Tray bleaching status and insights.

OBJECTIVE: To provide an update on tray bleaching for various tooth discoloration conditions, including a complete examination form as well as an information and consent form. CLINICAL CONSIDERATIONS: Since the bleaching process was first documented in 1989, it has become a safe, successful, and conservative treatment for consistently whitening the color of patients' natural teeth. Though initially used on a limited basis, the process has expanded to include bleaching nicotine and tetracycline stains, single dark teeth, brown spots, reducing white spots, caries control as well as color change from aging. Ten percent carbamide peroxide is the material most used in research and has shown to be the most effective with the least amount of adverse side effects, including sensitivity or gingival irritation. Bleaching overnight using a smooth nonscalloped, nonreservoir vacuum-formed tray has been shown to be the method of choice for most clinicians, leading to greater patient compliance and an overall successful treatment. When possible, conservative bleaching treatment should be considered prior to more invasive, irreversible procedures such as veneers, or crowns to meet patients' esthetic requirements. Because of its basic pH, and potential for caries inhibition, complete restorative treatment does not have to be performed prior to initiating bleaching, making it an extremely flexible treatment. CONCLUSION: With a thorough bleaching analysis, proper treatment of appropriate discolorations over an ideal timeframe, tray bleaching is a powerfully predictable tool in restorative dentistry. CLINICAL SIGNIFICANCE: Tray bleaching with 10% carbamide peroxide should be the first consideration for treatment of discolorations of any type, with varying times of treatment, even in the presence of mild decay.

Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson's disease?

In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia.

A 3.7 kb fragment of the mouse Scn10a gene promoter directs neural crest but not placodal lineage EGFP expression in a transgenic animal.

Under physiological conditions, the voltage-gated sodium channel Nav1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Nav1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Nav1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5 µm). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (∼10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Nav1.8 transcript (95%), Nav1.8-immunoreactivity (70%), and TTX-R INa (100%), although not all Nav1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Nav1.8-immunoreactivity confirmed Nav1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R INa recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Nav1.8 beyond sensory neurons. Overall, Scn10a-EGFP transgenic mice recapitulate the majority of the Nav1.8 expression pattern in neural crest-derived sensory neurons.

Effect of Short-Duration, Localized Carbamide Peroxide Application to Remove Enamel Staining on Bond Strength of Resin Cement to Enamel.

UNLABELLED: Objective Peripheral enamel staining is often noticed after removal of long-term veneer or crown provisional restorations. Application of carbamide peroxide (CP) easily removes the stain, but the potential for immediate bonding with a resin-based cement is questionable. This project tested the short-term, shear bond strength of a commercial, photo-curable, resin cement to bovine enamel after application of a 10% concentration of CP placed for different exposure times. MATERIALS AND METHODS: Bovine enamel was flattened and polished. Surfaces had either no CP application (control), or 10% CP applied for 10, 20, or 30 seconds. Teeth were acid-etched, rinsed, dried, and controlled sized stubs of a commercial resin cement were photocured onto the treated surfaces. The shear bond strength of each specimen was determined using a universal testing machine, and results were compared using an analysis of variance at a preset alpha of 0.5 (n = 10/group). RESULTS: No significant differences (p = 0.819) in shear bond strength were found among any CP cleaning treatments or the experimental (nontreated) control. CONCLUSIONS: Short-term application of 10% carbamide peroxide prior to acid etching, to remove enamel stains in teeth prepared to receive ceramic veneers or crowns, does not reduce immediate shear bond strength of resin-based cement to enamel. CLINICAL SIGNIFICANCE: Clinicians can confidently apply 10% CP for short-term, localized stain removal on enamel and not be concerned about affecting subsequent bond strength of a resin-based cement to enamel. (J Esthet Restor Dent, 2016).

ß-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3.

