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In the renal collecting duct, water reabsorption is regulated by the antidiuretic hormone vasopressin (AVP). Binding of this hormone to the vasopressin V2 receptor (V2R) leads to insertion of aquaporin-2 (AQP2) water channels in the apical membrane, thereby allowing water reabsorption from the pro-urine to the interstitium. The disorder nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to concentrate pro-urine in response to AVP, which is mostly acquired due to electrolyte disturbances or lithium therapy. Alternatively, NDI is inherited in an X-linked or autosomal fashion due to mutations in the genes encoding V2R or AQP2, respectively. This review describes the current knowledge of the cell biological causes of NDI and how these defects may explain the patients' phenotypes. Also, the increased understanding of these cellular defects in NDI has opened exciting initiatives in the development of novel therapies for NDI, which are extensively discussed in this review.
- osmoregulation
- protein trafficking
- genetic disorder
- collecting duct
- lithium
- pharmacological chaperones
maintaining body water homeostasis is of vital importance for proper functioning of most physiological processes in the human body. Under normal conditions, the glomerular filtration rate (GFR) of the two kidneys amounts 180 l/day. Of this huge volume, also called the pro-urine, ∼90% is reabsorbed in the proximal tubule and descending limb of Henle's loop, which is a constitutive process. According to need, the remaining fluid can be reabsorbed in the collecting duct. This process is tightly regulated by an elegant system, which allows the body to adapt to periods of water load or water restriction. The key hormone in this process is the antidiuretic hormone arginine-vasopressin (AVP), which is secreted by the posterior pituitary in response to states of hypovolemia or hypernatremia (94). In healthy individuals, secreted AVP will be transported by the blood to the kidney, where it can bind to vasopressin V2 receptors (V2R), which are mainly present on the basolateral (interstitial) side of the principal collecting duct cells (112). The activated V2R will induce an increase of intracellular cAMP levels via the stimulatory Gs protein and adenylate cyclase, which will eventually lead to activation of protein kinase A and to phosphorylation of aquaporin-2 (AQP2) water channels (45, 68). Phosphorylation of at least three of four monomers of an AQP2 tetramer is then sufficient to redistribute AQP2 homotetramers from storage vesicles to the apical membrane, rendering this membrane permeable to water (63, 157). Following an osmotic gradient of sodium and urea, water will then pass the apical membrane via AQP2 and will leave the cells on the basolateral side via AQP3 and AQP4 (57, 69), thereby compensating for the hypovolemic or hypernatremic state of the body. This process is summarized in Fig. 1. When sufficient water is reabsorbed to restore homeostasis, serum vasopressin levels will decrease (94), and AQP2 will be internalized from the apical membrane, resulting in decreased water reabsorption. Katsura et al. (67) showed that this AVP-regulated recycling of AQP2 can occur at least six times with the same repertoire of AQP2 molecules. In addition to its direct regulation of water transport, AVP also increases sodium transport in the collecting duct via the epithelial sodium channel (ENaC) (8, 38) and urea transport via the UT-A1 transporter (141).
Malfunctioning of water reabsorption can lead to a variety of disorders, which can be of central or renal origin. Centrally, in the syndrome of inappropriate secretion of antidiuretic hormone, AVP levels are abnormally increased, leading to excessive renal water reabsorption, which might result in life-threatening hyponatremia (118). The most common causes of the syndrome of inappropriate secretion of antidiuretic hormone are neoplasia, like nonmalignant lung carcinoma, neurological disorders, congestive heart failure, liver cirrhosis, preeclampsia, and drugs like thiazide diuretics or selective serotonin reuptake inhibitor antidepressants. These effects have recently been reviewed in more detail and will not be discussed here (11, 110).
At the other extreme is diabetes insipidus (DI), in which patients are unable to concentrate their urine, resulting in polyuria and, consequently, polydipsia. With central DI, humans lack the ability to produce functional AVP and therefore to actively concentrate their urine. Sometimes, this is due to AVP gene mutations (3, 6, 44, 48, 128). Administration of the synthetic AVP homolog 1-desamino-8-d-arginine vasopressin (DDAVP), however, is usually able to drastically decrease urine output in these patients. A well-studied disturbance of water homeostasis, and the main topic of this review, is nephrogenic diabetes insipidus (NDI). In this disorder, patients are unable to concentrate their urine, despite increased serum AVP levels. This review focuses on the molecular causes underlying NDI and how this information may aid in identifying novel therapies for this disorder.
Most commonly, NDI is acquired due to several conditions, which can be divided into three different groups.
Electrolyte Disturbances
Two clinically important electrolyte abnormalities, hypokalemia and hypercalcemia, lead to polyuria and urinary concentration effects. Hypokalemia is found in up to 21% of hospitalized patients, develops in ∼50% of patients with secondary hyperaldosteronism or using furosemide/thiazide diuretics, and may lead to the development of polyuria, NDI, and reduced AQP2 expression (89, 171). Indeed, in potassium-deprived rats, a 70% reduction in expression and a redistribution from the plasma membrane to intracellular vesicles were observed for AQP2 compared with control rats (89). This effect has been attributed to a reduced pituitary AVP release, blunted renal response to AVP, intrarenal PGE2 production, and impaired AVP-sensitive adenylate cyclase, but might also be due to a reduced interstitial tonicity, as hypokalemia-induced NDI coincides with a severe downregulation of major renal sodium and urea transporters (39, 60), and an elevated tonicity increases AQP2 expression in vitro (50, 66, 151).
Hypercalcemia, which is mostly due to primary hyperparathyroidism and malignancies such as lytic bone disease or humoral hypercalcemia, causes NDI, leading to severe dehydration (123). Studies using excess vitamin D or parathyroid hormone rat models reveal that hypercalcemia-induced NDI is accompanied by a reduced GFR and interstitial tonicity and an increased urinary and fractional sodium excretion (166). The reduced expression of type 2 Na-Pi cotransporter, type-3 Na/H-exchanger, Na-K-ATPase, and Na-K-2Cl cotransporter in hypercalcemia-induced NDI likely contributes to the increased urinary sodium excretion and decreased urine concentration (166). Moreover, hypercalcemia-induced NDI coincides with diminished total and apical membrane expression of AQP2, at normal AQP2 mRNA levels, whereas AQP3 expression is also reduced (37, 165). The effects on AQP2 are ascribed to activation of the apical calcium-sensing receptor (CaSR) by hypercalciuria, which is thought to subsequently induce the internalization of AQP2 as a means of reducing antidiuresis and preventing renal stone formation (142, 154). Although the underlying molecular mechanism for the effect on AQP2 is still poorly understood, Sands et al. (142) identified in an elegant study a signaling pathway linking renal water and calcium metabolism, as in purified apical endosomes from inner medullary collecting duct (IMCD) cells; they found besides AQP2 and the CaSR, PKCδ, PKCζ, and Gαq/Gα11 GTP binding proteins, the latter two of which had been reported earlier to interact with the CaSR. In line with these findings, Procino et al. (125) found later that CaSR-mediated downregulation and internalization of AQP2 in transfected renal cells by extracellular calcium coincide with a strong activation of PKCs, reduced forskolin-induced cAMP levels, and increased F-actin content. The role of decreased cAMP levels in hypercalcemia-induced NDI is further corroborated by the finding of Wang et al. (165) that treatment of such rats with cAMP-phosphodiesterase inhibitors prevents polyuria and reduced AQP2 expression.
Urinary Tract Obstruction
Urinary tract obstruction is a serious clinical condition, which in children is usually due to congenital abnormalities of the kidneys and urinary tract, whereas in adults is mostly caused by stones, enlargement of the prostate, and urinary tract neoplasms. After removal of the obstruction, a marked polyuria develops, which is restored to normal in time, although a somewhat decreased maximum concentrating ability persist for a long time (43). Although the mechanism remains poorly understood, several studies in rats, especially by the Frøkiær team (41, 81, 82, 122), have shown that obstruction-induced NDI is likely due to reduced expression of major renal sodium-transporting proteins [NHE3, Na-K-ATPase, NaPi-2, NKCC1, and the sodium-chloride cotransporter (NCC)] and AQP1–4, all along the nephron (for a recent review, see Ref. 42). A recent study shed some light on the underlying mechanism, as Norregaard et al. (113) found that the reduction in AQP2, NHE3, and NKCC1 expression in the inner medulla, but not in other parts of the kidney, coincided with increased cyclooxygenase-2 (COX-2) expression and prostaglandin release from interstitial cells in rats with bilateral ureteral obstructions. Also, treatment with the COX-2 inhibitor parecoxib prevented downregulation of these transporters. It remains to be determined whether COX-2 inhibitors can shorten the period of NDI after the obstruction is removed.
Lithium-Induced NDI
Lithium, which is the drug of choice for treating bipolar disorders, is successful in reducing both manic and depressive symptoms in 70–80% of patients and reduces the excessive mortality rate observed in this illness (27). Unfortunately, development of NDI is a common side effect. Because 0.1% of humans are on lithium therapy and severe forms of this side effect present in ∼10–20% of patients, lithium-NDI is the most common acquired form of NDI (150). Chronic lithium treatment decreases the GFR (13) and, considering the narrow therapeutic index of lithium (0.6–1.2 meq/l), toxicity resulting from severe dehydration is a problem of significant clinical importance in lithium-NDI. Moreover, lithium-NDI is associated with hyperchloremic metabolic acidosis, renal tubular acidosis (35, 70, 107, 132), and increased natriuresis. Rat studies revealed that lithium-NDI coincides with decreased total AQP2 expression and a reduced expression of AQP2 in the apical membrane (88). Further rat studies revealed that the effect depends on the period of lithium treatment, as short-term (10–14 days) treatment downregulates AQP2 expression without affecting renal morphology, whereas long-term (i.e., 4 wk or longer) treatment also causes an increase in intercalated cells at the expense of principal cells (25, 70, 80). The lithium-induced natriuresis is suggested to be due to the reduced expression in some, but not all, renal segments, of several salt-transporting proteins, such as NCC, the α- and β-subunits of ENaC, and the Na-K-ATPase (80, 108, 109, 131). The mechanism underlying the metabolic and distal tubular acidosis in lithium-NDI is poorly understood. Surprisingly, with long term-lithium treatment, it coincides with strongly increased expression levels of apical H+-renal ATPase, which cannot be explained by the increased number of intercalating cells, and altered expression of several other acid-base transporters (70).
Recent studies shed some light on the mechanisms underlying the reduced AQP2 levels in lithium-NDI. As indicated for electrolyte and obstructive NDI, the reduced AQP2 expression in lithium-NDI might be due to a reduced interstitial osmolality (131). Also, Rao et al. (126) arrived at the suggestion that increased PGE2 expression, which counteracts AVP-induced AQP2 total and plasma membrane expression, might explain AQP2 reduction in lithium-NDI (126). In an elegant study, these authors found that polyuria in COX-1-deficient mice treated with lithium for 4 days resulted in increased COX-2 expression and PGE2 release from interstitial cells and that polyuria and PGE2 release were blunted on inhibition of COX-2 expression. Similar data were observed in Brattleboro rats, indicating that the observed effects were independent from AVP. In contrast, however, lithium-NDI due to a 4-wk lithium treatment in rats coincided with reduced COX-1 and COX-2 levels in the inner medulla, which were strongly increased with dehydration (75). At present, an explanation for these differences is lacking.
