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The story of a painting, the analysis that everyone can do within himself in his contemplation and the inner motion that can arise inevitably bind to the reasons linked to the author and his personal experience. In front of the work of Giorgio De Chirico one remains always amazed if only because the normal consciousness of the impassibility that exists in everyone is affected, the immobility that becomes universal and shows us its exact opposite, the mental dynamism of an instant.Understanding Giorgio De Chirico means an act of faith towards a permanent classicism that pervades in a new language the road to the memory of an ever-evolving Western world. The metaphysics that launches G. De Chirico in the figurative cosmos is the apotheosis of silence, it is the enjoyment of a momentary stasis that preludes to an early sensitivity, that of seeing forms as monuments whose meaning is radical, without emphasis, immutable and imperishable, it is other but not significant for what we observe, it is enigma.Giorgio De Chirico leaves us with a dialectical sphinx or an admonitory warning from Delphi that they can go to perturb daily life through sudden sensations, the humanity that he paints is not to say anything, there is only, and simply in his own existence , there is a short representative circle, a yearning for transcendence.
We remain disoriented, we enter into a vortex of space / time suspension that brings us back to the level of metaphysics, of a reality that goes beyond and which inspires the paths of the continuous search for truth.
Knowledge is in the essence of things and intelligence is in its own awareness, in its self-certification that allows it to learn the universal things, the things in which, as in the metaphysics of G. De Chirico, have subject and object coincide.
A beautiful intuition of the reality that carries out the mystery is given to us by the artist in one of his writings when he recounts the experience that led him to paint the work The Enigma of an Autumn Afternoon:
"…, I will now say how I had the revelation of a painting that I exhibited this year at the Salon d'Automne and whose title is: The Enigma of an Autumn Afternoon During a clear autumn afternoon I was sitting on a bench in the middle of Piazza Santa Croce in Florence It was certainly not the first time I saw this square, I had just come out of a long and painful intestinal disease and I was in a state of almost morbid sensitivity. to the marble of the buildings and fountains, it seemed to me convalescent: in the middle of the square stands a statue representing Dante wrapped in a long cloak, which clasps his work against his body and inclines his thoughtful head to the ground. The statue is in white marble, but the weather gave it a gray tint, very pleasant to behold.The autumn sun, lukewarm and without love illuminated the statue and the facade of the temple.I had the strange impression of seeing all those things for the first time composition of the picture appeared to my spirit; and every time I look at this painting I relive that moment. A moment, however, that is an enigma for me, because it is inexplicable. Therefore I like to call enigma also the work that derives from it. ".
Nietzsche, Schopenhauer and Eraclito are the reference point of G. De Chirico for the recovery of classicism, in the works there is a total confluence of philosophical quotations that become pictorial visions.
The poetic suggestion of the ancient mediterrranean culture is lasting in the work of G. De Chirico. It shows the instinct of man towards nature and the rational process stripped of illusions to deepen the perception of reality leaving to highlight the incomprehensibility.
He wrote: "We who know the signs of the metaphysical alphabet know what joys and what pains are enclosed within a portico, the corner of a street or even in a room, on the surface of a table, between the sides of a The limitations of these signs constitute for us a kind of moral and aesthetic code of representations and, moreover, with the light we create a new metaphysical psychology of things in painting: the absolute consciousness of the space that must occupy an object in a frame and of the space that divides objects between them establishes a new astronomy of things attached to the planet by the fatal law of gravity: meticulously careful and prudently weighed use of surfaces and volumes constitutes canons of metaphysical aesthetics ".
So here is how the knowledge of the world and its sensory application involves us in an intellectual step of great depth to open to the thought, to the mind, an aesthetic visibility that offers immortal concepts, concepts that can bring back even past suggestions, memories, signs intangibles that reshape our life.
In G. De Chirico there is a deep oneiric involvement as a metaphorical mythological and heroic syntax that lead us to understand his creative stimuli and to dwell on the difference between the images produced by the imagination and those produced by the dream. The images of the fantasy are accompanied by their arbitrariness, while those of the dream are true and real and possess an objective thickness of things and reality. G. De Chirico is the artist of the mystery, the one that puts before us the concerns of the fear of the unknown. The human condition is reflected in a clear existential reflection, the purity of time is given by what remains immobile, from that archaic sense that will always be found in the search for the classic revisited with a contemporary perspective, the mystery is the key element that holds in life the play of mirrors in which mythology and modernity are reflected.
G. De Chirico is an intellectual of his time who maintains important relationships with writers and artists of the early twentieth century, he will give great impetus to the Italian culture recognized in the world and will be a point of reference for the avant-gardes, will open the way to surrealism.
The metaphysics of G. De Chirico is a journey in which we find ourselves defending the path that our intellect makes in the face of riddles and questions and it is like navigating the karstic river of the mind to reach the sea of immortality, we find ourselves to mirror oneself in the dream of one's own conscience so as to recognize the value and the thickness of the soul in signs that alternate between amazement and perplexity, it is an adventure moved between aesthetics and apparent immobility.


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Apple Galette
I grew up on an apple orchard, so I know my apples! And this time of year is the absolute BEST for fresh, crisp, juicy, flavorful apples. (None of that mushy mealy stuff!) The farmers markets are brimming with them right now, and lots of orchards offer picking. This dish is a more savory version of my recent apple and honey galette, so you can see the full recipe there. But basically you just spread slices of brie on pie dough (1 small wedge?), layer with apple slices (1-2 apples?), then sprinkle with herbs de provence, olive oil and salt before baking for about 20 min at 350. You can substitute brie with any soft cheese and other herbs like rosemary or thyme as well.
By Erin Gleeson for The Forest Feast
Chard Tart
This Chard Tart could also be considered a free form quiche or galette. No matter what you call it, it's pretty great for breakfast, lunch or dinner! Slice the chard thinly and throw those stalks right in the mix as well (they are so pretty!). If you like your shallots (or you could use onion) more caramelized, you can cook those first (on medium) and throw the chard in for the last few minutes. Make your own dough or buy some from the store. I used whole wheat pizza dough, but for something a little richer, you could use pie crust. Enjoy!
By Erin Gleeson for The Forest Feast
Butternut Apple Tart
I know fall is here when my CSA starts to brim with apples and squash. This savory tart is very comforting when the weather starts to cool. I used a pre-made pie crust, but you can certainly make your own. It works for breakfast, lunch or dinner and is great with an herb side salad. This recipe concludes my guest recipe series at Anthology Magazine, please click here for more pictures and details. Bon Appetit!
