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304 Dogwood Street SW, Isanti, MN 55040
About the Listing
Only re-location makes this sale possible. Pride in ownership shines through out this unique split level with insulated heat and air conditioned attached garage, tile floors, custom woodwork, concrete patio deck, privacy fence, storage shed with electric, all appliances, irrigation, finished up and down with not a detail missed!
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Property Details for 304 Dogwood Street SW, Isanti, MN 55040
Bedrooms: 3
Bathrooms: 2 Full
Lot Size: 0.26 Acres
Lot Dimensions: 80x149x78x165
Year Built: 2001
Garage Dimensions: 3 car
Garage: Attached Garage, Insulated Garage, Heated Garage, Driveway - Asphalt
Style: (SF) Split Entry (Bi-Level)
Water: City Water/Connected
Sewer: City Sewer/Connected
Square Feet: 2140
Above Ground Sq Ft: 1070
Below Ground Sq Ft: 1070 (approx)
Room Information for 304 Dogwood Street SW, Isanti, MN 55040
Main Floor
Living Room: 17x12
Dining Room: 11x10
Kitchen: 12x10
Bedroom 1: 14x13
Bedroom 2: 11x10
Deck: 12x12
Foyer: 9x9
Lower Floor
Family Room: 36x12
Bedroom 3: 14x12
Laundry: 9x9
Dining Room Description: Informal Dining Room, Eat In Kitchen, Breakfast Area
Family Room Characteristics: Lower Level
School Information for 304 Dogwood Street SW, Isanti, MN 55040
School District: Cambridge-Isanti
School District Phone: 763-689-6188
Interior Features for 304 Dogwood Street SW, Isanti, MN 55040
Appliances: Range, Microwave, Exhaust Fan/Hood, Dishwasher, Refrigerator, Washer, Dryer, Air-To-Air Exchanger
Air Cond: Central
Heating: Forced Air
Fireplaces: No
Basement: (1070 sq Finished) Full, Finished (Livable), Drain Tiled, Egress Windows
Exterior Features for 304 Dogwood Street SW, Isanti, MN 55040
Lot Description: Tree Coverage - Light
Lot Dimensions: 80x149x78x165
Roof: Asphalt Shingles, Age Over 8 Years
Zoning: Residential-Single
Financial Considerations for 304 Dogwood Street SW, Isanti, MN 55040
Tax Amount: $2,490
Taxes w/Assessments: $2,490
Tax/Property ID: 160820140
Tax Year: 2016
Monthly Payment = $0
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Similar Listings For Sale
The data relating to real estate for sale on this web site comes in part from the Broker Reciprocity Program of the Regional Multiple Listing Service of Minnesota, Inc. Real estate listings held by brokerage firms other than the owner of this website are marked with the Broker Reciprocity logo or the Broker Reciprocity thumbnail logo and detailed information about them includes the name of the listing brokers.


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On One Hand: Petition ApprovalThere are two service centers in the United States which handle K-1 (fiance) visa petitions from all 50 states: one in California, the other in Vermont. Once the petit...
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A K-3 visa is necessary before an individual can bring his foreign spouse to the U.S. The visa application is processed by U.S. Citizenship and Immigration Services. The processing time for a K-3 v...
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These ladies short and bright beach shorts from O'Neill are sure to get you noticed on holiday by the pool this summer. The ONeill Ladies Sleeping Beauty boardshorts feature pretty yellows, pinks and greens; set against a crisp white base.The Sleeping Beauty ONeill Ladies boardshorts feature an all-over floral design, making them easy to team with loads of other colours in your surf clothing wardrobe. They have two front pockets and one rear pocket with a key loop. On the waistband of the ONeill Sleeping Beauty swim shorts there is subtle embroidered O'Neill surf logo branding detail. These boardies are made from a quick drying polyester and they measure approximately 22.9cm in length. Like most surf shorts they have a fixed waistband, with a Velco fly and triple popper fastening closure.These great ONeill womens shorts are available in Pink AOP (all over print). Plenty of choice and colour for all the surf clothing and bikinis in your wardrobe.FEATURES: ONeill shorts with a pretty floral designSubtle woven O'neill brandingMade from diamond ripstop polyesterSPECIFICATION: Fly = Velcro Fly with Popper FasteningLength = 22.9cmPocket = Side Pockets and Rear Pocket with Key Loop
Produkterna levereras av självständiga detaljhandlare belägna runt om i Europa. Leveranstiderna och fraktavgifterna varierar beroende på var återförsäljaren har sitt säte och det valda leveranssättet.
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Vi skickar en leveransbekräftelse till din e-postadress så snart din beställning har gått iväg. Du kan också kontrollera beställningens status på Min profil → Mina beställningar.
Leveranstiden till svåråtkomliga ställen är längre.
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Town of CaryHome Menu
Cary Action Sports
The Town of Cary's action sports venue is open to the public year-round. All ages and skill levels are permitted on course with a valid waiver. Skateboards, inline and quad skates, and non-folding scooters participate during SK8 sessions. Riders on any type of bicycle without training wheels are permitted in BMX sessions. You won't find a workout quite like being in an action sports park! Sk8-Cary is staffed and has a pro-shop for your equipment needs. The park is outdoors and may close without notice due to moisture on the ramps. For more information, call the park at (919) 380-2970.
Sk8-Cary Action Sports Master Plan
Community input has been collected and consultants have developed recommendations. As more information becomes available, it will be added to the Master Plan project page
Anyone on the course MUST have a valid waiver on file
- Adult waiver (18 and older)
- Minor waiver (under 18, must be signed by parent or legal guardian in front of Sk8-Cary staff, or it may be notarized)
Partnership Opportunities Available
The Town of Cary Parks, Recreation & Cultural Resources welcomes financial and in-kind support from the community. Sponsorship packages that can be tailored to meet you or your company's needs are available for specific programs, facilities and/or events. Contact Cary Parks, Recreation & Cultural Resources at (919) 469-4061 if you are interested in exploring available opportunities.


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TY - JOUR T1 - Laser ablation processes investigated using inductively coupled plasma atomic emission spectroscopy (ICP-AES) JF - Applied Surface Science Y1 - 1998 A1 - Xianglei Mao A1 - Adeline C. Ciocan A1 - Oleg V. Borisov A1 - Richard E. Russo KW - ablated mass KW - ablation KW - ablation process KW - analytical performance KW - atomic emission KW - atomic emission spectroscopy KW - atomic line ratio KW - atomic-emission KW - beam KW - behavior KW - brass KW - c KW - ca KW - constant KW - cu KW - density KW - duration KW - e KW - electron KW - electron number densities KW - electron number density KW - emission KW - emission spectroscopy KW - emission-spectroscopy KW - energies KW - energy KW - excitation KW - excitation temperature KW - glass KW - icp KW - icp-aes KW - inductively coupled plasma KW - inductively-coupled-plasma KW - intensities KW - intensity KW - laser KW - laser ablation KW - laser ablation mechanisms KW - laser ablation process KW - laser beam KW - laser sampling KW - laser wavelength KW - laser-ablation KW - laser-wavelength KW - lasers KW - line KW - mass KW - mass-spectrometry KW - mechanism KW - mechanisms KW - mg KW - model KW - multicomponent KW - multicomponent sample KW - nanosecond KW - number KW - number density KW - performance KW - picosecond KW - picosecond laser KW - plasma KW - power KW - process KW - properties KW - property KW - pulse AB -
The symbiotic relationship between laser ablation mechanisms and analytical performance using inductively coupled plasma-atomic emission spectroscopy are addressed in this work. For both cases, it is important to ensure that the ICP conditions (temperature and electron number density) are not effected by the ablated mass. By ensuring that the ICP conditions are constant, changes in spectral emission intensity will be directly related to changes in laser ablation behavior. Mg ionic line to atomic line ratios and excitation temperature were measured to monitor the ICP conditions during laser-ablation sample introduction. The quantity of ablated mass depends on the laser pulse duration and wavelength. The quantity of mass removed per unit energy is larger when ablating with shorter laser wavelengths and pulses. Preferential ablation of constituents from a multicomponent sample was found to depend on the laser beam properties (wavelength and pulse duration). For nanosecond-pulsed lasers, thermal vaporization dominates the ablation process. For picosecond-pulsed lasers, a non-thermal mechanism appears to dominate the ablation process. This work will describe the mass ablation behavior during nanosecond and picosecond laser sampling into the ICP. The behavior of the ICP under mass loading conditions is first established, followed by studies of the ablation behavior at various power densities. A thermal vaporization model is used to explain nanosecond ablation, and a possible non-thermal mechanism is proposed to explain preferential ablation of Zn and Cu from brass samples during picosecond ablation. (C) 1998 Elsevier Science B.VVL - 129 N1 -


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*From the Departments of Respiratory Medicine (Dr. Piitulainen), Clinical Chemistry (Dr. Carlson), Surgical Pathophysiology (Dr. Ohlsson), and Pediatrics (Dr. Sveger), Lund University, University Hospital, Malmö, Sweden.
