Digital Gangrene as a Paraneoplastic Manifestation of Peripheral T-cell Lymphoma Not Otherwise Specified Type.

BACKGROUND: Peripheral T cell lymphoma (PTCL), not otherwise specified (NOS) is a heterogenous group of predominantly nodal T cell lymphomas that generally presents with lymphadenopathy with or without extra nodal involvement. Acral vascular syndrome clinically presents as digital ischemia with Raynaud's phenomenon and acral cyanosis. Although, this condition is commonly associated with connective tissue disorder, smoking and vasculitis, its association with lymphoid malignancy is very rare. Here, we present a case report of a patient with digital gangrene of all toes and fingers as a presenting symptom of PTCL-NOS. CASE DESCRIPTION: A 62 year old male presented with digital ischemia associated with pain, low grade fever, loss of appetite and significant weight loss of 6 kilograms over a period of 3 months. On examination, he was found to have bilateral inguinal and axillary lymph nodes with gangrenous changes over toes and fingers but peripheral pulses were palpable. On evaluation he had anemia, elevated ESR and CRP. CT angiogram revealed thinned out digital arteries with multifocal areas of narrowing. Patient was screened for other causes of digital gangrene and was tested negative for ANCA, ANA, cryoglobulins and viral markers. Lymph node biopsy with IHC was suggestive of peripheral T-cell lymphoma-NOS and was started on CHOP regimen. Lymph nodes size decreased and gangrenous changes resolved. CONCLUSION: Though digital ischemia is a rare paraneoplastic presentation of lymphoma, it should be considered if there is a rapid progression of gangrene. Early initiation of chemotherapy may result in the reduction of further progression of digital gangrene and thus prevent permanent disability. In our patient, progression of gangrene was prevented even though it was an aggressive variant of T cell lymphoma.

Correlation of Vertical Dimension of Occlusion in Parents and Their Offspring: A Cephalometric Study.

BACKGROUND: Establishment of optimal vertical dimension of occlusion (VDO) for prosthetic patients, either complete denture or fixed full mouth rehabilitation, is a vital step to discern at a pleasing esthetics and harmonious function. None of the experiments in the literature studied the hopeful inheritance of the VDO from a parent to offspring. PURPOSE: The aim of this study was to establish the dominant mode of inheritance of VDO from parents to offspring using cephalometric landmarks. MATERIALS AND METHODS: Following the inclusion criteria, 20 families were selected and explained about the study design. Individual cephalograph of father, mother, and offspring were traced out of bony landmarks. The reference planes were delineated for the measurements from maxillary incisal (I) tip and mesio-palatal cusp tip of maxillary first molar (M) to palatal (PP) and inter-foramina (IFP) planes. RESULTS: In all the distances measured, there exists a statistically significant difference between both father and son and mother and son. For the measured IPP, MPP, and IIFP distances, there is no statistically significant difference existed between father and daughter. However, in MIFP distance, there is a significant difference between father and daughter. Except for the IIFP distance between mother and daughter (P = 0.08), in all other measured distances, there existed a statistically significant difference. CONCLUSION: There is no dominant mode of inheritance from the parent to the son with respect to the measured parameters. Inheritance was observed to be stronger between father and daughter than between mother and daughter.

Isolation of active coagulant protein from the seeds of Strychnos potatorum - a potential water treatment agent.

The application of natural coagulants for decentralized water treatment is gaining importance as a part of global sustainable initiative. This study focuses on the isolation of active coagulation components responsible for water clarification with respect to Strychnos potatorum seeds. The active coagulant components, protein and polysaccharide, were successfully isolated, dialysed and subjected to gel permeation chromatography. The polysaccharide was isolated with the saline extraction method and characterized using FTIR and NMR spectroscopy. Protein was precipitated with 80% ammonium sulphate solution combined with dialysis and gel permeation chromatography using Sephadex G-50. SDS-PAGE revealed that the isolated protein has a molecular weight of 12 kDa. The small-scale coagulation assay suggests that the protein fraction has superior coagulation activity than the isolated polysaccharide residue. The active coagulant fractions reported in this study would be helpful in deploying cheaper and simple methods in scaling up the coagulant fraction from these seeds acting as a potential water treatment agent.