By Erin Gleeson for The Forest Feast
Peach Ricotta Tart
I was so happy to have this recipe featured yesterday on a website I love, A Cup of Jo, as "The Best Peach Tart You'll Ever Have"!. This peach tart (technically a galette) is simple, pretty and delicious! Just roll out one store bought pie crust (or make your own, if you fancy). I used the kind that comes rolled in the long red Pillsbury box in the refrigerated section. Spread a thin layer of ricotta cheese over the dough, leaving about a 1 inch border. Sprinkle the ricotta with a bit of cinnamon and sugar, then layer thinly sliced peaches over the cheese. Fold and pinch the corners over to make a little crust, then bake for 20 minutes or so on a cookie sheet at 350 degrees until browned. Before serving, I like to drizzle a little good olive oil and add a pinch of coarse sea salt to each slice.
You'll need: 1 (pre-made) crust, 2 to 3 peaches (no need to peel), 1 small tub ricotta, cinnamon, sugar, olive oil, sea salt. Bon appetit!
by Erin Gleeson for The Forest Feast


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Millions of lymphocytes enter and exit mammal lymph nodes (LNs) each day, accessing the parenchyma via high endothelial venules (HEVs) and egressing via lymphatics. Despite this high rate of cellular flux and the many entry and exit sites within a given LN, the number of lymphocytes present in a resting LN is extraordinary stable over time, raising the question of how this steady-state is maintained. Here we have examined the anatomic details of lymphocyte movement in HEVs, finding that HEVs create pockets within which lymphocytes reside for several minutes before entering the LN proper. The function of these pockets was revealed in experiments performed under conditions in which lymphocyte egress from the LN was compromised by any of several approaches. Under such conditions, the HEVs pockets behaved as "waiting areas" in which lymphocytes were held until space was made available to them for entry into the parenchyma. Thus, rather than being simple entry ports, HEVs act as gatekeepers able to stack, hold and grant lymphocytes access to LN parenchyma in proportion to the rate of lymphocyte egress from the LN, enabling the LN to maintain a constant steady-state cellularity while supporting the extensive cellular trafficking necessary for repertoire scanning.
Despite the constant entry and exit of lymphocytes in the noninflamed state, LNs manage to maintain their cellularity over time, indicating the existence of tightly regulated control mechanisms that balance access and egress of cells.1 Naive lymphocytes enter LNs via HEVs and exit via lymphatic vessels.2 The number of HEVs and lymphatic exit sites in an individual LN is quite high, with these sites showing substantial topographic separation throughout the LN. This raises the question of how a LN manages lymphocyte traffic at these many dispersed sites to maintain homeostasis, a critical issue because LNs provide key survival signals such as IL-7 and BAFF (B-cell activating factor) to T and B cells, respectively.3,4 As a resting LN is believed to secrete defined amounts of such survival signals, increases in lymphocyte number beyond that properly supported by the survival factors available could lead to cell death and repertoire contraction. Likewise, too few cells would limit the number of specific cells available at any time for antigen-driven activation, diminishing the efficiency of immune responses. Interestingly, mice grafted with multiple thymi do not harbor massively enlarged LNs despite high numbers of circulating lymphocytes, suggesting that LNs auto-regulate the number of cells they house and nourish.5,6 Altogether, these observations suggest that LNs adapt lymphocyte entry and exit fluxes to constantly host a fixed number of lymphocytes under steady-state conditions. In this study, we investigate this possibility and demonstrate that, in addition of being passive entry doors for lymphocytes, HEVs are traffic control checkpoints able to create "waiting areas" in which lymphocytes accumulate and are held until space is made available to them in the parenchyma as a consequence of lymphocytes egress. This simple scheme provides an elegant way for the LN to maintain a constant cell number while supporting the high flux of cells needed for effective utilization of the adaptive immune repertoire.
C57BL/6, RAG2°/°, actin-CFP,7 Ubiquitin-Cre EsR18 , and C57BL/6 ubiquitin-GFP mice were purchased from The Jackson Laboratory and maintained in the CIML and/or Skirball animal facilities. Ubiquitin-Cre EsR1 were crossed with S1P1flox/− mice kindly provided by R. L. Proia.9 For the generation of chimeras, C57BL/6 RAG2°/° ubiquitin-GFP mice were γ-irradiated (twice with 500 rads) from a cesium source and were reconstituted with various mixtures of bone marrow cells indicated in the main text (minimum of 2 × 106 bone marrow cells per mouse). Chimeras were used at 8 weeks after reconstitution. All procedures performed on animals in this study have been approved by the ethical committee on animal research of Marseille (N°1-03112009, France).
RA3-6B2 antibody specific for B220, 17A2 specific for the CD3 complex, Meca-79 specific for PNAd, 3E2 antibody specific for ICAM-1, MEL-14 specific for CD62L were purchased from BD Biosciences Pharmingen. ERTR-7 and Desmin antibodies were purchased from Acris Antibodies. These antibodies were visualized by direct coupling to Pacific blue, allophycocyanin, Alexa Fluor–488, –568, –647, or through the use of Alexa Fluor–488, –568, –647 or -biotin coupled secondary antibodies. Nuclear staining was performed with Sytox 63 (Invitrogen).
LNs were harvested and fixed in a 0.05M phosphate buffer containing 0.1M L-lysine (pH 7.4), 2 mg/mL NaIO4, and 10 mg/mL paraformaldehyde (PLP) for 12 hours, then washed in phosphate buffer and dehydrated in 30% sucrose in phosphate buffer. LNs were snap frozen in Tissue-Tek (Sakura Finetek). Twenty-micrometre frozen sections were cut and then stained with the indicated antibodies as previously described.10 Immunofluorescence confocal microscopy was performed with a Leica SP5 confocal microscope. Separate images were collected for each fluorochrome and overlaid to obtain a multicolor image. Final image processing was performed with Imaris Version 7.2.3 software (Bitplane) and Adobe Photoshop.
Homing assay
Total cells were purified from the LNs and spleens of WT mice and stained with either CMFDA (0.5μM) or CMTMR (2μM; Invitrogen) at 37°C for 15 minutes. The indicated numbers of cells were adoptively transferred intravenously. One hour later, blood, auricular and inguinal LNs were harvested.