Correspondence to: Tomas Sveger, MD, PhD, Department of Pediatrics, University Hospital, SE-20502 Malmö, Sweden; e-mail: email@example.com
Background: Clinical and biochemical signs of lung and liver disease have been followed prospectively in a birth cohort of individuals with α1-antitrypsin (AAT) deficiency.
Objective: At age 26 years, the focus was on clinical health, lung and liver function tests, and plasma markers of the protease/antiprotease balance. The effect of early childhood environment and symptoms was also studied.
Methods: Eligible individuals were 26-year-old subjects with AAT deficiency (PiZ, n = 122; PiZ −, n = 2; PiSZ/S−, n = 53) and control subjects (PiMM, n = 44). Of the original AAT-deficient subjects, 119 completed the clinical examination and 134 answered the questionnaire.
Results: The prevalence of respiratory symptoms did not differ between the PiZ and SZ groups. Sixteen percent of PiZ and 14% of PiSZ subjects had asthma. Four current smokers (67%) and 22% of ex-smokers/never-smokers reported recurrent wheezing (p = 0.03). No difference in FEV1 or FEV1/FVC ratio was found between the PiZ, SZ (5% being smokers), and MM individuals (all nonsmokers). A decreased FEV1/FVC ratio was found in PiZ subjects with neonatal cholestasis, compared to remaining PiZ subjects (p = 0.02). Recurrent wheezers at age 2 years with AAT deficiency had decreased FEV1/FVC ratio (p = 0.025) at age 26 years. None had clinical symptoms of liver disease. Six percent of PiZ and 9% of PiSZ subjects had a marginal increase of serum alanine aminotransferase; 7% of PiZ and 4% of PiSZ had abnormal γ-glutamyl transferase test results. The PiZ and SZ individuals had decreased plasma albumin (p = 0.0002). Secretory leukocyte protease inhibitor (SLPI) was increased in PiZ and SZ subjects compared to PiMM subjects (p = 0.0001). Neutrophil lipocalin was decreased in PiZ subjects (p = 0.0004) and PiSZ subjects (p = 0.001) compared to PiMM individuals. The elastase/AAT complex concentration was lower in AAT-deficient subjects (p = 0.0001).
Conclusion: Twenty-six-year-old PiZ and SZ individuals (5% smokers) had normal lung function test results, and 4 to 9% had marginal deviations in liver test results. Analyses of SLPI and neutrophil lipocalin, a marker of neutrophil activity, indicate compensatory changes in the AAT-deficiency state.
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Akbar Waheed joined the Georgetown University men's basketball staff as an assistant coach in May 2016.
Waheed came to the Hilltop after spending the 2015-16 season as an assistant coach at Hofstra University. The Pride finished the 2015-16 season with a 24-10 record and an appearance in the National Invitation Tournament (NIT).
"Akbar will be a tremendous addition to our staff,' Thompson said. "His strengths are multi-faceted, he has a history of identifying, evaluating, recruiting and developing young men. Each aspect is essential. He is extremely smart and is a tireless worker."
Waheed, who spent the 2014-15 season as a scout with the Oklahoma City Thunder of the National Basketball Association, has nearly 15 years of NCAA Division I coaching experience, with stops at Niagara and Boston College, in addition to Hofstra.
In his career as an assistant coach, Waheed has been part of five postseason teams, including two squads that advanced to the NCAA Tournament. Prior to spending the 2014-15 season with the Thunder, Waheed worked at Boston College from 2010 to 2014.
Waheed spent 11 years as an assistant to Joe Mihalich at Niagara University, where the Purple Eagles averaged nearly 19 wins per season and earned four postseason tournament berths. During his time at Niagara, the Purple Eagles posted a 206-135 record, earned an NCAA Tournament win, a pair of NCAA Tournament berths, two Metro Atlantic Athletic Conference (MAAC) Championships, two trips to the NIT and two MAAC regular season titles. He was a part of four 20-win seasons in Buffalo.
A skilled recruiter and strong developer of talent, Waheed helped recruit and develop a multitude of players that have gone on to the professional ranks, most recently Olivier Hanlan (Utah Jazz) and Reggie Jackson (Oklahoma City Thunder).
Waheed graduated from Niagara in 1999 with a degree in communications. He earned his master's degree in school counseling from Niagara in 2007.
Waheed was a standout at Gonzaga College High School, helping the team reach a national rank as high as No. 6 in the country when he was a junior.
Waheed and his wife, Nicole, have three children, daughter Infiniti, and sons, Akbar III and Jahlil.


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Easy Living. Seeking cozy comfort that leaves a nice cushion in your budget? Look no further than the Adrian Taupe collection! The full look offers a ... see more
Adrian Sofa - Taupe$359.99
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text: hi, When my 360 tried updating for the latest update I lost all my game saves due to the hard drive reading 'unformatted' I didn't reset the xbox or anything, but when it was done, so was my HD and all my saves for over 40 games. What hurt was Bully, and Crackdown as I was about 80% done with those. To get these achievements would make me restart at the beginning for everything besides Modern Warfare 2 which when I logged in had my completion %'s correct. It is likely the XBOX,so I am using my spare. I spoke to xbox they didn't seem to want to deal with it, just apologetic. Can we now at least back these up on usb?? ironic


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|Home | About | Journals | Submit | Contact Us | Français
Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Affected cases commonly present with oral and ocular dryness, thought to be the result of inflammatory cell-mediated gland dysfunction. To identify important molecular pathways involved in SS, we used high-density microarrays to define global gene expression profiles in peripheral blood. We first analyzed 21 SS cases and 23 controls and identified a prominent pattern of overexpressed genes that are inducible by interferons (IFNs). These results were confirmed by evaluation of a second independent dataset of 17 SS cases and 22 controls. Additional inflammatory and immune-related pathways with altered expression patterns in SS cases included B and T cell receptor, IGF-1, GM-CSF, PPARα/RXRα, and PI3/AKT signaling. Exploration of these data for relationships to clinical features of disease revealed that expression levels for most IFN-inducible genes were positively correlated with titers of anti-Ro/SSA (P<0.001) and anti-La/SSB (P<0.001) autoantibodies. Diagnostic and therapeutic approaches targeting IFN signaling pathway may prove most effective in the subset of SS cases who produce anti-Ro/SSA and anti-La/SSB autoantibodies. Our results strongly support innate and adaptive immune processes in the pathogenesis of SS and provide numerous candidate disease markers for further study.
Lymphocytic infiltration into exocrine glands is a hallmark of Sjögren's syndrome (SS) pathogenesis. Disruption of target organ function, particularly salivary and lacrimal gland secretion, may lead to severe and irreversible damage. The extent to which the exocrinopathy affects saliva and tear production varies, but moisture can be virtually nonexistent and lead to corneal scarring, blurred vision, rampant dental caries, recurrent oral infections, and difficulty with speaking, swallowing and eating1; 2. Extraglandular manifestations in SS are also common, heterogeneous, and may involve the skin and genitourinary tracts, as well as the hematologic, neurologic, respiratory, gastrointestinal, vascular, and musculoskeletal systems. Approximately half of SS cases experience lymphocytic mediated organ damage3. Increased risk of lymphoma in SS cases has been established, with estimates as high as 44-fold4. Approximately half of SS cases present an accompanying autoimmune rheumatic disease, most commonly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or scleroderma5.
The molecular basis of SS is not well defined, but includes production of autoantibodies, dysfunction of molecular water transport processes, dysregulation of apoptosis, and cytokine activity abnormalities4; 6–8. A role for viral infection in SS has long been suspected but difficult to establish. Numerous viruses have been considered, including Epstein-Barr virus (EBV), cytomegalovirus, hepatitis C virus, human herpes virus 6, coxsackie virus and several retroviruses9; 10. Specific evidence supporting these candidate viruses vary, but include such properties as the ability to directly infect cells in the salivary gland and/or immune system, sequence similarities between viral proteins and autoantigens (particularly La/SSB) suggesting molecular mimicry, elevation of viral antibodies or viral sequences, association between viral infection and lymphoma, and association of symptoms mimicking SS following viral infection. Regardless of the specific virus, mechanisms of host-virus relationships that control or perpetuate latency/re-activation cycles of viral replication and inflammatory responses, such as production of IFNs, are likely to be important in SS.
