Yet, in all your upheaval, the one thing to remember is that transitioning from being married to getting (and being) divorced is that it happens in cycles: a calm period followed by upheaval. Rinse and repeat. Several times. You start feeling somewhat settled and positive about your future, only to have another change take place that makes you feel you are back at square one. But you are not – it just feels that way. Reminding yourself that divorce is a journey that takes lots of time and moving forward eventually becomes easier.
So, awareness about the process, what to expect and more importantly what not to expect, is key.
1) To feel secure that you made the right decision. You will have moments when you ask yourself, 'what have I done?' 'Did I make the wrong decision?' Feelings of security sometimes feel fleeting, other times they will drag on with what seems like forever. Only towards the end of your divorce – if even then – will you feel secure in your decision. It takes a long time to get to this place. Give yourself the time and space you need.
2) That moments of calm will last. They will not. They may linger longer as time progresses. Remember that divorce and feelings of calm do not go hand in hand – but also remember that this doesn't mean that feeling calm and centered will not occur. They will, but with a lot of fits and starts.
3) That the decisions you made today will stay with you and carry you through. Making decisions is a continual reassessment process. You will have to reaffirm your decisions for yourself time and time again. Things change. Circumstances change. People change.
4) Your friends will always be your friends. We would like to believe (and hope) this is true, but it doesn't always work out that way. Sometimes friends remain friends with the ex-spouse and sometimes with you. It just depends. Sometimes it's hard to remain friends with someone who's in the midst of a divorce due to divorce contagion! The fear that being close to someone who is divorcing might cause their marriage to crumble and possibly end in divorce. Many unhappy married people are frightened that their friend's divorce may bring their marital issues into the spotlight (because sometimes it does!). And, they don't want them around your spouse, giving them ideas or possibly – gulp – the courage to leave their marriage.
Remember that relationships will change. Some should. Many times the invitations for the couples' events will stop arriving and you will find yourself having to create new relationships with other single people or couples who enjoy having single friends!
5) Listening to others will help you make the right decision. Many people will turn to their friends and family to help them make the right decision during a divorce. Because everyone has their own life experiences, their views will be based on and sometimes biased because of them. Although friends and family do provide a lot of support, people can often miss listening to their 'inner voice' and will not make their own decision based on their particular situation. This is the tricky part; you have to find the balance between getting the support you need and want and making decisions that will be good for you and your family.
Remember, divorce – like marriage and other major life transitions – takes time. It is a journey – a journey of your own.


text:
Ibrexafungerp: A Novel Antifungal Agent That Is Easier to Pronounce Than Spell
Geena Kludjian, PharmD, Jason Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS*
Contagion, Contagion, August 2021 (Vol. 06, No. 04), Volume 6, Issue 4
The first antifungal medication, amphotericin B deoxycholate, was approved in 1958 for the treatment of fungal infections. It wasn't until 15 years later that flucytosine was introduced and 15 years after that when azole antifungals were brought to market in the 1990s.1 Echinocandins, introduced in the 2000s, provided broad-spectrum antifungal coverage with minimal toxicity compared with the preceding agents. Since that time, the FDA has approved no new classes of antifungal agents. Although the current antifungals used in clinical practice provide sufficient coverage against a plethora of fungal species, resistant species and strains are evolving rapidly. The multidrug-resistant fungus Candida auris is a specific species of Candida that is emerging as a serious global health threat; it has high rates of resistance to azoles and amphotericin B, correlating to poor clinical outcomes.2
Ibrexafungerp (Brexafemme) is a first-in-class triterpenoid approved by the FDA on June 1, 2021, for the treatment of vulvovaginal candidiasis (VVC) in adult and postmenarchal pediatric females.3 In this article we review the agent's mechanism of action, pharmacokinetic properties, safety and efficacy, and place in therapy.
About That Name
Ibrexafungerp has a unique name that can be understood by breaking it down. "Ibrexa" is the fantasy prefix, "fung" refers to the mechanism of action targeting (1,3)-β-D-glucan synthase (similar to caspofungin), and "erp" is derived from triterpenoid. In 2019, the United States Adopted Names Council approved the use of the "-fungerp" stem for this new class of triterpenoid antifungals.4
Pharmacology and Microbiology
Similar to echinocandins, ibrexafungerp is an inhibitor of (1,3)-β-D-glucan synthase; however, it is structurally different and interacts with the enzyme in a different way. Due to this difference there is limited potential for cross-resistance with echinocandins, which has been confirmed in in vitro studies, as ibrexafungerp was shown to retain activity against echinocandin-resistant strains of Candida species (spp).5,6
Ibrexafungerp is active against Candida spp (including C auris), Aspergillus spp, and Pneumocystis, and inactive against Cryptococcus spp, Mucorales, and Fusarium spp. It is also active against some other less common molds.7 Ibrexafungerp has demonstrated activity against biofilms produced by Candida spp, with similar activity to that of echinocandins but significantly higher than that of fluconazole (P < .001).8
Unlike the echinocandins, ibrexafungerp is highly bioavailable and can be given both intravenously and orally. Ibrexafungerp is available as 150-mg oral tablets and administered at 300 mg given 12 hours apart for 2 doses, which completes the regimen in a single day.3 Plasma concentrations peak around 4 to 6 hours after oral administration. Administration with a high-fat meal increased the maximum concentration and area under the curve by around 32% and 38% compared with fasting, respectively, but this is not considered clinically significant. Ibrexafungerp can be taken with or without food.3 Protein binding is 99.6% to 99.8% and the mean steady state volume of distribution is approximately 600 L.3 Tissue to blood ratios for several organs have been estimated in a single-dose pharmacokinetic analysis in rats, which found extensive distribution in vaginal tissue; the lung, kidney, liver, and spleen; bone marrow; muscle; and skin, but minimal distribution in central nervous system tissue and the spinal cord.9 Ibrexafungerp is hepatically cleared and mainly eliminated in the feces and bile (~90%), with approximately 1.5% urinary elimination. Dose adjustments are not required for renal or hepatic impairment. The half-life is approximately 20 hours, supporting the single-day dosing.3 Currently, no data exist on crushing or breaking the oral tablets.
Drug-Drug Interactions
Ibrexafungerp is extensively metabolized by the cytochrome P450 pathway and is affected by drugs that induce or inhibit this pathway. Because it is a substrate of cytochrome P3A4 (CYP3A4), coadministration of the drug with strong CYP3A4 inhibitors increases its concentration and a 50% dose reduction is recommended.3 Avoid coadministration with moderate to strong CYP3A4 inducers, such as rifampin, which may reduce concentrations of ibrexafungerp. Ibrexafungerp is also a CYP3A4, P-gp, and OATP1B3 transporter inhibitor, but the clinical significance of this is not of concern for the short duration of treatment for VVC.3 Concomitant use with pantoprazole for 5 days resulted in decreased ibrexafungerp exposure by 25%, though this was not considered clinically significant at the current approved dose.3
Two phase 3 clinical studies evaluated the safety and efficacy of ibrexafungerp compared with placebo for the treatment of VVC. VANISH 303 and VANISH 306 (NCT03734991 and NCT03987620) were randomized, double-blind, placebo-controlled trials that included nonpregnant postmenarchal patients aged 12 and older with a diagnosis of symptomatic acute VVC.3 More than 90% of patients with baseline cultures were culture positive with C albicans. The investigators in both trials evaluated clinical cure, defined by the complete resolution of signs and symptoms, at test of cure at 8 to 14 days post treatment. According to the data, patients receiving ibrexafungerp showed complete response rates compared with those receiving placebo of 50% vs 28% (P = .001) in VANISH 303, and 63.5% vs 44.9% (P = .009) in VANISH 306. Adverse effects among patients were minimal and mainly gastrointestinal in nature.3
Several other ongoing phase 2 and 3 clinical trials are being conducted to evaluate the role of ibrexafungerp in patients with recurrent VVC (CANDLE, NCT04029116), invasive aspergillosis (SCYNERGIA, NCT03672292), refractory invasive fungal infections (FURI, NCT02244606), and invasive infections due to C auris (CARES, NCT03363841). Highlighting the CARES study in particular, investigators evaluated the safety and efficacy of ibrexafungerp 750 mg twice daily for 2 days, then 750 mg once daily for up to 90 days in hospitalized patients with documented candidiasis or candidemia caused by C auris. Interim results have demonstrated a complete or partial response in 8 of 10 patients (80%).10 FURI has also shown positive results thus far, with investigators reporting that 46 of 74 patients (62%) experienced complete or partial responses and 18 of 74 (24%) had stable disease at the time of analysis.10
Adverse Effects, Warnings, and Precautions
Based on data from clinical trials in patients with VVC, the adverse effect profile of single-day ibrexafungerp is generally favorable. Gastrointestinal adverse effects were the most common, including diarrhea (16.7%), abdominal pain (11.4%), nausea (11.9%), dizziness (3.3%), and vomiting (2.0%).3 A press release for the FURI and CARES studies stated that ibrexafungerp was well tolerated overall and that investigators had identified no safety signals warranting changes to the studies.10 In contrast to many azole antifungals, ibrexafungerp does not cause QTc prolongation.3
The use of ibrexafungerp is contraindicated in pregnancy, as data from animal studies have shown a potential for fetal harm. During treatment with the agent, the use of effective contraception is advised. Concentrations in breast milk are unknown.
Investigators in in vitro studies have evaluated the potential for resistance to ibrexafungerp, finding an association with mutations in the FKS2 gene. The clinical relevance of this is not yet known, but it has been established that ibrexafungerp retains activity against most echinocandin- and fluconazole-resistant strains of Candida spp.3,5,6
Place in Therapy
Although fluconazole is an inexpensive, well-tolerated, single-dose agent that is effective in the majority of VVC cases, ibrexafungerp is an option for patients who either fail fluconazole therapy or may be unable to receive it. Ibrexafungerp is available orally and has a favorable adverse effect profile.
Beyond VVC, ibrexafungerp has the potential to advance the care of patients with invasive fungal infections, including those caused by resistant Candida spp. Clinical data evaluating inpatient use in more invasive and resistantinfections are pending. There is currently insufficient data to support the use of ibrexafungerp in patients with these infections, and clinicians should note that the dosing regimens under study are different from the approved VVC regimen. The drug interactions that are not clinically relevant with a single-day dosing regimen may warrant caution or necessitate dose modification for other uses.
Geena Kludjian, PharmD, is an infectious diseases clinical pharmacy specialist at Cooper University Hospital in Camden, New Jersey.
Jason C. Gallagher, PharmD, FCCP, FIDP, FIDSA, BCPS, is a clinical professor at Temple University (TU) School of Pharmacy and a clinical pharmacy specialist in infectious diseases at Temple University Hospital in Philadelphia, Pennsylvania. He also is director of the PGY2 Residency in Infectious Diseases Pharmacy at TU.
Nett JE, Andes DR. Antifungal agents: spectrum of activity, pharmacology, and clinical indications. Infect Dis Clin North Am. 2016;30(1):51-83. doi:10.1016/j.idc.2015.10.012
Chaabane F, Graf A, Jequier L, Coste AT. Review on antifungal resistance mechanisms in the emerging pathogen Candida auris. Front Microbiol. 2019;10:2788. doi:10.3389/fmicb.2019.02788
Brexafemme. Package insert. SCYNEXIS, Inc; 2021. Accessed June 22, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214900s000lbl.pdf
Boden J. How ibrexafungerp got its name. IDStewardship.com. April 22, 2021. Accessed June 21, 2021. https://www.idstewardship.com/ibrexafungerp-got-name/
Pfaller MA, Messer SA, Rhomberg PR, Borroto-Esoda K, Castanheira M. Differential activity of the oral glucan synthase inhibitor SCY-078 against wild-type and echinocandin-resistant strains of Candida species. Antimicrob Agents Chemother. 2017;61(8):e00161-17. doi:10.1128/AAC.00161-17
Nunnally NS, Etienne KA, Angulo D, Lockhart SR, Berkow EL. In vitro activity of ibrexafungerp, a novel glucan synthase inhibitor against Candida glabrata isolates with FKS mutations. Antimicrob Agents Chemother. 2019;63(11):e01692-19. doi:10.1128/AAC.01692-19
Jallow S, Govender NP. Ibrexafungerp: a first-in-class oral triterpenoid glucan synthase inhibitor. J Fungi (Basel). 2021;7(3):163. doi:10.3390/jof7030163
Marcos-Zambrano LJ, Gómez-Perosanz M, Escribano P, Bouza E, Guinea J. The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp. J Antimicrob Chemother. 2017;72(7):1969-1976. doi:10.1093/jac/dkx010
Wring S, Borroto-Esoda K, Solon E, Angulo D. SCY-078, a novel fungicidal agent, demonstrates distribution to tissues associated with fungal infections during mass balance studies with intravenous and oral [14C]SCY-078 in albino and pigmented rats. Antimicrob Agents Chemother. 2019;63(2):e02119-18. doi:10.1128/AAC.02119-18
SCYNEXIS announces positive results from interim analyses of ongoing phase 3 studies (FURI and CARES), demonstrating oral ibrexafungerp's ability to treat severe fungal infections in the hospital setting. Press release. SCYNEXIS. March 2, 2021. Accessed June 22, 2021. https://www.scynexis.com/news-media/press-releases/detail/233/scynexis-announces-positive-results-from-interim-analyses
Download Issue : Contagion, August 2021 (Vol. 06, No. 04)
PublicationsHEALTHCARE-ASSOCIATED INFECTIONS (HAI)Contagion, August 2021 (Vol. 06, No. 04)
Detecting Sepsis Earlier
Adhering to Standard for Sepsis Treatment Did Not Reduce Mortality
Ferring's Microbiome Health Index Measures Gut Microbiota After Antibiotics

