tuberculosis virulence factors and the downregulation of immunodo

tuberculosis virulence factors and the downregulation of immunodominant M. tuberculosis proteins (Dahl et al., 2003). Numerous genes of unknown function are also differentially regulated by relMtb in M. tuberculosis. Therefore, studying the mycobacterial AZD2281 mw stringent response may provide insights into the identification of novel M. tuberculosis genes involved in pathogenesis. Our laboratory recently established M. smegmatis as a useful tool for studying rel-dependent M. tuberculosis genes. Using a strain of M. smegmatis inactivated for relMsm (mc2155Δrel), we showed that the regulation patterns of M. tuberculosis genes

hspX and eis on multicopy plasmids mimicked the observed Rel-dependent regulation of these genes on chromosomes in M. tuberculosis (Dahl et al., 2005). Direct correlations do not always exist between cellular transcriptional activity and corresponding protein expression (Anderson & Seilhamer, 1997; Gygi et al., 1999; Skiba et al., 2010). The expression of bacterial virulence factors can occur at the levels of transcriptional regulation, mRNA stability, translational

frequency, and protein stability (Dorman & Smith, 2001). We have previously reported a global transcriptional difference between wild-type M. tuberculosis (strain H37Rv) and H37RvΔrelMtb (Dahl et al., 2003), and a goal of the current study is to compare Selleck Etoposide relMtb-dependent differences in protein patterns between strains with and without Rel. Mycobacterium tuberculosis strains (H37Rv and H37RvΔrel) have been described previously (Dahl et al., 2003) and were grown in Middlebrook 7H9 medium supplemented with albumin, dextrose and catalase, and 0.2% glycerol+0.05% Tween 80. Cultures were grown to the stationary phase at 37 °C in rolling flasks. Mycobacterium smegmatis strains (mc2155 and mc2155Δrel; described in Dahl et al., 2005) were grown in 7H9 with 0.2% glycerol+0.05% Tween 80 at 37 °C by shaking or on 7H10 agar plates. Hygromycin (50 μL mL−1) was added to M. smegmatis cultures to ensure plasmid stability in strains. To prepare

lysates for antibody production, 50-mL aliquot of 3-week-old culture of M. tuberculosis H37Rv clonidine were pelleted by centrifugation and washed 3 × in phosphate-buffered saline (PBS) before suspending in 1 mL of lysis buffer [0.3% SDS, 200 mM DTT, 30 mM Tris (pH 7.5)], and breaking cells open with glass beads (0.5 mm diameter) using a FastPrep FP120 bead-beating device (ThermoSavant). Cells were shaken at a speed of 6.5 m s−1 for 45 s and then incubated on ice for 5 min. This cycle was repeated 5 × before samples were boiled for 10 min to enhance cell lysis. Samples were then bead-beaten again five more times, as described above. Lysed samples were centrifuged at 12 000 g for 10 min at 4 °C to remove cellular debris. Supernatants were filter sterilized (0.22 μm) and stored at −20 °C until being mixed with a Titermax Gold adjuvant (Sigma), as recommended by the manufacturers.

Prior work had shown that alpha-band activity was differentially

Prior work had shown that alpha-band activity was differentially deployed depending on the modality of the

cued task. Here, we asked whether this activity would, in turn, be differentially deployed depending on whether participants had just made a switch of task or were being asked to simply repeat the task. It is well established that performance speed and accuracy are poorer on switch than on repeat trials. Here, however, the use of instructional cues completely mitigated these classic switch-costs. Measures of alpha-band synchronisation and desynchronisation showed that there was indeed greater and earlier differential deployment of alpha-band activity on switch www.selleckchem.com/products/MDV3100.html vs. repeat trials. Contrary to our hypothesis, this differential effect was entirely Selleckchem Androgen Receptor Antagonist due to changes in the amount of desynchronisation observed during switch

and repeat trials of the visual task, with more desynchronisation over both posterior and frontal scalp regions during switch-visual trials. These data imply that particularly vigorous, and essentially fully effective, anticipatory biasing mechanisms resolved the competition between competing auditory and visual inputs when a rapid switch of task was required. When individuals are required to switch rapidly from execution of one task to another, goal-related task networks and attentional mechanisms are engaged to reconfigure task-specific networks, suppressing activity within circuits responsible for performance of the old task and amplifying preparatory neural

