA sequence can be uniquely described by three independent distributions, i.e., the distributions of the bases of purine/pyrimidine, of amino group/keto group and of strong/weak hydrogen bonds along the sequence. The three distributions are invariant in some sense under the transforms of the DNA group, indicating that the three distributions are inherent for the sequence. The mathematical format of the theory lays a foundation for further development. The applications of the theory to analyse some DNA sequences are presented.
Interactive image-guided neurosurgery

Interactive image-guided (IIG) surgery involves the synchronal display of the tip of a surgical device on preoperative scans. This display allows the surgeon to locate the present surgical position relative to the final site of surgical interest. A technique for IIG surgery based on a 6-degrees-of-freedom articulated arm is presented. Design accuracy for the arm is less than 0.1 mm, and the present implementation has a submillimetric accuracy. The display can show the surgical position on any tomographic image set with simultaneous display on up to three image sets. Laboratory results and clinical applications are discussed. <<ETX>>
Marginal Zone, but Not Follicular B Cells, Are Potent Activators of Naive CD4 T Cells1

The early involvement of marginal zone (MZ) B lymphocytes in T-independent immune responses is well established. In this study we compared the abilities of MZ and follicular (FO) B cells to collaborate with T cells. After immunization with soluble hen egg lysozyme, both MZ and FO B cells captured Ag and migrated to T cell areas in the response to hen egg lysozyme. MZ B cells were far superior to FO B cells in inducing CD4+ T cell expansion both in vitro and in vivo. MZ, but not FO, B cells, after interaction with T cells, differentiated into plasma cells, and in addition they stimulated Ag-specific CD4+ T cells to produce high levels of Th1-like cytokines upon primary stimulation in vitro. These results indicate that MZ B cells rapidly and effectively capture soluble Ag and activate CD4+ T cells to become effector T cells. The enhanced capacity of MZ B cells to prime T cells in this study appeared to be intrinsic to MZ B cells, as both MZ and FO B cell populations express an identical Ag receptor.
Hypoxia-associated protein expression in primary central nervous system diffuse large B-cell lymphoma: does it predict prognosis?

Hypoxia-associated proteins are commonly expressed as a consequence of disturbances in microcirculation. However, the clinical relevance of the proteins has never been studied in primary central nervous system lymphoma (PCNSL). The expression of hypoxia-inducible factor 1α (HIF-1α) and its downstream proteins, vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT-1), were evaluated in a central nervous system (CNS) lymphoma xenograft model and in human PCNSL tissue. In the CNS lymphoma xenograft model, the expression of HIF-1α, VEGF, and GLUT-1 co-localized in subsets of lymphoma cells adjacent to necrosis. In tumor specimens from 51 patients with PCNSL, positive HIF-1α staining was found in 26 patients (51.0%), positive VEGF in 30 (58.8%), and positive GLUT-1 in 17 (33.3%), and HIF-1α showed a significant correlation with VEGF (p < 0.05). However, no significant association was seen between hypoxia-associated protein positivity and unfavorable clinical characteristics. Thus, the results failed to show an association with shorter overall survival or time to progression, except that the percentage of lymphoma cells positive for GLUT-1 (>20%) was significantly associated with worse survival. In conclusion, hypoxia-associated proteins were expressed in PCNSL, suggesting a hypoxic microenvironment. However, the prognostic relevance of these proteins for PCNSL was not demonstrated in this study.
Reannotation of Yersinia pestis Strain 91001 Based on Omics Data.

Yersinia pestis is among the most dangerous human pathogens, and systematic research of this pathogen is important in bacterial pathogenomics research. To fully interpret the biological functions, physiological characteristics, and pathogenesis of Y. pestis, a comprehensive annotation of its entire genome is necessary. The emergence of omics-based research has brought new opportunities to better annotate the genome of this pathogen. Here, the complete genome of Y. pestis strain 91001 was reannotated using genomics and proteogenomics data. One hundred and thirty-seven unreliable coding sequences were removed, and 41 homologous genes were relocated with their translational initiation sites, while the functions of seven pseudogenes and 392 hypothetical genes were revised. Moreover, annotations of noncoding RNAs, repeat sequences, and transposable elements have also been incorporated. The reannotated results are freely available at http://tody.bmi. ac.cn.
Semi Dynamic Parameter Tuning for Optimized Opportunistic Spectrum Access