Analysis of direct effects of lithium on AQP2 expression have been hampered by the availability of a cell line endogenously expressing AQP2 in response to AVP. Recently, such a cell line was generated (49). We found that these murine cortical collecting duct (mpkCCD) cells are well suited for studying the effects of lithium on AQP2 in more detail, as treatment with clinically relevant concentrations of lithium resulted in a marked reduction in, and reduced plasma membrane expression of, AQP2 (83). Surprisingly, lithium did not affect AVP-induced cAMP generation, phosphorylation or stability of AQP2, or the phosphorylation of the AQP2 transcription factor, the cAMP responsive element binding protein (CREB). Instead, it caused a decrease in AQP2 mRNA levels, indicated that lithium reduces AQP2 gene transcription or mRNA stability. Although further data need to be obtained, an effect of lithium on AQP2 gene transcription is in line with our findings that lithium does not affect AQP2 protein levels in transfected Madin-Darby canine kidney (MDCK) cells in which AQP2 expression is directed from a non-AQP2-related promoter (Shaw S, Li Y, et al., unpublished observations). Our data seem to contradict earlier studies in which it was found that lithium treatment of rats interfered with adenylate cyclase activity, cAMP generation, and PKA activation in isolated renal tubules (26). However, whereas these rats were chronically treated with lithium and, therefore, the observed effects might be due to the changed cellular constitution of their renal collecting ducts (25) and/or reduced sensitivity of the renal collecting duct due to increased circulating AVP levels in lithium-NDI rats (83), our data are obtained with only a 2-day (cells) or short-term (rats) lithium treatment, periods at which a changed cellular constitution of cell layer and renal tubules was not observed (25).
Congenital NDI can be divided into X-linked and autosomal recessive and dominant NDI. Here, we will discuss the genes and proteins involved in these forms of congenital NDI in humans and those only found in animals.
X-Linked NDI
The X-linked and most prominent form of congenital NDI is caused by loss-of-function mutations in the AVPR2 gene, encoding the V2R (19, 85), which is a member of the family of G protein-coupled receptors (GPCR; Fig. 2). Over 180 AVPR2 gene mutations have been described (http://www.medicine.mcgill.ca/nephros), of which many result in severe interference with receptor signaling, thus making the principal cells of the collecting duct insensitive to AVP. The molecular mechanism underlying this insensitivity, however, differs among mutants. As upcoming pharmacological treatments for NDI likely depend on the underlying mechanism, we recently divided GPCR mutations into general and particular V2R mutations in five different classes according to their cellular fate (30, 129) (Fig. 3A and Table 1).
Class I comprises all mutations that lead to improperly processed or unstable mRNA, like promoter alterations, exon skipping, or aberrant splicing. This class also holds frame-shift and non-sense mutations, which result in truncated proteins like V2R-Q119X, -W293X, and -R337X.
Class II mutations are missense or insertion/deletion of one or more nucleotide triplets, resulting in fully translated proteins. Due to the mutation, however, mutant receptors are misfolded and retained in the endoplasmic reticulum (ER), as the ER is the organelle that has the cellular quality control over proper folding and maturation of synthesized proteins. Misfolded proteins are subsequently mostly targeted for proteasomal degradation (40). Intracellular entrapment of missense V2R mutants and their rapid degradation likely represent the most important cause for NDI, as >50% of the mutations in V2R are missense mutations and cellular expression revealed that most of these result in ER-retained proteins. The extent of ER retention, however, may differ among mutants and may represent differences in their folding state. Hermosilla et al. (51) recently reported that of eight V2R mutants that are retained, only three were strictly kept in the ER, whereas the five other mutants were transported to the ER-Golgi intermediate compartment, followed by retrograde transport to the ER.
Class III comprises similar mutations to class II, but the resulting mutants are not considered misfolded by the ER and can continue their itinerary to the plasma membrane. However, these mutations disturb binding of the stimulatory Gs protein, leading to reduced activation of adenylate cyclase and thus formation of cAMP.
Class IV mutations also result in full-length receptors expressed at the cell surface, but here the mutation interferes with, or reduces, AVP binding. These mutations especially involve residues thought to be in or close to the AVP binding pocket, of which V2R-ΔR202 is a clear example (2).
Finally, class V mutations allow normal protein synthesis and maturation, but they cause misrouting to different organelles in the cell. The NDI R137H mutation, located in the well-conserved DRY/H motif of GPCRs, is a member of this class, as V2R-R137H is constitutively internalized from the plasma membrane and therefore only briefly available to bind AVP (10, 15).
Sometimes, mutants do not exert a full phenotype of a particular class and then often also show features of another class. For example, some V2R missense mutants are partially ER retained (class II) but are also partially expressed in the plasma membrane, where they might show a reduced G protein coupling (class III) or AVP binding (class IV). Indeed, V2R-R113W, -G201D, and -T204N stably expressed in polarized MDCK cells are partially ER retained, whereas a considerable fraction is expressed in the basolateral membrane (129). As such, this provides an explanation for the observed small antidiuretic response to high doses of DDAVP in NDI patients harboring such mutations (124) (Table 1). For a full interpretation of these increased urine osmolalities with DDAVP, blood osmolalities and sodium levels are also important but have only been reported for a few patients (Table 1).
Autosomal Recessive NDI
Approximately 10% of the patients diagnosed for NDI have mutations in the AQP2 gene, which is mapped to chromosome 12q13 (34, 140). Of these, >90% suffer from recessive NDI. Most, but not all (28, 34), of these patients are of consanguineous lineage and have inherited two identical mutant AQP2 alleles. In total, 34 AQP2 mutations have been described, of which 27 are involved in recessive NDI (Table 2). Of this group, 78% comprise missense mutations. On expression of the encoded mutants in cell systems, nearly all mutants were misfolded and trapped in the ER (class II), followed by rapid proteasomal degradation (31, 33, 84, 90, 92, 104, 152). Consistent with their extensive degradation, AQP2 proteins could not be detected in the urine of patients with recessive NDI due to AQP2 gene mutations, in contrast to those of healthy controls or of a female V2R NDI patient (32, 65). Although ER retained, overexpression in oocytes, where a fraction of the AQP2 mutants are found in the plasma membrane, revealed that AQP2-L22V, -A47V, -G64R, -T125M, -T126M, -A147T, and -V168M are functional as water channels on a molecular level (23, 90, 92, 104). Interestingly, AQP2-V168M yielded a less severe misfolding than other AQP2 mutants in NDI, which might explain the relatively mild form on NDI in a Mexican family encoding this mutant (20). In general, however, the urine concentrating ability of patients with recessive NDI due to AQP2 mutations are severely affected (urine osmolality <100 mosmol/kgH2O), indicating that in vivo plasma membrane expression of functional AQP2 mutants is negligible. The inability of these AQP2 mutants to form heterotetramers with wild-type AQP2 (wt-AQP2), leaving only the formation of wt-AQP2 homotetramers, likely explains the healthy phenotype of the parents (64). For this, an increased wt-AQP2 expression from the normal allele does not seem to be necessary, because the AQP2 heterozygote knockout mouse, which has a healthy phenotype, expresses about half of AQP2 found in normal mice (173).
Most mutations in autosomal recessive NDI are found in between the first and the last transmembrane domain (Table 2). As this segment forms the AQP2 water pore (105), the misfolding resulting from mutations in this part of the protein illustrates the sensitivity of the pore to structural changes. Recently, one mutation in recessive NDI was found outside this region. Surprisingly, this mutation encodes the P262L exchange in the AQP2 COOH tail, a location that was until then destined to result in dominant instead of recessive NDI (28). This mutation was found in two independent patients, encoding, besides AQP2-P262L, AQP2-A190T and AQP-R187C mutants. Expression in oocytes revealed that the latter two mutants were ER retained (class II). The retention of AQP2-P262L in intracellular vesicles of polarized MDCK cells on stimulation with forskolin provided an explanation for its involvement in NDI, as in the patient neither AQP2-P262L nor AQP2-A190T/R187C would be expressed in the apical membrane of principal cells. However, the observed retention in a non-ER compartment was in still in line with a pattern encountered for AQP2 mutants in dominant NDI. Indeed, as found for mutants in dominant NDI, AQP2-P262L escaped the ER and formed heterotetramers with wt-AQP2, but not AQP2-A190T or AQP-R187C. On coexpression with wt-AQP2, however, wt-AQP2 appeared to target the wt-AQP2/AQP2-P262L complexes to the apical membrane, indicating that, in contrast to AQP2 mutants in dominant NDI, the apical sorting signals of wt-AQP2 overrule the retention signals in AQP2-P262L, thereby explaining the involvement of AQP2-P262L in recessive instead of dominant NDI. The cellular phenotypes of patients in autosomal recessive and dominant NDI and their parents are summarized in ⇓Fig. 5.
Autosomal Dominant NDI
Being diagnosed in only seven families, autosomal dominant inheritance is the least prominent form of NDI. The mutations identified in these families comprise nucleotide deletion, insertion, as well as missense mutations (Table 2). By definition, these mutations are only found in one AQP2 allele. As water-selective AQPs are structurally similar and it was shown that, while expressed as homotetramers, an AQP1 monomer is the functional unit (59, 149, 159), we reasoned that AQP2 mutants in dominant NDI should be able to interfere with the functioning of wt-AQP2. Indeed, on expression in oocytes, these AQP2 mutants were not ER retained and were able to form heterotetramers with wt-AQP2 (64). Due to the mutation, however, these molecularly functional AQP2 mutants were missorted (class V) and, because of the formation of heterotetrameric complexes with wt-AQP2, also targeted wt-AQP2 to other subcellular destinations. Extrapolated to the principal cells of patients, this would lead to severely decreased amounts of AQP2 in the apical membrane, explaining the dominant mode of inheritance of NDI in their families (64).
Clinical analyses of patients with recessive and dominant NDI due to AQP2 mutations revealed three interesting differences (62, 78, 91, 103) (Table 2). First, the symptoms of NDI (polydipsia, polyuria) are already noticeable at birth in recessive NDI, whereas in dominant NDI they often become apparent in the second half of the first year or later. Second, urine osmolalities of patients with recessive NDI never exceed 200 mosmol/kgH2O, whereas those of dominant NDI are sometimes higher. Third, patients with dominant NDI sometimes show a transient increase in urine concentration shortly after DDAVP administration or dehydration. This transient increase seems not to be related to the identified AQP2 mutation, because some patients in the AQP2-insA family did not respond. The observation that a dominant disease is subclinically "milder" than the recessive form is not restricted to NDI, because it is also found for long-QT syndrome, myotonia congenita, osteochondrodysplasias, and Robinow syndrome/brachydactyly (1, 164, 168, 175).
