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\"Oruviral Puratchi\" from Sarkar by A. R. Rahman, Srinidhi Venkatesh. Released: 2018. Track 2 of 5. Genre: Tamil.
\"Praaptham\" from Chekka Chivantha Vaanam by A.R. Rahman, Karthik. Released: 2018. Track 7. Genre: Tamil.
\"Hayati\" from Chekka Chivantha Vaanam by Shiv, A.R. Rahman, Mayssa Karaa. Released: 2018. Track 5. Genre: Tamil.
\"Kalla Kalavaani\" from Chekka Chivantha Vaanam by A.R. Rahman, Shakthisree Gopalan, Lady Kash. Released: 2018. Track 4. Genre: Tamil.
\"Sevandhu Pochu Nenju\" from Chekka Chivantha Vaanam by Arjun Chandy, Sathyaprakash D, A.R. Rahman, Sunitha Sarathy. Released: 2018. Track 3. Genre: Tamil.
\"Neeli Kanumallo\" from Nawab by Nakul Abhyankar, A.R. Rahman. Released: 2018. Track 2. Genre: Telugu.
\"Bhaga Bhaga\" from Nawab by Shakthisree Gopalan, A.R. Rahman. Released: 2018. Track 1. Genre: Telugu.
\"Mazhai Kuruvi\" from Chekka Chivantha Vaanam by A.R. Rahman. Released: 2018. Track 2. Genre: Tamil.
\"Bhoomi Bhoomi\" from Chekka Chivantha Vaanam by A.R. Rahman, Shakthisree Gopalan. Released: 2018. Track 1. Genre: Tamil.
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West Bloomfield resident Sophia Beaulieu, 14, participated in "American Ninja Warrior Junior," which was scheduled to air March 2.
Photo provided by 'American Ninja Warrior Junior'
WBHS student shows off skills on 'American Ninja Warrior Junior'
By: Sherri Kolade | West Bloomfield Beacon | Published February 28, 2019
Beaulieu said her agility, endurance and determination were tested on the physically challenging show.
Photo provided by Deb Beaulieu
WEST BLOOMFIELD — West Bloomfield resident Sophia Beaulieu, 14, knows how to perform body-twisting feats and maneuvers that show off her physical prowess — while suspended over water, no less.
Beaulieu was a contestant on "American Ninja Warrior Junior" through Universal Kids last fall, which was scheduled to air March 2.
The petite powerhouse, a ninth-grader at West Bloomfield High School, trains at The Edge Training Center in Commerce Township. She was invited out to Los Angeles last May to be on the show as a Junior Ninja.
"It was super cool, a great experience," Beaulieu said, adding that she met a ton of people from NBC's "American Ninja Warrior" show.
"American Ninja Warrior Junior," according to a press release, celebrates "real kids" tackling an obstacle course with "dedication and skill."
Nearly 200 Junior Ninjas from throughout the country faced off on head-to-head courses in three age brackets: ages 9-10, 11-12 and 13-14.
The courses featured well-known "Ninja Warrior" obstacles, such as the Sonic Swing, Tic Toc, the Spin Cycle and the Warped Wall.
The Junior Ninjas were mentored by All Star Ninja Mentors, the press release states.
Three final winners — one per age bracket — were scheduled to be crowned the first-ever "American Ninja Warrior Junior" champions.
Beaulieu could not disclose at press time whether she had won or lost.
"Over the last number of years, we have received an outpouring of letters and videos asking when is there going to be a 'Ninja' show for kids?" Arthur Smith, CEO of A. Smith & Co. Productions and executive producer of the "American Ninja Warrior" franchise, said in the press release. "People are going to be amazed at how talented and dedicated these young Ninjas are. They're remarkable, and to know that they've been inspired by our show is immensely gratifying."
Beaulieu's mom, Deb Beaulieu, said that her daughter was the kid who always "climbed the walls," and getting her involved in physical activities was a great outlet for her — from playing basketball in her earlier years to gymnastics and beyond.
Sophia Beaulieu said she wants people to know that she can do it.
"I can't wait for them (the public) to see … (the) results," she said. She was on the set for about three days, filming for about six hours per day.
"They used a blurb she used in her video, 'I want to show them that power comes in little sizes,'" Deb Beaulieu said of her daughter, who is 5 feet 2 inches tall and weighs 90 pounds. "If you look at her, you wouldn't think she is a powerhouse. … More often than not, a lot of people underestimate her."
For more information, visit www.universalkids.com.
West Bloomfield police, Kroger team up to fight hunger
Temporary polling locations announced for special election in West Bloomfield
West Bloomfield resident launches fishing show
West Bloomfield to open senior services location at Orchard Mall
Cat hoarding case heads to court
Construction to begin soon at Orchard Lake Middle School