processes for the anticipated novel task (Foxe & Simpson, 2005; Foxe et al., 2005). That is, competition between two potential task-set configurations must be resolved so that an effective strategy shift can be enacted. Often there is a significant performance cost in Nintedanib (BIBF 1120) terms of both speed and accuracy upon the first instance of a new task that is taken to reflect these reconfiguration processes (Jersild, 1927; Wylie & Allport, 2000; Wylie et al., 2004b, 2009). Under many such task-switching scenarios, switch costs dissipate rapidly, with near ceiling levels of performance achieved on just the second instance of the new task (De Sanctis et al., 2009). The implication is that the anticipatory neural reconfigurations necessary for optimal performance of a new task are not always achieved in one step; rather, it often takes performance of at least one instance of the new task to reach optimal performance (Wylie et al., 2003a). Alternatively, if an informational cue informs participants of an upcoming task switch, and sufficient time is then allowed to elapse between the cue and the stimulus to be acted upon, individuals can accomplish an entirely effective task-set reconfiguration in that little or no switch cost is then observed (Wylie et al., 2009).

, 2008) Translocation of CagA and by which induced IL-8 producti

, 2008). Translocation of CagA and by which induced IL-8 production in infected AGS cells is also blocked by cholesterol depletion (Lai et al., 2008; Murata-Kamiya et al., 2010). The presence of a single Glu-Pro-Ile-Tyr-Ala (EPIYA) motif in the C-terminal region of CagA was shown to be crucial for membrane localization (Higashi et al., 2005). Delivery of CagA with more phosphorylation motifs was found to induce a higher level of phosphorylation in epithelial

cells, which may therefore influence Atezolizumab datasheet the severity of the clinical outcomes (Argent et al., 2004). However, the detailed role of lipid rafts in membrane tethering of CagA remains to be elucidated. In this study, we investigated the effects of various CagA truncation mutants on the association between CagA and lipid rafts and on IL-8 induction. Our results provide evidence that the CagA C-terminal EPIYA-containing region is targeted to membrane rafts, which allows CagA-mediated induction of IL-8. Helicobacter pylori 26695 (ATCC 700392) was used as a reference strain and contains a cagA gene with three C-terminal EPIYA motifs (ABC-type) (Higashi et al., 2005). Clinical strain v669 was isolated from a patient with gastric cancer and contains a cagA gene with four C-terminal EPIYA motifs (AABD-type) (Lai et al., 2002). Helicobacter pylori strains

were recovered from frozen stocks on Brucella blood agar plates (Becton Dickinson). Construction of the cagA (∆CagA) and cagE (∆CagE) knockout strains were performed using the kanamycin resistance cassette (Kmr) from pACYC177 and the erythromycin resistance cassette (Eryr) from pE194, BTK phosphorylation respectively, by the natural transformation method as we described previously (Lai et al., 2008). PCR and western blot analysis were employed to confirm the correct insertion of antibiotic resistance cassettes into the target genes. Various expression constructs encoding CagA truncation mutants were generated based on the H. pylori 26695 cagA sequence and v669 as illustrated in Fig. 3a. cagA fragments were amplified using PCR from H. pylori 26695 and v669 genomic DNA as described previously (Lai et al., Org 27569 2002). The CagA-ΔN mutant

was generated from strain 26695 by amplification of sequence encoding amino acids 645–1186 using primers CagA-CTD59F and CagA-CTDR (Table 1). The primers used for PCR introduced a BamHI site at the 5′ end and an XbaI site at the 3′ end. The BamHI–XbaI fragment was then ligated into pEF1 expression vector (Invitrogen). Similar procedures were used to obtain the 669CagA-ΔN mutant from strain v669 using primers CagA-CTD59F and CagA-CTDR. To generate the CagA-ΔC mutant, a fragment encoding amino acids 1–358 was amplified using primers CagA1-F and CagA-1R. The primers used for PCR introduced a BamHI site at the 5′ end and an EcoRI site at the 3′ end. The BamHI–EcoRI fragment was then inserted into pEF1 to derive pEF1-CagA1. A fragment encoding amino acids 357–707 was amplified using primers CagA2F and CagA2R.

