TheraBand elastic tubinga was used to

provide resistance during each exercise. Subjects were required to complete at least 19 out of the 24 treatment sessions (∼80%) to remain in the study. In addition, if a patient missed 3 consecutive treatment sessions, their participation in the study was terminated. All subjects completed the required number of treatment sessions over the 8-week intervention period. Patients assigned to the posterolateral hip exercise group performed 2 exercises: EPZ-6438 cost one targeting the hip abductors and the other targeting the hip external rotators. Hip abductor strengthening was performed with patients positioned sidelying on a treatment table. Elastic tubing was tied just above the ankle at one end and attached to the bottom of the treatment table at the other (fig 2). The length of tubing was individualized across patients based on their lower limb length (distance from the anterior superior iliac spine to the medial malleolus). The distance between the exercise limb and the bottom of the treatment table was adjusted to remove slack from the tubing. Patients were allowed to hold on to the edge of the table

for stabilization purposes. The exercise was performed against the resistance by abducting the hip from 0° to 30°.24 Hip external rotator strengthening was performed with patients seated at the edge of a treatment table and the knee flexed to 90° (fig 3). A strap was used to prevent sagittal and frontal plane motion of the thigh. Elastic tubing was tied around the ankle and was secured to a rigid pole.

The length of tubing was individualized see more across patients based on thigh length (distance from the anterior superior iliac spine to the medial femoral epicondyle). The distance between the exercise limb and pole was adjusted to remove slack from the tubing. The exercise was performed against the resistance by externally rotating the hip from 0° to 30°.15, 16, 24 and 25 Patients assigned to the quadriceps exercise group also performed 2 exercises. find more For the first exercise, the patient was seated at the edge of a treatment table, and the knee was flexed to 30° (fig 4). Elastic tubing was tied around the ankle and was secured to the bottom of the treatment table. The length of tubing was individualized across patients based on lower leg length (distance from the lateral femoral epicondyle to the medial malleolus). The distance between the exercise limb and the bottom of the treatment table was adjusted to remove the slack from the tubing. In accordance with previous studies, patients performed the exercise against resistance by extending the knee from 30° of knee flexion to full knee extension.12, 14 and 24 For the second exercise, patients stood with elastic tubing passing beneath both feet while holding one end of the tube in each hand (fig 5).

0 mg/ml and 0.5 mg/ml (Fig. 2A and

B). Because coating was performed at a concentration of 1.0 mg/ml, the observed effects on phagocytosis were not caused by the binding of different amounts of Aβ-peptides to the PSPs. Of note, compared to the other Aβ-peptide variants, more Adriamycin Aβ(2–40) bound to the PSP at the lower coating concentrations of 0.1 mg/ml and 0.05 mg/ml. During the phagocytosis of Aβ-peptide-coated PSPs, the expression of several pro- and anti-inflammatory markers were examined by flow cytometry and ELISA. Coating of the PSPs with Aβ(1–42), Aβ (2–40), Aβ (2–42) and Aβ (3p–42) caused a 25–35% decrease in MSRI expression on the phagocytes compared to uncoated PSPs (p < 0.05). No significant effect was observed for Aβ(1–40) – or BSA-coated ZD1839 PSPs ( Fig. 3A). Additionally, no significant alteration of the IL1 receptors or of CD206 was observed after coating the particles with Aβ peptides ( Fig. 3B–D). The IL-10 and TNFα levels were measured in cell culture supernatants after 72 h of phagocytosis of the Aβ-coated PSPs (Fig. 3E and F). The measurements were well above the limit of detection (1.56 pg/ml), and the coefficient of variation

was below 25%. Compared to the phagocytosis of uncoated PSPs, the IL-10 levels were decreased by 20–30% only in monocytes treated with Aβ(x–42)−coated PSPs (p < 0.01). Neither Aβ(x–40)− nor BSA-coated PSPs changed the IL-10 expression in monocytes. The TNFα levels were only increased