Multiple genes are thought to increase disease susceptibility to SS, including human leukocyte antigen (HLA) loci, interleukin 10 (IL-10), Fas, Fas ligand (FasL), and more recently, interferon regulatory factor 5 (IRF5)11; 12. Other polymorphisms have been found to be associated with various clinical features of SS. For example, association of anti-Ro/SSA autoantibody with the 52kD Ro/SSA gene13, Ig KM and GM genes with clinical presentation of SS14, and apoE with early onset of SS have been described15.
Developments in high-throughput transcriptional profiling employing microarray technology have dramatically expanded our ability to identify key molecular pathways related to disease. Previous studies using microarray approaches in SS have been limited to studies of salivary tissue in relatively small cohorts of cases. These studies have identified over-expression of interferon (IFN)-inducible genes in salivary gland tissue from SS cases16; 17, similar to that seen in other autoimmune diseases18.
The identification of biomarkers for SS in peripheral blood mononuclear cells (PBMCs) or whole blood (WB) cells offers a very practical alternative to current approaches for diagnosis and classification of SS cases19. Furthermore, peripheral blood has proven to be informative for advancing our understanding of related autoimmune diseases including SLE, RA, psoriasis, and multiple sclerosis18. In the present study, we sought to identify important disease associated pathways and explore correlations of gene expression profiles to relevant clinical features of SS.
As an initial discovery effort, global mRNA transcript levels were measured in PBMCs of 21 SS cases and 23 healthy controls (Cohort 1) using Affymetrix U95A2 GeneChips containing 12,626 oligonucleotide probe sets. Demographic features of participant cohorts are shown in Table 1. To identify differentially expressed transcripts between SS cases and controls, we used three data filtering criteria: Welch t-test P-value ≤ 0.001, mean fold change ≥ 1.5 and mean expression difference ≥ 100. A total of 425 mRNA transcripts representing 382 unique genes were identified as differentially expressed in SS cases (Figure 1A, Supplementary Table 1). Approximately 40 genes were identified more than once by multiple probesets on the Affymetrix arrays. Significance levels for some transcripts reached P-values < 10−14 and fold-changes as high as 24 (Table 3, Supplementary Table 1). We observed 129 overexpressed and 296 underexpressed mRNA transcripts in SS cases relative to controls.
Unsupervised hierarchical cluster analysis was conducted to visualize patterns of the 425 differentially expressed transcripts (Figure 1A). Of the 129 overexpressed transcripts, 46% (n=59) are known to be inducible by IFNs (Figure 1A, Supplementary Table 1). Genes in this cluster include interferon-induced protein 35 (IFI35, P= 1.34 × 10−11), myxovirus (influenza virus) resistance 1 (MX1, P= 9.94 × 10−8), 2′5′-oligoadenylate synthetase 1 (OAS1, P= 1.05 × 10−7), interferon regulatory factor 7 (IRF7, P=1.98 × 10−7), and OAS 2 (P=3.15 × 10−7).
We then used INGENUITY PATHWAYS ANALYSIS (IPA) software (ver. 5.5) to facilitate the systematic identification and grouping of differentially expressed genes into biological networks. Fifty-nine functional categories were identified by IPA as statistically significant for the 425 differentially expressed transcripts. Table 2 presents the top 20 most significant biological function categories (see Supplementary Table 2 for a list of all functional categories and sub-categories). Cell death was the most significant biological function with sub-category p-values ranging from 2.55×10−11 to 2.96×10−3, followed by cellular growth and proliferation (P = 3.67×10−8 to 1.72×10−3) and immune and lymphatic system development and function (P = 2.39×10−9 to 2.83×10−3).
IPA also identified 42 statistically significant canonical pathways from our list of differentially expressed transcripts in Cohort 1 (Supplementary Table 1). As shown in Figure 2, IFN signaling was the most significant pathway (P = 1.57×10−5) followed by B cell receptor signaling, IGF-1 (insulin-like growth factor-1) signaling, GM-CSF (granulocyte macrophage-colony stimulating factor) signaling, PPAR (peroxisome proliferator-activated receptor) signaling, PPARα/RXRα activation, T cell receptor signaling, PI3/AKT (phophatidylinosital 3-kinase) signaling, acute phase response signaling, and JAK/STAT (janus kinase/signal transducer and activator) signaling among others (Figure 2). In general, transcripts involved in IFN signaling and protein ubiquitination were largely overexpressed while the majority of transcripts from other pathways identified were underexpressed in SS cases versus controls. Significant overlap of differentially expressed genes was apparent across the 42 canonical pathways. For example, five genes (RRAS, KRAS, PIK3CA, PIK3R1, PIK3CG) are multifunctional transcription factors or signaling molecules involved in over 20 of the 42 canonical pathways we identified. In addition, over 57% of the genes shown in Figure 2 mapped to the top 9 most statistically significant pathways (P < 0.001) identified by IPA. Within these 9, two sets of pathways were closely related: PPARa/RXRa activation/signaling and B cell/T cell receptor pathways. Of the remaining 33 pathways, 15 consisted entirely of genes that directly overlap with other pathways in Figure 2.
We next evaluated an independent group of 17 cases and 22 controls (Cohort 2, Table 1). Affymetrix U133A GeneChips with an expanded representation of 22,283 oligonucleotide probe sets were used to measure RNA transcript levels in this independent Cohort. In addition to expanding the overall number of transcripts assayed in Cohort 2, we were also able to utilize more recently developed blood collection procedures that stabilize RNA transcript levels at the time of phlebotomy (see Methods). As opposed to selecting a few transcripts for validation studies of our results from Cohort 1 (commonly done by quantitative PCR), this comparison provided a much more comprehensive approach for confirmation of the differentially expressed pathways through replication in an independent set of cases and controls.
Using the same 3-step data filtering approach (Welch t-test P-value ≤ 0.001, mean fold change ≥ 1.5 and mean expression difference ≥ 100), 120 RNA transcripts in 100 genes (18 underexpressed and 102 overexpressed) were identified as differentially expressed in cases relative to controls (Supplementary Table 3). Cluster and pathway analysis of significant transcripts were used to identify gene expression patterns (Figure 1B, Figure 2). Similar to the results in Cohort 1, the prominent signature of overexpressed IFN-inducible genes was observed in Cohort 2 (Figure 1B). Comparison of differentially expressed transcript lists for Cohort 1 and Cohort 2 resulted in identification of a total of 38 genes common to both cohorts, the majority (n=34, 89%) of which represented IFN-inducible transcripts (Table 3). Thus, these genes represent a reproducible "IFN signature" identifiable in peripheral blood of SS cases.
Table 4 provides the results for selected IFN and IFN pathway regulators in both Cohorts 1 and 2. In general, the majority of IFN genes encoding the IFNs themselves were not differentially expressed in peripheral blood. In contrast, interferon regulatory factor 7 (IRF7), a key transcription factor involved in downstream signaling events triggered through IFN or Toll-like receptors, was upregulated by over 2-fold in both datasets (Cohort 1 P=5.57×10−6, Cohort 2 P=1.98×10−7). Approximately 66% of the transcripts in this group were differentially expressed by 2-fold or greater in at least one cohort.
It is possible that the difference in age observed between cases and controls in Cohort 1 (mean for cases = 57, mean for controls = 31) may have contributed to a larger number of differentially expressed transcripts indentified in Cohort 1 (n = 425 in Cohort 1 and n = 120 in Cohort 2). However, we believe that the use of whole blood in Cohort 2 is likely to have a greater impact in our ability to detect differential expression, since an excess of globin transcripts in whole blood microarray experiments has been shown to mask signatures of biological relevance and produce fewer significant results when compared directly with PBMCs. Moreover, a direct comparison of our list of differentially expressed genes observed in Cohort 1 with a list of genes related to aging provided by the GenAge Database (http://genomics.senescence.info/genes/) resulted in very few overlaps (n=15). Additional evidence to support association with SS for all of these 15 genes exists, either through results of other undergoing microarray studies (Moser KL, unpublished data), inclusion in significant biological pathways with several other genes identified as differentially expressed in this study, or previous reports in the literature. Finally, despite the difference in number of differentially expressed transcripts between Cohorts 1 and 2, many of the significant canonical pathways were observed in both Cohorts. Using IPA, 10 statistically significant canonical pathways were identified in Cohort 2, nine of which were also observed in Cohort 1 (Figure 2, indicated in bold). One additional pathway, antigen presentation, was statistically significant in Cohort 2 (P=0.0025). In Cohort 1, the antigen presentation pathway was ranked 43rd and fell just below the threshold for significance (P=0.056).
Thus, using two independent cohorts, alternative versions of microarray GeneChips, and varying sample compositions of either PBMCs (Cohort 1) or WB (Cohort 2), we have observed consistent, reproducible overexpression of IFN-inducible gene expression patterns and identified several additional pathways characterized by downregulated patterns of gene expression in pSS cases compared with normal controls.
