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Proximal tubule cells extract dicarboxylates from filtrate and blood, using cotransporters located in the brush border [sodium dicarboxylate cotransporter (NaDC-1)] and basolateral cell membrane (NaDC-3). We expressed the human NaDC-3 (hNaDC-3) in Xenopus laevis oocytes and characterized it by the two-electrode voltage-clamp technique. At −60 mV, succinate (4 carbons) and glutarate (5 carbons) generated inward currents due to translocation of three sodium ions and one divalent dicarboxylate, whereas oxalate (2 carbons) and malonate (3 carbons) did not. The cis-dicarboxylate maleate produced currents smaller in magnitude, whereas the trans-dicarboxylate fumarate generated currents similar to succinate. The substituted succinate derivatives, malate, 2,2- and 2,3-dimethylsuccinate, and 2,3-dimercaptosuccinate elicited inward currents, whereas aspartate and guanidinosuccinate showed hardly detectable currents. The C-5 dicarboxylates glutarate and α-ketoglutarate produced larger currents than succinate; glutamate and folate failed to cause inward currents. Kinetic analysis revealed, at −60 mV, K0.5 values of 25 ± 12 μM for succinate and 45 ± 13 μM for α-ketoglutarate, values close to the plasma concentration of these compounds. For both compounds, the K0.5 was independent of voltage, whereas the maximal current increased with hyperpolarization. As opposed to the rat and flounder orthologs, hNaDC-3 was hardly inhibited by lithium concentrations up to 5 mM. In the absence of sodium, however, lithium can mediate succinate-dependent currents. The narrow substrate specificity prevents interaction of drugs with dicarboxylate-like structure with hNaDC-3 and ensures sufficient support of the proximal tubule cells with α-ketoglutarate for anion secretion via organic anion transporter 1 or 3.
- α-ketoglutarate
- folate
- kidney
- tricarboxylic acid cycle intermediates
- lithium sensitivity
- succinate
kidney proximal tubule cells are involved in the uptake and metabolism of tricarboxylic acid cycle intermediates, which include a variety of di- and tricarboxylates such as succinate, citrate, and α-ketoglutarate. In the proximal tubule epithelium, the di- and tricarboxylates are taken up from both the luminal and the basolateral side through sodium-coupled transport systems, thereby allowing maintenance of intracellular concentrations of dicarboxylates three- to fourfold higher than those in the plasma (7, 11, 14, 15, 26).
In conjunction with the organic anion transporters 1 and 3 (OAT1, OAT3; for reviews, see Refs. 2, 7, 26), sodium dicarboxylate cotransporter (NaDC-3) indirectly drives the secretion of a variety of endogenous and exogenous organic anions. By Na+-coupled uptake, NaDC-3 provides roughly half of the intracellular α-ketoglutarate used for organic anion/dicarboxylate exchange through OAT1 and OAT3 (7).
In recent years, the luminal as well as basolateral dicarboxylate transporters from different species including humans have been cloned (for reviews, see Refs. 11, 14, 15) and designated as NaC1 or the aliases NaDC-1 and SDCT1, and NaC2 or the aliases NaDC-3 and SDCT2 (for a review, see Ref. 11). NaDC-1 was localized to the luminal membrane as demonstrated by Western blot analysis using luminal membrane fractions and a polyclonal antibody directed against a 60-amino-acid peptide from NaDC-1 (19). Basolateral localization of human (h) NaDC-3 was by a polyclonal antibody raised against the fusion protein of glutathione S-transferase (GST)-hNaDC-3 (25).
Functional characterization of heterologously expressed transporters has been primarily performed in human retinal pigment epithelial cells or Xenopus laevis oocytes using radiotracer flux or two-electrode voltage-clamp techniques (for reviews, see Refs. 11, 14, 15). These experiments confirmed the results obtained in the intact rat kidney, isolated, perfused tubules, and vesicles from either luminal or basolateral membranes and revealed that all members perform Na+-coupled cotransport of various tricarboxylic acid cycle intermediates. The stoichiometry of sodium-anion symport is 3:1. The coupling of three Na+ to one generally divalent anion renders the symport electrogenic, with a net transfer of one positive charge across the cell membrane. Transport is thought to be ordered with sodium binding to the transporter before the anion, and lithium can act as a competitive inhibitor to sodium.
As tested with various NaDC-1 orthologs, NaDC-1 has a substrate preference for succinate (K0.5 0.18–1.1 mM) and citrate (K0.5 0.32–6.8 mM). Significant cis-inhibition of radiolabeled succinate uptake was observed in decreasing potency with succinate, fumarate, malate, oxaloacetate, and citrate. Substrate-associated currents were measured with succinate, α-ketoglutarate, glutarate, oxaloacetate, fumarate, and malate (11, 14, 15). NaDC-3 prefers 2,2-dimethylsuccinate over succinate and cis-inhibition of succinate uptake was demonstrated with 2,2- and 2,3-dimethylsuccinate, succinate, glutarate, α-ketoglutarate, fumarate, citrate, malonate, glutamate, maleate, and pyruvate. Significant currents (>20% of control) were evoked by α-ketoglutarate, fumarate, malate, succinate, and the dimethylsuccinates.
Despite many similarities, NaDCs show species differences. Rat renal NaDC-1 (SDCT1, rNaC1), located in the brush-border membrane, has a much higher affinity for succinate (5) than the orthologs from rabbit and human kidneys (18). Moreover, lithium only slightly inhibited human NaDC-1 (18) but strongly decreased transport by NaDC-1 and NaDC-3 from other species (5, 6, 17, 24). Although lithium is used for treatment of bimodal disorders in humans (21), it is not known whether hNaDC-3 and, hence, the supply of proximal tubular cells with dicarboxylates for metabolism and organic anion secretion are impaired at pharmacological lithium concentrations. Finally, endogenous derivatives of dicarboxylates, like folate, guanidinosuccinate, and quinolinate, have not yet been tested as putative substrates of NaDC-3. In uremic patients, guanidinosuccinate and quinolinate concentrations in plasma are increased (23) with possible side effects in renal dicarboxylate transport.
The aim of the present study was to determine the specificity of human NaDC-3 for di- and tricarboxylates and its interaction with lithium.
In vitro transcription of cRNA.
Sodium-dependent dicarboxylate transporter NaDC-3 cDNAs from human (24) kidney were used as a template for cRNA synthesis. Plasmids were linearized with NotI, and in vitro cRNA transcription was performed using T7 mMessage mMaschine Kit (Ambion, Austin, TX). The resulting cRNA was suspended in purified, RNAse-free water to a final concentration of 1 μg/μl.
Oocyte preparation and storage.
Stage V and VI oocytes from X. laevis (Nasco, Fort Atkinson, WI) were separated by treatment with collagenase (Typ CLS II, Biochrom, Berlin, Germany) and maintained afterwards at 16–18°C in control solution (in mM): 110 NaCl, 3 KCl, 2 CaCl2, 5 HEPES/Tris, pH 7.5. One day after removal from the frog, oocytes were injected with 30 nl of cRNA coding for hNaDC-3 and maintained at 16–18°C in control solution supplemented with 50 μM gentamycin and 2.5 mM pyruvate. After 3 to 4 days of incubation with daily medium changes, oocytes were used for electrophysiological studies. Oocytes injected with water served as controls.
Electrophysiological studies.
Electrophysiological studies were performed by the conventional two-microelectrode voltage-clamp method (3, 4). Oocytes were superfused with control solution and after stabilization of the membrane potential, single oocytes were clamped at −60 mV and the current induced by 1 mM succinate was measured to demonstrate functional expression of the hNaDC-3 protein. Voltage pulses between −90 and +10 mV, in 10-mV increments, were applied for 5 s each and steady-state currents were recorded to obtain current-voltage (I-V) relationships. In general, the I-V protocol was applied first under control conditions and then 30 s after changing the superfusion to the test solution. The difference between the steady-state currents measured in the presence and absence of substrates was considered as substrate-induced current, ΔI. Water-injected controls showed no substrate-dependent currents in response to mono-, di-, and tricarboxylates.
All chemicals were purchased from Sigma (Taufkirchen, Germany) or Merck (Darmstadt, Germany). Control solution was prepared as a five times concentrated stock solution. Appropriate dilution and addition of the test substrate were performed at the day of the experiment. Sodium-free solutions were obtained either by equimolar substitution of all sodium by N-methyl-d-glucamine or lithium.
Interactions of lithium with hNaDC-3.
Application of succinate (1 mM) to hNaDC-3-expressing oocytes yielded potential-dependent inward currents that were larger in amplitude at negative than at positive clamp potentials (Fig. 1A, •). These succinate-associated currents were, in contrast to succinate-induced currents observed in oocytes expressing rat or mouse NaDC-3, only marginally affected by increasing lithium concentrations. As measured in paired experiments in five oocytes from three donors, in the absence of lithium, currents induced by 1 mM succinate were −56 ± 6, −44 ± 5, −32 ± 4, and −22 ± 3 nA at −90, −60, −30, and 0 mV, respectively (Fig. 1A, •). These currents only slightly decreased in response to increasing concentrations of lithium. In the presence of 5 mM lithium, succinate-induced currents decreased to −41 ± 5, −32 ± 4, −26 ± 3, and −18 ± 3 nA (Fig. 1A, ▵). When at a holding potential of −90, −60, and −30 mV (Fig. 1B), the succinate-induced currents were plotted as a function of increasing lithium concentrations, residual lithium-insensitive currents of 73, 72, 81, and 81% of the initial current persisted.