Interestingly, all AQP2 mutations in dominant NDI are located in its COOH terminus (Figs. 4 and 5 and Table 2), which underscores the importance of this segment in trafficking of AQP2. Of the seven mutations described, six have shown or are likely to introduce a missorting signal. The first reported AQP2 mutant, AQP2-E258K, is missorted to the Golgi complex in oocytes, but to late endosomes/lysosomes in polarized cells (52, 103). This mutant is strongly retained in oocytes. Deletion of a small segment containing the E258K mutations greatly restored cell surface expression and water permeability, indicating that the introduced Lys instead of the loss of E258 caused the dominant feature (103). Although starting at different positions, all +1 frameshift mutations 721delG, 727delG, del763–772, and del812–818 resulted in a similarly extended COOH-terminal tail. In MDCK cells, AQP2–727delG localized to late endosomes/lysosomes, and to some extent the basolateral plasma membrane, whereas the other three mutants were present exclusively in the basolateral membrane (7, 78, 91). The molecular signature causing the missorting of these AQP2 mutants has remained elusive. In contrast, an adenosine insertion at position 779 (insA) found in another patient yields a +2 reading frame shift, resulting in a different and slightly extended COOH-terminal tail. Detailed analysis in MDCK cells revealed that this mutant was transported to the basolateral membrane, due to the introduction of two basolateral sorting signals in the changed COOH-terminal segment (62).
Finally, one family with dominant NDI was found in which R254 was exchanged for a leucine (29). In contrast to the others, this mutation did not introduce a missorting signal, but interfered with S256 phosphorylation of AQP2 by PKA. Consequently, the formed wt-mutant complexes were retained in intracellular vesicles that are likely similar to the storage vesicles in which unstimulated wt-AQP2 accumulates. This was supported by the similar subcellular distribution of AQP2-R254L, unstimulated wt-AQP2, and AQP2-S256A, which mimics nonphosphorylated AQP2, and their partial colocalization with the early endosome antigen-1 (EEA-1) marker protein.
Genes in Nonhuman NDI
To identify the physiological role or proteins, gene deletion by homologous recombination is often employed in mice. Using this knockout strategy, mice lacking AQP2 or the V2R appeared to suffer from severe NDI, resulting in perinatal death (173, 174). In contrast, mice lacking AQP3, SPA-1, Foxa1, CLC-K1, or all three nitric oxide synthase (NOS) isoforms, or expressing overactive PDE-III, showed milder forms of NDI (12, 76, 86, 93, 101, 106, 111, 156). While a role of AQP3 (exit of water from principal cells) ands PDE-III (reduced intracellular cAMP levels) in AVP-induced AQP2-mediated water transport is obvious, this is not so clear for the others. The signal-induced proliferation-associated gene-1 (SPA-1) protein, which is a GTPase-activating protein (GAP) for Rap1 containing a PDZ binding domain, directly bind AQP2 and has a role in its routing. However, its precise function in AQP2 trafficking now needs to be uncovered. Foxa1 is a member of the winged helix family of transcription factors and is expressed in the collecting ducts of the kidney. However, as the expression of the V2R and AQP2 are not affected, its molecular role is still unclear. As an increased interstitial tonicity is essential for water reabsorption, it would be interesting to determine whether the lack of Foxa1 reduces expression of renal salt transporters. The kidney-specific CLC-K1 chloride channel mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla and is involved in the generation and maintenance of the hypertonic medullary interstitium. While administration of DDAVP to these mice did not increase urine concentration, it is at present unclear whether this is only due to a reduced interstitial tonicity or also to reduced principal cell V2R or AQP2 expression. NDI in the triply nitric oxide synthase (NOS) knockout mice coincided with reduced membranous AQP2 expression associated with tubuloglomerular lesion formation and provide clear evidence of a critical role of the NOS system in maintaining renal homeostasis.
Although an occurrence of the loss of the three NOS proteins in humans is unlikely to be encountered, there is no report indicating that the lack of any of the above-mentioned genes causes NDI in humans. In fact, in nearly all our congenital NDI patients we have identified V2R or AQP2 gene mutations. Moreover, the discovery that humans lacking AQP3 are without any clinical phenotype (135) and that the lack of V2R or AQP2 is lethal in mice but not in humans seem to indicate that the urine concentrating mechanism is more sensitive in mice. Therefore, whereas the above-mentioned proteins might have a role in human renal osmoregulation, mutations in their genes are likely to lead to a subclinical phenotype in human water homeostasis or no phenotype at all.
Conventional Therapies
The most important component of treatment for NDI is replacement of urinary water losses by adequate supply of fluid, in combination with a decreased solute diet to decrease obligatory water excretion. Diuretics such as hydrochlorothiazide and amiloride have been shown to effectively lower urine volume in NDI, which is, at least for hydrochlorothiazide, more pronounced in combination with a low-salt diet (36, 71). The combined administration of hydrochlorothiazide with either a prostaglandin synthesis [or cyclooxygenase (COX)] inhibitor such as indomethacin (2 mg·kg−1·day−1) or the potassium-sparing diuretic amiloride was shown to be much more effective in reducing urine volume than the thiazide-diuretic alone (4, 58, 73, 74, 97, 127). Long-term use of prostaglandin-synthesis inhibitors, however, is often complicated by gastrointestinal and hematopoietic side effects. In addition, renal dysfunction has been described during indomethacin therapy, most often consisting of a reduction in GFR. Because of the known gastrointestinal safety of selective COX-2 inhibitors compared with nonselective COX inhibitors, a potential role for these drugs in the treatment of NDI has been put forward. In one male NDI infant, the effectiveness of a specific COX-2 inhibitor (rofecoxib) in decreasing urinary free water losses was indeed demonstrated (121). Nevertheless, in view of the recent discovery that prolonged use of that particular COX-2 inhibitor can cause severe cardiac side effects (148), we believe that COX-2 inhibitors should not be used in the treatment of NDI until it has been strictly determined which of these specific inhibitors are completely safe. However, while decreasing urine volume to a great extent, these treatments do not completely overcome the excess of water excretion, as adult patients with this conventional treatment still void 8–10 liters/day. Therefore, efforts into development of tailored therapies have been initiated.
Tailored Therapies
In general, renal gene therapy has been hampered by a low level of accessibility and the absence of selectivity of gene transfer techniques to and expression in particular renal cells (54, 79). In contrast, however, with the realization that success of pharmacotherapy depends on the cellular process disturbed by the disease-causing mutation, tailored pharmacotherapy has become highly promising:
Antibiotics to Bypass Stop Codons
A future therapy for patients harboring premature stop codon mutations (class I) is based on the ability of aminoglycoside antibiotics to cause translational read-through. Indeed, a gentamicin analog caused read-through of nonsense V2R mutants in vitro and in vivo (143, 147). However, the efficiency by which aminoglycosides confer read-through depends strongly on the nucleotides flanking the premature stop codon, and on the compound used, and some aminoglycosides exert toxic effects on the kidney, which severely limits their clinical use.
ANP and the cGMP Pathway
The paradigm for vasopressin signaling involves cAMP-mediated PKA activation, which results in the functionally critical phosphorylation of AQP2 on S256 in vitro and in vivo (29, 45, 63, 68, 157). As the AQP2 S256 phosphorylation site also fulfils the requirements for phosphorylation by cGMP kinase, Brown and co-workers (21, 22) came to the brilliant idea that the lack of cAMP generation in patients with X-linked NDI might be bypassed by pathways that activate cGMP kinase. Indeed, in an elegant study, they could show that acute elevation of cGMP levels by nitric oxide (NO), which thus plays an important role in renal water homeostasis (101), l-arginine, and atrial natriuretic peptide (ANP), led to AQP2 membrane insertion in both transfected cells and regions of the kidney collecting duct (21). This occurred without increasing intracellular cAMP levels and is thus independent of the V2R signaling pathway. Consistently, inhibitors of type 5 cGMP phosphodiesterases, like sildenafil, also induced the phosphorylation and plasma membrane translocation of AQP2 in these specimen (22). In vivo, chronic ANP infusion also induced an increased S256 phosphorylation and apical targeting of AQP2, but as ANP also induces natriuresis, it is at present unclear whether these effects are due to hypovolemia-induced increases in AVP release (167). It will be exciting to uncover whether ANP or other cGMP kinase-activating compounds will be beneficial for patients with X-linked NDI.
"Pharmacological Chaperones" to Rescue V2R Mutants
Very promising are also the approaches recently developed for class II V2R mutants. While their in vivo expression is likely low, transient overexpression of class II mutant proteins in oocytes or HEK293/COS cells, with which a small fraction are often expressed in the plasma membrane, allows the determination of whether such mutants are molecularly functional. Indeed, using such techniques, several (partially) ER-retained V2R and AQP2 mutants in NDI appeared to be functional at the molecular level, as the AQP2 mutants conferred water permeability, whereas the V2R mutants were able to mediate a cAMP response on stimulation with DDAVP (23, 90, 92, 104, 124, 129, 170). In line with these findings, some patients harboring functional and partially ER-retained V2R mutants showed an increased urine concentration in response to high doses of AVP (95) (Table 1).
An important step forward in a putative treatment of these patients was the discovery that stabilization of mutant receptors by cell-permeable V2R antagonists, like SR121463B, aid in the mutant's folding, thereby facilitating their translocation to the plasma membrane (99, 153) (Fig. 3B). Because of their assistance in receptor folding, such cell-permeable ligands are termed pharmacological chaperones (14, 98). Although V2Rs with mutations at residues of major structural importance could not be rescued (e.g., H80R, W164R, S167L), the plasma membrane expression of most class II V2R mutants was restored (172). To be of therapeutic use, the rescuing antagonist has to be displaced by AVP after translocation of the V2R mutant to the basolateral membrane. As the competition between AVP and the rescuing ligand at the plasma membrane will determine functional rescue, low-affinity V2R ligands, like the V1R inverse agonist SR49059, are thought to be clinically more successful than high-affinity compounds such as SR121463B (15). Indeed, Bernier et al. (16) recently found that SR49059 showed a small, but significant, reduction in water intake and urine output in five NDI patients with missense V2R mutations, thus demonstrating the proof-of-principle that pharmacological chaperones can also rescue mutant V2R in vivo. Of great importance for this treatment, the relatively high blood levels of SR49059 came with a minimum of side effects, which is due to their high specificity for the V2R. As several other V1R and V2R antagonists have been developed and have been or are close to FDA approval, it will be exciting to find out to what extent they are able to relieve X-linked NDI caused by functional class II V2R mutants.
In conclusion, research on congenital NDI during the last 15 years has evolved from the identification of the genes involved and analysis of the cellular fate of the V2R and AQP2 mutants to the development of different strategies to bypass or overcome the inability of V2R mutants in X-linked NDI to mediate an antidiuretic response. While it is at present unclear whether a remedy for autosomal NDI can be developed, further development of the above-mentioned highly promising approaches and, especially, clinical testing of these separate or combined strategies in patients with X-linked NDI is anticipated to bring us an exciting scientific and clinical future, as it will tell us whether we can relieve or cure the major form of congenital NDI, 50 years after its first discovery (87).
This work was supported by a grant from the Dutch Kidney Foundation (PC104) to P. M. T. Deen and N. V. A. M. Knoers.
- Copyright © 2006 the American Physiological Society


