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We have used fluorescent latex beads, with or without covalently conjugated OVA, to facilitate study of Ag trafficking in the mouse lung and draining peribronchial lymph node (LN). At 6 h, and up to 48 h after intranasal administration, beads were observed as intracellular clusters in the tissue parenchyma. Flow cytometry of bead-positive (bead+) cells from the bronchoalveolar lavage demonstrated that a majority of these cells are CD11c+, F4/80+, and CD11b−. Furthermore, fluorescent microscopy confirmed that a major subset of bead+ cells in the lung tissue was also CD11c+. In the draining peribronchial LNs, small numbers of beads were present in the subcapsular sinus as early as 6 h after inhalation. By 12 h and beyond, bead+ cells had localized exclusively to the LN T zone. OVA-conjugated latex beads, in addition to stimulating brisk proliferation of naive, OVA-specific DO11.10 transgenic T cells in vitro, could also recruit OVA-specific T cells in vivo. In some cases, bead+ APCs and CD4+ Th1 cells were found adjacently localized in the lung tissue 6 h after airway challenge. Thus, interactions of bead+ APCs with Ag-specific CD4+ T cells occurred earlier in the peripheral airways than these same interactions occurred in the draining peribronchial LN. Lastly, after adoptive transfer, in vitro differentiated Th1 cells accumulated at peripheral sites in the lung tissue and airways before Ag challenge and therefore were ideally positioned to influence subsequent immune reactions of the airway.
The immune response of a host to pathogens or exogenous Ags has classically been separated into an initial innate response, beginning immediately after encounter with Ag, and a later adaptive response, which begins hours to days after the initial challenge (1). Situated at the crossroad of these two systems is the peripheral dendritic cell (DC),3 influenced by the microenvironment of innate effectors and yet competent to prime lymphocytes that regulate the adaptive response. DCs sample Ags in the periphery, acting as sentinels at remote sites (2), then travel to lymph nodes (LNs) to prime naive T cells that circulate through these lymphoid organs (3, 4, 5, 6).
In the lung, Ag sampling is mediated by an extensive network of Ag-presenting DCs in the airway epithelium, as well as in alveolar septae and around airspaces (7, 8). These cells show high activity for Ag uptake and are capable of presenting Ag to T cells when cultured in vitro (9, 10). In vivo, pulmonary DCs migrate to the regional LNs after encounter with Ag (11, 12, 13), up-regulate costimulatory molecules in the process (14), and acquire potent activity for priming naive T cells and initiating a primary immune response (15, 16, 17, 18).
In addition to Ag-induced activation of DCs, the overall number of lung DCs also increases in response to a variety of stimuli (19), including proinflammatory cytokines (20, 21), soluble Ag (11), and microbial pathogens (22). Furthermore, DCs in the lung epithelium manifest a short ∼2-day half-life, suggesting that they are readily adapted to rapid and continuous sampling of the local environment (23).
Because they present airway Ags so efficiently, lung DCs are thought to be key regulators of T cell-dependent airway diseases such as asthma and allergic airway inflammation (24) (reviewed in Refs. 25 and 26). Indeed, it has been shown that DCs are indispensable for generating chronic eosinophilic airway inflammation in a mouse model of allergic airway disease (27). Furthermore, intratracheal administration of DCs differentiated and incubated with Ag in vitro leads to efficient sensitization of naive animals for a subsequent airway challenge (17). Adoptive transfer of Ag-specific T cells, together with intratracheal instillation of Ag-incubated DCs, permits simultaneous study of T cell activation/proliferation and DC migration (18). In other models, it has been possible to colocalize DC/T cell interactions by labeling DCs ex vivo with one fluorescent dye and T cells with another, permitting their direct visualization in lymphoid tissues (6). However, all of these studies have used DCs differentiated and expanded in vitro. The behavior of in vitro differentiated DCs vs those of naturally occurring in vivo APCs has not been well defined. To study naturally differentiated APCs and track their migration and interactions under in vivo conditions, we developed a system to tag airway DCs with a fluorescent marker that could be easily visualized.
In this study, we used 0.4-μm fluorescent latex beads as a model Ag, because these beads can be detected by both flow cytometry and fluorescence microscopy. We visualized them in the lung after intranasal (i.n.) administration, followed them during subsequent trafficking to the regional LNs, and observed them as they localized to the LN T zone. Bead+ cells in the bronchoalveolar lavage (BAL) fluid and lung tissue were further characterized by flow cytometry. Lastly, by covalently conjugating the widely used immunogen OVA to blue fluorescent beads and using T cells from a DO11.10 transgenic (Tg) mouse (28) tagged with a red fluorophore, we visualized in situ the arrival of APCs in the draining LN, the time course of T cell recruitment to the lung, and T cell/APC interactions along the way.
This dual-labeling approach provides a flexible system for investigation of not only signals that control the trafficking of Ag, but also the localized interaction between native APCs and Ag-responsive T cells. Data obtained by tracking Ags temporally as well as spatially suggest that, under some circumstances, previously activated T cells first see their Ag in the peripheral tissues of the lung and not in the LN. Furthermore, we make the novel observation that Th1 cells not only accumulate more readily after an airway challenge but are already present at higher numbers in the airway lumen before a primary Ag challenge. Therefore, these cells are positioned to play a specialized role in initiating or modulating inflammatory pathologies of the airway, and fluorescent beads have allowed us to study their rapid interactions with native APCs.
Materials and Methods
C57BL/6 and BALB/c mice were obtained from The Jackson Laboratory (Bar Harbor, ME). DO11.10 TCR Tg mice (28) had previously been backcrossed to BALB/c for more than 10 generations and then bred to RAG2-deficient mice (RAG2−/−), also on a BALB/c background. All mice used were female and 6–10 wk of age at the time of Ag challenge. Mice were housed in microisolator cages in a specific pathogen-free facility and provided with food and water ad libitum, according to protocols approved by the Washington University Institutional Animal Care and Use Committee. All mice appeared healthy, and regular monitoring of sentinels showed no serological or histological evidence of respiratory tract infection.
Fluorescent beads
The 0.431-μm carboxylate-modified fluorescent beads were obtained from Sigma-Aldrich (St. Louis, MO) at a concentration of ∼2.3 × 1012 particles/ml (catalog nos. L3280 and L4030). Before i.n. administration, beads were washed three times in sterile PBS by centrifugation at 16,000 × g for 12 min and were resuspended in sterile PBS (Life Technologies, Grand Island, NY) at a final concentration of ∼7.5 × 1010 particles/ml. Conjugation of beads to OVA was conducted in 25 mM MES (pH 6.1), 1 mM 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, with beads at 7.5 × 1010 beads/ml, and 2 mg/ml OVA (all from Sigma-Aldrich). Conjugation reactions were rotated overnight in the dark at room temperature followed by two washes in 25 mM MES. Immediately before use, beads were washed twice in sterile PBS and resuspended at ∼7.5 × 1010 particles/ml. After conjugation, beads were stained with rabbit polyclonal anti-chicken egg albumin (Accurate Chemical and Scientific, Westbury, NY), and then with a FITC-conjugated anti-rabbit Ig (Sigma-Aldrich) to assess the fraction of beads conjugated to OVA. More than 40% of beads were positive for OVA as assessed by flow cytometry.
Recovery of lung and airway leukocytes
Mice were anesthetized with 75 mg/kg ketamine (Fort Dodge Animal Health, Fort Dodge, IA) and 1 mg/kg medetomidine (Orion, Espoo, Finland), and were humanely sacrificed. The trachea was cannulated and cells were recovered by flushing the lungs with four aliquots of 0.8 ml of sterile-filtered 2% FCS (HyClone Laboratories, Logan, UT) in PBS. RBCs were lysed using lysis buffer (0.15 M NH4Cl, 10 mM Tris (pH 7.5)), and nucleated cells were counted using a hemacytometer. Parenchymal lung cells from the left lobe were obtained after lavage by mincing the tissue in 23 μg/ml Liberase (Boehringer Mannheim, Indianapolis, IN) with 30 μg/ml DNase I (Sigma-Aldrich), incubating at 37° for 30 min and pressing through a 70-μm filter (BD Biosciences, Franklin Lakes, NY).
Histology and immunohistochemistry
In all cases, BAL was performed before harvesting lung tissue. After tying off the left mainstem bronchus, the left lung was removed for enzymatic digestion. The right lung was inflated with 50% OCT compound (Tissue-Tek; Sakura Finetek, Torrance, CA) in sterile PBS and frozen on dry ice. Seven-micrometer sections were cut, fixed in acetone for 10 min, and stored at −20°C until staining. Where indicated, sections were stained with a biotin-conjugated monoclonal anti-CD11c mAb (BD PharMingen, San Diego, CA) and then with streptavidin-FITC (BD PharMingen). Frozen sections of peribronchial LNs were stained with FITC-conjugated monoclonal anti-CD4 (BD PharMingen) and biotin-conjugated monoclonal anti-B220 (BD PharMingen) and then with Alexa-350-conjugated neutravidin (Molecular Probes, Eugene, OR). Sections were examined using a fluorescence microscope (BX-60; Olympus, Melville, NY). T cells that were 5-(and 6)-carboxytetramethylrhodamine (TAMRA)-positive and bead+ APCs were counted as colocalizing if, at ×400 magnification in a 7-μm section, they showed cell-cell contact. Analysis of slides for determination of colocalization was performed in a blinded fashion with a random selection of sections. Statistical significance between groups was assessed using an unpaired Student's t test with equal variance.
i.n. administration of beads
To deliver fluorescent beads i.n., mice were lightly anesthetized with either Metofane (methoxyflurane; Schering-Plough Animal Health, Union, NJ) or a ketamine/xylene mixture, given 40 μl of beads (∼3 × 109 beads) in sterile PBS on the nostrils, and allowed to recover in a supine position.
