This year's conference theme, "Nature's Best Hope, Our Role as Educators" showcased a full day of sessions intended to connect people with nature, integrate environmental education into the school day, and cultivate environmental leaders.

In acknowledgement of National POW/MIA Recognition Day, Delaware Code (Title 29, Section 408) requires Delaware State agencies, including all public schools, to display a POW/MIA flag each year on the third Friday in September.

DOVER, DE (July 1, 2022) – The Delaware Division of Public Health (DPH) is pleased to be recognized by the Office of Disease Prevention and Health Promotion (ODPHP) within the U.S. Department of Health and Human Services (HHS) as a Healthy People 2030 Champion. As a Healthy People 2030 Champion, DPH has demonstrated a commitment to helping […]

Ten individuals and six groups will be honored with the 2022 Governor’s Outstanding Volunteer Awards during a ceremony to be held Dec. 1 at the Executive Banquet & Conference Center in Newark. The award recipients will be recognized for exceptional contributions and outstanding dedication to service and volunteerism in Delaware.

DOVER, DE (Dec. 6, 2022) ­– The Delaware Division of Public Health (DPH) would like to recognize High 5 Hospitality as the first hospitality group in Delaware to have all its restaurants achieve the Bronze Fork award as part of the Restaurant Accolade Program. High 5 Hospitality restaurants include Buffalo Wild Wings, Eggspectation, Jersey Mike’s Subs, Limestone BBQ, […]

New campaign underway to highlight support, services available to First State caregivers NEW CASTLE, Del. (Jan. 30, 2023) — The Delaware Department of Health and Social Services (DHSS) has launched a new campaign designed to raise awareness around the many resources available to those who care for and support an older adult or someone living […]

NEW CASTLE – Governor John Carney will present the 2024 Governor’s Volunteer Service Awards to 17 individuals, six groups, seven emerging youth leaders, and one corporation during an April 4 ceremony to recognize their exceptional volunteer service. The ceremony, to be held at the Modern Maturity Center in Dover, will celebrate significant contributions to communities […]

Register online at https://us06web.zoom.us/webinar/register/WN_5tCSTHX4QLmo1JoCQ3rozA Dover, DE – On Tuesday, April 26 at 1:00 p.m. the Delaware Department of Correction invites you to join its next “DOC Insider Series” webinar with a focus on Cognitive Behavioral Therapy.  The DOC Insider Series provides members of the public with an inside the walls look at Delaware’s correctional programs, practices, […]

Dover, DE – The Delaware Department of Correction (DOC) announced today that it has been recognized within the corrections industry for the best correctional officer recruitment video of 2022.  Corrections1.com, the top online source of information and resources for corrections officers, recently identified the Delaware DOC as producing one of the five best correctional officer recruitment videos from the […]

Governor John Carney honored Delaware state employees during Public Service Recognition Week, highlighting their dedication and exceptional contributions. The event, held at the Modern Maturity Center, celebrated the commitment of government workers to the welfare of Delaware communities.

As warmer weather brings people outdoors and potentially in contact with ticks, the Delaware Division of Public Health (DPH) is recognizing Lyme Disease Awareness Month this May. According to DPH’s Office of Infectious Disease Epidemiology, Lyme disease is the most common tick-borne disease in Delaware, with over 300 cases reported each year. Lyme disease is spread […]

Delaware students recently brought home awards from the SkillsUSA National Leadership and Skills Conference.