Induction of lymphocyte sequestration in LNs on FTY720 and SEW-2871 treatment
When indicated, mice received either 100 μg of FTY720 (Cayman Chemical Company) intraperitoneally or 1.2 mg SEW-2871 (Cayman Chemical Company) gavage. Experiments were conducted 36 (FTY-720) or 8 (SEW-2871) hours later, at the peak of lymphopenia.
Tamoxifen treatment of Ubi-cre ESR1 × S1P1flox/− chimera
Animals were treated with 2 mg of 4-hydroxy-tamoxifen intraperitoneally (Sigma-Aldrich) for 3 consecutive days. Mice were used 9 days after the first injection of tamoxifen.
Quantification of lymphocyte densities inside and outside LN HEVs
Immunofluorescence images were segmented into HEVs and the rest of the LN according to PNAd staining. As PNAd is present on the luminal surface of HEV ECs, HEVs areas were defined as 20 μm concentric rings centered on PNAd labeled structures. The numbers of pixels of each area as well as the numbers of adoptively transferred lymphocytes (CMTMR+) present in each area were measured using ImageJ Version 1.44R software (National Institutes of Health). For each LN slice, the densities of CMTMR+ lymphocytes inside HEVs were divided by the densities of CMTMR+ lymphocytes outside HEVs. A small ratio reflects the cells ability to efficiently gain access to the LN parenchyma while an elevated ratio reflects a delay in this process. For each condition, a minimum of 3 different LNs (> 3 different sections per LN) and 1000 cells were counted per mouse. P values were calculated using 2-tailed unpaired t test.
Morphometric analysis of HEV
The height of the endothelium of HEVs was measured in LN sections obtained from RAG-2°/°ubiquitin-GFP mice using a protocol previously described.11 In brief, the outer contour length of GFP+ HEVs and the area covered by GFP+ HEV ECs (including the HEV pockets) were measured with ImageJ software (National Institutes of Health). Endothelium-height was calculated as HEV-surface-area divided by HEV-contour-length, and expressed in arbitrary units.
Electron microscopy
PLP-fixed LNs were rinsed in 0.1M phosphate buffer and postfixed for 1 hour in OsO4. LNs were then rinsed in water, dehydrated through graded concentrations of acetone (50, 70, 95, 100% pure, 3 times) before incubation for several hours in a 1:1 vol/vol acetone-Epon mixture. LNs were then incubated overnight in pure Epon before final embedding in Epon. Eighty millimeter thick LN sections were generated using a LEICA Ultracut S ultramicrotome. Sections were stained with uranyl acetate followed by lead citrate and were imaged using a CM12 Philips microscope.
PLP-fixed LNs were rinsed in 0.1M phosphate buffer and immersed for 1 hour in a 20% glycerol solution. LNs were then frozen in liquid nitrogen and freeze-cracked before being dehydrated through graded concentrations of ethanol. LNs were desiccated with hexamethyldisilazane and affixed on aluminum stubs with adhesive, coated with gold-palladium, and examined in a SEM (JEOL 6700F, Japan) microscope with an accelerating voltage of 3 kV.
2-P microscopy of lymphocytes immigration in HEVs.
The right popliteal LN of anesthetized ubiquitin-RAG2°/°GFP mice reconstituted with actin-CFP bone marrow cells (2.5% isofluorane in an air/O2 mix) was surgically exposed and imaged with a Zeiss LSM-7 MP system fitted with a 20× water immersion lens (NA = 1.0, Plan-Apochromat, Zeiss). The 2P laser was a Spectra-physics Maï-taï Deepsee tuned to 860 nM. Singles slices of shallow HEVs were imaged between 50-120μM below the capsule and repeated every 4 seconds to create 3D datasets (x, y, and time) that were then processed with Imaris software (Bitplane) and Adobe After Effects (Adobe).
Lymphocytes accumulate in "pockets" below endothelial cells
As the entry site for circulating blood lymphocytes, we hypothesized that HEVs may play a key role in regulating resting LNs cellularity by coupling lymphocyte entry with the rate of exit across lymphatic endothelium. To test this hypothesis, we first generated chimeric mice in which HEVs (and other stromal cells) express the green fluorescent protein (GFP). RAG2°/° ubiquitin promoter-GFP transgenic animals were irradiated and reconstituted with wild-type bone marrow cells. Chimeric LNs were harvested, stained for peripheral node addressin (PNAd) and nuclei (Figure 1A) or for CD3 and B220 (Figure 1B), then analyzed by confocal microscopy. As expected and previously observed, all PNAd+ HEVs were GFP+ and harbored typical cobblestone endothelial shapes with numerous embedded lymphocytes.12 Interestingly, a close examination revealed that T and B cells were frequently packed together into HEV pockets and that these structures were able to house up to 4-5 lymphocytes (Figure 1).13,14 Using electron microscopy, we confirmed these results and observed that lymphocytes nested in these pockets were separated from the HEV lumen via a very thin membrane of the HEV endothelial cell (EC; Figure 1C). To determine whether these cells were localized between 2 ECs or within a true pocket formed by single ECs, we took advantage of the asymmetry of HEV ECs. HEVs ECs express molecules such as intercellular adhesion molecule-1 (ICAM-1) on their luminal/lateral face (Figure 2A).15 If the lymphocytes embedded in these pockets were localized between 2 ECs, one would expect them to be entirely surrounded by the ICAM-1 staining of the 2 adjacent ECs membranes (Figure 2A right panel). On the other hand, if the lymphocytes present in these pockets were held by a single EC, the inner membrane of this EC should surround them and hence not be positive for ICAM-1 (Figure 2A left panel). Using such strategy, we determined that lymphocytes nested in these pockets were not localized between 2 HEV ECs (Figure 2B). To distinguish between a situation in which lymphocytes are retained within ECs (emperipolesis) and a situation in which they are nested below ECs, we stained the chimeric LN sections with anti-Desmin and ERTR-7, 2 Abs, respectively specific for myofibroblasts and the conduit system secreted and ensheathed by these cells. Confocal images of HEVs revealed that lymphocytes nested in HEV pockets were localized between the membrane of GFP+ Desmin− EC and the membrane of the GFP+ Desmin+ myofibroblasts that ensheath the ERTR-7 conduit system. Altogether, these results suggest that lymphocytes nested in lymphocytes pockets do not accumulate within ECs but below them (Figure 2C).