redpajama_set_name: RedPajamaCommonCrawl


Summer started beautifully. My West Coast family came to visit for a few weeks, trips to amusements and NYC were had and healthy eating was all the rage. Plus, I was making significant progress in my novel and looked forward to its completion. Then, it nearly went up in flames – literally!
The days that followed allowed me the opportunity to retrieve some of my belongings, those that could be salvaged. My laptop was one of those treasured items. It was wet on top and likely soaked inside, but my father baked it in the oven, on a low temperature, and we were able to use it long enough to get my files off. It hasn't been used since as I do not trust that it's safe to use. Who knows how damaged it got on the inside, and I'm not taking another chance with my work!!!
While the work I'd put in on my novel did not perish, my mind has been focused elsewhere. On dealing with insurance issues, figuring out where to live next, and spending time with friends and family. I don't know about you, but I live a day-to-day existence. As a result, I sometimes get lost in the present without looking ahead at what's possible and being thankful the experiences I've already had.
Having nearly lost the work that I'm very proud of, I felt the enormity of the project that remained. As such, I stalled my progress and left "Gracie" standing alone in the forest once again. The sun is shining, birds are chirping, and the opportunity is in front of me. I just need to keep my fingers typing and my character moving.


text:
Anglican Church offers wedding-baptism
← return to Out of Context
By Carleton Bryant The Washington Times - July 23, 2009, 07:53AM
The Anglican Church has introduced a combination wedding and baptism liturgy to encourage marriage in Britain, where 40 percent of children are born out of wedlock, the Times of London is reporting.
Senior bishops say the "hatch and match" service does not veer from the Church's teachings, but some clergy disapprove.
"It is a shame that what should be a bride's day now stands to be hijacked by screaming kids," one bishop said.
Another joked: "It's a pity they haven't put in a funeral for grandma as well."
The new service is advertised as the one-stop hitch and rinse.
Now there's talk about celebrating Christmas and Easter on the same day — just save time, you know.
If they really want to make their services more convenient, they should install a drive-through lane at the chapel.
And they could validate your parking.
Carleton Bryant
Carleton Bryant is the assistant managing editor for strategic planning and development/special projects for The Washington Times. He previously served as The Times' Metropolitan desk editor, Features desk editor and an assistant National desk editor, as well as a National and Metropolitan reporter. He currently writes a humor blog and weekly humor column — both titled "Out of Context" — ...
Muriel Bowser presses Chad Wolf for inauguration security
Longtime Maryland Senate president Thomas V. Mike Miller announces retirement
Peter Newsham resignation surprises top D.C. lawmaker
Rock & Roll Hotel closes in D.C., cancels all shows
Karl Racine, D.C. attorney general, files school residency fraud lawsuits against 7 parents


text:
UK lawmakers call for probe of Lloyds, KPMG over HBOS fraud
LONDON: British lawmakers called for an investigation by law enforcement and regulatory agencies into the handling by Lloyds Banking Group of a fraud at its HBOS Reading unit more than a decade ago and into the role of auditor KPMG.
The call by the All Party Parliamentary Group (APPG) on Fair Business Banking comes after the publication online on Tuesday of an internal 2013 report alleging serious misconduct by the lender over the handling and disclosure of the fraud.
The lawmakers said allegations that HBOS had concealed the fraud, one of Britain's worst-ever banking scandals that saw six people jailed for a total of 47 years last year, should be subject to "full, forensic and expeditious investigations by regulators".
Lloyds reiterated the bank's statement that the internal 2013 report had been provided to Britain's Financial Conduct Authority (FCA) and to the police in 2014. "We strongly refute the allegations with regards to KPMG's knowledge and involvement in the report, which we believe to have no basis in fact," a KPMG spokesperson said.
"We have cooperated fully with the detailed investigations undertaken, including those by the PRA / FCA and the FRC (watchdogs), none of which concluded that our work did not meet the applicable audit standards of the time."
The internal report by Scottish businessman Neil Mitchell, a frequent critic of Britain's big banks, alleged that HBOS executives knew of the fraud as early as 2004 and failed to properly disclose it, with far-reaching implications given Lloyds' takeover of HBOS in 2009.
Lloyds did not address the substance of the report's allegations that it misled investors over its financial health by not disclosing the fraud earlier. Britain's financial watchdog is conducting a probe into HBOS and what its executives knew of the fraud, while a retired judge is probing whether Lloyds then properly investigated the incident after it brought HBOS in 2009.— Reuters
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text:
import mxnet as mx

def matrix_fact_net(factor_size, num_hidden, max_user, max_item, sparse_embed=True):
    # input
    user = mx.symbol.Variable('user')
    item = mx.symbol.Variable('item')
    score = mx.symbol.Variable('score')
    if sparse_embed:
        # user feature lookup
        user_weight = mx.symbol.Variable('user_weight', stype='row_sparse')
        user = mx.symbol.contrib.SparseEmbedding(data=user, weight=user_weight,
                                                 input_dim=max_user, output_dim=factor_size)
        # item feature lookup
        item_weight = mx.symbol.Variable('item_weight', stype='row_sparse')
        item = mx.symbol.contrib.SparseEmbedding(data=item, weight=item_weight,
                                                 input_dim=max_item, output_dim=factor_size)
    else:
        # user feature lookup
        user = mx.symbol.Embedding(data=user, input_dim=max_user, output_dim=factor_size)
        # item feature lookup
        item = mx.symbol.Embedding(data=item, input_dim=max_item, output_dim=factor_size)
    # non-linear transformation of user features
    user = mx.symbol.Activation(data=user, act_type='relu')
    user = mx.symbol.FullyConnected(data=user, num_hidden=num_hidden)
    # non-linear transformation of item features
    item = mx.symbol.Activation(data=item, act_type='relu')
    item = mx.symbol.FullyConnected(data=item, num_hidden=num_hidden)
    # predict by the inner product, which is elementwise product and then sum
    pred = user * item
    pred = mx.symbol.sum(data=pred, axis = 1)
    pred = mx.symbol.Flatten(data=pred)
    # loss layer
    pred = mx.symbol.LinearRegressionOutput(data=pred, label=score)
    return pred