NEWARK, Del. – First Spouse Tracey Quillen Carney on Thursday recognized September as Literacy Month with a proclamation presentation at the University of Delaware Early Learning Center. Literacy Month is intended to recognize the extensive efforts of literacy partners to promote reading as an essential skill and a lifelong pleasure.   “It’s important to show our […]

Read the in depth Review of ADATA XPG PRECOG Gaming. Know detailed info about ADATA XPG PRECOG configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

1. Vicky Kaushal looks unrecognisable as Parashurama in Mahavatar first look. Check first poster, release date  Hindustan Times
2. Mahavatar First Poster: Vicky Kaushal Takes On The Role Of "The Eternal Warrior Of Dharma"- Parashurama  NDTV Movies
3. Vicky Kaushal drops powerful FIRST LOOK as Lord Parashurama for ‘Mahavatar’  TOI Etimes
4. entertainment News Live Today November 13, 2024: Vicky Kaushal looks unrecognisable as Parashurama in Mahavatar first look. Check first poster, release date  Hindustan Times
5. Vicky Kaushal to play Chiranjeevi Parashurama in Amar Kaushik’s Mahavatar  India Today

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

Small-scale fishers play a fundamental role in feeding people—they use sustainable methods of catching and processing fish products and are a significant force in the employment and livelihoods of millions of people internationally—yet, until now, they have been excluded from climate and biodiversity conferences. For the first time at COP 16, which closed in Cali, […]

Title: Health Tip: Recognizing COPD
Category: Health News
Created: 8/25/2010 10:10:00 AM
Last Editorial Review: 8/25/2010 12:00:00 AM

Title: Health Tip: Recognizing Hay Fever
Category: Health News
Created: 8/28/2014 7:35:00 AM
Last Editorial Review: 8/28/2014 12:00:00 AM

The poly(A) signal, together with auxiliary elements, directs cleavage of a pre-mRNA and thus determines the 3' end of the mature transcript. In many species, including humans, the poly(A) signal is an AAUAAA hexamer, but we recently found that the deeply branching eukaryote Giardia lamblia uses a distinct hexamer (AGURAA) and lacks any known auxiliary elements. Our discovery prompted us to explore the evolutionary dynamics of poly(A) signals and auxiliary elements in the eukaryotic kingdom. We use direct RNA sequencing to determine poly(A) signals for four protists within the Metamonada clade (which also contains G. lamblia) and two outgroup protists. These experiments reveal that the AAUAAA hexamer serves as the poly(A) signal in at least four different eukaryotic clades, indicating that it is likely the ancestral signal, whereas the unusual Giardia version is derived. We find that the use and relative strengths of auxiliary elements are also plastic; in fact, within Metamonada, species like G. lamblia make use of a previously unrecognized auxiliary element where nucleotides flanking the poly(A) signal itself specify genuine cleavage sites. Thus, despite the fundamental nature of pre-mRNA cleavage for the expression of all protein-coding genes, the motifs controlling this process are dynamic on evolutionary timescales, providing motivation for future biochemical and structural studies as well as new therapeutic angles to target eukaryotic pathogens.

As a major type of structural variants, tandem duplication plays a critical role in tumorigenesis by increasing oncogene dosage. Recent work has revealed that noncoding enhancers are also affected by duplications leading to the activation of oncogenes that are inside or outside of the duplicated regions. However, the prevalence of enhancer duplication and the identity of their target genes remains largely unknown in the cancer genome. Here, by analyzing whole-genome sequencing data in a non-gene-centric manner, we identify 881 duplication hotspots in 13 major cancer types, most of which do not contain protein-coding genes. We show that the hotspots are enriched with distal enhancer elements and are highly lineage-specific. We develop a HiChIP-based methodology that navigates enhancer–promoter contact maps to prioritize the target genes for the duplication hotspots harboring enhancer elements. The methodology identifies many novel enhancer duplication events activating oncogenes such as ESR1, FOXA1, GATA3, GATA6, TP63, and VEGFA, as well as potentially novel oncogenes such as GRHL2, IRF2BP2, and CREB3L1. In particular, we identify a duplication hotspot on Chromosome 10p15 harboring a cluster of enhancers, which skips over two genes, through a long-range chromatin interaction, to activate an oncogenic isoform of the NET1 gene to promote migration of gastric cancer cells. Focusing on tandem duplications, our study substantially extends the catalog of noncoding driver alterations in multiple cancer types, revealing attractive targets for functional characterization and therapeutic intervention.