We next wanted to explore the association between dysregulated pathways and clinical measures of SS. To maximize our statistical power, we generated a third, larger dataset consisting of a total of 36 SS cases and 22 controls (Cohort 3). All data for Cohort 3 was generated from whole blood using the Affymetrix U133A GeneChips containing 22,283 probesets. We combined all available data from Cohort 2 with new data from Cohort 1 subjects who were resampled using PAXgene tubes (and thus, assayed from whole blood and assayed using the U133A GeneChip to be amenable for combining with Cohort 1 data). Because Cohort 3 included all subjects from both Cohort 2 and most subjects from Cohort 1, analysis of this third dataset was not considered independent from the results described above, but did allow more statistically robust results given the large sample size for correlation analyses (see Methods). The clinical variables evaluated included saliva production measured by whole unstimulated salivary flow (WUSF), tear flow measured by Schirmer's test (ST), and titers of anti-Ro/SSA and anti-La/SSB autoantibodies determined by ELISA.
Figure 3a shows the hierarchical cluster graph of 223 RNA transcripts in 193 genes (197 overexpressed and 86 underexpressed) identified as differentially expressed between Cohort 3 SS cases and controls using the three-filter criteria (Supplementary Table 4). The distributions of clinical variable values are shown in Figure 3b. Correlation coefficients for RNA expression values with tear flow, salivary flow and autoantibody titers (measured in the same sample for each individual) were estimated for the 223 differentially expressed RNA transcripts in the group of 36 SS cases. Healthy controls were not included in these analyses so that we could assess significant correlations defined within the case group only.
As shown in Figure 3c, most of the correlation tests did not reach statistical significance (P > 0.05) for salivary flow or tear flow (WUSF and ST, respectively). This is an expected result since all SS cases are ascertained based on reduced values for these clinical variables. Of the 223 RNA transcripts, only 11 were significantly correlated with salivary flow (5%) and 17 for tear flow (8%). Of the 86 underexpressed RNA transcripts, ≤ 6% correlated with titers of anti-Ro/SSA and anti-La/SSB autoantibodies (3 and 5 transcripts, respectively). In contrast, a large proportion of the 197 overexpressed RNA transcripts were positively correlated (P < 0.05) with titers of anti-Ro/SSA (n=89 or 45% of the transcripts) and anti-La/SSB (n=76 or 39% of the transcripts). Approximately two-thirds of the RNA transcripts that were correlated with anti-Ro/SSA and/or anti-La/SSB autoantibodies are known to be IFN-inducible genes. Correlations between the clinical variables tested and transcripts involved in other dysregulated pathways identified in Cohorts 1 and 2 (e.g. B/T cell receptor signaling, IGF1R, GM-CSF signaling, etc.) were not observed (Figure 3).
We have applied microarray technology to define global gene expression profiles in pSS and identified several key pathways that are dysregulated in cases versus normal controls. Our study is the first to demonstrate that upregulation of IFN-inducible gene expression is prominent in peripheral blood cells of many SS cases, and correlates with high titers of anti-Ro/SSA and anti-La/SSB. In addition, analysis of two independent cohorts revealed evidence for dysregulation of signaling through the B cell/T cell receptors, IGF-1, GM-CSF, PPARα/RXRα, and several cytokine pathways that appear to be consistent across all SS cases.
Microarray-based studies in human pSS have previously focused on the identification of disease associated pathways in saliva or in minor salivary gland tissue from relatively small cohorts (10 or fewer cases plus controls)16; 17; 20; 21. A common finding across the four studies reported to date is upregulation of IFN-inducible genes. Genes overexpressed in our data generated using peripheral blood that have also been reported as upregulated in minor salivary glands and/or saliva from SS cases include interferon-induced transmembrane proteins 1 (9–27, IFITM1) and 3 (1-8U, IFITM3), promyelocytic leukaemia (PML), transporter 2 ATP-binding cassette (TAP2), spleen tyrosine kinase (SYK), guanylate binding protein, 2 (GBP2), and interferon-induced protein 44 (IFI44)16; 17; 20. These genes and others that show similar consistency across multiple sample types underscore both the local and systemic nature of IFN pathway dysregulation. Furthermore, these genes may serve as especially attractive targets for development of clinically useful biomarkers. Disease markers that are both central to pathology in target tissues (e.g. salivary glands) and potentially more feasible to assay through saliva or serum-based diagnostic tests would provide a significant improvement over the current approaches to classification of SS cases.
In recent years, upregulation of IFN pathway signaling has been noted in a growing list of autoimmune disorders, including psoriasis, multiple sclerosis, rheumatoid arthritis, dermatomyositis, primary biliary cirrhosis, and insulin-dependent diabetes mellitus 18. The IFN-inducible gene expression profile we report in SS is remarkably similar to the "IFN signature" that has been observed in similar studies of peripheral blood in SLE, present in a majority of cases22 (Moser KL, unpublished observations). In addition to overlap of certain clinical features in both SLE and SS, production of anti-Ro/SSA and anti-La/SSB autoantibodies are common in both disorders. In our study, the IFN signature in SS was significantly correlated with high titers of anti-Ro/SSA and anti-La/SSB. Although the precise underlying disease mechanism connecting IFN pathway activation and autoantibody production is unclear, these results provide further support to link both innate and adaptive immune responses to the pathogenesis of disease.
Activation and control of IFN-inducible genes may be dysregulated due to abnormal levels or activity of a class of transcription factors known as interferon regulatory factors (IRFs). For example, IRF-1 and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I IFN system; IRF-1 functions as a transcriptional activator, and IRF-2 represses IRF-1 function by competing for the same cis elements23. Evidence from our data sets suggests IRF-1 is upregulated and IRF-2 is downregulated in SS cases. Such an imbalance is consistent with upregulation of IFN-inducible genes. Furthermore, IRF-5 and IRF-7, both upregulated in our data, play a crucial role in the expression of type I IFN genes, cytokines and some chemokines24; 25. Interestingly, EBV regulates and uses IRF-7 as a secondary mediator for several target genes involved in latency and immune regulation. In addition, Ning et al. have demonstrated that the virus activated factor of Sendie virus binds to IRF7 IFN stimulating element and can directly activate IRF7 transcription independent of IFN-triggered JAK-STAT pathway 26. Finally, genetic association of polymorphisms in IRF5 and STAT4, directly involved in IFN pathway signaling, with both SLE and SS has been reported12; 27–30
Collectively, these observations indicate that overexpression of IFN responding genes in SS may result not from overexpression of IFN genes themselves but rather from effects mediated more directly by viral infection and/or genetic variants in IRFs and other IFN pathway mediators that contribute to altered signaling. The potential role of the Type I interferon system in SS was recently reviewed by Nordmark et al31. Current data supports a mechanism of disease in which an initial viral infection induces Type I interferon production in salivary glands, leading to apoptosis or necrosis of glandular epithelial cells and exposure of autoantigens such as anti-Ro/SSA and anti-La/SSB followed by activation of adaptive immune responses (both locally and systemically). Production of autoantibodies (including anti-Ro/SSA and anti-La/SSB) that form immune complexes with nucleic acids may trigger prolonged activation of IFN pathways through Toll-like receptor-medicated stimulation of plamacytoid dendritic cells31. Additional production of IFNs, as well as cytokines known to be relevant to SS including, IL-12, IL-6, TNF, CXCL10, and CCL3, can be produced by pDCs, leading to recruitment and perpetuation of a continuous cycle if not properly downregulated32. Consequently, this process leads to impaired function of affected exocrine glands and potential systemic manifestations commonly seen in SS patients. Our results showing correlations between IFN pathway activation and autoantibodies bring up important considerations for the development of improved diagnostic and therapeutic strategies. We propose that development of biomarkers which reflect the IFN signature and therapies directed against IFN pathway activation are most likely to be successful in the subset of patients with high-titers of anti-Ro/SSA and/or anti-La/SSB.
IPA identified 59 functional categories associated with the list of differentially expressed genes identified in Cohort 1. We found these categories to be too broad for the development of hypotheses of disease mechanisms, and as a result, have focused our attention on canonical pathways. In addition to upregulation of an IFN-inducible gene expression pattern, we identified over 40 additional canonical pathways that were differentially expressed in our PBMC dataset using IPA. However, these pathways do not appear to be independent of each other. Close examination of the genes included in these pathways revealed a significant amount of overlap, most likely reflecting the extensive "crosstalk" that occurs among closely related biological pathways. These results suggest that certain pathways, such as those initiated through B or T cell receptor signaling, account for the seemingly large number of the pathways identified by using approaches such as IPA.
