Soon-Tae Lee, Wooseok Im, and Jae-Jun Ban contributed equally to this work.
Received 2016 November 3; Revised 2016 November 25; Accepted 2016 November 29.
Huntington's disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect.
We developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line. Exosomes were then harvested from these cells using an optimized protocol. The exosomes (Exo-124) exhibited a high level of miR-124 expression and were taken up by recipient cells.
When Exo-124 was injected into the striatum of R6/2 transgenic HD mice, expression of the target gene, RE1-Silencing Transcription Factor, was reduced. However, Exo-124 treatment did not produce significant behavioral improvement.
This study serves as a proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases.
Huntington's disease (HD) is a genetic neurodegenerative disease that is caused by the abnormal expansion of CAG repeats in the gene encoding huntingtin. HD results in devastating neurological symptoms, including cognitive impairment, neuropsychiatric symptoms, and involuntary choreiform movements . Although the precise mechanisms of HD neurodegeneration remain unclear, one of the mechanisms involves alterations of transcriptional regulators, such as RE1-Silencing Transcription Factor (REST) . Mutant huntingtin no longer silences the activity of REST, and this loss results in increased binding of REST to RE1/neuron restrictive silencer element, producing transcriptional dysfunction . Thus, many therapeutic approaches have attempted to restore normal REST expression .
MicroRNAs (miRNAs) are short, non-coding RNAs of ~22 nucleotides that regulate gene expression by suppressing the translation of mRNA. We and others have previously shown that the expression of miRNAs is altered in HD  and that miR-124 is one of the key miRNAs that is repressed in HD [6,7]. In HD, decreased expression of miR-124 increases the level of its target gene, REST, resulting in the repression of key target genes such as brain-derived neurotrophic factor . miR-124 induces adult neurogenesis in the subventricular zone  and regulates the cell cycle in striatal neurons . Given that the HD striatum exhibits decreased neurogenesis, which leads to brain atrophy [11,12], the delivery of miR-124 may be a feasible way to induce neural regeneration. However, naked miRNAs are vulnerable to degradation, and our recent experiments using naïve miR-124 in HD showed little therapeutic effects .
Exosomes are endocytic nano-vesicles (< 100 nm) that are released by cells and that can deliver miRNA to recipient cells . Recently, because of their significance in normal physiology and disease progression, exosomes have been actively studied as a type of therapeutic agent [15-17] and drug delivery vehicle . Exosomes can be isolated from various tissues [19-22], and many cells in the central nervous system also release exosomes, which participate in the intercellular transfer of DNA, RNA, or misfolded proteins; as a result, exosomes have been implicated in development, normal function, and pathogenesis . Considering the importance of miRNA and exosomes in neurodegenerative diseases, exosomes containing miRNAs that are abnormally altered in neurodegenerative diseases should be studied to characterize their effects on disease models. Here, we investigated the feasibility of exosome-mediated therapeutic delivery of miRNA in a HD model.
Mature miR-124 was cloned into the pSUPER plasmid to overexpress the miRNA in cells. HEK 293 cells were transfected with the pSUPER-miR-124 vector using Lipofectamine 2000 (Life Technologies, Carlsbad, CA, USA) according to the manufacturer's instructions. The pSUPER-miR-124-transfected cells were cultured in medium containing Zeocin (500 μg/mL) to select for cells expressing miR-124. The medium was changed every 2 or 3 days until single-cell colonies formed (2–3 weeks). Single colonies were isolated and regrown for 2 weeks with Zeocin media, and miR-124 expression was tested using quantitative reverse transcription polymerase chain reaction (qRT-PCR).
HEK 293 cells overexpressing miR-124 were cultured in exosome-free Dulbecco's modified Eagle's medium (DMEM; Gibco Invitrogen/Life Technologies, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (FBS; Gibco Invitrogen/Life Technologies) and 1% penicillin-streptomycin at 37°C in a 5% CO2 incubator. To deplete bovine exosomes, DMEM containing 10% FBS was centrifuged at 100,000 g for 15 h, and the supernatant was used for cell culture. Culture supernatants were harvested after 5 days. Cells and cellular debris were eliminated from the conditioned medium by centrifugation at 3,000 g for 10 min at room temperature. The conditioned medium was treated with citrate (3 mM, 6 mM) for 2 days at 37°C. Exosomes were isolated using the Exo-Quick exosome precipitation kit (System Biosciences, Mountain View, CA, USA) according to the manufacturer's specifications. Briefly, 5 mL of conditioned medium was thoroughly mixed with 1 mL of Exo-Quick exosome precipitation solution, and the solution was incubated for 24 h at 4°C. The conditioned medium was centrifuged at 1,500 g for 30 min, and then the supernatant was removed and centrifuged at 1,500 g for 5 min. The exosome pellet was resuspended in buffer.
Exosomes were labeled with PKH67 (Sigma-Aldrich, St. Louis, MO, USA) according to the manufacturer's protocol. Briefly, the exosome pellet was suspended in 100 μL PBS and then diluted in 1 mL of Diluent C. The solution was then rapidly mixed with a freshly prepared solution of 4 μL of PKH67 dye in 1 mL of Diluent C. The mixture was incubated for 5 min. Labeling was stopped by the addition of 2 mL of 1% BSA in PBS for 1 min. The samples were washed 2 times with 25 mL of PBS and then centrifuged at 120,000 g for 100 min. After labeling, the PKH67-labeled exosomes were stored in PBS containing 2% paraformaldehyde until flow cytometric analysis (BD Biosciences Pharmingen, San Jose, CA, USA). PKH67 fluorescence was evaluated using the green channel, and the data were analyzed using WinMDI software (Windows Multiple Document Interface for Flow Cytometry, West Lafayette, IN, USA). Fluorescently stained sections of brains that were injected with PKH67-labeled exosomes were analyzed using an inverted microscope (BX61, Olympus Corporation, Tokyo, Japan).
RNA was isolated using Trizol (Thermo Fisher Scientific, Asheville, NC, USA), and the level of miR-124 was quantified using the mirVana qRT-PCR miRNA Detection Kit and TaqMan miRNA assays (Ambion, Applied Biosystems, Foster City, CA, USA). All reactions were run in triplicate on an ABI PRISM 7,000 sequence detection system (Applied Biosystems). Relative expression levels were calculated using the comparative threshold cycle (Ct) method (relative expression levels = 2-∆Ct) and were normalized to the expression of the control, snoRNA202, which was measured in the same samples using an endogenous snoRNA detection kit (Ambion, Applied Biosystems).
The animal study was approved by the Institutional Animal Care and Use Committee of Seoul National University Hospital, which was accredited by the International Association for the Assessment and Accreditation of Laboratory Animal Care. We used the R6/2 line of transgenic HD mice [B6CBATg(HDexon1)62Gpb/3J, The Jackson Laboratory; 6 female and 6 male mice; 111 CAG repeats] and their wild type (WT) littermates (6 female and 6 male mice) at 6 weeks of age. These mice were obtained by crossing ovarian transplant hemizygous females with B6CBAF1/J males. Genotyping was performed using PCR . An expanded CAG repeat in exon 1 of the HD gene is sufficient to cause a progressive neurological phenotype in these transgenic mice . The mice were housed in groups with ad libitum access to food and water and a 12-h light/12-h dark cycle.
To inject exosomes, 6-week-old (42 days) mice were anesthetized via intraperitoneal injection of 1% ketamine (30 mg/kg) and xylazine hydrochloride (4 mg/kg) and then positioned in a stereotaxic apparatus. All exosomes obtained from 5 mL of conditioned medium were suspended in 12 μL of PBS. In the exosome injection group (Exo-124), a 30-gauge Hamilton syringe was used to inject the exosome suspension into the bilateral striatum (2 μL of suspension per hemisphere) at the following coordinates: AP + 0.38 mm, ML ± 2.0 mm, and DV -3.5 mm from Bregma. The exosomes were slowly injected over a period of 5 min. The needle was left in position for another 5 min and then gently removed. All animal experiments and procedures complied with the NIH Guide for the Care and Use of Laboratory Animals.
Rota-Rod performance was assessed using an accelerating Rota-Rod (San Diego Instruments, San Diego, CA, USA) as previously described . The speed of the Rota-Rod was set to linearly increase from 4 to 40 rpm over 3 min. The mice were initially trained on the Rota-Rod for three consecutive days. Three trials were conducted per day, with a 30-min rest period between trials. The trials and tests were terminated if the animal fell off the rungs or gripped the device and completed two consecutive revolutions. At each age, mice underwent three trials, and the mean latency to fall was calculated.
When the mice were 8 weeks old (1 week after the exosome injection, n = 3), histological evaluations were performed as previously described . Briefly, the animals were deeply anesthetized and then perfused through the heart with 10 mL of cold saline and 10 mL of 4% paraformaldehyde in 0.1 M PBS. Sections (20 μm thick) were counter-stained with DAPI (Sigma-Aldrich, St. Louis, MO, USA), and PKH67 fluorescence was analyzed using a microscopic imaging system (Carl Zeiss, Thornwood, NY, USA).