redpajama_set_name: RedPajamaGithub


Refugees vary greatly in their ability to integrate into their new society. Many do their utmost to learn the German language. Some attempt to understand the customs of Germany and how society functions here. Most would like to make German friends, as it is easier to get used to a new environment when one has a support network. Yet, there is a feeling among many others, particularly the elderly, who hope day and night for a quick return to Syria, that it must be possible to live here without making any effort to integrate.
These individuals prefer to live in places where their countrymen have already settled. They want to make friends without the barriers posed by language and culture. And, of course, they need a satellite dish so that they can continue to watch their familiar Arabic television programmes.
For people in this category, the task of integration is extremely difficult, if not downright impossible. Initially new arrivals are sent to German language classes organised by the state Job Centres. However, the Job Centres and the requirement to acquire a new language alone cannot force people to speak German. As the saying goes, you can bring a horse to water, but you can't make it drink.
I recently saw a Palestinian wedding on Sonnenallee in Neukolln, a Berlin district with a large Arab and Turkish population. The event immediately brought to mind life in a Palestinian camp near Damascus. The rituals, ceremony and songs that were sung were exactly the same. Nothing had changed for these people, with the possible exception that they now had the opportunity of enjoying a life of greater prosperity. I made an effort to observe any signs of integration. I did not find a single one.
Many of the Syrian refugees I have met so far in Berlin have complained that the Job Centre has exerted pressure upon them to learn German. One man even started to lecture me about human rights, claiming that being forced to learn a language is incompatible with these lofty principles. He then continued, "We constantly have to see how we can integrate ourselves. But are all Germans integrated?" He wanted to know if there were also Germans who did not live in harmony with mainstream society, raising the examples of isolated, aggressive former criminals. "What, then, is the big deal with integration – you can get by just fine without it!"
Young refugees have an easier time adapting. Falling in love is the simplest and, at the same time, most important reason for embarking on the long path of integration into a new society. The young men traversing this path of love are the lucky ones, who eventually succeed in correctly employing "der," "die," and "das" – and even, someday, in mastering the dative case.
Those who do not enjoy such an opportunity attempt to find other means of fostering contact with Germans. With the few words they have acquired, they talk untiringly to all the salespeople in every store. Even if they don't want to, the latter are forced to listen, barely able to understand the gibberish uttered as a result of a handful of German lessons. After all, the newcomers might become regular customers.
Others opt for the easiest integration route – via fashion. They tear their pants, put on absurdly shaped hats (without knowing that only a small percentage of German football and carnival fans don such headgear – and even then only on certain occasions) and wear oversized headphones. They obviously want to show that they are a part of this modern society.
Yet, these are only superficial attempts, more of an imitation of integration. Real integration goes deeper. It should manifest itself in a different, liberal orientation towards Western values and be accompanied by the conviction that individual freedoms, including equal rights for women, are incontrovertible central pillars of this new social order. Those who truly want to integrate into mainstream society have to accept these values and, ideally, internalise them.
I recently observed a man who looked as if he could have been a fashion model. He was lovingly embracing an Asian woman. Had he been an Arab, he would have had trouble presenting her to his mother, taking into consideration the beauty ideal prevalent in the Arab world. In our strict and superficial society, you still hear the brutal saying: "she will never find anyone to marry." In Germany, by contrast, there is the wonderful adage: "there′s a lid for every pot".
Our traditionalists are uncomfortable with any attempts to explain such a wonderfully free and unprejudiced love. Yet, it shows that the "love of a woman" entails more than supposed outward beauty, guaranteed virginity and the recommendation of the bride's mother – presented to the mother of the potential groom with the ubiquitous gift of cookies.
Most young men in Syria have had pre-marital relationships, in secret of course. During their years at university, clandestine couples are far from uncommon. Things only become problematic should they desire to cement such a relationship in marriage. This is because it is the role of the mother to search out a wife for her eligible son. It is clear that this practice results in numerous problems – ranging from a boring married life all the way to divorce.
Here in Germany, the young as well as the old have the guaranteed freedom to decide for themselves who will be their partner in life. There are no necessarily unwanted or forced marriages that arise out of or are guided by the desires or needs of the extended family.
One part of real integration begins when the newcomers give up their prejudices against open pre-marital relationships between men and women and then embrace the wonderful idea that you can find your own partner. For me, the European-Asian pair was a wonderful expression of this idea. Their families and society accept the free will of the couple to share their lives together. I can even imagine that their parents did not even raise questions concerning the origin, appearance, or even level of education of the partner chosen by their child. It is a matter of trust and respect.
Immigrants have to learn to respect individual preference, as evidenced in the variety of lifestyles here in Germany. For instance, I met a young Lebanese man who is married to a woman at least 25 years older than himself. The difference between them did not appear to bother them. As far as I know, they live a completely normal life in Berlin – together.
But what would happen if they took a trip to Lebanon? Would it be easy for him to present his wife to his mother, who is probably the same age? Could the two of them walk through a city or even his home village hand in hand? I find it difficult to imagine. I am certain that he would find many excuses not to introduce her to his family.
Daily life in Germany confronts people from Arab countries with previously unknown experiences. Those who have felt embarrassed upon seeing a man and a women wildly making out in public for the first time will soon find this pales into insignificance when they two men or two women kissing.
And since this is something that you see constantly, at least here in Berlin, it is very probable that most refugees will, over the course of time, cease making comparisons with their old homeland. Slowly, the new impressions will set in motion an intellectual process of integration.
Those who nonetheless decide to hold on to their old values with all their might only serve to exclude themselves from the process of integration. They will soon find themselves enclosed by a wall built of their own making – yet one so high that they will no longer even be able to see what is going on around them.


text:
Vintage Military Gear
Military jackets have long been worn by non-military personnel for their aesthetic, symbolic, and functional qualities. In fact, military outerwear has historically dictated trends in civilian men's and women's clothing. The widespread imagery of soldiers in uniform popularized these garments, while the institutional focus on specific designs codified the style. Then there are the utilitarian aspects of these pieces; they are often both water-repellant and warm, making them practical as well as fashionable choices for everyone from rebellious youths to button-down professionals.
In general, military jackets and coats are divided into two categories, dress and fatigue. Dress uniforms are worn for special occasions and decorated with insignia or awards. Fatigues are used on a daily basis to perform all manner of duties. Today, popular military jacket styles come from both dress and fatigue uniforms worn throughout the history of modern warfare.
Pea coats, which are worn these days by men and women alike, were first produced for sailors in the European navies of the late 1700s. Originally termed P-jackets for the coarse twill pilot's cloth used in their manufacture, these coats were most commonly made of a fabric called Melton wool, named after the English town of Melton Mowbray where the material was made. Pea coats are generally identified by their dark navy blue color, wide lapels, and double-breasted front with large decorative buttons, which often bear an anchor imprint. Fashionable 20th-century manufacturers include Sterlingwear and Fidelity, both of Boston, Massachusetts.
The first American Army uniform policy was drafted in 1779. A "blue, open waistcoat" was described in the standard dress code, yet divisions among states and differences in regional resources resulted in a wide variety of military clothing. Military jackets from this period are generally characterized by their blue color with gold buttons and contrasting red trim. Conversely, the British uniform of the period featured a red-colored jacket with white or blue facings, thus spawning the slang term Red Coats used during the Revolutionary War.
The Civil War presented the first opportunity for Americans to establish true military uniform regulations; blue fabric was used for Union uniforms, gray for the Confederacy. Jackets of this era tend to be characterized by their knee-length woolen tails, long row of closely spaced gold buttons down the front, gold piping or embroidery, and a simple stand-up collar. Intricately crafted metal buttons often identify the coat's manufacturer, while differing shoulder straps denote the officer's rank.
As the rules of battle and technologies of war shifted at the beginning of the 20th century, military uniform designers moved away from brightly colored dress uniforms and toward clothing that was less expensive to produce and less visible to the enemy. In the late 1800s, British troops first donned khaki uniforms, derived from a regional fabric British Indian recruits wore in the Peshawar district of India. These khakis became the official uniform during the Second Boer War, and the material quickly spread among many other militaries and expanded into all types of clothing production. Khaki-colored jackets made from a variety of fabrics have been worn in every major conflict of the 20th century.
Debate over who originated the iconic trench coat still ensues, as both Burberry and Aquascutum of England claim the style. Thomas Burberry created a durable, waterproof fabric he called gabardine in the late 1870s, which was later used in the design of Burberry's classic "officer's raincoat" in 1901. Aquascutum's claim dates to the 1850s and the Crimean War. Regardless of its actual inventor, this innovative outerwear was manufactured by both companies for soldiers during World War I. After the war, civilians swiftly adopted the style...
The familiar jacket many associate with the standard military look that we think of today was developed during World War II. These coats usually featured olive green fabric with a single row of buttons down the front and breast pockets on each side. In 1942, the U.S. military began a program to establish functional uniform guidelines for combat divisions anywhere in the world. Modeled after British military attire, the resulting M-1943 outfit was designed for cold weather and worn by U.S. troops during the invasion at Normandy.
One piece in the ensemble was a hip-length semi-dress jacket made from olive green wool that could be worn formally or in combat. These coats came to be known as "Eisenhower" or "Ike" jackets, as they were used by General Dwight D. Eisenhower, who also wore them after the war while he was president. Since the coats were meant to be worn under a water-repellent outer layer and over various undergarments, their sleeves were baggy and they were loose fitting in the back. Ike jackets were frequently adorned with various patches, pins, or service stripes signifying the owner's rank and military achievements.
World War II also saw the rise of the leather bomber or pilot flight jacket, a style most closely associated with the Type A-2 jacket, which was officially adopted by the U.S. Air Force in 1931. The U.S. Air Force Catalog from the era describes the jacket as "seal brown horsehide leather, knitted wristlets and waistband (skirt)." It was produced for the Air Force by companies like Werber Sportswear and Aero Leather Clothing Co. In the 1980s, the style was reissued by the Air Force to wide acclaim, yet the cut was less fitted and the jacket proved less durable than the original A-2s.
High-altitude flight crews often wore the B-3 Shearling Bomber Jacket, which was originally designed in 1926 for the British RAF by parachutist Leslie Irvin. As World War II progressed and aviation technology improved, flight altitudes increased, exposing pilots and crews to lower air temperatures. Thus the F2 Heated Flight Jacket, which consisted of a wool shell surrounding electrical heating devices.
Regardless of model, these flight jackets were frequently personalized with detailed artwork beyond just the wearer's troop or rank—for many contemporary jacket collectors, the more individualized and detailed the artwork, the more valuable the jacket. Individual servicemen often customized their jackets with images ranging from pin-up girls and Donald Duck to tallies of bombs dropped and battlefield kills.
The MA-1 Nylon Flight Jacket was released in 1955, and later redesigned by Alpha Industries to include an orange lining for reversible wear during search-and-rescue operations. Alpha revamped many classic flight jackets from the late 1950s onward, and is today the largest supplier of outerwear for the U.S. Military.
Marching-band-style jackets are also closely linked with military uniforms. These bands were developed at the same time as early armies—their purpose was to direct troops and give signals on the battlefield. Contemporary marching-band uniforms are strikingly similar to those worn during the Revolutionary War era, complete with detailed armbands and rows of elaborate facings.
In 1967, The Beatles' "Sgt. Pepper's Lonely Hearts Club Band" album cover instantly popularized a highly decorative military-band-style jacket, a double-breasted look complete with ornate, contrasting piping designs across the front and sleeves, with epaulets on each shoulder.
Standard issue M-65 Field Jackets from the Vietnam War era are the most widely available vintage military jackets today. Made of a lighter olive-green canvas than their predecessors and fitted with plastic zippers or buttons instead of metal ones, M-65s featured cargo pockets and were generally unpersonalized since rank insignia was simply pinned onto the jacket rather than sewn.
Source: www.collectorsweekly.com
Vintage Military
Antique Military surplus
Surplus Military weapons