redpajama_set_name: RedPajamaCommonCrawl


Tendinopathies are common and difficult to resolve due to the formation of scar tissue that reduces the mechanical integrity of the tissue, leading to frequent reinjury. Tenocytes respond to both excessive loading and unloading by producing pro-inflammatory mediators, suggesting that these cells are actively involved in the development of tendon degeneration. The transcription factor scleraxis (Scx) is required for the development of force-transmitting tendon during development and for mechanically stimulated tenogenesis of stem cells, but its function in adult tenocytes is less well-defined. The aim of this study was to further define the role of Scx in mediating the adult tenocyte mechanoresponse.
Equine tenocytes exposed to siRNA targeting Scx or a control siRNA were maintained under cyclic mechanical strain before being submitted for RNA-seq analysis. Focal adhesions and extracellular matrix-receptor interaction were among the top gene networks downregulated in Scx knockdown tenocytes. Correspondingly, tenocytes exposed to Scx siRNA were significantly softer, with longer vinculin-containing focal adhesions, and an impaired ability to migrate on soft surfaces. Other pathways affected by Scx knockdown included increased oxidative phosphorylation and diseases caused by endoplasmic reticular stress, pointing to a larger role for Scx in maintaining tenocyte homeostasis.
Our study identifies several novel roles for Scx in adult tenocytes, which suggest that Scx facilitates mechanosensing by regulating the expression of several mechanosensitive focal adhesion proteins. Furthermore, we identified a number of other pathways and targets affected by Scx knockdown that have the potential to elucidate the role that tenocytes may play in the development of degenerative tendinopathy.
Musculoskeletal injuries are common and affect people of all ages, fitness levels, and socioeconomic groups, as well as many animal species, including horses and dogs [1, 2]. Tendon and ligament injuries in particular account for a significant percentage of musculoskeletal injuries each year, with this number expected to rise along with an increasingly sedentary and aging population . Because dense collagenous tissues such as tendon and ligament are slow to heal and the natural healing process often results in the formation of scar tissue, these injuries are particularly problematic . The inability to regain normal tissue structure and mechanical properties often leads to tissue degeneration and chronic reinjury. Despite the frequency at which these injuries occur, and the associated loss of function and productivity they engender, there are few effective treatments available . Tendinopathies are particularly difficult to treat due to their chronic and degenerative nature, which no current treatments are able to adequately resolve. This lack of treatment options is due in part to a lack of understanding of the basic biology of resident tendon cells, called tenocytes. Tenocytes are responsible for the synthesis and maintenance of the normal tendon extracellular matrix architecture in response to physiological load . Decreased production of collagen and upregulation of catabolic enzymes and pro-inflammatory mediators by tenocytes in response to both excessive loading and unloading implicates these cells as a primary driver of degenerative tendinopathy [6, 7]. A better understanding of how tenocytes sense and respond to physical strain could therefore lead to more effective treatments.
Much of the available information regarding tenocyte behavior has been gleaned through investigation of the basic helix-loop-helix transcription factor, scleraxis (Scx). Scx is frequently used as a tendon marker, and is critically involved in both the development of force-transmitting tendons in mice and the tenogenic differentiation of stem cells [8–10]. Mechanical load increases Scx expression [11, 12] and Scx is required for the pro-tenogenic effects of cyclic strain on stem cells . Scx also plays a part in regulating the response to mechanical load in adult mice, with decreased expression following tendon unloading and increased expression in response to physiological load [14, 15]. Taken together, this information demonstrates an important, but not well-characterized, role for Scx in tenocyte mechanotransduction.
To gain better insight into how Scx facilitates tenocyte mechanotransduction, we used small interfering RNA (siRNA) to knock down expression of Scx in adult equine tenocytes and subsequently exposed them to cyclic mechanical load. The resulting transcriptome was sequenced with RNA-sequencing (RNA-seq) technology and compared to that of control tenocytes. We hypothesized that Scx mediates tenocyte mechanotransduction via regulation of a specific subset of previously unidentified, mechanoresponsive genes.
For the initial transcriptome study, tenocytes were isolated from the superficial digital flexor tendon (SDFT) of a 5-year-old light breed female donated to the Virginia-Maryland College of Veterinary Medicine (VMCVM) for reasons unrelated to this study. All procedures, including tissue harvest, were performed with IACUC approval. Immediately following euthanasia by barbiturate overdose, the tensile region of both SDFT were aseptically excised, stripped of the paratenon, minced into small pieces (2-5 mm), and digested in growth medium (Dulbecco's modified Eagle's medium [DMEM; 4.5 g/L glucose], 10% FBS, 2 mM L-glutamine, 50 μg/mL ascorbic acid, 25 mM HEPES, 100 units/mL penicillin, and 100 μg/mL streptomycin) containing 0.075% collagenase type 2 (Worthington Biochemical, Lakewood, NJ) and 0.06 μg/mL α-ketoglutaric acid overnight at 37 °C, 5% CO2, and 90% humidity. Cells were strained, pelleted, and plated at 6000/cm2 in growth medium. Growth medium was exchanged every 3 days and cells were passaged upon reaching 70% confluence using 0.25% trypsin-EDTA. For cohort validation studies, tenocytes were isolated and passaged in the same manner from the SDFT of 6 additional light breed horses (mean age 5.8 ± 3.3 years; 4 females, 2 castrated males) donated to the VMCVM for reasons unrelated to this study and under IACUC approval. Tenocytes were used at passage 3 for all experiments.
Tenocytes were transfected (Nucleofector™ system, Lonza, Cologne, Germany) with a siRNA targeting the equine Scx mRNA (Sense: 5'-AGAGAAAGUUGAGCAAGGAtt-3′, Antisense: 5'-UCCUUGCUCAACUUUCUCUgg-3′, GenBank ref. NM_001105150.1; Silencer™ Select, Ambion, Life Technologies, Carlsbad, CA) or a non-targeting scramble siRNA control (Silencer™ Select Negative Control No. 1, Catalog #4390843, Life Technologies). Transfection efficiency was evaluated using a fluorescein-conjugated scramble siRNA (sc-36,869; Santa Cruz Biotechnology Inc., Dallas, TX) and counting labeled cells by fluorescent microscopy. Cells were resuspended at 1 × 106/100 μL in Nucleofector™ Cell Line Solution V (Lonza) containing 10 nmol siRNA or scramble control, transferred to cuvettes, and nucleofected using the T20 program. Cells were recovered in growth medium for 15 min at 37 °C before plating at 200,000 cells/well on flexible silicone culture plates (UniFlex® Collagen type I coated; Flexcell International, Hillsborough, NC). Cells were allowed to adhere for 24 h before being synchronized in culture medium containing 1% FBS. After 18 h, cells were exposed to cyclic uniaxial strain (1%, 0.5 Hz, 2 h) every 24 h for 3 days. Thirty minutes after completion of the final strain cycle, cells were collected into guanidine isothiocyanate-phenol solution (TRIzol® Reagent, Invitrogen, Carlsbad, CA) for RNA isolation. The experiment was repeated 3 times to generate 6 total samples for sequencing (3 siRNA and 3 scramble controls). Cohort samples for validation by qPCR were generated in the same manner.
Total RNA was isolated by column purification according to manufacturer instructions (Direct-zol Microprep, Zymo Research, Irvine, VA) and evaluated both spectrophotometrically for quantity (NanoDrop, Thermo Scientific, Waltham, MA) and by electrophoresis for RNA integrity (Bioanalyzer, Agilent, Santa Clara, CA). RNA from the same samples submitted for RNA-seq and the additional cohort were isolated and converted to cDNA for use in qPCR validation studies (High-Capacity cDNA Reverse Transcription Kit, Applied Biosystems, Foster City, CA).
cDNA library prep and sequencing was performed at the Biocomplexity Institute at Virginia Tech. Total RNA (1 μg per sample) was enriched for polyA RNA (PrepX PolyA mRNA isolation kit, Wafergen, Fremont, CA) and converted to cDNA libraries (PrepX RNA-seq for Illumina Library Kit, Wafergen). Libraries underwent 13 rounds of PCR to generate the final cDNA libraries for sequencing. Individual sample libraries were clustered and sequenced on the Illumina HiSeq 2500 (average of 26.9 million paired end reads for scramble control and 29.3 million for Scx siRNA). Raw sequence data were evaluated for quality (FastQC)  and adaptor sequences and low quality reads were removed using Trimmomatic  prior to being aligned to the reference genome (EquCab2) using HISAT2  and mapped to known features (Ensembl EquCab2 version 90) using HTSeq . Differential gene expression between scramble control and Scx knockdown samples was determined using DESEQ2 . All fold changes are shown relative to the scramble control and on a log2 scale, unless otherwise stated. Genes with a ± 1.5 log2fold change and an adjusted p-value of p < 0.05 were used in functional annotation and gene ontology (GO) enrichment analysis of differentially expressed genes using the PANTHER Classification System (version 13.0, http://www.pantherdb.org/) and a false discovery rate of 0.05. KEGG Pathway analysis was performed with the DAVID Bioinformatics Resource (version 6.7, https://david.ncifcrf.gov/) and significance set at p < 0.05 as evaluated by modified Fisher Exact test (EASE score). Sequence data generated in this study have been submitted to National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO, https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE110567. Differential expression analysis and normalized counts for all genes and samples are included as Additional file 1.
Minor groove binding primer-probe sets were purchased (Scx, assay #Ec03818452_s1, Life Technologies) or designed for genes of interest identified by the transcriptomic analysis (Primer Express®, Applied Biosystems; Table 1). All primer-probe sets had an efficiency of > 90% as determined by serial dilution against a known template (TaqMan™ Master Mix, Life Technologies; StepOnePlus™ Real-Time PCR System, Applied Biosystems). Relative gene expression was calculated using the ΔΔCt method and the housekeeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH) [21, 22]. Data are shown relative to the average of the scramble control samples for each gene.
Cells were exposed to either the scramble control or Scx-targeting siRNA and plated on collagen type I coated tissue culture polystyrene (TCP) plates in the same manner described above for cells plated on silicone bottom plates. After 3 days in culture, cells were fixed in prewarmed 4% paraformaldehyde in dPBS + 0.3% TritonX-100 for 15 min at room temperature. Differences in cytoskeletal and focal adhesion morphology were investigated using a focal adhesion staining kit following manufacturer's instructions (FAK100, MilleporeSigma, St. Louis, MO). Five random fields were acquired at 20× magnification per condition for each horse and used for analysis of cell morphological features (CellProfiler version 3.0.0, http://cellprofiler.org/).
Tenocytes were cultured on silicone bottom plates as described above, or on collagen-coated TCP. Scratches were created using a 200 μL pipette tip 30 min following the end of the final strain cycle. Monolayers were rinsed once with dPBS to remove debris and covered with fresh culture medium containing 1% FBS. Images were taken at 0, 3, 5, 8, and 12 h post scratch formation to monitor cell migration into the scratch area (ImageJ, National Institutes of Health, Bethesda, MD).
where F = applied force, k = spring constant of the cantilever, d0 = deflection point during cell contact, α = half open angle of the tip, v = Poisson's Ratio (0.5), and δ = indentation [23, 24]. Triplicate force distance curves were collected and averaged for at least 8 cells per condition and repeated for each horse in the cohort (n = 7).
All statistical analyses were performed using SAS Studio 3.6 (SAS Institute Inc., Cary, NC). Unpaired Student's T-Tests were used to assess differences in gene expression, cell stiffness, and morphometric data. Migration assay data were analyzed by mixed model ANOVA with Tukey's post hoc testing using the PROC GLIMMIX procedure. Model fit was evaluated by examining studentized residual plots. Statistical significance was set at p ≤ 0.05. Box and whisker plots represent the median value and 25th and 75th percentiles, with whiskers denoting the minimum and maximum values. All remaining data are shown as mean ± SD.
Transfection efficiency using the described protocol was > 95% beginning approximately 24 h post-nucleofection and remained > 95% until at least 96 h. Exposure to Scx siRNA using the described protocol resulted in an average knockdown of approximately 57% (p < 0.001), as measured by qPCR, in cDNA made from the same samples submitted for RNA-seq (Fig. 1a). As an initial validation of the RNA-seq data, Scx expression was compared between the two methods. The current annotation of the equine genome (EquCab2) does not include Scx as a feature, presumably due to the poor quality of the equine genome upstream of the Scx gene and incomplete information regarding the 3′ end of the Scx coding region. Alignment of RNA-seq reads to the equine Scx mRNA sequence (NM_001105150.1) revealed a substantial GC bias that decreased the total number of mapped reads (Fig. 2). Nevertheless, in samples exposed to Scx siRNA, the number of reads mapping to the Scx mRNA was significantly decreased (p = 0.014) compared to the scramble control (Fig. 1b).
A total of 11,166 annotated transcripts (out of 26,922) were detected in tenocytes, with 10,231 expressed in both control cells and those exposed to Scx siRNA. An additional 747 genes were expressed in only the control cells and 188 were expressed only in the Scx knockdown cells. The top 25 most highly expressed genes, regardless of Scx knockdown, are shown in Table 2. Vimentin (VIM), a fibroblast marker, was the most highly expressed gene in our dataset. The two major tendon extracellular matrix proteins, collagen types Iα2 (COL1A2) and IIIα1 (COL3A1), were among the most highly expressed genes and were unaffected by Scx knockdown. The small leucine rich proteoglycans decorin (DCN) and lumican (LUM) were both highly expressed and significantly (p < 0.001 for both) increased in Scx-depleted tenocytes; however, the fold changes did not meet the inclusion criteria (log2 fold change of >/< 1.5) to be considered for differential expression (LUM = 1.21 log2 fold change, DCN = 0.72 log2 fold change). To further confirm the identity of the cells as tenocytes, data were examined for expression of tendon-enriched genes . Sixty out of 68 of the previously reported tendon-selective genes were present in our dataset (Table 3). The data were also parsed for changes in the expression of other tendon-related genes (Table 4). Expression of collagen types Iα1 (COL1A1) and 5α1 (COL5A1) were decreased, as was expression of the glycoproteins tenascin-C (TNC) and cartilage oligomeric matrix protein (COMP) and the proteoglycan aggrecan (ACAN). Expression of matrix metalloproteinases (MMP) -1 and − 3 was relatively low and unaffected by Scx knockdown. Conversely, MMP-13 expression was increased and MMP-2 expression was decreased in Scx-depleted cells.