Facile synthesis of plasmonic zein nanoshells for imaging-guided photothermal cancer therapy.

We demonstrate facile and green synthesis of gold deposited zein nanoshells (AuZNS) using environmental benign solvent ethanol. Water soluble glycol chitosan is used for stabilization as well as for cationic functionalization of zein nanoparticles. Gold deposition is performed via ex-situ method at ambient conditions. AuZNS is of size around 100 nm and shows high inertness and biocompatibility even at double the therapeutic dosage. The absorbance is tuned at 808 nm for imaging-guided plasmonic photothermal therapy of cancer. Highly effective killing of cancer cells irrespective of their chemorefractory status is noticed at a very low therapeutic dosage of 25 µg and 5 min of biologically acceptable (500 mW) 808 nm laser irradiation. AuZNS also exhibit better X-ray attenuation in comparison to the commercially available iodine based contrast agent.

Structure dependent luminescence, peroxidase mimetic and hydrogen peroxide sensing of samarium doped cerium phosphate nanorods.

Rare earth phosphates have been used extensively in luminescent phosphors, bio-imaging, catalysis, and sensors. However, there is a need to correlate the structural-chemical changes associated with stability and performance. In the present work, hydrothermally synthesized CePO4:Smx (x = 0, 5 and 10 mol%) nanorods were annealed at different temperatures to understand the modulations in structure as well as optical and enzyme mimetic properties. As prepared samarium doped cerium phosphate (SCP) nanorods crystallized in a hydrated hexagonal structure transformed into an anhydrous hexagonal and a monoclinic structure on annealing at 400 °C and 800 °C, respectively. Though temperature did not affect the rod-like morphology of the SCP, the lattice strain changed from compressive to tensile. Monoclinic SCP exhibited excellent emission until 5% Sm3+ doping while the quenching effect dominated at 10% Sm3+. Monoclinic SCP samples demonstrated higher peroxidase-like enzymatic activity in comparison to natural enzyme HRP and hexagonal SCP. A mechanism for the enhanced peroxidase-like activity of the monoclinic structure was proposed based on the fluorescence property of terephthalic acid and the surface peroxo complex using Raman spectroscopy. Fluorimetric detection based on the luminescent quenching effect of the monoclinic SCP nanorods treated with different concentrations of hydrogen peroxide showed a linear response from 0 to150 µM concentration with a detection limit (LOD) of 3.17 µM H2O2. Our results demonstrate the importance of structure for enzyme mimetic activity.

Ataxia in a Young Female.

Neurofibromatosis type 2 (NF2) is a genetically inherited disorder characterized by the presence of multiple central nervous system tumours, most pathognomonic being bilateral vestibular schwannomas with or without peripheral manifestations in the form of cataract or cutaneous neurofibromas. NF2 is an uncommon disorder compared to NF1. We describe a classical case of neurofibromatosis type 2 with florid clinical manifestations and characteristic neuroimaging features. We also briefly describe the literature pertaining to this rare disorder. The case also emphasizes the fact that NF2 should be considered in the list of differentials for ataxia especially when it is associated with sensory neural hearing loss.

Tunable transport property of oxygen ion in metal oxide thin film: Impact of electrolyte orientation on conductivity.

Quest for efficient ion conducting electrolyte thin film operating at intermediate temperature (~600 °C) holds promise for the real-world utilization of solid oxide fuel cells. Here, we report the correlation between mixed as well as preferentially oriented samarium doped cerium oxide electrolyte films fabricated by varying the substrate temperatures (100, 300 and 500 °C) over anode/ quartz by electron beam physical vapor deposition. Pole figure analysis of films deposited at 300 °C demonstrated a preferential (111) orientation in out-off plane direction, while a mixed orientation was observed at 100 and 500 °C. As per extended structural zone model, the growth mechanism of film differs with surface mobility of adatom. Preferential orientation resulted in higher ionic conductivity than the films with mixed orientation, demonstrating the role of growth on electrochemical properties. The superior ionic conductivity upon preferential orientation arises from the effective reduction of anisotropic nature and grain boundary density in highly oriented thin films in out-of-plane direction, which facilitates the hopping of oxygen ion at a lower activation energy. This unique feature of growing an oriented electrolyte over the anode material opens a new approach to solving the grain boundary limitation and makes it as a promising solution for efficient power generation.