Interleukin-2 receptor by coating the particles with Aβ2–40. The reduced expression of MSRI and the lower secretion of IL-10 indicate an induction of a proinflammatory polarization of monocytes during phagocytosis of Aβ(x–42) coated PSP. To assess the effects of Aβ-peptides on the phagocytosis of in vitro-differentiated phagocytes, THP-1 macrophages were analyzed in the assay described above. In contrast to human monocytes, the phagocytosis activity of THP-1 macrophages was not increased after adding soluble Aβ-peptides to the cell culture medium ( Fig. 1C). Similar to freshly prepared monocytes, coating PSPs with all tested Aβ-peptides resulted in increased phagocytosis (p < 0.0001) ( Fig. 1D). Among the untruncated Aβ(1-x) peptides, Aβ(1–42) was more active than Aβ(1–40) in stimulating the phagocytosis of PSPs (p < 0.05). Coating PSPs with N-terminally truncated Aβ(2–40) and Aβ(2–42) resulted in higher MFI values when compared to Aβ(1–40)− and Aβ(1–42)-coated PSPs, respectively (p < 0.05). The strongest induction of phagocytosis was observed with Aβ(2–42); compared to uncoated PSPs, the MFI values increased by 150% (p < 0.0001). Interestingly, Aβ(3p–42) was less effective than Aβ(2–42) in THP-1 macrophages, which is in contrast to our observations in primary human monocytes. Fluorescent, AF488-labeled E.

Second, the outcome of plant–plant interactions in plant communities – and especially the SGH – has been increasingly cited in recent years to be dependent on species-specific effects between facilitators IGF-1R inhibitor and beneficiaries,

thus promoting niche differentiation (sensu Tilman, 1982) and resource use complementarity ( Liancourt et al., 2005, Callaway, 2007 and Gross et al., 2009; see Maestre et al., 2009 for a refined SGH taking into account these aspects). Accordingly, the fact that species architecture and species diversity may differ between TAE and extratropical environments also questions the global validity of plant–plant interaction models, which have been designed outside the alpine tropics. Herein, we review the ecological and environmental features of TAE in comparison with other alpine ecosystems. We then discuss the current state of knowledge on patterns and process of plant–plant interactions in TAE. We conclude by suggesting potential

avenues for future research on plant–plant interactions in TAE, including priority Vorinostat purchase hypotheses to be tested, methodological approaches, and how current and future knowledge in this field may extend the conceptual framework of plant–plant interactions in alpine environments worldwide. Tropical alpine areas are defined as regions that are located above the natural high-altitude treeline, within 23°26′N and 23°26′S (Smith and Young, 1987, Körner, 2003 and Nagy and Grabherr, 2009). The lower altitudinal limit of TAE occurs between 3400 m and 3900 m a.s.l. although they may develop as low as 2000 m in various tropical Farnesyltransferase islands, presumably because of a lack of tree species adapted to high altitude and/or a stronger aridity occurring in these types of TAE (Leuschner, 1996). The upper altitudinal limit commonly extends to between 4600 m and 5000 m a.s.l. (Smith and Young, 1987 and Luteyn, 1999). The term ‘tropical alpine’ encompasses a variety of regional terms

referring to such areas, including páramo, puna, afro-alpine, and zacatonal (see Smith and Young, 1987, for a detailed review on terms). The majority of TAE (probably more than 90% of the total area) are located in the Andes, between Venezuela and Chile–Argentina (Jacobsen, 2008). Further north, a relatively large area of dry TAE occurs in Mexico between 3000 m and 5000 m a.s.l. (Nagy and Grabherr, 2009). Residual páramo ecosystems also occur in Costa Rica (highest point: 3810 m) and Panama (3475 m; Luteyn, 1999). In Africa, most TAE are located in the eastern mountain ranges of the continent (White, 1983) but an isolated alpine zone has also been described on the volcanic Mount Cameroon (4095 m; Letouzey, 1985). New Guinea harbours the most extensive TAE in South-east Oceanic Asia (4884 m; Smith, 1994) with an area of approximately 700 km2 (Buytaert et al., 2011).

The upper layer of water in the Sea of Marmara is replenished by this cold water from the Strait of Istanbul for approximately 3–4 months (Beşiktepe et al. 1994). The temperature

increase due to atmospheric heating in the upper Capmatinib molecular weight layer of the Sea of Marmara does not compensate for the temperature decrease caused by advection of the cold water into the upper layer. In the summer months, a cold intermediate layer identified as a tongue-shaped extension towards the south is generally observed in the Strait of Istanbul. Its temperature is about 11–12 ° C in the southern exit of the strait in June and July (Altıok et al. 2000). This cold layer is examined by the temperature transects through the strait shown in Figure 6 for July 1997–2000. The temperature transects in July can be a good explanatory plot for the transition of cold water through the strait, because the temperature difference is higher between the layers. In general, all the transects (Figure 6) show that there are three different water masses in the strait, as can be seen from the T-S diagrams. The thickness of CIW and its temperature change every year. In 1997, cold intermediate