Of the 11,166 annotated transcripts detected, 1002 genes met the threshold for differential expression (411 upregulated and 591 downregulated genes in Scx depleted tenocytes compared to controls). GO analysis of differentially expressed genes revealed a number of biological processes affected by Scx knockdown (Table 5). Downregulated genes exhibited significant enrichment in processes involved in cell-matrix adhesion (4.8-fold, p = 0.037), transmembrane receptor protein tyrosine kinase signaling pathway (2.8-fold, p = 0.046), cell differentiation (2.1-fold, p = 0.006), and developmental processes (1.6-fold, p = 0.007), among others. Genes upregulated by Scx knockdown showed significant enrichment in processes including oxidative phosphorylation (6.6-fold, p = 0.02), mitochondrion organization (5-fold, p = 0.009), translation (3.2-fold, p = 0.011), and transcription from RNA polymerase II promoter (1.97-fold, p = 0.022).
Differentially expressed genes were overlaid onto KEGG database pathways to further define specific pathways affected by Scx knockdown (Table 6). In agreement with the GO analysis, the extracellular matrix-receptor interaction (3.5-fold, p = 0.014) and focal adhesion (2.3-fold, p = 0.017) pathways were enriched in genes downregulated by Scx knockdown. Pathways represented by upregulated genes included oxidative phosphorylation (6.4-fold, p < 0.001), ribosome (6.4-fold, p < 0.001), and several neurodegenerative diseases, including Parkinson's (6.3-fold, p < 0.001), Alzheimer's (4.4-fold, p < 0.001), and Huntington's disease (3.8-fold, p < 0.001).
To confirm the biological significance of the transcriptomic data, the relationship between Scx knockdown and focal adhesions suggested by the GO and KEGG analyses was further explored. Several differentially expressed, focal adhesion-related genes, were chosen for validation of the sequencing data by qPCR in both the original samples submitted for sequencing and the additional cohort (n = 7 horses total). Exposure to Scx siRNA resulted in significantly decreased Scx gene expression compared to controls (Table 7; p = 0.036). The remaining genes quantified by qPCR showed comparable downregulation to the RNA-seq results (Table 7), and included several adaptor proteins and those that facilitate force transduction via focal adhesion linkage to the actin cytoskeleton (talin 1 and 2 [TLN1, TLN2], filamin B and B [FLNB, FLNC]; Fig. 3). Other downregulated genes, including breast cancer anti-estrogen resistance protein 1 (BCAR1, also known as p130Cas) and SHC adaptor proteins 3 and 4 (SHC3, SHC4), are key players in the regulation of cell migration by acting as scaffolds for tyrosine kinase-related signaling. Also downregulated in tenocytes exposed to Scx siRNA were several extracellular matrix components (collagen types Vα1, VIα2, and IVα2, laminin subunits α5 and β2, heparan sulfate proteoglycan 2, and thrombospondin 2), integrin subunits α3 and β3, and two regulatory subunits of protein phosphatase 1 (12B and 12C).
Changes in cytoskeletal and focal adhesion structure in response to Scx knockdown were examined by immunofluorescent staining for the actin cytoskeleton and vinculin, a protein found in mature focal adhesions that was unaffected by Scx knockdown (Fig. 4). No overt differences were seen in the cytoskeletal organization; however, tenocytes exposed to Scx siRNA had decreased cytosolic staining of vinculin and longer vinculin-containing focal adhesions compared to controls (7.2 ± 4.3 and 4.9 ± 2.6 μm, respectively; p < 0.001). In addition, tenocytes exposed to Scx siRNA were approximately 40% softer than control cells (p < 0.001), as measured by atomic force microscopy (Fig. 5). Scx knockdown had no significant effect on cell area or nuclear shape (Table 8).
There was no difference in cell migration between tenocytes exposed to Scx siRNA and a scramble control siRNA when cultured on collagen-coated TCP (p = 0.065; Fig. 6). When migration assays were performed on silicone membranes, however, there was a significant two-way interaction between plate type and Scx knockdown (p = 0.025). Though tenocytes tended to migrate slower on the silicone membrane overall, cells exposed to Scx siRNA were significantly slower to migrate on silicone compared to TCP at 12 h post-scratch creation (p < 0.001; Fig. 6).
By using a broad, transcriptomic approach followed by biological validation, we identified several novel Scx-mediated processes with important implications in understanding tenocyte behavior. Equine tendon fibroblasts exposed to siRNA targeting Scx were softer, showed an impaired ability to migrate on softer surfaces, and exhibited differences in focal adhesion morphology compared to controls. Together, these findings suggest a potential role and mechanism for Scx in modulating tenocyte mechanotransduction. The results of our study identify interesting new avenues for investigation into tenocyte biology that have the potential to advance our understanding of how physical cues play a role in the development of tendon disorders.
Despite the plethora of information available about the role of Scx in development, few studies have examined the role of Scx in adult tenocytes. A recent in vitro study demonstrated that Scx knockdown in adult equine tenocytes did not affect the expression of common tendon-related genes or the ability to reorganize a 3D collagen matrix . Several groups have reported increased Scx expression in tendons following mechanical load or injury in vivo; however, it appears that the increase in Scx expression is due to proliferation of cells from the tendon periphery and their subsequent migration into the tendon core rather than increased expression by resident tenocytes themselves [15, 26, 27]. In fact, using a murine patellar defect model and Scx-GFP reporter mice, Dyment et al. reported that Scx expression in tenocytes located in the tendon core adjacent to the injured area sharply decreased following injury and remained decreased for at least 7 days before slowly recovering . This suggests that there are at least two Scx-positive cell populations involved in tendon repair and remodeling, though their contributions to overall Scx expression need further clarification. In our study, care was taken to remove the paratenon/epitenon prior to cell isolation in order to examine the effects of Scx knockdown in tenocytes from the tendon parenchyma specifically, though we cannot rule out the presence of endotenon-derived cells.
Scx expression is frequently used as a marker of tenocyte identity, but it is also expressed in other tissues [28, 29]. Tenomodulin (TNMD) and thrombospondin 4 (THBS4) are enriched in tendon compared to other tissues in humans and rats ; however, the use of TNMD as a marker of tenocyte identity in horses is less supported, as similar levels of TNMD are found in both tendon and bone  and at least one study was unable to detect TNMD expression in normal equine SDFT . In our dataset generated from passaged tenocytes, we observed low levels of THBS4 expression and undetectable levels of TNMD. Despite this, many other tendon selective genes were expressed. Interestingly, a number of these genes, including asporin (ASPN), C-C Motif Chemokine Ligand 2 (CCL2), Laminin Subunit Alpha 5 (LAMA5), and Wnt Family Member 5B (WNT5B), were significantly affected by Scx knockdown. These findings suggest that Scx plays an active role in promoting adult tenocyte identity.
Exposure to Scx siRNA resulted in significantly decreased Scx mRNA as measured by both RNA-seq and qPCR. Scx is not included in the current version (EquCab2) of the equine genome annotation. Therefore, to evaluate Scx expression in our dataset, we mapped sample reads against the Scx mRNA. It is important to note that Scx mRNA is relatively small (957 bp containing two exons), GC-rich (~ 70% overall), and contains regions of stark GC content disparity, ranging from 50 to 80%. As a result, coverage across the Scx mRNA was reduced. GC bias between samples and genes in RNA-seq data are well-documented effects and there are numerous tools to account for these biases in analysis pipelines [32, 33]. Within-transcript bias is also relatively common, but correcting for it is less defined. Use of GC unaware transcript estimation methods can lead to errors in transcript abundance, especially when examining differential isoform expression . In the case of Scx, there are no documented transcript variants; however, care should be taken in evaluating the expression of Scx in transcriptomic studies, as low levels of expression may relate to bias in the sequencing technology and not a biological phenomenon.
Functional annotation and GO analysis showed that Scx knockdown significantly downregulated pathways involved in focal adhesion and extracellular matrix-receptor interactions in our study. Focal adhesions are large protein complexes that form the physical link connecting the cytoskeleton to the extracellular matrix through the binding and activation of transmembrane proteins called integrins . Integrins themselves are direct mechanosensors, and upon activation facilitate the recruitment of many cytosolic proteins to the plasma membrane to form the intracellular portion of the adhesion complex . The protein talin, in particular, anchors the actin cytoskeleton to the focal adhesion by force-dependent interaction with the cytosolic tail of the β3 integrin (ITGB3) [37, 38]. Talin is a critical mechanosensor, and loss of talin impairs cell migration and extracellular substrate sensing [39, 40]. Following talin activation, the cytosolic protein vinculin is recruited to the focal adhesion and interacts with talin to stabilize the complex . Increased presence of vinculin is indicative of decreased focal adhesion turnover and more mature adhesion, which inhibits cell migration [41, 42].
Other proteins recruited in response to integrin binding, including BCAR1 and the SHC adaptor proteins, enable the integration of physical and chemical cues into downstream pathway activation in response to mechanical stimulation. Increased BCAR1 expression correlates with increased invasive potential of cancer cells, and silencing of BCAR1 or SHC3/4 results in decreased migratory ability [43–46]. Expression of both talin isoforms (TLN1 and TLN2), ITGB3, BCAR1, and SHC3/4 were decreased in tenocytes following Scx knockdown in our study. Consistently, tenocytes exposed to Scx siRNA had longer vinculin-containing focal adhesions, indicating decreased focal adhesion turnover. Despite the presence of longer focal adhesions, there was no effect of Scx knockdown on tenocyte migration on TCP. Interestingly, Scx-depleted tenocytes migrated more slowly on softer silicone membranes, whereas control cells were unaffected by the change in substrate stiffness. As many of the genes affected by Scx knockdown function as link proteins at the interface between integrins and the actin cytoskeleton, this substrate stiffness-dependent migration effect could reflect an inability to generate proper cytoskeletal traction.
In further support of a role for Scx in modulating cytoskeletal tension, tenocytes exposed to Scx siRNA exhibited a significant decrease in cytoskeletal stiffness compared to controls. Previous studies have reported that cells alter their cytoskeletal tension in response to environmental changes in order to maintain a predetermined tensional homeostasis [47, 48]. Loss of tensional homeostasis in tenocytes leads to upregulation of MMP-13 and downregulation of COL1A1 [49, 50]. Recovery of cytoskeletal tension in tenocytes occurs through actin-mediated interaction with the local environment . In our study, we observed a similar increase in MMP-13 and decrease in COL1A1 expression, in addition to reduced cytoskeletal stiffness. Inability of the tenocytes to form adequate focal adhesion to actin cytoskeleton connections due to decreased expression of the key adaptor proteins seen in our study (i.e. TLN1/2, FLNB/B, SHC3/4) would impair ability of tenocytes to sense and respond to changes in substrate stiffness and could therefore result in reduced cytoskeletal stiffness.
The relationship between cell stiffness and migratory capacity varies between cell type and disease state. In cancer, decreased cytoskeletal stiffness can be used as an accurate measure of metastatic potential, with cancerous cells being softer than the surrounding healthy cells [52, 53]. In non-cancerous cells, the relationship is less clear. A study by Kole et al. found that in normal 3 T3 fibroblasts, non-migratory cells were significantly softer than migrating cells, indicating that an increase in cytoskeletal stiffness is a prerequisite for directed cell migration . Other studies have shown that disturbed cytoskeletal architecture or connections results in cells with decreased cytoskeletal stiffness and migratory capacity [55, 56]. We observed similar cell behavior in our study, with softer tenocytes migrating more slowly than their stiffer counterparts on softer surfaces. Substrate stiffness, cytoskeletal tension, and migratory capacity are inextricably linked in all cell types. Future studies in tenocytes will help to elucidate the specific relationships and mechanisms involved.
We validated the transcriptomic data by showing that Scx knockdown resulted in slower migrating, softer tenocytes; however, the pathway analysis points to a broader role for Scx in tenocyte homeostasis. Intriguingly, GO term and KEGG pathway analysis showed that a significant number of genes upregulated in response to Scx knockdown are involved in pathways related to neurodegenerative diseases (e.g., Alzheimer's, Huntington's, and Parkinson's). These particular diseases develop, in part, due to dysregulation of the unfolded protein response (UPR), a homeostatic mechanism that has evolved to counter endoplasmic reticular (ER) stress as a result of misfolded proteins . Correspondingly, GO term analysis showed upregulation of many anabolic processes and a concurrent decrease in genes related to protein folding in Scx-depleted cells. ER stress and the UPR are implicated in development of organ fibrosis in heart, lung, and liver disease [58–60]. As the development of fibrotic scar tissue is a major consequence of tendon injury and the main reason for reinjury, this suggested connection between Scx and ER stress in tenocytes warrants further investigation.
This study is the first to identify specific roles for Scx in adult tenocytes by exposure to siRNA targeting Scx and subsequent RNA-seq interrogation. We confirmed the biological significance of the transcriptomic data by demonstrating that Scx knockdown results in the formation of abnormal focal adhesions, decreased cytoskeletal stiffness, and an impaired ability to migrate on soft substrates. Our data suggest that Scx facilitates tenocyte mechanosensing in part by regulating the expression of several focal adhesion components and genes involved in maintaining cytoskeletal tension. Whether this is the result of direct or indirect gene regulation by Scx remains to be clarified. We also identified other genes and pathways affected by Scx knockdown that point to a larger role for Scx in maintaining adult tenocyte homeostasis. Further exploration of these novel Scx-mediated targets has the potential to advance our understanding of how mechanical strain can lead to tendon injuries.
The authors thank Andrew Ford for his invaluable assistance and guidance in the atomic force microscopy studies and Dr. Roderick Jensen for the helpful discussions regarding transcriptomic analysis.
This work was supported by internal funding from the VMCVM. AECN received graduate fellowship support from the Stamps Family Charitable Foundation. Publication costs for this article were supported by the Virginia Tech Open Access Subvention Fund.
Data supporting the results of this study are included as Additional file 1 and are available under accession number GSE110567 at the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO, https://www.ncbi.nlm.nih.gov/geo/).
AECN and LAD conceived the study and design with assistance from RES; experiments were performed by AECN; data were analyzed by AECN, LAD, and SRW; the manuscript was written and edited by AECN and LAD. All authors read and approved the final manuscript.
Collection of equine tissues for cell isolation was approved by the Virginia Tech IACUC under protocols 14–128 and 15–059.
Andrews S. FastQC: a quality control tool for high throughput sequence data. Available online at: [http://www.bioinformatics.babraham.ac.uk/projects/fastqc/]. Accessed 2 Aug 2018.