text:
'Breaking Dawn Part 2′ Star Marisa Quinn Gushes About Costar Kristen Stewart for 'Letting the World Say Whatever They Want to Say' (EXCLUSIVE VIDEO)
Marisa Quinn is ready to experience the Twilight phenomenon first hand.
The actress — and self-proclaimed Twi-hard — takes on the role of struggling vampire Huilen in upcoming Twilight Saga finale Breaking Dawn – Part 2. Like her character, Quinn is still coming to terms with being part of the Twilight phenomenon.
"I didn't… More »

subset: commoncrawl


text:
Known for its striking multicolored kernels, Indian corn is a type of flint corn originally grown as a cereal crop. It commonly appears in harvest or Thanksgiving decorations in the United States and is among the easiest garden plants to cultivate. Most gardeners grow Indian corn for decorative purposes, harvesting the ears for use during the autumn season. Preserving Indian corn is a matter of drying it thoroughly and protecting it from exposure to moisture. If properly preserved, Indian corn will last a long time, providing color in seasonal centerpieces and wreaths for many years.
Things You'll Need
- Indian corn
- Twine
- Shellac
- Small paint brush
Harvest the Indian corn one to two weeks after the silk tassels turn brown. Waiting until the silk dries out ensures that the kernels have fully matured and achieved their characteristic coloration.
Prepare the corn for drying by pulling the husk away from the cob. Do not fully detach the husk since it is needed to hang the corn for thorough drying.
Create several small bundles of corn by tying twine around the base of the husks. Tie a loop at the end of the twine and hang it in a warm, dry area with good air circulation. Avoid basements or other damp areas since they may encourage the growth of mildew or mold on the kernels.
Dry the corn for one to two weeks, or until the kernels are too hard to create a dent with your fingernail.
Apply several light coats of shellac to the kernels, starting with very little and building up a fairly thick layer. Applying shellac deepens the color of the kernels and provides a shiny finish. Allow the shellac to dry thoroughly before handling them.
Related Searches
- "Buffalo Bird Woman's Garden: Agriculture of the Hidatsa Indians"; Waheenee; 1999
- Photo Credit Jupiterimages/Photos.com/Getty Images
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text: Home Gallery Video Jenny Craig Cheers to Kirstie Alley's Weight Loss Jenny Craig: Cheers to Kirstie Alley's Weight Loss Published on Jan 04, 2016 Rate this Ad You must be registered to rate the ad. Please Login or Register Now About Description In new TV, print and digital ads created by agency LRXD, Alley returns to the set of "Cheers," to show off her 50 pound weight loss to former cast members. CreditsDateJan 01, 2016Agency:LRXD Chief Creative Officer/CEO:Kelly ReedyClient:Jenny CraigAssociate Creative Director:Humble TVClient:Jenny CraigDirector:Rudi SchwabExecutive Producer:Eric BerkowitzExecutive Producer:Persis KochExecutive Producer:Shannon LordsLine Producer:Dana DiscordiaProduction Supervisor:Dana EudailyDirector of Photography:Pascal LebeguePost-Production Company:Humble TVEditorial Company:Idolum Music Company:Audio NetworkMusic Company:APMSound Design:Rocky Mountain RecordersCCO:Erik KikerAssociate Creative Director:Mandy StevensIntegrated Producer:Kristen Del CalzoHead of Production:Chris SpanosEditor:Robin SchmachtenbergerExecutive Integrated Music Producer:Kristen Del CalzoDirector of Client Services:Blakely StricklandAccount Director:Megan GonzalezBusiness Affairs:Talent DirectSee more credits Industryhealth Latest Creativity News on Ad Age Anomaly Adds Two Partners, TBWA London Has a New CCO, We Are Unlimited Bolsters Creative Team Hear Our New Tagline Podcast: Engineering Creativity With Shannon Boodram and More Yahoo Asserts 'OG' Fantasy Sports Status in New Campaign Related work Jenny Craig: 10 Pounds Down LRXD Jenny Craig: Monica Lewinsky Latinicity Food Hall + Lounge: Latinicity Ad Campaign LRXD


text:
We are the exclusive seller of
Store-Plus brand storage units and over the years have built up a
strong relationship with their manufacturer. This allows us to offer
you the very best price on their products, such as the overlap bike store.
These bike stores are made using
quality dip treated timbers and feature double doors for easy access.
Protect your precious bicycle for the elements and theft.
Copyright © 2000 - 2016. Shedstore.co.uk is a trading division of Taylored Investments Ltd. All rights Reserved. Shedstore ® is a registered trademark.Taylored Investments Ltd, H1 Coventry Place, Blackpole East, Worcester, WR3 8SG. Telephone 0333 003 0518.
All prices include VAT. *Free delivery area varies by product range, see individual product pages for details. †Restrictions apply, see product lead-time and post code checker for availabilityAll sizes quoted are approximate. Products where shown painted have been decorated for photography purposes only.


text:
Thing One on the walk, ruffed by the wind.
Mia and two Murphys. It is going to be a short year for pasture, we are still recovering from two dry years. And to be truly sustainable I can only run a very small flock of sheep. After that the land suffers. So the lambs will be leaving the farm after a few weeks on the good pasture. I am sorry to say that I have decided that Mia will leave too. This was a hard decision. But the right one.
She was my first hand reared sheep but the agony she goes through every year, when I have to go in and pull out all those dead lambs one after the other is just beyond cruel. Awful. This has happened twice now and she has only just survived each time. And she is still lacking vigor. I have only a few paddocks and it is impossible to keep her away from the ram in the fall. It would be evil of me to allow her to get pregnant and then lose all her lambs in the most terrible way year after year. She cannot breed. Sad, but one of the things we have to deal with as organic/sustainable farmers is taking out the ones who get infections or cannot breed. I am sorry.
Lets think about something else for a minute. The walls have been clad, and the men come back today to tape and mud the cracks. Suddenly the room looks small and echoey. However we are moving forward at a rapid rate now.
Apple blossom. This is where we stand under the apple trees and inhale…
then exhale. There are some beautiful moments on the little farm that allow us breathing space to deal with the difficult ones. There breathe in…
then breathe out. Cherry blossom.
The grapes are leafing out..
And the peaches are setting.
New trees in the daily view. Mr M's on the far right (North), by the yellow fire hydrant, once the leaves come out you will see the trees better.
And a roof for the Coupe. A great accomplishment. The black on the side of the old house is builders paper, once the roof is finished they will start that side.
Good morning my darling friends. I hope you do not feel too bad about Mia. But my promise at the beginning of this blog is that I will tell you the truth of things. You all know about life and its ups and downs. No need to go into it. Every life is like this. We just see it more clearly and simply on a farm.
Author was collected into a cage last night in case she needs an operation today. I will take her in to the vet shortly. She has become more and more lethargic in the last 24 hours. For two days she has slept in the empty indoor pig pen. Both her kittens were lost. She was too young being only a kitten herself.
This is not a happy clappy post is it. Let's go back to the apple blossom and stand under there for a while, listen to the bees and breathe in that heady scent. It will be better soon.
Have a lovely day.
your quiet friend, celi


text:
|Tariq Rahman
|Sonia Rahman
|Played by
Tariq Rahman is the husband of Sonia Rahman, who cheated on him with Sharif Nazir for seven years.
Tariq's wife, Sonia, turned up on the Nazirs' doorstep while Sharif and his wife Yasmeen were holding 45th wedding anniversary celebrations. It transpired that Tariq had thrown Sonia out of the marital home, suspicious that she didn't love him any more. Despite Sharif ordering her to leave fearing that she would to reveal his affair to Yasmeen, Yasmeen told Sonia that she could stay with them for as long as she needed to. Sonia then promised Sharif that she wouldn't say anything about their sordid history.


text:
The new collection has arrived, discover the new patterns !
Quick and easy to use, this yarn winder will help you mix yarns from several balls to make one single ball. The new yarn balls are made in the blink of an eye, and are well made. It's a real creativity-booster! Comes with mount, yarn guide, and instructions. Dimensions: 22 cm x 13.5 cm
Ref : 13491
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text:
McCall's 5074; Copyright 1959; Front buttoned blouse, box pleated skirt and single breasted vest. Blouse has convertible neckline, long set-in sleeves gathered into buttoned bands. Lined vest is dart fitted, reaches about one inch below waistline. Four-gore skirt, made on wide waistband, fastens at front with buttons and hooks and eyes. Slight gathers at top of pleats.
Links to reviews/blog postsEdit
- sydcam123 Bust 38 UNCUT
Add a photo to the gallery by clicking the "modify" button below.
[insert your username, and make sure your preferences allow for people to contact you via e-mail. Do not list your email address here!]