Opportunistic spectrum access (OSA) is a hot topic in cognitive radio context. The main challenge of the OSA is to define improved spectral usage schemes, through the utilization of frequency holes in licensed bands. The multi armed bandit (MAB) is a reinforcement learning technique that can provide the secondary user with the adequate rules, in order to perform simultaneously 1) the exploitation of its external environment and 2) the exploration of the accumulated knowledge by transmitting in the identified white spaces. However, the MAB is sensitive to the non-stationarity of the channels' statistical characteristics. Thus, in this paper, we address an offline sensitivity study to optimize the parameter tuning in the used MAB allocation strategies. Also, we propose a semi dynamic parameter tuning scheme to achieve an online update of the MAB parameters. This adaptive MAB solution enhances the performance of the secondary user in dynamic environments.
Potent inhibition of human immunodeficiency virus type 1 (HIV-1) replication by inducible expression of HIV-1 PR multimers

Constructs were generated in which expression of human immunodeficiency virus type 1 (HIV-1) protease (PR) was placed under control of the HIV-1 long terminal repeat, thus requiring the HIV-1 Tat protein for expression of PR. The activity of PR was assessed by cotransfection with a construct producing a Gag substrate. Expression of PR as an intramolecular multimer resulted in a large increase in PR activity in comparison with the level obtained with the expression of PR as a monomer. A cytotoxic effect of PR expression was also exhibited by the constructs expressing PR multimers. CD4+ T-cell lines were generated with a construct producing PR as a linked tetramer and screened for PR activity and inducibility. The replication of HIV-1 in these cell lines was several orders of magnitude reduced in comparison with that in cell lines not expressing PR. Infection in these cell lines could be detected early after infection but disappeared over time. Infection of the PR-expressing cell lines could be increased several orders of magnitude by the addition of a specific inhibitor of PR, U75875 (Upjohn), after infection of the cells, demonstrating that the potent inhibition of HIV-1 replication in these cells was directly due to the expression of PR.
Evaluation of Selected Parameters of the Inflammatory Response to Endoscopic Retrograde Cholangiopancreatography

Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is a well-established method in diagnosis and management of biliary and pancreatic diseases. The procedure carries the risk of serious complications; the most common is pancreatitis. The severity of ERCP-related pancreatitis largely depends on the inflammatory response to the procedure. Aims The aim of our study was to evaluate the inflammatory response after diagnostic and therapeutic ERCP based on monitoring of plasma concentration of the following substances: amylase, lipase, white blood cells, interleukin 6 (IL-6), C-reactive protein (CRP), hydrogen peroxide, malonylodialdehyde (MDA), and conjugated dienes (CD). Methodology The study was performed on 40 patients who were divided into two groups according to the procedure performed: Group1–28 patients after ERCP with endoscopic sphincterotomy (ES) and Group 2–12 patients after diagnostic ERCP. The parameters were measured before ERCP and 2, 24, and 48 hours after the procedure. Results After diagnostic and therapeutic ERCP, the increase in plasma concentration of amylase, lipase, IL-6, and CRP were observed. Acute pancreatitis developed in three of the patients from group 1. The increase in lipase and CRP concentration was significantly higher after therapeutic ERCP with ES than after the diagnostic procedure. Asymptomatic hyperamylasemia and hyperlipasemia occurred more often after therapeutic than diagnostic ERCP. A positive correlation between the increase of IL-6 and CRP concentration was found. After uncomplicated diagnostic or therapeutic ERCP, no increase of reactive oxygen species and lipid peroxidation products was observed. Conclusion Diagnostic ERCP stimulates a systemic inflammatory response, the intensity of which is magnified after ES. After uncomplicated ERCP, the balance between oxidative and anti-oxidative mechanisms is retained.
Evolutionary Story of Mammalian-specific Amelogenin Exons 4, “4b”, 8, and 9

Amelogenin gene organization varies from 6 exons (1,2,3,5,6,7) in amphibians and sauropsids to 10 in rodents. The additional exons are exons 4, 8, 9, and “4b”, the latter being as yet unidentified in AMELX transcripts. To learn more about the evolutionary origin of these exons, we used an in silico approach to find them in 39 tetrapod genomes. AMEL organization with 6 exons was the ancestral condition. Exon 4 was created in an ancestral therian (marsupials + placentals), then exon 9 in an ancestral placental, and finally exons “4b” and 8 in rodents, after divergence of the squirrel lineage. These exons were either inactivated in some lineages or remained functional: Exon 4 is functional from artiodactyls onward; exon 9 is known, to date, only in rodents, but could be coding in various mammals; and exon “4b” was probably coding in some rodents. We performed PCR of cDNA isolated from mouse and human tooth buds to identify the presence of these transcripts. A sequence analogous to exon “4b”, and to exon 9, could not be amplified from the respective tooth cDNA, indicating that even though sequences similar to these exons are present, they are not transcribed in these species.
Intestinal microbiota profiles associated with low and high residual feed intake in chickens across two geographical locations