water is observed along the strait below the warmer upper layer. On the south side of the strait Navitoclax in vivo (at station B2), the temperature of the upper layer decreases to 19 °C but is 24 °C on the north side (at station K0). Temperature transects show that the temperature of the upper layer suddenly decreases after the constricted part of the strait in the south. Owing to the geometry of the strait, the upper layer flows in three-dimensional circulations (Özsoy et al. 1998). This causes vertical mixing between the layers, and the temperature PDK4 decreases. In 1998, the warmer

upper layer disappears along the strait. The upper depth limit of the 8 °C isotherm at station K0 is shallower than the one at station K2 (Figure 6). There is also a significant difference in temperature between these two stations at the surface (20.5 ° C at station K2 and 14.5 °C at station K0). This feature could be due to the anticyclonic eddy formation sometimes observed in the Black Sea exit of the strait (Sur et al. 1996). Eddy formation in the Black Sea exit of the strait generally causes a rise of CIW along the strait (Sur et al., 1994 and Sur and Ilyin, 1997). In this case, colder water entrains into the upper layer along the strait, as in July 1998. In 1999, the amount of CIW is too small, so that a thick warmer upper layer is observed along the strait. CIW is observed only as a thin layer in the northern part of the strait. As mentioned above, the thick (∼ 30 m) Danubian water layer most likely prevents the entrance of CIW into the strait. Due to the smaller amount of cold water in the strait, the temperature decrease of the surface layer is not fully observed after the contraction region in the south of the strait. But this is not an indication of less mixing in the region.

These somewhat overlapping skill sets are interdependent—a weakness

or strength in one weakens or strengthens all three. Developing communication process and content skills, without ongoing and commensurate awareness and development of the values, personal ethics, and capacities that underlie those skills, can lead to manipulation rather than effective interaction. On the other hand, developing our values, capacities, and other perceptual skills without ongoing development of the process and content skills needed to demonstrate those values and capacities is inadequate, and the risk is that patients and others will not see nor experience that we hold these values (e.g. we may incorrectly perceive that because we feel empathy we are demonstrating it, or because we intend to listen carefully, we are doing

so) [31]. Communication is an essential clinical skill with considerable science behind it, not an optional Crizotinib molecular weight add-on and not ‘simply’ a social skill at which we are already adept. An extensive body of research developed over the past forty years in human medicine, shows that improving clinical communication in specific ways leads to numerous significant outcomes of care [4], [13] and [32] ( Box selleck compound 2). Improving clinical communication in specific ways leads to better outcomes, including: 1. More effective consultations for patients and clinicians • Greater accuracy Our values, capacities, and communication skills also help us discern which way of relating is called for at any given moment. Developing and enhancing the capacity for flexibility, relational versatility,

and “differential click here use of self”—i.e., the ability to adjust interpersonal skills based on the needs of different patients, families, the changing nature of the problem, and context—is central [7], [9], [33] and [34]. Through actions and words, clinicians espouse values in healthcare. Given our responsibilities and involvement with people’s lives at their times of greatest vulnerability, clinicians need to live by these values. We need to develop learning environments and practice settings that strengthen and reinforce our values. The values espoused in the International Charter for Human Values in Healthcare, and the specific clinical communication skills needed to demonstrate them, underpin efforts to strengthen the ongoing development of core values in medical/healthcare education and clinical programs at all educational levels. Two such programs that reflect International Charter values are briefly described below, as a means of demonstrating the potential impact of the International Charter and the translation of its values into action. For some time, Branch and others have worked to study and implement ways to enhance core values in medical education [12], [13], [35], [36] and [37].

