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Fasting metabolism and immunity are tightly linked; however, it is largely unknown how immune cells contribute to metabolic homeostasis during fasting in healthy subjects. Here, we combined cell-type-resolved genomics and computational approaches to map crosstalk between hepatocytes and liver macrophages during fasting. We identified the glucocorticoid receptor (GR) as a key driver of fasting-induced reprogramming of the macrophage secretome including fasting-suppressed cytokines and showed that lack of macrophage GR impaired induction of ketogenesis during fasting as well as endotoxemia. Mechanistically, macrophage GR suppressed the expression of tumor necrosis factor (TNF) and promoted nuclear translocation of hepatocyte GR to activate a fat oxidation/ketogenesis-related gene program, cooperatively induced by GR and peroxisome proliferator-activated receptor alpha (PPARα) in hepatocytes. Together, our results demonstrate how resident liver macrophages directly influence ketogenesis in hepatocytes, thereby also outlining a strategy by which the immune system can set the metabolic tone during inflammatory disease and infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The recent advent of CRISPR and other molecular tools enabled the reconstruction of cell lineages based on induced DNA mutations and promises to solve the ones of more complex organisms. To date, no lineage reconstruction algorithms have been rigorously examined for their performance and robustness across dataset types and number of cells. To benchmark such methods, we decided to organize a DREAM challenge using in vitro experimental intMEMOIR recordings and in silico data for a C. elegans lineage tree of about 1,000 cells and a Mus musculus tree of 10,000 cells. Some of the 22 approaches submitted had excellent performance, but structural features of the trees prevented optimal reconstructions. Using smaller sub-trees as training sets proved to be a good approach for tuning algorithms to reconstruct larger trees. The simulation and reconstruction methods here generated delineate a potential way forward for solving larger cell lineage trees such as in mouse., Competing Interests: Declaration of interests The authors declare no competing interests. Worm image in Figure 1 was modified from Caenorhabditis elegans hermaphrodite adult-en.svg from Wikimedia Commons by K. D. Schroeder, CC-BY-SA 3.0. The schematic cell lineage of C. elegans in Figures 1 and 6 was generated using the cell lineage web visualization tool CeLaVi available at http://celavi.pro (Salvador-Martínez et al., 2020)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Liver fibrosis is a strong predictor of long-term mortality in individuals with metabolic-associated fatty liver disease; yet, the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely understood. Using cell-type-resolved genomics, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a network of fibrosis-activated transcription factors, as exemplified by the transcription factor Elf-3 (ELF3) and zinc finger protein GLIS2 (GLIS2). Indeed, ELF3- and GLIS2-controlled fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell gene programs. Thus, interconnected transcription factor networks not only promoted hepatocyte dysfunction but also directed the intra-hepatic crosstalk necessary for NASH and fibrosis progression, implying that molecular "hub-centered" targeting strategies are superior to existing mono-target approaches as currently used in NASH therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The G AL4 T echnique for R eal-time a nd C lonal E xpression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide., (Copyright © 2019 Olson et al.)

