Microsoft notes it can pay bug bounty participants more than $20,000, depending on the vulnerability's severity and the report's quality. Just make sure you don't use the flaw on unsuspecting users.

Redmond's pitch for its latest tablet is a crazy man screaming at himself.

Saudi Crown Prince Mohammed bin Salman has “blood on his hands” in the killing of journalist Jamal Khashoggi, a top aide to Turkey’s president said, in his country’s first direct accusation against the power behind the Saudi throne.

The United States, France, and the United Nations are falling into an all too familiar trap in the Central African Republic (CAR) of financing transition elections before armed militias have been disarmed and their communal hold broken. Exclusionary and botched elections could trigger another wave of violence and deepen the crisis.

Lipid II is an essential precursor of the bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II-binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e. HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against E. faecium than nisin (1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.

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.

Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections (cSSTI) caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1600 mg) dose, placebo, and oral moxifloxacin 400 mg in 4 separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time-point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (QTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for QTc were slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 hours postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 with having a lower confidence bound ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and QTcF interval with a slope of 0.227 ms per mg/L (90% CI: 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

Antibiotic resistance is a global concern; however, data on antibiotic-resistant Ureaplasma spp. and Mycoplasma hominis are limited in comparison to similar data on other microbes. A total of 492 Ureaplasma spp. and 13 M. hominis strains obtained in Hangzhou, China, in 2018, were subjected to antimicrobial susceptibility testing for levofloxacin, moxifloxacin, erythromycin, clindamycin, and doxycycline using the broth microdilution method. The mechanisms underlying quinolone and macrolide resistance were determined. Meanwhile, a model of the topoisomerase IV complex bound to levofloxacin in wild-type Ureaplasma spp. was built to study the quinolone resistance mutations. For Ureaplasma spp., the levofloxacin, moxifloxacin and erythromycin resistance rates were 84.69%, 51.44% and 3.59% in U. parvum and 82.43%, 62.16% and 5.40% in U. urealyticum, respectively. Of the 13 M. hominis strains, 11 were resistant to both levofloxacin and moxifloxacin, and five strains showed clindamycin resistance. ParC S83L was the most prevalent mutation in levofloxacin-resistant Ureaplasma strains, followed by ParE R448K. The two mutations GyrA S153L and ParC S91I were commonly identified in quinolone-resistant M. hominis. A molecular dynamics-refined structure revealed that quinolone resistance-associated mutations inhibited the interaction and reduced affinity with gyrase or topoisomerase IV and quinolones. The novel mutations S21A in the L4 protein and G2654T and T2245C in 23S rRNA and ermB gene were identified in erythromycin-resistant Ureaplasma spp. Fluoroquinolone resistance in Ureaplasma spp. and Mycoplasma hominis remains high in China, the rational use of antibiotics needs to be further enhanced.

Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (HCoV-229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication.

Importance No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.

The records involved conversation logs between Microsoft support agents and customers across the globe, dating back to 2005. Most of the records were redacted of customer contact information, but not all.

The Velocity Micro Raptor Z55a is a clean, straightforward gaming desktop with excellent performance. It's a bit pricey, though, and doesn't do a lot to differentiate itself from its rivals.

For a limited time, you can get a Dell Optiplex 9020 Micro computer for as low as $269.99 with a full 1-year warranty as part of an off-lease refurbished sale from the PCMag Shop.

Today you can save up to 30 percent on select laptops, networking devices, and storage drives at Amazon. Also, the highly anticipated game Cyberpunk 2077 is $10 off when you pre-order it.

Alongside a new protected area of storage, OneDrive and Office 365 storage options are changing for the better.

The 256GB Samsung EVO Select microSDXC card is back at just $39.99, the Echo Dot is half off, and the MacBook Air is $150 off.

Snag the Samsung EVO Select 512GB microSDXC card for $88, one of its lowest prices ever. Also, the 75-inch Samsung QLED 4K TV is more than $1,000 off and a Dell XPS 15 is $300 off.

The start of November has brought a ton of great deals, with some matching last year's Black Friday prices. The 512GB Samsung EVO Select microSDXC card is only $78.

Microsoft's new write-once storage medium is constructed from quartz glass, stores data using lasers, and uses machine learning algorithms for decoding.

Even with the increase in streaming competitors, Netflix remains at the top of the pack—but how long will its dominance last?

C. Michael Cotten
Jan 1, 2009; 123:58-66
ARTICLES

John Penders
Aug 1, 2006; 118:511-521
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CNA Staff, Apr 2, 2020 / 02:50 pm (CNA).- The statue of the Nazarene of Saint Paul will be processed April 8 through the streets of Caracas to help the faithful observe Holy Week.