At the age of 8 weeks (1 week after the exosome injection), the mice were sacrificed by decapitation, and the brains were immediately removed. Homogenates of each hemisphere were separately and serially processed for Western blotting and RNA work. Western blotting was performed using antibodies against REST (Abcam, Cambridge, UK), doublecortin (DCX; Santa Cruz Biotechnology, Santa Cruz, CA, USA), or β-actin (Santa Cruz Biotechnology). The blots were developed using enhanced chemiluminescence reagents (Pierce, Rockford, IL, USA) and digitally scanned (GS-700; Bio-Rad, Hercules, CA, USA). The optical density of each band relative to that of the β-actin band was determined using Molecular Analyst® software (Bio-Rad). For real-time PCR, total RNA was isolated from each hemisphere using QIAshredder and RNeasy kits (Qiagen, Valencia, CA, USA). miR-124 levels were measured using the mirVana qRT-PCR miRNA Detection Kit and TaqMan miRNA assays (Ambion, Applied Biosystems).
All data in this study are presented as the mean ± standard deviation. The Mann-Whitney U test was used for nonparametric, inter-group comparisons. SPSS 17.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analyses. A two-tailed p-value < 0.05 was considered significant.
We first generated a miR-124-expressing cell line by transfecting the miR-124 expression vector into HEK 293 cells. miR-124 expression was confirmed by real-time PCR (data not shown). We harvested exosomes from the medium used to culture these cells, as presented in Figure 1A. Based on previous reports , we added citrate and Mg2+ during the procedure to protect the RNA contained in the exosomes. Figure 1B shows the harvested exosome pellets.
Generation of Exo-124. A: Diagram showing the procedure used to generate Exo-124. We repeatedly harvested Exo-124 from HEK 293 cells overexpressing miR-124. B: The harvested Exo-124 pellets. C: Expression of CD9 and CD63 in Exo-124. Exosomes harvested from the conditioned medium expressed CD9 and CD63, whereas exosomes from the normal control medium did not express these markers. D: Compared to the control exosomes (Exo-ctr), Exo-124 expressed a high level of miR-124, as measured by real-time PCR (n = 3 per group). *p < 0.05.
We evaluated the pellets by blotting for CD9 and CD63, which are tetraspanin proteins that are expressed at the cell surface and thus serve as exosome markers [14,27]. The exosomes expressed both CD9 and CD63 (Figure 1C), whereas centrifugation of unused culture medium did not produce any CD9- and CD63-bearing materials. We thus confirmed the presence of exosomes.
We then measured the expression of miR-124 in the exosomes. Control exosomes (Exo-ctr) harvested from naïve HEK 293 cells that were not transfected with miR-124 expressed very low levels of miR-124. On the other hand, miR-124-enhanced exosomes (Exo-124) harvested from HEK 293 cells that were transfected with the miR-124 expression vector expressed much higher levels of miR-124 (Figure 1D). Thus, we moved forward to in vitro and in vivo applications of Exo-124.
To confirm intercellular transfer of the exosomes, we labeled the exosomes with PKH67 and added Exo-124 to the culture medium of HEK 293 cells for 24 h. After Exo-124 treatment, the PKH67 fluorescence of the recipient HEK 293 cells was confirmed by flow cytometry (Figure 2A, B, and C) and immunocytochemistry (Figure 2D). These results demonstrated that Exo-124 produced by our isolation and treatment protocol was efficiently taken up by recipient cells.
Delivery and therapeutic effects of Exo-124 in a HD model. A, B, and C: Exo-124 was labeled with PKH67. The labeled Exo-124 exhibited PKH67 fluorescence (B), whereas the unlabeled Exo-124 did not (A), as revealed by flow cytometry (C). D: When Exo-124 was added to the culture medium of HEK 293 cells, the cells exhibited PKH67 fluorescence. E: When Exo-124 was injected into the striatum of R6/2 HD mice, Exo-124 was taken up by the striatum and corpus callosum. F: One week after the injection of Exo-124, the level of miR-124 expression in the brains of the Exo-124-injected R6/2 mice was similar to that in the control mice, with a slight trend toward an incremental increase in miR-124 expression (n = 3 for the control and 5 for the Exo-124 group). G and H: The injection of Exo-124 significantly decreased REST expression in the R6/2 mice, as measured by western blotting (G) and densitometry (H) (n = 3 for the control and 5 for the Exo-124 group). However, the level of Dcx was not changed. I: The injection of Exo-124 also did not significantly affect Rota-Rod performance (n = 5 per group). *p < 0.05. HD: Huntington's disease, REST: RE1-Silencing Transcription Factor.
Because previous studies have demonstrated the efficacy of exosome-mediated delivery of miRNA , we proceeded directly to the therapeutic application of Exo-124 in R6/2 HD transgenic mice. We injected Exo-124 into the striatum of 6-week-old R6/2 mice. Upon analysis 1 week later, PKH67-labeled Exo-124 had been taken up by the striatum (Figure 2E). We measured miR-124 expression in the mice and found that the Exo-124-treated R6/2 mice exhibited slightly higher levels of miR-124 expression compared to the control (non-treated) R6/2 mice, but this difference was not significant (Figure 2F). We hypothesized that the endogenous abundance of miR-124 in the brain masked the effect of delivery. Thus, we measured brain levels of REST protein, the key target protein of miR-124, and we found that REST expression was lower in the Exo-124-treated R6/2 mice than in the control R6/2 mice (Figure 2G and H). Next, because the miR-124-REST system regulates neurogenesis, we measured Dcx (doublecortin) expression in the brain and found that Exo-124 treatment had no effect on Dcx protein levels (Figure 2G and H). Moreover, at 7 weeks of age, no differences in Rota-Rod performance were observed between the Exo-124-treated R6/2 mice and the control R6/2 mice (Figure 2I).
In this study, we demonstrated the feasibility of exosome-based therapeutic delivery of miR-124 in a HD model. We could generate Exo-124 from a miR-124-overexpressing cell line, enabling stable and efficient generation of miRNA-bearing exosomes. In addition, when Exo-124 was delivered to the striatum, it reduced the expression of REST. However, Exo-124 had little effect on Rota-Rod performance.
The delivery method is one of the critical issues in the development of miR-based therapeutics for neurological diseases. When using antagomirs, the antisense inhibitor oligonucleotides of miRNAs, it is possible to use naked formulations and to deliver them via stereotaxic injections into the brain . However, when miRNAs themselves are delivered, it is necessary to use additional methods to protect the miRNAs from degradation, such as lipid-based delivery systems, poly-(lactic-co-glycolic acid) particles, or viral vectors . The exosome method is more physiological and less immunogenic, and if the exosomes are engineered to express specific surface ligands such as integrins, the exosome method can be used to selectively reach specific target cells .
Exosomes or extracellular vesicles can deliver not only miRNAs but also mRNAs, non-coding RNAs, cellular proteins, or even prions . Under natural conditions, exosomes mediate cross-talk between neurons and other cells, such as microglia and immune cells . Exosomes regulate development and normal brain function and also contribute to synaptic plasticity and regeneration [23,32,33]. In disease conditions, exosomes can be used to deliver RNAi, antigens for cancer immunotherapy, and therapeutic chemicals. In the present study, we showed that naïve miRNAs can be packed in exosomes and delivered as a therapeutic treatment for neurodegenerative diseases.
Although we showed that exosome-encapsulated miRNAs could be transferred to recipient cells in vitro, the current method must be further developed for in vivo applications. Because the therapeutic efficacy of Exo-124 was modest, it may be necessary to increase the dose of miRNAs packed in the exosomes. In addition, because the therapeutic effect of miR-124 might be limited, it is necessary to test whether the delivery of other miRNAs via the exosome method might have greater therapeutic effects. Candidate miRNAs might include miR-9, miR-22, miR-125b, miR-146a, miR-150, and miR-214 [7,34-36]. Moreover, differences in the tissue distribution and efficiency of target gene repression should be compared between systemic injections, such as intravenous or subcutaneous methods, and local injection for future in vivo applications. In this case, for targeted delivery to the brain, we can add integrin ligands or peptides that recognize transferrin receptors [37,38]. Overall, the current study provides a proof of concept for exosome-based delivery of miRNAs to the brain, warranting further studies of this method.
This work was supported by the National Research Foundation of Korea (NRF) (2014R1A2A1A11051520), Korea Health 21 R & D Project (HI14C2348) by the Ministry of Health & Welfare, Republic of Korea, the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3C7A1914002).
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The need to effectively understand, manage, and document suicide risk is increasing at an exponential rate. On September 1, 2017, the California Governor signed Assembly Bill (AB) 89, requiring psychologists to get trained in suicide prevention. It is speculated that the same will eventually be required of Marriage and Family Therapists. How comfortable are you when a client alludes to experiencing suicidal ideation? This lecture will cover the phenomenology of suicide; how to gather the right information; and developing/documenting a solid risk formulation that sufficiently justifies a specific outcome. Case examples will demonstrate how systemic principles can be utilized to collaboratively promote short and long-term client safety across a continuum of care.
David Rogers is a licensed marriage and family therapist with a private practice in Folsom. David manages a team of mental health workers at two emergency departments for Sierra Mental Wellness Group. He designed and implemented Sierra's Continuing Education division and develops cutting-edge training which he delivers across interagency divisions. David is a nationally certified trainer in Assessing and Managing Suicidal Risk (AMSR). He is currently researching explanatory factors associated with advanced brief strategic paradoxical intervention and remains passionate about translating research into practical results.