Dual responsive magnetic composite nanogels for thermo-chemotherapy.

With the onset of hyperthermia and their advantage in increasing vascular perfusion and permeability in the cancer milieu, thermo-responsive polymers have become an attractive candidate for designing therapeutic nano-vehicles for targeted on-demand delivery of bioactive agents. For this purpose, we developed a dual (thermo- and pH-) responsive nanotherapeutic composite system rendering a combinational therapy of hyperthermia mediated drug delivery. This composite system comprises of magnetic chitosan-g-PNVCL (MCP) polymeric nanogels loaded with anticancer drug, Doxorubicin (DOX). The size distribution and the stability of the MCP nanogels have been characterized using DLS and Zeta-potential studies. XRD and TG-DTA confirms the presence of magnetic nanoparticles loaded onto MCP nanogel. ICP-AES analysis was done to determine the amount of iron content in the MCP nanogels. The magnetic property of the MCP nanogels was estimated to be ∼37 emu/g using Vibrating Sample Magnetometer (VSM). The heating ability of MCP nanogels was calculated to be ∼204W/g for the concentration of 2mg/mL using time-dependent Specific Absorption Rate (SAR) method. Magnetic field induced thermo-responsive and pH responsive drug release studies were carried out and it was found that MCP nanogels have a good on-demand drug release properties. The DOX-MCP nanogels were evaluated for its in vitro killing efficacy of breast cancer cells MCF 7 and MDAMB 231 cells with synergistic effects of both hyperthermia and chemotherapy in presence of magnetic field at the concentration of 2mg/mL. Thus, MCP nanogels can be a potential dual modal on-demand hyperthermia mediated drug delivery platform for the breast cancer treatment.

Dissolved Oxygen Scavenging by Acoustic Droplet Vaporization using Intravascular Ultrasound.

Modification of dissolved gas content by acoustic droplet vaporization (ADV) has been proposed for several therapeutic applications. Reducing dissolved oxygen (DO) during reperfusion of ischemic tissue during coronary interventions could inhibit reactive oxygen species production and rescue myocardium. The objective of this study was to determine whether intravascular ultrasound (IVUS) can trigger ADV and reduce DO. Perfluoropentane emulsions were created using high-speed shaking and microfluidic manufacturing. High-speed shaking resulted in a polydisperse droplet distribution ranging from less than 1 micron to greater than 16 microns in diameter. Microfluidic manufacturing produced a narrower size range of droplets with diameters between 8.0 microns and 9.6 microns. The DO content of the fluids was measured before and after ADV triggered by IVUS exposure. Duplex B-mode and passive cavitation imaging was performed to assess nucleation of ADV. An increase in echogenicity indicative of ADV was observed after exposure with a clinical IVUS system. In a flow phantom, a 20% decrease in DO was measured distal to the IVUS transducer when droplets, formed via high-speed shaking, were infused. In a static fluid system, the DO content was reduced by 11% when droplets manufactured with a microfluidic chip were exposed to IVUS. These results demonstrate that a reduction of DO by ADV is feasible using a clinical IVUS system. Future studies will assess the potential therapeutic efficacy of IVUS-nucleated ADV and methods to increase the magnitude of DO scavenging.

Pilot scale thin film plate reactors for the photocatalytic treatment of sugar refinery wastewater.