Free fatty acids receptor 3 (FFA3, GPR41) and 2 (FFA2, GPR43), for which the short-chain fatty acids (SCFAs) acetate and propionate are agonist, have emerged as important G-protein-coupled receptors influenced by diet and gut flora composition. A recent study (Kimura et al., 2011) demonstrated functional expression of FFA3 in the rodent sympathetic nervous system (SNS) providing a potential link between nutritional status and autonomic function. However, little is known of the source of endogenous ligands, signaling pathways, or effectors in sympathetic neurons. In this study, we found that FFA3 and FFA2 are unevenly expressed in the rat SNS with higher transcript levels in prevertebral (e.g., celiac-superior mesenteric and major pelvic) versus paravertebral (e.g., superior cervical and stellate) ganglia. FFA3, whether heterologously or natively expressed, coupled via PTX-sensitive G-proteins to produce voltage-dependent inhibition of N-type Ca(2+) channels (Cav2.2) in sympathetic neurons. In addition to acetate and propionate, we show that ß-hydroxybutyrate (BHB), a metabolite produced during ketogenic conditions, is also an FFA3 agonist. This contrasts with previous interpretations of BHB as an antagonist at FFA3. Together, these results indicate that endogenous BHB levels, especially when elevated under certain conditions, such as starvation, diabetic ketoacidosis, and ketogenic diets, play a potentially important role in regulating the activity of the SNS through FFA3.

Highly restricted usage of Ig H chain VH14 family gene segments in Slp65-deficient pre-B cell leukemia in mice.

Mice deficient for the adapter protein Slp65 (also known as Blnk), a key component in precursor-BCR (pre-BCR) signaling, spontaneously develop pre-B cell leukemia. In these leukemias, proliferation is thought to be driven by constitutive Jak3/Stat5 signaling, mostly due to autocrine production of IL-7, together with high surface expression of the pre-BCR. In this study, we investigated whether particular IgH specificities would predispose Slp65-deficient pre-B cells to malignant transformation. Whereas V(H)-D-J(H) junctions were diverse, we found highly restricted Ig V(H) gene usage: 55 out of 60 (~92%) leukemias used a V(H)14/SM7-family gene, mainly V(H)14-1 and V(H)14-2. When combined with surrogate or conventional L chains, these V(H)14 IgH chains did not provide increased proliferative signals or exhibit enhanced poly- or autoreactivity. We therefore conclude that pre-BCR specificity per se did not contribute to oncogenic transformation. Remarkably, in a high proportion of Slp65-deficient leukemias, the nonexpressed IgH allele also harbored a V(H)14-family rearrangement (10 out of 50) or was in the germline configuration (10 out of 50). V(H)14-1 and V(H)14-2 gene regions differed from their neighboring V(H) genes in that they showed active H3K4me3 histone modification marks and germline transcription at the pro-B cell stage in Rag1-deficient mice. Taken together, these findings demonstrate that in Slp65-deficient mice, malignant transformation is largely limited to particular pre-B cells that originate from pro-B cells that had restricted IgH V(H) region accessibility at the time of V(H)-to D-J(H) recombination.

Film thickness of crown disclosing material and its relevance to cementation.

STATEMENT OF PROBLEM: Regardless of the type of indirect restoration being fabricated, optimizing fit at cementation is a challenge. Several disclosing agents have been recommended to identify intaglio surface contacts that may result in incomplete seating and poorly adapted margins. The International Organization for Standardization has established a standard of 25 µm for the maximum film thickness for water-based cements. To accurately predict the clinical behavior of a luting cement, the disclosing agents themselves should have a film thickness no greater than 25 µm. PURPOSE: The purpose of this study was to determine the film thickness of 2 disclosing products, a spray-on powder (Occlude Indicator Marking Spray) and a silicone disclosing agent (Fit Checker). MATERIAL AND METHODS: The film thickness of the 2 disclosing products was determined by using optically flat glass cylinders according to the method set forth in International Organization for Standardization Standard 9917 for water-based cements. Because the silicone product is fast setting, the load was applied within 10 seconds of completing the mix. The spray-on product was allowed to dry before applying the load, in accordance with its intended clinical use. The film thickness of both products was determined with a load of 150 N applied for 30 seconds. Additional determinations were made for the silicone product at both 100 N and 50 N applied for 30 seconds and at 150 N applied for 90 seconds. An additional film thickness determination for the spray-on product was made with no load applied. The film thickness data for the various loads and intervals for the silicone product were analyzed with a 1-way ANOVA and the Tukey-Kramer multiple comparison test (α=.05). A t test (unequal variance, 2-tailed) was used to compare the spray-on and silicone products as measured at a load of 150 N applied for 30 seconds. RESULTS: The average film thickness of Fit Checker ranged from 16.7 to 23.7 µm, with the two 150-N groups significantly lower than the others, whereas that of Occlude was 67.7 µm unloaded and 48.4 µm when loaded. The film thickness of Fit Checker was significantly less than that of Occlude for the 150 N, 30-second group. CONCLUSION: Within the limitations of this study design, Fit Checker had a film thickness that satisfied the 25-µm limit imposed on water-based luting cements in the International Organization for Standardization standard, whereas Occlude Spray did not.