text:
Professor and Section HeadDr. Ghulam Haider Khalid MBBS, DTCD, FCPS (Med & Pul)
Associate ProfessorDr. Tahir IqbalMBBS, MCPS, FCPS
Dr. Naheed GulMBBS, FCPS
Assistant Professors
Dr.Nadia SaeedMBBS., FCPS, MCPS, MRCP(UK)
Dr. Neelum ZakaMBBS., FCPS, MCPS
Dr. Mazhar Ali MuftiMBBS.,DABIM
Dr. Mahmood MajeedMBBS.,DABIM
Dr. Mian Amjad SohailMBBS.,D.Cardiology (UK), DABIM
Dr. Wajid Yar KhanMBBS.,MD (USA), DABIM
Dr. Osama IshtiaqMBBS.,MCPS, FCPS
Senior Registrar
Dr. Tehzeeb Zehra MBBS, IMM[Med], FCPS
Dr. Rahila AmirMBBS, FCPSDr. Nosheen Zahoor MBBS,FCPS
Dr. Sana Tahir Virk MBBS,FCPS-I
Dr. Bilal MustafaMBBS,FCPS-I


text:
Sony's SMTC introduces 4K and HDR capabilities to Indian broadcasters
Published: ASIA
INDIA: Sony India has made updates to its Sony Media Technology Center (SMTC) in Mumbai with the addition of 4K and HDR production equipment to the facility. The inclusion of the new technologies to the SMTC are the result of a collaboration between the manufacturer and Whistling Woods International (WWI), a Mumbai-based institute for film, communications and media, which aims to promote 4K and HDR content creation in India's broadcast sector.
In particular, Sony is going to use the new equipment at the centre to deliver training for 4K live production in sports and drama while emphasising its XAVC 4K/HDR acquisition format. The training will explore seamless integration between existing HD and 4K workflows, while demonstrating the manufacturer's products, such as the HDC-4300 broadcast camera, reportedly designed for broadcasters making the transition from HD to 4K. Seminars covering 4K cinematography cameras and OLED monitors are also expected to be run.
The facility, which also demonstrates the manufacturer's 3D technical equipment, now has the capability to demonstrate and provide expertise on the full 4K content creation workflow, from acquisition through to postproduction. The facility is open to students as well as media professionals, who can attend the seminars, or familiarise themselves with the products.
'SMTC was launched in India in 2011 by Sir Howard Stringer, then chairman, CEO and president of Sony Corporation, and Subhash Ghai, chairman of Whistling Woods International,' said Mikio Kita, deputy senior GM, media segment business division, PSSG, imaging products and solutions sector at Sony. 'Since then, SMTC has been providing training to leading media professionals and students of WWI. SMTC is Sony's first and only such facility in India, and fourth such facility in the world. With this collaboration between SMTC and WWI, the first phase of 4K cinema market development has been established successfully.'
'With 4K and HDR becoming important tools in the broadcasting and filmmaking fields, SMTC will act as a great platform for aspiring filmmakers and industry professionals,' added Shinya Koshie, national head of the professional solution division at Sony India. 'Sony is delighted to provide technology innovation by enhancing the Sony Media Technology Center.'


text:
The first boss you want to fight is Eye Of Cthulu the easiest boss of all because it will be much more easier to get the demonite bars to create lights bane,war axe of the night and demon bow.
The best armour for this battle is silver or for a challenge you could be naked LOL.
For beginners guide to kill him, get the merchant and buy at least 500 ninja stars(cant spell name of it)because while he is summoning the servant of cthulu,it will rapidly kill them and attack eye of cthulu.
The best time to kill him is when he is summoning servants of cthulu but if you want to attack him when he charges three times at you thats ok but be careful.
After attacking him a couple of times,he becomes amgry and shows his mouth.You would have to be much careful and it will become a little bit easier because defense becomes low and his attack becomes high.
After killing Eye Of Cthulu he will drop demonite ore and you smelt them at the furnace
Recommendations:I strongly recommend making war axe of the night because it will be effective for the Eater Of Worlds and lights bane if you want to get nights edge(I do know 1.1.1 is out)
Summoning:suspisous looking eye(6 lenses)
Thx for reading and next blog will come out about eater of worlds and how to destroy it!!!


text:
I met a nice guy the other day - he was with his young son and I was with mine. We've been texting a bit - I sent him a funny FB post and he sent me a very funny but raunchy YouTube video. It's called "Who's F*******?" And it shows different couples talking about f****** each other as if they are talking about being in love, like an EHarmony commercial (you should check it out, it's hysterical). While I found it funny, do you think it's a bit inappropriate for him to have sent that so soon? Is this a red flag or am I overreacting?
Most Helpful Guy
You're not overreacting, sometimes there are boundaries that shouldn't be prematurely crossed. It's like a person calling me by a nickname I have never asked him to call me by and I would remind him that we're not friends. Kind of a respect thing.11|00|0


text:
PHILDELPHIA -The University of Pennsylvania women's lacrosse team relied heavily on goalkeeper Lucy Ferguson last week in a pair of games, and her efforts were recognized by the Ivy League with its Defensive Player of the Week honor.
Ferguson made 23 saves over the course of two games, and boasted a .575 save percentage for the week as No. 14 Penn went 1-1 in a loss at No. 1 Maryland and a win over Dartmouth.
Ferguson made a career high 15 saves against the Terrapins in College Park, limiting the defending national champions to 12 goals -- the second-fewest Maryland has scored all season.
On Saturday, she made eight saves as the Quakers improved to 2-0 in the Ivy League with a 10-5 win over Dartmouth. Ferguson made seven of her eight saves in the second half -- including three on Big Green free positions.
Through eight games this season, Ferguson leads the Ivy League in both goals-against average (7.24) and save percentage (.513). Her save percentage is No. 6 nationally, while her goals-against average ranks No. 11 among all goalkeepers.
Ferguson is the sixth weekly award winner for the Quakers this season, and the third player to earn Defensive Player of the Week. Her selection marks the second consecutive Defensive Player of the Week award winner for the Red and Blue.
Penn Weekly Award Winners for2015
February 23 --Megan Kelly, Defensive Player of the Week
March 2 --Nina Corcoran, Offensive Player of the Week
March 9 --Tory Bensen, Offensive Player of the Week
March 16 --Tory Bensen, Co-Offensive Player of the Week
March 16 --Meg Markham, Defensive Player of the Week
March 23 -- Lucy Ferguson, Defensive Player of the Week