Several of the canonical pathways and dysregulated genes (outside of the "IFN signature") represent interesting and potentially important new avenues for further investigation. For example, B cell/T cell receptor signaling was significantly dysregulated in this study. One of the genes in these pathways, PTPRC or protein-tyrosine phosphatase, receptor-type, C (also known as CD45, CD45R, and Ly5), is a major leukocyte cell surface molecule that suppresses JAK kinase and negatively regulates cytokine receptor signaling 33. PTPRC is essential for activation of T cells and B cells, and important for integrin-mediated adhesion and migration of immune cells. In our data, PTPRC was overexpressed in cases versus controls, consistent with enhanced downregulation of other B/T cell pathway genes observed. Targeted disruption of PTPRC has been shown to enhance cytokine and interferon receptor-mediated activation of JAK and STAT proteins33. Furthermore, genetic associations of variants in PTPRC have been reported with multiple sclerosis, Grave's disease and Hashimoto's thyroiditis34. In murine models, genetic variants in PTPRC lead to lymphoproliferation and severe autoimmune nephritis with autoantibody production and alterations in cytokine production. Thus, evaluation of PTPRC and other related genes in lymphocyte signaling pathways may be informative in further defining autoimmune responses in SS.
The insulin-like growth factor 1 receptor (IGF1R) was underexpressed in our study, consistent with a study of SS minor salivary glands by Katz et al35. Low levels of IGF1R have also been shown in the non-obese diabetic mouse model of experimental autoimmune sialadenitis36. Dysregulation of this pathway may result in the inability of IGF-1 to exert its homeostatic, protective effect in salivary tissue and lead to glandular atrophy and disfunction35.
Altered signaling through PPARα/RXRα pathways also offers intriguing clues to SS pathogenesis. PPARs (peroxisome proliferator-activated receptors) are nuclear receptors that when activated by ligand, form a functional transcriptional unit upon heterodimerization with retinoid X receptors (RXRs) 37. PPARα and related family members are critical modulators of environmental and dietary stimuli, and play a key role in downregulating inflammatory responses37; 38. In immune cells, PPARα inhibits inflammatory pathways through sequestration and repression of c-jun and NF-κB transcription factors38; 39. Underexpression of PPARα in SS cases relative to controls, as observed in our study, is thus consistent with a pro-inflammatory process. Interestingly, studies in experimental autoimmune encephalitis, a murine model of multiple sclerosis (MS), have demonstrated baseline lower expression levels of PPARα in CD4+ T cells from females relative to males, resulting in increased NF-κB and c-jun activity, higher production of IFN γ and tumor necrosis factor and thus, differential regulation of PPARα between genders may contribute to increase risk of disease in females with MS and other autoimmune diseases40. Agonists of PPARα have been proposed as a potential therapeutic approach in MS and several other autoimmune and inflammatory disorders associated with decreased PPARα expression such as psoriasis and atopic dermatitis41. Furthermore, PPARα agonists have been proposed as an effective therapeutic intervention for treatment of dry eye in SS42. Thus, further studies should be considered to explore the potential application of PPARα agonists as novel therapeutic agents.
In summary, using varying peripheral blood cell populations (mononuclear cells and whole blood), two independently collected cohorts of cases and controls, and two different versions of Affymetrix GeneChips (U95A and U133A), we have shown a consistent upregulation of IFN inducible genes in SS cases. Our results further show that this pattern is most prominent in the subset of cases serologically defined by increased titers of anti-Ro/SSA and anti-La/SSB autoantibodies. We also identified numerous additional signaling pathways that collectively support a significant role for both innate and adaptive immune dysregulation in SS. These results should foster multiple lines of further investigation including genetic and functional studies that will hopefully lead to new insights into pathogenesis of this complex autoimmune disorder.
All protocols used in this study were approved by the University of Minnesota Institutional Review Board. All participants provided written informed consent before entering the study. All SS cases met the 2002 Revised European Criteria proposed by the American European Consensus Group (AECG)19. Accordingly, cases were classified with SS if they had an autoimmune component (detection of anti-Ro/SSA and/or anti La/SSB autoantibodies) and/or evidence of lymphocytic infiltration through labial salivary gland histopathology, plus characteristic symptoms (dry eyes and dry mouth) and signs (decreased tear flow measured by Schirmer's test or decreased unstimulated whole salivary flow). Cohorts 1 and 2 consisted of independent subjects. Cohort 3 included 19/21 cases from Cohort 1 (samples redrawn, see below) plus all 17 cases from Cohort 2. Two of the cases in Cohort 1 also met the ACR criteria for SLE.
Controls were asymptomatic for dry eyes, dry mouth, and had no self-reported family history of autoimmune diseases. The first group of controls (n=17) consisted of all female Caucasians with an average age of 31, which were used for comparison with Case Cohort 1. The second group of controls (Cohort 2) was all female with 21/22 reporting Caucasian ancestry. These controls had a mean age of 51 and were used for analysis of both Case Cohorts 2 and 3.
Data collection procedures consisted of subject interviews, completion of a detailed questionnaire, review of medical records, physical examination, Schirmer's test without anesthesia (5 minutes), unstimulated salivary flow measurement (15 minutes), and phlebotomy for RNA extraction and determination of anti-Ro/SSA and anti-La/SSB autoantibodies.
Total RNA was extracted from PBMCs by Trizol (GIBCO/BRL, Invitrogen, Carlsbad, CA) or from whole blood using the PAXgene Blood RNA method (QIAGEN/BD, Valencia, CA). The methods for preparation of complimentary RNA (cRNA) were provided by the manufacturer (Affymetrix, Santa Clara, CA; GeneChip technical manual). Briefly, 5 to 10 mg of total RNA of each sample was converted into double stranded complimentary DNA (cDNA) using a Superscript cDNA synthesis kit (Invitrogen, Carlsbad, CA) with a oligo(dT)24 primer. After second-strand synthesis, labeled cRNA was generated from the cDNA sample by an in vitro transcription (IVT) reaction using BioArray labeled biotin ribonucleotides (Enzo, New York, NY). The labeled cRNA was purified using RNAeasy spin columns (Qiagen, Valencia, CA). Fifteen micrograms of each cRNA sample was fragmented by mild alkaline treatment, at 94°C for 35 min in fragmentation buffer (Tris Acetate PH.8.1/1M, 150 mM MgoAc and 500mM KoAc). Fragmented cRNAs were hybridized to Affymetrix Human U95Av2 or U133A GeneChips.
All Cohort 1 samples were collected in CPT tubes and processed within 4 hours of phlebotomy. However, given ex vivo changes that can be observed in expression levels for a substantial fraction of genes shortly after phlebotomy43, whole blood was directly collected into PAXgene tubes for Cohorts 2 and 3, which contain an RNA stabilizing agent. As a result, blood sample composition for Cohorts 2 and 3 (whole blood) were different than for Cohort 1 (peripheral blood mononuclear cells). A total of 19 subjects were drawn twice; first for inclusion in Cohort 1 and later for inclusion in Cohort 3.
The levels of anti-Ro/SSA and anti-La/SSB autoantibodies in the serum of SS cases and controls were measured by ELISA (Immunovision, Springdale, AR). Absorbance was measured at 490 nm. The cutoff absorbance value above which antibody levels were considered positive was set to the mean plus 2-times the standard deviation of titer values for controls.
Initial data processing involved several quality control checks assessing the starting and amplified RNA and the overall hybridization process. Quality control criteria included: 1) the ratio of 3′ to 5′ probe sets should be less than 3; 2) more than 30 percent of genes should be called 'present'; and 3) the murine sequences received an 'absent' call while human "housekeeping" sequences received a 'present' call.
We used GeneData Expressionist database and software (http://www.genedata.com) for further processing and analyzing the data. The MAS 5.0 (Affymetrix Microarray Suite 5) algorithm was used for data normalization. Gene expression intensity for each array was scaled to 1500 intensity units to allow comparison across all arrays. The scaled expression intensities were imported into GeneData Analyst (version 4.2) for statistical analysis.
In all 3 Cohorts, transcripts were defined as differentially expressed and selected for cluster analysis if, for the mean comparison between SS cases and healthy controls, the following criteria were met: 1) P-value of 0.001 or less from Welch t-tests; 2) change in mean expression of at least 1.5-fold; 3) mean expression difference of at least 100 units22. Hierarchical cluster analysis was applied to the 3 datasets using CLUSTER software and visualized using TREEVIEW software44.
Pearson correlation estimates and p-values between transcript levels and clinical variable measurements (anti-Ro/SSA, anti-La/SSB, WUSF, and ST) were computed for each of the differentially expressed transcripts. P-values of correlations for each transcript were plotted as a moving window average across units of 5 transcripts45.