Analysis of cell phenotype by flow cytometry
Flow cytometry was performed using a FACSCalibur and data were analyzed with CellQuest software (BD Biosciences, Mountain View, CA). All Abs, with the exception of the biotin-conjugated monoclonal anti-F4/80 (Caltag Laboratories, Burlingame, CA) and rat anti-NLDC-145 (Bachem, Torrence, CA), were purchased from BD PharMingen and include FITC-conjugated anti-CD11c, anti-CD4, and anti-CD11b; PE-conjugated anti-CD11b; and biotin-conjugated anti-CD11c and anti-B220. Biotin conjugates were detected using streptavidin-conjugated APCs (BD PharMingen). After lysis of red cells, nonspecific Ab staining via FcR was blocked with supernatant from hybridoma 2.4G2 (American Type Culture Collection, Manassas, VA). Stained cells were stored at 4°C in 1% paraformaldehyde/PBS until just before analysis.
Assessment of lymphocyte proliferation in vitro
CD4+ lymphocytes were purified from the spleens of RAG2−/− DO11.10 TCR Tg mice (kindly provided by O. Kanagawa, Washington University, St. Louis, MO) using anti-mouse CD4 Dynabeads and the mouse CD4 DETACHaBEAD system (Dynal BioTech, Lake Success, NY), according to the manufacturer's instructions. CD11c+ cells were purified from the Liberase-digested lungs of naive mice using a FITC-conjugated anti-CD11c mAb (BD PharMingen), anti-FITC magnetic beads, and a magnetic column (Miltenyi Biotec, Auburn, CA). Purity of CD11c+ cells after magnetic sorting, as assessed by flow cytometry, was >94%. Purified T cells (3 × 105) were cultured in 200 μl of Iscove's medium supplemented with 10% FCS (HyClone Laboratories), 0.1 mM nonessential amino acids, 2 mM sodium glutamate, 1 mM sodium pyruvate, 100 U/ml penicillin, 100 μg/ml streptomycin, and 5.5 μM 2-ME (all from Life Technologies) together with 2 × 104 CD11c+ cells and 20 μg of soluble OVA, 10 μl of fluorescent beads only, or 10 μl of fluorescent beads conjugated to OVA. Cells were cultured for 3 days at 37°C under 5% CO2. One microcurie of [3H]thymidine (Amersham, Arlington Heights, IL) was then added to each well, and the culture was continued for an additional 24 h. Cells were harvested on a PHD cell harvester (Cambridge Technology, Watertown, MA), and incorporation was measured on a scintillation counter (LS3801; Beckman Coulter, Fullerton, CA).
Adoptive transfer of T cells
OVA-specific T cells were differentiated in vitro into Th1 or Th2 cells as previously described (29, 30, 31). On day 7 of culture, cells were centrifuged over Histopaque 1119 (Sigma-Aldrich) to remove dead cells, and they were washed twice in PBS. Before labeling, a sample of Th1 and Th2 cells were stained for expression of CD25 and CD69. Levels of these activation markers were the same between the two groups, suggesting that there was no gross difference in the activation status of the two cell populations. Cells were then fluorescently labeled by incubation for 15 min at 37°C with 6 μg/ml TAMRA-succinimidyl ester (SE) (Molecular Probes) in Ca2+- and Mg2+-free PBS. Fluorescently labeled cells were washed twice in sterile PBS and transferred to anesthetized, naive animals i.v. via retro-orbital injection. Naive CD4+ T cells were recovered from spleens and LNs of RAG2−/− DO11.10 Tg mice, and sorted using anti-mouse CD4 Dynabeads and mouse CD4 DETACHaBEAD (Dynal BioTech). Then they were incubated with TAMRA-SE and injected as described above. Purity of naive CD4+ cells was >95% as determined by flow cytometry.
Fluorescent beads are taken up by cells of the lung
To investigate factors that control Ag uptake, trafficking, and presentation in the mouse lung, we have used fluorescent latex beads as a model inhaled Ag. The beads are well suited for this purpose because they are readily taken up by phagocytic cells, visualized by fluorescence microscopy, and quantitated by flow cytometry. Furthermore, they can also be modified by covalent coupling to immunogens and followed in parallel to immunogen-specific T cell responses. To test their behavior as particulate Ags, we administered 3 × 109 0.4-μm fluorescent latex beads in 40 μl of sterile PBS to lightly anesthetized C57BL/6 mice. At various times later, the mice were sacrificed, their lungs were harvested, and frozen sections of lung were analyzed by fluorescence microscopy to determine the locations of the beads.
Beads were detected in lung cells as early as 2 h after i.n. instillation and remained present until at least 46 h later. This observation is congruent with other studies demonstrating that lung DCs harvested after Ag challenge retain the ability to present Ag in vitro up to 7 days after initial administration of the Ag (11). The majority of beads detected in this fashion resided within cells of the lung, and not free in the airways, based upon their localization adjacent to 4′,6′-diamidino-2-phenylindole-positive nuclei (Fig. 1⇓, A and B). Beads were also found in large quantities in cells recovered by BAL (Fig. 1⇓, C and D). Fluorescence microscopy in conjunction with Wright-Geimsa staining demonstrates that beads could be found in >50% of BAL cells and that the majority of these cells were of the monocyte/myeloid phenotype.
Bead+ lung cells are CD11c+ and bead+ BAL cells are CD11c+F4/80+CD11b−
To identify phenotypic characteristics of bead+ lung cells, we performed Ab staining of frozen lung sections followed by dual fluorescence microscopy. Using an anti-CD11c Ab, we determined that >30% of the cells in the lung that had taken up fluorescent beads were also CD11c+ (Fig. 1⇑, E and F). Analysis by confocal microscopy confirmed that beads were present within the CD11c+ cells (data not shown). To permit broader characterization of bead+ cells, we performed flow cytometry on cells positive for bead uptake. Bead+ cells are easily differentiated from those that have not taken up beads (Fig. 2⇓). By gating on bead+ cells, we were able to then test for expression of CD11c and CD11b, F4/80, or NLDC-145 on these same cells (Fig. 2⇓ and Tables I⇓ and II⇓). The markers CD11b, F4/80, and NLDC-145 were chosen because of their suggested differential expression among the myeloid and lymphoid DC subsets (32, 33, 34).
At 6 and 12 h after instillation of beads, most bead+ cells from the BAL were also positive for the DC marker CD11c (>80%). In turn, a great majority of these CD11c+ cells were negative for the myeloid-specific marker CD11b. For example, at 6 h compare 85.9% CD11chighCD11b− vs 2.7% CD11chighCD11b+ (Table I⇑). By 24 and 48 h, a greater portion of bead+ BAL cells were low or negative for expression of CD11c compared with the populations at 6 or 12 h, although they remained negative for CD11b expression. This CD11clow/−CD11b− population of cells also showed lower side light scatter and forward light scatter values than the bead-positive population at 6 h. It remains unclear whether this increase in the CD11clow/−CD11b− subset at 24 and 48 h represents a newly emigrated population of cells entering into the airway lumen or merely indicates the down-regulation of surface markers on cells, which phagocytosed beads at some earlier time. To continue characterization, staining with F4/80 revealed that >85% of bead+ BAL cells were also F4/80+ at all times examined (Table II⇑). Furthermore, of all bead+ cells at 6 and 12 h, ∼65% of these were F4/80+CD11chigh.
In the lung tissue itself, regardless of the time after challenge, ∼25% of bead+ cells are CD11c+CD11b−, with a majority (50–60%) being CD11clow/−CD11b−. As in the BAL, <10% of bead+ lung leukocytes are either CD11c−CD11b+ or CD11c+CD11b+. Flow cytometry data regarding CD11c positivity correlate closely with those obtained using tissue staining and then dual fluorescence microscopy (∼30%). For bead+ cells recovered from the lung, nearly equal numbers of CD11c+F4/80+, CD11clow/−F4/80+, and CD11clow/−F4/80− populations were observed (Table II⇑). Lastly, at 6 and 12 h, ∼20% of bead+ cells from the BAL or lung were also NLDC-145+.
OVA covalently conjugated to fluorescent latex beads can stimulate OVA-specific CD4+ T cells in vitro
To enhance the utility of fluorescent beads as a model Ag, we tested whether beads would be recognized by Ag-specific CD4+ Tg T cells if covalently conjugated to the Ag recognized by the transgenic TCR. For this purpose, we tested whether CD11c+ lung cells given OVA-conjugated fluorescent beads could stimulate proliferation of OVA-specific DO11.10 Tg T cells. CD11c+ lung cells were recovered from naive, wild-type animals; incubated with OVA-conjugated fluorescent beads, beads alone, or unconjugated OVA (soluble OVA); and then cultured for 96 h with CD4+ DO11.10 Tg T cells. When CD4+ DO11.10 T cells were stimulated with OVA-conjugated beads using CD11c+ cells from the lung as APCs, robust proliferation was observed at 96 h (Fig. 3⇓). Beads alone stimulated no proliferation over background.
i.n. administered fluorescent beads traffic to the T cell zone of peribronchial LNs
Other studies have demonstrated that in vitro differentiated DCs traffic from the skin to the draining LN within 24 h (6). To determine whether fluorescent beads administered i.n. exhibit a similar temporal progression, we analyzed the accumulation of beads in peribronchial LNs harvested at varying times after challenge. Small numbers of beads (2–3 bead+ cells/section) were detected in peribronchial LN sections as early as 6 h after i.n. administration. These bead+ clusters initially localized exclusively in the subcapsular sinus (Fig. 4⇓A). In contrast, 12 h after challenge, peribronchial LNs showed large numbers of bead+ clusters (>10 per section) in nearly each section examined (20 sections from eight mice). Furthermore, by this time the majority of fluorescent bead+ cells were localized within the T zone of the LN (Fig. 4⇓B). By 24 and 48 h, there was a further increase in the number of bead+ cells per LN section, showing similar exclusive localization to the T zone (Fig. 4⇓C).