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this is the largest ever exhibition staged by chinese artist ai weiwei
ai weiwei (70 articles)
ai weiwei is a chinese contemporary artist, working in sculpture, installation, architecture, curation, photography, film, and social, political and cultural crafts.
ai weiwei + HHF-designed upstate new york retreat goes on sale for $5.25 million
ai weiwei life cycle exhibition in los angeles addresses global refugee crisis
ai weiwei's beijing studio is turned to dust by chinese authorities
ai weiwei-designed UTA artist space opens in beverly hills
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ai weiwei's first ever exhibition in sao paulo, brazil is his largest ever staged – covering a total area of 8,000 square meters. entitled 'ai weiwei: RAIZ,' the colossal retrospective, developed and curated by marcello dantas, arrives in brazil to showcase the artist's life story through his most iconic works, along with the new works that arose from a deep immersion into brazil and its traditions. the exhibition will be open to the general public at the OCA in ibirapuera park, são paulo.
all images by carol quintanilha
ai weiwei left his country of origin in 2015 and now stands out on the international stage for his interest in social and humanitarian issues, including the world immigration crisis. among his best known works are his large-scale productions that present a tension between the contemporary world and the traditional chinese production methods and ways of thinking. such as his 1995 'dropping a han dynasty urn,' a work that portrays the artist intentionally dropping an urn which dates back to the 2,000-year-old han dynasty. this subversive and transformative action is presented as a photographic triptych that is renowned worldwide.
ai weiwei's immersion into brazilian culture relied on the consultation of designer paula dib. dib introduced him to brazilian communities, local artisans, and regional resources of which he was not previously aware. this resulted in new works made with wood, seeds, roots, fabrics and leather. ai weiwei unveiled and absorbed this local culture and prepare objects of art that represent biodiversity, the human landscape, and brazilian creativity. 'ai weiwei: RAIZ' is at the OCA exhibition space at ibirapuera park in são paulo until january 20th, 2019.
kat barandy I designboom
ai weiwei addresses the global refugee crisis with his 'life cycle' exhibition in los angeles
ai weiwei captures the global refugee crisis in documentary film 'human flow'
ai weiwei brings bicycles, boats and bold political statements to buenos aires
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Train2Game News Wrestler Tag Teams with Razer
Posted on August 20, 2018 by Train2Game Blogger Team
RazerTM, the leading global lifestyle brand for gamers, today announced its partnership with Kenny Omega, one of the highest rated professional wrestlers of all time and the current International Wrestling Grand Prix (IWGP) heavyweight champion in Japan.
Under this partnership, Kenny Omega will represent Razer as a gaming lifestyle ambassador in public events and campaigns. An avid fighting game player, his top product choices include the Razer Panthera Evo fight stick and Razer Thresher Ultimate headset for PlayStation 4.
"I've always been a supporter of Razer and their products, so joining their team is really exciting," said Omega. "To rise to the next level in wrestling or gaming, a true support system is needed, and that's where Team Razer comes in. Their top-quality devices and fashion-forward gear are the best on the market, and I'm proud to be working with a company whose motto is 'for gamers, by gamers' that is just as driven to win as I am."
Over his 18-year career, Omega starred in wrestling leagues all over the world, including Premier Championship Wrestling, World Wrestling Entertainment, Ring of Honor Wrestling Entertainment and New Japan Pro Wrestling.
Omega's many recent achievements include 13 Match of the Year awards in Japan. He is the only foreigner to ever win the prestigious G1 tournament in Japan, and was named "Wrestler of the Year" by Sports Illustrated in 2017.
In addition to wrestling, Omega is also a long-time aficionado of anime and video games, and he is a huge fan of "Street Fighter." Earlier this year at E3 2018, he triumphed over WWE Superstar Xavier Woods in a high-octane "Street Fighter: Arcade Edition" showdown.
Min-Liang Tan, co-founder and CEO of Razer, said: "Esports is becoming so mainstream that today's pro-gamers can come from anywhere. Kenny Omega is a great addition to Team Razer's roster of elite athletes, and I can't wait to see him dominate the competition both in the ring and in gaming."
For more information on Team Razer visit https://www.razer.com/team.
For more information on Kenny Omega:
This entry was posted in 2, Developer, game, games, Games Developer, train, train 2 game, Train2Game, www.train2game-news.co.uk and tagged developer, game, Games Developer, games industry, Kenny Omega, New Japan Pro, Peripherals, Razer, Ring of Honour, TNA, train, Train2Game, Wrestler, Wrestling, WWE by Train2Game Blogger Team. Bookmark the permalink.