INGENUITY PATHWAYS ANALYSIS (IPA; version 5.5) software (https://analysis.ingenuity.com) was used to determine significant functional categories and canonical pathways based on our lists of significant transcripts. IPA tests associations between specified genes and sets of functional genes that are part of biologically relevant networks according to literature findings. Right-tailed Fisher's exact tests are used to measure the likelihood that such associations are due to chance. The proportion of genes mapped to a specific canonical pathway that are specified by the user is taken into account for the computation of P-values.
This study was funded by NIH NIAMS RO1 AR050782 and the Phileona Foundation (KLM). The authors are grateful for resources provided by the University of Minnesota Supercomputing Institute and the Affymetrix core. We also thank Carolyn M. Meyer, Amber N. Leiran, Liliana Tobon, Daniella Machado, and Julie Ermer for their technical assistance and Jennifer Lessard for assistance with graphics. Finally, we thank the study participants without whom this study would not be possible.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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CD-adapco is the world`s largest independent CFD focused provider of engineering simulation software, support and services. We have over 30 years of experience in delivering industrial strength engineering simulation. The scope of our activities extends well beyond software development to encompass a wide range of CAE engineering services in both CFD and FEA. We have over ...
based in London, UNITED KINGDOM.
Osprey based in Whitstable in the United Kingdom, has been involved with Pollution Management, Energy Conservation and Dust Control since we started trading in 1985. Over the years we have built up unique skills in working with our clients to achieve ideal solutions without entailing excessive costs. From fully tailored dust & emission control systems to straightforward ...
based in Whitstable, UNITED KINGDOM.
Instrumatic a/s is a Danish company specialized in the development and manufacturing of emission monitoring equipment, designed especially for harsh environments. Instrumatic is known for is high quality products, and recognized by the product brands OXYTRON and OXYDAN.
based in Ry, DENMARK.
NILU Polska is involved in research regarding broadly defined environment protection and activities for transferring BATs into the Polish market, especially in the scope of energetic use of biomass, waste management and emission reduction. Our mission is a work for sustainable development by providing services based on current scientific research and best practices. We ...
based in Katowice, POLAND.
Pentol has become the leading European manufacturer of:Fuel oil additives for crude and heavy fuel oil fired.power stations, petrochemical plants and refineries,Flue Gas Conditioning for coal fired power stations we started to develop and produce additives and the corresponding dosing equipment. Today we are market leader for flue gas conditioning systems in Europe and a ...
based in Basel, SWITZERLAND.
For 30 years, EnviroCare International has designed and manufactured pollution control systems across a wide range of industrial and municipal applications for clients worldwide. Each of our over 1,000 installations is custom engineered and fabricated to meet the exact specifications of our clients and their individual applications. We offer advanced solutions to the ...
based in American Canyon, CALIFORNIA (USA).
Palas develops and builds fine dust monitoring devices, nanoparticle measurement systems, aerosol spectrometer systems, aerosol generators (for solid and liquid particles, dilution systems and filter (media) test systems. With more than 50 patents filed since 1983, Palas is continuously setting standards in the field of aerosol technology. Palas innovations result in ...
based in Karlsruhe, GERMANY.
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A 12-year-old boy who played a Scottish gangster in The Wee Man has become the youngest person to scoop a Bafta New Talent Award.
Daniel Kerr, who played a young Paul Ferris, drew raves for his mature performance in a movie that otherwise earned mixed reviews from critics.
"It just felt fantastic to even be nominated, it was a night to remember. I must be doing something right to win a Bafta," he said, after picking up his gong for Best Acting Performance. "I could relate to Paul Ferris as a young boy, getting up to mischief."
The Glaswegian actor's idol is James McAvoy, and he's already mimicking the Shameless actor by mixing low budget indie fare with huge blockbusters. Kerr filmed Disney's Maleficent, starring Angelina Jolie and due out in 2014, over the summer.
His stepfather Iain Kerr said that the production was shrouded in secrecy. "We only got a certain section of script that he's in," he said. And while Mr Kerr was sure Daniel had been telling his friends he had tea with Jolie, he said their interaction was more limited: "I think he gave her a nod and a wink, he says she winked back."
Kerr has been acting since the age of four, but he struggled to find an agent in Scotland. His current agent, Jess Bell, said she was astonished he hadn't already been picked up when he travelled to Manchester for an audition three years ago.
"He was the sweetest little thing," she said. "But when we said 'be a bully' he could do it, and he could be vulnerable too. He could turn it off and on, and cry too."
Mr Kerr said Daniel is broadly unaware of his own talents and isn't starry or affected.
"We keep him grounded, he still comes home and does his homework. You see these kids with [ideas above] their station but he's got a good grounding in family life."
- More about:
- Actors And Actresses
- Cinema
- Independent Cinema


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Sleeps 8
Bedrooms 4
Bathrooms 2
Pets Yes
- Off road parking
- Ground floor bedroom
- Open fire
- Smoke-free
- Garden / Patio
- Washing machine
- Seaside
- Broadband / WiFi
Gwenver Beach Collection
Sennen Cove 1.7 miles. Perfect for beach and coastal holidays and short breaks, these properties are set in a stunning location with private access to Gwenver beach close to Sennen Cove, 5 miles from Lands' End and 9 miles from the ancient market town of Penzance. As soon as you arrive down the private drive you feel immediately relaxed with amazing sea views all the way. The properties are well-equipped and two have a balcony where you can sit out with your morning cup of tea and enjoy your surroundings. The nearby beach is sandy and around 150 yards long and with some of the best surfing conditions in Cornwall it is surprising that it never gets too crowded. For those who want to relax and watch the surfing action the beach is a real suntrap located at the base of steep granite cliffs. With superb coastal walks in either direction right from the door walkers will also be in their element here. Adjoining is Sennen Cove with Whitesands beach, one of the cleanest in Europe and named in the top 20 secret beaches in the British Isles. Sennen Cove still retains much of the atmosphere of an old fishing village, with a small number of local fishing boats plying their trade from the harbour. With Sennen having a great pub, a top class restaurant, a café, fish and chip shop as well as a village shop you will have all the ingredients for a great holiday whatever time of year.
Sleeps 4 | Bedrooms 1
7 nights from 304.00
Sleeps 4 | Bedrooms 2
7 nights from 364.00
Sleeps 6 | Bedrooms 3
7 nights from 414.00
The property
You approach this large, spacious house which is set in extensive grounds along a private sweeping drive with the amazing ocean views on your left.
Enter into the large entrance hall with a seating area overlooking and opening out onto the sheltered, walled courtyard, which provides a real suntrap and is perfect for alfresco dining.
There are four bedrooms at this superb holiday home, with the master double boasting French doors that lead you out onto the courtyard.
There's also a twin room on the ground floor, and another double and twin are accessed up just three steps.
Stairs lead to a first floor, informal sitting room with wonderful views of the garden and sea, and there's also another welcoming, first floor sitting room to relax in, a ground floor dining room and a delightful conservatory with windows on each side to make the most of the amazing views.
With a well-equipped kitchen and two bathrooms, both with baths and separate showers completing the accommodation, you have all you need for the perfect family holiday home.
Note: This property is 100 yards from Refs 932663, 932664 and 932665, together they sleep 22.
Four bedrooms: 1 x double, 1 x ground floor double, 1 x twin, 1 x ground floor twin. Bathroom with bath, separate shower, basin and WC. Ground floor bathroom with bath, separate shower, basin and WC. Kitchen. Dining room. Two first floor sitting rooms, one with open fire. Conservatory.
- Gas central heating with open fire
- Gas range double oven with gas hob, microwave, fridge, freezer, washer/dryer, TV with Freeview, DVD, WiFi, selection of books, games and DVDs
- Fuel, power and fuel for fire inc. in rent
- Bed linen and towels inc. in rent
- Off road parking for 4 cars
- Front courtyard with furniture and BBQ
- Two well-behaved pets welcome
- Sorry, no smoking
- Shop and pub 1.7 miles.
About the location
St Just 5 miles; Penzance 9 miles.
The small fishing village of Sennen Cove is situated close to Land's End in Cornwall. The village has a lifeboat station, church, a couple of shops, a café plus two popular gastropubs. The town of St Just is the nearest town to Land's End and has several monument and prehistoric antiquities, including a Bronze Age settlement at Cape Cornwall. The town also has a town hall, a church, shops and pubs, and Plain-an-Gwarry, a theatre used for miracle plays in medieval times. Porthcorno, which has the outdoor Minack Theatre is situated 5 miles away. The village of Mousehole is within a short drive where stargazy pie can be sampled. Also within reach is the town of Penzance, which boasts winding streets, shops, clubs, restaurants and a harbour, from where day trips to the Scilly Isles can be enjoyed. A lovely base for your Cornwall adventure.