Th1 cells preferentially accumulate in the lung and BAL of mice after i.n. challenge with OVA-conjugated beads
Other groups have shown that naive T cells first encounter their Ag in the regional LN. To test whether previously activated cells follow the same paradigm, we combined analysis of OVA-conjugated fluorescent beads and migration of OVA-specific Tg T cells. In vitro differentiated DO11.10 Th1, Th2, or naive CD4+ cells were labeled with the fluorescent dye TAMRA-SE and transferred i.v. to naive BALB/c mice. Three days later, these mice were challenged i.n. with one administration of OVA-conjugated beads and were examined at various times.
The total number of cells recovered by BAL in all three groups of mice increased less than 2-fold over the entire period of evaluation. However, in contrast, the number of TAMRA+ cells recovered from the BAL of mice given labeled Th1 increased more than 10-fold, from a value of 1.9 ± 0.37 × 103 at baseline to over 26.7 ± 0.98 × 103 at 48 h (Fig. 5⇓A). Significantly, neither mice given Th2 cells nor mice given naive CD4+ T cells exhibited a substantial increase in the number of TAMRA+ cells in the BAL cells at any time after a single airway challenge. These results are consistent with prior findings from our laboratory (30). Importantly, the relative proportion of Th1 cells did not increase in either the nondraining inguinal LN or the spleen between baseline and 48 h after airway challenge (data not shown). This indicates that the accumulation of Th1 cells in the airway was specifically localized to the region of Ag challenge.
Percentages of TAMRA+ cells in the lung parenchyma were also analyzed. Th1 cells at baseline were represented at a higher frequency in lung tissue than either Th2 cells or naive, undifferentiated cells (Fig. 5⇑B). There were modest increases in the percentage of lung Th1 cells over the 48 h after OVA challenge and smaller transient changes in Th2 cells. The failure to detect a substantial increase in naive or Th2 cells in the BAL or lung was not due to a gross loss or death of these populations, because both groups could be found at other anatomical locations, including the peribronchial LN, nondraining inguinal LN, and spleen (Fig. 4⇑D and data not shown).
T cells are positioned to encounter Ags in the regional LNs early after Ag challenge
As shown in Fig. 4⇑D, naive TAMRA+ T cells are present in the T zone of the peribronchial LN before an airway challenge. This is also true, to a lesser extent, for mice given Th1 cells (data not shown). Conjugated fluorescent beads administered to naive, wild-type mice, as shown earlier, traffic to the T zone of the LN between 6 and 12 h. Transfer of Ag-specific Th1, Th2, or naive cells did not affect this time course, and bead+ cells do not reach the T zone 6 h after i.n. administration of beads. At 12 h, some bead+ cells are found in the T zone and can be seen localized adjacent to fluorescently labeled T cells (Fig. 4⇑E). Higher magnification verifies the proximity of this localization (Fig. 4⇑F). This type of APC/T cell interaction in the LN continues to occur at higher frequency 24 and 48 h after Ag challenge.
Adjacent localization of Th1 cells and APCs in the lung 6 h after Ag challenge
Because large amounts of the Ag remained in the lung over the first several days, we reasoned that APC/T cell interactions might be occurring in the peripheral lung tissue at time points before, or directly concurrent with, initial presentation of Ag to T cells in the draining LN. To test this, we investigated localization of TAMRA-labeled T cells and bead+ APCs in the lung 6 h after challenge with OVA-conjugated beads.
As demonstrated in Fig. 6⇓, at 6 h after i.n. Ag challenge, OVA-specific Th1 cells were found in much higher numbers per high power field (HPF) than either Th2 or naive cells (Fig. 6⇓A). In contrast, the numbers of bead+ APCs/HPF were relatively constant between groups (Fig. 6⇓B). Significantly, Th1 cells were found colocalizing with bead+ APCs 4-fold more frequently than either Th2 or naive cells (Fig. 6⇓C). T cell-APC interactions characterized as colocalization are depicted microscopically in Fig. 4⇑, G and H. The frequency of these interactions appeared to be dependent upon the subset of helper cells transferred, because the average number of interactions per T cell was 0.072 interactions/Th1 cell (7.2%), but only 0.018 interactions/Th2 cell (1.8%). T cells and bead+ APCs were also frequently found in close proximity, but without apparent cell-cell contact (data not shown). The latter were consistent with cell-cell interactions in the process of development and were found to occur around vessels or in collections of cells at branching points of alveolar walls. In total, these studies substantiate the hypothesis that in vitro differentiated Th1 cells are capable of localizing adjacent to APCs in the peripheral lung tissue on a time course that precedes detection of the same Ag or APC/T cell interaction in the draining LN and that the frequency of this early colocalization is dependent upon the CD4+ T cell subtype, being substantially more common with Th1 cells than Th2 cells.
This study was designed to investigate the behavior of Ag, Ag-transporting cells, and Ag-specific CD4+ T cells in mice after administration of Ag via the airway. As a particulate Ag we have used fluorescent latex beads, with or without covalently conjugated OVA, to facilitate the study of native APC trafficking in the mouse lung. Beads, when given alone, are rapidly engulfed by cells of the lung and can be seen gathered together in "bead+ clusters" as early as 2 h after administration. How long they remain in the lung remains undefined, but we have observed their continued persistence for at least 48 h after the initial i.n. administration.
We have used both histological and flow cytometric approaches to define the phenotype of cells responsible for bead uptake. In both BAL and lung samples, a large fraction of bead+ cells express the cell surface marker CD11c. CD11c has been described by Steinman and colleagues (35) as a specific marker for splenic DCs and is present on at least a subset of DCs from other lymphoid organs (33, 34). In this study, bead+ cells recovered by BAL, a majority of which are CD11c+ by flow cytometry, appeared by Wright Giemsa staining to be myeloid in origin. Their high expression of CD11c argued against an exclusive macrophage designation (36), and so we postulated that these bead+ cells belonged to the myeloid DC subset. However, particularly within the first 12 h, bead+ cells are predominantly CD11c+CD11b−, with CD11b being a marker commonly positive on myeloid DCs. This suggests then that bead+CD11c+CD11b− cells represent a unique subset of airway DCs. Alternatively, they may simply represent incompletely committed precursor cells of monocytic origin. It is of interest that the macrophage marker F4/80 is highly expressed on this same bead+CD11c+ subset. High expression of F4/80 does not preclude the classification as DCs because other groups have shown that some subsets of DCs, before culturing and when freshly isolated from tissues, also express the macrophage marker F4/80 (34). We speculate then, based upon bead+ cells being CD11c+F4/80+CD11b−, that this subset may represent a cell type similar to the CD11c+F4/80+ epidermal Langerhans cell (37) and may perform a similar function in trafficking Ag from the periphery to the draining LN.
Another report published recently used FITC-conjugated OVA to track DCs in the mouse lung and LNs (38). The phenotypic markers expressed on APCs in that study and on those reported in this study differ substantially. These differences might be explained in several ways. First, our model evaluated the phenotype of all cells that took up the fluorescent Ag. Our only inclusion criterion was that cells be positive for bead uptake. Secondly, our system uses a particulate rather than a soluble Ag. Although it is unclear what difference particulate vs soluble nature of the Ag makes in terms of Ag delivery or cellular uptake, this difference may drive the selection of different phagocytic subsets. Finally, our model highlights the identity and surface marker characterization of Ag-positive BAL cells. The study by Vermaelen et al. (38) focuses on tissue phagocytes and not BAL cells.
After uptake from the airway, beads trafficked efficiently to the peribronchial LN on a time course that closely approximates that seen in other systems. Ingulli et al. (6) demonstrated the appearance of dye-labeled DCs in the draining lymph 24 h after s.c. injection, whereas other studies have observed the appearance of intratracheally administered DCs in the peribronchial LNs 36 h post-administration (16). Vermaelen et al. (38) detected initial accumulation of FITC-conjugated OVA in the peribronchial node 6 h after administration. However, in this latter case, the Ag was soluble and early arrival may represent rapid draining via lymph channels and sinuses, as has been demonstrated to occur in other situations (39). In our model, the appearance of cell-associated particulate Ag in the peribronchial node began ∼6 h after challenge. However, at this early time, beads were localized exclusively to the area of the subcapsular sinus. Based upon this observation, we speculate that the sinus represents a location where bead-bearing cells first enter the LN, trafficking only later to the T cell zone. Twelve hours after i.n. instillation, bead+ clusters were seen in the T zone of the LN, with peak accumulation in this area by 24 h. Using these observations as a foundation, we envision true T cell/APC interactions in the LN to begin in earnest only 6–12 h after administration of the particulate Ag.
Because of this time course and the fact that large amounts of Ag remain in the peripheral tissue, we hypothesized that productive Ag/APC/T cell interactions might occur in the lung periphery before the Ag reached the T zone of the draining LN. Given the fact that nearly one-third of all bead+ cells in the lung (>75% in the BAL) are positive for CD11c and that CD11c+ lung cells are capable of presenting beads and their conjugated Ags to OVA-specific T cells in vitro, we reasoned that CD11c+ cells responsible for taking up Ag in the lung might also be capable, in vivo, of presenting this same Ag to T cells residing in the surrounding lung tissue.
Our data demonstrating colocalization of bead+ APCs and OVA-specific T cells are consistent with this hypothesis, namely that some T cells first encounter their Ag at a peripheral site outside the LN. Our ability to observe Th1/APC interactions in distal airspaces 6 h after Ag challenge provides evidence that previously activated T cells may encounter Ag in extralymphoid compartments quite early in a secondary immune reaction. This is in contrast to what we and others have observed using naive or undifferentiated cells (40). Furthermore, because beads are already gathered together in clusters 2 h after administration, we believe that T cell/APC interactions are capable of occurring even earlier than 6 h. Whether or not this early interaction occurs at a higher frequency appears to be dependent on the subset of the T cell involved.