Recent evidence indicates that histamine, acting on histamine 1 receptor (H1R), resets the circadian clock in the mouse suprachiasmatic nucleus (SCN) by increasing intracellular Ca2+ concentration ([Ca2+]i) through the activation of CaV1.3 L-type Ca2+ channels and Ca2+-induced Ca2+ release from ryanodine receptor-mediated internal stores.
In the current study, we explored the underlying mechanisms with various techniques including Ca2+- and Cl−-imaging and extracellular single-unit recording. Our hypothesis was that histamine causes Cl− efflux through cystic fibrosis transmembrane conductance regulator (CFTR) to elicit membrane depolarization needed for the activation of CaV1.3 Ca2+ channels in SCN neurons. We found that histamine elicited Cl− efflux and increased [Ca2+]i in dissociated mouse SCN cells. Both of these events were suppressed by bumetanide [Na+-K+-2Cl− cotransporter isotype 1 (NKCC1) blocker], CFTRinh-172 (CFTR inhibitor), gallein (Gβγ protein inhibitor) and H89 [protein kinase A (PKA) inhibitor]. By itself, H1R activation with 2-pyridylethylamine increased the level of cAMP in the SCN and this regulation was prevented by gallein. Finally, histamine-evoked phase shifts of the circadian neural activity rhythm in the mouse SCN slice were blocked by bumetanide, CFTRinh-172, gallein or H89 and were not observed in NKCC1 or CFTR KO mice.
Taken together, these results indicate that histamine recruits the H1R-Gβγ-cAMP/PKA pathway in the SCN neurons to activate CaV1.3 channels through CFTR-mediated Cl− efflux and ultimately to phase-shift the circadian clock. This pathway and NKCC1 may well be potential targets for agents designed to treat problems resulting from the disturbance of the circadian system.
Histamine, a neurotransmitter/neuromodulator produced by tuberomammillary nucleus (TMN) neurons in the hypothalamus , has a crucial role in regulating brain arousal . A large body of evidence indicates that histamine is also a potent regulator of the mammalian circadian time-keeping system. Histaminergic fibers from the TMN densely innervate the master circadian clock suprachiasmatic nucleus (SCN) in the rat [3–5] and exogenously applied histamine exerts a phase-shifting effect on the circadian neural activity rhythms recorded in the hamster and mouse SCN slices maintained in vitro [6, 7] and on the circadian behavior rhythms manifested in rats . Moreover, histamine synthesis inhibition disrupts circadian activity rhythms in the rat  and reduces the phase shifts of circadian activity rhythms induced by light in the hamster .
It is well established that 4 different types of histamine receptors (i.e., H1R ~ H4R) mediate histaminergic actions and that the H1R, which is linked to the Gq/11-phospholapase C (PLC) pathway, mediates a majority of excitatory actions of histamine in the central nervous system [2, 10]. The Gq/11-PLC pathway leads to diacyl-glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) production [2, 10]. While DAG can cause Ca2+ influx through the transient receptor potential cation channel (TRPC), IP3 induces Ca2+ release from the internal stores via IP3 receptor [10, 11].
Recently, we demonstrated that histamine, acting on H1R, increases intracellular Ca2+ concentration ([Ca2+]i) in mouse SCN neurons by a novel mechanism driven by CaV1.3 L-type Ca2+ channels as well as Ca2+-induced Ca2+ release from ryanodine receptor (RyR)-mediated internal stores and this is the molecular mechanism underlying the histamine-induced phase delay of circadian neural activity rhythm in the SCN . In the present study, we sought to delineate the novel signaling mechanisms leading to L-type Ca2+ channel opening after H1R activation. Prior works have shown that histamine regulate Cl− conductances in neurons [13, 14] and that, in some SCN neurons, the electrochemical gradient for Cl− is set toward the extracellular side due to the Cl−-importing activity of Na+-K+-2Cl− cotransporter isotype 1 (NKCC1) [15, 16]. Therefore, we hypothesized that histamine causes Cl− efflux to elicit membrane depolarization needed for L-type Ca2+ channel activation. We considered the possibility that the cystic fibrosis transmembrane conductance regulator (CFTR) may mediate the histamine-induced Cl− efflux because Allen Brain Atlas (, http://www.brain-map.org) indicates the presence of CFTR mRNA in the mouse SCN. Prior works also indicate that H1R is positively coupled through the Gβγ protein to the cAMP signaling pathway [18, 19], which can lead to CFTR activation by stimulating protein kinase A (PKA) [20–24]. Here we present results indicating that the Gβγ-cAMP/PKA-CFTR pathway links H1R to L-type Ca2+ channels and this pathway is essential for the phase delay of the circadian clock induced by histamine.
The procedures of experiments employed in the current study were approved by the Animal Research Policies Committees of Korea University College of Medicine and Korea Institute of Science and Technology. Also, they conformed to the guidelines of National Institutes of Health of the United States of America.
Male C57BL/6 mice (B6 mice, 3–6 week-old) bred in Korea Institute of Science and Technology were used for Ca2+ imaging, Cl− imaging, enzyme immunoassays (EIA) and extracellular single-unit recording experiments. In addition, male knock-out (KO) mice (3–6 week-old) for NKCC1 (Slc12a2−/−) or CFTR (B6.129P2-Cftrtm1Unc/J), obtained from Professor Min Goo Lee at Yonsei University (Seoul, Korea), were used in some of these experiments. Before being used, the mice were housed in group cages (4–6/cage) in a vivarium (22–24 °C) with a 12 h/12 h light/dark cycle for ≥ 1 week. The times of lights-on and -off in the vivarium were designated as zeitgeber time (ZT) 0:00 h and ZT 12:00 h, respectively.
Brain slices were prepared between ZT 10:00 h and ZT12:00 h. Under urethane anesthesia (1.25 g/kg, i.p.), the brain was quickly resected and put in aerated (95 % O2/5 % CO2) ice-cold artificial cerebrospinal fluid (ACSF), which was composed of (in mM) 124 NaCl, 1.3 MgSO4, 3 KCl, 1.25 NaH2PO4, 26 NaHCO3, 2.4 CaCl2 and 10 glucose. After being chilled in the ACSF for 1–2 min, the brain was cut into slices (300–400 μm thickness) in ice-cold ACSF using a vibroslicer (World Precision Instruments or Leica VT100S). The slices containing the SCN were selected and kept in aerated (95 % O2/5 % CO2) ACSF at room temperature (R/T, 30–60 min) before being used for SCN cell dissociation or being transferred to an electrophysiological recording chamber, which was continuously perfused with aerated (95 % O2/5 % CO2) ACSF (35 °C).
The hypothalamic slices incubated in aerated ACSF as above were used for SCN cell dissociation. The procedures for the cell dissociation were identical to those described previously .
The Ca2+ imaging methods employed in this study were identical to those described previously . [Ca2+]i was expressed as the ratio of intensities of the fura-2 emission fluorescence of 510 nm, excited at 340 and 380 nm. All the Ca2+-imaging experiments (as well as Cl−-imaging study, below) were carried out between ZT 13:00 h and ZT 18:00 h.
where F is the fluorescence at each time point and F0 is the average of the fluorescence measured at the first ten time points.
Brain slices (350-μm thickness) were prepared from B6 mice (4 ~ 5 week-old) as described above. After being treated with drugs (see Results) for 30 min starting at ZT 14:00 h, the slices were mounted on a silicon rubber stage chilled with dry-ice powder. The SCN on both the left and right sides were punched out from the frozen section with the use of a blunt needle (21 G) under a dissecting microscope. The SCN punches from each hypothalamic slice were pooled in 0.1-N HCl solution (300 μl) and then sonicated with Bioruptor (COSMO BIO, Japan) at 4 °C. The concentration of cAMP was determined with the use of Cyclic AMP EIA kit (Cayman Chemical, MI) according to the manufacturer's protocol. The protein content was determined with Pierce™ BCA Protein Assay Kit (Thermo scientific, MA). Following centrifugation at 1,000 g for 10 min, the supernatant was diluted 1:2 with EIA buffer (Cayman Chemical). All SCN samples were acetylated prior to the determination of cAMP level by EIA. The assays were performed in duplicate, with measurement at λ = 405 nm on a micro plate reader (SPECTRA max plus 384, Molecular Devices, CA).
On the first day, the slice was treated with histamine for 30 min from ZT 14:00 h. In certain experiments, histamine was applied to the slice along with bumetanide (NKCC blocker), gallein (Gβγ blocker), CFTRinh-172 (CFTR blocker), H89 (PKA blocker) or KT5720 (PKA blocker). The application of these drugs commenced at ZT 13:50 h and lasted for 50 min. Control slices were challenged neither with histamine nor with any of the blockers above.
On the second day, single-unit recordings were obtained extracellularly from the SCN at ZT 1:00–15:00 h. To detect the time at which the peak of circadian firing activity rhythm of SCN neurons occurs (i.e., a reliable marker of the phase of circadian clock ), we plotted against ZT the average firing rates of randomly sampled single units for sequential 2-h periods with 1-h lags . To quantify the phase shift resulting from a drug treatment, we measured the difference of the time-of-peak found in the experimental slice from the average time-of-peak of control slices [12, 25].
Drugs and chemicals utilized in the present study were from Sigma-Aldrich (St. Louis, MO) or Tocris Bioscience (Bristol, UK). The solutions of histamine (100 μM; [26–28]), 2-pyridylethylamine (100 μM; [29–33]) and amthamine (20 μM; [34–36]) were prepared in ACSF or HEPES-buffered saline. The solutions of bumetanide (10 μM; [16, 37, 38]), CFTRinh-172 (50 μM; [39–41]), gallein (100 μM; [42–44]), H89 (10 μM; [45–47]), KT5720 (1 μM; [48–50]), bicuculline (30 μM; [51–53]) and strychnine (1 μM; [54–56]) were prepared by diluting the stock solutions with ACSF or HEPES-buffered saline; the solvent of stock solutions was dimethyl sulphoxide and its final concentration was 0.01–0.003 %. The drug solutions were applied to SCN slices or dissociated SCN cells by peristaltic pump or gravity-fed bath-perfusion system .
Numerical data are expressed as the mean ± SEM. Student t-test and Mann–Whitney Rank Sum test were employed to compare two independent data sets with and without normal distribution, respectively. Paired samples having normal distribution were compared with paired t-test while paired samples without normal distribution with Wilcoxon Signed Rank test. One-way analysis of variance (ANOVA) and pairwise comparison with Student-Newman Keuls tests were performed to compare ≥3 independent data sets having normal distributions, while Kruskal-Wallis one-way ANOVA on ranks and pairwise comparison with Student-Newman Keuls tests were performed to compare ≥ 3 data sets lacking normal distributions. Chi-square test was used to determine whether there is a significant difference between the expected frequencies and the observed frequencies in one or more categories. P < 0.05 (two-sided) was considered significant.
To test our hypothesis, we first examined how the NKCC inhibitor bumetanide affects the histamine (100 μM, 30 s)-elicited rise in [Ca2+] in dissociated SCN neurons and whether NKCC1 KO mouse neurons would show an altered histamine response. Bumetanide (10 μM) attenuated the histamine-elicited Ca2+ rise in 41 of 105 cells (0.54 ± 0.06 to 0.20 ± 0.05) or converted the rise into fall in 40 of 105 cells (0.47 ± 0.04 to −0.31 ± 0.12) (Fig. 1a). In the remaining cells, it did not affect (7 of 105 cells; 0.77 ± 0.09 vs. 0.78 ± 0.09) or enhanced the histamine-elicited Ca2+ increase (17 of 105 cells; 0.32 ± 0.06 to 0.61 ± 0.08) (Fig. 1a). These effects of bumetanide were statistically significant [t(104) = 8.302, p < 0.001, paired t-test]. Likewise, histamine-evoked Ca2+ response was reduced in SCN neurons prepared from NKCC1 KO mice. In the KO mice, histamine application caused Ca2+ rise in 31 % of the neurons (28 of 90 cells from 2 mice) with an average increase of 0.30 ± 0.04 (Δ ratio 340/380). In wild-type mice, histamine application resulted in an increase in Ca2+ level in 60 % of the neurons (116 of 192 cells from 3 mice) with an average increase of 0.50 ± 0.03 (Δ ratio 340/380). Thus, in NKCC1 KO mice, the proportion of cells showing histamine-induced Ca2+ response was significantly reduced [Chi-square(2) = 44.282, p < 0.001, Chi-square test] as well as the average magnitude of the response [U = 2120, p < 0.001, Mann–Whitney Rank Sum test]. Taken together, these results support the hypothesis that histamine induces the efflux of NKCC1-accumulated Cl− in at least a subset of SCN neurons and through that mechanism increases [Ca2+]i.
In order to obtain more direct evidence that histamine causes Cl− efflux in SCN neurons, we next performed Cl−-imaging experiments using the fluorescent Cl− sensor MQAE. Bath application of the H1R agonist 2-pyridylethylamine (100 μM, 30 s) but not the H2R agonist amthamine (20 μM, 30 s), resulted in a reliable decrease in [Cl−]i in a subset of dissociated SCN cells (450 of 1121 cells from 26 mice) (Fig. 1b, left trace); the average peak amplitude of the H1R agonist-induced Cl− response (ΔF) was 0.054 ± 0.003 (n = 450). In the remaining cells, H1R agonist produced either an increase (ΔF = -0.069 ± 0.003, n = 375) (Fig. 1b, right trace), or no change in [Cl−]i (n = 296). After bumetanide (10 μM) treatment, the H1R agonist-induced decrease in [Cl−]i was converted into an increase [n = 81 cells from 4 mice, ΔF = 0.053 ± 0.003 to −0.094 ± 0.003; t(80) = 35.258, p < 0.001, paired t-test)] while the H1R agonist-induced increase in [Cl−]i was enhanced [n = 80 cells from 4 mice, ΔF = -0.038 ± 0.002 to −0.094 ± 0.004; t(79) = 15.929, p < 0.001, paired t-test) (Fig. 1c). Collectively, these results indicate that histamine causes efflux of NKCC1-accumulated Cl− in a subset of SCN neurons.
Previous work suggests that H1R is positively linked to cAMP signaling pathway through the Gβγ protein [18, 19], and it is well known that cAMP is a strong PKA activator [57, 58]. Thus, we next explored the possibility that the Gβγ protein arising from the activation of H1R promotes the cAMP production to activate PKA and ultimately to bring about histamine-induced responses in SCN neurons. To this end, we examined whether H1R activation leads to the increase in cAMP level in the SCN and, if so, the treatment of gallein (Gβγ protein inhibitor) blocks this increase, and whether gallein and the PKA blocker H89 suppress the H1R agonist-elicited Ca2+ and Cl− responses in dissociated SCN cells. We found that application of the H1R agonist 2-pyridylethylamine (100 μM, for 30 min starting at ZT 14:00 h), but not the H2R agonist amthamine (20 μM, for 30 min starting at ZT 14:00 h), resulted in a significant increase in cAMP content in the SCN and this effect was precluded by co-applied gallein (100 μM) [one-way ANOVA: F(3,17) = 3.828, p = 0.029, Student-Newman-Keuls pairwise comparison tests: Control vs. H1R agonist: p = 0.037, Control vs. H2R agonist: p = 0.170; Control vs. H1R agonist + gallein: p = 0.635; H1R agonist vs. H2R agonist: p = 0.289; H1R agonist vs. H1R agonist + gallein: p = 0.043; H2R agonist vs. H1R agonist + gallein: p = 0.153] (Fig. 2). Moreover, we discovered that both gallein (100 μM) and H89 (10 μM) generally suppressed the H1R agonist (100 μM, 30 s)-elicited Ca2+ and Cl− responses (Fig. 3). Thus, taken together, these results suggested that the H1R-Gβγ-cAMP/PKA pathway mediates histamine-elicited responses in SCN neurons.
In order to better understand the histaminergic regulation of Cl− in SCN neurons, we then explored the possible role of CFTR, the PKA-activated Cl− channel. Specifically, we examined the effects of the CFTR inhibitor CFTRinh-172 on histamine (or H1R agonist)-induced responses in SCN cells. We found that the application of CFTRinh-172 (50 μM) blocked both Cl− efflux [ΔF: 0.111 ± 0.035 to 0.003 ± 0.003, n = 41 cells from 4 mice; W = -861, p < 0.001, Wilcoxon Signed Rank test; Fig. 4a and b, left panel] and influx [ΔF: −0.108 ± 0.011 to 0.002 ± 0.002, n = 38 cells from 4 mice; W = 741, p < 0.001, Wilcoxon Signed Rank test; Fig. 4b, right panel] induced by 2-pyridylethylamine (H1R agonist; 100 μM, 30 s) in SCN cells. Furthermore, we discovered that CFTRinh-172 attenuated significantly the histamine (100 μM, 30 s)-elicited Ca2+ rise in SCN neurons [0.53 ± 0.05 to 0.15 ± 0.03, n = 31 cells from 3 mice; t(30) = 6.849, p < 0.001, paired t-test] (Fig. 4c). Collectively, these results indicated that CFTR mediates histamine-induced Cl− fluxes in SCN neurons.
Our previous work has indicated that, in order to reset the circadian clock, histamine raises [Ca2+]i in SCN neurons by activating the CaV1.3 L-type Ca2+ channels through H1R, and secondarily by causing Ca2+-induced Ca2+ release from RyR-mediated internal stores . Meanwhile, the results described above suggest that the Gβγ-cAMP/PKA-CFTR pathway is responsible for linking H1R to L-type Ca2+ channel. To further test this hypothesis, we investigated how the pharmacological blockade or genetic removal of Gβγ, PKA, CFTR or NKCC1 altered the histamine-elicited phase delay of circadian neural activity rhythm in the mouse SCN slice. In the control slices, the peak of the circadian neural activity rhythm occurred at ZT 6.00 ± 0.33 h (n = 6; Fig. 5a and k). In the histamine (100 μM)-treated slices, the peak was phase-delayed about 6 h to ZT 11.67 ± 0.21 h (n = 6; Fig. 5b and k) by the next cycle [6, 12]. This histamine effect on the circadian phase was almost completely blocked by the co-applied inhibitors of Gβγ (gallein, 100 μM), PKA (H89, 10 μM; KT5720, 1 μM), CFTR (CFTRinh-172, 50 μM) and NKCC (bumetanide, 10 μM) (Fig. 5c-f and k), but not by the GABAA receptor antagonist bicuculline (30 μM) or the glycine receptor antagonist strychnine (1 μM) (Fig. 5g, h and k). In addition, the histamine-elicited phase delays were absent in KO mice lacking CFTR and NKCC1 (Fig. 5i-k). In control experiments, we found that application of the blockers alone or the genetic loss of CFTR and NKCC1 did not alter the phase of the circadian rhythm. The time of peak electrical activity of SCN neurons recorded in the slices treated with either gallein [ZT 6.5 ± 0.3 h, n = 4; p = 0.242, t(8) = −1.265, t-test], H89 [ZT 5.8 ± 0.3 h, n = 4; p = 0.610, U = 14.5, Mann–Whitney Rank Sum Test], CFTRinh-172 [ZT 5.5 ± 0.3 h, n = 4; p = 0.242, t(8) = 1.265, t-test] or bumetanide alone [ZT 6.5 ± 0.3 h, n = 4; p = 0.242, t(8) = −1.265, t-test] was not significantly different from that of neurons recorded in drug-untreated, control slices (ZT 6.00 ± 0.33 h, n = 6). Likewise, the time of peak electrical activity of SCN neurons recorded in the slices from CFTR KO [ZT 6.3 ± 0.5 h, n = 4; p > 0.999, U = 12, Mann–Whitney Rank Sum test] or NKCC1 KO mice [ZT 6.0 ± 0.4 h, n = 4; p > 0.999, U = 12, Mann–Whitney Rank Sum Test] was not significantly different from that of neurons recorded in the slices from wild-type animals (ZT 6.00 ± 0.33 h, n = 6). Thus, taken together, the results from the functional assay further supported our hypothesis that the Gβγ-cAMP/PKA-CFTR pathway links H1R to CaV1.3 L-type Ca2+ channels in SCN neurons, leading to the resetting of the circadian clock (Fig. 6).
In a recent communication  we reported that, in order to reset the circadian clock in the mouse SCN, histamine increases [Ca2+]i in SCN neurons by activating the CaV1.3 L-type Ca2+ channels through H1R, and secondarily by causing Ca2+-induced Ca2+ release from RyR-mediated internal stores. Moreover, we provided evidence that IP3 and DAG, the downstream of PLC, are not involved in the H1R-mediated rise in [Ca2+]i. In the current study, we explored the signaling mechanism that links the H1R to the CaV1.3 channels and obtained the results indicating that, in a subset of SCN neurons loaded with Cl− by NKCC1, histamine causes Cl− efflux through H1R to produce membrane depolarization needed for the activation of CaV1.3 channels. CFTR is well known as anion channel whose malfunction leads to dysregulation of epithelial fluid transport in the lung, pancreas and other organs, resulting in cystic fibrosis [22, 24, 59]. In this study, we present evidence that CFTR mediates the histamine-elicited Cl− efflux in SCN cells while the Gβγ-cAMP/PKA pathway downstream of H1R activates the CFTR. Studies have provided evidence that histamine-activated Cl− channels are expressed in mammalian brain [13, 14] and that CFTR mRNA exists in the mouse SCN (, http://www.brain-map.org). Also, it has been reported that H1R is positively coupled through the Gβγ protein to the cAMP signaling pathway [18, 19], which can activate CFTR by up-regulating PKA [20–24]. Nevertheless, the H1R-mediated signaling pathway that involves CFTR has never been reported. To the best of our knowledge, the current study is the first to provide the evidence for the existence of such a signaling pathway. Also, this study is the first to present evidence indicating that CFTR has a functional role in the circadian time-keeping system.
In the current study we noticed that, even after the blockade of CFTR, a significant proportion of SCN neurons still responded to histamine with an increase in [Ca2+]i although the magnitudes of the responses were significantly smaller. This finding suggests that mechanism(s) other than the membrane depolarization arising from CFTR-mediated Cl− efflux also contributes to the L-type Ca2+ channel activation by histamine. The possible mechanisms include the direct activation of the Ca2+ channel by PKA [60–63] and the blockade of leak K+ channels through the H1R-coupled Gq/11 protein , which can produce the membrane depolarization needed for the activation of the Ca2+ channels. Whether these mechanisms operate in SCN neurons for the histaminergic activation of L-type Ca2+ channels and, if so, whether they work along with the "CFTR" mechanism in the same cells await further investigation.
The results of the current study indicate that NKCC1 is crucial for the histamine-elicited increase in [Ca2+]i in SCN neurons and the subsequent resetting of the circadian clock in the SCN. By importing Cl−, NKCC1 provides the driving force for the histamine-elicited Cl− efflux through CFTR which produces membrane depolarization needed for the activation of L-type Ca2+ channels. Our data do not suggest that histamine effects depend on GABAergic and/or glycinergic transmission, the polarity and strength of the postsynaptic responses of which can be regulated by NKCC1. This view is consistent with the finding that histamine caused [Ca2+]i to rise in dissociated SCN neurons which were no longer under synaptic control. Moreover, it is consistent with the observation that both bicuculline and strychnine had no significant effects on the histamine-elicited phase delay of the circadian neural activity rhythm in the SCN slice.
The present study demonstrates that, in certain SCN cells (~33 % cells examined), H1R activation led to Cl− influx, instead of efflux. This is presumably because of that, in these cells, the NKCC1 activity was low or absent such that the electrochemical gradient for Cl− was set toward the intracellular side. At present, we do not know the functional significance of the histamine-induced Cl− influx. However, it is unlikely that this Cl− flux promoted histamine to phase-delay the circadian pacemaker in the SCN, since the blockade of NKCC1 by bumetanide, which converted the H1R agonist-induced Cl− efflux into influx in some cells and enhanced the H1R agonist-induced Cl− influx in other cells, resulted in a complete blockade of the histamine-elicited phase shift.
A variety of evidence indicates that histamine is a potent regulator of the phase of the circadian system. Prior work has shown that histamine application onto SCN neurons in the rat and hamster hypothalamic slices increases or decreases the electrical activities of these cells [64–66] while bath-applied histamine phase-shifts the circadian neural activity rhythms recorded in hamster and mouse SCN slices [6, 7, 27]. The inhibition of histamine synthesis by α-fluoromethylhistidine decreases the phase shifts of circadian activity rhythms induced by light in the hamster . Injection of histamine into the cerebral ventricle in the rat leads to the phase shifts of circadian activity rhythms  and decreases the time needed to entrain activity rhythms to an abruptly advanced light–dark cycle . In our own work, we demonstrated that histamine acts on H1R to alter the phase of the circadian clock in the mouse SCN and this effect depends on the increase of [Ca2+]i which results from the activation of CaV1.3 L-type Ca2+ channels and Ca2+-induced Ca2+ release from RyR-mediated internal stores . In the present study, we further explored the signal transduction mechanisms and present evidence that the Gβγ-cAMP/PKA-CFTR pathway is intercalated between H1R and the L-type Ca2+ channels. These results clearly delineate a novel signaling mechanism that underlies the histamine-induced resetting of the circadian clock.
More broadly, there are many remaining questions about the role of histamine in the generation of circadian rhythms in vivo and the functional significance of the phase control remains unclear. Among the complications is evidence for species-specific differences as Scott et al.  showed that the hamster SCN is almost devoid of histaminergic fibers and that histamine has only a weak phase-shifting effect on the free-running locomotor activity rhythm. In addition, the inhibition of histamine synthesis by α-fluoromethylhistidine or the KO of histidine decarboxylase gene disrupted the circadian activity rhythm in the rat  and lowered the levels of wheel-running and spontaneous locomotor activities in mice in both light–dark and dark-dark conditions . These findings raise the possibility that histamine may be involved in the generation of the rhythms as well as phase control. The receptor mediating these effects is less clear. Studies on H1R KO mice found disrupted diurnal feeding rhythm  but essentially normal locomotor activity rhythms . In contrast, the H3R KO mice exhibited a greatly reduced locomotor activity rhythm but normal rhythms in clock gene expression . Unfortunately, the studies with the KO mice did not examine whether these genetic manipulations altered the photic regulation of the circadian cycle. Taken together, these data indicate that histamine is a potent regulator of the circadian time-keeping system in some mammals and suggest that the H1R signaling is important for phase control while the H3R signaling may be more important for regulation of the amplitude of circadian rhythms in activity.
In summary, we present experimental results indicating that, in order to activate Ca 1.3 L-type Ca channels in SCN neurons and ultimately to phasedelay the circadian clock in the SCN, histamine recruits the H1R-G -cAMP/PKACFTR pathway in the SCN neurons loaded with Cl by NKCC1. This pathway and NKCC1 may well be potential targets for drugs designed to treat clinical problems resulting from the disturbance of the circadian system.
The experimental procedures employed in the present study were approved by the Animal Research Policies Committees of Korea University College of Medicine and Korea Institute of Science and Technology.
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) to Y. I Kim (NRF-2011-0022529 and No. 2014R1A2A1A11049900) and Korea University Grant (K1031781; Y.I.K), and by KIST institutional program, Project No. 2E25210 (C.J.L.), and Brain Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning, NRF-2012M3C7A1055412 (C.J.L.), and WCI Program of National Research Foundation (C.J.L.). Y.S.K., Y.-B.K., W.B.K., S.W.L. and Y.I.K. were supported by the Brain Korea 21 Project from 2009 to 2014. Y.S.K. and C.S.C received support from the O'Keefe Foundation.
Y.S.K., S.B.O., H.C.H., C.S.C., C.J.L. and Y.I.K. conceived this project. Y.S.K., Y.-B.K., W.B.K. and S.W.L. performed the experiments and analyzed the results. Y.S.K., C.S.C. and Y.I.K. wrote the manuscript. All authors read and approved the final manuscript.