HEVs pockets dynamically modulate HEV shape
HEVs are characterized by cuboidal cells as opposed to the typical flat endothelial cells found in regular venules.13,14 To determine whether this shape is an inherent property of the HEV EC themselves or if it arises as a result of the presence of lymphocytes in these pockets, we treated chimeric mice with an anti-CD62L blocking antibody for 1 hour (Figure 3). Under these conditions, lymphocyte rolling on HEVs—and hence LN homing—is blocked.16 On such treatment, lymphocyte pockets in HEVs disappeared and HEVs concomitantly flattened (Figure 3A). Morphometric analysis demonstrated that the height of LN HEV decreased on anti-CD62L treatment, representing about 68% of the height of untreated HEVs (Figure 3B). Therefore, these data suggest that the typical cobblestone shape of HEV ECs is not intrinsic but rather results from the continuous and transient accumulation of lymphocytes within these pockets. These observations also demonstrate that these holding sites are not preformed, rigid hollow caverns within which lymphocytes accumulate, but rather spaces created by the accumulation of trafficking lymphocytes that have not yet passed into the perivascular channel (PVC) on their way into the LN parenchyma. In agreement with this concept, we never observed HEVs in which pockets were free of lymphocytes.
If HEV pockets are not rigid but adaptable structures, we reasoned that they should be highly dynamic structures continuously altered in size and location by lymphocyte migration from blood to LN parenchyma. To appreciate such dynamics, we irradiated RAG2°/° ubiquitin-GFP mice and reconstituted them with actin-CFP bone marrow cells, allowing us to image the immigration of endogenous CFP+ lymphocytes through the GFP+ HEVs. Reconstituted mice were anesthetized and their popliteal LN surgically exposed for 2-Photon (2P) imaging. Because the HEV EC membranes forming these pockets are ∼ 100 nm thick (Figure 1C) and highly motile in X, Y, and Z directions, dynamic imaging of entire HEV pockets was not possible. Therefore, we examined highly resolved single "slices" of shallow HEVs to appreciate the overall dynamics of HEV ECs. In these videos, the continuous ballet of CFP+ cells entering the GFP+ HEVs revealed that HEV pockets are highly dynamic structures moving in many directions as a result of lymphocyte displacement (supplemental Video 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article).
HEVs adapt lymphocyte entry to lymphocyte egress in the LN
If HEVs are the site of adjustment of lymphocyte entry into the LN to maintain constant cell number in the face of ongoing egress, one would expect them to limit LN access to blood-circulating lymphocytes if the cellularity of this LN is maximal, whereas when the population of a resting LN decreases as a result of lymphocytes egress, HEVs should immediately counterbalance this cellular loss by allowing the entrance of blood circulating lymphocytes. The capacity of HEV EC to generate transient collections of trafficking lymphocytes would provide an elegant solution to this adjustment requirement—lymphocytes could be "stored" within the EC, being held there when the LN was "full" and released if the population declined as lymphocytes exited the LNs. Such a system makes sense in LNs that are densely packed organs with an only slowly changeable volume that imposes space limitations. If this concept is correct, blood circulating lymphocytes should less efficiently enter the parenchyma of a LN in which lymphocyte egress is blocked and in which cellularity would be maintained at a maximum. As a first attempt to test this hypothesis, we treated wild type (WT) mice with FTY-720 and SEW-2871, 2 drugs known to interfere with the sphingosine-1-phosphate (S1P) pathway involved in lymphocytes egress from lymphoid organs.17,18 Such treatment induces the sequestration of lymphocytes in SLOs and leads to a concomitant lymphopenia (supplemental Figure 1A). Drug-treated and control animals were injected intravenously with WT labeled lymphocytes and euthanized 1 hour later. The LNs were sectioned, stained for PNAd expression, and the ratio of labeled lymphocyte densities in HEVs and LN parenchyma calculated for each condition. The results showed that many more of the transferred lymphocytes in FTY-720 and SEW-2871 treated mice remained in the HEVs during the homing assay compared with control animals, indicating a reduced capacity to access the LN parenchyma (Figure 4A-B and supplemental Figure 1C). These results, while consistent with the general expectations of our model, are not black and white. However, drug-induced lymphopenia is never total and some cells still egress the LNs of treated mice, potentially allowing the entry of the same number of cells according to our hypothesis. In a control animal, the cohort of labeled cells injected in the mouse represents a small percentage of the endogenous blood-circulating lymphocyte population. Therefore, many more endogenous "black" cells than labeled transferred cells enter the untreated LNs during the 1 hour homing assay. On the contrary, in drug-treated animals, the great majority of endogenous cells is sequestered within SLOs and therefore no longer circulates in the blood (supplemental Figure 1A). In addition, a higher fraction of blood circulating T cells is composed of effector/memory CD62Llo cells that no longer compete with the transferred cells in the LN homing assay (supplemental Figure 1B). As a consequence, if the HEVs of control and treated animals were supporting the same influx of cells, many more transferred cells should have accessed the LN parenchyma of treated mice during the 1 hour homing assay. Despite this, we observed that lymphocytes transferred in drug-treated mice were delayed in their capacity to access the LN parenchyma.