Total replacement of sodium by lithium, as performed in paired studies with four hNaDC-3-expressing oocytes from four donors, revealed the following results. In the presence of sodium, steady-state currents showed in the absence (Fig. 2A, ▪) and presence (1 mM, Fig. 2A, □) of succinate near-to-linear I-V relationships throughout the tested potential range. Succinate-induced currents (Fig. 2C, •) were inwardly directed within the potential range between −90 and 0 mV, in support of the proposed coupling of three sodium ions for each divalent succinate. When all sodium was replaced by lithium (Fig. 2B), steady-state currents in the absence (Fig. 2B, ▵) and presence of succinate (1 mM, Fig. 2B, ▴) showed again near-to-linear I-V relationships. The succinate-associated currents (Fig. 2C, ○), however, differed markedly from those obtained in the presence of sodium. These currents increased in amplitude as the potential depolarized (Fig. 2C, ○). For comparison, the succinate-induced currents in the presence of sodium decreased from −44 ± 5 nA at −90 mV to −30 ± 7 nA at −30 mV (Fig. 2C, •) and changed in the presence of lithium from 3 ± 2 nA at −90 mV to −7 ± 2 nA at −30 mV (Fig. 2C, ○). When all sodium was replaced by N-methyl-d-glucamine, succinate-induced currents were completely abolished (data not shown).
Substrate specificity: Carbon chain length and different substitutions at C-2 and C-3.
Citric acid cycle intermediates consist of carboxylates with a chain length of four to six carbons connected either by single or double bonds and different substitutions at C-2 or C-3. The substrate specificity of tricarboxylic acid cycle intermediates irrespective whether they are mono-, di-, or tricarboxylates at physiological pH was tested by measuring currents induced by these compounds at a holding potential of −60 mV (Fig. 3). The data are expressed as a percentage of the succinate-induced currents in the same oocytes. The substrate concentration used was 1 mM, which should yield maximal-inducible currents, at least in the case of succinate. Succinate, α-ketoglutarate, fumarate, malate, and oxaloacetate produced currents of similar amplitude. Currents of <20% of control were observed in the presence of citrate, isocitrate, and cis-aconitate. These substances are predominatly trivalent at physiological pH, and the small currents observed may be due to the low concentration of divalent substrate present at pH 7.5.
Succinate- and α-ketoglutarate-induced currents were examined to identify the substrate concentration at half-maximal current (K0.5) for these substrates under voltage-clamp conditions in the range between −90 and 0 mV. Succinate as well as α-ketoglutarate showed potential-dependent inward currents that saturated at concentrations >0.5 mM. In the case of succinate, application of higher concentrations decreased substrate-dependent currents (data not shown) most probably due to intracellular accumulation. As determined in four oocytes from three donors, the K0.5 for succinate was ∼25 μM independent of membrane voltage (Fig. 4A). The succinate-induced maximum current at saturating concentrations (ΔImax) increased as the membrane voltage was made more negative (Fig. 4B). Similar results regarding K0.5 and ΔImax were obtained for α-ketoglutarate. K0.5 was ∼35 μM independent of membrane voltage (Fig. 4C), and ΔImax again increased as the oocytes became hyperpolarized (Fig. 4D, 4 determinations from 3 donors).
The ratio ΔImax/K0.5 indicates the transport efficiency of the transporter for a given substrate (Table 1). ΔImax/K0.5 decreased in the order succinate ∼ glutarate > α-ketoglutarate, indicating that transport efficiency was not dependent on the length of the carbon backbone, and substitution at C-2 influenced transport efficiency.
In addition to succinate, other C-4 and C-5 dicarboxylates, which are not members of the tricarboxylic acid cycle, were also translocated via hNaDC-3. The data are plotted as percent of the succinate-induced currents in the same oocytes. The introduction of two methyl groups at C-2 (2,2-dimethylsuccinate, 2,2-DMS) increased substrate-dependent current to 152 ± 4% (Fig. 5). However, the substitution at C-2 and C-3 with either methyl-(2,3-dimethylsuccinate), (2,3-DMS) or sulfhydryl-groups (2,3-dimercaptosuccinate, DMSA, succimer) reduced the current to 74.5 ± 5 and 28 ± 7%, respectively, compared with succinate (4 oocytes from 4 frogs). Aspartate and glutamate differ from succinate and glutarate, respectively, by the presence of a positively charged NH3+ group at C-2. This substitution decreased aspartate- and glutamate-associated currents to 18 ± 12 and 3 ± 1% of control (3 oocytes from 3 donors). Fumarate and maleate are both C-4 dicarboxylates and differ with respect to the trans- and cis-position of their COOH groups. Fumarate exhibited currents comparable in magnitude to succinate (see Fig 3), whereas maleate induced barely detectable currents (Fig. 5).
Divalent dicarboxylates with shorter chain lengths like oxalate (C-2) and malonate (C-3) showed no substrate-induced currents (<20% of control, 5 oocytes from 5 frogs). Among the monovalent C-3 carboxylates tested, pyruvate (5 oocytes from 5 donors) and lactate (3 oocytes from 3 donors) expressed currents of 25 ± 13 and 19 ± 7% of control.
Interactions of other dicarboxylates and related compounds that may be substrates of hNaDC-3: Folate, quinolinate, and guanodinosuccinate.
As shown in Fig. 6A, folate, formally an N-substituted glutamate derivative with two COOH groups, seemed not to be a substrate of hNaDC-3. At −60 mV in paired experiments with four oocytes from four donors, succinate (1 mM, Fig. 6A, •) induced an inward current of −26 ± 1 nA, whereas the folate-associated current was −1 ± 1 nA (Fig. 6A, ○). Folate concentrations up to 10 mM did not induce substrate-dependent currents (data not shown). Folate, however, was able to alter succinate-induced currents. Compared with succinate (1 mM, Fig. 6B, •), simultaneous application of succinate (1 mM) and folate (0.5 mM, Fig. 6B, ○) resulted in small inward currents at potentials more negative than −60 mV and outward currents were seen at potentials more positive than −60 mV (paired experiments with 4 oocytes from 4 donors).
Quinolinate, a cyclic dicarboxylate derived from trypthophan metabolism, showed compared with succinate (Fig. 7A, •) small potential-dependent inward currents (Fig. 7A, ○). However, whereas the succinate-evoked currents reversed at positive potentials, the quinolinate-induced currents reversed at −36 ± 15 mV. Picolinate (1 mM), a cyclic monocarboxylate, did not induce currents at all (Fig. 7A, ▪). These experiments were performed with eight oocytes from three donors. In addition, quinolinate (0.5 mM) was not able to inhibit the currents elicited by succinate. As determined in seven oocytes from three donors, the currents measured in the simultaneous presence of succinate (1 mM) and quinolinate (0.5 mM; Fig. 7B) were not significantly different from those induced by succinate alone (1 mM, Fig. 7B, •).
Guanidinosuccinate is a toxin present in uremic plasma up to concentrations of 0.35 mM (23). As observed in paired experiments on nine oocytes from seven donors, at −60 mV the currents induced by 1 mM (Fig. 8A, ○) and 10 mM guanidinosuccinate (▪) were −1 ± 1 and −3 ± 1 nA, respectively, whereas the succinate-induced current (•) reached −33 ± 15 nA. Guanidinosuccinate was able to inhibit to some extent the succinate-evoked current (Fig. 8B, ○). At −60 mV and in paired experiments in seven oocytes from three donors, the current determined in the simultaneous presence of guanidinosuccinate (0.5 mM) and succinate (1 mM) was 76.9 ± 15.1% of the current produced by succinate (1 mM) alone.
Mammalian NaDCs are plasma membrane transporters mediating the cellular entry of a variety of dicarboxylates that are intermediates in the tricarboxylic acid cycle (e.g., succinate, fumarate, malate, and α-ketoglutarate) in an electrogenic sodium-dependent fashion (11, 14, 15). Accordingly, the transport can be visualized by cell membrane depolarization, and, under voltage-clamp conditions, by an inward current. Succinate-induced currents were a linear function of the holding potential, being smaller at less negative potentials and reversing at positive potentials. This behavior is in accordance with an electrogenic cotransport of three sodium ions with one dicarboxylate, a property shared by all NaDCs. However, there are significant functional differences between NaDC-1 and NaDC-3 with regard to the cation effect. When sodium was replaced by choline or cesium, substrate-dependent inward currents were abolished in oocytes expressing the rabbit NaDC-1 (17). During substitution of sodium by lithium, however, succinate-induced inward currents were observed (17), which decreased as the membrane depolarized. This indicated that the Li+-succinate−2 stoichiometry is most likely 3:1 in rabbit NaDC-1. When these studies were repeated in oocytes expressing hNaDC-1, no such succinate-induced currents were detected in the presence of lithium (27), indicating species differences with respect to the ability of Li+ to support succinate transport.
During total replacement of sodium by lithium, succinate induced outward current deflections at holding potentials that changed into inward current deflections at potentials less negative than −50 mV in oocytes expressing mouse NaDC-3 (16) and hNaDC-3 (this study). These currents were much smaller than the inward currents induced by succinate in the presence of sodium. The nature of the current deflections seen in the presence of lithium is unclear. If three Li+ would be cotransported with succinate, the currents should be inward at all tested potentials, as found for rbNaDC-1 (17). The cotransport of two Li+ with one succinate would result in an electroneutral process not visible by the two-electrode voltage-clamp technique. In case of cotransport of one Li+ with one succinate, outward currents increasing with depolarizing membrane potentials should be observed. I-V relationships in the presence of lithium revealed a small decrease in conductance when succinate was added. Therefore, succinate appears to inhibit rather than to induce a current in the presence of lithium. The mechanism of this process remains to be determined.