In addition to early APC/Th1 cell interactions in the tissue, it was interesting to observe that Th1 cells were also recovered in much higher numbers than Th2 or naive cells from the BAL fluid of animals in the absence of challenge by Ag. As shown in Fig. 5⇑C, Th1 cells number in the thousands in the BAL of naive mice before challenge, whereas Th2 or naive cells are observed at the very limits of detection. This is despite the fact that in vitro differentiated Th1 and Th2 cells have similar levels of the activation markers CD25 and CD69 before transfer and have been stimulated for the same duration in vitro. This suggests that the different behavior of Th1 and Th2 cells is not due to differences in their state of activation. Furthermore, Th1 cell numbers do not increase over time in either the spleen or the nondraining inguinal LN, indicating that there is specific accumulation of these cells in the lung and airways after airway challenge. The precise reason Th1 cells accumulate in the BAL, particularly in the absence of overt inflammation, remains undefined. It is certainly possible that differential expression of chemokine receptors (41) or ligands (42), differential thresholds of stimulation (43), or expression of other currently unidentified signaling molecules leads to preferential recruitment or retention of Th1 cells in the distal airspaces, even in the absence of inflammation. In this regard, Th1 localization to peripheral lung sites is reminiscent of specific Th1 recruitment to the peritoneal cavity under Ag-dependent and Ag-independent inflammatory scenarios (44).
The relatively rapid accumulation over time of TAMRA+ Th1 cells in the BAL of mice after airway Ag challenge is not, in fact, unexpected. Earlier adoptive transfer studies in our lab demonstrated the accumulation of Th1 cells in the BAL of challenged animals with only minimal recruitment of Th2 cells (31). We predict that predominance of Th1s in the BAL 24 h after a primary airway challenge localizes this subset in an environment where they are capable of responding almost immediately to a second inhalation of Ag. Furthermore, coupled with early Th1/APC interactions in an airway response, peripheral localization would allow Th1 cells to exert a profound influence over the outcome of not only the ongoing immune response, but over subsequent immune responses as well. Th1 modulation of an immune response might occur in a multiplicity of ways, including the release of specific inflammatory mediators at the site of Ag encounter or the recruitment, directly or otherwise, of cells types known to be pathogenic (30).
It is clear from our own experience and that of others (38), that fluorescent Ags provide a powerful way of tracking Ags and APCs in vivo. When combined with fluorescent labeling of other cells, visualization in this fashion helps clarify issues of migration and cell contact. Together with data tracking fluorescent Ag to the peribronchial LN, we conclude that, after airway challenge, a significant portion of previously activated Th1 cells first encounter inhaled Ag in the periphery of the lung. The presence of the cells at these peripheral sites facilitates a T cell-mediated response immediately upon subsequent inhalation of immunogen or Ag. Predominance of specific T helper subsets at sites of primary Ag contact (e.g., the skin, the lung, the gut) is important for understanding the regulation of subsequent allergic and nonallergic immune reactions. Additional studies using fluorescently labeled cells and beads will permit better characterization of cell interactions immediately upon Ag uptake, help elucidate the role of inflammatory proteins in bead/Ag handling using genetic knockout animals, and begin to define the differences in the handling and immunogenicity of soluble vs particulate Ags.
We thank R. Stephens, L. Mandik-Nayak, and C. Zindl for careful review of the manuscript and helpful discussions, G. Huang and G. Schweitzer for technical assistance, E. Ford for maintenance of mice and cutting of sections, and L. Scharpen for general support.
↵1 This work was supported by National Institutes of Health Grants AI 34580 (to D.D.C.), HL 56419 (to D.D.C.), and GMS 07200 (to C.A.B.). D.D.C. is an investigator of the Howard Hughes Medical Institute.
↵2 Address correspondence and reprint requests to Dr. David D. Chaplin at the current address: Department of Microbiology, University of Alabama, 845 19th Street South, BBRB 276/11, Birmingham, AL 35294-2170. E-mail address: dchaplin{at}uab.edu
↵3 Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; i.n., intranasal; BAL, bronchoalveolar lavage; Tg, transgenic; TAMRA, 5-(and 6)-carboxytetramethylrhodamine; SE, succinimidyl ester; HPF, high power field.
- Received May 14, 2001.
- Accepted October 15, 2001.
- Copyright © 2001 by The American Association of Immunologists


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Information and Communication Technology
Global Customer Experience Platforms Market 2019-2026: Analyzed by Business Growth, Development Factors, Application and Future Prospects
Top Key Players - Qualtrics, Zendesk, Oracle, OpenText Corp, SAS Institute Inc., Adobe, Cisco, Zoho Corporation Pvt. Ltd., Tech Mahindra Limited, Software AG, Tata Consultancy Services Limited, Google Forms, and SurveyMonkey.
Global Customer Experience Platforms Market Report contains latest, sufficient and most developed market data and valuable information. Besides, the information is again checked and confirmed by the market specialists before distributing it through the market report and giving it to the customer. The investigation of Global Customer Experience Platforms Market report clarifies a market engaging quality examination, wherein each fragment is focused on dependent on its market estimate, development rate, and general allure. These bits of knowledge will prompt a significant thoughts, better decision making and better business techniques.
Customer experience platform is a platform created by the businesses so that they can interact with the customers and get their views and feedback on their product or services. This software collects the data like feedback, views, complaints etc. so that they can use them to improve their services and make their business better. They also help the customers if they face any problems or issues. This is a very good technique to build up a good relationship with the customers.
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Key Market Competitors: Global Customer Experience Platforms Market
Few of the major competitors currently working in the customer experience platforms market are Avaya Inc., IBM Corporation, Huawei Technologies Co. Ltd., Qualtrics, Zendesk, Oracle, OpenText Corp, SAS Institute Inc., Adobe, Cisco, Zoho Corporation Pvt. Ltd., Tech Mahindra Limited, Software AG, Tata Consultancy Services Limited, Google Forms, and SurveyMonkey.
Segmentation: Global Customer Experience Platforms Market
Global customer experience platforms market is segmented on the basis of:
- Interaction Point– Stores, Websites, Email, Call Centre, Mobile Apps, Social Media
- Deployment– On-Premise, Cloud Deployment
- Platforms– Windows, iOS, Android
- Vertical– IT & Telecommunication, BFSI, Healthcare, Consumer Goods & Retail, Hospitality, Transportation & Logistics, Media & Entertainment, Government
- Enterprise Size- Small Enterprises, Medium Enterprises, Large Enterprises
- Geography– North America, South America, Europe, Asia-Pacific, Middle East and Africa
Table of Content:
01: Executive Summary
02: Scope of The Report
03: Market Landscape
04: Market Sizing
05: Market Segmentation by Product
06: Five Forces Analysis
07: Customer Landscape
08: Geographic Landscape
09: Decision Framework
10: Drivers and Challenges
11: Market Trends
12: Vendor Landscape
13: Vendor Analysis
Table of Contents Available For this Market Download Free TOC : https://databridgemarketresearch.com/toc/?dbmr=global-customer-experience-platforms-market
Recent Developments
- In November 2018, Zoho Corporation Pvt. Ltd. launched "Zoho CRM Plus", their new customer experience platform that provides all of its departments such as sales, marketing, customer support and operations under one platform enabling the users of this platform complete transparency and segregation of their feedbacks.
- In September 2018, Adobe announced the launch of "Adobe Experience Platform", formerly known as "Adobe Cloud Platform" industry's first open customer experience platform that enables the data scientists and analytics to extract all the customer database and preferences from one place as it creates one single view of this database for extraction as well as viewing purposes.
Browse Related Reports:
Global Content Services Platforms Market By Component (Solutions, Services), Deployment Type (0n-Premises, Cloud), Organization Size (Small and Medium-Sized Enterprises, Large Enterprises), Vertical (Banking, Financial Services, and Insurance, Government and Public Sector, Healthcare and Life Sciences, Energy and Utilities, IT and Telecom, Education, Manufacturing, Legal, Others), Geography (North America, South America, Europe, Asia-Pacific, Middle East and Africa) – Industry Trends and Forecast to 2026
Global Intelligent Process Automation Market By Technology (Natural Language Processing, Machine and Deep Learning, Neural Networks, Virtual Agents, Mini Bots and RPA, Computer Vision, Others), Component (Solutions, Services), Vertical (Banking, Financial Services, and Insurance, Telecommunications and IT, Transport and Logistics, Media and Entertainment, Retail and E-Commerce, Manufacturing, Healthcare and Life Sciences, Others), Application (IT Operations, Business Process Automation, Application Management, Content Management, Security, Others), Geography (North America, South America, Europe, Asia-Pacific, Middle East and Africa) – Industry Trends and Forecast to 2026
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Topic Page: Horney, Karen (1885 - 1952)
As one of the second generation of psychoanalysts following Sigmund Freud (1856–1939), Karen Horney (1885–1952) is acknowledged as the first feminist in the field of psychoanalysis. She was a founding member of the Berlin Psychoanalytic Institute, where she actively trained and taught. But during her lifetime, very few of her early colleagues in Berlin or Vienna anticipated the profound paradigm shift in the theory of psychodynamic treatment she was about to create in the decades following her pivotal move to the United States in 1932.
Horney began her clinical practice in Berlin in 1910, and by 1924, she was writing extensively on the limitations of Freud's instinct-driven theory of psychoanalysis, especially as applied to women. After her immigration to the United States, she made contact with sociologists, anthropologists, and philosophers of her day and was especially close to Margaret Mead, Ruth Benedict, Harold Lasswell, Abram Kardiner, Erich Fromm, and John Dollard. Learning that psychoanalysis cannot be divorced from the society in which one lives, Horney absorbed sociocultural understanding into her psychoanalytical framework. This led to her first major work in 1937, The Neurotic Personality of Our Time, a critique of Freud's commitment to a 19th-century philosophy of knowledge where behavior was fundamentally attributed to the discharge of psychosexual energy. This was her first challenge to the idea of the universality of Freud's assumptions.