Because ECs express many S1P receptors, including S1P1, these drugs are not perfect tools for examining the issue of cellular trafficking.19 Unfortunately, S1P1°/° mice are not viable and using their fetal livers as a source of progenitors fails to generate chimeric mice with normal levels of lymphocytes.17,20 We therefore generated a mouse in which S1P1 deletion can be conditionally induced just in lymphocytes. Ubiquitin-Cre ESR1 mice were crossed to S1P1flox/− mice. In the former mice, the cre enzyme is released in the nucleus of all cells on tamoxifen injection while in the latter, all cells possess a functional S1P1 allele flanked by 2 lox P sites while the other allele is not functional. In these double transgenic mice, all cells are S1P1 sufficient but are expected to genetically lose S1P1 expression on tamoxifen injection. Because we wanted to generate mice in which only lymphocytes would show loss of S1P1 expression, we irradiated RAG 2°/° ubiquitin-GFP mice and reconstituted them with either WT bone marrow or a mixture of bone marrow cells isolated from RAG 2°/°WT (80%) and ubiquitin-Cre EsR1-S1P1flox/− (20%). These mice will be referred to as S1P1flox/− chimeras. In these chimeric mice, all cells should be S1P1 sufficient before tamoxifen injection but only lymphocytes (and 20% of the remaining hematopoietic cells) would become S1P1 deficient on tamoxifen injection. Reconstituted chimeras were treated or not with tamoxifen and 1 week later, their lymphopenia was evaluated as a result of lymphocytes sequestration in SLOs (supplemental Figure 2). In tamoxifen-treated S1P1flox/− chimeras, we observed a 70% reduction of blood lymphocytes, indicating that S1P1 deficiency on lymphocytes is sufficient to induce their sequestration in LNs. We then adoptively transferred a cohort of labeled WT lymphocytes in the various groups of mice and after 1 hour stained LNs sections for PNAd expression (Figure 5A-B). The data show that lymphocytes accessed the LN parenchyma of untreated S1P1flox/− chimeras and WT chimeras treated with tamoxifen equally. In contrast, in tamoxifen-treated S1P1flox/− chimeras, we observed that the lymphocytes were impaired in this process, indicating that lymphocyte sequestration in LNs controls the influx of blood circulating lymphocytes. We then focused our attention on the GFP+ PNAd+ HEVs of these different groups of mice, wishing to investigate if the lymphocytes were specifically held in the LN HEV pockets of S1P1flox/− chimeras treated with tamoxifen. As presented in Figure 5A and C, most transferred lymphocytes had already left the HEVs of controlled LNs during the 1 hour homing assay. On the contrary, HEVs of the tamoxifen-treated S1P1flox/− chimera contained numerous labeled lymphocytes confined to these pockets, indicating that these structures that only transiently hold lymphocytes in a normal situation were still occupied by lymphocytes in overloaded LNs.
Overall, these data suggest that HEVs are more than passive transfer points for lymphocytes from blood to LN parenchyma. By accommodating lymphocytes in pockets where they can be held outside of the PVC until needed to replace exiting lymphocytes, HEVs behave as traffic control checkpoints that flexibly adapt to the needs of the resting LN as it seeks to balance lymphocyte entry and exit rates. This in turn allows the LN to constantly function at its maximal capacity at steady state.
Given the extreme cellular density of a LN, one could wonder how the space freed by cells leaving in the medulla would immediately be available to cells present in HEVs located hundreds microns away. Importantly, lymphocytes do not physically exit the parenchyma from LN medullary sinuses but from thinner cortical sinuses located nearby HEVs.21-23 Therefore, the juxtaposition of entry and exit sites would confine the regulation of entry/exit fluxes to very restricted regions of LNs. By itself, this juxtaposition is not sufficient to explain how the cellular density of the parenchyma is constantly sensed by the ECs and/or the nested lymphocytes. However, when lymphocytes exit HEV pockets, they enter the PVC and adapt a typical elongated shape likely imposed by the small diameter of the PVC.24 Lymphocytes further progress into this narrow corridor until they find an exit point (flap) formed by the membranes of 2 adjacent FRCs through which they squeeze out in the parenchyma.12 In a fully loaded LN, the cellular pressure in the parenchyma may narrow the diameter of the PVC and concomitantly increase the resistance of the exit flaps. In this situation, the lymphocytes would be retained for a longer period of time in the pockets until lymphocytes exit in the cortical sinuses and release some pressure on the flaps and the PVC.
While hypothetical, this model resolves another logistical issue. When a few lymphocytes exit the parenchyma via a given cortical sinus, our model suggests that the nearby HEVs should counterbalance this cellular loss. As an HEV is formed by hundreds of ECs able to retain lymphocytes, how can each of these ECs know the number of cells they should individually release from their pockets? As ECs constantly replace the lymphocyte content of the underlying PVC, it is likely that any lymphocyte exiting the PVC would be immediately replaced by lymphocytes nested in the closest EC sitting on top of this portion of the PVC, thus linking local pressure relief to trafficking and flux through the HEV pockets.
One question that arises from our observations is how lymphocytes nested in HEV pockets exit from these structures to access the PVC. To date, the most important directional cues known to attract and retain naive lymphocytes are chemokines such as CCL21 or CXCL13.25-29 Interestingly, in 1976, Anderson et al observed that on a subcutaneous injection of horseradish peroxidase, this small tracer "crossed the reticular sheath, penetrated spaces between endothelial cells where it surrounded emigrating lymphocytes, and then entered the venular lumen."13 In 2000, the same group described the function of the conduit system and demonstrated that this network of reticular fibers was involved in the transport of lymph-borne chemokines to the abluminal and luminal surfaces of HEVs.30 Altogether, these results suggest that lymph-borne chemokines are transported from the conduit system to the basal membrane of the HEV before their presentation on the luminal side of the HEV, possibly creating a local gradient of chemokines that lymphocytes nested in the HEV pockets may sense to find the exit site toward the PVC.
One question that still animates numerous debates in the field is the exact mode of lymphocyte migration across HEV ECs. While some of these studies suggested that lymphocytes migrate between 2 adjacent ECs (paracellular migration),13,31,32 others have claimed that lymphocytes migrate within the EC (transcellular migration), possibly via the formation of transendothelial channels.33-36 Our data do not support or reject any of these models and the precise cascade of events leading to the entry of lymphocytes into the HEV pockets remains to be definitely determined.
In summary, our data provide new insight into how HEVs adjust lymphocyte entry fluxes to balance lymphocyte exit fluxes in noninflamed LNs. Such control may of course be switched off or overridden during an active immune response. After inflammation, HEVs located in the draining LN increase their capacity to recruit naive lymphocytes and, at the same moment, lymphocytes egress is transiently blocked, a phenomenon known as the "LN shut down."37,38 Instead of creating a bottleneck situation as one would expect from a simple application of our pressure-gated access model, this combination of events induces a tremendous LN swelling because of a massive increase in total cell numbers, despite the presumed structural limitation of the surrounding capsule. Given the results presented here, we suggest that there must be mechanisms that relieve the physical constraint of pressure build-up because of excess cell entry and subsequent proliferation (eg, tension release within the structure of the capsule) and/or change the gating behavior we have described, mechanisms whose unraveling should prove valuable for better understanding lymphoid tissue function in health and disease.
The online version of this article contains a data supplement.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.
The authors thank B. Bréart, S. Schwab, and R. Proia for providing the bone marrow cells of Ubi-cre ESR-1 × S1P1flox/− mice and constructive comments on the manuscript.
This research was supported in part by CNRS, Inserm, the Agence Nationale de la Recherche, the Association pour la Recherche sur le Cancer, the Institut National du Cancer, and the Intramural Research Program of NIAID, National Institutes of Health.