To apply these biotechnological

procedures, GDC973 better knowledge of the physiological and metabolic interactions between S. cerevisiae and non-Saccharomyces wine yeast is needed. In this context, controlled multi-starter fermentations might be an interesting way to investigate yeast interactions during wine fermentation. In this review, we will discuss the recent developments regarding yeast interactions in multi-starter wine fermentation, while focusing on the influence on the yeast growth and the analytical and aroma profile of the wine. Due to the non-sterile environment during wine fermentation, different yeast species and/or strains can be involved in several interactions through the production of toxic compounds, or as a result of competition for nutrients. In terms of inhibitory interactions that are mediated by metabolites with toxic effects, the most evident example is the production of find more ethanol by S. cerevisiae. Indeed, the selective pressure exerted by high levels of alcohols has been defined as the main factor responsible for the

dominance of S. cerevisiae towards other non-Saccharomyces yeast [3]. Together with ethanol, other factors can have strong selective pressure in mixed wine fermentation. In particular, the production of medium-chain fatty acids and high amounts of acetic acid can negatively affect the growth of a co-fermenting yeast species. Cell-to-cell contact appears to be also involved in the interactions between S. cerevisiae and other non-Saccharomyces species, such as Torulaspora delbrueckii, Hanseniaspora uvarum and Kluyveromyces thermotolerans (now reclassified as Lachanchea thermotolerans) [20]. Another mechanism that regulates the presence and dominance of yeast species

during wine fermentation is the involvement of oxygen. Unoprostone Reduced oxygen availability under grape juice fermentation might have an important role as a selective factor in mixed cultures. Indeed, low tolerance to low available oxygen exhibited by K. thermotolerans and T. delbrueckii could in part explain their relative competitiveness, and consequently their rapid death in the presence of S. cerevisiae [21]. For a broader understanding of the complex phenomenon of microbial interactions a multifactorial approach is required. We belief that this kind of approach may be a useful tool to investigate on the influence of these different factors affecting the presence and the dominance of yeast strain in mixed fermentation.

The second part of this review provided complimentary

evidence showing the link between vestibular Capmatinib ic50 dysfunction and vestibular stimulation upon cognitive and psychiatric symptoms. In particular, the key cognitive domain linked to vestibular function is spatial memory. Several psychiatric symptoms are commonly linked to vestibular function, including depression and anxiety with some preliminary reports of mania and psychosis also being linked to vestibular function; however, findings remain inconclusive and further research is warranted. Given the lack of biological diagnostic markers for psychiatric disorders and the associated controversies and difficulties accompanying the current subjective diagnostic assessment techniques for psychiatric illnesses (DSM-TR-IV and /V (Blais and Malone, 2013; Zimmerman, 2013)), it appears reasonable to suggest that objective measurement of the neural function of the vestibular system may provide a rich source of addition information that could provide significant insights into cognitive and psychiatric symptomatology and potentially a technique

that could Verteporfin nmr detect vestibular functioning could contribute to a more objective diagnosis of psychiatric illnesses. “
“Neuroinflammation is recognized as early event or key accelerant in the pathobiology of persistent CNS infections, HIV associated cognitive decline, prion diseases, and neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s Diseases. The discovery of cannabinoid receptors, identification of

their naturally occurring ligands, and increase in understanding of the physiologic role of the endogenous cannabinoid (endocannabinoid) system, has advanced the exploration of cannabinoid receptor compounds for novel CNS therapies (Piomelli, 2003 and Mechoulam and Parker, 2013). The CB1 receptor is abundant in the brain (Howlett et al., 2002), signals progenitor cells, neurogenesis and development (Aguado et al., 2007 and Diaz-Alonso et al., 2012), can be neuroprotective, and mediates many of the psychoactive effects of cannabinoids (Mackie, 2005 and Monory et al., 2007). The CB2 receptor is present mainly on immune cells of both the periphery triclocarban and CNS (Howlett et al., 2002). Its activation is immunomodulatory, regulatory and neuroprotective (Atwood and Mackie, 2010), through reduction of microglia/macrophage activation, migration (Romero-Sandoval et al., 2009 and Fraga et al., 2011), and decrease in proinflammatory cytokines and toxins (Cabral and Griffin-Thomas, 2009 and Bouchard et al., 2012). That CB2 expression increases in disease states associated with neural inflammation (Benito et al., 2008 and Pacher and Mechoulam, 2011) adds to its appeal as a therapeutic target.