While this is an important work, it does not fully explain the sl

While this is an important work, it does not fully explain the slow and incomplete transition towards patient-centred care. We wonder if pharmacists’ own mental barriers are a missing piece. In our comparison of two legislatively progressive jurisdictions, community pharmacists in Northern Ireland provided more patient-centred responses Selleck Dinaciclib than community pharmacists in Alberta (P = 0.013), although both described product-focused roles in 39–45% of their responses. The product focus of pharmacists was also borne out in the word-cloud analyses, with very little use of patient-care terminology to describe what a pharmacist does. To our knowledge this is the first study to use short telephone

interviews which elicit a ‘top of mind’ or automatic response to compare how community pharmacists from Alberta and Northern Ireland describe what a pharmacist does. This approach engages certain

unconscious mental processes which affect and influence the judgements, feelings and behaviours of the person.[35] In the literature it has been reported that individuals’ automatic response does not usually match their self-reported attitudes.[36] The slight deception and restriction of response were intended to remove some of the effects of social desirability bias.[37] We think that our findings are generalisable to pharmacy practice in Alberta and Northern Ireland because the key demographic features of our samples are similar to regional averages (Table 3). A potential limitation of the present study relates to the fact that pharmacists’ responses were restricted Target Selective Inhibitor Library high throughput by the study question and our request for a brief response. If they had more time to think about their responses there is a chance that they would have been different. Nevertheless, the intention of using this methodology was to prevent pharmacists from thinking too much about their answer, thereby eliciting a ‘top of mind’ or automatic response and to avoid some of the effects of social desirability bias. Another potential limitation is the use of word clouding which represents a visualisation of Avelestat (AZD9668) the frequency

of the reported words. This method may not take into account the context in which the words were used. Also the use of open questions has the potential to introduce recall bias as this approach assumes that if a term was not reported then that term is not relevant. The higher degree of patient-centred responses provided by Northern Ireland pharmacists might be explained by the differences in contracts and payment schemes between Northern Ireland and Alberta. In Northern Ireland community pharmacists are paid for offering certain patient-centred services such as smoking cessation and minor ailments management,[33] while in Alberta (and Canada in general) the current model of reimbursement provides pharmacists with dispensing fees only (as in the traditional system of practice).

Such pharmacologic treatments are now commonly used on children (

Such pharmacologic treatments are now commonly used on children (sometime extremely young) during long periods (2–5 years) with the rationale to maximize the impact on a growing skeleton. However, some concerns have been raised about the equivocal efficiency on the fracture reduction [4] and [5], the accumulation of those long life drugs

and the impact of inhibiting bone remodelling over long periods, which results in the build-up of poor quality, highly mineralized bone [1] and [6]. Selleck Dasatinib It is recognized that the bone tissue is highly responsive to dynamic loading and is able to adapt its architecture and mass to the mechanical loading environment [7], [8] and [9]. Bone remodelling is sensitive to strain magnitude [10] and [11], frequency [12] and [13], number of loading cycles [14], strain rate [15] and rest periods between stimulation [16]. In addition to bone response to high peak strains [17] and [18], there is also evidence of bone adaptation at low strain but high frequency loading [9] and [19]. Because high strain exercises in patient suffering from OI may result in fracture, high frequency low amplitude whole body mechanical

vibration (WBV) is an attractive low-impact and drug-free approach to stimulate bone formation. The therapeutic impact of Selleck Dinaciclib WBV treatment has been observed on muscle strength, motion, posture and bone density in various osteopenic populations: young women [20] and [21], post-menopausal women [22], [23], [24] and [25] or children with disabling conditions like cerebral palsy [26] or with OI [27] but no effect has been observed on healthy adults [28]. However more investigations are required to confirm the impact of WBV on

bone mass and to identify the most efficient vibration parameters and the most responsive target population [29], [30], [31], [32] and [33]. Numerous studies have investigated the influence of WBV on bone formation using a large variety of animal models (sheep, rat, mouse) [34], [35], [36] and [37], age (growing, young or old adults) [38], [39] and [40], Mirabegron vibration frequency (from 20 to 90 Hz) [41], [42] and [43], maximum peak acceleration (from 0.1 to 3 g) [43] and [44], treatment duration (from 10 to 30 min) and treatment length (from 2 weeks to 1 year). A significant osteogenic effect was observed in the trabecular bone of both the femoral condyle and tibial metaphysis of adult sheep (1 year treatment, 30 Hz, 0.3 g) [35] and [36]. In adult mice, an osteogenic response to WBV is observed in the tibial metaphysis with a non-dose dependent response to acceleration (5 weeks treatment, 45 Hz, 0.1, 0.3 and 1 g) [44]. An influence of the mouse genotype was observed: the osteogenic response to WBV inversely correlated to the low (C57Bl/6J), medium (BALB/c) or high (C3H) bone density of the mouse strain (2 to 3 weeks treatment, 45 Hz, 0.25 g) [37].

