Author Mark O'Connell visited preppers, paranoiacs and prophets worldwide for "Notes From an Apocalypse." Now he says "the world will go on."

Speaking to Variety, Olivia Munn detailed director Bryan Singer's unprofessional behavior while filming the 2016 blockbuster "X-Men: Apocalypse."

Pearl Jam didn't intend for their new album, "Gigaton," to be a coronavirus hymnal. Yet it rises to the occasion with glimmers of hope, resilience and even ecstasy.

"Betty," the new series from "Skate Kitchen" and "The Wolfpack" director Crystal Moselle, premieres Friday on HBO.

One person died after the collapse of a well that was under construction in the 4900 block of W. Road 225 N. in Bargersville.

Take Away English reports on the total solar eclipse? Did you witness this extremely rare event?

Writer Chris Terrio has responded to the controversy in interviews, pointing to issues over cut scenes between Rose Tico (Tran) and Leia (Carrie Fisher).

The true star of “Resident Evil 3” is its supurb graphics engine.

Conservatives had this Common Core thing all wrong, it was said. We’d be proven wrong by history. Common Core, pushed by President Barack Obama, was going to work. It wasn’t like all the other liberal education plans. A new study by the Pioneer Institute reveals that, no, we were right all along. The study, released…

The post New Study Confirms We Were Right: Reading, Math Scores Have Collapsed Thanks to Obama, Common Core appeared first on The Western Journal.

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research

7 May 2020 , Volume 96, Number 3

7 May 2020 , Volume 96, Number 3

M. M. Kapustei and P. V. Slyusarchuk
Theor. Probability and Math. Statist. 99 (2020), 101-111.
Abstract, references and article information

(American Chemical Society) When a dead body is found, one of the first things a forensic pathologist tries to do is estimate the time of death. There are several ways to do this, including measuring body temperature or observing insect activity, but these methods don't always work for corpses found in water. Now, researchers are reporting a mouse study in ACS' Journal of Proteome Research showing that certain proteins in bones could be used for this determination.

Quentin Perraud
Apr 1, 2020; 19:589-607
Research

Bacteria secrete siderophores to access iron, a key nutrient poorly bioavailable and the source of strong competition between microorganisms in most biotopes. Many bacteria also use siderophores produced by other microorganisms (exosiderophores) in a piracy strategy. Pseudomonas aeruginosa, an opportunistic pathogen, produces two siderophores, pyoverdine and pyochelin, and is also able to use a panel of exosiderophores. We first investigated expression of the various iron-uptake pathways of P. aeruginosa in three different growth media using proteomic and RT-qPCR approaches and observed three different phenotypic patterns, indicating complex phenotypic plasticity in the expression of the various iron-uptake pathways. We then investigated the phenotypic plasticity of iron-uptake pathway expression in the presence of various exosiderophores (present individually or as a mixture) under planktonic growth conditions, as well as in an epithelial cell infection assay. In all growth conditions tested, catechol-type exosiderophores were clearly more efficient in inducing the expression of their corresponding transporters than the others, showing that bacteria opt for the use of catechol siderophores to access iron when they are present in the environment. In parallel, expression of the proteins of the pyochelin pathway was significantly repressed under most conditions tested, as well as that of proteins of the pyoverdine pathway, but to a lesser extent. There was no effect on the expression of the heme and ferrous uptake pathways. Overall, these data provide precise insights on how P. aeruginosa adjusts the expression of its various iron-uptake pathways (phenotypic plasticity and switching) to match varying levels of iron and competition.

7 May 2020 , Volume 96, Number 3

The lessons of COVID-19 are yet to crystallise, but the evidence so far has yielded some early insights of developments that are likely to shape the national and global agenda for the immediate future. The speed and scale of the spread of the...

OBJECTIVE

To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice.

On May 9, 1980, a Liberian freighter rammed a bridge in Florida's Tampa Bay, collapsing part of the span and dropping 35 people to their deaths.

Darren Sammy and Devendra Bishoo shared five wickets to trigger India's collapse on the second day of the opening Test against the West Indies in New Delhi.

Rockville, Maryland : National Institute on Drug Abuse, 1986.

Pier Luigi Conti, Daniela Marella, Fulvia Mecatti, Federico Andreis.

Source: Bernoulli, Volume 26, Number 2, 1044--1069.

Abstract:
In this paper, a class of resampling techniques for finite populations under $pi $ps sampling design is introduced. The basic idea on which they rest is a two-step procedure consisting in: (i) constructing a “pseudo-population” on the basis of sample data; (ii) drawing a sample from the predicted population according to an appropriate resampling design. From a logical point of view, this approach is essentially based on the plug-in principle by Efron, at the “sampling design level”. Theoretical justifications based on large sample theory are provided. New approaches to construct pseudo populations based on various forms of calibrations are proposed. Finally, a simulation study is performed.