0 × 105 cells/μl. U87ΔEGFR cells (5 μl) were injected into athymic rats (F344/N-rnu/rnu; CLEA Japan, Inc, Tokyo, Japan), and U87ΔEGFR cells (2 μl) were injected into athymic mice (BALB/c-nu/nu; CLEA Japan, Inc). The animals were anesthetized and placed in stereotactic frames (Narishige, Tokyo, Japan) with their skulls exposed. Tumor cells were injected with a Hamilton syringe (Hamilton, Reno, NV) into the right frontal lobe (in the athymic rats: 4 mm lateral and 1 mm anterior to the bregma at a depth of 4 mm; in the athymic mice: 3 mm lateral and 1 mm anterior to the bregma at a depth of 3 mm),

and the syringe was withdrawn slowly after 5 minutes to prevent reflux. The skulls were then cleaned and the incision was sutured. PBS, bevacizumab (for the athymic mice and rats: 6 mg/kg), cilengitide (for the athymic mice LDN-193189 ic50 and rats: 10 mg/kg), or a combination of bevacizumab and cilengitide of the same amount was administered three times per week intraperitoneally, starting on day 5 after tumor

cell implantation. Athymic rats harboring U87ΔEGFR brain tumors were killed at 18 days after tumor implantation and six times administration of PBS, bevacizumab, cilengitide, or the combination of bevacizumab and cilengitide. The brains were removed and fixed Regorafenib purchase immediately by perfusion of 2% glutaraldehyde. After fixation in 2% osmium tetroxide, the samples were dehydrated and embedded in Spurr’s resin. Thin sections poststained with salts of uranium and lead were cut to approximately 60 nm using an ultramicrotome (Leica EM UC6; Leica,

Wetzlar, Germany). The samples were observed under a transmission electron microscope (Hitachi H-7650 TEM; Hitachi, Tokyo, Japan). For histopathologic analysis, athymic rats harboring U87ΔEGFR brain tumors were killed at 18 days after tumor implantation. Athymic rats Erastin ic50 were anesthetized, killed by cardiac puncture, perfused with 100 ml of PBS, and fixed with 50 ml of 4% paraformaldehyde (PFA). The brains were removed and stored in 4% PFA for 12 to 24 hours. Hematoxylin and eosin (HE) staining was performed as described previously [13]. For immunohistochemistry of PFA perfusion-fixed frozen sections, snap-frozen tissue samples were embedded in optimal cutting temperature compound for cryosectioning, and 16-μm-thick sections were processed for indirect immunofluorescence. After blocking non-specific binding with 10% normal goat serum, the slides were incubated overnight at 4°C with primary antibodies, including those targeting rat endothelial cell antigen 1 (RECA-1; 1:20, mouse monoclonal; Abcam, Inc, Cambridge, United Kingdom), von Willebrand factor (1:250, rabbit polyclonal; Abcam, Inc), integrin αvβ3 (1:100, mouse monoclonal; Abcam, Inc), and integrin αvβ5 (1:75, mouse monoclonal; Abcam, Inc). After three washes with PBS containing 0.

Diese Probleme werden weiter unten diskutiert, zusammen mit einer kurzen Übersicht über die Daten, auf denen sie beruhen. Die LD50-Werte (= mediane letale Dosis) für

Eisen(II)-sulfat, -succinat und -gluconat nach einer einzelnen oralen Dosis liegen für Mäuse bei 560, 320 und 230 mg Fe/kg Körpergewicht. Eine ähnliche Reihenfolge hinsichtlich der durch diese Komponenten induzierten, eisenabhängigen Schädigungen wurde MAPK inhibitor auch bei männlichen Ratten nach wiederholter oraler Gabe von 50 und 100 mg Fe/kg Körpergewicht über 12 Wochen [122] beobachtet sowie für die emetische Wirkung und die gastrointestinale Schädigung bei Katzen und Kaninchen [123]. Die Mechanismen der Eisenhomöostase und die beobachteten Schäden sind beim Menschen und bei Nagetieren ähnlich. Jedoch gibt es hinsichtlich der quantitativen Aspekte der Eisenkinetik beträchtliche Unterschiede zwischen Mensch, Ratten und Mäusen und sogar zwischen verschiedenen Mausstämmen. Dies macht die quantitative Extrapolation von Daten aus Tierversuchen auf den Menschen schwierig wenn nicht unmöglich [124], [125] and [126]. Die prozentuale Eisenresorption nach oraler Einnahme beträgt 10 bis 20% oder weniger. Daher verbleiben 80 bis 90% des konsumierten Eisens im Darmlumen und können dort durch verschiedene Mechanismen in toxischen und therapeutischen www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html Dosen beträchtlichen Schaden auslösen. Überdosierung oraler