Horney's cultural critique convinced her that no amount of amending Freud's theories at the margins was going to be effective in rescuing psychoanalytic therapy from a culture-bound posture leading to a closed system of thinking. Within 2 years, she presented the field with a comprehensive review of every aspect of the closed superstructure Freud had imposed on his great discovery of free association. Her 1939 text, New Ways in Psychoanalysis, acknowledged the indisputable importance of Freud's work but also questioned libido theory and, therefore, Freud's entire theory of instincts, which proved to be a most difficult historic moment for both theorists and practitioners of existing orthodox psychoanalysis.
Having deeply immersed herself for nearly three decades in assessing the clinical usefulness of Freud's theoretical structures, Horney was now prepared to offer her own genuinely original formulations of psychoanalysis and psychoanalytical treatment. She called her approach "a constructive theory of neurosis" to highlight differences from Freud's essentially pessimistic view of instincts and civilization as pitched in endless war with each other.
In her view, emotional distress is not instinct driven but is the result of conflicting and compulsive characterological trends in the personality, developed as an attempt to find safety from anxiety, vulnerability, shame, and self-hate. Healthy, genuine needs give way to compulsive drives that by their nature create "vicious circles of unattainable goals." These splits are unintegrated and thus render the patient fragile and vulnerable. Describing both interpersonal and intrapsychic dynamics, Horney carved out three prominent narcissistic constellations, each with its own transference and counter-transference implications. In her 1945 book Our Inner Conflicts, she initially described the movements toward, against, and away, vis-à-vis the other, as compulsive character trends; later, she referred to them as compulsive character solutions with the corresponding intrapsychic dynamics of compliance, dominance, and detachment, respectively.
No less crucial is Horney's change in the focus of psychoanalysis from the instinctual conflicts of the past to the immediately present cutting edge of character conflict. The emerging dynamic becomes framed in the experiential here-and-now. The psychodynamics of this theoretical change in how to treat inner conflict, coupled with the importance of the practitioner's involvement in the patient's phenomenological present, is richly formulated in her 1950 book Neurosis and Human Growth: The Struggle Toward Self-Realization. The work, which some say is Horney's magnum opus, was the culmination of her efforts to describe human pathology in the context of human possibility.
Horney was an experience-near theorist committed to careful listening to the immediate narrative. The posture, therefore, emphasizes a moment-to-moment immersion in the phenomenological world of each client. As the analytic therapist focuses on the dynamic present, dissociative states representing disconnected characterological structures come more clearly into focus, and with that, the characterological present becomes more relevant than the historical past. As the treatment proceeds, the therapist and eventually the patient become witnesses to the cutting edge of conflict created by split-off parts of the personality. In the midst of these conflicts, it is incumbent on the therapist to maintain an empathic, introspective, and subjective attunement to the process as it unfolds.
Immersion in the phenomenological present creates an evolution in language away from constructs such as ego, guilt, and objectivity toward the more experience-near language of self, shame, and subjectivity. With these metapsychological changes, Horney anticipated contemporary theories of self-psychology, intersubjectivity, and relational schools of thought. She opened up the complex and often painful interplay between the authentic self, the overidealized self, and the self-hating self. The mechanisms that have come to the fore in this paradigm shift are those of disavowal, splitting, dissociation, and fragmentation.
In addition to anxiety, panic, and depression, Horney brought into the center of treatment specific characterological issues such as diffuse self-dissatisfaction, identity, loneliness, confusion, and lack of direction, and a range of addictive disorders. Many of these narcissistic disturbances have become endemic in contemporary life and are now a major focus of treatment. In the psychodynamics she chose to emphasize, Horney anticipated much of contemporary theorizing, although her prescience (for the historical reasons cited) has been decidedly underacknowledged.
As the phenomenological perspective progressively draws a patient into subjectivity and self, it inevitably draws him or her into shame itself. Shame can go by many different names—discomfort, awkwardness, embarrassment, ridicule, stigmatization, loss of face, humiliation. Each term forms a useful continuum for the therapist to help approximate a patient's subjective moment. Shame is an emotion that often cannot be frontally identified, or often even named. As suggested, shame is inhibited by even subtle objectified postures by the therapist. Objectification blocks access to shame because it creates the threat of distance. Conversely, subjective immersion is the gateway through which a patient's shame can reveal itself. As the therapy proceeds and as greater levels of deeper attunement become possible, the patient will increase the growing intensity of self-expression. What started out as a feeling of awkwardness, for example, may step by step enter into issues of embarrassment, disrespect, hurt, and humiliation.
The therapeutic posture Horney emphasized was finding the past in the present rather than the present in the past. This change in posture brought many dimensions of psychic conflict into bold relief. She saw disavowed, dissociated, or unacknowledged shame as connecting the damaged self to the real self, maintaining that symptoms were a means of staying safe and keeping hope alive. Again, this was placing human pathology squarely in the context of human potentiality.
Both Horney's clinical theory and her clinical posture placed her remarkably close to contemporary work with patients with trauma histories and their attendant characterological disturbances. The spectrum of trauma is seen as extending from any rupture in empathic attunement from childhood all the way to grave physical or sexual abuse in childhood or adulthood. On the other hand, incorporating trauma into classical theory has been difficult. Classical theory, as a model based on instinctual drive, gives insufficient attention to relational attunement and cultural bias; thus, theorists and clinicians have found it difficult to find a "rightful place" for trauma and its attendant feelings in Freudian dynamics.
Since Horney emancipated psychoanalytical psychology from its cultural restraints, the field has grown enormously. The paradigm shift has led to an explosion of theoretical and clinical work by many, stressing some of the most vital issues of our day. Each of these innovative works has left behind an outdated, objectified view of psychoanalysis and contributed to a subjectively vibrant fusion of science and humanism.
See also Cyclical Psychodynamics; Experiential Psychotherapy; Feminist Psychoanalytic Therapy; Intersubjective Group Psychotherapy; Phenomenological Therapy; Self Psychology
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text: NASDAQ:SONM - Sonim Technologies Stock Price, Forecast & News Adding Choose a watchlist: Adding You have already added five stocks to your watchlist. Upgrade to MarketBeat Daily Premium to add more stocks to your watchlist. Adding Sonim Technologies Inc Please log in to your account or sign up in order to add this asset to your watchlist. Log In and Add $2.42 +0.12 (+5.23 %) (As of 12/12/2019 02:31 PM ET) Add Compare Today's Range$2.28Now: $2.42▼$2.4450-Day Range$2.14MA: $2.52▼$3.2452-Week Range$2.10Now: $2.42▼$18.26Volume464,962 shsAverage Volume134,901 shsMarket Capitalization$49.17 millionP/E RatioN/ADividend YieldN/ABetaN/A ProfileAnalyst RatingsAdvanced ChartEarningsInsider TradesInstitutional OwnershipHeadlinesSocial Media Share on FacebookShare on TwitterShare on LinkedInShare on RedditShare on StocktwitsPrint this articleShare by Email Sonim Technologies, Inc. provides ruggedized mobile phones and accessories for task workers. It offers ruggedized mobile phones, such as Sonim XP8, Sonim XP5s, and Sonim XP3 based on the Android platform that are capable of attaching to public and private wireless networks; industrial-grade accessories, including remote speaker microphones, multi-bay charging accessories, and in-vehicle hands-free voice communications solutions; and cloud-based software and application services. Sonim Technologies, Inc. sells its mobile phones and accessories primarily to wireless carriers in the United States and Canada. The company was formerly known as NaviSpin.com, Inc. and changed its name to Sonim Technologies, Inc. in December 2001. Sonim Technologies, Inc. was incorporated in 1999 and is headquartered in San Mateo, California. Industry, Sector and Symbol Stock Exchange NASDAQ Industry Telephone & telegraph apparatus Sub-IndustryN/A SectorComputer and Technology Current SymbolNASDAQ:SONM Previous Symbol CUSIPN/A CIKN/A Webhttp://www.sonimtech.com/ Phone650-378-8100Debt Debt-to-Equity Ratio0.34 Current Ratio2.22 Quick Ratio1.38Price-To-Earnings Trailing P/E RatioN/A Forward P/E RatioN/A P/E GrowthN/A Sales & Book Value Annual SalesN/A Price / SalesN/A Cash FlowN/A Price / Cash FlowN/A Book ValueN/A Price / BookN/AProfitability EPS (Most Recent Fiscal Year)N/A Net IncomeN/A Net MarginsN/A Return on EquityN/A Return on AssetsN/AMiscellaneous Employees321 Outstanding Shares20,360,000Market Cap$49.17 million Next Earnings Date1/29/2020 (Estimated) OptionableNot Optionable Receive SONM News and Ratings via Email Sign-up to receive the latest news and ratings for SONM and its competitors with MarketBeat's FREE daily newsletter. NASDAQ:SONM Rates by TradingView Sonim Technologies (NASDAQ:SONM) Frequently Asked Questions What is Sonim Technologies' stock symbol? Sonim Technologies trades on the NASDAQ under the ticker symbol "SONM." How were Sonim Technologies' earnings last quarter? Sonim Technologies Inc (NASDAQ:SONM) posted its earnings results on Wednesday, October, 30th. The company reported ($0.30) earnings per share (EPS) for the quarter, missing the Thomson Reuters' consensus estimate of ($0.14) by $0.16. The company earned $28.85 million during the quarter, compared to the consensus estimate of $31.25 million. View Sonim Technologies' Earnings History. When is Sonim Technologies' next earnings date? Sonim Technologies is scheduled to release their next quarterly earnings announcement on Wednesday, January 29th 2020. View Earnings Estimates for Sonim Technologies. What price target have analysts set for SONM? 6 Wall Street analysts have issued twelve-month price targets for Sonim Technologies' shares. Their forecasts range from $6.00 to $19.00. On average, they anticipate Sonim Technologies' share price to reach $12.17 in the next twelve months. This suggests a possible upside of 403.8% from the stock's current price. View Analyst Price Targets for Sonim Technologies. What is the consensus analysts' recommendation for Sonim Technologies? 