text:
Vandna Gupta (born 17 December 1994) is an Indian weightlifter who  placed fourth in the women's 63 kg weight class at the 2014 Commonwealth Games at Glasgow.
Vandana Gupta is from Lucknow and married Sandeep Tomar on 28 February 2017.

References

External links

Living people
1994 births
Indian female weightlifters
Sportswomen from Uttar Pradesh
Sportspeople from Lucknow
21st-century Indian women
20th-century Indian women
Weightlifters from Uttar Pradesh
Weightlifters at the 2014 Commonwealth Games
Commonwealth Games competitors for India

redpajama_set_name: RedPajamaWikipedia


Well, it's Friday, and another weekend is upon us. Here in the States, we have a long weekend because Monday we are observing Memorial Day to honor our soldiers who gave their lives so that we may enjoy our freedom and way of life. We don't have any special plans for Monday, so we'll probably put up our flag and take it easy at home.
Last night a huge storm passed over the area and dumped a lot of rain down on us. It was pretty scary and there's a lot of flooding, although the area that our house is in is not in any danger. But it is still scary because we live on the edge of tornado country.  I imagine that with climate change happening more quickly than we thought, the severe weather will only get worse. Scary to think about!
Anyways, today's photo is of my Chromebook which is still very useful. I am actually using it right now to type this blog post! I realize that one of the things that is important to me in my electronics is battery life. That's one reason I love my Kindle (lasts months on a single charge) and my Chromebook (10 hours continuous battery life!). I also realize that I cannot just use a tablet as my main mobile device because I need a real keyboard. The laptop form-factor is perfect for me to work on my blog. But, I know that I need another more robust computer as well, to run Lightroom and store all my photos, handle backups, downloads, and general computing. So, a two computer setup is essential at this time in my life.
Well, I am going to read my book. It's an action-packed fantasy page-turner! I am enjoying "Furies of Calderon" very much so far.
A few years ago when I needed a new laptop, I got a Toshiba Portege, because I needed a laptop light enough to carry around all the time. But then last year, I finally got a tablet, the LG G Pad X8.3, and with an inexpensive AmazonBasics Bluetooth keyboard (and I got the "Apple" one by accident, but it's always worked fine with all my Android devices, though they have a specifically Android one too), I'm all set for writing/blogging/whatever on the go. So now the laptop lives at home. 🙂 You should look into the keyboard my friend!
I have a tablet too, and I bought a bluetooth keyboard to go with it. It works ok, but I didn't like setting it up, which meant turning on the tablet, angling it using the case, then turning on the keyboard… I know, not really too bad, but flipping open the lid on the Chromebook is easier for me, and the keyboard is much nicer than my bluetooth one. This Chromebook is really light and portable too. It looks like you have a nice setup as well… perfect for on-the-go!