Eisenpräparate verursacht Erosionen der Schleimhaut in Magen und Darm. Das Erbrechen von Blut

und blutiger Durchfall sind die ersten Symptome einer akuten Eisenvergiftung, gefolgt von einer symptomfreien Zeit von bis zu 24 Stunden. Gastrointestinale Stenosen sind mögliche Langzeitfolgen solcher Schädigungen und können chirurgische Eingriffe erforderlich machen. Orale Dosen von 180 bis 300 mg Fe/kg Körpergewicht können beim Menschen tödlich sein; orale Dosen unter 10 bis 20 mg/kg Körpergewicht sind nicht akut toxisch und scheinen einen NOAEL für diese Effekte zu repräsentieren [122]. Kleinkinder sind besonders gefährdet [127], da sie durch Zufall oder unglückliche Umstände leicht einer im Verhältnis zum Körpergewicht hohen ADAM7 Dosis Eisen ausgesetzt sein können. Diese Effekte zeigen eine deutliche Dosis-Wirkungs-Beziehung. Die dafür erforderlichen Dosen sind jedoch viel zu hoch, um auf dieser Grundlage eine Obergrenze für die Eisenaufnahme mit der Nahrung abzuleiten. Die Einnahme oraler Eisenpräparate in therapeutischen Dosen löst häufig Übelkeit, Erbrechen und Beschwerden im Oberbauch aus [128], [129], [130], [131] and [132]. Diese Effekte scheinen auf eine Irritation der Schleimhaut sowie eine veränderte gastrointestinale Motilität zurückzugehen und sind von der Konzentration des labilen Eisens im Lumen abhängig [133]. Mit steigender Dosis nimmt auch der Prozentsatz der betroffenen Patienten zu [134]. Der LOAEL für Beschwerden im vorderen Darm liegt bei Einzeldosen zwischen 50 mg Fe [128], 60 mg Fe [130] oder gar 80 mg Fe bei Schwangeren [135].

Developing a comprehensive suite of rules for Bering Strait vessel traffic will require action locally, nationally, and internationally. That said, many management actions can be taken one at a time or amended as time goes by, so that maritime safety and environmental protection can be improved in stages while respecting cultural values as traffic increases and experience is gained. At the same time, a framework such as this paper presents can put each individual management action in context, to measure progress and to make sure important steps are not overlooked. The Arctic Marine Shipping

Assessment [3] provided the first comprehensive review of Arctic shipping. Based on data collected from all Arctic states, AMSA determined that Arctic vessel traffic is diverse and includes bulk carriers, container ships, general Selleck MG-132 cargo, government vessels, oil/gas service and supply vessels, passenger ships, pleasure crafts, tankers, tugs/barges, and fishing vessels. All of these vessel types can be found in the Bering Strait region (Fig. 2). In 2013, the U.S. Coast Guard counted 440 transits of the Bering Strait, as some vessels went through more

than once (Rob Hynes, pers. comm.). Additional traffic crossed the waters between St. Lawrence Island and the Bering Strait, but did not travel north of Bering Strait itself. Traffic of nearly all types can be expected to increase, though patterns will vary. Destination shipping, for example, serves mines, oilfields, and other industries in Northern Alaska, Northwestern Canada, and Northeastern Russia. The CAL101 volume of this traffic will depend on the level of industrial activity in these areas. The volume of shipping transiting the Arctic will depend on the viability of the Northern Sea Route in Russia, which is affected by ice conditions as well as economic and administrative considerations. Traffic through or along the NSR has increased exponentially, from just 2 vessels in 2009 to 71 vessels in 2013. Expert opinion suggests that cargo throughput

is likely to increase from 1.36 million tons in 2013 to 4 million tons by 2015 and 65 million tons Parvulin by 2020 (Rob Hynes, pers. comm.). The bulk of vessel traffic will occur during the ice-free season, currently summer and fall. Changes in freeze-up and break-up may extend this season in both directions, particularly with ice-breaker escorts, but winter traffic will still require significant ice-breaking capacity. At present, this is limited primarily to research vessels, though ice-strengthened commercial transits may increase before long. Subsistence activity by boat, likewise, requires open water, and in recent years has been possible through much of the winter in open leads and polynyas, the areas of temporary or recurrent open water amid sea ice [19].