In our experiments on hNaDC-3, up to 5 mM Li+ only slightly inhibited succinate-induced currents. A comparably small effect of Li+ was found with hNaDC-1 (18), whereas rodent NaDC-1 and NaDC-3 were strongly inhibited by lithium (6, 10, 17, 18), indicating again species differences. The plasma concentrations of lithium used for the treatment of bimodal disorders are in the range of 0.8–2 mM (21). At these concentrations, neither hNaDC-1 nor hNaDC-3 is inhibited, suggesting that therapeutic concentrations of lithium do not affect reabsorption of succinate and other dicarboxylates either from the tubular lumen or from the peritubular capillaries. The observed increase in urinary citrate excretion during lithium therapy can, therefore, not be attributed to an effect on NaDC-1 and NaDC-3 and suggests that a distinct transporter for citrate is affected. Such a transporter has not yet been identified in the human kidney.
hNaDC-3 has a broad substrate specificity for 4- and 5-carbon, terminal dicarboxylic acids in the trans-configuration, including the tricarboxylic acid cycle intermediates succinate and α-ketoglutarate. The kinetic constants for hNaDC-3 as derived from the two-electrode voltage-clamp studies agree quite well with previous data. The K0.5 for succinate was in the range of 30 μM in agreement with the K0.5 of 20 ± 1 μM obtained in human retinal pigment epithelial cells transfected with hNaDC-3 but is lower than the K0.5 of 102 ± 20 μM in hNaDC-3-expressing oocytes (24). In the potential range between −90 and 0 mV, the K0.5 for succinate was not affected by the membrane potential, suggesting that binding of succinate to the transporter is voltage independent. Similar findings were obtained for α-ketoglutarate showing a potential-independent K0.5 of 40 μM. Importantly, these K0.5 values are in the range of the circulating plasma concentrations of succinate and α-ketoglutarate, which lie between 10 and 40 μM (26). The transport efficiency, ΔImax/K0.5, for succinate and α-ketoglutarate differed by a factor of 2.1 for hNaDC-3. As opposed, succinate was translocated 15 times more efficiently than α-ketoglutarate in hNaDC-1 (27), indicating differences in the substrate binding and translocation between hNaDC-1 and hNaDC-3.
Besides succinate and α-ketoglutarate, hNaDC-3 translocated the dicarboxylic tricarboxylic acid cycle intermediates fumarate, malate, and oxaloacetate, as visualized by the respective substrate-induced currents. With the tricarboxylates citrate, isocitrate, and cis-aconitate, much smaller currents were observed, indicating a considerably slower translocation. At 25°C, the pKs of citrate are 3.1, 4.8, and 6.4, respectively. Therefore, at physiological pH, less than 10% of citrate is present as a divalent anion. This implies that at a total concentration of 1 mM citrate, ∼0.1 mM citrate−2 was responsible for the observed small inward current. The total plasma concentration of citrate is 0.135 mM (26). At pH 7.4, less than 0.014 mM of citrate is present as a divalent anion, a concentration too low to interact significantly with hNaDC-3. Because citrate is excreted in healthy humans, another transporter responsible for translocation of citrate and presumably other trivalent carboxylates such as isocitrate and cis-aconitate must be present in the kidneys. Similar findings with respect to citrate were observed with hNaDC-1 (27).
Among other carboxylates, the moncarboxylate pyruvate showed small substrate-dependent inward currents. This finding fits with another study, in which uptake of radiolabeled pyruvate into hNaDC-3-expressing oocytes was demonstrated (9). In addition, the monocarboxylate lactate (this study) and the monovalent anion dimercapto-1-propane sulfonate showed inward currents of small amplitude in oocytes expressing either hNaDC-3 or fNaDC-3 (3), demonstrating that the NaDC-3s from different species are able to handle monovalent anions, at least to a small extent.
hNaDC-3 also interacted with dicarboxylates substituted with two methyl groups (2,2-DMS, 2,3-DMS) or two mercapto groups (2,3-DMSA). 2,2-DMS induced a current larger than that evoked by succinate, whereas 2,3-DMS produced a considerably smaller current. Rat NaDC-3 transported 2,3-DMS with high affinity (K0.5 27.2 ± 2.2 μM), and 2,3-DMS evoked ∼60% of the succinate-induced current (6). In contrast, rat NaDC-1 showed low affinity for 2,3-DMS (K0.5 272 ± 3 μM) and evoked only 17% of the succinate-evoked current (6). Thus NaDC-1 does not appreciably interact with 2,3-DMS. In a previous study on flounder NaDC-3 (3), we showed that the K0.5 for 2,2-DMS was independent of voltage, whereas the K0.5 for 2,3-DMS increased with decreasing voltage, suggesting that the position of substituents at the succinate molecule determines the voltage dependence of the apparent affinity. The second 2,3-disubstituted compound, DMSA, contains a backbone of four carbons, two negatively charged COOH groups and two vicinal sulfhydryl groups, which are highly active in chelating free heavy metals like lead and mercury within cells or blood (1). Heavy metals are predominantly deposited within renal proximal tubule cells (28). Therefore, renal detoxification requires the entry of uncomplexed DMSA via a transport system (28). In the present study, we provide evidence for the translocation of DMSA by human NaDC-3. Once within the cell, DMSA can chelate heavy metals and thus contribute to detoxification. Thus hNaDC-3 appears to be instrumental for the increased renal heavy metal excretion during administration of DMSA.
Folate is freely filtered at the glomerulus and undergoes active reabsorption as well as secretion in the proximal tubule (8, 12). OAT1 (20) and OAT3 (22) can facilitate uptake of folate or folate derivatives like methotrexate across the basolateral membrane. Because folate possesses a 5-C backbone similar to glutarate and glutamate, we investigated its interaction with hNaDC-3. Folate, however, did not induce any current most probably due to its bulky substitution at C-2. However, folate markedly interfered with succinate-induced currents, which were no longer a linear function of the holding potential, and reversed at about −60 mV rather than at positive voltages. Such a change in succinate-induced current was observed earlier with flufenamate and was attributed to the occurrence of a K+ conductance, the nature of which remained unclear (4).
Circulating uremic toxins have been proposed to facilitate progression of chronic renal failure. The monovalent organic anions indoleacetate, indoxyl sulfate, hippurate, and p-hydroxyhippurate are handled by OAT1 (13). We tested here the dicarboxylic uremic toxins, guanidinosuccinate and quinolinate (23). Neither guanidinosuccinate nor quinolinate was able to induce substrate-dependent currents. Guanidinosuccinate, but not quinolinate, inhibited succinate-induced currents up to 20%. Thus the cyclic dicarboxylate quinolinate is not a substrate of hNaDC-3, whereas guanidinosuccinate may act as an inhibitor in uremia.
Taken together, the human NaDC-3 shows affinities for succinate and α-ketoglutarate matching their plasma concentrations. For translocation, C-4 and C-5 dicarboxylates with the COOH groups in trans-configuration are preferred. Substituted dicarboxylates do not induce currents when a positively charged NH2 group is present as in aspartate, glutamate, or guanidinosuccinate or when the substitution is too bulky as in folate. The narrow substrate specificity prevents hNaDC-3 from reacting with anionic drugs and enables it to continuously provide proximal tubule cells with dicarboxylates as fuels and with α-ketoglutarate as exchange partner during anionic drug secretion via OAT1 and OAT3.
This research was supported by Deutsche Forschungsgemeinschaft Bu 998/2–2, 3 to B. C. Burckhardt.
The authors thank V. Ganapathy for the generous gift of the hNaDC-3 clone. The help of I. Markmann and S. Holpert during the course of the experiments and E. Thelen in preparing the figures is gratefully acknowledged.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2005 the American Physiological Society


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Global Financial Crisis and Policy Responses in Southeast Asia : Towards Prudent Macroeconomic Policies
The global fi nancial crisis hit the Southeast Asian economies through fi nancial and real sectors by the combination of lower global demand and tighter credit demand effect. The challenge for policymakers in this region is not just to prevent the escalation of the crisis and to mitigate the downturn, but also to ensure a good starting position once the rebound sets in. Policymakers should avoid taking on an excessive level of debt or creating the conditions for an infl ationary bubble by the current reaction to the global slowdown. A prudent counter-cyclical policy is necessary, and we should not ignore the medium and long-term sustainability.
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Sorouh wins Cityscape Abu Dhabi's best developer award
Sorouh Real Estate announced that its flagship project, The Gate District, Shams Abu Dhabi has won the Cityscape award for 'Best Commercial Project,' at the Cityscape Real Estate Awards ceremony held last night at Emirates Palace Hotel.
The awards ceremony sought to recognize and reward real estate industry professionals and companies that have shown outstanding performance and achievement in key market and project areas. Projects were judged by a team of high profile real estate industry experts from across the world.
For the 'Best Commercial Project' award, Sorouh won based on its outstanding and innovative approach to the overall strategy of the development. The multi-use Gate District project of Shams Abu Dhabi outshone other project nominees in its category for showing world-class standards of design, sustainability, energy efficiency and innovation.
"We are thrilled to have won this prestigious award which acknowledges our efforts to offer life in perfect balance – in all of our projects," said Mounir D. Haidar, Sorouh CEO.
The award was collected by Haidar at an exclusive Gala dinner attended by senior executives and dignitaries from the Middle East real estate industry.