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Spice Girls musical Viva Forever to open at the Piccadilly Theatre
Brand new musical Viva Forever! based on the songs of the Spice Girls comes to London in November 2012.
Viva Forever!, a brand new show that features the songs of the Spice Girls, one of the world's most successful girl groups, will open at the Piccadilly Theatre in London in November 2012. Produced by Mamma Mia! producer Judy Craymer, Viva Forever! will have a book by Ab Fab's Jennifer Saunders.
The show will be directed by Paul Garrington, who is closely associated with Judy Craymer's Mamma Mia! having directed productions in Germany, Sweden, Holland, Korea, Japan, Spain and Russia, and shows including The Pet Shop Boys musical Closer the Heaven.
Viva Forever! is a modern fable of camaraderie, love and loyalty based on the songs of the Spice Girls.
The Spice Girls launched their brand new musical Viva Forever!, coming to the West End's Piccadilly Theatre this November.
Featuring 16 of the Spice Girls' greatest hits, the show follows the highs and lows of a mother and daughter as they work their way through a TV reality singing contest. The show is set against the unforgettable songs of the world's greatest ever girl band, including Spice Girls hits Wannabe, Say You'll Be There, Mama, Stop and of course the title song, Viva Forever.
The Spice Girls launch the new musical Viva Forever! based on 16 of their songs
Book tickets to Viva Forever! at the Piccadilly Theatre in London
👤Paul Raven 📅26 June 2012
Tags: Jennifer Saunders, Judy Craymer, Paul Garrington, Piccadilly Theatre, Spice Girls, The Spice Girls, Viva Forever
Stars on the West End stage in London in 2022
Moulin Rouge! The Musical sets new West End premiere date for January 2022
Liisi LaFontaine to headline 'Moulin Rouge! The Musical' in London's West End
Jennifer Saunders
Jennifer Saunders to return to West End in 'Blithe Spirit' this September