KM Harris
Jul 1, 1992; 12:2685-2705
Articles

Thomas Schikorski
Aug 1, 1997; 17:5858-5867
Articles

Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted PET along with postmortem assays to investigate time course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from [¹¹C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in nontransgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[¹¹C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory, but not excitatory, synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits. Our findings indicate that tau-induced disruption of the inhibitory synapse may be a critical trigger of progressive neurodegeneration, resulting in massive neuronal loss, and PET assessments of inhibitory versus excitatory synapses potentially offer in vivo indices for hyperexcitability and excitotoxicity early in the etiologic pathway of neurodegenerative tauopathies.

SIGNIFICANCE STATEMENT In this study, we examined the in vivo status of excitatory and inhibitory synapses in the brain of the rTg4510 tauopathy mouse model by PET imaging with (E)-[¹¹C]ABP688 and [¹¹C]flumazenil, respectively. We identified inhibitory synapse as being significantly dysregulated before brain atrophy at 2 months of age, while excitatory synapse stayed relatively intact at this stage. In line with this observation, postmortem assessment of brain tissues demonstrated selective attenuation of inhibitory synaptic constituents accompanied by the upregulation of cFos before the formation of tau pathology in the forebrain at young ages. Our findings indicate that selective degeneration of inhibitory synapse with hyperexcitability in the cortical circuit constitutes the critical early pathophysiology of tauopathy.

Nitric oxide (NO) is an important signaling molecule that fulfills diverse functional roles as a neurotransmitter or diffusible second messenger in the developing and adult CNS. Although the impact of NO on different behaviors such as movement, sleep, learning, and memory has been well documented, the identity of its molecular and cellular targets is still an area of ongoing investigation. Here, we identify a novel role for NO in strengthening inhibitory GABA_A receptor-mediated transmission in molecular layer interneurons of the mouse cerebellum. NO levels are elevated by the activity of neuronal NO synthase (nNOS) following Ca²⁺ entry through extrasynaptic NMDA-type ionotropic glutamate receptors (NMDARs). NO activates protein kinase G with the subsequent production of cGMP, which prompts the stimulation of NADPH oxidase and protein kinase C (PKC). The activation of PKC promotes the selective strengthening of α3-containing GABA_ARs synapses through a GABA receptor-associated protein-dependent mechanism. Given the widespread but cell type-specific expression of the NMDAR/nNOS complex in the mammalian brain, our data suggest that NMDARs may uniquely strengthen inhibitory GABAergic transmission in these cells through a novel NO-mediated pathway.

SIGNIFICANCE STATEMENT Long-term changes in the efficacy of GABAergic transmission is mediated by multiple presynaptic and postsynaptic mechanisms. A prominent pathway involves crosstalk between excitatory and inhibitory synapses whereby Ca²⁺-entering through postsynaptic NMDARs promotes the recruitment and strengthening of GABA_A receptor synapses via Ca²⁺/calmodulin-dependent protein kinase II. Although Ca²⁺ transport by NMDARs is also tightly coupled to nNOS activity and NO production, it has yet to be determined whether this pathway affects inhibitory synapses. Here, we show that activation of NMDARs trigger a NO-dependent pathway that strengthens inhibitory GABAergic synapses of cerebellar molecular layer interneurons. Given the widespread expression of NMDARs and nNOS in the mammalian brain, we speculate that NO control of GABAergic synapse efficacy may be more widespread than has been appreciated.

As a result of the pandemic, USPS, which has run at a loss for years, is even more cash-strapped. It expects to lose $2 billion each month during the pandemic. That prompted Postmaster General Megan Brennan to ask Congress for $50 billion in funds -- $25 billion to offset lost revenue from declining mail volume due to the pandemic, and another $25 billion for modernization.

Bank of Spain Working Papers by Henrique S. Basso and Juan F. Jimeno

Pertussis is a poorly controlled vaccine-preventable disease. Verifying outbreaks is challenging owing to nonspecific clinical presentations and imperfect diagnostic tests. Exclusive reliance on highly sensitive polymerase chain reaction has been associated with pseudo-outbreaks.

Contamination of specimens with vaccine derived Bordetella pertussis DNA from pediatric clinic surfaces likely resulted in misdiagnoses. Standard practices, liquid transport medium, and lack of polymerase chain reaction cutoffs for discerning weakly positive (contaminant) DNA are contributory, but modifiable factors. (Read the full article)

Former Newcastle defender Philippe Albert reveals the tactics of the English club's memorable victory against Barcelona in 1997.

Objectives: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Yet, data of which combinations are most effective is lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa.

Methods: We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, meropenem, minocycline, rifampicin, temocillin, thiamphenicol or trimethoprim by automated time-lapse microscopy using predefined cut-off values indicating inhibition of growth (≤10⁶ CFU/mL) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments.