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- Sorouh receives 'Best Mixed Use Future Project Award' at Cityscape Abu Dhabi 2011
- Mounir Bouchenaki awarded
- Abu Dhabi Urban Planning Council Wins Best Residential Project Award at Cityscape Abu Dhabi
- Abu Dhabi projects win top awards
- Emirates Palace wins 2 awards for the Best Hotel and Best Spa in Abu Dhabi


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X-Factor, the After Effects 6.5 plug-in that uses networked computers to speed previews of scenes, has been updated to version 1.5 by developer GridIron Software. The new version adds support for network rendering, and support for network drives and Windows XP Service Pack 2.
The plug-in uses Macs and Windows PCs on a network to speed up the previewing of heavy-duty AE scenes. These computers need to have the AE and GridIron rendering nodes installed. The new version also allows users to render scenes using the plug-in, rather than the Professional version of After Effect's own network rendering system.
GridIron has also confirmed that it's developing the system for use within other 'video packages', though the company would not be more specific than that.


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Grinding Meat Tips
Interested in grinding meat yourself? Here are some tips to make your task easier.
Making burgers moves into a totally different dimension once you start grinding meat yourself. After tasting the difference in good quality coarse-ground meat the chances are pretty good that you will become hooked and rarely revert to buying pre-ground meat.
Buying a Meat Grinder
Grinders come in all shapes and sizes. Examples are electric stand alone models, food processor attachments and hand models. Most work pretty well and are fine for domestic use. Before you buy a meat grinder here are some aspects you might want to consider:
- you don't want to spend half the day grinding meat. On the other hand neither do you want to pay through your neck for a turbo-charged monster if you only intend grinding a couple of pounds at a time. Discuss your requirements with the manufacturer/retailer before you make your purchase. There are so many alternatives available that you are sure to find one that matches your needs. Something else to keep in mind is that hand models tend to use quite a lot of elbow grease, especially the larger ones.
- the grinder must be easy to strip and assemble. The inside of the body should be relatively easy to access to facilitate cleaning.
Replacement Parts
- check whether cutting knives, cutting plates, and thrust washers are reasonably priced and readily available.
Cutting Plates
- check the sizes of the plates that come as standard equipment with the grinder to see whether they meet your needs. Here are some guidelines:
1/8" (3.0mm) - Fine
9/64"(3.5mm) - Medium Fine
5/32"(4.0mm) - Medium
3/16"(4.8mm) - Medium Coarse
1/4" (6.5mm) - Coarse
3/8" (9.5mm) - Very Coarse, for pre-grinding
Generally when grinding meat for burgers a coarse and a medium plate should be sufficient.
Cutting Knives
Buy a separate knife for each plate, they will stay sharp much longer. Mark the knife (back) and one side of the plate (outer edge) with a punch or hacksaw to prevent mixing them up. The reason for this is that the knife and the plate wear with use and develop a very close fit against each other which cuts the meat much better. Use the knife with a different plate and it has to wear again to adapt to the new surface which does not have the same properties as the first plate. Even when using a matched knife and plate you'll want to assemble the grinder so that the knife always cuts against the same side of the plate.
Grinding Meat
Pretty simple really, cut all the meat into small cubes not bigger than 1"(25mm) and if you are adding extra fat cut the fat into much smaller cubes, maybe 1/4 the size of the meat. This allows you to distribute the lesser volume of fat more evenly. The same principle applies if you add a second meat type, like bacon, which is less in volume than your primary meat.
Spread the meat cubes in a single layer on your work surface and then distribute the fat (or second meat type) evenly over the meat. Spice the layer of meat, turn it over (spatula/egg lifter works well) and spice the other side as well.
If you intend binding the mixture for patties with a little fresh bread crumbs soaked in some cool stock and a bit of egg now is the time to distribute this evenly over the meat.
Mix everything through lightly with your hands and put the mixture into the freezer until it is very cold (just before it starts to freeze). A very cold mixture makes grinding meat a walk in the park and delivers excellent results. Although I don't go to such extremes I know of people who also put the grinder parts into the freezer prior to grinding meat and they claim great results.
Choose the plate size according to the quality and tenderness of the meat. With tender meat a coarse cut is preferred. Tough meat would warrant a medium cut and very sinewy meat would require a fine cut.
Follow the manufactures instructions to grind the meat. The threaded retaining ring on the front of the grinder needs to be pretty tight to force the cutting plate to seat tightly up against the knife otherwise you wont have much success with grinding meat. Use a pushing stick and never your fingers to force the meat cubes into the grinder and down onto the worm.
Stoppages are usually caused by sinews getting wrapped around the knife. This is generally due to a loose retaining ring, a blunt or dull knife, or the meat not being cold enough. Always unplug an electric grinder from the wall socket before attempting to clear a stoppage.
After Grinding
If you are new to this or if you are trying out a new recipe the next step after grinding is to put the ground meat into the refrigerator.
Don't clean up quite yet.
Take a small sample of ground meat and make a miniature patty. A heaped teaspoon is enough. Fry it in a pan and taste the texture and spicing. Here's how to correct some common errors.
Too Tough
- If the ground meat is a bit tough you will want to put it through the grinder a second time. If it is very tough or sinewy do this using a plate with smaller holes.
Not Enough Spice
- If it is only a bit of spice that is needed spread the ground meat out in a thin layer on the work surface and sprinkle the extra spice evenly over it. Mix through gently with your hands.
Too Much Spice
- If the ground meat is too spicy get some more fresh meat and grind it without adding any spice. Spread the over-spiced meat out in a thin layer and distribute the unspiced meat evenly over it. Mix through gently with your hands.
Refrigerate the ground meat until you are ready to mold the patties.
Cleaning the Grinder
No tricks here. It's just important after grinding meat to completely strip the grinder and wash it and all the parts meticulously. A bottle brush works well with small grinders. After rinsing and drying I make a habit of spraying the cutting plate and knife lightly with cooking spray to prevent them from rusting. Assemble the grinder to keep all the parts safely together and cover with a cloth to keep dust out.
Grinding meat is an extremely rewarding experience and once you start you probably will not restrict yourself to only making great tasting burgers. Ground meat dishes will also take on a whole new meaning and then of course there is that whole new world of making your own sausage that lies ahead!
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- Item No.
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Product Information for Stefco Industries Center Pull Towel
Highlights for Stefco Industries Center Pull Towel
Marketing Information
Center Pull Towels are designed to fit in most center pull dispensers and reduce cross-contamination since you only touch the towel you will be using. Cost-effective towels are perforated to ensure one-at-a-time dispensing. Towels are also absorbent, strong, convenient and hygienic. Design helps minimize the risk of crossover contamination and reduce over-consumption and waste. Ideal for restrooms, kitchens, breakrooms, health-care facilities, food preparation and other areas where sanitation is important. Each roll contains 600 sheets.
General Information
Country of OriginUnited States
Recycled Content40%
Assembly RequiredNo
Green CompliantYes
Green Compliance Certificate/AuthorityDesign for the Environment (DfE)
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By the late 1920s, the foundation of the modern Chrysler Corporation was formed. The Chrysler brand was cast as the premium marque, followed by DeSoto and Plymouth. In 1928, the corporation purchased Dodge.
Early Chrysler models were known for innovation, by including high compression engines and carburetor air filters ahead of everyone else. From the mid-1930s until the late 1940s, Chrysler was one of the top selling brands in America. The innovation continued as the Chrysler brand offered the first one-piece curved windshields, replaceable oil filters and downdraft carburetors.
Early on, Chrysler was a design pioneer with its Airflow design. An Imperial model was introduced, marketed briefly as a separate brand, but always designed with Cadillac and Lincoln in mind. After World War II the first hemispheric-head or HEMI V8 engines appeared, giving the brand a distinct performance advantage that propelled sales. With the new engines, the first Chrysler 300 models were introduced.
Like other American manufacturers, Chrysler vehicles were upsized from the late 1950s to the mid-1970s. During that time, the company led the industry by introducing several firsts, including a push-button transmission, power steering and a torsion bar suspension.
The 1960s brought new and updated models to the Chrysler line, as the Saratoga and Windsor were dropped and the Newport added. The 1970s saw the introduction of the Chrysler Cordoba, a personal luxury coupe and the smallest model of that era. As consumer acceptance for smaller models caught on, the compact Chrysler LeBaron followed.
During the 1980s, the brand's most important product made its debut. The Chrysler Town & Country wasn't the first Chrysler Corporation minivan, but it raised the segment's visibility and allowed Chrysler to acquire new customers. In the 1990s, Chrysler brought out the Concorde and 300M large sedans, as well as the midsize Cirrus sedan and Sebring coupe. That was also the decade Daimler and Chrysler merged, a relationship that was terminated within 10 years of its founding.
Throughout the early part of the new millennium, fresh products were introduced, including the small Chrysler PT Cruiser and the next generation Chrysler 300. The Sebring became the Chrysler 200 and, along with the 300 and the Town & Country, these vehicles compose the brand's entire model line.
Until 2014, Chrysler was marketed as a premium brand to compete with Buick and defunct Mercury. With Daimler exiting Chrysler and Fiat taking over in recent years, the brand has been mainstreamed and now competes with the likes of Toyota, Chevrolet, Hyundai, Nissan, Ford, Kia, Honda, Mazda, Volkswagen and Mitsubishi.


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The Viola Project is looking for teaching artists!
Using the works of William Shakespeare, The Viola Project unites and empowers girls from diverse backgrounds so they may grow up to be whoever they want to be.