text:
"Kiwanuka - Michael Kiwanuka" Album Review
Label Polydor
Producers Danger Mouse
In the space of a few years Michael Kiwanuka has gone from a relatively obscure musician dabbling in an array of genres somewhat unsuccessfully, to one of the hottest names in British music. The debut album was folksy and charming, and the follow-up layered and brooding. His third album Kiwanuka continues the evolution of the singer-songwriter with an album of much wider ambition, and a flawless quality of production to match.
As with his previous work, Kiwanuka here sounds timeless without feeling dated. The music is more polyphonic than ever, with complex orchestras of instrumentalists bringing his vision to vinyl. The lyrics, too, elicit a contemporary sense of angst that evokes as many memories of mid-century revolution as it does modern-day tensions. Kiwanuka has often been topical (without being overtly political) and here he delves deeper still into racial anxieties, self-doubt and spirituality. Crucially, the songwriting is as brilliant as ever, and with producer-to-the-stars Danger Mouse at the helm, it sounds as a tight and fully realised vision, with barely a detail amiss.
If I had one criticism of the previous album, Love & Hate, it was that it was relentlessly dour. Kiwanuka manages to add a bit more variety to the tracklist, and nowhere is this clearer than in the opening track and lead single You Ain't the Problem, a remarkably catchy, upbeat number which simultaneously manages to blend the spirit of retro soul with a fresh digital veneer.
The delicately orchestrated Piano Joint (This Kind of Love) and its mesmerising intro track provide one of the album's most atmospheric moments. Understated and raw, it is classic Kiwanuka. The album then offers yet another completely different flavour with Hero, a funky slice of classic rock that pays homage to the civil rights movement and brings to mind sounds of Jimi Hendrix in his heyday.
These different moods and styles keep the album fresh without feeling disparate or disjointed. It is a testament to Kiwanuka's talents that he can bring together all these different influences and make them all sound distinctly like a Kiwanuka song. Kiwanuka looks a likely album of the year contender, and marks another fine addition to the discography of one of the world's most talented musicians.
Must Listen :
You Ain't the Problem
Piano Joint
"Secret Cinema presents: Stranger Things" Review
Let me begin by asking you a hypothetical. Would you pay £70 per person to attend a film screening where you dress up as a character in the movie and spend an hour or two hanging out in an interactive environment themed after the movie? If the answer is yes then Secret Cinema is probably something you would enjoy.
But let me ask a follow up. Would you pay the same price for the above product but without the film screening? The answer, of course, depends on how well they've executed the rest of the experience.
I am a fan of Secret Cinema, and this is the fifth of their productions that I have attended. I love the concept of immersive entertainment and enjoy the addition of interactive elements to these worlds. It's safe to say I am an even bigger fan of Stranger Things, a show upon which I have lavished great praise on this blog, and is very much in the running for 2019's best TV show. Despite these favourable predispositions, I unfortunately have to report that this is the first Secret Cinema production that I have attended and felt that it was simply not worth the money.
Secret Cinema presents: Stranger things represents the company's first foray into television. The usual Secret Cinema formula is this:
Create an atmospheric location themed after a movie
Dress up and spend an hour or two hanging out at said location, eating, drinking, dancing, and partaking in various themed activities/missions
Watch the film in a comfortable and atmospheric setting full of inebriated, like-minded people who are really into the whole experience.
It is reasonable to wonder how they would adapt this formula to a TV show. After all, a whole season of Stranger Things might last some ten hours or so. Do they just show the finale? The first episode? Some mash up or remix of the season? The answer, it turns out, was none of the above.
To their credit, Secret Cinema have done a fine job in creating their atmospheric location. This production's converted warehouse is broadly divided into two sections: Starcourt mall and the July 4th town's fair. Both areas have been lovingly and lavishly recreated from the show, and filled with various shops, bars and other curiosities containing references to the show. You can get an ice cream from Scoops Ahoy, or a burger from Benny's Burgers. You can try your luck at the videogame arcade, or get a coke float at a bar playing 80s music videos. And then for some reason there's a Coach shop selling modern handbags. The food was actually pretty tasty.
There are various activities throughout the venue including fairground games and dancing. Every now and again the cast members will hold a dance-off or science quiz to break things up a bit. In addition, each attendee will receive a mission to seek out one of the cast members and do a little sleuthing to solve a mystery. This is a good idea in theory, but the missions are themselves very simple and superficial. My contact just told me to look someone up on a computer and... that was it. The results of that search didn't have any more clues, there was no more puzzle to solve, they just referred back to it at the end of the evening, "You remember that guy you read about? I found him!". It was a five minute task made longer by the fact that you have to queue for 20 minutes to speak to the contact, and then another 20 minutes to use one of the only two available computers.
This highlights the first problem with this production, which is increasingly an issue with Secret Cinema. They clearly aren't making any money on these lavish, but brief productions and the best idea they seem to be able to come up with to solve this problem is to cram an ever greater number of people into a room with little regard for comfort or experience. That and a Coach sponsorship, apparently.
You will find actors floating about the venue performing as characters from the show, and the casting here is actually pretty remarkable. The likenesses are very impressive. The guy playing Alexei I'm still not entirely convinced wasn't the actual actor from the show. They have a script and storyline that they follow throughout the show, and from what I saw they do a good job of it. The storylines themselves are pretty forgettable and derivative, more references and callbacks to the show rather than actual stories. It's also very difficult to get involved or follow what's happening due to the fact that every cast member will invariably have about 100 people gathered around them at all times, and they don't wear microphones. If you're short like me, then you might as well just not bother.
Then the finale. For the first time in Secret Cinema history, there is no screening. Instead there's a 20-30 minute theatrical montage, loosely following the events of the three seasons of Stranger Things. There isn't really much to follow here, it's mostly the actors miming while various out-of-context sound clips of the TV series are played in the background. Notably there isn't even any seating for this performance, the audience is entirely standing (I can only imagine that this is so that they can cram more paying customers into the venue). As before, this makes it very difficult to actually see much of what is happening, especially if you're short. And... then it's over. That's it, there's no payoff at the end, not even really a goodbye. Just get the heck out and maybe spend some more money at our bars before you go. I couldn't help but feel like I had just spent £70 as a cover charge for an 80s themed bar.
The theatrical performance, as it is, is not terrible, it's just... nothing substantial. There are moments of fun, like briefly breaking out into Never Ending Story, but those moments are far too brief (in fact they only play the opening one or two lines of the song - licensing reasons maybe?). There's nothing there that justifies that finale over, say, watching an episode of the series instead.
At this point it is worth remembering the history of Secret Cinema. Initially, the concept was just: watch a movie in a themed room, with some limited interaction for flavour. The company did not start off as this immersive theatre company, that only came recently. I love immersive theatre. There are some companies that do it very well indeed (see: Punchdrunk). Secret Cinema currently is nowhere near that level. They've done a decent job at recreating a few scenes from Stranger Things, but when you look closer there's surprisingly little detail and not all that much exploring to be done.
Whereas other immersive productions might have you explore fully-realised, lived-in settings full of interactive items and flavour providing clues as to the larger story, Secret Cinema's settings still far too often just feel like the bare essential props on a fold-out table. The theatrical efforts feel more like rehashed references than anything worth paying attention to, and the interactive activities remain largely pointless and superficial busywork.
In the past this wasn't so much of a problem, since these immersive elements were merely garnish for the screening. But in a show like this where the interactive elements are the actual meat of the experience... it's just not sufficient. It's not deep enough or interesting enough to form the central focus of a production, it doesn't feel like anything more than a superficial knowing wink to the fans. It still feels like garnish, only now there is nothing at the centre of the experience to be garnished.
And then there is the price. The £70 (or more) entry fee is comparable to previous productions, only now the core of the experience (the screening) has been removed, and seemingly replaced by nothing. This might not have been a problem had they substantially improved the interaction and other immersive elements of the experience, but they haven't it's largely the same as what we have seen from them before.
So I am a bit torn on how I feel about this production. On the one hand, I did have fun. Of course it is fun to dress up as an 80s stereotype and hang out in a themed bar doing various themed activities based on an IP that you love. But it all feels so insubstantial. On the balance I would say I enjoyed the experience more than not, but the pricing makes it difficult to recommend. If the £70 per person ticket fee for a film screening with interactive elements was already unpalatable to some, charging the same price for those same interactive elements but no screening is crazy.
Ultimately I think this is the big takeaway here. Immersive entertainment can, of course, be done without a film screening. If Secret Cinema want to produce shows that focus solely on the other elements of the production, they need to significantly improve the quality of those elements, or significantly reduce the price.
"Disco Elysium" Videogame Review
Developed by ZA/UM
Published by ZA/UM
Genre Role-playing game
The videogame industry in 2019 is worth $120 billion. It is the largest entertainment industry in the world, more lucrative than film, music, or television. As with other forms of entertainment, this rapid growth has seen an incentive towards products that are safe, marketable, and mainstream. It's an increasingly rare pleasure to come across an original title that is willing to try something a bit more experimental, and Disco Elysium is definitely a true original.
Set in the fictional city of Revachol, Disco Elysium sees you play a somewhat eccentric cop waking up from what appears to have been an excessive bender that has induced retrograde amnesia. You don't know who you are, or even at first that you are a cop, but there is a dead person hanging outside from a tree, and you are here to investigate his murder.
Disco Elysium is based on a home-brew pen and paper RPG developed by lead writer Robert Kurvitz, and it is clear that a great deal of thought has been put into the world-building. Revachol is not from our world, but it is rich and believable enough to happily immerse one's self. Players will recognise many themes the world around us, racism and class inequality, political dogma, sexism and corruption. This is one of the keys to Disco Elysium. While the setting is fictional and contains occasionally fantastical elements, it always aims to create a somewhat grounded experience and is the more powerful for it. The characters are fleshed out and feel like real people with believable motivations. The game world that has been created is not the largest you will see in this genre, but it is so dripping with history and personality that you could spend hours just poring over every detail and believe it was a real place.
The game plays out in an isometric RPG format that sees the player explore the (mostly) open environment searching for clues, talking to suspects, and learning more about the world around them. It features standard RPG tropes such as inventory management, branching dialogue trees and skill checks, but this is pretty much where the similarities end.
Notably, there is no combat system in Disco Elysium. That is not to say that there won't be occasion where the player needs to get into a scrap or use deadly force, but it is realistically rare and always executed through the dialogue system. Whereas other RPGs will typically see the player rack up kill counts in the hundreds or even thousands, in this game it's more likely to be just a handful, if that. It is a design choice that plays into the game's grounded tone, and makes those moments of action all the more effective for their rarity. This is indicative of the game as a whole. Pretty much all the gameplay is carried out through the dialogue and skill checks system, which makes the skills system itself absolutely key to playing this game.
Most RPGs feature a skills system, where players earn experience points and level up skills to varying effect. In most games, these systems are fairly basic: add a point to strength to increase your attack power, add a point to charisma to increase your ability to persuade people, etc. Disco Elysium does things a bit differently. This game has some 24 different skills, each one essentially a different component of the player's personality. Add points to the "authority" skill to increase the player's forcefulness, or "interfacing" to improve their dexterity. Others are more intangible in nature, for example the "espirit-de-corps" skill which represents the extent to which the player embodies the spirit of the police force, or the "Inland Empire" skill which represents the player character's mastery of their own instincts. The Disco Elysium skill system somewhat uniquely also combines elements of a traditional "party" system, with each skill essentially being its own character. Dialogue will frequently feature a back-and-forth between the different skills and personalities, bouncing ideas and feedback around, representing the inner-monologue of the player character.
The other significant addition to gameplay comes in the "thought cabinet", essentially Disco Elysium's equivalent of a perk system. Various actions, events, and chance occurrences will introduce you to certain "thoughts", of which there are 53 in the game, only 12 of which can be used in any single playthrough. These vary quite radically in content and effect, from various political beliefs and artistic musings, to the belief that your character may secretly be an ageing rock star. These thoughts start off as vague concepts, the effect of which will not be immediately clear until you spend in-game time to "internalise" them. These can ultimately have both positive and negative consequences, which vary from skill and stat modifiers to opening up completely new dialogue and gameplay options.
These two systems are extraordinarily robust. Rather that merely conferring a particular stat boost, they fundamentally affect the identity and personality of the player character in a way that allows for some very unique and deeply customisable playthroughs. From the numbers above, you can probably infer that there are a staggering array of different combinations, ensuring that no two characters are likely to be identical.
So Disco Elysium presents an RPG experience that is quite different to what most players will be accustomed. It is a very "talky" game, slow-paced with only brief spurts of action. At the same time, it is not the sort of game you can really "lose", and failing skill checks simply takes you down a different story path. The focus is very much on the story and the choices that you make. The reason this all works is the exceptional quality of writing. Disco Elysium features some of the finest writing I have seen in a videogame, tackling big, complex ideas with depth and sensitivity and an impossibly sharp wit. This game is often laugh-out-loud funny and I was surprised by how often I had to pause and take a moment to get the laughs out of my system. The amount of care that has been put into the dialogue is really remarkable, reacting to big and small decisions, the items equipped, and even just dumb luck (like wearing a particular item at a certain time of day).
Yet there are some aspects of this game that leave a sour taste in my mouth. Primarily: the game is just way too short, particularly compared to what has been widely advertised and discussed in pre-release previews. I completed my first playthrough in just under 25 hours, with all side quests completed and, quite frankly, taking my time to enjoy the setting and explore. When you consider that other RPGs (eg Pillars of Eternity, Skyrim) can run a hundred hours or more, it really puts the slight scope of this game into perspective. Pre-release hype had described Disco Elysium as a massive open world adventure, full of memorable characters, and a play time of 90+ hours, but it is clear that this grossly stretches reality. This game really just has you solve the one case, in one fairly modest-sized map (divided into three areas). Most characters you really only meet the one time for one quest and then never see again. It is clear that the 90+ hour estimate is supposed to include multiple playthroughs, making it a highly misleading claim at best. Even with that, it's hard to see how you could get four or more playthroughs (for 90+ hours) of unique content.
Now don't get me wrong: what is here is quite excellent. I just wish there was more of it. It is far more limited in scope that you will probably be expecting, and certainly nowhere near as grand an adventure as has been advertised. Ultimately it is what it is, but it's important that you know what to expect before you buy, especially when it is being priced the same as a AAA blockbuster game, rather than the more modest indie game that it is.
It's less of a concern, but Disco Elysium also commits some grievous RPG sins, including time-limited quests (without warning), and whole areas being closed off after certain quests (again without warning), rendering some quests inoperable. I've also encountered a small number of bugs (some of which required a restart). Not a massive issue, but can be very frustrating for completionist players who don't make regular backup saves.
Disco Elysium is undoubtedly one of the more memorable gaming experiences I have had in years. The slower, more thoughtful gameplay makes for a welcome change of pace from the more obsessed games in the genre, and some of the better written scenes will live very long in the memory. I found myself frustrated with the game at times for the reasons above, but ultimately just disappointed that the whole experience was as short as it was, rather than the grand, world-spanning adventure that had been billed. I sincerely hope that future expansions/sequels are in the offing, and look forward to seeing what this talented team come up with next.