Objectives: This study aimed to determine the prevalence of mental illness in offenders referred to psychiatrists from January 2011 to March 2016 and any associations between crime and mental illness in these offenders., Methods: Case notes of offenders referred to psychiatrists at the Siu Lam Psychiatric Centre from 1 January 2011 to 31 March 2016 were reviewed. Data on sex, age on admission, educational level, principal psychiatric diagnosis, index offence, source and reason of referral, and outcome were collected., Results: Case notes were reviewed for 4492 offenders (75% males) aged 14 to 93 (mean, 40.6) years. Of these, 68% were referred by the courts for psychiatric report and 32% were referred by correctional institutions for psychiatric assessment and treatment. Approximately 73% of them had a diagnosable mental disorder. The most common principal psychiatric diagnoses were schizophrenia and related disorders (25%), mental and behavioural disorders due to psychoactive substance use (20%), and mood disorders (9%). The most common index offences were theft and related offences (22%), acts intended to cause injury (20%), and illicit drug offences (11%). Offences involving violence were more prevalent in males than in females (p < 0.001). In terms of the three most common principal psychiatric diagnoses, 'acts intended to cause injury' was most prevalent in those with 'schizophrenia and other related disorders' than in those with the other two diagnoses (31% vs 19% vs 17%, p < 0.001). 'Theft and related offences' was most prevalent in those with mood disorders than in those with other two diagnoses (38% vs 20% vs 18%, p < 0.001). 'Illicit drug offences' was most prevalent in those with 'mental and behavioural disorders due to psychoactive substance' than those with other two diagnoses (22% vs 8% vs 6%, p < 0.001)., Conclusions: The prevalence of mental disorders among offenders referred to psychiatrists is high. The pattern of associations between crime and mental disorders in these offenders is comparable with that reported in overseas studies. As Siu Lam Psychiatric Centre is the only facility in Hong Kong for mentally ill offenders, our sample is representative, and our results provide cross-sectional pattern of forensic psychiatric service utilisation in Hong Kong.

Objectives: This study aimed to validate the Correctional Mental Health Screen (CMHS) in the Hong Kong prison population and determine the prevalence of psychiatric disorders among remand prisoners in Hong Kong and the associated factors of mental illness., Methods: This cohort study was conducted at the Lai Chi Kok Reception Centre and the Tai Lam Centre for Women in Hong Kong. Remand prisoners aged ≥21 years were recruited between May and August 2014. Sociodemographic and clinical data were collected. Each remand prisoner was assessed using the appropriate CMHS for males or for females, then interviewed by a specialist psychiatrist using the Structured Clinical Interview for DSM-IV for current affective disorder and psychotic disorder for cross-validation., Results: A total of 245 remand prisoners were recruited (150 males and 95 females; mean age, 25.8 years). Of them, 51% (55% males and 44% females) had a lifetime history of psychiatric disorder, whereas 39.6% (46% males and 29.5% females) had a current psychiatric disorder. The most common psychiatric disorder was substance use disorder (>36%), followed by mood disorder (>20%), psychotic disorder (5.3%), and lifetime neurotic disorder (3.7%). Living in a public housing estate (odds ratio [OR] = 1.99), a history of childhood conduct problem (OR = 2.40), and a forensic history (OR = 1.97) were associated with an increased risk of having a psychiatric disorder. The CMHS had good diagnostic efficiency after cross-validation with the Structured Clinical Interview for DSM-IV., Conclusion: Psychiatric disorders are prevalent in remand prisoners in Hong Kong. The CMHS is an effective tool to screen remand prisoners for timely treatment of prisoners with mental health needs.

Reconstructing the lineage relationships and dynamic event histories of individual cells within their native spatial context is a long-standing challenge in biology. Many biological processes of interest occur in optically opaque or physically inaccessible contexts, necessitating approaches other than direct imaging. Here we describe a synthetic system that enables cells to record lineage information and event histories in the genome in a format that can be subsequently read out of single cells in situ. This system, termed memory by engineered mutagenesis with optical in situ readout (MEMOIR), is based on a set of barcoded recording elements termed scratchpads. The state of a given scratchpad can be irreversibly altered by CRISPR/Cas9-based targeted mutagenesis, and later read out in single cells through multiplexed single-molecule RNA fluorescence hybridization (smFISH). Using MEMOIR as a proof of principle, we engineered mouse embryonic stem cells to contain multiple scratchpads and other recording components. In these cells, scratchpads were altered in a progressive and stochastic fashion as the cells proliferated. Analysis of the final states of scratchpads in single cells in situ enabled reconstruction of lineage information from cell colonies. Combining analysis of endogenous gene expression with lineage reconstruction in the same cells further allowed inference of the dynamic rates at which embryonic stem cells switch between two gene expression states. Finally, using simulations, we show how parallel MEMOIR systems operating in the same cell could enable recording and readout of dynamic cellular event histories. MEMOIR thus provides a versatile platform for information recording and in situ, single-cell readout across diverse biological systems.