6 Wall Street analysts have issued "buy," "hold," and "sell" ratings for Sonim Technologies in the last year. There are currently 1 hold rating and 5 buy ratings for the stock, resulting in a consensus recommendation of "Buy." View Analyst Ratings for Sonim Technologies. Has Sonim Technologies been receiving favorable news coverage? Media coverage about SONM stock has trended very negative on Thursday, InfoTrie reports. InfoTrie identifies negative and positive press coverage by reviewing more than six thousand news and blog sources. The firm ranks coverage of publicly-traded companies on a scale of negative five to five, with scores closest to five being the most favorable. Sonim Technologies earned a news impact score of -3.1 on InfoTrie's scale. They also assigned headlines about the company a news buzz of 0.0 out of 10, meaning that recent press coverage is extremely unlikely to have an effect on the company's share price in the near future. View News Stories for Sonim Technologies. Are investors shorting Sonim Technologies? Sonim Technologies saw a decrease in short interest in the month of November. As of November 29th, there was short interest totalling 204,500 shares, a decrease of 14.9% from the November 14th total of 240,200 shares. Based on an average trading volume of 204,500 shares, the days-to-cover ratio is currently 1.0 days. Approximately 1.6% of the shares of the stock are short sold. View Sonim Technologies' Current Options Chain. Who are some of Sonim Technologies' key competitors? Some companies that are related to Sonim Technologies include DASAN Zhone Solutions (DZSI), Communications Systems (JCS), AltiGen Communications (ATGN), Clearone (CLRO), Zoom Telephonics (ZMTP), Franklin Wireless (FKWL), Westell Technologies (WSTL), One Horizon Group (OHGI), Sunworks (SUNW), MER Telemanagement Solutions (MTSL), Alvarion (ALVRQ), Electronic Tele-Communications (ETCIA), Lattice (LTTC) and Zoom Technologies (ZOOM). What other stocks do shareholders of Sonim Technologies own? Based on aggregate information from My MarketBeat watchlists, some companies that other Sonim Technologies investors own include AT&T (T), Acreage (ACRGF), U.S. Auto Parts Network (PRTS), Vaxart (VXRT), Aurora Cannabis (ACB), Canopy Growth (CGC), GTT Communications (GTT), L Brands (LB), BioCryst Pharmaceuticals (BCRX) and Activision Blizzard (ATVI). Who are Sonim Technologies' key executives? Sonim Technologies' management team includes the folowing people: Mr. Robert J. Plaschke, CEO & Director (Age 55)Mr. James M. Walker, Chief Financial Officer (Age 70)Mr. Peter Liu, Sr. VP of Operations (Age 51)Mr. Joseph T. Hooks, Chief People Officer & Chief Admin. OfficerMr. Charles Becher, Chief Sales & Marketing Officer (Age 51) When did Sonim Technologies IPO? (SONM) raised $50 million in an IPO on Friday, May 10th 2019. The company issued 3,600,000 shares at $13.00-$15.00 per share. Oppenheimer and Lake Street acted as the underwriters for the IPO and National Securities Corporation was co-manager. When did Sonim Technologies' lock-up period expire? Sonim Technologies' lock-up period expired on Wednesday, November 6th. Sonim Technologies had issued 3,571,429 shares in its initial public offering on May 10th. The total size of the offering was $39,285,719 based on an initial share price of $11.00. Shares of the company owned by major shareholders and company insiders are now eligible to be traded as a result of the end of the lock-up period. Who are Sonim Technologies' major shareholders? Sonim Technologies' stock is owned by many different of retail and institutional investors. Top institutional investors include Oppenheimer & Co. Inc. (0.30%) and Millennium Management LLC (0.23%). Company insiders that own Sonim Technologies stock include Brc Partners Opportunity Fund,, John Kneuer and Robert Plaschke. View Institutional Ownership Trends for Sonim Technologies. Which institutional investors are selling Sonim Technologies stock? SONM stock was sold by a variety of institutional investors in the last quarter, including Millennium Management LLC. View Insider Buying and Selling for Sonim Technologies. Which institutional investors are buying Sonim Technologies stock? SONM stock was bought by a variety of institutional investors in the last quarter, including Oppenheimer & Co. Inc.. Company insiders that have bought Sonim Technologies stock in the last two years include Brc Partners Opportunity Fund, and John Kneuer. View Insider Buying and Selling for Sonim Technologies. How do I buy shares of Sonim Technologies? Shares of SONM can be purchased through any online brokerage account. Popular online brokerages with access to the U.S. stock market include Vanguard Brokerage Services, TD Ameritrade, E*TRADE, Robinhood, Fidelity and Charles Schwab. What is Sonim Technologies' stock price today? One share of SONM stock can currently be purchased for approximately $2.42. How big of a company is Sonim Technologies? Sonim Technologies has a market capitalization of $49.17 million. Sonim Technologies employs 321 workers across the globe.View Additional Information About Sonim Technologies. What is Sonim Technologies' official website? The official website for Sonim Technologies is http://www.sonimtech.com/. How can I contact Sonim Technologies? Sonim Technologies' mailing address is 1875 South Grant Street Suite 750, San Mateo CA, 94402. The company can be reached via phone at 650-378-8100 or via email at [email protected] MarketBeat Community Rating for Sonim Technologies (NASDAQ SONM)Community Ranking: 2.3 out of 5 ( )Outperform Votes: 34 (Vote Outperform)Underperform Votes: 41 (Vote Underperform)Total Votes: 75MarketBeat's community ratings are surveys of what our community members think about Sonim Technologies and other stocks. Vote "Outperform" if you believe SONM will outperform the S&P 500 over the long term. Vote "Underperform" if you believe SONM will underperform the S&P 500 over the long term. You may vote once every thirty days. This page was last updated on 12/12/2019 by MarketBeat.com StaffFeatured Article: How is net asset value different from market price?


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ABSOLUTELY STUNNING! So healthy and delicious, it had the lightest consistency. Adding this to our regular monthly fall/winter meals. Thanks!!
Curried Coconut Cauliflower Soup - Lunch Version
Curried Coconut Cauliflower Soup - Lunch Version
Inspired by the tantalizing curries of India this Curried Coconut Cauliflower Soup is a perfect paleo lunch to warm up your afternoon.
- 2 tablespoons Olive Oil
- 1 ½ cups dice Onion
- 1 cup dice Carrot
- 3 cups dice Cauliflower
- 4 cups Vegetable Broth/Stock
- 2 tablespoons Curry Powder
- ¼ teaspoons Thyme, Dried
- ¼ teaspoons Black Pepper
- ¼ teaspoons Salt
- 13 ½ fluid ounces Coconut Milk, Canned
- 1 cup chop Cashews, Raw
Cooking Instructions
Freeze For Later Cooking Day Directions
Make From Frozen Serving Day Directions
Nutrition Facts
- Servings Per Recipe
- 6 Servings
- Serving Size
- about 1 cup Amount Per Serving
- Calories
- 330
- Total Fat
- 27g
- Saturated Fat
- 14g
- Trans Fat
- 0g
- Cholesterol
- 0mg
- Sodium
- 590mg
- Total Carbohydrates
- 18g
- Fiber
- 4g
- Sugar
- 6g
- Protein
- 7g
- WW Freestyle
- 12
- Diabetic Exchanges: 5 Fat
- 0 Fruit
- 0 Milk
- 0 Other Carb
- 0 Starch
- 2 Veg
- 0 Lean Meat
Categoriessoup/stew/chili, wwfreestyle11-12, wwfreestyle11-12, wwfreestyle, kosher, diet, allergen, paleo, whole30, vegetarian, vegan, fall, winter, spring, dairy-free, gluten-free, gluten-free-dairy-free, gaps, low-carb, real-food, egg-free
10 CommentsJoin the discussion
Is the coconut milk in a can, or something like silk coconut milk?
Coconut milk in a can.
WOW! This was so easy and delicious! Thank you so much!
How many quarts does this make?? I'm shopping now and just realized it doesn't say, help!!
Elise, it makes about six 12-ounce servings.
I made this tonight and find it lacks flavor, but smells amazing. Any tips? Did you use a special curry powder?
One thing to check first is that you are using fresh spices. Old spices can effect the flavor of a dish. Another tip, I often add my curry spices during the saute stage since these spices are highly aromatic and heating them brings out the flavor. Just add them for the last few minutes of your saute time and stir to coat, then add the broth. Hope that helps! You can always add more curry powder to taste if you like!
So easy to make and delicious! I left out the cashews, but otherwise made it exactly as directed.
Perfect go to for cooler fall weather, I will be making (and freezing) this one again. Fresh spices are key. I forgot the cashews, but didn't miss them.


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Network effects. They make the tech world spin around, in the pursuit of growth.
Why? Easy: because CAC is halved for every single user that brings another one. Then it becomes a third, if another user is added, and so on.
The key consequence of the network effect is scale. In the time it took you to recruit a user, you can simply plant seeds and some of the branches will take care of themselves.
Upon further study, people have classified these network effects. Not a lot of people, since it's still a young/immature concept — but since it's the gate to a very heavy golden treasure, it happened.
I find it interesting how both Uber and Facebook have network effects, though they're different. Yes, buzzword alert, we're talking about Uber and Facebook.
They're both one of the fastest growing companies we've seen. And not coincidentally, they've gathered users extremely fast — but in different ways.
Facebook scaled as the telephone — the more people use it, the better it becomes.
Uber's situation is the same, but with a caveat: the more people from the opposite side use it, the better it becomes.
In other words, the more drivers you have, the better it is for you, as a rider.
Too many riders? Surge pricing.
Too many drivers? Less profit for each.
Nonetheless, Uber's valuation still uses 11 digits and I wouldn't be surprised if soon enough they'd hit 12 digits (unless the Black Swan event occurs).