Arlington, VA, August 30, 2011 — Today Washington Business Journal announced Fulcrum IT Services, LLC, has been ranked as one of the 50 Fastest Growing Companies in the greater Washington region. This is the second consecutive year Fulcrum IT has made this prestigious list. Qualifications were based on three consecutive years of revenue growth.
"We are very pleased to be ranked among the Fastest Growing Companies and honored to be recognized among the area's top performers. It is an especially meaningful recognition to be among the fastest growing companies in such a challenging environment," said Jeff Handy, CEO of Fulcrum IT.
Finalists will be honored on October 6, 2011, during an awards dinner at The Ritz-Carlton, Tysons Corner.
Today Washington Business is owned and operated by American City Business Journals, the nation's largest publisher of metropolitan business newspapers. American City Business Journals also includes Bizjournals, the new media division, which operates the Web sites for each of the company's 41 print business journals. Washington Business Journal has been Greater Washington's leading source of business news and information for more than 20 years, providing over 150,000 business executives with comprehensive news on local people and their companies, as well as industry trends, tips and strategies and award-winning critical analysis. For more information, please visit http://washington.bizjournals.com.


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Divorce statistics update
The Times reported yesterday that the Ministry of Justice, who published that Weston-Super-Mare was a divorce 'hot spot', is actually false as 92% of petitions are filed by the site Divorce Online who say they were advised to use the Court there because it had more capacity!
However, the December 2012 Office of National Statistics report stated that:
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Based on marriage, divorce and mortality statistics for 2010, it is estimated that the percentage of marriages ending in divorce is 42%.
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text:
Q: What is the most flexible way to design a scheduler for automatic task completion, which is also practical to implement? Let's say you have some number (C) of cats and some number (M) of mice and some number (H) of holes that the cats may be able to find mice in.  This is just to generalize a problem and if anything that follows doesn't make real world sense, please remember it's just to provide a silly example so we have something to talk about.
Assuming it takes a non-negligible amount of CPU time to check whether cat c can find mouse m in hole h, how would you design a database to keep track of which combinations you've already checked?  What if you need to prioritize the checking of certain combinations?  What if you want to be able to schedule the processing of mice M1 to M5 with cats C4 to C9 and holes H3 to H7?  What if you want to process this in order of holes first (as in, hole H3 gets checked for all combinations of mice and cats before hole H4) or cats first (C4 for all combinations of others before C5), etc?
Is there some very clever way of generalizing this to N number of things to be combined?  For example, what if we needed to add in some number of dogs?  Is there some clever way of allowing complicated scheduling prioritization without being overly complicated?  What should I be reading to sort out this problem?
The design I'm thinking about right now is something like this:
table: scheduled_tasks
columns: first_cat, last_cat, first_mouse, last_mouse, first_hole, last_hole, completed?, cat_order (ie. 1), mouse_order (ie. 2), hole_order (ie. 3)
the _order columns would indicate which loop is the outermost, essentially.
table: completed_tasks
columns: cat, mouse, hole, when_completed
or possibly...
table: completed_tasks
columns: first_cat, last_cat, first_mouse, last_mouse, first_hole, last_hole
which would have first_cat = last_cat, first_mouse = last_mouse, etc. initially and then automatically group together adjacent rows to more quickly search through which tasks had already been completed to avoid doing redundant work.
What would be a good way to generalize this?  Perhaps the scheduler program should make a new table if we add more dimensions (ie. dogs) to the mix, or perhaps the table structure should be made more flexible.  For example, rather than first_cat, last_cat, ..., there would be a related table "entities_to_cycle" (or something like that) which would have columns: entity, first, last.
Anyway, what are your thoughts on this?
I'm also tagging this PHP/MySQL because I'll be using those to implement this.  If this affects your answer, please make a note of where your answer is affected.
Last note:  If there are several hundred thousand tasks to be completed, then it seems that breaking the tables up (generalizing and normalizing) would make searching/inserting much more time consuming...

A: well part of this question i think is answered like this:
cat
-----
cat_id
name

mouse
------
mouse_id
name

hole
------
hole_id
name

mouse_hole
-----------
moue_hole_id
mouse_id
hole_id

either do this part in memory, or save the values in a sturcture like:
cat_task
---------
cat_id
mouse_hole_id
status(?)

A: Here's one idea: Store a table with columns
Cat(Int), Mouse(Int), Hole(Int), Found(Bool)

and create an index on Cat, Mouse, Hole, (Cat, Mouse), (Cat, Hole), (Mouse, Hole).
This way you can efficiently look up which MousesMice and Holes you've explored for a given cat, or which Holes you've explored for a given Mouse+Cat, etc.