LEGAZPI CITY (Bicol Standard) -- A graduate of Bicol University-Legazpi topped the mining engineer licensure exams.
Santiago Buemia Agripa Jr. placed first with a rating of 92.9 percent, the Professional Regulation Commission announced Friday.
The PRC also said that 282 out of 326 passed the Mining Engineer Licensure Examination given by the Board of Mining Engineering in Manila, Baguio and Davao this August 2018.


Fortitude Farm offers a fun and educational summer camp where campers will learn basic horsemanship, participate in daily riding lessons, mounted games, horse themed arts and crafts, and the Friday show where they will be able to show off their newly acquired skills.
Fortitude Farm is a safe, friendly, state of the art hunter/jumper facility with high quality school horses and knowledgable staff.
Come join us for a fun, horse filled summer!


text:
Q: How to judge html's custom attribute has the one property in jquery I have define a custom attribute called "data-children",use as:

But how can I judge the property has "test04":
var $collection=$('div').attr('data-children')
……//then what can I do?

A: Since it returns a string, you can use the match method of the string object. I would suggest using the data method, though, if possible.
if ($('div').data('children').match(/(^|\s+)test04(\s+|$)/)) {
}

redpajama_set_name: RedPajamaStackExchange


text:
Sensação é uma marca de chocolate da Nestlé. O doce é conhecido pelo sabor morango e as versões ilustres de ovos de Páscoa. Sensação é composto por açúcar, cacau, leite condensado, xarope de glicose, soro de leite em pó, leite em pó integral, umectante sorbitol, emulsificantes lecitina de soja e ricinoleato de glicerila, aromatizantes e corante artificial vermelho bordeaux. Uma unidade (tablete individual) contém 178 quilocalorias, 26 gramas de carboidratos, 1.4 gramas de proteínas, 7.3 gramas de gorduras (4,4 gramas de gorduras saturadas), 1.6 gramas de fibra alimentar e 11 miligramas de sódio.

Chocolates da Nestlé


text:
Matt Bevin: Poll shows GOP Kentucky governor unpopular and trailing Democratic challengers
Scott Wartman
Republican Kentucky Governor Matt Bevin has angered many people in the past year.
Bevin has fought a much-publicized battle with teachers over pensions.
He blocks people on social media who criticize him.
And Bevin often clashes with the media, most recently in his video lambasting the Louisville Courier-Journal launching a one-year partnership with nonprofit ProPublica to investigate Kentucky state government.
Like President Trump, Bevin was an outsider businessman who rode voter dissatisfaction with establishment politicians into office. Once there, he hasn't softened his often confrontational approach, especially on social media.
Now a poll released Tuesday showed Bevin growing more unpopular with Kentuckians and trailing his Democratic challengers.
Independent polling firm Mason-Dixon Polling & Strategy found 38 percent of Kentuckians approved of their governor's performance while 53 percent disapproved. Mason-Dixon, based in Jacksonville and Washington, D.C., interviewed 625 registered Kentucky voters Dec. 12-Dec. 15. The poll has a margin of error of 4 percentage points.
Bevin fared only a little better in the conservative bastion of Northern Kentucky, where 40 percent of people surveyed approved and 51 percent disapproved.
A year ago, more Kentuckians approved of Bevin, 45 percent, compared to 41 percent who disapprove, according to Mason-Dixon.
This is not good news for Bevin as he faces re-election in 2019.
The two Democratic candidates running for governor next year, Attorney General Andy Beshear and Kentucky House Minority Leader Rocky Adkins both led Bevin in Mason-Dixon's polling. Beshear led by 8 percentage points, 48 percent to 40 percent while Adkins led by only 1 percentage point, 42 percent to 41 percent.
Secretary of State Alison Lundergan Grimes, a prominent Democrat who is mulling a gubernatorial run but hasn't announced, trailed Bevin by 1 percentage point, 46 percent to 47 percent.
The poll pointed out Kentucky Republicans often trail in the early stages of elections, including Bevin in 2015 when he first won election for governor, and Senate Majority Leader Mitch McConnell.
"Given this recent history, it is far from over for Bevin," the pollsters wrote in the study. "However, Beshear is a formidable opponent who won four years ago in a GOP-friendly state election."


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There's a lot of action from brands on corporate social responsibility (CSR) because evolved consumers are increasingly rewarding brands that are more vocal when it comes to topical themes like sustainability, and a better understanding of the eco-system in which they operate.
From recycling packaging materials (Amazon recently started doing that in India), to working with partners (in the supply chain) that adhere to established practices in diversity, a lot is happening.
But there's one brand that I hold as a torchbearer of CSR, and it doesn't even retail in India, yet.
It's the American outdoor clothing brand Patagonia. The most striking aspect of Patagonia is that they call themselves, in their mission, as 'The Activist Company'! Their mission, literally, is 'We're in business to save our home planet'.
Now, corporate (parent) groups like HUL have website that puts their social consciousness up front. If you look at HUL's website, the product list is a small part, amidst their efforts on sustainable living, including a specific section on Kodaikanal, for which they are usually criticized the most. But HUL's website is not an e-commerce website – it is more like a corporate brochure.
Compare that to Patagonia. The website is an e-commerce engine where you can shop all their products.
And in that shop, they have, up front, amongst the 6 highlights in the carousel, one that talks of 'a film about people, rivers, and the fight for the future of wild fish and the environment that supports them'.
You cannot buy anything in this tab, but it still is one of the 6 main highlights in the homepage! It's almost akin to having this giant billboard inside their store… and it does not sell anything except a cause.
Beyond that, their relentless focus on their mission is all over their online shop front.
You'd expect 'Inside Patagonia' to be about their leadership team, company info etc. Of course, it is, but almost like an after-thought! Look at what precedes the basic company details!
The level of their environmental consciousness is unlike any other brand I have seen, so much that it is all over the place on their e-commerce shop-front where most brands focus exclusively on the 'buyer' and not necessarily the 'conscious consumer'. For Patagonia, both those tags seem the same – they are perhaps looking at the conscious buyer as their target segment and that explains this sharp focus on their mission.
I don't know if they are getting rewarded monetarily (in the market) for this specific focus, or if it can be attributed to their product quality and range (since I have never used their products or visited their stores, being in India). But this is a model I am in awe of, that a for-profit brand can go to this extent putting their values and beliefs so explicitly unlike most other brands that put it as just another page under 'About Us'.
While reading about Patagonia, I also figured that they are a private company, and a 'benefit corporation'.
As per definition, in the United States, a benefit corporation is a type of for-profit corporate entity, that includes positive impact on society, workers, the community and the environment in addition to profit as its legally defined goals!
So, a benefit corporation's directors and officers operate the business with the same authority and behavior as in a traditional corporation, but are required to consider the impact of their decisions not only on shareholders but also on employees, customers, the community, and local and global environment.
I don't know if India has something similar to 'benefit corporation', but it is perhaps high time we created this model for the simple reason that we have the 2nd largest population on the planet.


Maxwell: that is SOOOO Faraday. Just meowin'.
We know that one real well. HOL funny.
MOL! They may not smell so good pretty soon! Hahahaha.
Love this picture. It is terrific. Wonder if he picked them up?? MOL.
FaRADaY: um, that would be a NO> That's what MOMMIES are for!
This looks like something Ernie would do!
This totally hit home cos every Caturday when Pop does the vacuuming, he says that to me! I never pick them up tho and he has to bend over.