National Institutes of Health
Contribution: S.L.S., C.M., R.N.G. and M.B. designed research; S.L.S., C.M., I.M., A.J. and J.P.L. performed the experiments; and R.N.G. and M.B. wrote the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Marc Bajénoff, Centre d'Immunologie de Marseille Luminy, Parc Scientifique et Technologique de Marseille Luminy, Case 906, 13288 Marseille, France; e-mail: firstname.lastname@example.com.
Author notes
C.M. and S.L.S. contributed equally to this work.


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Twin Blades of Fury increases Varian's Attack Speed by an additional 15%, and Basic Attacks increase his Movement Speed by an additional 10%.
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- Description
DetailsLike the name suggests the bespoke colour ranges of this elegantly rustic floor encorporate the tones of medium to dark Muscavado brown. Sofly distressed detail and cross sawn finish add to the authentic look of this extra wide plank floor, whilst adding total strenght and toughness to the surface. Suitable for all household and commercial applications and with underfloor heating. 240mm wide x 15mm thick x 1900mm lengths. 4mm Veneer of real wood alow for future sandings, Matching chevron also available.
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A black Maryland lawyer who was detained in court earlier this month by a deputy who thought he was a suspect masquerading as a lawyer filed a complaint with the Harford County Sheriff's Office this week, alleging the action was racially motivated.
The lawyer, Rashad James, who works for Maryland Legal Aid's community lawyering initiative, has asked the Sheriff's Department to begin an internal investigation and to record the complaint in the deputy's personnel file.
Mr. James appeared at a hearing at Harford County District Court on March 6 on behalf of a client, who was not present. A sheriff's deputy approached Mr. James in the hallway after the hearing and called him by his client's name, according to the complaint.
Mr. James corrected him and provided his driver's license to prove his identity, but the deputy was not convinced. He directed Mr. James to an interview room and detained him for 10 to 15 minutes while Mr. James made phone calls to confirm his identity, his lawyers said.
"It was a series of events that we firmly believe none of which would have occurred had Mr. James been white," Andrew D. Freeman, one of Mr. James's lawyers, said.
The experience was "surreal," Mr. James said on Thursday. "The entire time I made sure that I stayed calm, that I was respectful, that I complied."
The Sheriff's Department is investigating Mr. James's complaint.
"We take all complaints seriously," Sheriff Jeffrey R. Gahler said in a statement, adding that the department would "take immediate and appropriate administrative action" if it found the complaint had merit.
Since the complaint was filed on Tuesday, Mr. James's lawyers have received phone calls and emails from nearly a dozen people with stories of racial discrimination in Harford County, in northeastern Maryland.
"I think this is just another example of law enforcement in particular viewing black males suspiciously, second-guessing them or presuming that they're up to no good when they're doing rather ordinary things," said Chelsea Crawford, another lawyer for Mr. James.
She referred to the episode as "lawyering while black."
Mr. James's situation is the latest example of black people being detained or having the police called on them while engaging in everyday activities, such as sitting in a Starbucks or leaving an Airbnb home.
Black professionals have also spoken out about encountering bias while on the job and having their credentials questioned. Last October, a Delta flight attendant asked a black doctor who was trying to help a passenger in distress if she was "actually an M.D."
Mr. James said he was ready to shift his focus back to his clients. He said that nothing like this had happened to him before in the courtroom and that he felt it was important to tell his story.
"By speaking up, I hope that it will encourage other persons to speak up," he said.


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We have sprung forward as of March 12th with the changing of the clocks and March 20th marks the first official day of the Spring season. Each year without fail I get ridiculously excited for these seasonal changes, Spring especially.
Spring comes with so many positive connotations: renewal, youth, new life, awakening, and transformation. We might not realize how deeply we are effected by these changes or metaphors, but if we look a little deeper we can see how in small ways the seasons affect us all.
The winter season creates shorter days. Less sunlight naturally affects our energy levels. Growing up in Florida I did not have to worry about cold weather. Winters in the Southeast actually had more of an energizing effect than anything else. Being up North now, my energy levels dramatically dip when the time "falls back" and the sun sets at 4:30pm.Read more


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The reality is that a Style is being learned & the fact is subjective entirely. The point is that we learned the way harder while the finding process of the top ten best-dressed actors showing off their styles.
Prince William was doing Duke of Cambridge while his duty. He was in love with a navy-blue suit and it was a well-known and well enjoyable dress. The famous dressings of Prince William are Navy trousers & tie, max texture light blue jacket & sky color shirt.
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David Beckham appeared on here in this list because of two decades, he had an experimental & relatable style at the same time. Overcoat with Jeans & a beanie in Paris with minimal look with all black looks.
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HRH Prince of Wales was spotted in the royal weddings. The Host was in a pink shirt and patterned pocket with square & shading and looking like a flower show, Albeit with the fewer pairs of the Tights.
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Timothee Chalamet becomes a variable moment of the men's-wear. He was dressed down in the silk bomber. It looks for slouchy jeans. Proved that "Suites are a Young man's game". Fits in the bursting colors and in a bold pattern.
Jeff was at his first time on the list. He dressed the overtones 'dgaf'. He wore things like a man with half his age and might be struggling to pull it off. He wore a Gucci shirt and boldly printed Prada. Roll neck with the white jeans & a suede jacket with the whole wardrobe.
Donald Glover was not only who the Donald Glover is. He is a new renaissance man. His style is wavy. In cheekily unbuttoned silk shirts & very soft, black tuxedos, regal, purple Gucci ring.


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Instagram can work preferred for certain organizations over others.It has in excess of 800 million month to month clients, and is proceeding to develop. Also, on the grounds that it's a piece of Facebook, you know there is immense weight for it to succeed. In any case, does Instagram work for your business?
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The primary misstep made by advertisers is in posting things online without an invitation to take action. Set a target for each post and utilize the goal to build up your suggestion to take action, for instance "register now" or "purchase now."
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The examination on Instagram enable your business to perceive how well your different crusades are functioning. You need to change over to a business record to get to the devices. The devices will at that point help you have a comprehension of how your devotees are drawing in with your substance, so you can show signs of improvement results.
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Pick two time spots, day and night, and see when the vast majority of your commitment happens. At that point include posts relentlessly, or diminish your posting on the off chance that you are getting a littler measure of commitment.