redpajama_set_name: RedPajamaStackExchange


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Kidnapped Nigerian Boys Are Freed
HawkEye 360 Supports NGA RF GEOINT Pilot Program, Ships Satellites
Australian dollar rises to new high as Rio Tinto begins reputation recovery
Supporters urged authorities to rescue hundreds of abducted schoolboys in the northwestern state of Katsina, Nigeria, on Thursday.
Photo: kola sulaimon/Agence France-Presse/Getty Images
Joe Parkinson
and Gbenga Akingbule
Updated Dec. 17, 2020 8:07 pm ET
More than 300 schoolboys kidnapped by gunmen from their boarding school in northwest Nigeria last week were handed over to security agencies late Thursday, Nigeria's government said, prompting outpourings of relief and joy across Africa's most populous nation after fears they would become long-term hostages of jihadist militants.
Shortly after 8 p.m. on Thursday, Aminu Bello Masari, the governor of Katsina state, announced in a televised interview that 344 of the boys had been handed over in the forest of neighboring Zamfara state and would be immediately driven to Katsina for medical treatment.
The release comes six days after the students were seized from their dormitories at the Kankara Government Science Secondary School in Katsina and driven into the nearby forest, marking one of the largest mass school kidnappings in history. President Muhammadu Buhari praised the military and security agencies in a statement that offered prayers for the full recovery of the victims. They "endured significant hardships in the course of their ordeal," the statement said.
Local newspaper The Katsina Post tweeted images of dozens of schoolboys jammed onto the back of trucks, some looking dazed, but others sporting wide smiles for the camera as they headed toward home. Government officials said the boys would be given new clothes before an audience with the president on Friday.
More on the Abducted Schoolboys
The boys' parents were celebrating after a week of acute stress and anxiety.
Jamila Mani Abdullahi, whose two sons, 17-year-old Abdulganiyu and 15-year-old Ahmed, are among those kidnapped, said she had gathered with dozens of other parents on hearing the news. "We are celebrating and grateful," she said over the phone, the sounds of whoops and cheers resounding in the background. "We cannot wait to be reunited with them."
Many of the details around the kidnapping, in a remote agricultural area with poor communication, remain murky, including the total number of victims and the true identity of their captors.
It couldn't immediately be determined if the group released included all the boys who were taken in the raid. Several who escaped said that some had died during the abduction and their march through the forest. Others said that the kidnappers had stopped to count the hostages and tallied more than 500 boys.
Jihadist group Boko Haram claimed responsibility for the kidnapping, saying on Tuesday it had seized the students to punish them for "un-Islamic practices."
That claim was met with surprise by some analysts, as it marked a dramatic departure from the extremist group's usual area of operation in the country's northeast. Others said Boko Haram leader Abubakar Shekau has expanded the group's sway to the northwest, brokering new alliances with heavily-armed criminal networks.
Hours before the governor's announcement on Thursday, Boko Haram released a video purporting to show dozens of the schoolboys. In the grainy six-minute video, the hostages said that some of their classmates had died during their captivity and begged for the government to negotiate their release.
Notes on the News
Today's headlines, news in context, and good reads you may have missed, with Tyler Blint-Welsh.
Analysts speculated on whether the captors were given anything in exchange for the hostages. The government hasn't confirmed whether it believes the kidnappers were Boko Haram and denied that it paid a ransom.
The mass abduction came six years after the kidnapping of 276 schoolgirls in the town of Chibok, an abduction that ignited the global #BringBackOurGirls campaign. After three years, 103 were freed for a ransom that people involved said included the exchange of five imprisoned militants and €3 million, about $3.7 million. The government has denied paying a ransom. .
The news capped an emotionally fraught day where the schoolboys families' hopes were raised, then dashed, then ultimately delivered.
More than 20 parents had been gathered around the school courtyard around lunchtime when rumors began to swell that a deal had been struck to free their sons. Their body language shifted from grief to hope and the mournful schoolyard became awash with excited chatter and some began to celebrate.
Then the news broke that Boko Haram had released the video purporting to show the schoolboys.
"Please, sir, you have to send all the soldiers and armies and the jets back," said one boy, visibly terrified, apparently referring to the Nigerian military's rescue effort.
The parents' hearts sank as they heard no new updates from the government. But shortly after nightfall, calls to parents from local officials confirmed there would be a deal.
"God is great!" exclaimed a beaming Dalmatu Yusuf, whose 15-year-old son is also among the missing. Mr. Yusuf said the parents were expecting to see their children on Friday.
Teenagers Binta Umma and Maimuna Musa were kidnapped by Boko Haram in Madagali, Nigeria, in 2016. They were forced into marriage and sent to die on a suicide mission. In this video, the girls tell the story of their survival. Photo by Jonathan Torgovnik for The Wall Street Journal (Originally published July 26, 2019)
The news also marked a positive end to a grim week for President Buhari, a native of Katsina state who hadn't commented on the news since Saturday. A former general who briefly governed Nigeria in the 1980s as a military dictator, Mr. Buhari returned to power by winning the 2015 elections on a promise to restore security to the north following the Chibok kidnapping.
In his first term, Mr. Buhari overhauled the armed forces and chased Boko Haram into remote strongholds in the forests of the northeast. He has since claimed that the insurgency has been technically defeated.
But since last year, the militants have been advancing, overrunning dozens of smaller military bases and looting weapons. According to the U.S. Council on Foreign Relations, the period since July 2018 has been deadlier for Nigeria's security-service personnel than any other time in the decadelong conflict.
The Kankara kidnapping has reignited fears over school security across the whole of Nigeria's north. Boarding schools across four states have closed in response and it is unclear when they will open again.
Bulama Bukarti, an analyst at the Tony Blair Institute for Global Change based in London, said the news of the schoolboys' release was "the story we needed at the end of a truly awful week," but stressed that it had also demonstrated the barbarity of Boko Haram and its expansion into the northwest of Nigeria.
"This should be of grave concern for governments in the region," he said.
Write to Joe Parkinson at joe.parkinson@wsj.com
Appeared in the December 18, 2020, print edition as 'Abducted Schoolboys Are Released in Nigeria.'


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Microsoft says it warned Bill Gates about flirting in 2008
AP Last Updated: Oct 19, 2021, 10:15 AM IST
Brad Smith, then Microsoft's general counsel and now its president and vice chair, and another executive met with Bill Gates after the company discovered his inappropriate emails to a mid-level employee, the Wall Street Journal reported.
Bill Gates, cofounder and former chairman of Microsoft.
Redmond, Washington: Microsoft executives in 2008 warned Bill Gates to stop sending flirtatious emails to a female employee but dropped the matter after he told them he would stop, the company revealed.
The Wall Street Journal was first to report that Brad Smith, then Microsoft's general counsel and now its president and vice chairman, and another executive met with Gates after the company discovered inappropriate emails to a mid-level employee.
The newspaper reported that Gates didn't deny the exchanges, and members of the Microsoft board who were briefed on them declined to take further action because there wasn't any physical interaction between Gates and the employee.
Microsoft declined comment on Monday except to confirm the Journal's reporting. Smith didn't return a request for comment made through the company.
In a written statement, Gates' private office said "these claims are false, recycled rumours from sources who have no direct knowledge, and in some cases have significant conflicts of interest". It declined further comment.
The reported 2008 warning came more than a decade before similar alleged behaviour led the Redmond, Washington-based company to hire a law firm in 2019 to investigate a letter from an engineer who said she had a sexual relationship with Gates over several years.
Cyber-safety
That investigation preceded Gates' departure from Microsoft's board last year, but did not come to light publicly until after Bill Gates and Melinda French Gates announced in May they had decided to end their marriage of 27 years. The divorce was finalised in August. The former couple still jointly runs the Bill & Melinda Gates Foundation.
Gates was Microsoft's CEO until 2000 and since then has gradually scaled back his involvement in the company he started with Paul Allen in 1975. He transitioned out of a day-to-day role in Microsoft in 2008 and served as chairman of the board until 2014.
Microsoft spokesperson Frank Shaw told the Journal that the 2008 warning from company executives happened shortly before Gates retired as a full-time employee. Shaw told the newspaper that Gates had suggested meeting the employee outside of work in emails that were flirtatious and inappropriate but "not overtly sexual".
The latest disclosure about Gates adds to concerns raised by a Microsoft investor asking fellow shareholders to support a proposal that would force the company to investigate its workplace harassment policies and release a report about them.
"Reports of Bill Gates' inappropriate relationships and sexual advances towards Microsoft employees have only exacerbated concerns, putting in question the culture set by top leadership, and the board's role holding those culpable accountable," says the proposal from Arjuna Capital on the agenda of Microsoft's annual shareholder meeting next month.
Microsoft urged investors to reject the proposal in a note filed with regulators last week, arguing it is unnecessary because the company has already adopted plans to publicly report how it is implementing its policies on sexual harassment and gender discrimination.
bill gatesmicrosoftbrad smithsatya nadellame too movement
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We have completed an exciting partnership project with Lovell, Ingleton Wood and other local companies that will provide much-needed respite accommodation at Norwich City Community Sports Foundation (CSF)'s hub 'The Nest'.
Watch a 'before and after' video of the refurbishment
The project involved renovating a dilapidated cottage at The Nest site in Norwich. Adults accompanying young people's residential trips will now have somewhere to stay.
CSF runs a range of programmes that use sport, education and the pull of Norwich City Football Club to engage with different groups in the community. The cottage project was part of its #BuildTheNest fundraising campaign to complete the second phase of development works at The Nest.
Broadland staff used their volunteer days to do the work (and some staff members donated additional time0.
Broadland's Development Director, Andrew Savage, says:
To see the enthusiasm of all the volunteers and the generous donations was inspiring. Our internal maintenance, planned works and landscape teams who were involved with the project are extremely proud of what has been achieved. It was great to be involved.
Simon Medlar, Lovell Regional Managing Director for East Anglia, said:
I'd like to personally thank each supplier and subcontractor involved for their hard work and commitment throughout. I've been blown away by the generosity of those involved, donating both materials and time, which has led to the fantastic end-result of this renovation.
Ian Thornton, Chief Executive Officer at Norwich City Community Sports Foundation, said:
We are incredibly grateful for the support of Lovell and all the suppliers and subcontractors that have come together to make the cottage look so fresh and new.
It will be such an asset to the site to have these facilities for adults supporting residential visits, and we look forward to welcoming residential groups back to The Nest when conditions allow for it.
More than 40 local companies as well as those further afield were involved in the refurbishment, which is worth over £50,000. This included remodelling the internal layout and substantial works to fix leaks, stabilise the structure, treat damp and woodworm, and remove asbestos, as well as a complete re-fit, and both internal and external redecorations. The main work was completed in late February 2020, with final touches being finished following lockdown and in accordance with Lovell's strict COVID secure guidelines for its workplaces and construction sites.