text:
|Publication number
|Publication type
|Application number
|Publication date
|Apr 24, 2012
|Filing date
|Feb 19, 2009
|Priority date
|Feb 19, 2009
|Fee status
|Also published as
|Publication number
|Eric Hsiao
|Original Assignee
|Sony Corporation, Sony Electronics Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (31), Referenced by (1), Classifications (19), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention relates generally to programming a TV with a channel map.
When a customer first sets up a new TV or moves from one area to another, he has to initiate a autoprogramming scan for channels, which can take upwards of thirty minutes. Specifically, setting up a TV, using its own tuner as opposed to using an external cable or satellite set-top box, requires a time-consuming process which searches the input signal (typically a coaxial cable for cable TV customers) to create an internal database called a channel map that it will use for tuning. Even with optimizations to the algorithm for autoprogramming, an inordinate amount of time is still required.
Accordingly, as understood herein, with an internet connected television, a channel map can be acquired from a network server, bypassing the need to autoprogram. The network server maintains a list of channel map tuning data for geographical areas, and for those areas without map data, conventional autoprogramming can be done.
Accordingly, a TV executes logic that includes presenting a prompt on a TV for a user to input information representing geographic area for which a channel map is desired into a TV. The logic also includes receiving the information at the TV and transmitting the information to a network server. The information is correlatable to a list of TV signal providers. The logic also includes receiving, at the TV, the list from the network server, presenting the list on the TV, receiving a user selection of a TV signal provider on the list, and sending the user selection to the network server. The TV receives from the network server a channel map associated with both the user selection of a TV signal provider and the geographic area.
In example embodiments the TV can receive an update to the channel map. The update may be received in response to an update command entered into the TV and sent to the server. Or, the update can be received in response to an automatically generated update query sent from the TV to the server. Yet again, the update may be received automatically by the TV from the server without an update query or update command being sent from the TV to the server.
If desired, the prompt for a user to input information representing geographic area may be presented only upon a determination that the TV communicates with the server, and otherwise an autoprogram operation is executed. A user of the TV can be allowed to interrupt a process of receiving a channel map from a server and cause an autoprogram operation to be executed.
In another aspect, a network server executes logic including receiving from a TV over a network a location of the TV, downloading a channel map based on the location, and subsequently providing updated channel map information to the TV.
In another aspect, a network-enabled TV has a TV processor that can send a geographic location to an Internet server and in response receives back a list of TV service providers for the location. A TV display controlled by the TV processor displays the list. A user input device is manipulable by a person to select a provider from the list to thereby generate a select signal, which is sent from the TV to the server. A tangible data storage medium is accessible to the processor. The processor stores on the storage medium channel map information received from the server in response to the select signal.
The details of the present invention, both as to its structure and operation, can best be understood in reference to the accompanying drawings, in which like reference numerals refer to like parts, and in which:
As described in greater detail below, an internet-connected TV has the ability to download a channel map database from a network server provided by a TV manufacturer or by another entity. The channel map corresponds to the customer's geographic area and TV service provider (such as a cable company). The TV subsequently uses this channel map for all its tuning activities, since the example channel map includes tuner-related data such as frequency, physical and virtual channel mappings, and modulation. The channel map is comparatively small and can be downloaded in only a few seconds using, e.g., a digital subscriber line (DSL) connection, thus avoiding the need to perform a more prolonged autoprogram operation.
Accordingly, referring initially to
The TV 12 typically includes a wireless receiver 22 such as an infrared receiver for receiving user command signals from a remote control 24. The remote control 24 typically includes one or more manipulable input elements 26 such as keys for enabling a user to input commands to the TV processor 14.
As shown in
In any case, the server 30 includes one or more server processors 34 accessing a server data storage medium 36. As described in greater detail below, the example storage medium 36, which may include disk and/or solid state storage, contains a database of channel maps grouped by geographic area, with each area typically being associated with at least one and generally plural TV service providers. As channel map can be provided for each service provider in each area.
Now referring to
On the other hand, once it is determined that a network connection has been established between the TV 12 and Internet 32, the logic flows to block 42 to prompt the user to enter the geographic location of the TV. An example GUI of this is shown in
Once the geographic location information is entered into the TV 12, the TV 12 uploads the information to the server 30, which receives the information at block 46. The server 30 then accesses the channel map database to look up the available TV service providers in the entered location. This list is returned to the TV 12 and displayed thereon at block 48.
In the example shown in
In some implementations the user may be given option to override the downloaded channel map at anytime by manually selecting autoprogram by, e.g., selecting an autoprogram selector element 57 shown in
Also, a channel map update feature may be provided. In the example embodiment shown in
In addition to or in lieu of the above update feature,
In addition to or in lieu of the above update features,
While the particular DOWNLOADING TV CHANNEL MAP BASED ON LOCATION AND PROVIDER is herein shown and described in detail, it is to be understood that the subject matter which is encompassed by the present invention is limited only by the claims.
|Cited Patent
|Filing date
|Publication date
|Apr 8, 1996
|Sep 30, 1997
|Lucent Technologies Inc.
|Accessing a video message via video snapshots
|Feb 8, 1996
|May 5, 1998
|U.S. Philips Corporation
|Pay TV method and device which comprise master and slave decoders
|Mar 5, 1999
|Apr 17, 2001
|Sharp Laboratories Of America, Inc.
|On-screen electronic resources guide
|Apr 11, 1997
|May 14, 2002
|Starsight Telecast Inc
|Interactive computer system for providing television schedule information
|Jan 12, 1999
|Dec 3, 2002
|Sony Corporation
|Apparatus and method increasing speed of receiving television broadcasts
|Jan 26, 2000
|Jun 1, 2004
|Viaclix, Inc.
|User terminal for channel-based internet network
|Mar 20, 2003
|Mar 7, 2006
|Sony Corporation
|System and method for facilitating TV channel programming
|Dec 21, 1999
|Aug 29, 2006
|Sony Corporation
|Default source setup for channel numbers
|Jan 5, 1998
|Dec 19, 2006
|Gateway Inc.
|Integration of internet sources into an electronic program database list
|Aug 7, 1998
|Aug 9, 2001
|Peter Rae Shintani
|Configurable remote control unit using a removable memory device
|Mar 26, 2001
|Oct 4, 2001
|Marco Sasselli
|Method for managing subscriber credits in a paytv system
|Dec 18, 2000
|May 16, 2002
|Sue-Ken Yap
|Context sensitive information access artifacts
|Nov 28, 2001
|Jul 4, 2002
|Satoru Maeda
|Information processing method and apparatus and recording medium
|Mar 28, 2001
|Oct 3, 2002
|Koninklijke Philips Electronics N.V.
|Seamless control of input TV signals
|Jul 30, 2001
|Feb 6, 2003
|Digeo, Inc.
|System and method for using user-specific information to configure and enable functions in remote control, broadcast and interactive systems
|Nov 1, 2002
|Apr 3, 2003
|United Video Properties, Inc., A Corporation Of Delaware
|Internet television program guide system
|Oct 18, 2002
|May 8, 2003
|Kuo Chih Jen
|Smart card enabled secure computing environment system
|Dec 10, 2001
|Jun 12, 2003
|General Instrument Corporation
|Methods, systems, and apparatus for tuning television components using an internet appliance
|Jan 18, 2002
|Jul 24, 2003
|General Instrument Corporation
|Remote wireless device with EPG display, intercom and emulated control buttons
|Dec 31, 2002
|Jul 1, 2004
|Kurt Kopchik
|Method and apparatus for wirelessly establishing user preference settings on a computer
|Mar 9, 2004
|Sep 2, 2004
|Akihiro Muto
|Information processing apparatus and method, and distribution medium
|Oct 17, 2005
|Jun 1, 2006
|Sony Corporation
|System and method for facilitating TV channel programming
|Jul 27, 2006
|Feb 21, 2008
|Sharp Laboratories Of America, Inc
|Television system having internet web browsing capability
|Jun 13, 2001
|Mar 6, 2002
|Sharp Kabushiki Kaisha
|Method and device for recording and reproducing television programs
|Title not available
|Title not available
|Title not available
|Title not available
|Title not available
|Title not available
|Mar 1, 2004
|Nov 4, 2004
|Sony Electronics, Inc.
|System and method for facilitating tv channel programming
|Citing Patent
|Filing date
|Publication date
|Jan 22, 2013
|Jun 9, 2015
|Apple Inc.
|Multi-driver earbud
|U.S. Classification
|725/38, 725/39, 725/54, 725/48, 725/51
|International Classification
|Cooperative Classification
|European Classification
|Feb 19, 2009
Owner name: SONY CORPORATION, JAPAN
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:HSIAO, ERIC;REEL/FRAME:022283/0690
Effective date: 20090218
Owner name: SONY ELECTRONICS INC., NEW JERSEY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:HSIAO, ERIC;REEL/FRAME:022283/0690
Effective date: 20090218
|Dec 4, 2015
|Maintenance fee reminder mailed
|Apr 24, 2016
|Lapse for failure to pay maintenance fees
|Jun 14, 2016
|Expired due to failure to pay maintenance fee
Effective date: 20160424


text: Urstadt Biddle Properties Inc. (NYSE: UBA and UBP) announced today that it has acquired the 30,940 square foot Bethel Hub Shopping Center in Bethel, CT. The Bethel Hub center was purchased with cash for $9,000,000. The center is co-anchored by a 7,596 square foot Rite Aid Pharmacy and a 13,884 square foot Caraluzzi's liquor store, other tenants in the center include People's Bank, which occupies a 2,500 square foot pad site with a drive-through, Soups Salads and More, Pizzeria Lauretano, a cleaners, and a Laundromat. The Bethel Hub Shopping Center was built in the 1950's and was subsequently expanded in 1967 and 1977. The shopping center is currently 100% occupied. The Bethel Hub Shopping Center is a very desirable retail destination located in the center of Bethel, CT. that is well protected due to the high barriers to entry. The center is highly visible at the intersection of Greenwood Avenue (Connecticut 302) and Grassy Plain Street. The shopping center is across the street from two prominent retail attractions in Bethel, the famous Sycamore Drive-In, which attracts diners from all over the county, and The Bethel Cinema. Willing Biddle, CEO of Urstadt Biddle Properties Inc. said, "We are pleased that our acquisition program has again found us a desirable community shopping center in our own back yard of Connecticut. This acquisition helps to further one of our company goals of investing in high quality grocery or drugstore anchored shopping centers in the suburban areas surrounding New York City." James Aries, Director of Acquisitions at Urstadt Biddle Properties Inc. adds, "We are pleased to have concluded our second transaction with this seller. The Bethel Hub Shopping Center is well-located in the heart of Bethel and has exhibited very little tenant turnover in its history. The center has been on our radar for some time and we are thrilled to finally own it. Sellers have faith in our ability to close quickly and without complication."


text:
Rev. Dwight D. Gill, Senior Servant
And we know that all things work together for good to them that love God, to them who are the called according to his purpose. Romans 8:28 KJV
We at New Hope Baptist Church of East Orange trust and believe that God has called us to love and serve everyone that comes in contact with our church.
Sundays at 7:45 am & 11:00 am & 5:00 pm
Sundays at 9:30 am
Wednesdays at 11:45 am and 7:30 pm
Women's Bible Study - Fridays at 7:00 pm
Men's Intensive - Saturdays at 8:00 am
"Striving in unity to win souls for Christ
through love and service"
New Hope Baptist Church, is prayerfully seeking to fulfill the position of our beloved retiring Senior Pastor, after 23 years of dedicated service.
All interested individuals MUST complete the attached questionnaire in order to be considered for the position of Senior Pastor of New Hope Baptist Church of East Orange. The Questionnaire must be mailed with the résumé and other supporting documentation to the address provided by May 1, 2017.
Download the following forms
Senior Pastor Vacany Description
Senior Pastor Vacancy Questionaire
Daily Calendar
Find out about our regularly scheduled events at New Hope.


text:
What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
Reward coupon after submissionAsked by amanantal on December 02, 2016 at 03:47 AM
I am wondering if you guys offer a solution to provide a reward coupon code to a member, after each time he submits the form?
For example, if my member fills the survey and submit, he gets a reward coupon code "1234" to use on my website for online shopping? But as this coupon code is only one time use, it will be taken out of the list of coupon codes that I provided to be used after submit button.
Aman Antal
JotForm Support
I assume that you will have two different forms and that your online shopping form on your website is JotForm form.
On your fist form that will provide your users reward coupon code you can use Unique ID widget to create unique code.
You can display Unique ID on Thank you page of your first form or you can send your users unique ID via Autoresponder email.
Then inside of your second form you can create coupon codes and use Unique ID code from first form as coupon code name. Inside of this guide you can find how to add coupon code in the payment form: https://www.jotform.com/help/233-How-To-Add-Coupon-Code-in-the-Payment-Form
If you want that coupon code is used only once that you will need to set Coupon Limit to 1.
However please note that if you want to allow your users to use coupon codes right after they submit first form you will need to set coupon codes in advance inside of your second form. Unique ID will be increase by 1 each time your form is submitted, so you can predict future codes.
In case that you want to create coupon code after you receive submission from first form, than you will need to inform your users that they will not be able to use coupon code right away.
Hope this will help. Let us know if you need further assistance.


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This Hannibal Lecter Pop! vinyl figure is coming as an exclusive to SDCC this year. Isn't he just the cutest knife-wielding murderer? There are even more great exclusives like a SpongeBob SquarePants/Teenage Mutant Ninja Turtle mashup figure, Disney Mystery Minis, and Firefly's Mal and Jayne as retro-style action figures. You know you want them all, but how are you going to fit all the loot in your luggage for the trip home?
See more pictures after the break.
(via The Mary Sue)


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Link: 40 Creative Twitter Theme Backgrounds
http://dzineblog.com/2009/02/40-beautiful-twitter-theme-backgrounds.html »
http://dzineblog.com/2009/02/40-beautiful-twitter-theme-backgrounds.html »
http://www.smashingmagazine.com/2009/01/16/the-ultimate-collection-of-free-vector-packs/ »
http://visualrinse.com/2008/12/14/a-love-letter-to-the-world-of-goo-yay-for-great-game-design/ This is an interesting article, and accompanying video, talking about what make good game and interface design. Certainly a »
http://www.noupe.com/icons/50-most-beautiful-icon-sets-created-in-2008.html [Update: Original link dead!] http://www.noupe.com/freebie/50-most-beautiful-icon-sets-created-in-2008.html [Update 2: New link found!] »
There's nothing like a good round of tutorials to help your Monday morning procrastination inspiration. If you haven't already seen them, I'd suggest having a look »
Introduction Web design enevitably has some hangovers from the early days. The web is, and always has been, really nothing more than a network of documents. »
Here's a neat little site - ajaxload. There's nothing better than letting your user know when they're waiting for something, and although a simple animation can't »
Psdtuts (Photoshop-document tutorials) hit the scene a little while ago on digg, and I've had it on my RSS subscriptions ever since. Off like a dynamo »
DONTCLICK.IT and pr0jects are a couple of outstanding Flash-based sites I've come across this month. Don't Click.it, as the name may suggest, »
Free fonts, Free Vectors indeed. Where to go for free fonts? Urbanfonts and / or Betterfonts. Where to go for free Vector Art? Vecteezy. Free Brushes (for »


text: Hey guys, since making own Answers Wiki is popular, I did did this for Lost. it will help us, to search for all the answers and questions we needed. By the way, some users don't understand why some mysterious are already solved. Lost Answers will helping us with everything I hope.--Station7 08:07, March 19, 2010 (UTC)