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text: I like lists. So here is my list of the best skin care products for every skin type. I have also included a non-exhaustive list of product suggestions with links to my reviews in those instances where I have reviewed the product. Do you have a top skin care product that you would add or… Continue Reading


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I've seen tiles at stores that had various quotes on vinyl attached to the tile and have long admired them--but they were always out of my price range. Once I got my cricut--I had a solution! I've found a wide variety of tiles at my local hardware store. And instead of vinyl--I use cardstock. This particular tile is made with a stone tile and blue textured cardstock. I used my Make The Cut program to design the lettering and then cut using my cricut. To attach the wording, I used Aleen's tacky glue and positioned the lettering. To protect the wording from damage, I painted mod podge glue over the top, being careful not to get any on the tile (you can see the residue if you do). I've discovered that this is very inexpensive gift to give. It only takes an hour or two to put it together and people love it! TFL!!
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In the coming days, the Big House will be getting a frosty makeover.
While ice-making equipment will be arriving at Michigan Stadium later this week, HBO cameras already have invaded the dressing rooms of both the Detroit Red Wings and Maple Leafs. You can almost hear Leafs coach Randy Carlyle bleeping about it, too.
Indeed, the Winter Classic is less than a month away and preparations are in full force, the keys to the Big House having been handed over to the NHL after the Michigan-Ohio State football game on Nov. 30.
"This is our biggest game ever," NHL chief operating officer John Collins said in a phone interview.
And, arguably, the "biggest" celebration of the sport we have ever seen.


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The general stuff:
Soy and Pepper is about recipes, cooking experiments, bento (lunch boxes), thoughts on food and dining and just about anything food-related that I come across. It is an East-meets-West food blog that features food and recipes ranging from Chinese, Thai and Japanese, to British and Mediterranean.
Who is behind Soy and Pepper?
I am an ethnic-Chinese from Singapore currently living in Vancouver, Canada with my husband. I don't have any formal culinary or photography training but I do love cooking and eating and taking photographs and it's been a very enjoyable learning process. My deep interest in food and cooking developed particularly after I moved to the UK. Like many overseas students and expatriates (especially from Asian countries), I miss the delicious, cheap and huge variety of food from home. Since I could not get most of those dishes in restaurants here (at least not easily or cheaply), I started to cook them myself to satisfy my cravings. One thing led to another and soon I found myself cooking, shopping, planning, reading and thinking about food almost all the time!
And I must also acknowledge the husband (AP) who happily munches through my cooking and offers feedback on what works and what doesn't. Thank goodness he has a wide and relatively adventurous palate (for a Brit anyway, heh). And he also waits patiently for his dinners while his wife snaps way too many photos.
Why a food blog?
In 2007, I found that food posts have started to take over my personal blog quite a bit and I would like to devote more space to food and cooking. Having another journal where I can specify the tags and posts to food and recipes also make it easier for me to search for particular ingredients or recipes, since I use this food blog as a personal reference/archive as well. I enjoy playing with different ingredients, recipes, techniques, presentation, and capturing the cooking process and end product the best I can in pictures and in words. It is a nice creative outlet for me and a very tasty hobby!
Why 'Soy and Pepper'?
I love cooking and eating all types of cuisine, from Chinese, Thai and Japanese to British, Italian and French. I therefore wanted a blog title to reflect this East-meets-West approach that I take to food and 'Soy and Pepper' came to mind.
(Yakun Kaya Toast, Singapore Changi Airport, Terminal 2, Arrival Hall)
In Singapore and Malaysia, there is a traditional breakfast of soft-boiled eggs with kaya toast, a sort of fusion breakfast as a result of British colonial past. Instead of being placed in an egg cup, the soft-boiled egg is cracked open into a saucer. Dark or light soy sauce and white pepper is added to taste and then eaten with slices of butter and kaya (egg and coconut jam) toast. It seems fitting that my blog title should reflect this meal that is so strongly associated with where I came from.
What's with all the bento stuff?
Making bento is another hobby/lifestyle that I picked up in mid-2007. After years of packing boring sandwiches into work, making and taking bento lunches into work made our lunches much more interesting and is much cheaper and often healthier than cafeteria food. The reasons behind why I do bento can be found here.
What camera do you use?
The older photos (prior to February 2008) were taken with a point-and-shoot Canon Powershot A75. I later gave in to a beginner's digital SLR, the Canon EOS 400D (Digital Rebel XTi in North America). The lenses I use are Canon EF-S 18-55mm f/3.5-5.6, Canon EF 28-105mm f/3.5-4.5 USM and Canon EF 50 mm f/1.8 II.
Anything else?
I am a food enthusiast who is always on the look-out for new ideas and tips on improving aspects of my cooking and photography. Comments are very welcome (although those of a solicitous or rude nature will be quietly deleted; I do not respond to spam or trolls). I can also be contacted at nilmandra[at]soyandpepper[dot]com.
If you are an overseas Singaporean or Malaysia, I hope you are similarly inspired to recreate food from home and that this website gives you some useful information to do so. Happy cooking!
(Updated 19 August 2008)
Wednesday, 14 November 2007
About Soy and Pepper
The general stuff:
22 comments:
- sohcool said...
I happened to get into your blog from TasteSpotting. And when I saw the 'Mee Hoon Kueh' post , I knew you must be a singaporean like me. Will bookmark your blog. I count on making some of the dishes featured here.
- 22 April 2008 at 07:29
- Nilmandra said...
Sohcool: Thanks! I see that you're just across the Channel in France. *waves* There are a good number of foodblogs out there by Singaporeans and Malaysians, all trying to recreate the taste of home :) Hope you enjoy some of the recipes here.
- 23 April 2008 at 07:10
- WillD said...
Hi from Chicago, IL, USA. Saw your roast chicken/coriander rice photo on Tastespotting and left a comment. Have bookmarked your blog. Great recipes! I will definitely be making more recipes...Yaki Udon with Beef is next!
- 3 May 2008 at 08:44
- Nilmandra said...
Hi Will, thanks for dropping by and I hope you enjoy trying out the recipes. The yaki udon with beef seems to be a hit with most people!
- 3 May 2008 at 08:58
- Mrs Ergül said...
Hi there! I'm so glad to find another food blog by a fellow Singaporean :)
- 9 June 2008 at 18:49
- Nilmandra said...
Hi Mrs Ergül, nice to meet you too! Hope you like the recipes here, and I'll stop by your food blog.
- 10 June 2008 at 11:03
- Anonymous said...
Hi there, just want to let you know that your blog was the one that inspired me to start doing my own bentos to bring to work! Thanks for getting me off my butt and eating better! :)
- 25 June 2008 at 13:04
- Anonymous said...
Hello everyone! I'm Silviya. I like that blog very much. There is something I want to ask. I'm not from USA, and there are some ingredients unfamiliar to me, or I just can't understand what to use instead. So, I would be very happy if You tell me what exactly is Heavy Whipping Cream? Is is something like cooking cream or?
Thank You
- 2 July 2008 at 09:18
- Nilmandra said...
Silviya: Sorry for the late response! I am in the UK and there tends to be three types of cream cold. Single cream, double cream and whipping cream (sometimes also called heavy whipping cream). Single and double cream are for pouring over desserts or for cooking (e.g. cream based sauces). Double cream has higher fat content and is thicker in consistency than single cream. If most cases, you can safely use single or double cream in cooking recipes, it will just differ in taste (double is thicker and richer in taste).
Whipping cream are made for specifically, well, whipping! The other two varieties will not whip. The side of the container may have instructions on whether the type of cream is suitable for pouring, cooking or whipping. Hope that helps.
- 8 July 2008 at 05:33
- Irene said...
Found your blog while researching on bentoing. Very inspiring. Also noticed that you've recently come to Vancouver. Welcome! That's my neck of the woods :)
I leave you with a site for some fun in Vancouver.
- 18 August 2008 at 11:13
- Nilmandra said...
Irene: Thanks for the welcome and the useful link!
- 19 August 2008 at 08:14
- pixen said...
hi Nilmandra,
I have an award waiting for you in my blog.
thank you for sharing your recipes and tips! Take care!
- 28 September 2008 at 16:18
- hezmanagirl said...
I've really loved reading your blog! Lots of ideas for tasty food to try and I enjoy the fact that your love of food always come through.
I'm going to England this autumn and was wondering if you could suggest some of your favorite places to eat?
Thank you.
- 9 February 2009 at 19:29
- Anonymous said...
Hi, I'm a first time visitor to your site! I really like your Japanese recipes; the idea of bento boxes, the cute liquid holders, and oh the yummy food you post about! :)
I do have a request that I was hoping you'd be able to address. Some of your pictures on your website do not link properly, especially the most current ones. I am not sure if it is just me, but if it isn't, could you please fix it? I'm a pictorial kind of gal!
Fellow Vancouverite :)
- 13 March 2009 at 23:13
- Anonymous said...
Hi again, I had sent a message a few minutes ago and it looks like the pictures are linking again. I really like your blog; wish that I could pack a bento as nice as yours for my hubby and I! :)
- 13 March 2009 at 23:54
- Carina said...
Hi, I am a Singaporean stay in Virginia right now. Yeah... same sentiments... miss singapore food so much. Your blog really made me feel like home. :)
- 23 June 2009 at 10:59
- Nilmandra said...
Carina: Thanks for the note and kind comment. I hope you get to try your hand at making dishes from home. It's really satisfying.
- 2 July 2009 at 20:58
- Saju said...
Just discovered you blog. I love it.
- 7 February 2010 at 14:38
- Mary, CookEatShare Author Support said...
I'd like to personally invite you to join the CookEatShare Author network. CookEatShare has had over 2.5 million unique visitors in 2009, and I think they will be interested in your content. Users will be guided to your actual blog, so this is a free way to increase page views and visitors to your site.