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Groundbreaking Held for New ECC Health Care Education Facility
Turning the soil for construction of the new Biotechnology and Medical Simulation Center at Edgecombe Community College are (from left) NC Rep. Joe Tolson; Dan Gerlach, president of the Golden LEAF Foundation; David Combs, Rocky Mount mayor; Leonard Wiggins, chair of the Edgecombe County Board of Commissioners; Lorenzo Carmon, Edgecombe County manager; Wick Baker, chair of the ECC Board of Trustees; Clark Curry, ECC respiratory therapy student and Student Ambassador; Dr. Deborah L. Lamm, college president; Rev. Wayne Hines, member of the Edgecombe County Board of Commissioners; and Jonathan Felton, vice chair of the Edgecombe County Board of Commissioners. The project is slated for completion in fall 2015.
Officials from federal and state government, Edgecombe County, the City of Rocky Mount, and Edgecombe Community College gathered on the college's Rocky Mount campus this morning for the official start of construction of the college's new Biotechnology and Medical Simulation Center.
About 100 gathered for the groundbreaking ceremony. Guests were able to envision the footprint of the 45,000-square-foot facility, as Barnhill Contracting Company has already begun site preparation.
Wick Baker, chair of the Edgecombe Community College Board of Trustees, welcomed the crowd. "Next fall, when this high tech facility opens, a new era in health care education will begin in Edgecombe County and eastern North Carolina," he said.
"This construction will usher in the latest model for health care education, which is realistic training through the use of patient simulators. As president of Vidant Edgecombe Hospital in Tarboro, I can personally attest to the excitement and anticipation we all share."
The cornerstone of the new facility is a simulated hospital environment. Rooms will be set up to function like emergency rooms, operating rooms, ICUs, operating rooms, nurses stations, and the back of an ambulance. The building will house 14 of the college's 22 health sciences programs. Planning for several new programs is under way.
Rocky Mount Mayor David Combs said the new facility "will continue to help us reach our vision for revitalization in downtown Rocky Mount."
He thanked Edgecombe County voters for making the project possible by approving a ¼ cent sales tax referendum in November 2012. Sales tax revenues will help fund construction.
The Golden LEAF Foundation contributed $1.5 million to the project. Construction costs are estimated at $9.8 million.
Lorenzo Carmon, Edgecombe County manager, said the Biotechnology and Medical Simulation Center will "transform our community and have a positive economic impact on Edgecombe County."
Also speaking during the groundbreaking ceremony were Leonard Wiggins, chair of the Edgecombe County Board of Commissioners; Dan Gerlach, president of Golden LEAF Foundation; Martin Moser, vice president of Barnhill Contracting Company; and Dr. Deborah Lamm, president of Edgecombe Community College.
Other officials who attended the groundbreaking included NC Rep. Joe Tolson and Betty Jo Shepheard, representing Sen. Richard Burr.
In her concluding remarks, ECC President Dr. Deborah Lamm expressed her appreciation. "Thanks to the support of all of you, the college will be able to expand and prepare the next generation of health care workers in this state-of-the-art facility, equipped with the latest technology. Thank you for making this project a reality."