Pilot scale thin film plate reactors (TFPR) were fabricated to study the solar photocatalytic treatment of wastewater obtained from the secondary treatment plant of a sugar refinery. Silver-impregnated titanium dioxide (TiO2) was prepared by a facile chemical reduction method, characterized, and immobilized onto the surface of ceramic tiles used in the pilot scale reactors. On 8 h of solar irradiation, percentage reduction of chemical oxygen demand (COD) of the wastewater by Ag/TiO2, pure TiO2, and control (without catalyst) TFPR was about 95, 86, and 22 % respectively. The effects of operational parameters such as, flow rate, pH, and addition of hydrogen peroxide (H2O2) were optimized as they influence the rate of COD reduction. Under 3 h of solar irradiation, 99 % COD reduction was observed at an optimum flow rate of 15 L h(-1), initial pH of 2, and addition of 5 mM of H2O2. The results show that Ag/TiO2 TFPR could be effectively used for the tertiary treatment of sugar refinery effluent using sunlight as the energy source. The treated water could be reused for industrial purposes, thus reducing the water footprint of the industry. Graphical Abstract Sugar refinery effluent treatment by solar photocatalytic TFPR.

Thermoresponsive polymeric gel as an on-demand transdermal drug delivery system for pain management.

The main aim of this work is to design a heat triggered transdermal drug delivery system (TDDS) using a thermoresponsive polymer, poly (N-vinyl caprolactam) [PNVCL] based gel, where in patients can themselves administer a pulse of drug on mere application of heat pad over the TDDS, whenever pain is experienced. The phase transition temperature of PNVCL was tuned to 35 °C by grafting it onto a pH sensitive biopolymer, Chitosan, to synthesize Chitosan-g-PNVCL (CP) co-polymer which render the gel both thermo- and pH-responsive property. The application of triggered delivery was explored by loading acetamidophenol (a model hydrophilic drug) and etoricoxib (a model hydrophobic drug). In vitro drug release experiments were performed at three different temperatures (25, 32 and 39 °C) at two different pH (5.5 and 7) to study its drug release with response to temperature and pH. Drug release profiles obtained were found to have enhanced release for both the drugs respectively at 39 °C (above LCST) and pH5.5 when compared to other release conditions. In vitro skin permeation of both the drugs performed in rat abdominal skin using Franz diffusion cell showed enhanced drug release when the skin was subjected to higher temperature (39 °C). Moreover, it was also found that skin permeation for hydrophobic drug was better than that of hydrophilic drug. The in vivo biocompatibility studies of the CP gel in rat skin proved that the gel is biocompatible. The results obtained demonstrated the potential use of the thermoresponsive CP gel as an on-demand localized drug delivery system.

Poly (caprolactone) microparticles and chitosan thermogels based injectable formulation of etoricoxib for the potential treatment of osteoarthritis.

This study aimed to evaluate Poly (caprolactone) microparticles (MPs) loaded composite injectable Chitosan gel (CICGs) as a dual purpose (visco-supplement and intra articular drug delivery depot) therapeutic agent for the treatment of Osteoarthritis. Etoricoxib (COX-2 inhibitor), a highly hydrophobic drug was chosen as a model drug for the study. When administered orally, Etoricoxib poses severe cardiovascular toxicity issues. So, we have attempted to deliver this drug intra-articularly, which could retain the drug longer in the joint region and thus could ameliorate these toxicity issues. CICGs were prepared by dispersing MPs in the chitosan-Ammonium hydrogen phosphate solution and incubated at 37 °C. Rheology studies proved that gels were stable and had visco-elastic properties comparable to that of existing visco-supplements. The in vitro drug release profiles of CICGs were found to be more controlled when compared to MPs and bare chitosan gel (BCGs). In vitro and in vivo biocompatibility studies proved that the gels were biocompatible. In vivo synovial drug clearance studies proved that CICGs had a better drug retention capacity than BCGs and MPs. In vivo fluorescence imaging results confirmed that CICGs could stay longer in the joint region when compared to BCGs and MPs. Thus this novel CICGs could be a potential dual purpose gel for the treatment of diseased joint regions especially for Osteoarthritis.

Synthesis, characterizations, in vitro and in vivo evaluation of Etoricoxib-loaded Poly (Caprolactone) microparticles--a potential Intra-articular drug delivery system for the treatment of Osteoarthritis.