Choose your network effect — and choose it wisely.
About Ch Daniel
I run Chagency_, an experiences design agency — we help SaaS CEOs reduce user churn. I write daily on this topic and in similar areas. Here are my best pieces.
If I've helped you, follow me here and reach out: LinkedIn | Twitter | Email | Quora | YouTube
I've also founded an app that went 0-200K users in its 1st year — The Legit Check App. See everything I do here: Chdaniel.com
If you want a more of a personal connection, here's how to have that.


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bringing the pieces together
Brittain Resorts & Hotels is a brand. The roots of the brand go back more than 40 years and three generations in Myrtle Beach. The foundation was laid long before the company was formed with roots beginning in the 1930's at the historic Chesterfield Inn in the heart of Myrtle Beach, S.C. The entire Brittain family worked as a team doing everything from making beds to washing dishes on the busy weekend nights while honing the every changing marketing and guest satisfaction skills paramount to establishing a robust repeat business base.
" Brittain Resorts & Hotels live by one simple principle; we make nothing until our owners do. We approach with the understanding that our pay is based 100% on performance. We must make the phone ring, Internet assessable, and build loyalty. "
digital marketing
Reach highly targeted audiences and gain immediate visibility in search engines through SEO and paid search. High-ROI online advertising will capture attention, drive brand awareness and increase direct bookings. Monitoring the latest trends in booking behaviors allows us to locate and convert the ever-evolving online shopper.
Social Media
Hotel email marketing is still a cornerstone to drive direct response and reinforce your brand. Social marketing has become THE tool to stay engaged with your guests. Guest reviews and social sharing have become the digital "Word of Mouth". Daily customizable campaigns on sites such as Tripadvisor, Facebook (over 1,000,000 fans) and Twitter show the customer we are accessible and listening.
Ongoing optimization and custom reporting ensures our website remains the most profitable distribution channel. Daily testing based on analytical feedback helps us increase conversion and maximize sales on every opportunity. Advanced software tracking allows us to measure the return on investment on every ad campaign in order to spend marketing dollars more effectively.
campaign tracking
increased conversion
ROI accountability
Good Controls and Cash Management.
- Human Resources
- Payroll
- Risk Management
- Accounts Receivable
- Accounts Payable
- P&L Reporting
- Benefits Administration
- Deposit Proofing
- Daily Revenue/Expense Controls
IT Department
System for Accounting, revenue collection, and tools to better control labor.
- IQware System
- DataVision
- Time Clocks
- Guest Internet
- Telephone Contracts
- Guest Surveys
Brittain Resorts & Hotels is able to leverage buying volume to take advantage of free shipping on many items we order, as well as, rebates. We recognize the ability to price bust on any one item however with a holistic approach we consider shipping, rebates/discounts, and item cost into the overall real cost.
Homeowner Relations
Daily involvement is a critical part of our success in having over a 90% retention of all our owners who sign up on our program. We are business partners and go beyond the daily renting, cleaning, and maintaining, to looking farther into the future and planning.
Property Managers
Daily involvement is critical to all successful business ventures. We understand and recognize no one person can do it all and while we practice and encourage the entrepreneurial mentality, we also recognize that we must trust but verify to ensure our managers are walking the walk. More than one set of eyes are checking your unit: Housekeeping, Maintenance, Homeowner Services and Property Managers.


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LOUISVILLE, KY (WAVE) - Louisville Metro Animal Services achieved a no-kill status for time and space on Thursday.
The no-kill status means LMAS didn't euthanize any animals last year due to overcrowding (time and space).
LMAS, the city's only open intake animal shelter, finished 2017 with a 93 percent live release rate — the best in its 52-year history, according to a statement from the Mayor's Press Office. A 90 percent live release rate is the minimum to become a no-kill shelter.
Last year, over 31-hundred dogs and cats were adopted through LMAS.
More animals were returned to their owners in 2017 - and there were 41 percent more adoptions.
"Our city value of compassion absolutely extends to the animals that enrich our lives," Mayor Fischer said in a statement. "That's why I'm so proud that Metro Animal Services has achieved a live release rate above 90 percent, thanks to the hard work of the LMAS team, their partners and volunteers.
Mayor Fischer and LMAS also celebrated the launch and overwhelming success of the Pay It Forward Free Adoptions Program, which they both cited as a primary contributor to the turnaround. Pay It Forward is funded solely through donations, which allows LMAS to waive adoption fees for certain cats and dogs
LMAS Director Ozzy Gibson, who was hired in 2016, was praised by Mayor Fischer for the agency's turnaround.
Key 2017 Animal Services stats:
- Zero animals euthanized for time or space
- 90.8% live release rate for canines
- 93.8% live release rate for felines
- 37% increase in animal returned to owners
- 41% increase in animal adoptions
Of course, there are still lots of animals waiting for their forever homes in WAVE country - head to wave3.com for a slideshow of adoptable dogs and cats.
Copyright 2018 WAVE 3 News. All rights reserved.


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We are a vsmall company with a wide range of skills and are specialist in solving your marking problems. We work closely with local suppliers to give imaginative and cost effective solutions.
Click on the links below to see some of the projects that we are involved with or have completed:
1) Etched Stainless Steel Product Plates Ribcraft Ltd
2) Wooden waymarkers for the Crown Estate
3) Unique sign for A Skills and Enterprise Centre
4) Wooden signs for A College Farm
1. Ribcraft LTD
Ribcraft maufacture a huge range of Rigid Inflatable Boats for leisure, sport and work.
How to display a makers CE plate, one for each type of boat, which reflects the quality of the product in a cost effective way.
The P&S Engraving solution:
The best material for a harsh salt water environment is stainless steel. This can be etched and paint filled to give a superb quality plate which has unrivalled durability. However the process is only really cost effective for large runs. In consultation with the Ribcraft team, we have developed
an elegant solution. Produce a generic high quality etched plate with a blank
space for Laser etching of individual boat's details. In this way we have utilised the economies of scale
of a large production run with a bespoke finishing service.
Problem Solved.
We also produce a range of one off labels in Acrylic laminates, including some safety signs that 'glow in the dark' Only engraving can give the durability required for labelling in extreme conditions.
2. The Crown Estate:
Waymark a range of walking and cycling trails at Nutcombe Bottom in the Dunster Forest, in a sympathetic way that is clear to follow and marked with the Crown Estates distinctive logo. Each walk to
be colour coded. All products to be as 'Green' as possible
The P&S Engraving solution:
Use locally sourced wood from the Local wood shop in Minehead, in this case a sweet chestnut tree
which actually came from the Crown's Dunster Forest at Nutcombe bottom. You can't get more
local than that - total miles travelled by the timber - about 20. The wooden finger is routed with the required lettering, which is painted in white.
This includes a routed circle to take the coloured disc with the walk route. Why white paint? - because as the wood weathers it will become much darker, the white text will remain legible for many years.
The waymarking discs are made from acrylic laminate the most colourfast material on the market.
3. Skills & Enterprise Centre
Design and manufacture a cost effective sign to be fitted in a sympathetic and durable manner on the Cedar cladding of the super new Skills and Enterprise centre at the West Somerset Community College, which reflects the quality of the new learning environment.
The P&S Engraving solution:
Design - call in the experts, who understand signage and the requirements of all media, as well as print.
Signmakers are so often confronted with a design made by graphic designers who think no further than what would look good on a business card and who have no idea what is possible and what the challenges and possibilities of signmaking technology are, and so produce designs which are very difficult
to make look good in a sign. We use
of Minehead, who understand these things.
Together a new design concept was developed which ended with a cost effective sign made of laser cut perspex, which was fitted to the cladding to allow for the natural movement of the wood.
A unique design solution, which met all of our clients criteria.
4. The College Farm
Design and manufacture cost effective signs to be fitted in a sympathetic and durable manner to the new farm buildings, which is on the Exmoor National Park. A natural look is of prime importance.
The P&S Engraving solution:
Cut lettering in thin plywood - allow it to soak in water based green wood preservative (Protec - made in Somerset) Then dry bond the lettering onto simple ply boards and then coat the whole with Danish oil.
A simple maintenance programme will ensure a long life.


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The day of your driving test is certainly stressful for many however it doesn't get to be! By now, you must have received lots of
Honda Accord – one of America's most loved family cars for decades due to its consistent evolution and remarkable execution. And if you're among us
Car accidents are erratic but often happen on the roads of North Hollywood due to the high traffic of vehicles and pedestrians. However, you may
We know that you have already spent a good amount of money on buying the mountain bike because you love the ambience of adventure. But,
If you're a fleet manager, chances are you know from experience how fuel costs can overshadow other operation expenses. Even worse, it can be difficult to
If you are a driver or own such a business that your routine work is to deal with the vehicle and driving them. If you
Although there are many similarities between cleaning tinted windows and normal windows, you should be especially careful with the materials and cleaners used when cleaning


text: Compare Quick view Champion Sports Stopwatch Set Champion Sports MSRP: Now: $51.31 Was: Shock-resistant durability for outdoor activities. Water-resistant for aquatic competitions. Takes measure of the competition up to 1/100 of a second. Lanyard Color(s): Assorted Precision: 1/100 Second Material(s): Plastic Time Format: Military Standard... MSRP: Now: $51.31 Was: Compare Quick view


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All formats/editions
'I'm going to love my baby and give her lots of attention,' Jade said. 'I'll show my mum she's wrong.'Jade, 17, is pregnant, homeless and alone when she's brought to live with Cathy. Jade is desperate to keep her baby, but little more than a child herself, she struggles with the responsibilities her daughter brings.Cathy is worried as soon as Jade arrives: she's never looked after a pregnant teenager before, but none of the mother and baby carers is free, and - seventeen years old, seven months pregnant and homeless - Jade is in a desperate situation.But Jade doesn't want to listen or advice and although her daughter is born safely it isn't long before Jade's in trouble with the police.Cathy knows that Jade loves her daughter with all her heart, but will she be able to get through to Jade in time to make her realise just how much she might lose?