Nixon or Clinton: Which model is President Ezer Weizman following?
Some politicians have called on Weizman to step down in return for a blanket pardon, such as that granted President Nixon by his successor, Gerald Ford.
But Weizman appears to want to emulate President Clinton and his dogged fight to remain in office despite the Monica Lewinsky affair. Weizman made it clear during a televised speech to the nation Sunday that he would neither resign nor take a leave of absence while police probe allegations he illegally received cash gifts from a French millionaire friend.
Weizman's decision not to step down has elicited across-the-board criticism from Israel's political community.
The Weizman affair, combined with other scandals that have shaken up Israeli politics in recent years, has also raised another, potentially more troubling question: Are the ethical norms that characterized the Zionist state in its early decades giving way now to a corrupt set of practices more worthy of a banana republic?
Weizman, Israel's seventh president, has acknowledged accepting hundreds of thousands of dollars in gifts from Sudan-born businessman Edouard Saroussi from 1988 to 1993, when he served as a legislator and Cabinet minister.
Weizman claims the money was a gift and that his longtime personal lawyer, Hanina Brandes, who was also Saroussi's lawyer, advised him this was legally permissible.
Attorney General Elyakim Rubinstein ordered a full-fledged police inquiry last week when evidence surfaced that Weizman had undertaken paid consultancy work for Saroussi's company in Africa in 1983 and 1984. Rubinstein was angered that the president's lawyers had not volunteered this information.
The still-mushrooming affair is a source of shame and real pain to virtually every Israeli citizen, both because of the warmth and sympathy many feel toward Weizman the man and because of the shadow it casts over the political system.
Aryeh Deri, the head of the fervently Orthodox Shas Party, was sentenced last April to four years in jail on charges of bribe-taking, fraud and breach of the public trust.
A top aide to former Prime Minister Yitzhak Rabin, Shimon Sheves, is the subject of an ongoing bribery trial.
Add to these the high-profile case of Ma'ariv publisher Ofer Nimrodi, who is facing charges of being involved in a murder conspiracy and subverting justice, and you have a worrying picture indeed.
The Bar-On Affair. In January 1997, Netanyahu appointed a little-known Jerusalem attorney, Roni Bar-On, as attorney general, but had to force him to resign 48 hours later under a storm of allegations that his nomination reflected an attempted "takeover" of the state's prosecution apparatus by a cabal of politicians.
There were allegations at the time that Bar-On was appointed as part of a deal to provide a plea bargain in the ongoing corruption case against Deri and to soft-pedal charges of telephone tapping then pending against Nimrodi.
Rubinstein, who was subsequently named attorney general, is now spearheading a veritable crusade by the state judicial machine to "purge" the political establishment of any vestiges of corruption.
This explains, say observers, the stern and unforgiving attitude adopted by Rubinstein and State Prosecutor Edna Arbel toward Weizman's alleged wrongdoing.
The Deri conviction. After his sentencing last year, Deri's appeal before the Supreme Court is slated to begin soon. When he was sentenced to four years, the court said last year the bribes were general goodwill payments rather than a quid pro quo for specific services rendered.
Those circumstances are not all that different from those alleged against Weizman.
This explains the insistence by the nation's law enforcement officials and of most of its politicians that Weizman face the music — and their reluctance to turn a blind eye, despite the president's long service to the state as soldier and statesman.
They fear that to do so would be to trigger huge Shas protests charging discrimination.
The prosecution and conviction of Deri set strict norms of conduct for public officials. Weizman is the first to be measured by them — and to be found lacking.
His decision not to step down, not surprisingly, was criticized by right-wing politicians, who have been angered by his forthright support for Barak's peace policies.
But the criticisms have come from across the political spectrum, including from three Cabinet ministers.
Justice Minister Yossi Beilin, who had publicly urged the president to take a leave of absence, said he "respected" Weizman's decision to stay in office.
But he called on him not to discharge two of his principal constitutional functions — swearing in judges and considering pardons — while the police inquiry against him was in progress.
On Monday, Weizman indicated that he intends to continue fulfilling those duties.
Minister of Absorption Yuli Tamir termed Weizman's television address "disappointing." She said he would be pressed publicly on the Saroussi affair wherever he went, and this would inevitably detract from the dignity of his high office.
Another minister, Yitzhak Levy of the National Religious Party, also voiced "shame and disappointment," saying the president had done "the precise opposite of what was expected" by not stepping down.
Man-in-the-street reactions to the president's dramatic appearance were harder to gauge.
There were certainly those who praised his courage and stubbornness — "Achla Gever," Hebrew for a "real he-man," was one of the phrases much in evidence on Sunday night.
But others felt he risked getting into even deeper waters by not quitting now.


These instructions show you how to make a crude BMW service light reset tool.
Instructions on how to make your own Angel Eye side lights.
Before doing this check how much they are to buy on EBAY as they are getting cheaper all the time for clones.
These instructions show you how to allow active the double lock (deadlock) of an alarm remote, normally only stage 1 locking occurs.
A common problem with the E36 is the sunroof. There are two Track control arms that force the roof to tilt. These are connected to plastic runners that frequently snap resulting in a roof that won't tilt. Here we will describe how to remove the roof and repair the mechanism. It will cost approx £26.50 to repair. You will only need a few tools, around two hours and a bit of patience!
There is a common fault with the Climate Control Computer where a capacitor fails, these instructions show you how to repair this at a fraction of the cost.


Every region's economy should be organized into three types of enterprises: cooperatives, key industries, and small private enterprises. Cooperatives would form the core of the economy. Except for a few large-scale, key industries and small private enterprises producing non-essentials, all production is to be organized under worker-owned and controlled enterprises. Cooperatives increase worker motivation and job satisfaction because they give workers control of the business as well as a stake in its profits. When cooperatives have access to the requisite inputs of production—capital, entrepreneurship, skilled labor, and competent management—they invariably out-perform private, free-market enterprises. Cooperatives are controlled by their worker members on the basis of one member, one vote. All members must purchase a membership share in the cooperative. This initial capital contribution gives each worker member a financial stake in the business. Thus workers' ownership rights are based on their functional role as workers, and not on the basis of their capital contribution.
Wage differences. Workers should be paid according to their skill level and their labor. This can be done through salary gradations, payment for piece work, or bonuses. Workers in cooperatives will receive dividends according to the profitability of their enterprise.
Psychological incentives. Non-material incentives are also very effective. Motivation increases when workers feel compatibility with their job, when their work environment is pleasant and safe, and when their work provides interest and challenge. Perhaps the most important psychological factor for increasing motivation is the ability to influence decision-making. Therefore, all enterprises should implement participatory management processes and teamwork to the greatest extent possible. Teamwork can reinforced by material incentives based on team performance.


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UEFA Champions League - Barcelona vs. PSG - Betting Odds and Game Preview - April 10th, 2013
After a 2-2 draw in Paris, Barcelona will host PSG on Wednesday, April 10th, 2013 in the second leg of the UEFA Champions League quarter-final.
Barcelona have made it to the semi-finals in each of the last five seasons and are looking to do it again with or without their star player Lionel Messi who is recovering from a hamstring injury and is questionable for Wednesday. PSG on the other are looking to stun the soccer world by beating the hosts who are undefeated in their last 20 UEFA Champions League home matches.
Barcelona 4/11
Draw 9/2
PSG 8/1
A $100 bet on Barcelona could bring $36 in profit while the same bet on PSG could bring back $800 in profit.
To Qualify Odds are:
Barcelona 1/9
$100 on Barcelona could bring $11 in profit while the same bet on PSG could bring $600 in profit.
A few interesting Goalscorers odds:
Lionel Messi 1/3
David Villa 8/13
Alexis Sanchez 11/10
Zlatan Ibrahimovic 7/4
A $100 bet on Messi to score could bring back $33 in profit, while the same bet on Zlatan Ibrahimovic could bring back $175 in profit.
Barcelona are clear favourites in the upcoming match, especially considering what they did to AC Milan in the 2nd leg of the Round of 16. Over the weekend Barca beat Mallorca 5-0 in the league. Mascherano and Puyol are sidelined for the match for Barca while Messi, Pedro and Adriano are under a question mark.
PSG eliminated Valencia in the Round of 16 and over the weekend they beat Stade Rennais FC 0-2 in the French Ligue 1. Thiago Motta and Thiago Silva are under a question mark for Wednesday.
Can PSG pull an upset at Camp Nou or do they still have some maturing to do before competing with a top team such as Barcelona? Can Barca repeat the all-star performance from the Round of 16 in front of their home fans and qualify for their sixth consecutive UEFA Champions League semi-final?
This should be a great game!


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The Ascension of Universal IDs in the Wake of Third-Party Cookies
March 25, 2021 Zach Atlasblog, cookie syncing, cookies, IdentityLink, LiveRamp, privacy, privacy sandbox, The Trade Desk, Unified ID, Unified ID 2.0, universal id
On March 18, 2021 we provided an overview of Google's Privacy Sandbox, a forum for Google and other players in the ad tech industry to propose privacy-centric tracking alternatives to the soon-to-be deceased third-party cookie. As a reminder, cookies are…
What Has Happened Since Apple Delayed the IDFA Opt-In and What Should Publishers Do Before it Is Enforced Next Year?
December 10, 2020 Eric Shiffmaniab specification, ios 14, privacy
In July, we covered Apple's announcement that with iOS 14, Apple will disable the IDFA by default and users must actively opt-in to share it with each app. We discussed how Apple got here and what publishers should start doing…
Apple "Killed" the IDFA, What Now for Mobile Ad Tech?
July 13, 2020 Eric ShiffmanApple, cookie, data privacy, device IFA, identifier for advertising, IDFA, privacy
You've seen the headlines. Apple has crippled, or killed, its identifier for advertisers (IDFA), leading to the apocalypse for ad-supported mobile publishing. Is it really the apocalypse? To learn the truth of how this latest change from Apple will affect…
Connected TV Addressable Advertising Is The Future, But How Do We Accomplish It In The Age of Privacy?
June 11, 2020 Eric ShiffmanCCPA, consent, CTV, GDPR, OTT, privacy
Connected TV adoption and viewership has been growing for years and has accelerated substantially due to the COVID-19 crisis. A recent study shows that the pandemic appears to be accelerating the cord-cutting shift, with 64% of respondents saying they cut…
CCPA: Initial Reactions, What We've Learned so Far, and What's Next for Ad Tech
March 19, 2020 Eric Shiffmanad tech, california consumer privacy act, CCPA, IAB, privacy, regulation, specification
The California Consumer Privacy Act (CCPA) is a landmark consumer privacy bill that took effect on January 1, 2020, though the California Attorney General cannot bring enforcement action until July 31, 2020. The intention of the act is to enhance…
5 trends in ad tech
November 7, 2019 Amanda Boughey5G, ACR, ad tech, AR, data, privacy, trends
As we're approaching the end of 2019, it's time to take stock of ad tech predictions and trends. Some of the predictions at the end of last year haven't taken shape, and others have skyrocketed. Here are five trends we're…