Intestinal microbe-host interactions can affect the feed efficiency (FE) of chickens. As inconsistent findings for FE-associated bacterial taxa were reported across studies, the present objective was to identify whether bacterial profiles and predicted metabolic functions that were associated with residual feed intake (RFI) and performance traits in female and male chickens were consistent across two different geographical locations. At six weeks of life, the microbiota in ileal, cecal and fecal samples of low (n = 34) and high (n = 35) RFI chickens were investigated by sequencing the V3-5 region of the 16S rRNA gene. Location-associated differences in α-diversity and relative abundances of several phyla and genera were detected. RFI-associated bacterial abundances were found at the phylum and genus level, but differed among the three intestinal sites and between males and females. Correlation analysis confirmed that, of the taxonomically classifiable bacteria, Lactobacillus (5% relative abundance) and two Lactobacillus crispatus-OTUs in feces were indicative for high RFI in females (P < 0.05). In males, Ruminococcus in cecal digesta (3.1% relative abundance) and Dorea in feces (<0.1% relative abundance) were best indicative for low RFI, whereas Acinetobacter in feces (<1.5% relative abundance) related to high RFI (P < 0.05). Predicted metabolic functions in feces of males confirmed compositional relationships as functions related to amino acid, fatty acid and vitamin metabolism correlated with low RFI, whereas an increasing abundance of bacterial signaling and interaction (i.e. cellular antigens) genes correlated with high RFI (P < 0.05). In conclusion, RFI-associated bacterial profiles could be identified across different geographical locations. Results indicated that consortia of low-abundance taxa in the ileum, ceca and feces may play a role for FE in chickens, whereby only bacterial FE-associations found in ileal and cecal digesta may serve as useful targets for dietary strategies.
Local fluctuations of the signed traded volumes and the dependencies of demands: a copula analysis

We investigate how the local fluctuations of the signed traded volumes affect the dependence of demands between stocks. We analyze the empirical dependence of demands using copulas and show that they are well described by a bivariate K copula density function. We find that large local fluctuations strongly increase the positive dependence but lower slightly the negative one in the copula density. This interesting feature is due to cross-correlations of volume imbalances between stocks. Also, we explore the asymmetries of tail dependencies of the copula density, which are moderate for the negative dependencies but strong for the positive ones. For the latter, we reveal that large local fluctuations of the signed traded volumes trigger stronger dependencies of demands than of supplies, probably indicating a bull market with persistent raising of prices.
Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis

The molecular mechanisms by which obesity increases the risk of cardiovascular diseases are poorly understood. The purpose of this study was to identify candidate biomarkers overexpressed in adipose tissue of obese subjects that could link expanded fat mass to atherosclerosis. We compared gene expression profile in subcutaneous adipose tissue (scWAT) of 28 obese and 11 lean subjects using microarray technology. This analysis identified 240 genes significantly overexpressed in scWAT of obese subjects. The genes were then ranked according to the correlation between gene expression and body mass index (BMI). In this list, the elastolytic cysteine protease cathepsin S was among the highly correlated genes. RT‐PCR and Western blotting confirmed the increase in cathepsin S mRNA (P=0.006) and protein (P<0.05) in obese scWAT. The circulating concentrations of cathepsin S were also significantly higher in obese than in nonobese subjects (P<0.0001). Both cathepsin S mRNA in scWAT and circulating levels were positively correlated with BMI, body fat, and plasma triglyceride levels. In addition, we show that the proinflammatory factors, lipopolysaccharide, interleukin‐lβ, and tumor necrosis factor‐α increase cathepsin S secretion in human scWAT explants. This study identifies cathepsin S as a novel marker of adiposity. Since this enzyme has been implicated in the development of atherosclerotic lesions, we propose that cathepsin S represents a molecular link between obesity and atherosclerosis.
Paclitaxel (Taxol)-induced NF-kappaB translocation in murine macrophages