In the second plot is the same quantity, this time for the most recent 4 hours and using the maximum time resolution of 15 seconds.
In the third plot, the bottom panel ("ch2") is again the 1 to 500 Angstrom SEM channel, but without any background subtraction. The top panel ("ch4") is the first-order SEM channel with a passband of 304 +- 40 Angstroms. This channel responds primarily to the very strong Helium 304 line, but is also sensitive to some 'hotter' lines (i.e., lines enhanced during solar events) in its passband, and can also be sensitive to background produced by energetic flare particles. For a rough indicator of the current flare background, see our PM flare plot. Other near-real time flare monitors are available from ACE/SIS and Soho/ERNE.
The SEM home page has a description of the SEM instrument. SEM is part of the CELIAS instrument package on the SOHO spacecraft. The SEM was designed and constructed by USC (Darrell Judge, Don McMullin, Howard Ogawa and colleagues), and is integrated into the CELIAS/STOF sensor (M. Hilchenbach, Lead Co-I). D. Hovestadt and E. Moebius were instrumental in getting the SEM added to the SOHO instrument payload. The data processing and presentation on this web page are courtesy the CELIAS/MTOF crew at U of Md.


JERUSALEM, Israel--(HSMN NewsFeed)--Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA ) announced today that it has begun commercially shipping Bupropion Hydrochloride Extended-Release Tablets, 150 mg, the generic version of Biovail Corporation's antidepressant Wellbutrin XL® Tablets, pursuant to its March 2007 agreement with Anchen Pharmaceuticals, Inc.
Wellbutrin XL® Tablets, 150 mg, marketed by GlaxoSmithKline, had U.S. sales of approximately $930 million for the 12 months ended March 2008, according to IMS data.
Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the world's leading generic pharmaceutical company. The Company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients, as well as animal health pharmaceutical products. Over 80 percent of Teva's sales are in North America and Europe.
This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause Teva's future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: Teva's ability to accurately predict future market conditions, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic versions of Allegra®, Neurontin®, Lotrel®, Famvir® and Protonix®, Teva's ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which Teva may obtain U.S. market exclusivity for certain of its new generic products and regulatory changes that may prevent Teva from utilizing exclusivity periods, competition from brand-name companies that are under increased pressure to counter generic products, or competitors that seek to delay the introduction of generic products, the impact of consolidation of our distributors and customers, the effects of competition on our innovative products, especially Copaxone® sales, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, the regulatory environment and changes in the health policies and structures of various countries, our ability to achieve expected results though our innovative R&D efforts, Teva's ability to successfully identify, consummate and integrate acquisitions (including the pending acquisition of Bentley Pharmaceuticals, Inc.), potential exposure to product liability claims to the extent not covered by insurance, dependence on the effectiveness of our patents and other protections for innovative products, significant operations worldwide that may be adversely affected by terrorism, political or economical instability or major hostilities, supply interruptions or delays that could result from the complex manufacturing of our products and our global supply chain, environmental risks, fluctuations in currency, exchange and interest rates, and other factors that are discussed in Teva's Annual Report on Form 20-F and its other filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made and the Company undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.


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Search - Let Me Go
Author: Helga Schneider
Unforgettable and deeply arresting, Let Me Go is a haunting memoir of World War II that "won't let you go until you've finished reading the last page" (The Washington Post Book World). In 1941, in Berlin, Helga Schneider's mother abandoned her along with her father and younger brother. Let Me Go recounts H... more »elga's final meeting with her ailing mother in a Vienna nursing home some sixty years after World War II, in which Helga confronts a nightmare: her mother's lack of repentance about her past as a Nazi SS guard at concentration camps, including Auschwitz, where she was responsible for untold acts of torture. With spellbinding detail, Schneider recalls their conversation, evoking her own struggle between a daughter's sense of obligation and the inescapable horror of her mother's deeds. « less
Buy New (Paperback): $11.69 (save 16%) or
Publisher: Penguin (Non-Classics)
Taunya H. (BlueskyinMaine) reviewed Let Me Go on 3/1/2007 + 14 more book reviews
This is a very interesting true story. The woman who wrote it is a journalist living in Italy; she finds out that her aged mother, who left the family when the author was a young girl, was a Nazi SS guard in the concentration camps.
Read All 1 Book Reviews of "Let Me Go"
Biographies & Memoirs >> General
Biographies & Memoirs >> Specific Groups >> Women
History >> Jewish >> Holocaust


Lights quickly ? full flames in less than 5 minutes and burns up to 3 hours. Burns 80% cleaner than wood. Use in an indoor, open hearth fireplace or outdoor fireplace or fire pit. UL approved safety classification for use in UL-listed factory built fireplaces. Chimney Safety Institute of America Accepted Product. Lights fully in less than 5 minute. Lights quickly ? full flames in less than 5 minutes and burns up to 3 hours.


BACKGROUND: The purpose of this study was to explore nurses' attitudes to the barriersof patient education as a right for getting information based on work situation of nurses, educational facilities in hospitals, and patients' situation.
METHODS: The study was conducted using a cross-sectional design. The populations consisted of 240 nurses affiliated in the Educational Hospitals. The data were gathered by a questionnaire. Demographicvariables and three domains were studied. Twenty questions were about their working situation, 4 questions about hospital educating facilities, and 12 questions were about patients' situation in hospital. The type and frequency of educationbarriers were evaluated, and variables associated with reportingan obstacle were analyzed.
RESULTS: In our questionnaire, we used a Likert scale for determining severity of three domains as the barriers of patient education that ranged from 0 to 4. Generally, it was obvious that educational condition in our hospitals was not good and most of the nurses believed that patient education is not their duties, facilities in hospitals are not sufficient and shortness of time is the most important cause of insufficiency of patient education.
CONCLUSIONS: The interactions of patient, physician and systemicfactors have implications for the implementation of patient education. The failure of adequate patient education maybe attributed to the lack of patient adherence, the failure of nurses'knowledge and skill level or the insufficient funding and organizationof necessary programs in the current health care system.
KEY WORDS: Attitude, health barriers, educational hospitals, Urmia.