Intra-articular Drug delivery systems (IA-DDS) deliver the drug directly to the diseased joint space with significantly lowered systemic toxicities. In this work, we explored Etoricoxib (COX-2 inhibitor)-loaded Poly caprolactone (PCL) microparticles (MPs) as a potential IA-DDS. MPs were prepared by Oil/Water (O/W) emulsion-solvent evaporation method. Formulation parameters like polymer to drug ratio, stabilizer concentration were optimized to get the maximum encapsulation efficiency. The prepared particles were characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction studies (XRD), and Differential Scanning Calorimetry (DSC). The particles were found to be spherical and smooth-surfaced using SEM. FTIR studies proved that there was no chemical interaction between the drug and the polymer. XRD and DSC studies confirmed that Etoricoxib existed in its amorphous form while PCL had retained its semi-crystalline phase during the micro-encapsulation process. In vitro drug release studies proved that there was controlled release of the drug from the MPs for nearly 28 days. In vivo synovial drug clearance studies on SD rats proved that drug leach out rate from the joint region to the systemic circulation was slow which indicated that MPs had a good drug retention capacity. In vivo fluorescence imaging results confirmed that MPs could stay longer in the joint region for almost a month. Thus, PCL microparticles could be a potential IA-DDS for the treatment of the diseased joint regions especially for Osteoarthritis.

Silymarin encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles: a prospective candidate for prostate cancer therapy.

Silymarin, a clinically proved hepato-protective herbal drug having significant anti-cancerous property towards prostate cancer, is inadequately utilized for cancer therapy due to its hydrophobic nature and poor bioavailability. In this work, we have developed silymarin Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin towards prostate cancer by single emulsion solvent evaporation technique. The prepared nanoparticles had an encapsulation efficiency of 60% and a loading efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous nature of the SNPs. In vitro drug release study demonstrated a slow and sustained release of encapsulated drug from the SNPs in physiological conditions. The hemocompatibility of the SNPs was established by in vitro hemolysis and coagulation assays. In vitro cell viability studies revealed preferential toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell migration assay showed a concentration and time dependent inhibitory effect of SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay suggested induction of apoptosis mediated death in PC-3 cells by the SNPs. Overall, the prepared SNPs proved as a promising candidate for prostate cancer therapy.

Smart design to resolve spectral overlapping of phosphor-in-glass for high-powered remote-type white light-emitting devices.

The white light-emitting diode (WLED) is a state-of-the-art solid state technology, which has replaced conventional lighting systems due to its reduced energy consumption, its reliability, and long life. However, the WLED presents acute challenges in device engineering, due to its lack of color purity, efficacy, and thermal stability of the lighting devices. The prime cause for inadequacies in color purity and luminous efficiency is the spectral overlapping of red components with yellow/green emissions when generating white light by pumping a blue InGaN chip with yellow YAG:Ce³âº phosphor, where red phosphor is included, to compensate for deficiencies in the red region. An innovative strategy was formulated to resolve this spectral overlapping by alternatively arranging phosphor-in-glass (PiG) through cutting and reassembling the commercial red CaAlSiN3:Eu²âº and green Lu3Al5O12:Ce³âº PiG. PiGs were fabricated using glass frits with a low softening temperature of 600°C, which exhibited excellent thermal stability and high transparency, improving life time even at an operating temperature of 200°C. This strategy overcomes the spectral overlapping issue more efficiently than the randomly mixed and patented stacking design of multiple phosphors for a remote-type WLED. The protocol for the current design of PiG possesses excellent thermal and chemical stability with high luminous efficiency and color purity is an attempt to make smarter solid state lighting for high-powered remote-type white light-emitting devices.

Green synthesis and characterization of selenium nanoparticles and its augmented cytotoxicity with doxorubicin on cancer cells.

Green synthesis of selenium nanoparticles (SeNPs) was achieved by a simple biological procedure using the reducing power of fenugreek seed extract. This method is capable of producing SeNPs in a size range of about 50-150 nm, under ambient conditions. The synthesized nanoparticles can be separated easily from the aqueous sols by a high-speed centrifuge. These selenium nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and elemental analysis by X-ray fluorescence spectrometer (XRF). Nanocrystalline SeNPs were obtained without post-annealing treatment. FTIR spectrum confirms the presence of various functional groups in the plant extract, which may possibly influence the reduction process and stabilization of nanoparticles. The cytotoxicity of SeNPs was assayed against human breast-cancer cells (MCF-7). It was found that SeNPs are able to inhibit the cell growth by dose-dependent manner. In addition, combination of SeNPs and doxorubicin shows better anticancer effect than individual treatments.