N-Arachidonyl glycine does not activate G protein-coupled receptor 18 signaling via canonical pathways.

Recent studies propose that N-arachidonyl glycine (NAGly), a carboxylic analogue of anandamide, is an endogenous ligand of the Gα(i/o) protein-coupled receptor 18 (GPR18). However, a high-throughput ß-arrestin-based screen failed to detect activation of GPR18 by NAGly (Yin et al., 2009; JBC, 18:12328). To address this inconsistency, this study investigated GPR18 coupling in a native neuronal system with endogenous signaling pathways and effectors. GPR18 was heterologously expressed in rat sympathetic neurons, and the modulation of N-type (Ca(v)2.2) calcium channels was examined. Proper expression and trafficking of receptor were confirmed by the "rim-like" fluorescence of fluorescently tagged receptor and the positive staining of external hemagglutinin-tagged GPR18-expressing cells. Application of NAGly on GPR18-expressing neurons did not inhibit calcium currents but instead potentiated currents in a voltage-dependent manner, similar to what has previously been reported (Guo et al., 2008; J Neurophysiol, 100:1147). Other proposed agonists of GPR18, including anandamide and abnormal cannabidiol, also failed to induce inhibition of calcium currents. Mutants of GPR18, designed to constitutively activate receptors, did not tonically inhibit calcium currents, indicating a lack of GPR18 activation or coupling to endogenous G proteins. Other downstream effectors of Gα(i/o)-coupled receptors, G protein-coupled inwardly rectifying potassium channels and adenylate cyclase, were not modulated by GPR18 signaling. Furthermore, GPR18 did not couple to other G proteins tested: Gα(s), Gα(z), and Gα(15). These results suggest NAGly is not an agonist for GPR18 or that GPR18 signaling involves noncanonical pathways not examined in these studies.

Short-chain fatty acids, secondary bile acids and indoles: gut microbial metabolites with effects on enteroendocrine cell function and their potential as therapies for metabolic disease.

The gastrointestinal tract hosts the largest ecosystem of microorganisms in the body. The metabolism of ingested nutrients by gut bacteria produces novel chemical mediators that can influence chemosensory cells lining the gastrointestinal tract. Specifically, hormone-releasing enteroendocrine cells which express a host of receptors activated by these bacterial metabolites. This review will focus on the activation mechanisms of glucagon-like peptide-1 releasing enteroendocrine cells by the three main bacterial metabolites produced in the gut: short-chain fatty acids, secondary bile acids and indoles. Given the importance of enteroendocrine cells in regulating glucose homeostasis and food intake, we will also discuss therapies based on these bacterial metabolites used in the treatment of metabolic diseases such as diabetes and obesity. Elucidating the mechanisms gut bacteria can influence cellular function in the host will advance our understanding of this fundamental symbiotic relationship and unlock the potential of harnessing these pathways to improve human health.

A foam column system harvesting freshwater algae for biodiesel production: An experiment and process model evaluations.