Region Information
This property offers the following short breaks:
- Winter
- Off-season
- Last minute
- Christmas


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Qualcomm (QCOM) was one of the great growth stories of the 1999 dot-com boom. Its stock blasted out of a base and soared more than 2,000% before finishing its big move with a spectacular climax run.
Times have changed. Today, Qualcomm is still on the cutting edge, but it's a mature company that pays a dividend.
Qualcomm makes chips and software for cellphones, whose carriers use either a CDMA or GSM platform. Most U.S. providers, such as Verizon (VZ), use CDMA. AT&T (T) and the rest of the world use GSM.
Qualcomm's chips are found in the iPhone and Samsung Galaxy and other Android devices.
In the most recent quarter, earnings fell 20% amid fears of slowing smartphone sales. But the stock quickly recovered and has moved higher despite a weaker market.
Analysts expect earnings to increase just 4% in the next report, but they see a 14% rise for the full year and a 12% increase in 2015.
The five-year annualized EPS growth rate is 21% and the Earnings Stability Factor is 6 on a 0 to 99 scale, with low numbers corresponding to steady earnings growth.
Qualcomm is in a hot industry group. As of Tuesday's IBD, the Electronics-Semiconductor Fabless industry group was ranked No. 13 out of 197 industry groups tracked by IBD. It was ranked No. 32 just six weeks ago.
The return on equity was an impressive 23% in 2013, well above the 17% benchmark investors should look for.
The company has no long-term debt.
Pretax margins last year were 38%, although that's the lowest in several years.
Qualcomm has offered a dividend since 2003, when it paid out 2.5 cents per share per quarter, adjusted for a stock split. That works out to a 2.1% annual yield.
The dividend is now 42 cents. The next dividend will be paid out June 25 to shareholders of record on June 2.


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Nirvana Short Light Grey Melange
Introducing the luxury sweat short in our new viscose french fabric.
Introducing the french viscose range. This has been designed to complete your look to take you to and from class, simply pull these pieces over your base layers, perfect for pre and apres yoga. The Nirvana Short, a great layering comfy, functional, yogi must have.


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Journeyman Commuter Leather Messenger Bag
Intrepid Bag Co
Journeyman Commuter Leather Messenger Bag
"The Journeyman Bag will become an asset in almost every travel situation" - CultOfMac.com
"A grownups messenger bag... because the bag you wear should send a message, not just deliver it" - InsideHook.com
"One step closer to our Indiana Jones fantasy" - DailyXY.com
"This bag will only get better looking with time" - Muted.com
Your commute just got cooler. The Journeyman is a cross-body minimalist messenger bag made from high-end, full-grain, Latigo Saddle Leather. Think of it as your Laptop wallet. Featuring an innovative laptop suspension technology for a 13" laptop or iPad Pro that gently cradles your tech, lifting it away from your back, allowing the bag to conform to you and not your stuff. The more you put in it the more comfortable it becomes!
The Journeyman's unique styling and fit makes it a true stand out with its 2" padded side-mounted strap that disperses weight evenly across your shoulders and stays in place perfectly. It will become your new lifelong traveling partner for all your EDC that only gets better with age. There is an adventure in every bag, we guarantee it.
Journeyman Features:
Yes if...
… You know what EDC stands for. #Everydaycarry
… You see Minimalism as a way of life, not just an art form
… You know the best pizza joint in each of the 5 boroughs
… You know the difference between SoHo, SoMa, and MoMA
… You navigate the concrete jungles like Tarzan in skinny jeans
… You have a complicated relationship with your mustache
… Your single speed bike costs more than most people's first car
… Your music collection is curated as fastidiously as the Louvre
… You live life one cold-brewed coffee at a time
… You decide what cafe to hit up based on internet speeds
… Your business suit hangs next to your wet suit
… You wait each year for that special craft brew
… You wonder why "early adopters" are always so late to the party
Lillium Leather Side Purse Hip Satchel
Intrepid Bag Co
Lillium Leather Side Purse Hip Satchel
Shipping now! Get em while they are hot.
"Made with an almost absurd attention to quality" - CultOfMac.com
"Lara Croft would totally rock these" - ChipChick.com
"So wild west it's ridiculous" - iMore.com
The Lillium is a European styled hands-free belt, cross body, and side purse made from the most durable and gorgeous top grain leather around. Its sleek gunslinger silhouette houses an iPad Mini (or iPhone 6 Plus!!) in a microsuede lined pocket. If Lara Croft carried an iPad Mini, this is how she would do it. 4 compartments mean there is room for a 7" tablet, smartphone, battery pack, cords, headphones, make up, credit cards, and more.
There are three versatile ways to wear the Lillium: Cross-Hip, Cross-Body, and Classic Shoulder Purse Style. Also, here is a little secret about the Lillium, there is a hidden Passport and money pocket on the back. The Lillium maintains its slim structure even at its fullest, leaving you ready for a day of adventure.
Yes if...
… You see yourself as an urban Lara Croft
… You are active and always on the go
… You've got more important things to do than carry a purse
… The world is your playground, and you like it rowdy
... You buck fashion trends and keep it timeless
... You value convenience and utility
... You are audacious and wondrous
… You'll try anything twice
... 'Wanderlust' is your favorite word
Still not sure? Read a day in the life of the Lillium Side Purse.
Tech Dopp Kit & Cord Organizer
Intrepid Bag Co
Tech Dopp Kit & Cord Organizer
In Stock Now, get them while we have them!
The Intrepid Tech Roll is a completely unique tuck-and-roll organizational system for all your small tech items such as: cords, hard drives, battery back up, plugs, and more. The brilliance in this design is that you do not have remove any of the items from the Smoke Grey canvas pockets to use them. Each has a pull-through plug opening that lets you both plug in and charge without removing anything from the cord organizer, so everything always stays organized and tangle free. In addition to the cord pockets there is a large covered pocket for storing a battery pack or hard drive. Just pull the plug through and you are ready to use it.
A zippered pocket is also there to put all your odds and ends in a safe place, with exterior specially sized mini pockets for SD Cards. This all folds up elegantly and compactly into a Mahogany leather exterior that speaks for itself, with wrap around straps for full secure expansion. This is especially great for travel because it is as simple as opening the Tech Dopp Kit and plugging in. No stray cords to lose. When you are finished, just tuck and roll.
Wayfarer Leather Messenger Bag
Intrepid Bag Co
Wayfarer Leather Messenger Bag
In Stock Now!
The Wayfarer Messenger bag is swimming with space and versatility for modern day explorers. The big brother of the Journeyman Commuter, this is the perfect bag for those who need to carry a bit more on their travels. Featuring an incredible body contouring design that can be worn comfortably in multiple ways: messenger bag style across the back, cross-body, or along the side on either shoulder.
Perfect for a day in the city even a weekend away, you can easily fit up to a 15" Macbook Pro (2016 model), iPad, a change of clothes, and all your other tech with room to spare. The front expanding pockets are perfect for an iPad Mini, a Macbook charger, and even our brilliantly useful Tech Roll.
Every detail has been carefully considered, from the marine grade UV-resistant stitching, the hand-pounded copper rivets on the lay-flat handle, the contoured angles on every side, to the USA sourced full grain coffee saddle leather. The Wayfarer will take you around the world and back in comfort and style. There is an adventure in every bag, we guarantee it.
Yes if...
... You are spontaneous and adventurous
... You like to be ready for anything
... Your vacations are more Indiana Jones than Rick Steves
... You are rugged, but enjoy the finer things too
... You are versatile, from the board room to the Serengeti
... You know 4 ways to start a fire, with a shoelace
... You are techy but all grown up
... You have so many hobbies you lost count
... Your bucket list is longer than the Amazon
... You are a professional in disguise
... You want things organized, but not oppressively so
... You are awesome
Still not sure? Read a day in the life of the Wayfarer Messenger Bag.
The Journeyman Commuter is designed to be your best friend, your everyday carry bag, and so much more.
Learn all about the amazing leather we use here at Intrepid Bag Co.
The Zinnia Convertible dives into exotic Marrakesh's marketplaces.
The Wayfarer Messenger safaris it up in the wild Serengeti.
-Jon Stokes, AllOutdoor.com
-Steve Sande, TUAW.com
-Seth Weintraub, 9to5Mac.com
-Charlie Sorrel, CultOfMac.com
-Josh, Seattle
-Chance Kinney, ChipChick.com


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Im getting periods thrice
Periods thrice a month and late in getting pregnant when I consulted my family doctor they said it is due to over weight and Harmon changes and now they say it is due to no egg formation for me only two eggs are forming so only they say.