All Formats/Editions
Click the Download button to download a copy of the MARC file.
Enter your FTP details below to send the MARC export file via FTP.
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by Cathy Glass
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318 Trimble Cres, Saskatoon
Fantastic opportunity to own this 2,594 sq ft 2-storey home in the heart of Willowgrove. High end finishes throughout. Hand scraped hardwood flooring in main floor living room, kitchen & dining areas. 9 foot ceilings on main floor and basement. Kitchen features walk-in pantry, custom cabinets and loads of counter space. Upstairs you'll find a grand master suite with a walk-in closet, 5 piece en-suite with jetted tub and deck off the master, along with 2 large bedrooms. The basement boasts a large family area with 7.1 surround sound. A full wet bar, another bedroom, bathroom and a bonus room with rubber flooring suitable for a home gym complete the basement. This home has in-floor heating in the basement and garage as well. The backyard is fully landscaped and includes your own putting green and rear gate access to Genereux Park and children's playground. Only minutes away from schools, shopping, dining and the Forestry Farm. Quick access to public transit with less than a 25 minute commute to the U of S. See the virtual tour by clicking on the film reel at the top of the listing and see the floor plan in Attachments.
Air Filter, Alarm Sys Rented, Air Conditioner (Central), Heat Recovery Ventilation, Humidifier, Natural Gas Bbq Hookup, Sump Pump, Underground Sprinkler, T.V. Mounts
Central Vac Attached, Central Vac Attachments, Satellite Dish, Garage Door Opnr/control(s), Dryer, Dishwasher Built In, Fridge, Microwave Hood Fan, Stove, Vac Power Nozzle, Window Treatment, Washer
Forced Air, Natural Gas, Hot Water, In Floor
Balcony(S), Deck, Fenced, Lawn Back, Lawn Front, Trees/Shrubs
Backs on to Park/Green Space, Corner, Cul-De-Sac, Irregular
The Saskatoon Region Association of REALTORS® (SRAR) IDX Reciprocity listings are displayed in accordance with SRAR's MLS® Data Access Agreement and are copyright of the Saskatoon Region Association of REALTORS®.
The above information is from sources deemed reliable but should not be relied upon without independent verification. The information presented here is for general interest only, no guarantees apply.
MLS®, REALTOR®, and the associated logos are trademarks of The Canadian Real Estate Association.


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The featured performer for this event is Kayla Williams. Kayla had the opportunity to perform for the Canada Winter Games Closing Ceremonies and has the performance filmed by TSN. Come and listen to her songs!
Start Date:
June 11, 2019
End Date: June 11, 2019
Start Time: 11:30 AM
End Time: 1:00 PM
Cost: $Free
Website: Event Website Link
Red Deer Downtown Business Association welcomes three new board members The Red Deer Downtown Business Association is pleased to welcome three new board members.Read More


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30-ft AIRSCREEN Outdoor Movie Package 1
- Actual Size: 35' Wide x 5' Deep x 26' Tall
- Setup Area: 40' Wide x 20' Deep
- Outlets: 2
- $1,299.99
Can comfortably accomodate crowds up to 1,200 people for your next outdoor event.
Over 500sqft of viewable screen (30ft W x 16'9" Tall) to bring your movie experience to the next level.
We promise it will leave a lasting impression on your guests!
Rental Price Includes:
30 Foot AIRSCREEN Rental (30' W x 16'9" Viewable 16:9 Ratio)
High Lumen HD Projector
Blu-ray players and sound mixer
QSC K12 2000 watt speakers
QSC 1000 watt Subwoofer
A microphone
Two event hosts to run the event
Popcorn machine rental can be added at an additional cost.


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Tower/bench scene with Jeannie and Todd.
Thank you, everyone, for your continued support with The Caging at Deadwater Manor. As you know, though Deadwater Manor is fictional, the book is set in the vicinity of my home. So, I thought I'd share a few photos of the area! Here's a sneak peek of one of the scenes in the book!
Tower/bench scene with Jeannie and Todd.
Welcome B2BCyCon Blog Hoppers!!
So excited to be part of the B2B Cyber Conference this year! I'll be participating in the Goodreads Author Showcase, Blog Hop, Genre Tour, Book Expo on April 7-9 and Author Interview on April 26 at 7 pm. I hope you have a chance to check out all the exciting activities going on at B2BCyCon - there are lots of talented authors and giveaways!
Check out my book, The Caging at Deadwater Manor, in the Thriller, Mystery, and Suspense genre. Also visit my booth at the Goodreads Thriller Author Showcase.
I've written a special post below on the background of the book. It was inspired by true events, and this is why...
Novel News
It's Getting Closer!
Hi everyone!
Wow! March 31st is approaching fast! I'm getting everything ready for the book release and preparing the final finishes to the book. Could you help me spread the word? If so, here are some ideas:
Have a good weekend! --Sandie
Like Thrillers? Check out this new book by the talented author, Jen Ponce, coming March 1!
Book Release Date Announced!
It's almost here - finally! The Caging at Deadwater Manor will be released on March 31, 2017!
I have hired a book promoter to help me get this book noticed. Suzanne Moore is a specialist with social media marketing and the Amazon ranking system. The idea is to gain as much exposure as possible prior to the release date and sell as many ebooks as possible on March 31. This will move my book up the ranks on Amazon who will then help me with promotions as well. Plus, if the book ranks high enough, this will be a great selling point for future books.
What's going on: ALOT!
We've already started book promotions as follows:
Thank you for all the support from my virtual team and others!
Have a good week. --Sandie
Happy New Year!
Happy New Year, everyone! I hope this year brings much happiness and success to you. I'm looking forward to an exciting 2017 with launching two books and finishing up my third novel. This will come with lots of outreach and promotions which I'm excited to learn and share with you.
The Caging at Deadwater Manor has now been signed over to me from my former publisher (I decided to leave them), so now I own both the book and the book cover. Waiting for this delayed the December release, but it will give me time to prepare for the upcoming release in March 2017. I'm currently looking at book promotion options, blog hops and other ways to get the word out. As soon as I have an exact date of release, I'll let you know.
My second book is a young adult historical time travel which I describe on my home page. This was actually the first book I wrote and I've held back publishing it due to the Irish Gaelic that I included, requiring additional editing time. This will be a series titled, "Time Lands," and is about a teenage girl from today who meets a guy from 1849 Ireland who's living through the Great Irish Hunger. I plan on having the main characters, Carly Matthews and Liam Healy, explore a different time period and history for each novel, all the while trying to evade the pursuit of Liam's old landlord who wants nothing more than to bring her "slave" back to her time. The historical settings for each novel in the upcoming series will be unusual ones that you don't hear about too much in school. I can't wait to bring this series to you and for you to join Carly and Liam on their adventures back through time. This book will be released in late 2017.
In the meantime, I'm currently writing a third novel titled, "Vision's Edge." This is another psychological thriller about a young man who is tortured by his past. I can't reveal much about the book for now, but I can say that he has a peculiar way of handling his pain.
Again, I hope you have a wonderful year ahead. Thank you for following my blog and watching for my upcoming book release!
Take care,
Hi Friends!
Since becoming an Indie author, I've been waiting for my official release from the publisher which should be coming soon and the back of the book cover which the artist is currently working on. In the meantime, I've completed a final read through and uploaded the final version to CreateSpace who will facilitate the softcover book and Kindle Direct Publishing (KDP) for distribution as an eBook. I'll be looking at Ingram Spark, Smashwords and Draft2Digital for non-Amazon publishing, but I need to learn more about this. In the meantime, I'm setting up the business information on Createspace and KDP. Until I hear from my former publisher, I'm in a holding pattern. I'm hoping to release the book on December 15, and I'll be sending out an announcement when it's ready. If you're interested in the announcement, add your email for my newsletter on the right side of this page. The release is getting closer!!
As you can imagine, seeing the book cover for The Caging at Deadwater Manor can conjure up memories of experiences or stories of old psychiatric hospitals or hauntings. My employer recently announced my upcoming book release on their newsletter, and I've had several coworkers stop by my office to share their experiences with me -- several of which have given me chills.
One such experience came from Nick Makris who grew up near Cedar Grove, New Jersey, home of the infamous psychiatric hospital named the Essex County Hospital Center (aka The Overbrook, sanatorium, asylum, etc.). The hospital opened in 1896 and was used to treat tuberculous and patients with mental illness. Nick remembers riding his bicycle several miles and seeing his grandfather who worked as a barber in the hospital when he was young. He later visited the hospital after it was abandoned and took pictures as part of a photography class -- forgotten photos that have been sitting in a shoebox until today. He gave me permission to use the photos to help promote my book, so I thought I'd share them as a blog post since they are right in line with the theme of my book. The pictures have an eery feel since Nick tried out different photography techniques during this visit back in 1993. Thank you, Nick!
Coincidentally, another coworker viewed the photos and mentioned that she had heard all sorts of stories about the patients and treatments at the hospital from a previous professor. She could barely look at the photos.
In my last newsletter, I asked which photo was from an actual psychiatric hospital in my latest trailer. If you guessed the first picture in the slideshow below - you were right!
How about you? Would you visit an old, abandoned psychiatric hospital?
Here are a view more internet sites I found about the hospital:
Both books are available in US & Internationally.
Sandie Will is an author who has released a new psychological thriller titled, The Takings. Sandie is the author of the award-winning Amazon #1 Bestseller The Caging at Deadwater Manor.
She can be found on Twitter as @SandieWillBooks and @RockHeadScience, Instagram @sandie_will, as well as her Facebook page at Sandie Will, Author.
"Enthusiasm with a scientist's rigor and a dollop of fun." --Rachel Stirling @Stirlingwriter
"Okay Twitter, stop distracting me. And YouTube, don't get any ideas..."--@brandi_evans
October 2019


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