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Home Anime News
Elementhunters, Tokyo Magnitude 8.0 premieres on Yey! this November
Two adventure anime titles previously aired on HEROtv in 2013.
Red Mendoza
©Tokyo Magnitude 8.0 Production Committee
Anime Pilipinas has learned that adventure anime titles Elementhunters and Tokyo Magnitude 8.0 premieres on ABS-CBN's digital terrestrial channel Yey! this weekend.
Both titles were previously aired on Filipino-language anime channel HEROtv, which is a sister channel of the terrestrial channel.
©Elementhunters Production Committee
Chemical elements had disappeared from the planet, causing forests, buildings and life itself to disappear. Research reveals that the elements have been flowing into another Earth on the another side of a dimensional wall that can only be accessed by those with flexible minds. A team of Element Hunters is formed to return the elements to Earth. (Synopsis from Anime News Network)
Elementhunters is a 39-episode anime series produced by NHK and HeeWon Entertainment, which was directed by Yoshiaki Okumura and Han Pyo Hong, while Naruhisa Arakawa handled series composition. The series first premiered in Japan on July 2009, and was first aired in the Philippines on HEROtv in December 2013.
Elementhunters premieres on Saturday, November 01, airing Every Weekends at 09:00pm.
In 2012, Mirai, a middle school freshman girl, goes to Tokyo's artificial Odaiba Island for a robot exhibition with her brother Yuuki at the start of summer vacation. A powerful tremor registering 8.0 on the JMA scale emanates from an ocean trench, the famed Tokyo Tower and Rainbow Bridge crumble and fall, and the landscape of Tokyo changes in seconds. With the help of a motorcycle delivery woman named Mari who they meet on Odaiba, Mirai and Yuuki strive to head back to their Setagaya home in western Tokyo. (Synopsis from Anime News Network)
Tokyo Magnitude 8.0 is an 11-episode anime series produced by anime studios BONES and Kinema Citrus, which was directed by Masaki Tachibana and Natsuko Takahashi handling series composition. The series first premiered in Japan on Fuji TV's noitaminA block in 2009, and HEROtv aired the anime in March 2013.
Tokyo Magnitude 8.0 premieres on Saturday, November 01, airing Every Weekends at 09:30pm.
Yey! is one of the digital terrestrial sub-channel of ABS-CBN, which is currently under test broadcast, and the second animation channel of the network after HEROtv.
Previous anime titles have also aired on Yey!, like Kirarin Revolution, Sgt. Keroro, Kuroko's Basketball and the Naruto series. The terrestrial animation channel were also the first channel air Marvel's anime adaptations, which includes Iron Man, Wolverine and Blade.
http://freedomstrikedispatches.wordpress.com
Anime Pilipinas Events Editor and Chief Correspondent, also concurrently reporter for a major media entity. A lifelong believer of Gundam SEED and Captain Earth but Aki Tomoya of Saekano is his spirit character.


Makulu Group is an organization doing business mainly in the repairs and Maintenance of different Technologies that are widely used to improve people's standards of living. It consists of three member companies currently which include; Makulu Technologies Limited, Makulu Institute of Mobile Technology, Makulu Agro-ventures. It is governed by a central management that runs, manages and develops the Group.
Carry out administrative and office activities as well as participating in the administrative functions in all the company projects.
Keep records of all inquiries in our call center database so as to generate a concise report that will enable management perform relevant decisions.
Communicate information from authorities of Makulu Group straight to each relevant staff through phone call, email or any availed media.
Communicating to all Makulu Group staff internally and compiling information from internal communication.


The Membran Entertainment Group is one of the music industry's leading European independents. Membran has one of the most effective multi-cultural team and distribution network of any independent music company in the world. Membran produces, sells and distributes its comprehensive media products both independently and through its experienced partners worldwide. Be it in the traditional retail outlets, the digital world or non-traditional as branded entertainment: Membran not only thinks and adapts in all the directions that the continually evolving world of entertainment demands – but it continues to exploit its potential to the maximum, using a powerful and global distribution network.
Membran's array of "in-house" labels offer productions in all styles and genres of music – ranging from jazz, classical, pop and rock, as well as a wide spectrum of genre and "theme" compilations and special limited edition exclusive boxes. Through its label-management services, Membran offers third party labels, artists or producers a complete service ranging from A to Z to enable the successful marketing, promotion and distribution of music designed for today's digital age worldwide.
Since its foundation in 1968 the company has expanded, becoming stronger and unique due to the huge numbers of classical music productions; Membran has not only received numerous awards and Media Prizes such as from the Association of German Music Schools, the German Record Critics' Prize, various nominations for the MIDEM Classical Award and more, making Membran a world leader in the Classical world – but the company also devotes its attentions to developments in the modern world of entertainment, continually broadening its horizons in the process. Both national and international acts and signings find their way to Membran, celebrating chart entries and enjoying the attention of both media and public as a result.


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Saultites In Out Of Town Bands Profile: Infathom
As August winds down, we still have a couple of monthly feature posts to share, and first, here's this month's Saultites In Out Of Town Bands Profile! For the first time in 10 months, we're looking at a band from the United States featuring a past or present Sault Ste. Marie resident, and this band has been keeping busy this year in the Upper Peninsula, so hopefully this month's profile is a good read! As always, we'll profile the local connections, history, and notable happenings of this band, even if they're not all from here, so let's get this profile going, and if anything's wrong or missing, please tell me! (Updated on November 26th, 2014) ----------------------------------------------------------------------------------
Infathom (Munising, Michigan)
Lineup: (Saultites in RED; ex-members in italics)
Dillion Semasky (vocals)
Sean Hayes (guitar)
Keegan Nebel (bass)
Cody Hayes (drums)
Josh Stadler (guitar)
Official MySpace page: http://myspace.com/infathom
Official YouTube channel: http://youtube.com/infathom
Official Facebook page: http://facebook.com/infathomband
Local Info: Though the members of Infathom are all from Munising in the U.P. (2½ hours west of Sault Michigan), I think only one member ever lived here in the past, and apologies if I'm lacking anything here. Frontman Dillion Semasky has lived and attended Sault Area High School in recent years, even launching a short lived local solo band named Novesane last year that didn't appear to take off, along with a brief stint with Half A Man in 2011-2012, and some recent original rap songs. However, he's best known for his work with Munising metal band Infathom, and if you're lucky, you might see them locally here and there!
Band Bio: Formed in the spring of 2008, Infathom started as a metal quartet playing a mixture of covers from bands like Avenged Sevenfold, Pantera, and Papa Roach, but would introduce originals into their set as well. Their first few years aren't easy to document online, but videos of jam sessions and some performances are floating around, including sets at Munising area talent shows. Unlike many similar bands in the area, Infathom are known to cover acoustic songs and ballads occasionally too, which adds to their repetoire nicely! The talented young band seemed to turn things up in 2011, adding second guitarist Josh Stadler to the band and playing at a number of major concerts in the Upper Peninsula, including LemmaFest in Sault Michigan and the PigFest and Turn It U.P. festivals in the Ishpeming area this summer. After a dormant period from 2011-2012, Infathom have been turning it up (albeit as a quartet again) with a number of U.P. concerts, including at least two a year in Chippewa County, so stay tuned for more!
I find that Infathom show a lot of versatility to their sound (especially given their ages), rather than playing one sound only, and I'm impressed overall! It's nice to see a young band focus on newer metal that doesn't have to involve death growling, and they cover some bands you don't see covered often, so they definitely stand out! Dillion Semasky's vocals range from a good clean singing tone to some nice aggressive metal singing that fits with a lot of genres, and the rest of the band shows talent too! I can't speak for Josh Stadler's work with Infathom, but the Hayes brothers mesh really well, Sean's guitar work is pretty impressive, and Keegan Nebel's bass work stands out most of the time as well! Infathom pull off softer songs well too, and when given the right scenario, Dillion can impress as a pure singer as much as a metal frontman! It's a shame that Infathom went on hiatus at what is probably their peak as a band, but hopefully they'll reunite sooner rather than later to rock the U.P. as only they can!
Though Infathom have no albums to my knowledge, they have plenty of original and cover material from live recordings to check out at their official MySpace page! If you're looking for videos, there's even more of those to watch and get a taste of Infathom, so just search for them on YouTube! The band's old 2009-2010 YouTube channel is the best for volume of videos, but the channels of bassist Keegan Nebel and user Michael Cole have some of the best quality recent videos, so I recommend both for interested fans! Here's Infathom playing their originals "Blissful Insanity" and "Dying Breed" at PigFest this past June!
And so ends the summer months for this monthly series at the SMS, but what out of town band are we profiling next month? I've chosen Paricide, an inactive metal quintet from Petrolia, Ontario (30 minutes southeast of Sarnia) that featured Sue Inside frontman & former Sault Ontario resident Shane Lipsit-Fraser in their lineup! Note that Paricide and the defunct local hardcore band Paraside are two completely different bands, in case someone gets them confused. Look out for our profile of Paricide at this time next week, between September 23rd and 29th! That's all for now, but stay tuned for more news and our review of Sykotyk Rampage's latest album "Zombies" this weekend! Thanks everyone!
Tags: dillion, infathom, metal, michigan, munising, sault, scene, semasky
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Last Month's Poll Results & This Month's Poll!!
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Sykotyk Rampage's New Albums, Half Past's New Vide...
"Soo Stories: A Rock N' Roll Scrapbook" Review!!
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Smeltzer Reunion Concert Review!!
A "New" Local Band, Woods V News, And Much More!!
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Hempfest 2011 Preview!!
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Mares of Thrace Concert Review!!
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A New Local Band, Two Newly Broken Up Bands, And T...
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Lots Of Assorted News And Notes!!