Answers (1)
Like the answers? Chat privately for 24 hours with the doctor of your choice
Hi there...I can understand your concern. Irregular menstrual cycles can be due to many reasons like anaemia, thyroid disorders, pcod, fibromas, stress, drug intake. You will need detailed clinical examination and further investigations including ultrasound abdomen and pelvis, hormonal profile. So kindly consult a gynaecologist for further evaluation.
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- A Catholic Life (Matthew) >> St. John Gualbert, Model of Forgiveness
- Aleteia (Daniel Esparza) >> The Doctrine of the Twelve Apostles: the Didaché
- Aleteia (John Burger) >> Kelsey Grammer offers grammar correction for abortion advocates
- Arise! Let Us Be Going! (Fr. George David Byers) >> UPDATE: "Denial of the denial denial" – North Carolina gun purchase permit
- CatholicHerald.co.uk (Catholic News Service) >> Vatican rejects Cardinal Sarah's ad orientem appeal
- CatholicHerald.co.uk (Luke Coppen) >> Morning Catholic must-reads: 12/07/16
- CatholicHerald.co.uk (Francis Phillips) >> Why caring for women is the best counter to our pro-choice culture
- Catholic Stand (Bob Drury) >> Agnosticism Wins the Debate: 'Does God Exist?'
- Catholic Stand (Anne Casey) >> The Lost Defender
- Clutching My Rosary >> Saint John Gualbert, Abbot
- Community in Mission (Msgr. Charles Pope) >> Who was Isaiah?
- Crisis Magazine (Stephanie Gordon) >> Marian Femininity Before and After "I Do"
- Dominicana Journal (Br. Hyacinth Grubb, O.P.) >> Don't be Nice. Be Excellent.
- Fr. Hunwicke's Mutual Enrichment (Fr. John Hunwicke) >> MEMORIAE GLORIOSAE
- Fr. Z's Blog (Fr. John Zuhlsdorf) >> Card. Nichols (Archd. Westminster) v. Card. Sarah about Mass 'ad orientem'
- Fr. Z's Blog (Fr. John Zuhlsdorf) >> ASK FATHER: How to "reclaim" my property for the Lord after a Hindu procession goes by?
- Fr. Z's Blog (Fr. John Zuhlsdorf) >> Jesuit v. Jesuit
- Fr. Z's Blog (Fr. John Zuhlsdorf) >> ASK FATHER: How to have 'ad orientem' Mass in a gymnasium church?
- LMS Chairman (Joseph Shaw) >> Catholic academics and pastors appeal to the College of Cardinals over Amoris laetitia
- LMS Chairman (Joseph Shaw) >> Photos of LMS AGM and Annual Mass in Westminster Cathedral
- National Catholic Register Bloggers (Edward Pentin) >> Catholic Scholars Appeal to Pope Francis to Repudiate 'Errors' in Amoris Laetitia
- National Catholic Register Bloggers (Edward Pentin) >> Father Lombardi: Cardinal Sarah's Ad Orientem Suggestion 'Misinterpreted'
- National Catholic Register Bloggers (Marcia Segelstein) >> Only a Virtuous Nation is Capable of True Freedom
- National Catholic Register Bloggers (Matthew Archbold) >> Why Can't Catholic Colleges Hire for Mission?
- New Liturgical Movement (David Clayton) >> Liturgical Form Manifested in the Mundane - the Famous K2 Telephone Box
- RORATE CÆLI (Adfero) >> Pope Venerable Pius XII speaks to us
- The Catholic Thing (Hadley Arkes) >> On the Alchemy of Party
- The New Emangelization - Catholic Men's Evangelization >> Catholic Men's Daily Devotional and Bible Study – 15th Week in Ordinary time – Tuesday – Matthew 11:20-24
- Views From the Choir Loft (Corpus Christi Watershed) >> The Vatican Has Already Responded To Cardinal Nichols Regarding "Ad Orientem"
- Vultus Christi (A Benedictine Monk of Perpetual Adoration) >> Sacra Liturgia Releases Official Text
Tuesday, July 12, 2016
Morning Roundup - St. John Gualbert, Abbot - Missa 'Os Iusti' - Commemoration: SS. Nabor & Felix, Martyrs - July 12th, 2016
Posted by Deo volente at 9:52 AM
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John Wallace
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this wiki
this wiki
John Wallace (John James Wallace) was born on September 2, 1904 in , IL. After going to high school at Emerson (Gary, IN), Wallace attended the University of Notre Dame. Wallace made his professional debut in the NFL in 1928 with the Chicago Bears. He played for the Dayton Triangles and Chicago Bears over the course of his 2 year career.


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Not issuing medals in 2017 would be a break from tradition. In the past, Liberal and Conservative governments have used medals 'to mark important anniversaries'
It's no secret that Mr. Harper likes his partisanship strong and undiluted, but he also likes it delivered on his behalf by someone else.
The federal government said it would introduce a bill Monday afternoon to boost the ability of the country's spy agency to monitor Canadians
Stephen Harper won't read this, and doesn't care what it says
The PM stacks the deck with his headline economic portfolios, while Rob Nicholson inherits a Royal Canadian Mess at defence. Plus Alberta makes tough choices on post-flood rebuilding, and Toronto embarrasses itself over transit yet again.
Stephen Harper's backbenchers have real power in a slim majority, and there's nothing he can do about it — except learn to live with it. Plus Brent Rathgeber's re-election chances, Quebec's "strange view of secularism" and the shocking spectacle of helmetless soccer.
When Tories attack Mulcair on ethics breaches, they speak from rich experience
No budget was provided for the latest media blitz, but with ads during NHL playoff games costing up to $95,000, the ad buy could easily be in the millions of dollars
Parliamentary House leader Peter Van Loan has denied that Conservative Sen. Mike Duffy ever promised to repay his P.E.I. housing allowance
This is the way boards of directors work at golf clubs and private schools. It is quite appalling that such hush-hush, boys-club protocols should still operate in the Parliamentary house of a G7 country


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This is how 2 referees rated Janet:
|Hourly Rate
|Casual Learner
My work takes up a lot of my time and I work from home with two West Highland Terriers for company, as my two children have now left home - one works full time in London utilising his computer science degree and the younger is working full time for an accountant in Bournemouth, having achieved AAT level 4 she is now studying ACCA. For relaxation I love walking the dogs, and I attend a weekly Yoga class and Ceroc (modern jive) session.
I have extensive experience of teaching Mathematics to GCSE; and at A level I am now teaching Pure modules (C1-4) for exam boards AQA and Edexcel only. I have been an examiner for a number of years. Since 1987 I have been a private tutor to pupils of all ages and abilities. Examination pass rates have been very good, both with classes and individual students.
Currently I am teaching Years **Telephone Number Removed** IGCSE online for an internet school, as well as providing one-to-one tuition at home.
I have always had an empathetic approach with students and I believe in being supportive to increase their confidence and enjoyment of Maths. It is important that they are well motivated to achieve their potential. I am hard working and enthusiastic about my subject.
|Date Registered:
|Date Last Logged In:
|Tutees Providing Feedback:
|Tutees Providing Positive Feedback:
|1 Av. 4.00/5.00
Tags: Wareham Maths tutor, Wareham GCSE Maths tutor, Wareham A-Level Maths tutor, Wareham Casual Learner Maths tutor


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Obtaining the correct executive search Houston for you
There comes a time with any enterprise when you must hire the very best, and only the most effective. The circumstances for this may change from business to business , it might be because you have a large deadline coming up and must rapidly employ some really great workers, or you may have had a high up executive position come availible. Irrespective of the reason, it is crucial that you then find the most effective in executive HR search Houston, in order to get the very best candidates for you personally. As a business you'll no doubt have interviewed and hired people before, so you may be tempted to just do this yourself, but it is crucial that you use expert executive search Houston to complete it. This really is simply because they have far more experience in narrowing down who is the very best candidate for a high profile job, and will know what to search for.
Because this position is not a regular position, the candidates must differ as well. There will be less learning on the job, for instance , anyone applying by way of an healthcare executive search organization will be expected to be in a position to adapt quickly and already know what's expected of them, so that they are able to start working efficiently straight away. Click here to see for yourself if you're still unsure. As a result of this, any executive search Houston will be searching for these kind of qualities , hardworking, organized and experienced are the primary ones, just because any executive position will likely be a high paying role, and so any person applying for this needs to demonstrate that they are worthy of such a high salary. This makes the job far more competitive, and so it is an incredibly good idea to leave it to an executive search business, simply because it takes a great deal of strain off of you, while nonetheless obtaining the most effective candidates.