The spliceosome is a eukaryotic multimegadalton RNA–protein complex that removes introns from transcripts. The spliceosome ensures the selection of each exon-intron boundary through multiple recognition events. Initially, the 5' splice site (5' SS) and branch site (BS) are bound by the U1 small nuclear ribonucleoprotein (snRNP) and the U2 snRNP, respectively, while the 3' SS is mostly determined by proximity to the branch site. A large number of splicing factors recognize the splice sites and recruit the snRNPs before the stable binding of the snRNPs occurs by base-pairing the snRNA to the transcript. Fidelity of this process is crucial, as mutations in splicing factors and U2 snRNP components are associated with many diseases. In recent years, major advances have been made in understanding how splice sites are selected in Saccharomyces cerevisiae and humans. Here, I review and discuss the current understanding of the recognition of splice sites by the spliceosome with a focus on recognition and binding of the branch site by the U2 snRNP in humans.

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2.

SIGNIFICANCE STATEMENT

The present study found that the effect of X-rays on v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) and organic anion transporting polypeptides (OATP)1A2 was temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of signal transducer and activator of transcription 3, which in turn binds to the upstream regulatory sequences of SLCO1A2, the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.

SIGNIFICANCE STATEMENT

This study examined the disconnect between the in vitro synergy and in vivo efficacy of elimusertib/temozolomide combination therapy by exploring systemic and central nervous system (CNS) distributional pharmacokinetics. Results indicate that the lack of improvement in in vivo efficacy in glioblastoma (GBM) patient-derived xenograft (PDX) models could be attributed to inadequate exposure of pharmacologically active drug concentrations in the CNS. These observations can guide further exploration of elimusertib for the treatment of GBM or other CNS tumors.

Over 4 decades of research support the link between Alzheimer disease (AD) and somatostatin [somatotropin-releasing inhibitory factor (SRIF)]. SRIF and SRIF-expressing neurons play an essential role in brain function, modulating hippocampal activity and memory formation. Loss of SRIF and SRIF-expressing neurons in the brain rests at the center of a series of interdependent pathological events driven by amyloid-β peptide (Aβ), culminating in cognitive decline and dementia. The connection between the SRIF and AD further extends to the neuropsychiatric symptoms, seizure activity, and inflammation, whereas preclinical AD investigations show SRIF or SRIF receptor agonist administration capable of enhancing cognition. SRIF receptor subtype-4 activation in particular presents unique attributes, with the potential to mitigate learning and memory decline, reduce comorbid symptoms, and enhance enzymatic degradation of Aβ in the brain. Here, we review the links between SRIF and AD along with the therapeutic implications.

Significance Statement

Somatostatin and somatostatin-expressing neurons in the brain are extensively involved in cognition. Loss of somatostatin and somatostatin-expressing neurons in Alzheimer disease rests at the center of a series of interdependent pathological events contributing to cognitive decline and dementia. Targeting somatostatin-mediated processes has significant therapeutic potential for the treatment of Alzheimer disease.

Shetland Library and the National Library of Scotland have been praised for "providing optimist for the future."

Actor Elliot Page and musician Rufus Wainwright were among the stars who honoured 2SLGBTQ+ charities at the inaugural PTP Pink Awards in Toronto Thursday, in the shadow of a U.S. election that has many worried about queer and trans rights.

While startups in highly regulated industries like healthcare and finance are almost certain to face heightened scrutiny, there are controllable factors that can offset these challenges.

The post The Startup Economy is Turbulent. Here’s How Founders Can Recognize and Avoid Common Pitfalls appeared first on MedCity News.

IBM Watson is bringing cognitive computing to education to bring personalized learning to kids around the world - transforming early childhood education to help kids grow smarter, stronger and kinder.

Armin Strom Cognac Watch � the watch with a drop of 1762 Gautier Cognac

#5MoreNow

Hi there everyone.

This is such a challenging time.