The purpose of this study was to examine the application of the mathematical model of drift flux to the experimental results of the effect of cationic trimethyl-ammonium bromide (CTAB)-aided continuous foam flotation harvesting on the lipid content in Chlorella vulgaris microalgae. An experiment was conducted to determine the effect of the operating conditions on the enrichment factor (EF) and percentage recovery efficiency (%RE), where the flow rates at the inlet and bottom outlet remained constant. Data for the binary system (without algae) and ternary system (with algae) in an equal-area foam column show that the EF decreases linearly with increasing initial CTAB concentrations ranging from 30 to 75 mg/L for three levels of the studied air volumetric flow rate range (1-3) L/min. The percentage harvesting efficiency increased with increasing initial CTAB concentration and air volumetric flow rate to 96 % in the binary systems and 94 % in the ternary systems. However, in the foam column with the riser used in the three systems, a lower volume of liquid foam in the upward outlet stream resulted in a lower RE% than that of the column without the riser. The objective function of EF for the system with algae increased when the initial CTAB concentration was increased from 30 to 45 mg/L in the foam column with a riser for all air flow rates, and after 45 mg/L, a sudden drop in the microalgae EF was observed. In the comparison between the foam column with and without the riser for the system with algae, the optimum EF was 145 for the design of the column with the riser and 139 for the column without the riser.

Recent advances and applicable flexibility potential of electrochemical processes for wastewater treatment.

This study examined >140 relevant publications from the last few years (2018-2021). In this study, classification was reviewed depending on the operation's progress. Electrocoagulation (EC), electrooxidation (EO), electroflotation (EF), electrodialysis (ED), and electro-Fenton (EFN) processes have received considerable attention. The type of action (individual or hybrid) for each electrochemical procedure was evaluated, and statistical analysis was performed to compare them as a new manner of reviewing cited papers providing a massive amount of information efficiently to the readers. Individual or hybrid operation progress of the electrochemical techniques is critical issues. Their design, operation, and maintenance costs vary depending on the in-situ conditions, as evidenced by surveyed articles and statistical analyses. This work also examines the variables affecting the elimination efficacy, such as the applied current, reaction time, pH, type of electrolyte, initial pollutant concentration, and energy consumption. In addition, owing to its efficacy in removing toxins, the hybrid activity showed a good percentage among the studies reviewed. The promise of each wastewater treatment technology depends on the type of contamination. In some cases, EO requires additives to oxidise the pollutants. EF and EFN eliminated lightweight organic pollutants. ED has been used to treat saline water. Compared to other methods, EC has been extensively employed to remove a wide variety of contaminants.

Long-term actions of BDNF on inhibitory synaptic transmission in identified neurons of the rat substantia gelatinosa.

Peripheral nerve injury promotes the release of brain-derived neurotrophic factor (BDNF) from spinal microglial cells and primary afferent terminals. This induces an increase in dorsal horn excitability that contributes to "central sensitization" and to the onset of neuropathic pain. Although it is accepted that impairment of GABAergic and/or glycinergic inhibition contributes to this process, certain lines of evidence suggest that GABA release in the dorsal horn may increase after nerve injury. To resolve these contradictory findings, we exposed rat spinal cord neurons in defined-medium organotypic culture to 200 ng/ml BDNF for 6 days to mimic the change in spinal BDNF levels that accompanies peripheral nerve injury. Morphological and electrophysiological criteria and glutamic acid decarboxylase (GAD) immunohistochemistry were used to distinguish putative inhibitory tonic-islet-central neurons from putative excitatory delay-radial neurons. Whole cell recording in the presence of 1 µM tetrodotoxin showed that BDNF increased the amplitude of GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) in both cell types. It also increased the amplitude and frequency of spontaneous, action potential-dependent IPSCs (sIPSCs) in putative excitatory neurons. By contrast, BDNF reduced sIPSC amplitude in inhibitory neurons but frequency was unchanged. This increase in inhibitory drive to excitatory neurons and decreased inhibitory drive to inhibitory neurons seems inconsistent with the observation that BDNF increases overall dorsal horn excitability. One of several explanations for this discrepancy is that the action of BDNF in the substantia gelatinosa is dominated by previously documented increases in excitatory synaptic transmission rather than by impediment of inhibitory transmission.