We disclose the highest CMAP amplitudes and axonal diameters in t

We disclose the highest CMAP amplitudes and axonal diameters in the Schwann-like cell autografted group. Our study also reveals unprecedented results on the in vivo maintenance of the stem cells for six weeks in the nerve tissue, which may be related to the superior characteristics of the conduit and extracellular membrane components employed. Prior to surgery, lentivirus-transduced SB203580 BMSC (BMSClacZ+) obtained in vitro reacted positively in the colorimetric assay for

lacZ activity, whereas untransduced BMSC did not ( Fig. 1, A and B). BMSClacZ+ differentiated in vitro in cells that were immunostained for beta-galactosidase ( Fig. 1, D, G and J), presented thin and long cell processes ( Fig. 1, H and K, arrows), and expressed the cell markers S100, p75NTR and Oct6 in the nucleus and cytoplasm ( Fig. 1, C, F and I) that were undetectable in undifferentiated cells. At surgery, three animals from group E died

most likely due to hypersensitivity to anesthesia maintenance. On the second day of the postsurgical period, one animal from group D died due to unexplained cause. Data that had been previously obtained for PLX4720 these animals were not considered in this study. Data analyses using the Kruskal–Wallis test disclosed no difference among groups regarding CMAP amplitude or latency prior to neurotmesis and three weeks after surgery (Fig. 2A). On the other hand, CMAP amplitude analyses made in the six-week postsurgical point revealed differences Ibrutinib clinical trial among the five groups (0.74 mA, 0.76 mA, 0.99 mA, 1.96 mA, 2.73 mA, respectively for groups A, B, C, D and E; p<0.001, Fig. 2A). Assessment by the Mann–Whitney test adjusted by the Bonferroni coefficient (alpha=0.005116)

disclosed a difference between any control group without Matrigel® (A or B) and any group of cell-containing Matrigel® (D or E): p=0.004 for each comparison, A vs. D; A vs. E; B vs. D; and B vs. E ( Fig. 2A). Other possible paired comparisons were not significant. These data indicate that CMAP amplitude is significantly higher for groups D and E six weeks after surgery. At the sixth week, groups D and E presented respectively 44.52% and 72.03% of their pre-injury CMAP amplitude values, whereas groups A, B and C had the ratios of 12.8%, 15.94% and 16.98% in the same period ( Fig. 2A). Therefore, some functional recovery has been observed for each study group. Qualitative histological analyses at the optical microscope of segments proximal and distal to the graft revealed that, in study groups A through D, the facial nerve has been reorganized in one to three fascicles in the distal segment, whereas group-E animals had the injured facial nerve reorganized in two to four fascicles after surgical repair. Nerve fascicles were surrounded by epineurium with fusiform cells. Mild reactive tissue infiltrate has been observed in all groups, though seemingly more intense in groups A and B.

This is widely known Well established journals seem to accept st

This is widely known. Well established journals seem to accept structural work if the SDS-PAGE (with Coomassie Blue stain) show >95% purity. There is another disturbing practice which is occasionally

seen that the band of the protein is shown at far end of the lane. This rules out detecting the presence of any proteolytic fragments or contaminating proteins click here of lower molecular weight. Not all applications of the proteins require the same level of purity. This is an important point since there is a three way trade-off between purity vs. number of steps vs. cost of production (Figure 1). Industrial enzymes used in many industries do not require high purity. Reasonable level of specific activity GSK2118436 molecular weight is sufficient. Proteins used for pharmaceutical applications (e.g. monoclonal antibodies or clot busters, hormones, etc.) not only require extremely high purity; regulatory agencies require that these preparations are specifically free of certain contaminants (Anicetti and Hancock, 1994 and Walsh and Headon, 1994) (Table 2). There is also a fairly widespread practice of measuring Km, Vmax and stability of proteins which are fairly impure. Unless, the preparation is standardized with respect to contaminants (like in commercially available industrial enzymes), such data actually cannot be relied upon (the reason for this is explained