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Home » Sports
Are Spectators An Essential Part Of The Game?
Written by NiveadhaLast Updated On: 22 Jan 2022
What Role Do Crowds Play?
What About Distraction?
Should We Eliminate Crowds Altogether?
Are Spectators Essential Then?
Spectators add a unique energy to the game that can be supportive and act as motivators to the respective teams.
Take a look at this:
Like a needle in a haystack#AUSvNZ pic.twitter.com/T6A29tKaYj
— cricket.com.au (@cricketcomau) March 13, 2020
After the COVID-19 hit, it was decided that the Australia versus New Zealand ODI Cricket match (2020) would be played in an empty stadium. This clipping is taken from that match.
But, where is the crowd of spectators in this short clip?
What's the most important role that spectators play in a sporting event between two sides?
As fun as it is to be part of the crowd that catches the ball or locates it during a cricket match, crowds play a far larger role.
How Can We Sometimes Keep Reading, But Not Understand Anything We Read?
In 1898, Normal Triplett conducted the first laboratory study that was deemed monumental for both social and sports psychology. He took people away from their natural habitat and bought them into a lab to experiment on them.
Although he was just looking at time taken for these cyclists while they cycled alone or together, it was a big leap in the way research was conducted from that point on.
Triplett's research bought cyclists into a laboratory to see how having an "audience" affected them (Photo Credit : baldyrgan/Shutterstock)
Social Facilitation
Triplett's study established that cyclists race faster when they have competitors than when they are alone. This single study set the wheels turning for research in social facilitation.
Social facilitation is the idea that people perform better when there are others present.
It's one thing to contend against other participants, but what about spectators? What role do they play?
Putting Cockroaches To Test
To answer this, in 1969, Zajonc and his colleagues came up with a rather innovative experiment. In the study, Zajonc trained cockroaches to race; he chose cockroaches because he believed these creatures had no fear of judgement, or rather, had nothing to lose. (pg 391, Social Psychology- Baron and Boshcomb)
Let's call these trained cockroaches the racers. Zajonc built them a transparent case and invited (read: forcefully placed) some other cockroaches as an audience. It so happened that those racers who had their species looking at them were able to race faster than those without.
Based on this, Zajonc concluded that having spectators around improved performance.
Cockroaches ran faster when watched by an audience (Photo Credit : Tarakan4ik/Shutterstock)
Although this seems pretty straightforward in the roaches, it may not be so simple in humans. We humans have a tendency to overthink and emotionalize everything.
Therefore, many times, when performing in front of someone we know will be judging us (cue: those dreaded pick and speak competitions in school), it often leads to evaluation apprehension. More specifically, we're scared of performing or talking or even participating in try-outs for fear of being ridiculed.
Zajonc, like Freud, never left loose ends. In his drive-theory of social facilitation, he explained that when others are present, we're in a state of physiological arousal, which leads us to pick a learned response and express it in front of them, thereby enhancing our performance.
However, if it were a new skill being put to test in front of an audience, then this performance could be hampered, which is probably why he picked cockroaches to race. What he's essentially saying is that if you're well prepared, you're sorted and will ace it. If you're not prepared, well, leave it to the gods.
If you have ever been a spectator at a cricket match, you know how noisy and loud it can be. Fans are cheering and screaming and dancing from start to finish. This can be distracting even for experienced athletes.
Also Read: Is There An Actual Home Field Advantage When A Sports Team Plays In Their Home Stadium?
At the recent ATP quarter final between Novak Djokovic and Denis Shapovalov, the crowd was a given a strict warning, as the Serbian fans kept taunting Shapovalov. After Shapovalov swore at the crowd once, the umpire intervened and told the audience to 'go home' if they couldn't be civil.
An entire stadium that's supporting a single team, can be de-motivating for the other team (Photo Credit : Bobak Ha'Eri/Wikimedia Commons)
Crowds are distracting, and can even ruin a player's focus, mental state, and change the outcome of the game. To decrease this cognitive load, many players are given pep talks and are trained not to let the crowd get the better of them. Controlling their attention to focus on the relevant things (the game they are playing) helps them get through the distractions. Many players completely 'blank out' this noise while focusing on the game.
After the Australia vs New Zealand cricket match played to an empty stadium, Australian bowler Pat Cummins observed that the match had been 'more relaxed'.
During the measles outbreak, some matches were played with a crowd, while other were played without. An initial analysis found no difference in performing without an audience, while a second analysis showed that teams actually played better without the audience.
While studies have found that a crowd-free environment is more relaxed, it's not what players are really looking for. After being told that stadiums would have to go empty earlier this year, LeBron James commented that he plays for his fans, and he wouldn't play in a stadium without them (he backtracked this statement later, once he understood the situation).
Then again, what real benefit do fans hold? Why have these boisterous and noisy humans filling the space, even though things could be much more laid back and relaxed without them?
Well, having a crowd could change the outcome of the game, and give the home team an easy pass. A 2014 study found that there actually is a 'home advantage' that exists when football teams play on their home ground. The crowds not only boost the player's performance, but also tend to bias the referees' decision in favor of the home team. The study suggested that the probability of winning a given game increased by 13% for the home team.
English football fans celebrating a win (2005/06) (Photo Credit : Flickr)
Another study observed that audience members who are supportive and act as motivators can also put the players under immense pressure. When this happens, the players 'choke'. The same supportiveness turns into immense self-focus and self-awareness, which results in disruptions to their learned and practiced responses.
What if the crowd at home turned abusive? The matches and the players' mindsets were significantly effected. A study conducted on basketball matches looked at the effect of abusive spectators on the performance of players; it noted that when the crowd was being anti-social and abusive, the home team made far more violations than the visiting team.
However, when the audience was calm, the violations happened significantly less.
It also turns out that the effect the audience is sports-specific. Be it encouragement or aggressiveness, the players are effected by it nonetheless. A study in the North American Journal of Psychology postulated that the crowds' jeers or cheers cannot be generalized. While a basketball player's free throws remained unaffected, a non-supportive crowd hurt baseball pitcher performance, and any kind of noise—jeers or cheers—led to worse performance in golfers.
In football games, players note that those who are in more stationary positions are more prone to hearing abuses. Some even dread standing near particular stands, as the crowd there can be extremely abusive and even racist.
While players say this, playing for the major leagues and international teams is exciting, as is the attention that comes from the rest of the world. The kind of love and support players receive can be overwhelming and extremely motivating. Most players of a particular sport would be accustomed to the nature of the game and the kind of fans that it attracts. So, as annoying as spectators can be at times, they are part of the game just as much as players are.
Though Zajonc reached this conclusion in a rather bizarre way, he was right when he said that the presence of an audience enhances one's performance on the field. It makes the atmosphere more joyful and the game more enjoyable.
The crowd seems to tell you what is happening; when the cheer goes high you know the team is playing well, and when they go 'ohh' in a desolate tone, you know that someone's out! When you hear excessive singing and cheering, you might accurately guess that someone's hit a boundary, or scored a goal.
Fans celebrating (Photo Credit : Oleksii Sidorov/Shutterstock)
Fans these days will do anything to make sure that their team wins. They do the strangest things to get the players' attention. The minute they see that it affects you, it only gets worse.
Any modern sport doesn't just require one to have the physical skill needed to play the game, but also demands the ability to block out the white noise. While the taunting and jeering affects players and diverts them from the game that they play, it seems that that is part of the experience too!
Also Read: How Are The Acoustics In A Soccer Stadium Engineered?
So yes, not only do spectators watch and support players, but they also increase the players' performance. However, this is only true when the players see their audience as motivators, or have a neutral stance towards them.
Studies have found that while performing online tasks, even the presence of virtual humans can produce this same effect. That is definitely something to keep in mind with all these online tournaments, events and teleworking going on!
Social Psychology by Pearson Paperback by R. Branscombe Nyla
The Sports Gene: Inside the Science of Extraordinary Athletic Performance
Social Psychology 14Th Edition
Tags: Audience, Home, One Day International, Performance, Road, Sports
Niveadha is a psychology graduate (Master of Science in Psychology) from Mount Carmel College, Bangalore, who works as a counselor and special educator. She tends to get bitten by the travel bug often, and floods her social media with a million pictures. You can find her at quaint little cafes sipping on tea and reading a new book every other day.
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text:
Marine & Coastal
Santarli clinches the WSH Innovation Award 2019
The annual Workplace Safety and Health (WSH) Awards aim to recognise companies and individuals who have upheld safety and health standards at their workplaces. This year, Santarli has been awarded the WSH Innovation Award 2019 for the Construction and Management of Staging Ground and Infilling Works Project.
Santarli's efforts in developing creative and viable solutions to tackle WSH hazards in terms of safety, health and productivity have been recognised through the construction and implementation of the Direct Discharge Platform where it overcame the challenges in the disposal of excavated materials.
Excavated materials from construction sites are transported to construction staging grounds to be recycled for infilling works. Traditionally at these staging grounds, the truck drivers will have to wait up to four hours as there is usually a long line of trucks waiting to dispose of the materials. The drivers are also exposed to fatigue, mental stress, and high levels of noise and air pollution while being in the queue. Also, there is the risk of trucks overturning during the transfer process from the tipper truck to the disposal barge.
The disposal process was tedious, inefficient and hazardous. Hence, a solution through the Direct Discharge Platform was innovated by Santarli. The direct discharge platform comprises a cantilever platform placed on top of the floating barge. By placing the platform on a floating barge, it ensures that the excavated materials are being deposited into the centre of the hopper barges. The floating barge will also rise and fall according to the seawater tide to make sure there is a safe distance between the platform and the hopper barge. Safety features such as the wheel stopper at the end of the platform will prevent the trucks from tipping over during the unloading process.
The direct discharge platform has tremendously improved the productivity of the disposal process and truck drivers. With the previous method, the process takes two trucks every 1.4 minutes but with the Santarli's implementation, four trucks can unload in every minute and each cycle only takes 15 minutes to complete. The overall disposal rate per platform also significantly increased from 12,000 tons to 32,000 tons per day.
"Our people are our greatest asset. Their safety and well-being in the workplace are the cornerstones in the formulation of our objectives, policies and work procedures. Safety always comes first."
Mr Andrew Seet, GM/Director of Santarli
Santarli donates $1 million to kickstart the Professor Chen Charng Ning Endowment Fund
A Safety Message from Santarli's Corporate HSE Manager
Congratulations to Mr Jewel Khan for achieving the Gold Award for WSH Supervisor Awards 2020
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The latest research on progeria, an extremely rare disorder that ages children before their time, offers new clues about the aging process.
Hutchinson-Gilford progeria syndrome (HGPS), also called progeria or premature aging syndrome, is a medical disorder in which a random genetic mutation causes cells in the body to die at a much faster rate than normal. Its name derives from the Greek and means "prematurely old." Progeria is so rare it occurs only once in every 8 million births; at the time this article was written, only 62 people around the world were known to be living with the disorder.
Rare diseases provide medical researchers a window to better understand how the body works. Recent groundbreaking research on progeria may not only be paving the way toward an effective treatment, but could explain some of the mysteries of aging, including cancer.
Although children with progeria have normal intelligence and motor control skills, they look older than they actually are. They appear normal at birth, but within 6 months to 2 years, symptoms of premature aging start to emerge. During this time, the child grows at a much slower rate in terms of height and weight than children of the same age. Clinical features of progeria include a disproportionately large cranium, small jaw, prominent scalp veins, baldness, wrinkled/thick skin, loss of body fat, cardiovascular disease and stroke, hearing loss, stiffness of joints and hip dislocation. If a doctor suspects a child has progeria, a genetic test may be performed to confirm a diagnosis.
Despite these sobering symptoms, most children with progeria can thrive and live remarkably healthy lives. However no cure exists and the life expectancy of a progeria patient is tragically short. Ninety percent succumb to complications related to atherosclerosis, or heart disease. Children with progeria may live to be 7-30 years old, but on average most die by age 13.
In 2003 an exciting medical breakthrough occurred when researchers discovered a mutation in the LMNA gene that produces lamin A protein. In normal circumstances, lamin A contributes to making proteins that hold the centers (nuclei) of cells together. When LMNA is mutated one of these proteins, now identified as progerin, is not produced properly making the nuclei unstable. Subsequently cells die prematurely, leading to symptoms of progeria.
Progeria is not simply accelerated aging. While it does resemble many of the characteristics seen in a typical aging population, important differences exist, including a lack of higher cancer rates.
"There is a subset of the features of aging that progeria is an excellent example for," says Jeffrey Innis, MD, PhD, a pediatric geneticist at the University of Michigan Medical School. "The research that's being done is trying to tease out the molecular mechanisms involved in making an individual appear to have features of aging in some areas but not others." Progeria children do not exhibit higher incidences of cancer, but they do suffer cardiovascular problems of someone 10 times their age.
The discovery of the progeria gene has spurred 3 clinical drug trials, including one between the Progeria Research Foundation and Children's Hospital Boston, where 28 children from 16 countries, ages 3-15, participated between 2007-2009. A new "triple drug trial" began in 2010 in Boston with 45 children from 24 countries, speaking 17 languages enrolled . All of the trials have involved trying to block the production of progerin, the protein made in the mutation. These medical research strides are giving progeria children and their families new hope for an effective treatment, and shedding new light on the phenomenon of aging.
Click here to download a reference of progeria quick facts.


On April 7, 2017 we made a visit to the Sunflower Orphanage. Located in the heart of Nha Trang, Sunflower cares for teenage orphans, while its sister orphanage, Dai An, cares for younger orphans in the countryside to the south of Nha Trang. We contacted the caregivers at Sunflower about their immediate needs, and they asked for some general supplies plus 2 classroom whiteboards to help the children with their lessons. Our team put together a project, and came to the orphanage with bags of rice, seasonings, laundry detergent, and 2 brand new whiteboards. We handed out treats and balloons to the orphans, and they quickly made a fun balloon game in the orphanage courtyard.