In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected to single tumor antigens. Given the heterogeneous expression of antigens on glioblastomas, we hypothesized that a bispecific CAR molecule would mitigate antigen escape and improve the antitumor activity of T cells. Here, we created a CAR that joins a HER2-binding scFv and an IL13Rα2-binding IL-13 mutein to make a tandem CAR exodomain (TanCAR) and a CD28.ζ endodomain. We determined that patient TanCAR T cells showed distinct binding to HER2 or IL13Rα2 and had the capability to lyse autologous glioblastoma. TanCAR T cells exhibited activation dynamics that were comparable to those of single CAR T cells upon encounter of HER2 or IL13Rα2. We observed that TanCARs engaged HER2 and IL13Rα2 simultaneously by inducing HER2-IL13Rα2 heterodimers, which promoted superadditive T cell activation when both antigens were encountered concurrently. TanCAR T cell activity was more sustained but not more exhaustible than that of T cells that coexpressed a HER2 CAR and an IL13Rα2 CAR, T cells with a unispecific CAR, or a pooled product. In a murine glioblastoma model, TanCAR T cells mitigated antigen escape, displayed enhanced antitumor efficacy, and improved animal survival. Thus, TanCAR T cells show therapeutic potential to improve glioblastoma control by coengaging HER2 and IL13Rα2 in an augmented, bivalent immune synapse that enhances T cell functionality and reduces antigen escape.

Purpose. The goal of this study was to investigate the effects of arm weight support training using the ArmeoSpring for subacute patients after stroke with different levels of hemiplegic arm impairments. Methods. 48 inpatients with subacute stroke, stratified into 3 groups from mild to severe upper extremity impairment, were engaged in ArmeoSpring training for 45 minutes daily, 5 days per week for 3 weeks, in addition to conventional rehabilitation. Evaluations were conducted at three measurement occasions: immediately before training (T1); immediately after training (T2); and at a 3-week follow-up (T3) by a blind rater. Results. Shoulder flexion active range of motion, Upper Extremity Scores in the Fugl-Meyer Assessment (FMA), and Vertical Catch had the greatest differences in gain scores for patients between severe and moderate impairments, whereas FMA Hand Scores had significant differences in gain scores between moderate and mild impairments. There was no significant change in muscle tone or hand-path ratios between T1, T2, and T3 within the groups. Conclusion. Arm weight support training is beneficial for subacute stroke patients with moderate to severe arm impairments, especially to improve vertical control such as shoulder flexion, and there were no adverse effects in muscle tone.

We present a pilot demonstration of an optical fiber based refractive index (RI) sensor involving the deposition of graphene onto the surface of a segment of a photonic crystal fiber (PCF) in a fiber-based Mach-Zehnder Interferometer (MZI). The fabrication process is relatively simple and only involves the fusion splicing of a PCF between two single mode fibers. The deposition process relies only on the cold transfer of graphene onto the PCF segment, without the need for further physical or chemical treatment. The graphene overlay modified the sensing scheme of the MZI RI sensor, allowing the sensor to overcome limitations to its detectable RI range due to free spectral range issues. This modification also allows for continuous measurements to be obtained without the need for reference values for the range of RIs studied and brings to light the potential for simultaneous dual parameter sensing. The sensor was able to achieve a RI sensitivity of 9.4 dB/RIU for the RIs of 1.33-1.38 and a sensitivity of 17.5 dB/RIU for the RIs of 1.38-1.43. It also displayed good repeatability and the results obtained were consistent with the modeling.

We present an all-fiber passively mode-locked fiber laser incorporating three-dimensional (3D) graphene as a saturable absorber (SA) for the first time to the best of our knowledge. The 3D graphene is synthesized by template-directed chemical vapor deposition (CVD). The SA is then simply formed by sandwiching the freestanding 3D graphene between two conventional fiber connectors without any deposition process. It is demonstrated that such 3D graphene based SA is capable to produce high quality mode-locked pulses. A passively mode-locked fiber laser is constructed and stable output pulses with a fundamental repetition rate of ~9.9 MHz and a pulse width of ~1 ps are generated from the fiber laser. The average output power of the laser is ~10.5 mW while the output pulse is operating at single pulse region. The results imply that the freestanding 3D graphene can be applied as an effective saturable absorption material for passively mode-locked lasers.