Results: All strains were intermediate or resistant to polymyxin B, anti-pseudomonal β-lactams, ciprofloxacin and amikacin. Genes encoding β-lactamases (e.g., bla_PAO and bla_OXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol and trimethoprim. Time kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem.

Conclusion: Positive interactions were frequently found with the tested combinations, also against strains that harboured several resistance mechanisms to the single drugs and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.

Many transferable quinolone-resistance mechanisms have been already identified in Gram-negative bacteria. The plasmid-encoded 65 amino-acid long ciprofloxacin-modifying enzyme, namely CrpP, was recently identified in Pseudomonas aeruginosa. We analyzed a collection of 100 clonally-unrelated and multidrug-resistant P. aeruginosa clinical isolates among which 46 (46%) were found positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. Those crpP-like genes were chromosomally located, as part of PAGI-like pathogenicity genomic islands.

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MIC_{ciprofloxacin} 0.25 mg/L, MIC_meropenem 2 mg/L) and CW44 (MIC_{ciprofloxacin} 0.5 mg/L, MIC_meropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log₁₀ CFU/mL) and biofilm (>8log₁₀ CFU/cm²) bacteria at 120h (MIC_{ciprofloxacin} up to 8 mg/L, MIC_meropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log₁₀ CFU/mL and ≤6log₁₀ CFU/cm² at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.

By Bishop Arthur Serratelli

Beneath the soil of every continent lie buried the ruins of fallen civilizations. The Sumerians, Akkadians, Mayans, Assyrians, Babylonians, Minoans, Romans: all of them, faded memories of past grandeur and glory. History records the collapse of at least thirty-two major civilizations that once thrived and prospered before our time. 

No great civilization is built in a day. No great civilization disappears in a single instant. Historians try to explain how these civilizations once so great have slowly vanished into the dustbin of history. Weather, economics, population decline, wars, politics are some of the reasons that they offer. But, ultimately, a civilization disappears when it loses its identity, forfeits its unity and jettisons its commitment to the common good.

Today’s relentless front-page news reports of scandal and sin (many times, stale news served up as current), the incessant discord of our politicians, the unending string of acrimonious tweets, and the rage of angry voices make one wonder whether or not we are facing the decline of our own civilization. Has our unity as a nation become so fragmented that it cannot be repaired?

The TV sitcoms, the talk shows, the din of warring cable news channels do little to promote serious discourse. Rather, they seem at times to make us despair of receiving unbiased reporting. They hardly inspire us to respond to the gospel’s clarion call for truth, justice, compassion and charity. Have we lost our commitment to the common good? Are we in the midst of an unstoppable decline of our nation? 

Some say this is the age of tolerance. As a result, good and evil, right and wrong, vice and virtue, truth and error are accepted as equally valid. But, this is not the age of tolerance. Those who are pro-life are marginalized. Those who cherish and protect the life of the child waiting-to-be-born, the elderly and the terminally ill are branded as bigots, unwilling to show compassion to those suffering. Those who accept the sanctity of marriage and human sexuality as designed by the Creator are vilified. We live at a time when some are not only intolerant to our basic Christian values, but are actively engaged to silence Christians, target the Church and reduce her to ruins. 

In an age of relativism, has it become almost impossible to dialogue rationally on the major issues that face us, such as poverty, migration, and the sanctity of life itself ? “Relativism is the order of the day. Good and evil, right and wrong, innocence and guilt – all these binaries are deliberately confused as antipodal extremes are brought into artificial congruence. Moral clarity is muddled and logical cogency diluted. All inherent preference is suspended out of a misguided attempt to achieve balance where there is none” (Brandon Marlon, “The Decline and Fall of Modern Civilization: 8 Simple Steps to Squandering It All,” The Algemeiner, January 22, 2015).

From the Church, we receive a rich heritage of truth, morality and charity. We have solid and clear moral principles given to us by Jesus. These are the solid building blocks with which to construct a just and peaceful society. Could it be that we ourselves are slowly abandoning these principles? How is it possible that those trained in the Catholic faith assume leadership roles in government and then jettison their Catholic morals? How is it that any one of us can remain complacent to the slow moral deterioration of our country? 

Our country will not collapse if we refuse to hand over our future to those who deny the existence of God and live as if this world is all that there is. Our society will not collapse if we are courageous enough to draw on our moral and spiritual heritage to solve the issues that divide us. Our nation will not collapse if we remain true to our identity given to us by our Founding Fathers as a nation founded on Judeo-Christian principles. Our courage as moral individuals to stand for justice, truth and compassion is the antidote to the collapse of our country.
 

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Emission of the green house at the current levels will cause catastrophe in most parts of the world with some ecosystems expected to collapse by 2030.

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