Please visit http://cookeatshare.com/blogs/apply for additional information or contact me at email@example.com for more information, to get unique link to claim and customize your profile.
- 8 March 2010 at 13:30
- June said...
I stumbled upon your blog when researching for recipe and gathering inspiration. Really like what you've done here! I currently live in the UK and am particularly inspired by what I see on your blog :) reminds me of home...
- 19 August 2010 at 03:27
- Anonymous said...
You are amazing. I shall love this place...
I like cooking as well, especially when moved here from China, but I am with Chinese/Asian food only, till now...
Thus I wish you find out/ create more and more recipe
- 10 September 2010 at 05:55
- Anonymous said...
i am looking for the recipe to make "belachan." i am not looking to make block shrimp paste. =) i am looking for the recipe for this sauce (similiarly to xo sauce). it has dried shrimp, chili pepper, etc inside and can be served over steamed rice or other dishes. maybe called sambal belachan?
- 24 May 2011 at 05:30


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Much like the beloved heroes of the franchise, the Harold & Kumar series is growing up. The third installment still features toilet humor and gasp, male and female nudity, but the jokes are a bit smarter and the direction is a tad sharper.
The film even touches on problems with Wall Street when Harold (John Cho), who has now climbed up the ladder of success at the investment firm of Brewster Keegan, must run for safety as the protesters pelt him with eggs. Read More...
[ 34 comments ] ( 1554 views ) | permalink | ( 2.9 / 840 )
Trick or treaters, snowstorm in the east, and Halloween be damned, "Puss in Boots" emerged victorious at the box-office against all odds. The DreamWorks 3D flick proved that this kitty has legs beyond the "Shrek" franchise.
("Puss in Boots" movie review)
(Enter our "Puss in Boots" contest)
Starring Antonio Banderas, Salma Hayek, and Zach Galifianakis, "Puss in Boots" claimed the top spot with $34 million. The Paramount-distributed film enjoyed huge support from family audiences as well as the Hispanic crowd which made 35 percent of its audience.
My interview with Antonio Banderas and Salma Hayek, click here
My interview with Zach Galifianakis, click here
My interview with Billy Bob Thornton and Amy Sedaris, click here
My interview with director Chris Miller, click here
Paramount also has the No. 2 movie of the Halloween weekend, the creepy "Paranormal Activity" which made $18.5 million. So far, the third installment of the popular horror franchise has sold $81.3 million worth of box-office tickets.
(My interview with director Henry Joost and Ariel Schulman for "Paranormal Activity 3" right here)
("Paranormal Activity 3" movie review right here)
Both Justin Timberlake and Johnny Depp were no match to the power of Puss! "In Time" starring Timberlake about the scarcity of time, debuted at No. 3 with $12 million while "The Rum Diary" featuring Depp entered at No. 5 with $5 million, a low debut for a movie with a $50 million budget.
It is indeed a great weekend for Paramount. Its remake of "Footloose" took the No. 4 spot with $5.4 million. Take that Johnny Depp!
Here's the Top 10 Box-Office Films for Halloween weekend 2011:
1. "Puss in Boots," $34 million
2. "Paranormal Activity 3," $18.5 million
3. "In Time," $12 million
4. "Footloose," $5.4 million
5. "The Rum Diary," $5 million
6. "Real Steel," $4.7 million
7. "The Three Musketeers," $3.5 million
8. "The Ides of March," $2.7 million
9. "Moneyball," $2.4 million
10. "Courageous," $1.8 million
[ 35 comments ] ( 2274 views ) | permalink | ( 3 / 2268 )
This week on Mannys Movie Weekend Giveaway, were giving away fun Puss in Boots prizes courtesy of Paramount Pictures! One lucky winner will get:
*** Puss in Boots Masks
*** Kitty Softpaws Masks
*** Puss in Boots magic beanstalk (well, not quite magical but its a plant)
*** Puss in Boots shades
*** Puss in Boots pencils
*** Puss in Boots Bandana
*** Puss in Boots Mini-posters
*** Puss in Boots shopping bag
How do you enter? Go to my Facebook page on http://www.facebook.com/MannytheMovieGuy, like the page, like the post, and just like me
We will draw the name of the winner on Friday, Nov. 4th!
Sorry international fans, but this is limited to U.S. residents only!
Thanks and GOOD LUCK!
My interview with Antonio Banderas and Salma Hayek, click here
My interview with Zach Galifianakis, click here
My interview with Billy Bob Thornton and Amy Sedaris, click here
My interview with director Chris Miller, click here
[ 32 comments ] ( 1346 views ) | permalink | ( 3 / 2206 )
Everything You Wanted to Know About "Paranormal Activity 3!" Directors Henry Joost and Ariel Schulman Talk About the Trailer, the "Fan Cam," and the Possible Sequel!
I love the Paranormal Activity franchise. The first one intrigued me, the second one scared me, and the third made me believe in the potency of the franchise. So I was happy as a clam to interview the directors of the third installment, Henry Joost and Ariel Schulman.
("Paranormal Activity 3" Movie Review)
One of the biggest questions the fans were asking was how come there were some scenes shown in the trailer that were not shown on the final cut?
But well get to that in a minute.
For now, lets congratulate Joost and Schulman for keeping the Paramount Activity tradition of no gore, just good old-fashioned scares alive!
Oh yeah, and lets congratulate them too for having the biggest box-office opening for a horror film ever, and for the biggest opening of any film in October!
In this interview, we talked about:
*** What spooked them to direct Paranormal Activity 3?
*** Scary movies versus Violent movies
*** The origin of the fan cam
*** And the biggie how come some scenes were not shown in the final cut? Are we going to find some footage in the DVD and Blu-Ray?
*** Is there going to be PARANORMAL ACTIVITY 4?
I really wanted to ask them about that hidden scene theyre talking about in the movie. Did you guys catch that?
Also, I want them to give Katie Featherston a bigger role in the fourth film!
Just sayin
Here's more info on "Paranormal Activity 3" from Yahoo:
The PARANORMAL ACTIVITY franchise continues with this third outing from Paramount Pictures. Oren Peli and Jason Blum return to produce the highly secretive feature.
Genres: Suspense/Horror and Sequel
Release Date: October 21st, 2011 (limited)
Distributors: Paramount Pictures
Directed by
Henry Joost
Ariel Schulman
Writing credits
Christopher B. Landon
Oren Peli characters
Cast (in alphabetical order)
Katie Featherston ... Katie
Sprague Grayden ... Kristi Rey
Lauren Bittner ... Julie
Chloe Csengery ... Young Katie
Christopher Nicholas Smith ... Dennis
Jessica Tyler Brown ... Young Kristi Rey
Brian Boland ... Daniel Rey
Dustin Ingram ... Randy Rosen
Mark Fredrichs ... Dr. Fredrichs
[ 38 comments ] ( 1380 views ) | permalink | ( 3 / 2278 )
"Puss in Boots" arrives in theaters today, Oct. 28th, HAVE FUN!
(Read my "Puss in Boots" movie review, right here)
Here's more info on "Puss in Boots" from Yahoo:
Way before Puss ever met Shrek, our suave and furry feline hero goes on a swashbuckling ride, as he teams with mastermind Humpty Dumpty and the street-savvy Kitty to steal the famed Goose that lays the Golden Eggs.
Genres: Action/Adventure, Animation, Comedy and Science Fiction/Fantasy
Release Date: November 4th, 2011 (wide)
Distributors: DreamWorks Animation/Paramount Pictures
Cast and Credits
Starring: Antonio Banderas, Salma Hayek, Zach Galifianakis,Billy Bob Thornton, Amy Sedaris
Directed by: Chris Miller
[ 40 comments ] ( 1534 views ) | permalink | ( 3 / 2211 )


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Aprende y Crea con Plantas, Taller Infantil en la Bio Granja
We had the first of 4 workshops with kids yesterday. I have no photos of the event because I completely forgot to take any so I have to leave you with the set up images. It was 2 non-stop hours, … Continue reading


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I alluded to our book themed wedding in a previous post. After discarding the math theme (somewhat sadly—although I was only ever semi-serious), we fully embraced a books, words and just a general literary theme. We are planning on including several ideas besides the book centerpieces, which to recap, look something like these (the two on the left):
Image via Green Wedding Shoes / Photo by ee Photography
I'd like to use a mix of books from family members and books that we bought ourselves. Some of my family members have already mentioned that they have copies of several classics, but the idea of having books to take from the wedding to start our own personal library is also a huge draw for me. In ten or twenty years, I want to be able to look at the books we bought (in our library of course) and know that they have been with us since the beginning. Mr. Lemur and I have started looking at old bookstores and thrift shops and buying just a handful of our favorite books at a time. An older man from our church who loves old books has also sweetly bought over twenty classics as a wedding present, which is so special!
But besides the book centerpieces, I love these inspiration pictures of crossword puzzle programs:
Image via Pretty Little Things / Photo by Martha Stewart Weddings
My idea is to use all the information you would normally have on a program—names of bridesmaids, groomsmen, etc.—plus some information about ourselves as the clues. We could also include a message of thanks at the bottom. I think I would have these sitting at each place setting for the reception. I don't think I would want guests working on them during the ceremony.
I have one more big "inspiration" to tie in our literary theme!
Image via Hostess With the Mostess / Photo by Courtney Jade Photography
So I may have gone a little crazy on the Scrabble inspiration…but how could I say no? I think my favorite is the label for the cake—it's just perfect! I am so doing this. Although, I love the ring shot with the Scrabble letters as well.