We demonstrate the generation of dark pulses from carbon nanotube (CNT) incorporated erbium-doped fiber ring lasers with net anomalous dispersion. A side-polished fiber coated with CNT layer by optically-driven deposition method is embedded into the laser in order to enhance the birefringence and nonlinearity of the laser cavity. The dual-wavelength domain-wall dark pulses are obtained from the developed CNT-incorporated fiber laser at a relatively low pump threshold of 50.6 mW. Dark pulses repeated at the fifth-order harmonic of the fundamental cavity frequency are observed by adjusting the intra-cavity polarization state.

Background Aims: Outcomes for patients with glioblastoma remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL) 13Rα2, human epidermal growth factor receptor 2, epidermal growth factor variant III or erythropoietin-producing hepatocellular carcinoma A2 has shown promise for the treatment of glioma in preclinical models. On the basis of IL13Rα2 immunotoxins that contain IL13 molecules with one or two amino acid substitutions (IL13 muteins) to confer specificity to IL13Rα2, investigators have constructed CARS with IL13 muteins as antigen-binding domains. Whereas the specificity of IL13 muteins in the context of immunotoxins is well characterized, limited information is available for CAR T cells., Methods: We constructed four second-generation CARs with IL13 muteins with one or two amino acid substitutions, and evaluated the effector function of IL13-mutein CAR T cells in vitro and in vivo., Results: T cells expressing all four CARs recognized IL13Rα1 or IL13Rα2 recombinant protein in contrast to control protein (IL4R) as judged by interferon-γ production. IL13 protein produced significantly more IL2, indicating that IL13 mutein-CAR T cells have a higher affinity to IL13Rα2 than to IL13Rα1. In cytotoxicity assays, CAR T cells killed IL13Rα1- and/or IL13Rα2-positive cells in contrast to IL13Rα1- and IL13Rα2-negative controls. Although we observed no significant differences between IL13 mutein-CAR T cells in vitro, only T cells expressing IL13 mutein-CARs with an E13K amino acid substitution had anti-tumor activity in vivo that resulted in a survival advantage of treated animals., Conclusions: Our study highlights that the specificity/avidity of ligands is context-dependent and that evaluating CAR T cells in preclinical animal model is critical to assess their potential benefit., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

We present an all-fiber bidirectional passively mode-locked soliton laser with a graphene-based saturable absorber for the first time to the best of our knowledge. Our design includes a four-port circulator to introduce different sections of cavity for the two counter-propagating pulses, so they have distinct output characteristics. Simultaneous bidirectional operation is achieved by appropriately adjusting the net cavity birefringence and loss. In the clockwise direction, the laser emits ~750 fs pulses at 1561.6 nm, with a repetition rate of 7.68 MHz. In the counter clockwise direction, the central wavelength, pulse width, and repetition rate are 1561.0 nm, ~850 fs, and 6.90 MHz, respectively.

Glioblastoma (GBM) is the most common primary brain tumor, and despite aggressive therapy with surgery, radiation, and chemotherapy, average survival remains at about 1.5 years. The highly infiltrative and invasive nature of GBM requires that alternative treatments for this disease be widespread and targeted to tumor cells. Immunotherapy in the form of tumor vaccines has the potential to meet this need. Vaccines against GBM hold the promise of triggering specific and systemic antitumor immune responses that may be the key to eradicating this unrelenting cancer. In this review, we will discuss past and present clinical trials of various GBM vaccines and their potential impact on the future care of GBM patients. There have been many promising phase I and phase II GBM vaccine studies that have led to ongoing and upcoming phase III trials. If the results of these randomized trials show a survival benefit, immunotherapy will become a standard part of the treatment of this devastating disease.

Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed that targeting HER2 in a glioblastoma (GBM) cell line results in the emergence of HER2-null tumor cells that maintain the expression of nontargeted tumor-associated antigens. Combinational targeting of these tumor-associated antigens could therefore offset this escape mechanism. We studied the single-cell coexpression patterns of HER2, IL-13Rα2, and EphA2 in primary GBM samples using multicolor flow cytometry and immunofluorescence, and applied a binomial routine to the permutations of antigen expression and the related odds of complete tumor elimination. This mathematical model demonstrated that cotargeting HER2 and IL-13Rα2 could maximally expand the therapeutic reach of the T cell product in all primary tumors studied. Targeting a third antigen did not predict an added advantage in the tumor cohort studied. We therefore generated bispecific T cell products from healthy donors and from GBM patients by pooling T cells individually expressing HER2 and IL-13Rα2-specific CARs and by making individual T cells to coexpress both molecules. Both HER2/IL-13Rα2-bispecific T cell products offset antigen escape, producing enhanced effector activity in vitro immunoassays (against autologous glioma cells in the case of GBM patient products) and in an orthotopic xenogeneic murine model. Further, T cells coexpressing HER2 and IL-13Rα2-CARs exhibited accentuated yet antigen-dependent downstream signaling and a particularly enhanced antitumor activity.

We present a scheme of fiber-connector-type carbon-nanotube-based saturable absorber (CNT-SA) with enhanced thermal damage threshold, in which the CNTs are deposited on the fiber connector end in a ring pattern for evanescent-field interaction instead of direct interaction. The thermal damage threshold of such CNT-SA is found to be increased by around 130% compared with an evenly deposited one. An all-fiber Fabry-Perot (FP) linear cavity passively mode-locked laser is further constructed incorporating the prepared CNT-SA, where the optical power is confined in a relatively short laser cavity to investigate the thermal damage threshold and the performance of the CNT-SA. Stable output pulses with a fundamental repetition rate of 211.84 MHz and a pulse width of 680 fs are generated from the fiber laser. The mode-locking operation can be maintained an intra-cavity average power of 30 mW, indicating that the CNT-SA can withstand a relatively high optical power without performance degradation.

Cancer-associated fibroblasts (CAFs), the principle component of the tumor-associated stroma, form a highly protumorigenic and immunosuppressive microenvironment that mediates therapeutic resistance. Co-targeting CAFs in addition to cancer cells may therefore augment the antitumor response. Fibroblast activation protein-α (FAP), a type 2 dipeptidyl peptidase, is expressed on CAFs in a majority of solid tumors making it an attractive immunotherapeutic target. To target FAP-positive CAFs in the tumor-associated stroma, we genetically modified T cells to express a FAP-specific chimeric antigen receptor (CAR). The resulting FAP-specific T cells recognized and killed FAP-positive target cells as determined by proinflammatory cytokine release and target cell lysis. In an established A549 lung cancer model, adoptive transfer of FAP-specific T cells significantly reduced FAP-positive stromal cells, with a concomitant decrease in tumor growth. Combining these FAP-specific T cells with T cells that targeted the EphA2 antigen on the A549 cancer cells themselves significantly enhanced overall antitumor activity and conferred a survival advantage compared to either alone. Our study underscores the value of co-targeting both CAFs and cancer cells to increase the benefits of T-cell immunotherapy for solid tumors.

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.

OBJECTIVES. To obtain information about basic knowledge towards mental disorders and to evaluate public attitudes towards mental disorders in the Hong Kong Chinese population. METHODS. Questionnaires which collected basic demographic information, opinions about potential stigmas and myths, and knowledge on case vignettes depicting fictional characters with symptoms of mental illness were delivered to subjects in a secondary school, 2 homes for the elderly, a private housing estate, and a public housing estate in Hong Kong. RESULTS. Completed questionnaires were collected from 1035 subjects. In general, the participants' acceptance of mental illness was good. Regular contacts with such patients were associated with better knowledge (t = -2.71, p < 0.01) and better acceptance (t = 2.77, p < 0.01) of mental illness. Younger participants aged 15 to 19 years had a lower level of knowledge about mental health problems compared with other age-groups (p < 0.001). CONCLUSIONS. Personal contact with people with mental illness may help to improve knowledge and acceptance. Younger people in secondary school should be the target and prioritised group for mental health education. Apart from the delivery of mental health knowledge, strategies to increase social contact of the public with people having mental illness could be considered in the design and implementation of anti-stigma programmes.