Science behind cisplatin-induced nephrotoxicity in humans: a clinical study.

OBJECTIVE: To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity. METHODS: We collected data from 18 patients undergoing cisplatin chemotherapy including serum electrolytes, creatinine, blood urea nitrogen (BUN) and urine potassium, sodium and pH levels before and after the cisplatin chemotherapy. All the patients had cancer and were treated with 40-50 mg/day cisplatin. Renal injury was assessed by measuring serum electrolytes, creatinine, BUN levels and urine potassium, sodium and pH levels. RESULTS: The five cycles of cisplatin based chemotherapy resulted in hypomagnesia (P=0.029), hypocalcaemia (P=0.001*), hypophosphatemia (P=0.003*), hypokalemia (P=0.001*) and increased serum creatinine (P=0.001*) and BUN (P=0.292*) levels. In urine analysis, decrease in potassium (P=0.024*) was found, except potassium there was no significant changes in sodium and urine pH. CONCLUSIONS: The present study demonstrates that, acute nephrotoxicity was observed in patients with different types of cancers undergoing cisplatin based chemotherapy due to electrolyte disturbances, when no corrective measures were initiated.

Synthesis of new oxamide-based ligand and its coordination behavior towards copper(II) ion: spectral and electrochemical studies.

A new ligand N,N'-bis{3-(2-formyl-4-methyl-phenol)-6-iminopropyl}oxamide (L) and its mono- and binuclear copper(II) complexes have been synthesized and characterized. The ligand shows absorption maxima at 249 and 360 with a weak transition at 455 nm. The ligand was found to be fluorescent and shows an emission maximum at 516 nm on excitation at 360 nm. The electronic spectra of the mono- and binuclear Cu(II) complexes exhibited a d-d transition in the region 520-560 nm characteristic of square planar geometry around Cu(II) ion. The ESR spectrum of the mononuclear complex showed four lines with nuclear hyperfine splitting. The binuclear complex showed a broad ESR spectrum with g=2.10 due to antiferromagnetic interaction between the two Cu(II) ions. The room-temperature magnetic moment values (micro(eff)) for the mono- and binuclear Cu(II) complexes are found to be 1.70 micro(B) and 1.45 micro(B), respectively. The electrochemical studies of the mononuclear Cu(II) complex showed a single irreversible one-electron wave at -0.70 V (E(pc)) and the binuclear Cu(II) complex showed two irreversible one-electron reduction waves at -0.75 V (E(pc)(1)) and -1.27 V (E(pc)(2)) in the cathodic region.

Activation of the p38 mitogen-activated protein kinase by type I interferons.

The p38 mitogen-activated protein (Map) kinase plays a critical role in the generation of signals in response to stress stimuli, but its role in interferon (IFN) signaling and its potential regulatory role in the activation of Jak-signal transducer and activator of transcription (Stat) pathway are not known. In the present study, we provide evidence that the p38 Map kinase is rapidly phosphorylated and activated during treatment of cells with Type I interferons (IFNalpha and IFNbeta). Furthermore, the Type I IFN-dependent activation of p38 regulates induction of the catalytic domains of MapKap kinase-2 and MapKap kinase-3, strongly suggesting the existence of an IFNalpha signaling cascade activated downstream of the p38 kinase. The engagement of this pathway in interferon signaling plays a critical role in interferon-dependent transcriptional regulation, as evidenced by the fact that inhibition of p38 activation results in abrogation of interferon-dependent gene transcription via interferon-stimulated response elements. Interestingly, inhibition of the kinase activity of the p38 blocks IFNalpha-induced gene transcription without inhibiting DNA binding or tyrosine phosphorylation of Stat proteins, suggesting that the p38 pathway acts in cooperation with the Stat pathway. Thus, the p38 kinase signaling cascade is activated by the Type I interferon receptor and plays a critical role in interferon signaling and interferon-dependent transcriptional regulation.