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Q: How to get a div popup by clicking submit button using fancy box / light box? my mark up

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Demo
HTML

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Captain Te M. R. Tomoana
(Person)
Works by this Author in Other Collections
New Roads for Welfare— Training Course at Paraparaumu, in Te Ao Hou
28 (Maori) Battalion
CHAPTER 13 — Orsogna
Italy Volume I: The Sangro to Cassino
II: On The Rapido
For several reasons, including lack of resource and inherent ambiguity, not all names in the NZETC are marked-up. This means that finding all references to a topic often involves searching. Search for Captain Te M. R. Tomoana as: "Captain Te M. R. Tomoana". Additional references are often found by searching for just the main name of the topic (the surname in the case of people).
The following collections may have holdings relevant to "Captain Te M. R. Tomoana":
Dictionary of New Zealand Biography, which has entries for many prominent New Zealanders.
Archives New Zealand, which has collections of maps, plans and posters; immigration passenger lists; and probate records.
National Library of New Zealand, which has extensive collections of published material.
Auckland War Memorial Museum, which has extensive holdings on the Auckland region and New Zealand military history.
Museum of New Zealand Te Papa Tongarewa, which has strong holdings in Tāonga Māori, biological holotypes and New Zealand art.
nzhistory.net.nz, from the History Group of the Ministry for Culture and Heritage.


text:
A
 Flutura Açka
 Ylljet Aliçka
 Gëzim Aliu (1977)
 Dritëro Agolli (1931)
 Mimoza Ahmeti (1963)
 Fatos Arapi
 Lindita Arapi
 Asdreni alias Aleksander Stavre Drenova
 Arbër Ahmetaj
 Ali Asllani
 Idlir Azizaj

B
 Frang Bardhi
 Eqrem Basha (1948)
 Sali Bashota
 Ilir Belliu
 Pjetër Bogdani
 Flora Brovina
 Pjetër Budi
 Gjon Buzuku

C
 Martin Camaj
 Nicola Chetta

Ç
 Andon Zako Çajupi
 Stefan Çapaliku
 Aleks Çaçi
 Zija Çela(1946)
 Romeo Çollaku
 Muhamet Çami-Kyçyku

D
 Rrahman Dedaj
 Jeronim De Rada
 Ridvan Dibra
 Ledia Dushi

E
 Rudi Erebara

F
 Gjergj Fishta
 Nezim Frakulla
 Anastase Frashëri
 Naim Frasheri
 Sami Frashëri

G
 Balil Gjini (1950)
 Fahredin Gunga
 Luigj Gurakuqi

H
 Gëzim Hajdari
 Sabri Hamiti
 Sinan Hasani
 Ali Hungurica
 Shefki Hysa

I
 Murat Isaku
 Abdylazis Islami

K
 Salih Kabashi
 Helena Kadare
 Ismail Kadare
 Hasan Zyko Kamberi
 Teodor Keko
 Vedat Kokona
 Ernest Koliqi
 Musine Kokalari
 Fatos Kongoli
 Mehmet Kraja
 Gazmend Krasniqi
 Milazim Krasniqi
 Mitrush Kuteli

L
 Teodor Laço
 Natasha Lako
 Arian Leka
 Luljeta Lleshanaku
 Bardhyl Londo

M
 Adelina Mamaqi
 Rudolf Marku
 Martin Mato
 Lekë Matrënga
 Din Mehmeti (1929-2010)
 Kim Mehmeti
 Esad Mekuli
 Mira Meksi (1960)
 Migjeni
 Ndre Mjeda
 Besnik Mustafaj (1958)
 Gjon Muzaka
 Bessa Myftiu
 Mehmet Myftiu (1930)

N
 Fan Noli
 Franz Nopcsa

P
 Ali Podrimja (1942-2012)
 Lasgush Poradeci
 Iljaz Prokshi
 Lek Pervizi

Q
 Dhori Qiriazi
 Rexhep Qosja

R
 Ibrahim Rugova
 Urani Rumbo (1895-1936)

S

 Zef Serembe
 Brikena Smajli
 Bashkim Shehu (1955)
 Filip Shiroka
 Azem Shkreli
 Edi Shukriu
 Xhevahir Spahiu
 Sterjo Spasse
 Hevzi Sylejmani
 Shpend Sollaku Noé

T
 Kasëm Trebeshina
 Agron Tufa (1967)

U
 Vorea Ujko

V
 Giulio Variboba
 Pashko Vasa
 Agim Vinca
 Ornela Vorpsi

X
 Bilal Xhaferr Xhaferri

Z
 Injac Zamputi
 Tajar Zavalani
 Moikom Zeqo
 Preç Zogaj (1957)
 Visar Zhiti
 Zef  Pervizi

Article connexe
 Littérature albanaise

redpajama_set_name: RedPajamaWikipedia


Phil. 1:20 "According to my earnest expectation and my hope, that in nothing I shall be ashamed, but that with all boldness, as always, so now also Christ shall be magnified in my body, whether it be by life, or by death.
21 For to me to live is Christ, and to die is gain."
To those who would�just slip away.
Why not let them�just slip away?
When, even natures cries, let them�just slip away.
Real love would allow them to�just slip away.
If so, let them�just slip away.
True love, allowing them to�just slip away.
Because we'd miss them so?
And, let them�just slip away.


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The Good Doctor' Season 4: Is Melendez finally back after his surprise return?
By Jonathan Edwards on November 10, 2020 Health & Wellness
The Good Doctor has seen dead characters return before as fantasy creations of the characters, but the return of Dr. Neil Melendez (played by Nicholas Gonzalez) at the beginning of the 4th episode of The Good Doctor was not until the previous episode that the character died after succumbing to the earthquake injuries.
WARNING: The following are spoilers for the end of The Good Doctor season 4 episodes 1 and 2
But without Dr. Claire Browne (Anthonia Thomas) having trouble coping with the COVID 19 pandemic in The Good Doctor, Season 4, Episodes 1 and 2, Melendez returned to her to keep her in mental shape.
Melendez's return in these two episodes has left fans of the NBC medical drama wondering if the character will reappear in Season 4, as he appears every time Claire is at a crisis point.
However, in a recent interview, the creator of The Good Doctor, David Shore, seemed to rule out Dr. Melendez returning. In an interview with TVLine, Shore said, "We can't rule it out, but we don't have any plans. I don't want to make too many promises in this regard.
Leading actor Freddie Highmore, seems to be more open to the idea of a return of the actor. He told TV Guide: "You never know. At least these first two episodes show that there's definitely the possibility [for him]to stay part of the show in some way, absolutely. As we would have said at the end of Season 3, I think that still applies today… hopefully he'll continue to be a part [of the series]in every possible way.
Although Shore seemed to be preventing a regular return for Melendez, The Good Doctor Season 4, the end of Episode 2 seemed to indicate that he would come back at some point. After spending most of "Frontline Part 2" trying to figure out who owned a mysterious set of military dog tags, Claire finally reunited them with their owner, who revealed that he had given them to his lover after they fought together in Vietnam.
After getting into her car after returning these dog tags to their original owner, Melendez reappeared and said, "That was beautiful… This room was full of stories as short as ours. But you… You have an amazing story to tell, and I can't wait to see it." Then he disappeared.
This seems to indicate that Melendez might return at some point, although according to Shore's remarks, it might not be for some time.
However, there have been several appearances of loved ones in the series. Dr. Shaun Murphy's (Freddie Highmore) brother Steve (Dylan Kingwell), for example, appeared in several episodes of the first and third seasons, although he died of course before the events of the "Good Doctor" began.
Shore has also hinted that Melendez's appearance version may have served its purpose, as Claire seems to be dealing with her grief better now than when her mother Breeze (Sharon Leal) died.
The creator of the Good Doctor told TVLine: "She is in a more mature place because she has had Dr. Melendez by her side for the past few months. I believe he helped her through her situation with her mother, and I believe his help through [this experience]helped her when [he died]. As he tells her in [episode 2], she is dealing with it this time. She's not running away.
The Good Doctor Season 4 will air Monday at 22:00 ET / 21:00 CT….
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Home / India News / Sushma Swaraj demands apology from Amazon for selling doormats with Indian flag
Sushma Swaraj demands apology from Amazon for selling doormats with Indian flag
The incident was brought to notice of Swaraj on Twitter to which she said all the products insulting the Indian flag should be immediately withdrawn.
IScreen grab of the listing for Indian-flag themed doormats on Amazon's Canadian site.(Ratnesh Mishra)
Updated on Jan 12, 2017 01:43 AM IST
Days after Hindustan Times reported about Amazon Canada offering Indian flag-themed doormats, external affairs minister Sushma Swaraj lashed out at the e-tailer on Wednesday and threatened to rescind visas of officials of the e-commerce giant if it did not offer an "unconditional apology".
In a series of tweets, Swaraj described the doormats as "unacceptable" after the matter was brought to her notice on Twitter. She warned that Amazon officials would not be given Indian visas and visas granted earlier would be rescinded if the e-tailer did not withdraw the product and apologise.
"Amazon must tender unconditional apology. They must withdraw all products insulting our national flag immediately," tweeted Swaraj, one of the most active Indian ministers on Twitter with nearly 7 million followers.
Amazon must tender unconditional apology. They must withdraw all products insulting our national flag immediately. /1
— Sushma Swaraj (@SushmaSwaraj) January 11, 2017
If this is not done forthwith, we will not grant Indian Visa to any Amazon official. We will also rescind the Visas issued earlier.
Swaraj also directed the Indian mission in Ottawa to take up the matter with Amazon.
Even before Swaraj took up the matter, Amazon's Canadian site had removed listings for the doormats after a series of protests by people from India and of Indian-origin.
Indian High Commission in Canada : This is unacceptable. Please take this up with Amazon at the highest level. https://t.co/L4yI3gLk3h
The doormats were described as "Personalised Durable Machine-Washable Indoor/Outdoor" items and featured a stylised version of the tricolour. They were available on Amazon.ca's marketplace from the vendor XLYL.
The Canadian chapter of the Overseas Friends of the BJP was among those who protested, and it condemned the "insult of the Indian flag" in a social media post.
The vendor, identified as Hana Houdek, removed the listings, which no longer appear on Amazon.ca's searches. XLYL still lists similar doormats featuring the flags of the United Kingdom and the United States.
Amazon removes product from its site
Later on Wednesday, Amazon.com removed the doormats from its Canadian website.
"The item is no longer available for sale on the site," a spokeswoman for Amazon said in an email.
Amazon's portal in Canada sells doormats fashioned around other national flags, but under Indian law any desecration of its flag is punishable with fines and imprisonment.
Amazon's official support account on Twitter had earlier responded to angry user comments on Twitter by saying the mats were not being sold on their Indian portal and the concerns had been escalated.