Malignant transformation of Slp65-deficient pre-B cells involves disruption of the Arf-Mdm2-p53 tumor suppressor pathway.

The adapter protein Slp65 is a key component of the precursor-B (pre-B) cell receptor. Slp65-deficient mice spontaneously develop pre-B cell leukemia, but the mechanism by which Slp65(-/-) pre-B cells become malignant is unknown. Loss of Btk, a Tec-family kinase that cooperates with Slp65 as a tumor suppressor, synergizes with deregulation of the c-Myc oncogene during lymphoma formation. Here, we report that the presence of the immunoglobulin heavy chain transgene V(H)81X prevented tumor development in Btk(-/-)Slp65(-/-) mice. This finding paralleled the reported effect of a human immunoglobulin heavy chain transgene on lymphoma development in Emu-myc mice, expressing transgenic c-Myc. Because activation of c-Myc strongly selects for spontaneous inactivation of the p19(Arf)-Mdm2-p53 tumor suppressor pathway, we investigated whether disruption of this pathway is a common alteration in Slp65(-/-) pre-B cell tumors. We found that combined loss of Slp65 and p53 in mice transformed pre-B cells very efficiently. Aberrations in p19(Arf), Mdm2, or p53 expression were found in all Slp65(-/-) (n = 17) and Btk(-/-)Slp65(-/-) (n = 32) pre-B cell leukemias analyzed. In addition, 9 of 10 p53(-/-)Slp65(-/-) pre-B cell leukemias manifested significant Mdm2 protein expression. These data indicate that malignant transformation of Slp65(-/-) pre-B cells involves disruption of the p19(Arf)-Mdm2-p53 tumor suppressor pathway.

The excitability of dorsal horn neurons is affected by cerebrospinal fluid from humans with osteoarthritis.

Changes in central neural processing are thought to contribute to the development of chronic osteoarthritis pain. This may be reflected as the presence of inflammatory mediators in the cerebral spinal fluid (CSF). We therefore exposed organotypically cultured slices of rat spinal cord to CSF from human subjects with osteoarthritis (OACSF) at a ratio of 1 part CSF in 9 parts culture medium for 5-6 days, and measured changes in neuronal electrophysiological properties by means of whole-cell recording. Although OACSF had no effect on the membrane properties and excitability of neurons in the substantia gelatinosa, synaptic transmission was clearly altered. The frequency of spontaneous excitatory postsynaptic currents (sEPSC) in delay-firing putative excitatory neurons was increased, as was sEPSC amplitude and frequency in tonic-firing inhibitory neurons. These changes could affect sensory processing in the dorsal horn, and may affect the transfer of nociceptive information. Although OACSF also affected inhibitory synaptic transmission (frequency of spontaneous inhibitory synaptic currents; sIPSC), this may have little bearing on sensory processing by substantia gelatinosa neurons, as sEPSC frequency is >3× greater than sIPSC frequency in this predominantly excitatory network. These results support the clinical notion that changes in nociceptive processing at the spinal level contribute to the generation of chronic osteoarthritis pain.

VERDI: VERsatile DIffractometer with wide-angle polarization analysis for magnetic structure studies in powders and single crystals.

The VERsatile DIffractometer will set a new standard for a world-class magnetic diffractometer with versatility for both powder and single crystal samples and capability for wide-angle polarization analysis. The instrument will utilize a large single-frame bandwidth and will offer high-resolution at low momentum transfers and excellent signal-to-noise ratio. A horizontal elliptical mirror concept with interchangeable guide pieces will provide high flexibility in beam divergence to allow for a high-resolution powder mode, a high-intensity single crystal mode, and a polarized beam option. A major science focus will be quantum materials that exhibit emergent properties arising from collective effects in condensed matter. The unique use of polarized neutrons to isolate the magnetic signature will provide optimal experimental input to state-of-the-art modeling approaches to access detailed insight into local magnetic ordering.

CD11c+ myeloid cell exosomes reduce intestinal inflammation during colitis.