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The Occult Mentors of Maria de Naglowska
Paperback, 249 Pages
Price: $99.00
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The Occult Mentors of Maria de Naglowska by Robert North This is the ultimate study of Maria de Naglowska and her relationship to the history of French Catholic Gnosticism, from the Cathars at Monsegur to Palaprat in Paris and the reformulation of many magico-masonic orders under the directorship of Papus and FUDOSI. North presents the teachings of the mysterious Groupe Polaires which Maria belonged to. The Group of UR was founded by Maria's primary mentor, Julius Evola. The group was funded by Mussolini's war council to experiment with Tibetan methods of soul transmigration and use of the Vril force. Maria's rituals in 1930's Paris may have been part of this plan. Occult scholar and author, Robert North also traces the true origin of western European sex magick. His section on Spiritualism and Free Love in the 19th Century points to the hitherto unknown origins of the sex magick doctrines of the O.T.O., the H.B. of L. and other similar groups.
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Product Details
- 9780557404759
- Copyright
- Robert North (Standard Copyright License)
- Edition
- Illus Grimoire 5 pb
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- Published
- April 23, 2010
- Language
- English
- Pages
- 249
- Binding
- Perfect-bound Paperback
- Interior Ink
- Full color
- Weight
- 2.15 lbs.
- Dimensions (inches)
- 8.5 wide x 11 tall
- Product ID
- 10660635
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Weighing in at just under 4 pounds, the CDi370DV portable CD-i player is lighter and less expensive than most multimedia-capable notebook computers.
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This article originally appeared in the 03/01/1996 issue of THE Journal.
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Product Description
Duck Fat Spray
NOW available in a convenient, easy-to-use spray can! Make POTATOES WITH PIZZAZZ and AWE-INSPIRING ASPARAGUS and CAPTIVATING CARROTS! Get the ULTIMATE SEAR on meats, poultry, fish and shellfish. Serve the CRISPIEST fried chicken. Get the flavor and crunch of fries without frying. Calamari, fish and chips, french fries and more are now delectable PERFECTLY ROASTED with Duck Fat Spray. Prepare the perfect confit. Be a baking star with this secret weapon that gives you golden, puffed and tender FLAKY PASTRIES…and MORE!
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North American communication networks in 2001 consumed 62 percent of selected fiber-optic filter value, claims a new report from market researcher ElectroniCast Corp. (San Mateo, CA). The European share will remain relatively flat at 24 percent, while the North American share will drop to 51 percent but grow in value to $254 million by 2011, claims the report. The Japan/Pacific Rim and Rest of World shares will climb rapidly, to a combined 25 percent of the market by 2011.
ElectroniCast's new report, "Fiber Optic Filters: Global Market Forecast," examines trends in the deployment of selected filters used in fiber-optic communication applications. It provides a ten-year forecast of global consumption of filter "elements" typically used in various modules. Forecasts are provided for North America, Europe, Japan/Pacific Rim, and Rest of World and segmented by the following filter technologies: Dielectric Interference (Thin Film Interference), Bragg Grating fiber, Waveguide Array Grating, and Mach-Zehnder (M-Z)/Other.
"Thin film elements that are used in WDM filter modules held the highest global consumption value in 2001,"explains ElectroniCast president Stephen Montgomery. "As the requirement for more wavelengths per module increases each year, Array Waveguide Gratings (AWGs) are more accommodating to higher wavelength counts; therefore AWGs will dominate the DWDM marketplace by 2011," he adds.
For more information or to purchase a copy of the report, visit ElectroniCast's Web site at www.electronicast.com.


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Hacked Or Nah? Funniest Reactions To Lil Wayne's Messy Breakup With Birdman
- By Bossip Staff
1 of 23
Hilarious Reactions To Lil Wayne Dumping Birdman
We're not really sure if Weezy broke up with longtime boo thang/father figure Birdman on Twitter over the shelving of "The Carter V" (that was slated to drop months ago) and, honestly, it doesn't matter because the internet reaction was absolutely hilarious.
Hit the jump for the funniest reactions to Weezy's (no-yet-official) breakup with Birdman.
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When it comes to health and wellness, keeping your body properly fueled is incredibly important. If you are active and in the gym, keeping enough energy on hand will help you push through your workouts, your busy days, and lead to better performance overall. Proper snacks and hydration help achieve the balance between meals, but having the right types of snacks on hand can be tricky. That's where we come in! Evolv Kitchen provides meal prep and meal delivery service to all of Florida, focusing mostly on delicious, convenient, and healthy meal prep options and signature meals. However, we also have a sweet spot for snacks, who doesn't.
Shop our growing snack menu and drink collection to round out your order with a recovery beverage.


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Neonatal Workshop, Saturday, 9 am to 2 pm
September 14, 2019 @ 9:00 am – 2:00 pm
We have a really cool new pattern (to help us use up scraps) for the September 14th Neo-Natal Workshop. Some sewing will need to be done in advance, so we are providing instructions so that if you would like to attend you can prepare. Click here for the pattern. Workshop participants will receive background fabric to use with the strips, batting and backing fabric and binding strips. If you have any questions about this pattern or would like to let us know that you will be attending, please go the Contact Us page on this website and send us an email. That way we will know how many kits to produce. Once signed up, closer to the date of the workshop, you will receive an email with information on the usual sewing supplies you will need to bring.


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Nisha Aur Uske Cousins 21st May 2015 Written Episode Update
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Nisha Aur Uske Cousins 21st May 2015 Written Episode, Written Update on TellyUpdates.com
The episode begins with, kabir turns to viraj and says I don't have to try to be close to nisha bcoz nisha is close to me get that.in police station kabir is tied up in jail,kabir says I wont run away plz untie me,and u cant do this to me I need a lawyer,police slaps kabir and asks him to be quite.dolly tells dadaji and others in house that sumit is innocent,leela and roopan get very happy,dolly says I was wrong and leaves crying.sumit outside the hosp with nishas mobile,he destroys nishas mobile and starts laughing.
Kabir is being torched and asked where are other jwellery.nisha starts getting conscious,ramesh calls doc,viraj is there too,police ask viraj to come to a side, doc goes to check nisha,virendra and suku are very happy,virendra informs gangwals house that nisha is back to conscious, nisha asks where is kabir mom, laxmi doesn't answer, nisha says say something where is kabir,laxmi says nisha take rest not now,nisha says papa where is kabir,doc says nisha calm down, nisha says suku where is kabir, virendra says kabir isn't here,nisha tries to get up,virendra says no use kabir is in jail,nisha says papa kabir isn't at fault he did nothing sumit jiju shd be in jail he pushed me down and jwellery bag was with sumit he is a culprit, he did this and not kabir.