Featured below are images of gates fabricated and installed by Wm. Lang & Sons Co. at GABP.
Please click on the images below to see examples of work completed at the Cincinnati Reds Great American Ball Park.
GABP Entrance Gates Fabricated & Installed by Wm. Lang & Sons Co.


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James D. Brunner, Ph.D.
Epigenetics and Gene Regulation
Phage Therapy
Persistence and Permanence of Reaction Networks
In order to understand global long term behavior of solutions of polynomial dynamical systems, I sought to determine whether or not solutions with positive initial conditions remain bounded, and bounded away from zero. A dynamical system on is said to be persistent if for any solution which starts in positive space, the system remains in positive space as time approaches infinity. In the context of population modeling, this means that no species becomes extinct. The stronger property permanence means that there exists a compact region which does not intersect the border of positive space such that any solution which begins in positive space ultimately resides inside this region. In other words, there exists a compact attracting region in positive space. Clearly, permanence implies persistence, and additionally it implies that solutions are uniformly bounded.
In our paper (arxiv link), we proved that an easily checked condition, termed tropically endotactic, on a differential inclusion in two dimensions was a sufficient condition for permanence of polynomial dynamical systems embedded in it.
This work was in collaboration with Prof. Gheorghe Craciun.
Equivalence of Reaction Network Models
Many results about reaction networks, including classical results on the existence of unique, stable, equilibrium depend on the structure of a graph underlying the network. In our paper (arxiv link), we investigate the overlap between classes of reaction networks, in the sense of dynamical equivalence.
This work was in collaboration with Prof. David Anderson, Prof. Gheorghe Craciun, and Prof. Matthew Johnston.
Confidence in Sampling an Epidemic
In response to the COVID-19 outbreak of 2020, I investigated the reliability of sampling during an epidemic by building a continuous stochastic model to simulate testing. In our paper (arxiv link), we introduced a method for simulating sampling of a population during the dynamic spread of a disease, with biased and imperfect testing. Our aim was to demonstrate that it is possible to estimate the reliability of an estimate of a given metric of disease spread using the model. We showed that biased sampling could still reliably estimate the sign of a trend in the spread of a with less than 10,000 tests performed each day, and that an actual estimate of the spread of disease could be made with an additional 1,000 unbiased tests per day.


In seniors with loss of memory or impaired mental function, the underlying dread of Alzheimer's disease runs rampant. However, the latest research indicates at least some of that worry might be baseless and that these issues may be the result of a much more treatable condition.
According to a Canadian Medical Journal Study, the symptoms some believe to be a product of Alzheimer's may actually be a consequence of untreated hearing loss.
In the Canadian study, researchers carefully assessed participant's functional capabilities associated with memory and thought and looked for any links to potential brain disorders. 56 percent of people evaluated for cognitive impairment had minor to extreme loss of hearing. Unexpectedly, a hearing aid was worn by only 20 percent of those.
A clinical neuropsychologist who served as one of the study's authors said the findings back up anecdotal evidence they've noticed when examining patients who are worried that they might have Alzheimer's. In many cases, it was a patient's loved ones who suggested the appointment because they noticed memory lapses or shortened attention.
While loss of hearing may not be the first thing an older adult thinks of when dealing with potential cognitive damage, it's easy to understand how one can confuse it with Alzheimer's.
Think of a situation where your best friend asks you for a favor. Case in point, perhaps they need a ride to the airport for an upcoming trip. What would happen if you couldn't hear their question clearly? Would you ask them to repeat themselves? Is there any way you would know that you were supposed to drive them if you didn't hear them the second time?
It's that kind of thinking that leads hearing specialists to believe some people may be diagnosing themselves erroneously with Alzheimer's. Instead, it may very well be a persistent and progressive hearing issue. If you didn't hear what someone said, then you can't be expected to remember it.
Given the link between aging and an increased probability of hearing loss, it's no surprise that people of a certain age could be experiencing these problems. The National Institute on Deafness and Other Communication Disorders (NIDCD) states that only 2 percent of adults aged 45 to 54 have disabling loss of hearing. Meanwhile, that number rises significantly for older age brackets, coming in at 8.5 percent for 55- to 64-year-olds; 25 percent for 65- to 74-year-olds; and 50 percent for people 75-years or older.
Progressive hearing loss, which is a common part of growing older, often goes neglected because people just accept it as part of life. In fact, it takes about 10 years on average for someone to seek treatment for loss of hearing. Worse yet, less than 25 percent of people will actually purchase hearing aids even when they actually need them.
Is it hard to have conversations in a crowded room so you avoid social situations?
Science has positively found a link between loss of hearing and Alzheimer's, however they're not the same. A Johns Hopkins study evaluated the mental capabilities of 639 people who reported no mental impairments, then followed their progress and aging for 12 to 18 years. The research found that the worse the hearing loss at the beginning of the study, the more likely the person was to develop symptoms of dementia which is a term that refers to impaired thought and memory.
There is one way you might be able to prevent any possible misunderstandings between loss of hearing and Alzheimer's, and that is to undergo a hearing assessment. This should be a part of your regular annual physical particularly if you are over 65.
If you think you may be confusing hearing loss with Alzheimer's, we can help you with a full hearing assessment. Make an appointment for a hearing test right away.


Ecclestone sustained the injury in the warm-up ahead of yesterday's second ODI.
A replacement for Ecclestone will be announced after the third ODI, due to take place in Mumbai on Thursday (3.30am GMT).
WATCH: Sophie Ecclestone in action for Lancashire Thunder in last year's Kia Super League.


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New houses 'better than derelict yard' say neighbours
Building firm's plan for four homes and two flats on Shrivenham Road yard site
By Aled Thomas Local Democracy Reporter
Four houses and two flats could be built on this derelict site at 203 Shrivenham Road
Houses being built on a the cleared site of a former tyre fitters would be a 'godsend', according to at least one neighbour.
Owner of a building firm John Reape has applied for planning permission to build six homes – four terraced houses and two flats – on the triangular plot of land behind his house in Shrivenham Road.
And residents behind and next to the proposed development seem to be in favour.
Mr Reape had gained planning permission for the site at 203 Shrivenham, Road previously but it had lapsed.
He said: "I think this would be a good use of this land – better than just leaving it empty. There used to be a building on the site, be we demolished that a while ago."
The building had become a target for vandals and other anti-social behaviour before it was knocked down. It has been used as a yard for Mr Reape's building business but his plans show four large terraced houses could be built along the alleyway separating the site form a very newly built block of flats, with gardens behind the houses and two parking spaces for every unit.
Mr Reape said: "There's a lot of housing coming in here – the flats next door are really new and just down the road there's a site where they are building 60 houses.
"We'll be aiming to build for the next level up form starter homes – these will be family homes, with three large double bedrooms in the houses and two bedrooms in the flats. There's clearly a need for housing in the area and I think this is a sensible use of the site."
If planning permission is granted by Swindon Borough Council, neighbours will be pleased.
Susan Rexworthy lives behind the site in Copse Avenue and will have a direct view of the houses.
She said: "I'm all in favour of it. I think it's a good thing. I know that there was permission there before.
"The yard's been used by the builder for his business and he's used it for burning waste before. He agreed to do it over the other side form us, but now there are flats over there, so they get it. It'll be much better with houses, and much nicer to look at.
"It would be a godsend, to be honest with you."
Sophie Harrigan has just moved into her home close to the site
She said: "I didn't know about the plans – but that would be better.
"It's not much to look at, at the moment. I don't mind that much but houses will be better.
"It's a nice area around here, so I think plenty of people will want to move here."
The plans are available to view and comment on at swindon.gov.uk using the reference S/19/0870.
Comments should be made to Swindon Borough Council by Tuesday, July 9.
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