It will be atop a popemobile used by St. John Paul II when he visited the country in 1985.

According to local tradition, the striking image was brought to Caracas from Seville in 1674. The wooden sculpture depicts Christ dressed in an ornately embroidered purple robe carrying his cross.

According to accounts, the image was processed in the city with prayers during a plague that broke out in Caracas in 1696, and the devotional act was credited with ending the pestilence.

The image was originally kept in a church dedicated to Saint Paul the Hermit, whose intercession was attributed to ending a plague in 1579. The wooden sculpture is now reserved in Saint Teresa Basilica, as Saint Paul’s church was demolished and replaced with a municipal theater by an anticlerical president in 1881.

The procession is held annually on Holy Wednesday.

Cardinal Baltazar Enrique Porras Cardozo, Archbishop of Merida and apostolic administrator of Caracas, said the “route will cover a great part of the city for veneration by its devotees,” and asked for understanding as the route itself has not yet been finalized and will be announced later.

According to local media, the prelate said in a letter that the image should be transported in accordance with safety and hygiene regulations to avoid spreading the coronavirus.

Porras said that the image should not be carried by people but transported by vehicle only and there should be another vehicle for a priest and assistant along with sound equipment for the prayers.

The archdiocese said that parishes can join the initiative and organize such a procession in their own areas as long as they observe the proper health precautions.

Finally, the archdiocese asked the faithful devotees of the Nazarene of Saint Paul to offer their prayers from their homes and to wait for the end of the coronavirus lockdown to visit the image in Saint Teresa Basilica.

Now we're typing with scan lines!

Microsoft originally sought to become a 'carbon neutral' company, meaning it could generate carbon emissions as long as it offset them through other means, but "in short, neutral is not enough to address the world's needs," says Microsoft President Brad Smith.

WHEN Tamsin Calidas stepped aboard a ferry bound for the Hebridean island that would become her new home, it was with hope for a fresh beginning, one far from the tumultuous events and near-death experience she had faced in the city streets being left behind.

A multi-disciplinary collaborative relationship, developed between Penn State EMS Energy Institute researchers and a Pittsburgh-based start-up company, may hold the answer to reducing global greenhouse gas (GHG) emissions while also paving the way to disrupt the chemical and material industries.

The books category has disappeared from the Microsoft Store and you'll no longer be able to access purchased or rented ebooks from July. Expect a full refund, though.

In the third extract from the new UEFA EURO 2016 technical report, the expert panel look at how crosses have become increasing important sources of goals.

• Football stars show how to practise skills without breaking safety rules – or windows!
• Federation raises funds for coronavirus and earthquake aid

A Scottish Parliament Committee will take evidence from a leading microbiologist, Professor Hugh Pennington, as it begins its scrutiny of the Government’s response to COVID-19.

Microsoft will probably deliver critical patches after it ends Windows 7 support in January 2020. But it's not guaranteed, so users and organizations should upgrade to Windows 10 now.

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLIs). In these fixed-dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, with BLI doses kept in ratios similar to those for the approved BL-BLIs. Such combinations have been introduced into clinical practice without mandatory drug development studies involving pharmacokinetic/pharmacodynamic, safety, and efficacy assessments being undertaken. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development.

The leading desktop operating system continues to improve, adding refinements, tool updates, new visuals, and more control over updates.

All the results and highights from Switzerland as Spain won the Women's U19 title for the second year in a row.

Vatican City, Mar 31, 2020 / 10:28 am (CNA).- Cardinal Philippe Ouédraogo of Burkina Faso has tested positive for the coronavirus, his archdiocese announced Tuesday. He is the second cardinal known to have tested positive for the virus, which is now a global pandemic.

Ouédraogo, 75, has been admitted to a medical clinic in Burkina Faso’s capital Ouagadougou.  He is “in good condition and his close collaborators are reported to be self-isolating,” a spokesman for Burkina Faso’s bishops’ conference, Fr. Paul Dah, told ACI Africa on March 31.

The cardinal is president of the African continental bishops’ conference, the Symposium of Episcopal Conferences of Africa and Madagascar (SECAM). He was elected to the post in July 2019. He has been Archbishop of Ouagadougou in Burkina Faso for ten years, and was made a cardinal by Pope Francis in 2014.

Ouédraogo is the second bishop from Burkina Faso known to have contracted COVID-19, as countries across Africa implement lockdowns and restrictions to slow the spread of the virus across the continent.