Every day we're having to sit and watch in disbelief as people lie to our faces about COVID-19, how bad things are, and what to do about it. We watch in disbelief as nonviolent protesters are arrested and accused of violence — while the police use tear gas, rubber bullets, pepper spray, and batons against them. We watch in disbelief as white women pull guns on Black people after saying the actual words, "White people aren't racist… No one is racist." Our president lies so often, so willfully, childishly, self-centeredly, and so without compunction that FactCheck.org, a nonpartisan advocate for voters that aims to reduce the level of deception and confusion in U.S. politics, has a Donald Trump archive that is 107 pages long. And now I read that we've started executing federal prisoners again — despite what we all know about how flawed our criminal justice system is.

It can be hard to keep on top of how awful everything is.

I wanted to provide a few clarifying links, and recommend a book.

First, if you're feeling overwhelmed by the number of people in denial around you — and the capacity for people to lie to themselves and others about reality — I want you to know that you're not alone. Also, you're not crazy. Also, THERE IS AN OBJECTIVE REALITY. Keep hold of it. And if you don't know what cognitive dissonance is — this might be a good time to learn! A couple links —

• Cognitive dissonance is a huge factor in people, especially white people, denying the existence of structural racism and refusing to acknowledge our own investment in it. For just one example of how this plays out, check out "The psychological phenomenon that blinds Trump supporters to his racism," from the Washington Post a year ago.

• Cognitive dissonance is also playing a huge role these days in the pandemic. Check out "The Role of Cognitive Dissonance in the Pandemic," at The Atlantic.

Cognitive dissonance, when handled badly, is a killer. It makes people inexcusably ignorant, hurtful, and destructive. I find it helpful to learn about it, so at least I know what we're up against — and also so that I can be better equipped to watch for it in myself, because after all, I was socialized into this society too. Maybe you'll also find it helpful, especially now. When you're surrounded by people who are lying to themselves… It can be incredibly disorienting! And distressing, if these are people who profess to care about you. Learn about cognitive dissonance and shine some light through the bullshit around you.

Next, on the not unrelated topic of "The Letter" ("A Letter on Justice and Open Debate," published on July 7 at Harper Magazine and signed by 153 writers, artists, academics, and journalists). I really liked Hannah Giorgis's thoughts about The Letter, over at The Atlantic: "A Deeply Provincial View of Free Speech". Giorgis skewers The Letter's vagueness. She also reminds us of what free speech actually is, and what threats to free speech actually look like. An excerpt: "Any good-faith understanding of principles such as free speech and due process requires acknowledging some basic truths: Facing widespread criticism on Twitter, undergoing an internal workplace review, or having one’s book panned does not, in fact, erode one’s constitutional rights or endanger a liberal society." Yes!

Finally, I'm listening to a really great audiobook: Until We Reckon: Violence, Mass Incarceration, and a Road to Repair, by Danielle Sered. Sered is the director of Common Justice, which is a program in Brooklyn that provides a survivor-focused alternative to incarceration for violent crime. What I love about this book is that while I've been aware that our criminal justice system is broken — and that it's a lie that prisons keep anyone safe — I hadn't realized that there are workable alternatives already in play. Sered presents an alternative to incarceration that creates not just safety, but healing. The program is very survivor-focused. Survivors are deeply involved in decisions about how the people who harmed them are held accountable. And since most people who commit violent crime have also been victims of violent crime, the program helps those who've caused harm to heal too. The book is realistic about why people harm each other, and about how to change the system. It's a good introduction to the growing movement of restorative justice, and reading it makes me hopeful.

A heads up that Sered has a crystal clear grasp of what it's like to have PTSD and is searingly articulate about how it feels to want and need a person who harmed you to accept responsibility for what they did. If you are a survivor — of any kind of harm, not just violence — parts of this book may be gutting. I recommend taking breaks now and then.