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August 19, 2010 by staff
Afpc, Brig. General A.J. Stewart took command of the Air Force Personnel Center on August 6, Randolf Air Force Base in Texas.
There were over 525 people attending the ceremony was Maj. Gen. McClain hand control of AFPC. It is now retiring from the Air Force having served for 33 years of service.
, Said Lt. Gen. Richard Newton, the Air Force A1, who presided over the ceremony: "This is something of a bittersweet day, I guess. KC has impacted the lives of many."
He continued to state that nevertheless AFPC welcomes a strong leader in general Brig AJ Stewart.
Newton said: "AJ, we have work to do ahead. But you are the right leader at the right time."
Brig. General A.J. Stewart, came from command of the Air Force Recruiting Service, which is also conveniently located in the same place. Brig. General A.J. Stewart said he is honored to be chosen to lead AFPC.
He said: "I hope they care as they take care of our nation."
Major General K.C. McClain, in turn thanked the airmen and civilians of the AFPC for their hard work during his two years as commander.
She said, "I am so very proud of this team. AJ, who is booking a first-class team and I know they will too."
Please feel free to send if you have any questions regarding this post , you can contact on
Disclaimer: The views expressed on this site are that of the authors and not necessarily that of U.S.S.POST.


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Online or In Store?
- StoreVote A
- OnlineVote B
Most Helpful Guy
Most Helpful Girl
I do a little bit of both, but if the online store has a really good exchange/return policy where I can go into the store to do either, then I'd pick online shopping any day!
There's so many coupon codes and discounts you could apply, but there also isn't any "pressure." Usually I wear just regular unimpressive clothing to go shopping, which makes sense in my eyes but I always see girls with full faces of makeup, the best clothes and heels (for some reason) and their hair done up to perfection.
That's the perfect opportunity for my girl brain to compare myself and feel bad about anything I try on. Some days I'd feel so much "pressure" I just wanted to give up on shopping and cry when I got home. Online stores don't have that experience for me, so I prefer the relaxed and laid back feeling that comes with it. Plus getting your package in the mail is like getting a present on Christmas.11|00|0


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This course is an excellent next step for those who have taken Basic Woodworking and Box Making. Each student designs and builds a small cabinet that has either a door, a drawer, or for those who are comfortable both. It is a great class for extending the skills and knowledge established in earlier projects.
Students learn topics such as:
- Introduction to Case Work & Cabinets
- Face frame Construction & Joinery
- Shelf Construction & Joinery
- Drawer Joinery, Construction & Installation
- Kicker and Runners
- Stops
- Door Construction, Joinery & Installation
- Hardware Selection & Installation
- Hinge – Selecting and Setting
- Handles – Design impact
- Locks – Selecting and Installing
- Spray Finishing with Lacquer
Student are expected to know all of the basics covered in Beginning Woodworking class and to have some experience with woodworking projects (Box and Table Making). This is an intermediate level class and is pivotal is developing skill sets.
Students who wish to apply to this class who have not taken any classes with Franklin Street should call and talk with us prior to doing so (813 503 7061). Students who design skills are still developing and who want to focus more construction techniques will be provided with a pre designed cabinet. This class is focused on sequencing, construction techniques and joinery rather than on design and finishing.
Click to Register for Cabinet Making
Dates: July 22nd – 28th, 2017, September 30th – Oct. 6th
Cost: $750
Materials Fee: $60 (wood available to students will include poplar, maple, walnut, cherry). Paid separately at start of class.
Deposit: $400
Tool Requirements: 6″ Square (preferably Starrett), writing materials, safety glasses & hearing protection (these are an example, all ear phones must be 21db or higher).


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Blue Hoodies for Unisex(1 Product)
Sort byMost popular first
- Your choice:
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Tennis-Point Tennis Apparel
Promotion Big Logo Hoody - Blue, White
£33.90£20.90Available sizes:
* All prices incl. VAT
The crossed out prices are the RRP.
The crossed out prices are the RRP.


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Face, Fat Transfer And Brow
Find out the key information you need around face, fat transfer and brow surgery at MyBreast, UK cosmetic surgery specialists. Enquire today!
Face, Fat Transfer And Brow
Surgeries are often combined to balance the upper and lower parts of the face.
- Eyelids
- Volumetric Facelift
- Brow and Lower Eyes
- Find out more about brow lifts, endobrow and open brow surgery.
For those who wish to achieve and maintain a more overall youthful appearance, a facelift (or rhytidectomy) in conjunction with a browlift (endobrow or open brow) and fat transfer (fat injections/fat graft) can deliver the desired results.
A facelift is particularly effective in targeting the signs of ageing around the jaw and neckline.
A fat transfer will restore volume and provide optimum results when combined with a facelift.
Find out more about facelift and fat transfer.
A brow lift addresses the ageing process in the upper part of the face and balances the effects of a facelift.
Find out more about brow lifts, endobrow and open brow surgery.


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DJ Angie Vu Ha
DJ Angie Vu Ha best known as Asia's Sexiest DJ and recently featured in the Top 10 Sexiest Supermodel DJs in the world.
The stunning Angie Vu Ha calls Hanoi home, but her good looks and talent behind the decks has taken her around the world – from the hottest catwalks to the biggest party destinations. She began modeling at the age of 17 – quickly cinching the title of Supermodel before moving on her other passion: music. As one of the sexiest women in Asia, this FHM cover girl is making waves behind the decks. Dishing out the hottest, Hip Hop, House, Electro and Dirty Dutch tracks; she prides herself on playing whatever it takes to get the dance floor going.
Also in 2011 Angie stepped into the studio to start her own music production. Her first release 'Cookies' gained instant support from BBC Radio 1's Judge Jules, Marco V, Lisa Lashes and Michael Woods and is one of the fastest selling tracks on the worlds number 1 legal mp3 download site 'Beatport'.
Her second release 'Cream' features the sounds of UK's vocalist Taya and received massive support from Gareth Emery, Marco V and Ministry of Sound Adam K. Formerly resident DJ at New Asia Bar, one of the world's finest clubs – Angie now spins internationally even headlining UK's Escape party in Singapore.
Now having been voted one of the 10 sexiest supermodel DJ's in the world she has over 245 press mentions to her name and is ready to keep on piling up the accolades – both for her music and her moves.
Website: www.angievuha.com


text:
Buy This Figure / Check Current Value On Ebay
Compare this Clone Trooper figure
If you like this Clone Trooper figure, you might also like:
Battle droids beware! The Grand Army of the Republic is on the attack! Clone troopers rise to the challenge when the Separatists unleash their battle droid army. Mighty soldiers by birth and instruction - clone troopers have the DNA of a Mandalorian warrior and undergo tough military training. From the infantry forces to the specialized units - clone troopers defend the Republic with their legendary strength and skill.
Born and bred for military combat - clone troopers are trained to defend the Republic at all costs.


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Clematis House Halls Gap
House, Halls Gap
Rated 5 out of 5 stars 25 reviews
Confirmation within 24hr
From $163 per night {{quote.pricing.message}} Total {{quote.pricing.price | format:'currency':'short'}} for
Min 2 - 4 nights stay
Clematis House is a modern four bedroom home close to Halls Gaps township. This house offers picturesque views of the mountain ranges that surround Halls Gap. We offer very affordable accommodation for up to two families or three couples. Take a 2km bike ride into the town centre or a short stroll to the local hotel. Unwind on the beautiful Clematis Falls hike or simply relax and watch the native wildlife come right to your door. Also enjoy the wood burning fireplace that is perfect for comfortable winter living.
Contains two queens beds,one double bed, one single bed, and a single bunk bed.
Accommadates a maximum of 9 people
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Select request booking to access the quote calculator and to check availability.
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p/n = per night, p/s = per stay, p/p = per person, p/np = per night and person. Ask the owner to arrange optional extras
Note: Pricing is subject to change, and a minimum stay period and other conditions may apply. You should confirm pricing with the property owner. Bookings paid through the Stayz online booking system incur a 2% Service Fee.
Prices listed based on 6 adults. Property has 6 beds and can sleep a maximum 9 people.
- Available
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text:
Using the "offers from" options you can filter merchants from regions which are most common in our database: the UK, Germany, Austria and Poland.
If a checkbox near a flag is selected, offers from merchants from that particular region will be displayed, otherwise they will not be visible.
If you select offers from "all regions", all offers from all merchants will be displayed. These incude offers from merchants in countries not listed here.
Power: 500W RMS 5x satellite (67W) 1x Subwoofer (165W) incl. remote control
Power: 120W RMS 2x satellite (60W) Special features: passive
Power: 540W RMS 5x satellite (60W) 1x Subwoofer (240W) Frequency range: 42Hz-20kHz Special features: remote control, LCD wired remote control
Power: 300W RMS 1x Subwoofer (150W) 2x satellite (75W) Frequency range: 20Hz-20kHz
Power: 300W RMS 2x satellite (75W) 1x Subwoofer (150W) Frequency range: 20Hz-20kHz Special features: incl. remote control & wired remote control
Power: 125W RMS 5x satellite (16W) 1x Subwoofer (45W) Frequency range: 40Hz-20kHz incl. remote control
Power: 200W RMS 5x satellite (20W) 1x Subwoofer (100W) Frequency range: 40Hz-20kHz
Power: 200W RMS 2x satellite 1x Subwoofer Frequency range: 35Hz-20kHz
Power: 200W RMS 2x satellite 1x Subwoofer
Power: 110W RMS 2x satellite Frequency range: 55Hz-20kHz