Intercellular communication is critical for homeostasis in mammalian systems, including the gastrointestinal (GI) tract. Exosomes are nanoscale lipid extracellular vesicles that mediate communication between many cell types. Notably, the roles of immune cell exosomes in regulating GI homeostasis and inflammation are largely uncharacterized. By generating mouse strains deficient in cell-specific exosome production, we demonstrate deletion of the small GTPase Rab27A in CD11c+ cells exacerbated murine colitis, which was reversible through administration of DC-derived exosomes. Profiling RNAs within colon exosomes revealed a distinct subset of miRNAs carried by colon- and DC-derived exosomes. Among antiinflammatory exosomal miRNAs, miR-146a was transferred from gut immune cells to myeloid and T cells through a Rab27-dependent mechanism, targeting Traf6, IRAK-1, and NLRP3 in macrophages. Further, we have identified a potentially novel mode of exosome-mediated DC and macrophage crosstalk that is capable of skewing gut macrophages toward an antiinflammatory phenotype. Assessing clinical samples, RAB27A, select miRNAs, and RNA-binding proteins that load exosomal miRNAs were dysregulated in ulcerative colitis patient samples, consistent with our preclinical mouse model findings. Together, our work reveals an exosome-mediated regulatory mechanism underlying gut inflammation and paves the way for potential use of miRNA-containing exosomes as a novel therapeutic for inflammatory bowel disease.

A mouse model for chronic lymphocytic leukemia based on expression of the SV40 large T antigen.

The simian virus 40 (SV40) T antigen is a potent oncogene able to transform many cell types and has been implicated in leukemia and lymphoma. In this report, we have achieved sporadic SV40 T-antigen expression in mature B cells in mice, by insertion of a SV40 T antigen gene in opposite transcriptional orientation in the immunoglobulin (Ig) heavy (H) chain locus between the D and J(H) segments. SV40 T-antigen expression appeared to result from retention of the targeted germline allele and concomitant antisense transcription of SV40 large T in mature B cells, leading to chronic lymphocytic leukemia (CLL). Although B-cell development was unperturbed in young mice, aging mice showed accumulation of a monoclonal B-cell population in which the targeted IgH allele was in germline configuration and the wild-type IgH allele had a productive V(D)J recombination. These leukemic B cells were IgD(low)CD5(+) and manifested nonrandom usage of V, D, and J segments. V(H) regions were either unmutated, with preferential usage of the VH11 family, or manifested extensive somatic hypermutation. Our findings provide an animal model for B-CLL and show that pathways activated by SV40 T antigen play important roles in the pathogenesis of B-CLL.

Laser illumination of flight crewmembers by altitude and chronology of occurrence.

INTRODUCTION: The illumination of flight crew personnel by lasers while they perform landing and departure maneuvers has concerned the aviation community for the past two decades. This study examines the frequency of illumination events in the United States by altitude and chronology of occurrence to determine where and when aviators and the flying public may be at greatest risk. METHODS: Reports of aircraft illuminated by high-intensity light sources are maintained in a database at the Federal Aviation Administration's Civil Aerospace Medical Institute. Reports of flight crewmembers exposed to lasers from January 1, 2004, to December 31, 2008, were collected and analyzed. RESULTS: Cockpit illuminations at or below 2000 ft (approximately 610 m) increased from 12.5 to 26.7% over the 5-yr period, while the percentage of illuminations between 2000 and 10,000 ft (approximately 610-3048 m) decreased from 87.5 to 58.4%. The months of November and December had the highest frequency of laser events (23%), while May and June had the least (12%). Sunday was the most likely day for an aircraft to be illuminated (18.3%), while Wednesday was the least likely day for such an incident (15.4%). More than 91% of all aircraft illumination events occurred between 1800 and midnight. CONCLUSION: The continuing increase in the number of laser illuminations reported at or below 2000 ft (approximately 610 m) represents an escalating threat to aviation safety. Information provided in this study may allow law enforcement to deploy their resources more efficiently to apprehend those responsible for these crimes.