Also, if you don't have time to read a book or if you can't access it right now while the libraries are in flux, I can recommend a recent podcast episode on the same topic. It's from the The Ezra Klein Show and it's the episode called: "A former prosecutor's case for prison abolition: Paul Butler on how our criminal justice system is broken — and how to fix it". I learned a LOT about how broken our criminal justice system is from that episode. I noticed that Ezra also has an even newer episode, an interview with sujatha baliga called "The transformative power of restorative justice." I haven't listened to that one yet, but it's on the same topic, so I'm guessing that's also an interesting and informative conversation.

Okay! So those are the things I wanted to share. Hang in there, everybody. I'll be writing another craft lesson blog post soon. Also, in Winterkeep news, I expect to have a cover (or several) to share with you soon! Be well, everyone.

My ITR3 for AY 2023-24 has been processed by CPC under OLD REGIME without recognizing the Taxation Option exercised undersection 115BAC for NEW REGIME by filing FORM 10IE during AY 2022-23 on 01-Jun-2022, which has been CONTINUED for AY 2023-24, as EVIDENT in the ITR3 filed for this Assessment Year. I have also Registered my grievance in this regard in the e-portal of the IT Department and have sought RECTIFICATION FIVE TIMES under Section 154 but have got the same RECTIFICATION ORDER repeating the same MISTAKE with processing done under OLD REGIME with TAX DEMAND of Rs.87,000. (Similar thing had happened in AY 2022-23 but it was corrected by RECTIFICATION). I am in continuous correspondence through email and written communication several times with the Department, including grievances raised on E-PORTAL, but the issue remains UNRESOLVED. I have also registered my grievance in this regard in CPGRAMS Portal of GOI which is pending.
I request advice on further course of action to resolve the issue including as to whether i can file an Appeal under Section 264 .
G S Prakash

My experiences in grad school were mostly happy ones, and I credit that to the fact that I was lucky to work with good people. I entered the lab of Charles Kimmel, working on zebrafish neuroscience, and stumbled my way through several projects before Chuck suggested a new one: he recommended that I use a […]

Highlights: People following the MIND diet experienced slower cognitive decline High diet adherence linked to a

Diabetes is a known risk factor for cognitive decline and dementia. The hallmark features of diabetes such as high blood sugar, insulin resistance, inflammation,

Emotion recognition is not solely based on facial expressions but involves a complex process where physical traits, cultural context, and background information

Socioeconomic status (SES) impacts cognitive health. Higher education, better jobs, and more wealth can lower dementia risk and improve recovery. (!--ref1--)

Aspen Dental Practices Remind Patients, Caregivers About Importance of Regular Oral Care for Mature Adults in Recognitio

OncoGenex Reports First Quarter Financial Results

Cogdell Spencer ERDMAN(SM) Announces New Contract in the Northwest Region

Clinical Study Results Show Nutrition 21's Chromax(R) Chromium Picolinate Improves Cognitive-Cerebral Function in Older

Ayurvedic medicine, commonly known as Ayurveda, is becoming popular across the globe day-by day due to its natural healing effects. Ayurveda is currently

Miscarriage should be recognized as a bereavement, and not as an illness, during the first 6 months of pregnancy, argues psychiatrist Nathan Hodson in

medlinkHandwriting/medlink enhances brain connectivity more than typing, emphasizing the importance of reintroducing handwriting activities for students

A founder who was an early mover in the race to build autonomous vehicles has raised $15 million for his next act: a startup that claims its AI can write enterprise software on its own. Cogna — as the U.K.-based startup is called — is led by Ben Peters, the technical co-founder of Five AI, […]

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More Netflix viewers watched dubbed versions of the South Korean drama “Squid Game” than subtitled versions. WSJ met one of the show’s English-language voice actors to see how dubbing foreign content is fueling the streaming giant’s growth. Photo Illustration: Sharon Shi

It's a Nobel moment for Artificial Intelligence. Purists often frown at the mention of Artificial Intelligence (AI). It has long been relegated to the periphery of science, dismissed by many as a mere novelty or, at best, a secondary discipline. But