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Michelle Hubenschmidt
Teacher Programs Manager
Michelle Hubenschmidt joined the Ashbrook Center in 2014 as a Teacher Programs Manager. She holds a Bachelor of Arts in History and Secondary Education from the University of Michigan. She taught 18 years in Polk County, Florida, where she created the Advanced Placement curriculum for History and Government and directed many programs for new and seasoned teachers in areas of classroom management, curriculum and clinical supervision. She is a National Board Certified Teacher and holds a master's degree in education from Cambridge College. Michelle received the James Madison Fellowship in 2010 and went on to earn a Master of American History and Government degree in 2012 from Ashland University. In 2013 the Sons of the American Revolution conferred their National History Teacher of the Year to her and she also received the 2013 Florida State History Teacher of the Year from the Florida Daughters of the American Revolution.


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Cambridge Analytica Researcher Responsible for Facebook Data Scraping Speaks Out
24 Apr Cambridge Analytica Researcher Responsible for Facebook Data Scraping Speaks Out
In an interview last Monday, the Cambridge University researcher who scraped information on millions of Facebook users aired his side and said that the accusations against him were a little bit misleading.
Aleksandr Kogan said that he did not carry out a hack, but instead merely "ordered" the data from Facebook which was a key feature of the system. He further revealed that Cambridge Analytica approached him in 2014 about his app and said that it will be adapted for commercial use without violating Facebook's rules.
In relation to his Russian roots and work ties, Kogan added that his accusers are being xenophobic as he only has a loose affiliation with a Russian university and nothing more. He also denied claims that he had anything to do with Russian interference with the US election.
Source: ABC News
Aleksandr Kogan, Cambridge University, Facebook


This thoughtfully designed home takes full advantage of the captivating views of the river/waterway and the Heritage Plantation Marina. Beautiful hardwood flooring is throughout the living, dining and breakfast areas. The inviting living room offers a wood burning fireplace (could easily be converted to gas) and French Doors overlooking an amazing sunroom and deck. The kitchen has rich wood cabinets that are complimented by dark granite counter tops and terra-cotta tile. Stainless appliances and a glass top range are sure to please the chief in the family. The kitchen is conveniently located between the formal dining area and the breakfast area. The Carolina room/sun room is a nature lovers dream. A beautiful spacious master retreat with private deck, en-suite bath and a generously sized walk-in closet round off a perfect first floor. Upstairs you find and awesome game room with a wet bar, wine cooler and refrigerator! The open deck takes full advantage of the all-encompassing views. Also, upstairs are two private guest rooms, a full bath and a large bonus room! The Heritage Plantation Owner's Clubhouse offers a 75 ft. pool, fitness area, hot tub and four Har-Tru clay tennis courts. There is a spectacular community-owned marina with a large party deck overlooking the Intra-coastal Waterway. For the boating enthusiast, there are wet slips, a ramp and dry storage. The Heritage Golf Club is consistently in the top 100 public golf courses.


Donohue moves the story of Orpheus and Eurydice to Quebec for this wondrously strange and dark tale of a woman turned into a puppet and her husband's search for her, even as he is suspected by the police. With its puppets that come to life between midnight and dawn, this is a rich tale drawing on myth and folklore – and the story of photographer Eadweard Muybridge.
Noted literary author Fowler presents 20 stories – ten fantasy, ten SF – from 2015 for this best-of-the-year anthology covering works from the US and Canada. The impressive roster of authors includes Sofia Samatar, Kelly Link, Catherynne M. Valente, Salman Rushdie, and Ted Chiang.
Le Guin's insightful non-fiction can be as intriguing as her SF, and this collection of recent work provides plenty of examples with 68 pieces, including talks, essays, book reviews and introductions, a poem, and a foreword on writing non-fiction.
Liu, one of China's most-respected SF authors, wraps up his epic Three-Body trilogy with this volume. Fifty years after the Doomsday Battle, Earth is profiting from the knowledge of their alien former enemies, who are themselves adopting aspects of Earth culture, but a long-forgotten program threatens the balance between the two worlds. Translated from the Chinese by Ken Liu.
Liu returns with the second book in his epic ''silkpunk'' fantasy series, the Dandelion Dynasty, drawing on the legends and history of ancient China. Former con man Kuni Garu, having ruled as Emperor Ragin for almost ten years, struggles to hold his empire together and maintain progress against intrigue, unrest, an unexpected invasion, and the schemes of his own grown children.
The fifth young-adult novel in Nix's highly popular Old Kingdom series follows Abhorsen-in-waiting Lirael, who finds her old friend Nicholas Sayre tainted with Free Magic and seeks help for him from the librarians of the Clayr, with whom she grew up; meanwhile, a messenger from the far north undertakes a desperate journey to reach Lirael with vital information.
Vassa braves a strange, chicken-legged, dancing store late at night, despite knowing that few customers leave alive, in this wonderfully warped and somewhat surreal young-adult fantasy. Based loosely on the Russian fairy tale of ''Vassilissa the Beautiful'', this quirky tale has the witch Baba Yaga running a chain of all-night stores in a city where the nights get mysteriously longer and longer.
Willis's latest novel is near-future SF in screwball romantic comedy mode – with touches of suspense and social satire, exploring what happens when you have too much connectivity. Briddey Flannigan gets a procedure to increase her emotional awareness of her boyfriend, but somehow develops a sort of telepathy that quickly becomes a curse. ''Crosstalk is a virtuoso performance that isn't just for show: both daffy and deep.'' [Faren Miller] Published 9/16 in the UK by Gollancz.


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La Mesa Names Billings To Head Fixed Operations
By: RVBusiness|Published on: May 3, 2018|Categories: Today's Industry News| 0 comments
Keith Billings
La Mesa RV Center announced the recent appointment of Keith Billings to the role of director of fixed operations for the corporation. In his new position, he will be directly responsible for all fixed operations of La Mesa RV relating to the service and parts departments.
According to a press release, Billings was involved in franchised auto dealer fixed operations for over 30 years, beginning his career as a lot porter while in high school. Most recently, he was affiliated with the Berkshire Hathaway Automotive Group having moved through all departments within that organization.
Billings stated, "While automotive has been my life, I'm grateful for this new opportunity in a related field. I see many parallels that the automotive industry has brought forward that we can now incorporate into the operations at La Mesa RV. I predict some very exciting developments to be announced by this forward thinking and progressive organization."
Bob Upton, president of La Mesa RV, commented, "We're excited and pleased to have someone with Keith's caliber and background join our organization. Our goal is to always provide an outstanding customer experience and with Keith's talents we're prepared to raise the bar to the next level."
Billings hails from Chicago but has been a resident of the Phoenix, Ariz., area after moving to the city as a child.
La Mesa RV currently operates 11 locations including San Diego and Davis, Calif.; Quartzsite, Phoenix, Mesa and Tucson, Arizona, Albuquerque, N.M., and Daytona Beach, Sanford, Port Saint Lucie and Fort Myers, Fla. Additional information about the company and products it offers can be found online at www.lamesarv.com.


Hardcover. London, Blackie & Son Limited, reprint, No date, Book: Good, Dust Jacket: Fair, No pub. date stated, but estimated ca 1950. Color illustrations by Cicely M. Barker. Wear, rubbing and tape repair to price clipped dust jacket with chunks missing from rear cover and lower front cover. Protected by mylar cover. Faint foxing to end papers and on a handful pages and plates.


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Wake Forest Seals Third Straight Title With Late Safety Over Vance
4:30 PM Justin
DURHAM, NC - The Wake Forest Cougars wrapped up a third consecutive perfect season with a 9-7 win in a defensive struggle for the 4AA State Championship with a tough Zebulon B. Vance team. Wake Forest nipped Vance with a safety in the final minute of the fourth quarter, surging into the lead for the first time late in the game and securing their 45th consecutive win.
Vance jumped into the lead on the second play of the game when Nyier Clark hauled in a 53-yard pass for a touchdown from Nigel Summerville to give Vance the lead 7-0 just 23 seconds into the ball game.
The two-time defending 4AA Champions from Wake Forest did not stay behind long, as after the teams traded possessions, Wake Forest mounted a 13 play, 52-yard drive that chewed up 5:45 off the first quarter clock. In typical Wake Forest fashion, the sustained drive was capped off by a three-yard touchdown run by Marquel Haywood, knotting the game at 7 with 1:36 to go in the first quarter.
4AA MVP Mateo Sudipo
Neither team scored for the balance of the game, with two defenses locked in a tightly contested field position battle for much of the rest of the game. In the closing minutes, the field position flipped in favor of the Wake Forest side when a 22-yard field goal attempt to potentially win the game was blocked by Vance and recovered by Vance at their own two-yard line.
In the shadow of their own goalposts, Vance mishandled the ball in the end zone, and in the chaos that ensued, the Wake Forest defense swarmed to the ball, tackling the quarterback in the end zone with just 32 seconds left for a safety and the decisive two points, lifting Wake Forest to a 9-7 win.
Vance was led by Most Outstanding Defensive Player Solomon Sutton, Jr. who had eight tackles in the game. Nyier Clark was chosen as the Most Outstanding Offensive Player for Vance with his five receptions for 78 yards and the lone Vance touchdown.
Wake Forest quarterback Mateo Sudipo was named the game's Most Valuable Player with his 8 for 15 performance amassing 71 yards on the night. Sudipo also intercepted a pass on the night, returning it for 46 yards and had a pass break up. The Most Outstanding Offensive player for Wake Forest was Maquel Haywood who rushed ten times for 20 yards and the lone Wake Forest touchdown of the game. Chance Smith was tapped as the Most Outstanding Defensive Player from Wake Forest, leading the team with seven tackles including one sack.
Story and photos courtesy of the NCHSAA
Posted in: 4AA , Cougars , NCHSAA , NCHSAAFB , NCHSFB , state championship , Vance , Wake Forest , Wallace Wade Stadium


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