Leela goes hosp,sumit asks mom is nisha conscious,leela says why but,sumit says nisha will tell truth mom,leela says oh god.virendra says nisha sumit saved ur life and ur blaming him,its kabir who did,nisha says mom ,laxmi says nisha sumit saved ur life,nisha says mom even u think kabir is at fault,listen everyone kabir did nothing,virendra says then why did he surrender,he has accepted all the blames and u instead of thanking sumit u are blaming him today u are alive bcoz of sumit, suku says uncle plz she just got conscious,virendra says then she shd think before she speaks,nisha says no no sumit shd be in jail n not kabir.
Sumit is being informed abt nisha,sumit and leela go to nisha and start acting they are very happy,nisha ignores them,leela says wow I am so happy to see nisha good and my son saved her I am very proud of him,nisha says u shd be ashamed of him,leela says u shd be thankful to sumit but,virendra says nisha,nisha says uncle plz I have proof where is my phone,laxmi and suku try to calm her down,doc asks nisha to calm down,ramesh say nisha calm down,virendra takes laxmi and ramesh and suku with him,sumit says nisha I pitty u,I told u don't mess with me and see and ur proof I destroyed it,leela smiles,sumit says yes ur phone is no more I broke it,poor thing this was deal with kabir I will give u blood and he will take all blames,leela says so better be quite after all u are blood related with sumit,virendra enters,leela says oh my child get well soon,and virendra ji we shall leave now,all leave,laxmi and ramesh enter.
Kabir is in jail, he asks what is the time,police says its 8,kabir smiles and says nisha must be conscious now.ramesh asks nisha what is in ur phone,laxmi says don't worry nisha all will be fine and say something,nisha says nothing Is left,laxmi says don't lose hope nisha and I know all will be fine,laxmi goes out.dadi and dadaji pray to god for nishas health,dadi thanks god for saving nisha,dadi asks dadaji why is she still tensed,dadaji says I don't know what to say I faced so many situation but this one I never thought abt it,I am happy for nisha but around her there is lot of hardship which is troubling me a lot, dadi says it's a sign that all will be fine see nisha is alright and I trust god and nisha she will bring everything to fine,roopan and leela enter and roopan says I agree with u after all that thief kabir is caught and sumit saved our nishu,leela says my sumit always cares for others, dadaji says I am always thankful to sumit,dadaji and dadi leave.
Ramesh is called by doc,he leaves, nisha is thinking abt kabir,she finds a letter bellow her pillow, she removes it and reads it,kabir says nisha don't lose hope, I think we were together just till here take care nisha.
PRECAP;laxmi goes to nishas room and finds she is missing,laxmi calls ramesh and tells him nisha is missing,nisha hiding there says sorry mom but I have to help kabir.
Update Credit to: Tanaya
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Price for 1 night 2 adults*
Located in Southeast Calgary, this eco-friendly hotel is within 3 miles (5 km) of Southcentre Mall, Heritage Park Historical Village and Chinook Centre. Southland Leisure Centre and Rodeo Arena are also within 3 miles (5 km). Calgary Heritage Station is 8 minutes by foot and Southland Station is 16 minutes.
Situated near the airport, this hotel is 0.6 mi (0.9 km) from Sunridge Mall and within 3 miles (5 km) of Casino Calgary and Aero Space Museum of Calgary. Calgary Zoo and Scotiabank Saddledome are also within 6 miles (10 km). Rundle Station is 15 minutes by foot and Marlborough Station is 27 minutes.
Located in the heart of Calgary, this eco-friendly hotel is within 1 mile (2 km) of Casino Calgary and Sunridge Mall. Calgary Zoo and Stampede Park are also within 6 miles (10 km). Marlborough Station is 11 minutes by foot and Rundle Station is 23 minutes.
Situated near the airport, this hotel is 1.8 mi (2.9 km) from Casino Calgary and 2.8 mi (4.5 km) from Calgary Zoo. Sunridge Mall and Calgary Elks Lodge and Golf Club are also within 3 miles (5 km).
Hotels in Dalemead start at C$90 per night. Prices and availability subject to change. Additional terms may apply.
Pack your bags—it's time to embark on a getaway. Whether you're craving a solo retreat or promising your family a vacation to remember, book one of the best hotels in Dalemead. These hotels are located within easy access of the city's hottest attractions and entertainment, so you won't miss a beat while you're in town. Spend the days exploring the local landmarks and the evenings getting to know the nightlife. After exploring the city from top to bottom, rest up at a hotel that speaks to you. Find the perfect place that matches your trip's vibe, from a trendy boutique to family-friendly accommodations.
Allow us here at Travelocity to pair you with up Dalemead hotels that suit your vacation preferences. Discover places with convenient on-site restaurants, around-the-clock service, and pools where your kids can make a splash. Some hotels may boast fitness rooms and spa services, while others feature game rooms and Wi-Fi access. To top it all off, you'll score cheap hotels in Dalemead that let you spend more on your activities and less on your lodging. Book and bundle your flight and hotel deals together today and save up to $537. It's time to explore a new city, and break out of your routine.
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Chowderfest Weekend-Merchant Mart
October 5 @ 10:00 am - 5:00 pm
|Recurring Event (See all)
One event on 11/20/2019 at 10:00 am
Saturday October 5–Merchant Mart.
Biggest shopping event of the year. Live music, beer and hard cider on tap, wine by the glass, dozens of merchants, food tent, family entertainment and games.


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Stamford Assistant Fire Chief resigns after hit and run
STAMFORD —Assistant Fire Chief William Smith resigned from the Stamford Fire Department on Friday, according a news release from Mayor Michael Pavia.
Pavia called for Smith's resignation after the Assistant Fire Chief allegedly crashed a city-owned vehicle into a parked car and left the scene at approximately 2:30 a.m. on Thursday
Stamford Police Chief Jon Fontneau says Smith later called to report the crash.
Police are investigating whether alcohol was a factor and awaiting results of toxicology tests.
Pavia said Smith has had a great career but said that Smith must resign or be subjected to "further action."
Smith, a 35-year veteran of the department, was honored for his work during Superstorm Sandy and was an incident commander during the 2011 Christmas fire that killed three young girls and their grandparents.
There is an ongoing criminal investigation, police said.