Interaction of bacterial lipopolysaccharide (LPS) with macrophages results in the induction of a cascade of cytokines that mediate the varied effects of LPS. An early intracellular signaling event that follows receptor engagement is the activation of transcription factor NF-kappaB. Nf-kappaB has been shown to be important for the induction of many LPS-inducible cytokine genes, including tumor necrosis factor alpha, interleukin-1beta, and interleukin-6. Previously, we and others have shown that the antitumor agent paclitaxel (Taxol) is able to mimic bacterial LPS in its ability to activate murine macrophages. In this report, we have extended these findings by demonstrating that paclitaxel, like LPS, is able to stimulate the translocation of primarily p50-p65 heterodimers of NF-kappaB to the nucleus. This activation is dose dependent and requires a concentration of > or =5 microM paclitaxel. The kinetics of NF-kappaB activation by paclitaxel are slower than those of LPS: by 15 min poststimulation, LPS-induced NF-kappaB activation was readily detected, whereas the paclitaxel-induced NF-kappaB activation was minimal. Moreover, paclitaxel- and protein-free LPS-induced translocation of NF-kappaB was seen only in macrophages derived from LPS-responsive C3H/OuJ mice and not from the LPS-hyporesponsive C3H/HeJ mice, a finding that is consistent with those of previous genetic studies linking paclitaxel responsiveness to the Lps gene. Finally, the LPS structural antagonist Rhodobacter sphaeroides diphosphoryl lipid A inhibited both LPS-and paclitaxel-induced NF-kappaB activation, suggesting a common receptor component in this activation.
Role of a Mitogen-Activated Protein Kinase Cascade in Ion Flux-Mediated Turgor Regulation in Fungi

ABSTRACT Fungi normally maintain a high internal hydrostatic pressure (turgor) of about 500 kPa. In response to hyperosmotic shock, there are immediate electrical changes: a transient depolarization (1 to 2 min) followed by a sustained hyperpolarization (5 to 10 min) prior to turgor recovery (10 to 60 min). Using ion-selective vibrating probes, we established that the transient depolarization is due to Ca2+ influx and the sustained hyperpolarization is due to H+ efflux by activation of the plasma membrane H+-ATPase. Protein synthesis is not required for H+-ATPase activation. Net K+ and Cl− uptake occurs at the same time as turgor recovery. The magnitude of the ion uptake is more than sufficient to account for the osmotic gradients required for turgor to return to its original level. Two osmotic mutants, os-1 and os-2, homologs of a two-component histidine kinase sensor and the yeast high osmotic glycerol mitogen-activated protein (MAP) kinase, respectively, have lower turgor than the wild type and do not exhibit the sustained hyperpolarization after hyperosmotic treatment. The os-1 mutant does not exhibit all of the wild-type turgor-adaptive ion fluxes (Cl− uptake increases, but net K+ flux barely changes and net H+ efflux declines) (os-2 was not examined). Both os mutants are able to regulate turgor but at a lower level than the wild type. Our results demonstrate that a MAP kinase cascade regulates ion transport, activation of the H+-ATPase, and net K+ and Cl− uptake during turgor regulation. Other pathways regulating turgor must also exist.
Interleukin-10 (IL-10) Counterregulates IL-4-Dependent Effector Mechanisms in Murine Filariasis

ABSTRACT Interleukin-10 (IL-10) was at first described as a Th2-associated cytokine, although more recent reports have shown that immunosuppression applies to both Th1 and Th2 cell responses, e.g., when produced by T regulatory cells. This concept when applied to human filariasis would argue that high parasite loads are associated with IL-10, while bona fide Th2 responses, mediated by IL-4, IL-5, and IL-13, are associated with parasite containment. To prove this relationship in a causal manner, we investigated the roles of IL-4 and IL-10 in a helminth infection model in which mice genetically deficient for IL-4, IL-10, or IL-4 plus IL-10 were infected with the rodent filaria Litomosoides sigmodontis. Compared to C57BL/6 wild-type and IL-10 knockout (KO) mice, IL-4 KO mice remained susceptible, exhibiting a remarkable number of live adult worms. Interestingly however, when the IL-10 gene was knocked out simultaneously with the IL-4 gene, the susceptibility of IL-4 KO mice was reversed. Although production of IFN-γ was increased in IL-4/IL-10 double-knockout mice, depletion of gamma interferon did not affect worm elimination, so it seems unlikely to be the major factor in mediating resistance in IL-4/IL-10 KO mice. Taken together, the results of this study add proof to the concept that has arisen for human filariasis that IL-10-dependent responses, which are associated with patency, are antagonistic to bona fide Th2 responses, which control parasite loads. The finding that knockout of IL-10 reversed a disease phenotype induced by knockout of IL-4 gives the first causal evidence of an antagonistic activity between IL-4 and IL-10 in an infection in vivo.
OSCILLATION AND ASYMPTOTIC BEHAVIOR OF A THIRD-ORDER NONLINEAR DYNAMIC EQUATION

In this paper we establish some new oscillation criteria for the third-order nonlinear dynamic equation (c(t) ( (a(t)x(t)) )γ ) + f(t, x(t)) = 0, t ∈ [a,∞)T on time scales, where γ ≥ 1 is a quotient of odd integers. Our results not only unify the oscillation theory for third-order nonlinear differential and difference equations but also are new for the q-difference equations and can be applied on different time scales. The results improve some of the main results in the literature in the case when γ = 1.