I think with these three ideas we've cemented the theme. I'd like to add more, but I also don't want to go overboard. Anything else I should add? Suggestions on projects that are impossible, possible, or really super easy (preferred)?
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Kentucky Counseling Services - starts with L
Welcome to the 50States Kentucky counselors directory. Find Kentucky Counselor phone numbers, addresses, and other contact info.
Go To: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Lklp Family Preservation
14 Logan Dr
Jeff, KY 41751


text:
Martini Hour 094, In Which We Hypocritically Mock Some of Adobe's Odd Feature Names
What's in a name? Does a feature that goes by any other name still function as well? This week we're enjoying making fun of the names of Adobe features that don't really make any sense. And who are we to complain? "Martini Hour" is never really an hour and this week we're drinking Manhattans. So join us on this vaguely hypocritical but otherwise entertaining discussion of goofy names for otherwise highly useful (for the most part) set of features in Photoshop, Illustrator, and InDesign. Like Martini Hour, you shouldn't be scared off by the names.
Here is a list of cryptically, oxymoronically, or just ridiculously named features that we enjoy making fun of this week:
Unsharp Mask: Classic example. Enough said.
Liquify: Descriptive name, but even InDesign doesn't recognize this unauthorized spelling (although in all fairness, Merriam-Webster allows it as a variant.)
Vibrance: some question as to whether this is really a word in the first place, and we should have mentioned this on "what you can stop doing" episode. (Stop cranking up the Vibrance and thinking your fooling anyone.)
Flip and Flop checkboxes in Vanishing Point: What exactly is the technical definition of "flopping" a selection? And I remain confused over the terms "Flip Horizontal and Flip Vertical" because I think they are going to spin around the axis that is mentioned. And they don't. Or they do. I can never remember.
Leading: OK, we all know what this means (the amount of space between the line of type and the line above it). Which, if you had no idea where this came from, you might actually think it was pronounced "LEED-ing." But it's not even old paste-up terminology, it's from hot metal days. Hot lead. Very sexy.
Expand: In Illustrator, it means nothing to do with making something bigger, but really has to do with breaking down to paths. It's doubly confusing because Photoshop actually seems to understand the conventional definition of the word expand.
Grow Similar: OK, once you break this down, it sort of makes sense. But it's still a funny name. And very useful (with any selection tool, not just the Magic Wand to which it is conventionally attached.) Grow similar what?
Transparency Flattener: Best worst-name command ever. In the several minutes it takes us to get there, it supplants the earlier Flip and Flop. Potentially the most confusing dialog box/panel ever.
Smart objects: Smart these days means "automatically filtered" and objects sounds like a programming thing. These are, of course, containers that protect your original document from distruction, the use of which is smart on your part, but not so much on the part of the tool.
Hide Edges: Who would know what this means? Edge usually refers to a literal edge of a selection or an area of rapid transition. Deke suggests "Hide Ants" instead. And also it comes with itinerant random behavior depending on whether you're working in Photoshop, Illustrator, and InDesign.
Glyphs: This one is very useful (especially for Mac users who don't have the Character Map). I guess if you think "heiroglyphs," you understand this is helping you find the character of the font that you may or may not be looking for. And you can make your own collections. Useful, but obscurely named.
Various modifiers on the names of Selection tools: What is the difference between direct, quick, and basic "selection"?
Art History brush: Not only is it stupidly named, but it adds a stupidly filteresque effect you would never want to do.
Live Junk: Illustrator calls things "live" when it means "dynamic" and there is no real relationship between the use of the word "live" in Live Trace, Live Paint, and the obscurely hidden "Live Color" tools. It's distracting and somewhat intimidating (because live things might harm you).
Pathfinder tool: Sounds like a scout whose helping you through uncharted territory. Great feature and in truth we couldn't come up with anything better.
Envelope distortion: We don't entirely understand where this name came from. If you can help us out, let us know. And even more importantly, can Deke please get it in Photoshop?
Eyedropper: If you have an icon for a tool that alludes to what it does, then what sense does it make to name it after the thing to which it is tangentially related. Or less obtusely, it's a color sampler, and we think of eyedroppers as spitters not suckers.
Attributes panel: Seems to be a grab-bag planel for which the name means nothing.
Art board: This allows them to not call these things pages. Because if they called them pages, they'd be reminding people of the dark ages when you could only have one.
Good times, goofy names. Won't you join us? Here's the regular-quality audio file. You can stream, or for best results, right-click and choose Download or Save. Here's the high-res version; you'll want to download rather than stream. And don't forget our usual plea to subscribe via iTunes.
What names make no sense to you? Or do you see logic where we don't? Let us know. Until next week (and for about 7 more---more on that next week), Cheers!
Eyedroppers suck, then squirt.
A good name is everything...
What a fun topic! I actually wrote up a long blog post about just this a while back. Here's a link:
Noce to see Deke and I share many of the same "issues" :)
BTW, Illustrator's feature is called "Envelope Distortion" purely because that's what other products called them. Blame the CorelDRAW folks for coming up with such a lousy name, and blame the Adobe folks for being lazy and just copying the phrase....
Mordy Golding


text:
Watch Two People Narrowly Escape Catapult Death at Amusement Park
Planning a fun trip to an amusement park this summer? Consider this: You might die. Or you might narrowly avoid death when a ride malfunctions, like the people in this video, who were almost shot into the air with only half their catapult working.


text:
|Publication number
|Publication type
|Application number
|Publication date
|20 Jul 2010
|Filing date
|30 Jul 2004
|Priority date
|26 May 2004
|Fee status
|Publication number
|William Brian Seymour
|Original Assignee
|William Brian Seymour
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (39), Non-Patent Citations (13), Referenced by (9), Classifications (9), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a continuation-in-part of U.S. patent application Ser. No. 10/853,718, entitled "Methods and Systems for Testing Evaluation Modules," by Brian Seymour, filed on May 26, 2004, which is incorporated herein by reference.
Methods and systems consistent with the invention evaluate the performance of electronic, software, and computer modules, and in particular evaluate electronic, software, and computer modules remotely over a network.
Electronic and software companies such as Texas Instruments, Analog Devices, Motorola, and Intel provide their business-to-business customers with "evaluation modules" ("EVM's") so the customers can evaluate the EVMs. EVMs may be hardware components or software components. For example, if Texas Instruments made a new graphics chip, a game software company may want to evaluate their game software on the new graphics chip. The evaluation would help determine if the new graphics chip met the need of the game software company. Typically, Texas Instruments would provide the game software company with the new graphics chip, i.e., an EVM, for evaluation purposes. Sometimes EVM's are manufactured and lent to customers for evaluation. Other times, EVMs are used to train existing and potential customers on the product. EVMs, however, can be expensive, and their physical distribution to potential customers is time consuming and slows down the evaluation process. Thus, providing each of many customers with an expensive EVM can be costly.
To avoid this cost, TechOnLine, the assignee of the current application, has provided the ability for customers to evaluate software and hardware (EVMs) remotely. As a result, customers can evaluate an EVM remotely without purchasing or otherwise obtaining the EVM. U.S. Pat. No. 6,708,327 ("the '327 patent"), entitled "System for Accessing and testing Evaluation Modules via a Global Computer Network," assigned to the same assignee as this current application, hereby incorporated by reference, describes testing EVMs remotely.
Systems consistent with the '327 patent provide customers with access via a computer network (such as the Internet) to EVMs such as electronic, software, and hardware components. Customers can then evaluate or be trained how to use the EVMs remotely. There is a need, however, to provide more flexibility for evaluating evaluation modules.
A system consistent with this invention evaluates the performance of a module via a network. Such a system comprises an evaluation module (EVM); a stimulator, separate from the EVM computer, for providing a stimulus to the EVM; an EVM computer running an end user interface for interfacing with the EVM computer, wherein the EVM computer monitors the performance of the EVM and controls the stimulator; and a terminal linked to the evaluation module computer through a network, wherein the terminal displays the end user interface.
A method consistent with this invention evaluates a performance of a module via a network. Such a method comprises running an end user interface in an evaluation module (EVM) computer for interfacing with the EVM computer, wherein the EVM computer evaluates the performance of an EVM and controls the stimulator; and displaying the end user interface on a terminal linked to the EVM computer through a network.
A method consistent with this invention evaluates a performance of a plurality of modules via a network. Such a method comprises running an end user interface in an evaluation module (EVM) computer for interfacing with the EVM computer, wherein the EVM computer evaluates the performance of a plurality of EVMs; providing the end user interface for allowing an end user to select a the plurality of EVMs for evaluation; displaying the end user interface on a terminal linked to the EVM computer through a network; evaluating the plurality of EVMs to create evaluation results; and displaying the evaluation results in the end user interface.
Both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention.
Reference is now made in detail to the present embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like parts.
Central system 10 connects to Internet 12 via a link 15. Central system 10 is further connected to EVM computer 19. Network 100 comprising central system 10, EVM computer 19, and EVM system 17, may be known as a "VirtuaLab," which is a trademark of the assignee of this application.
EVM system 17 represents the component or module to be evaluated by an end user using one of workstations 14, 16, or 18. EVM computer 19 provides an environment for EVM system 17 to operate, including, for example, providing power to EVM system 17 if it requires power. In the embodiment in
Web server 202 sends information to workstations 14, 16, or 18. Web server 202 comprises a web subsystem that connects to a web browser situated in one of workstations 14, 16, or 18. In one embodiment, web server 202 operates Apache 1.3.1 software by Apache Group which includes a high performance web server, an application development environment, integrated full-text searching, multimedia streaming, and site management tools. The Apache 1.3.1 software package also has support for HTTP, Java, and Telnet compatible browsers. One embodiment of the invention uses the World Wide Web (WWW) over the Internet, although other network environments may be used.