text:
Dan-Chief Technology Co. Ltd
A 33-year digital connectivity expert and experienced OEM and ODM manufacturer
TÜV-certified | Meeting ISO/IEC 11801-EC- and ANSI/TIA/EIA-568-C.2 standards
This Verified Supplier's Business Registration profile has been independently verified with relevant government agencies View BR Profile
MR Wang, Kai
Sales Manager
MR Liu, Conrad
Avg Response Time: More than 72h
Interested on this supplier's products? Click here to request for invitation to Private Showroom.
More products from this category
Model Number: 625B39AI-2-XX
Address: 8F., No. 12, Ln. 270, Sec. 3, BeiShen Rd., Shen Keng Dist., New Taipei, Taipei, Taiwan (22205)
Tel: (886 2) 26642008
Fax: (886 2) 26642328
Homepage Address: http://www.globalsources.com/danchief.co
Other Homepage Address: http://www.danchief.com
Registered Company: 登騏科技股份有限公司
Business Registration Number: 36185023
Company Registration Address: 新北市深坑區北深路3段270巷12號4樓
* In some jurisdictions, company names and addresses are registered in Chinese only.
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Supplier and product information updated June 05, 2017.
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text:
For the time EVER, in-person Spiceworks training is coming to California!
In 2010, Spiceworks is rolling out 1-day, intensive Spiceworks training events led by our very own product experts called Spiceworks Boot Camps.
Where will the Cali Boot Camp be?
Spiceworks Boot Camp will be held in San Diego, just a 2-3 hour drive from L.A.! Details below:
Spiceworks Boot Camp: San Diego
Date: Monday, April 12, 2010
Time: 9am-5pm
Location: Marine Village Conference Center
(1936 Quivira Way, San Diego, CA 92109)
Price: ONLY $99!
Registration link: http://spiceworksbootcampsandiego.eventbrite.com
Topics covered:
* Getting a Full Inventory of Your Network
* Using Monitors, Alerts & Reports
* Mapping Your Network
* Introduction to Help Desk & User Portal
* Customizing Your Help Desk & User Portal
* Making Spiceworks Do Even More for You: The Community & More
Don't miss out on this steal-of-a-deal training event & chance to meet fellow IT-ers! Snap on of the few spots HERE!
For more info & a schedule of stops for Boot Camps in 2010, check out our website HERE!
This discussion has been inactive for over a year.
You may get a better answer to your question by starting a new discussion.


text:
PHILADELPHIA -After digging itself into an early hole, the University of Pennsylvania men's basketball team fought almost all the way back in the final minutes against Navy. However, it was the Midshipmen who made the final plays as they escaped The Palestra with a 65-59 win on Wednesday night.
Penn lost at home for the first time this season and fell to 4-3, while Navy won its seventh-straight game and improved to 7-2 overall.
Antonio Woods led the comeback with 16 points, 13 of them coming in the second half. Sam Jones chipped in 12 points, making three three-pointers and snagging four rebounds. However, the Quakers turned the ball over a season-high 18 times on the night and missed three crucial free throws in the final minute -- one of them the front end of a 1-and-1 -- that contributed to the defeat.
The Quakers trailed for most of the first half, and were unable to get much going on the offensive end against an aggressive Navy defense. Penn turned the ball over 11 times in the first 20 minutes and went just 8-for-19 from the field. The Midshipmen capitalized on Penn's mistakes, holding an 18-0 advantage in points off turnovers en route to a 37-25 lead at the break.
Navy's lead reached 13 on two occasions early in the second half, but after that the Red and Blue chipped away, cutting the deficit to single digits four different times and finally bringing it down to six with a three from Jones and a layup from Woods that made it 52-46 with less than seven minutes to play.
After Navy capitalized on a layup and a foul, Woods once again cut the lead to six with a trey from the top of the arc with 4:45 remaining. Following a defensive stop, Jake Silpe finished at the rim, and then a Navy turnover led to Woods feeding Matt Howard for an emphatic fast-break alley-oop that made it a two-point game with two minutes to go.
Navy hit a pair of foul shots on its next possession to go up by four, 59-55, before Darien Nelson-Henry -- who was held to single digits in the scoring column for the first time this season, finishing with eight points -- converted both ends of a 1-and-1 on consecutive possessions to tie the game for the first time with just 1:03 left.
Navy quickly answered with a layup at the other end to take a two-point lead. With the Quakers in the bonus, Woods drew a foul near the basket, but the sophomore was unable to convert the front end of a 1-and-1. The rebound was tipped out to Howard, but the possession ended when Woods missed a jumper from the top of the key. This time Navy grabbed the board, and Penn was forced to foul. The Midshipmen connected on four free throws in the final seconds, sandwiching them around another pair of missed foul shots by Woods.
Penn lost on a night when it shot 50.0 percent from the field (compared to Navy's 44.4 percent); the Quakers had 14 assists on their 20 baskets.
The Quakers are back at it on Saturday, heading to George Mason for a 6 p.m. tipoff at the Patriots' EagleBank Arena.
Download: Penn_Navy.pdf


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Fifth Ave. lacks star attraction
OZONE PARK, N.Y. - The $125,000 Fifth Avenue, a division of the New York Stallion Stakes, has a history of producing fillies that have had successful careers, including Dat You Miz Blue, Beautiful America, and So Sweet a Cat.
At this stage in their careers, it doesn't look like there are any budding stars among the nine 2-year-olds entered in Sunday's Fifth Avenue at Aqueduct.
The main contenders are . Karakorum Splendor, a daughter of A. P Jet, finished a well-beaten second in the one-mile Maid of the Mist 15 days ago at Belmont. A return to six furlongs, the distance at which Karakorum Splendor won her maiden by 13 1/2 lengths, should be a bonus for the Jimmy Jerkens-trained filly.
Trained by Howie Tesher, Brassy Boots defeated males at Saratoga in the mud Aug. 29. The second- and third-place finishers, Up Like Thunder and Pelham Bay, each returned to win his next start.
Earlier in the summer, Brassy Boots finished third in a maiden race that was won by Balletto, the runner-up in last weekend's Breeders' Cup Juvenile Fillies at Lone Star Park.
In her last start, Brassy Boots finished fourth in the Joseph A. Gimma at Belmont on Oct. 3. She was beaten 5 1/4 lengths by Megascape.
Tesher isn't offering any excuses for the performance.
"It was unexplainable," he said. "This field might be a little easier."
Avery Hall won her debut by two lengths over a next-out winner at The Meadowlands on Oct. 9. She was cross-entered in Friday night's $67,000 New Jersey Futurity filly division at The Meadowlands. Trainer Cynthia Reese said Friday morning that Avery Hall may run instead in the Fifth Avenue.
Queecy Lake makes her first start for trainer Gary Contessa after an 11 3/4-length maiden win at Finger Lakes.
Ms. Litigator's last race could be a toss-out because it was run in the mud. She finished seventh in the Lady Fingers Stakes at Finger Lakes on Aug. 21. Her races on fast tracks are better.


text:
Charlamagne Says Reality Shows "Give Hoes An Opportunity" [VIDEO]
More Stories From Hip-Hop Wired
Leave a Comment
- Melody Carroll
he right
- Maliksmama
Main reason black folks stay losing. We're quick to push each other under the bus and in front of the train.
Hoes? I don't recall the last time I've seen white, Asian, African, Hispanic, or any other ethnic group get on tv, radio, or the internet and refer to their women as (insert any low down filthy name).
God help us!
- amiwill
It's not a crime to call a hoe a hoe. Are you raising your daughter to be like any of the ladies on love & hip hop?… also I remember plenty of slutt shaming for Monica Lewinsky.
- Self-Hating Negro Slayer
That ain't the point he was trying to make. Check out the other housewives, Mafia Wives, some of the white chicks on bad girls, and so on and so forth. White Men do not come at their ratchett women on a level like that.
- amiwill
I don't think you understand my comment. Why am I supposed to defend hoes and coonery because they happened to be black. Google the shows you named and check the comments. I know Italians that hate mafia wives.
- imsayintho
I agree with you totally….Charlamagne goes in on everyone and while he is a bit vulgar, he's honest and gives his opinion on every thing. And who cares about what race anyone is…..if it looks like a duck, walks like a duck and talks like a duck…its most likely a duck…all these "reality shows" are making our generation look stupid and desperate for a check…
- Billy Official
Im w you! Smh. He is just ignorant.. Little man.
- MsGV
I agree. Charla says some foul things about his own people all the time and the fact his popularity is growing is very disturbing. He praises Katy Perry who is dating a racist, disrespect Lil Kim about her face, says horrible things about Lil Mama, calls RHOA hos, says Justin Bieber should stop hanging with blacks and ACT white so he'll have a better reputation. etc. This guy is nuts. Noooo, he is just keeping it real. I never heard positive things from him ever. If you want to shock us Charla talk about history, culture, education and finances.
- Evans Machuka
look at this dinosaur headed monkey going off talking bullshit


text:
sorry this is kinda long...
so my boyfriend and I broke up a few days ago and it really hurt me because I cared about him a lot and he told me that love is fake and all this stuff this was after he pretty much ignored me for like a week during that week he wouldn't call me text me or anything he went from calling me every night and texting me every day to only talking to me if I talked to him first and after he told me love was fake I was done and sick of it so I told him we should just be friends for a while and that I wanted him to get his stuff today and he said he would. on Tuesday he texted me asking me why I was ignoring him and stuff which was dumb because I hadn't ignored him at all and he was just being dumb after that asking me if I was sad and stuff so I told him I had to go and was going to sleep early this morning at about 2 a.m he texted me saying yo so I texted back and said hi then out of no where he asked if I hated him and I told him no and asked him if he hated me he said no and then I fell asleep and now today he was supposed to come get his stuff but he hasn't texted me or anything today so I'm just wondering what you think is up with him why is he acting this way?
I have no clue what his problem is - guys' advice please?
sorry this is kinda long...
Have an opinion?
What Guys Said 1
Saying "Love is fake" is either an excuse for why he wants to break up and date some one else or it's his reason for wanting to just sleep with women instead of dating them. Either way it seems like he did lose interest and gave a minor attempt at turning it around by pointing out the fact that you weren't talking to him after he said that. I mean of course you aren't going to talk to him, that's like saying he doesn't love you. So that's my opinion of why he's behaving that way.11|00|0
What Girls Said 0
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As most people will know, the intumescent seal that is visible around the perimeter of a fire door assembly plays a crucial role in maintaining the performance of the assembly under fire exposure. Many other intumescent products will be present in the construction, however, and while they may not be so obvious, they all contribute in some way to the overall performance of the assembly and the safety of building occupants.
The perimeter intumescent seal may itself be concealed under the edge lipping of a door leaf but other examples include –
Today's fire door assemblies are highly dependent on intumescent technology and it is true to say that without the vital contributions from the intumescent elements, the fire integrity of the door assembly would be catastrophically compromised.
Further details are freely available from IFSA in the form of downloadable information sheets.
#1 - Intumescent Materials in Timber Fire Doors
or contact IFSA on
Tel: +44 (0) 1844 276928
Fax: +44 (0) 1844 274002
E-mail: email@example.com