later on). Finally, as may be clear from the above discussion, protein purity is a relative term. One of the most well characterized enzymes is bovine pancreatic RNase A (Richards and Wyckoff, 1971). Most of the work, including X-ray crystallography, has been carried out with a “pure” preparation obtained by Cell Penetrating Peptide a final ion-exchange chromatographic step (Richards and Wyckoff, 1971). However, this preparation shows multiple proteins when subjected to multiple counter-current distribution process (Richards and Wyckoff, 1971)! In general, crystallization can be both a purification strategy (Przybycien et al., 2004) as well as a criterion of reasonable purity (Dixon et al., 1979). Precipitation,

both with and without an interface with affinity interactions is another efficient, simple and scalable approach (Mondal et al., 2006, Mondal and Gupta, 2006 and Niederauer and Glatz, 1992). Most of the industrial enzymes these days are produced by recombinant methods wherein overexpression leads to a considerably less heterogeneous protein preparation. Many proteins upon overexpression in Escherichia coli as host end up as inclusion bodies. In recent years, in many cases these inclusion bodies are being considered as carrier-free immobilized preparation of fairly pure enzymes ( Garcia-Fruitos et al., 2012). One of the key parameters in biocatalysis is the amount of protein present in the biocatalyst preparation.

This study was supported by the National Natural Science Foundati

This study was supported by the National Natural Science Foundation of China (31271661), the National Basic Research Program of

China (2009CB118602), and the Public Service Sector (Agriculture) Research Program of China (201203100). “
“In crop breeding programs, genotypes are evaluated in multi-environment trials (METs) for testing their performance across environments and selecting the best genotypes in specific Ruxolitinib cost environments. Genotype × environment (GE) interaction is an important issue faced by plant breeders in crop breeding programs. A significant GE interaction for a quantitative trait such as grain yield can seriously limit progress in selection. Variance due to GE interaction is an important component of the variance of phenotypic means in

selection experiments [1]. GE interactions complicate the identification of superior genotypes [2] but their interpretation can be facilitated by the use of several statistical modeling methods. These methods may use linear models, such as joint regression analysis [3], [4] and [5], multivariate analytical methods such as AMMI (additive mean effects and multiplicative interaction) analysis [6] and [7], or GGE (genotype plus GE interaction) biplot analysis [8] and [9]. The linear regression of genotype values on environmental mean yield [3] and [4], frequently termed joint regression analysis, is undoubtedly the most popular method for analyzing GE interaction, owing to its simplicity and the ready applicability of its information on adaptive responses to locations other than the chosen test sites. Earlier, Finlay and Wilkinson [4] proposed the use of linear regression slopes as a measure of AG-014699 mw stability. Eberhart and Russell

[5] further proposed that both regression coefficients selleck kinase inhibitor and deviations from linear regression (S2di) should be taken into consideration in identifying stable genotypes, and suggested that a genotype with b = 1.0 and S2di = 0 would be regarded as stable. The AMMI model uses analysis of variance (ANOVA, an additive model) to characterize genotype and environment main effects and principal component analysis (a multiplicative model) to characterize their interactions (IPCA). The AMMI analysis has been shown to be effective; it captures a large portion of the GE sum of squares, clearly separating the main and interaction effects; and the model often provides an agronomically meaningful interpretation of the data [7]. Another powerful statistical model that addresses some of the disadvantages of AMMI is the GGE biplot. The method is effective for identifying the best-performing cultivar across environments, identifying the best cultivars for mega-environment differentiation, and evaluating the yield and stability of genotypes [8] and [9]. According to the GGE biplot, a highly stable genotype would have a shorter projection on to the average environment coordinate (AEC) abscissa, irrespective of its direction [9].

4 for stable stratification and equal to 1 for unstable stratific

4 for stable stratification and equal to 1 for unstable stratification. The boundary conditions for k and ε read: equation(14a) k=u∗3Cμ3/4+maxB0kd1Cμ3/43/4, equation(14b) ε=u∗3kd1, equation(14c) u∗2=τsρo, equation(14d) B=gρo∂ρ∂TFnρocp+∂ρ∂SFsalt, where d1 is the distance from the boundary to the centre of the nearboundary grid cell, κ von Karman’s constant, u* the friction velocity, τs the wind surface stress and B the buoyancy flux due to net selleck chemicals heat (Fn) and salt (Fsalt) fluxes. In the absence of momentum and buoyancy fluxes, minimum values of k and ε are applied. The constants are discussed

in greater detail in Omstedt & Axell (2003). The initial temperature and salinity conditions for the EMB were taken from January 1958. The temperature and BIBW2992 price salinity were 16.6 ° C and 38.5 PSU respectively, from the surface to a depth of 150 m. Then temperature and salinity changed linearly to 14.1 ° C and 38.7 PSU respectively, at a depth of 600 m. From a depth of 600 m to the bottom, temperature and salinity were set to 14.1 ° C and 38.7 PSU respectively.