End users may schedule evaluation time for evaluating EVM system 17. When an end user schedules evaluation time, the end user "leases" time on EVM computer 19 to evaluate EVM system 17. Lease management server 210 comprises the logic necessary to grant or not grant leases when an end user requests a lease. Database server 208 comprises data related to end users, leases, and "platforms." A platform is an EVM computer and EVM system pair. For example, in the embodiment of
Authentication server 216 authenticates end users. Authentication is process of identifying an individual, usually based on a username and password. Authentication may ensure that the individual is who he or she claims to be, but may say nothing about the access rights of the individual. In security systems, authentication is distinct from authorization, which is the process of giving individuals access to system objects based on their identity. Authentication server 216 makes information, such as system objects, in file server 204 available after an end user is authenticated and authorized.
User management server 214 provides user authorization. User management server 214 comprises a lightweight directory access protocol ("LDAP"). LDAP is a set of open protocols for accessing information directories. LDAP supports TCP/IP and makes it possible for an application running to obtain directory information, such as e-mail addresses and public keys. User management server 214 comprises end user information to determine what end users can and cannot do in central system 10. In other words, user management server 214 authorizes an authenticated user to perform "privileged" tasks.
Database server 208 processes database queries. In one embodiment, database server 208 uses an SQL database management software from Microsoft Corporation. In another embodiment database server 208 uses Oracle 8 database management system from Oracle Corporation, which provides scaleability. The database server 208 may be any SQL based database management system. Database server 208 may store information pertaining to end users, administrator accounts, as well as end user profile criteria. Database server 208 may also store client account information such as account balances, member profiles, and event information such as demonstrations. Database server 208 may be a dual processor computer optimized specifically for the Oracle 8 threading model. Database server 208 may require additional processors in high volume environments.
File server 204 is dedicated to storing files, processing queries for files, and obtaining files from disk array 206. Disk array 206 provides disk storage for web server 202, file server 204, database server 208, lease management server 210, remote desktop server 212, user management server 214, and authentication server 216. File server 204 may provide every end user with network storage space. The end user storage space may be available no matter what workstation 14, 16, or 18 the end user decides to use. Further, the end user storage space may be available no matter which EVM system the end user is evaluating, if there are multiple EVM systems.
Remote desktop server 212 is linked to EVM computer 19 and EVM system 17. Remote desktop server runs "sessions" such as session 302. A session may interact with EVM computer 19. Workstation 14 may open session 302 in remote desktop server 212 to evaluate EVM system 17. Remote desktop server 212 runs desktop 304, showing "A," in session 302.
In this embodiment, workstation 14 opens a browser 306 and desktop 304 appears in browser 306, showing "A." An end user, such as an engineer for example, may access a storage device 305 in workstation 14 through desktop 304 because session 302 may "map" storage device 305 to an input/output port running in session 302. In the embodiment of
In methods and systems consistent with the invention, end user workstation 16 may also connect to session 302. End user workstation 16 opens a browser 307 and desktop 304 appears in browser 307, showing "A." An end user, such as an supervisor engineer for example, may access a storage device 305 in workstation 14 through desktop 304 because session 302 may "map" storage device 305 to an input/output port running in session 302. Thus, the supervisor engineer at workstation 16, for example, may have access to the storage device 305 in workstation 14.
In the embodiment of
Workstation 14, workstation 16, remote desktop device 212, and EVM computer 19 may use the software program Secure Global Desktop Enterprise Edition by Tarentella. Alternatively, workstation 14, workstation 16, remote desktop device 212, and EVM computer 19 may use the software program Citrix MetaFrame Access Suite by Citrix corporation. Other remote desktop application software programs may be used.
Once the first user is authenticated, user management server 214 determines the privileges of the first user (step 406). The privileges of the first user may depend on, for example, the community to which the user belongs or the identity of the user himself. Different "platforms" may be available to the first user depending on the privileges of the first user. Each platform, for example, may be associated with a different EVM computer and a different EVM system. For example, the first user may only be allowed to view the platforms associated with the first user's community. Platforms available to the first user may also be limited to platforms that are not being leased to other users at that time or to platforms being leased to the first user at the time. Lease information may be stored by lease management server 210 as described above. Once the first user's privileges are determined (step 406), the available platforms are displayed (step 408). The first user selects an available platform and remote desktop server opens the selected platform in a session (step 410).
Then, authentication server 216 authenticates a shadow user (a supervisor using workstation 14, for example) (step 412). Authentication may require a login ID or username and a password, for example. If authentication server 412 successfully authenticates the shadow user (step 414), then process 400 moves on to step 416. Otherwise (step 414), process 400 ends. Once the shadow user is authenticated (step 412), user management server 214 determines the privileges of the shadow user (step 416). Once the shadow user's privileges are determined (step 406), the available platforms and/or platforms opened as sessions are displayed (step 408). The shadow user may select the platform that the first user previously selected and opened in a session if the session that the first user selected is available to the shadow user given the shadow user's privileges. Steps 402 through 422 of process 400 do not necessarily have to be performed that the that particular order.
The first user has the opportunity to deny access to the shadow user when system 10 asks the first user for permission for the shadow user to access the same session. If the first user grants permission to the shadow user (step 420) then the shadow user may successfully access the previously opened session selected by the first user (step 412). If the first user does not grant permission to shadow user (step 420), the process ends.
Once terminal 14 opens session 302 with desktop 304, the first user may evaluate EVM system 17. The first user may execute test code in EVM computer 19 that evaluates EVM system 17. The first user may monitor and control the test code executing in the EVM computer remotely through desktop 304 appearing in browser 306. Alternatively, or in addition, the first user may transfer test code to EVM system 17 from EVM computer 19 for execution in EVM system 17. The first user may monitor and control the execution of the test code from EVM computer 19 through desktop 304 appearing in browser 306. The shadow user may have the same privileges and be able to do the same things first user. The test code and EVM computer 19 evaluate, including measuring the performance of or demonstrating the capabilities of, EVM system 17. The definition of "evaluate" or "evaluating the performance" includes, but is not limited to, measuring the performance or demonstrating the capabilities of (e.g. for the purposes of training) EVM system 17.
Web cam 706 may capture more than images 712′-716′. Web cam 706 may capture the entire EVM system so that the end user can determine the physical state of EVM system 17, such as the position of a mechanical arm or other feature of EVM system 17.
Hardware 902 may take the form of a signal generator, a power supply, a logic analyzer, or a bus analyzer. Further, in another embodiment, hardware 902 may also measure a characteristic of EVM system 17. For example, EVM system 17 could be a web cam, as in
U.S. patent application Ser. No. 10/361,921, entitled "Methods, Apparatus, and Systems for On-line Seminars," assigned to the same assignee as this current application, is hereby incorporated by reference.
Other embodiments of the invention are apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
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text:
Visser commits to Edinburgh
Dutch winger Tim Visser has agreed a two-year contract extension to remain with Edinburgh until May 2013.
The 23-year-old, who moved to Murrayfield from Newcastle in June 2009 and is the only professional rugby player from Holland, was the leading try-scorer in the Magners League last season. He also won the Magners League Young Player of the Season award.
"My first thought when it came to deciding my future was always to stay at Edinburgh," said Visser. "I'm thrilled that I've got everything sorted out nice and early so that I can focus on helping the team enjoy a successful second half to the season, starting with the Heineken Cup match against Cardiff (on Saturday)."
Visser will be eligible to play for Scotland once he has completed 36 months of continuous residence in the country.
He added: "The Scotland aspect obviously is one more reason for committing myself to Edinburgh, but the main motivation was staying in a place and a team where I know I will improve.
"When I've completed the residency period, I'd love to be considered, but my overriding focus is doing well with Edinburgh and helping the team achieve."


text:
RAMBOUILLET, France (AP) Serbs agreed in principle Tuesday to give limited self-rule to majority ethnic Albanians in Kosovo, but the two sides failed after 17 days of intense negotiations to conclude a deal for ending their yearlong conflict. More talks were scheduled for March.
The partial settlement puts on hold, at least temporarily, NATO's threats to bomb Serb targets if the Serbs don't adopt the complex plan that would force them to withdraw troops from Kosovo and accept NATO peacekeepers.
After four days of strenuous personal diplomacy, shuttling between the two sides and even enlisting the help of 1996 GOP presidential candidate Bob Dole, Secretary of State Madeleine Albright accepted less than she had insisted on earlier.
There was no agreement on deploying NATO peacekeepers in the tense province to enforce the settlement, and the Serbs refused to give their consent to major elements of the self-rule sought by the ethnic Albanians.
According to senior U.S. officials, the Serbs still insist on Serbian courts for Serbs accused of crimes, refuse to permit the ethnic Albanians to have a president and are unwilling to cooperate with a war crimes tribunal looking into atrocities against civilians committed during the war that has claimed some 2,000 lives.
The Albanians also hedged. They were given two weeks for ''consultations'' with people in the province, and still are insisting on a referendum to vote for independence from Serbia at the end of the three-year autonomy trial period envisioned by the accord. The plan was formulated by the United States, Britain, France, Italy, Germany and Russia.
The settlement also calls for a restoration of the cease-fire that was arranged by U.S. envoy Richard Holbrooke last October and for the staged removal of Serbian troops and special police units but only after a NATO force is deployed to enforce the agreement.
In order to put a halt to the protracted negotiations, which ran through two deadlines, the ethnic Albanians and Serbs agreed to another round of talks in France, beginning March 15.
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