T-cell therapy with genetically modified T cells targeting CD19 or CD20 holds promise for the immunotherapy of hematologic malignancies. These targets, however, are only present on B cell-derived malignancies, and because they are broadly expressed in the hematopoietic system, their targeting may have unwanted consequences. To expand T-cell therapies to hematologic malignancies that are not B cell-derived, we determined whether T cells can be redirected to CD70, an antigen expressed by limited subsets of normal lymphocytes and dendritic cells, but aberrantly expressed by a broad range of hematologic malignancies and some solid tumors. To generate CD70-specific T cells, we constructed a chimeric antigen receptor (CAR) consisting of the CD70 receptor (CD27) fused to the CD3-ζ chain. Stimulation of T cells expressing CD70-specific CARs resulted in CD27 costimulation and recognition of CD70-positive tumor cell lines and primary tumor cells, as shown by IFN-γ and IL-2 secretion and by tumor cell killing. Adoptively transferred CD70-specific T cells induced sustained regression of established murine xenografts. Therefore, CD70-specific T cells may be a promising immunotherapeutic approach for CD70-positive malignancies.

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)" is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant "Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES)." This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications.

We report the first experimental observation of four-wave mixing (FWM) in single-walled carbon nanotubes (SWCNTs) deposited on a Dshaped fiber. FWM-based tunable wavelength conversion of a 10 Gb/s nonreturn-to-zero signal is demonstrated using a 5-centimeter-long CNT-deposited D-shaped fiber. A power penalty of 4 dB power is obtained in the 10 Gb/s biterror- rate measurements.

We demonstrate widely tunable wavelength conversion based on cross-phase modulation induced nonlinear polarization rotation in a carbon nanotubes (CNTs) deposited D-shaped fiber. A 5-centimeter-long CNT-deposited D-shaped fiber is used as the nonlinear medium for wavelength conversion of a 10 Gb/s non-return-to-zero signal. Wavelength tunable converted signal over 40 nm is obtained with around 2.5-dB power penalty in the bit-error-rate measurements.

We demonstrate widely tunable wavelength conversion based on four-wave mixing using a dispersion-shifted bismuth-oxide photonic crystal fiber (Bi-PCF). A 1-meter-long Bi-PCF is used as the nonlinear medium for wavelength conversion of a 10 Gb/s non-return-to-zero (NRZ) signal. A 3- dB working range of the converted signal over 35 nm is obtained with around 1-dB power penalty in the bit-error-rate measurements.

Background: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcepsilonRI aggregation., Results: Our data show that among 8,793 genes examined, 559 genes are differentially regulated in stimulated mast cells when compared with resting/unstimulated mast cells. The major functional categories of upregulated genes include cytokines, chemokines, and other genes involved in innate and adaptive immune-responses. We observed the increased expression of over 63 gene-transcripts following IgE-sensitization alone. Our data was validated using Real-Time-PCR; ELISA and western blot. We confirmed that IgE alone does not trigger mast cell-immediate responses, such as calcium signals, degranulation or protein-phosphorylation., Conclusion: This report represents a substantial advance in our understanding of the genome wide effects triggered by "passive sensitization" or active stimulation of human mast cells, supporting mast cells' potential involvement in a wide range of inflammatory responses.

We demonstrate extinction ratio improvement by using pump-modulated four-wave mixing in a dispersion-flattened nonlinear photonic crystal fiber. A 6-dB improvement in the extinction ratio of a degraded return-to-zero signal has been achieved. A power penalty improvement of 3 dB at 10(-9) bit-error-rate level is obtained in the 10 Gb/s bit-error-rate measurements.