The initial conditions for the turbulent model assumed only constant and small values for the turbulent kinetic energy Protein kinase N1 and its dissipation rate. The sensible heat flux Fh is given by equation(15) Fh−CHρacpaWa(Ts−Ta),Fh−CHρacpaWaTs−Ta, where CH is the heat

transfer coefficient and cpa the heat capacity of air. The latent heat flux Fe is calculated as equation(16) Fe=CEρaLeWa(qs−qa),Fe=CEρaLeWaqs−qa, where qs is the specific humidity of air at the sea surface, assumed to be equal to the saturation value at temperature Ts, calculated as equation(17) qs=0.622RsPaexpcq1TsTs+273.15−cq2, where Rs = 611, cq1 = 17.27, cq2 = 35.86, and Pa is the air pressure at the reference level. The specific humidity of air at the reference level qa is accordingly calculated as equation(18) qa=0.622RsRhPaexpcq1TaTa+273.15−cq2, where Rh is the relative humidity (0 ≤ Rh ≤ 1). The heat flux due to net long-wave radiation Fl is given by the difference between the upward and downward propagation of long-wave radiation ( Bodin 1979), according to: equation19) Fl=εsσsTs+273.144−σsTa+273.154a1+a2ea1/21+a3N2, where εs is the emissivity of the sea surface, σs the Stefan-Boltzmann coefficient, and a1, a2 and a3 = 0.68, 0.0036 and 0.18 are constants. Furthermore, Nc is the cloud coverage and ea is the water vapour pressure in the atmosphere, related to qa as follows: equation(20) ea=Pa0.622qa.

, 2009) The iceberg output used as forcing is derived from a mod

, 2009). The iceberg output used as forcing is derived from a modified version of Bigg et al., 1996 and Bigg et al., 1997 iceberg model, developed by Martin and Adcroft (2010) and coupled to ORCA025, an eddy-permitting global implementation of the NEMO ocean model (Madec, 2008), to simulate the trajectories and melting of calved icebergs from Antarctica and Greenland in the presence Selleck MK2206 of mesoscale variability and fine-scale dynamical structure. Icebergs are treated as Lagrangian particles, with the distribution of icebergs by size derived from observations (see Bigg et al.,

1997 and Table 1). The momentum balance for icebergs comprises the Coriolis force, air and water form drags, the horizontal pressure gradient force, a wave radiation force, and interaction GSK2118436 ic50 with sea ice. The mass balance for an individual iceberg is governed by bottom melting, buoyant convection at the side-walls and wave erosion (see Bigg et al., 1997). This configuration has been run for 14 years, and the associated freshwater fluxes used here are averages over years 10–14. Southern Hemisphere calving and melting rates are in near balance after 10 years, but further decades of simulation would be needed for global balance, due to slower equilibration of calving and melting in the Northern Hemisphere. An average pattern

of icebergs is our primary interest, which is why we settled for a relatively short integration time. For our purposes a detailed treatment of various mass loss processes is not necessary, because only the amount of freshwater release applied to the ocean is of interest. Nevertheless, the many different processes that affect the SMB

indicate that uncertainties are to be expected and distinction between mass loss processes and geographical locations needs to be made (Shepherd et al., 2012). The most obvious response Farnesyltransferase to increased atmospheric temperatures is the melting of ice. This mass loss can be associated with adding freshwater directly offshore of the coast of the region where the melt takes place. We designate this freshwater source as run-off, or R for short. Run-off is contrasted with another form of mass loss that produces icebergs. The calving of icebergs from glaciers we call ice discharge, or D. The important difference is that icebergs are free floating chunks of ice and can drift to other locations and melt. This last observation prompts us to introduce the distinction between near (N) and far (F) freshwater forcing. A near forcing is always adjacent to the coast of origin and a far forcing is not restricted like this. The output of the iceberg drift and melt simulation gives us the location and relative magnitude of the far source of freshwater forcing. We assume spatial patterns on an annual cycle for these contributions, with magnitudes varying in time. The scaling factors are provided by the mass loss projections in the two polar regions.