Another Burkina Faso bishop, Archbishop Emeritus Séraphin François Rouamba of Koupela, tested positive for COVID-19 after being admitted to Our Lady of Peace clinic for urgent treatment on March 19.

The 78-year-old archbishop has since been transferred to another hospital and is reportedly in stable condition, according to a March 25 statement from Bishop Laurent Birfuore Dabire of Dori, Burkina Faso.

Burkina Faso has the largest documented coronavirus outbreak in West Africa, with 249 documented cases as of March 31, according to Johns Hopkins University Coronavirus Resource Center.

The coronavirus has spread throughout the African continent to 47 countries, according to the Africa Center for Disease Control. In North Africa, Egypt, Algeria, and Morocco each have more than 500 documented cases, and the South African government has reported more than 1,300.

Three Nigerian states began two-week mandatory lockdown this week to combat the spread of the virus, including Lagos, Africa’s most populous city with more than 20 million people.

Zimbabwe and Mauritius have also implemented national shut-downs, and the bishops in South Sudan and Zimbabwe have suspended public Masses.

Cardinal Angelo De Donatis, vicar general of the Diocese of Rome, tested positive for coronavirus on March 30.

Other bishops in Italy, France, China, and the United States have also tested positive for COVID-19, and Bishop Angelo Moreschi, 67, died in the Italian city of Brescia on March 25 after contracting the coronavirus.

 

 

CNA Staff, Apr 6, 2020 / 01:00 pm (CNA).- Unable to lead the traditional Palm Sunday procession through Jerusalem, Archbishop Pierbattista Pizzaballa, OFM, apostolic administrator of the Latin Patriarchate of Jerusalem, blessed the city with a relic of the True Cross on April 5.

The annual procession, which recalls Christ’s entry into the city and the beginning of Holy Week, was cancelled in line with international efforts to curb the spread of COVID-19, with public gatherings and events suspended in Israel. 

“We decided since we cannot have the palm procession, to have anyway a moment of prayer this afternoon,” said Pizzaballa on Sunday. The archbishop led a short, multi-lingual “moment of prayer” at Dominus Flevit, a church located on the Mount of Olives.

The church, which is shaped like a teardrop, overlooks the city, and was built to mark the Gospel account of Jesus weeping as he envisioned the destruction of Jerusalem.

The prayer service ended with Pizzaballa raising a relic of the True Cross over the city in benediction. 

Jerusalem, said Pizzaballa, “is a symbol of the church, the symbol also of humanity. It is the house of prayer for all the people, according to the scriptures.”

“So when we cry [over] Jerusalem, together with Jesus, we cry [over] all our human fraternity, for this difficult moment we are living, for this sad Palm Sunday, this Easter we have to celebrate.”

Pizzaballa said that sadness over being unable to celebrate the liturgical feasts of Holy Week is real, but “maybe, in a way also very true, very essential.” 

“Today we have not celebrated the solemn and beautiful entrance of Jesus to the city of Jerusalem like every year, with faithful from all the parishes of the diocese and with pilgrims from all over the world,” Pizzaballa said during the prayer service.

“We have not raised our palms and olive branches to cry out ‘Hosanna’ to our king, Jesus the Christ.” 

Instead, the archbishop asked Catholics in the Holy Land and around the world to consider what the Lord may be trying to say during these times.

He noted that, while the people of Jerusalem in the Gospel greeted him with cheers on Palm Sunday, Jesus knew that “He came to Jerusalem, not to be on the throne like David, but to be put to death.” 

“The meaning that Jesus attributes to his ‘triumphal entry’ is different from the meaning that the people of Jerusalem saw in it,” he said.

“Perhaps this is the lesson that Jesus wants to teach us today. We turn to God when there is something that harms us. When we are in trouble, suddenly we all want to ask big and difficult questions.”

While people may be praying for an end to the COVID-19 pandemic as we often do for solutions  to other problems, the archbishop said that  “Jesus responds in His own way” to these prayers. 

“Precisely because Jesus says ‘yes’ to our deepest desires, He will have to say ‘no’ to our immediate desires,” he said.

Drawing comparisons between this year's Palm Sunday and the biblical Palm Sunday during Christ's earthly life, Pizzaballa said the story of Jesus’ entrance into Jerusalem “is a lesson on the discrepancy between our expectations and God’s response.” 

The crowd who greeted Jesus was disappointed that their salvation was not immediate, said Pizzaballa, but “Jesus’ entry into Jerusalem is truly the moment when salvation is born.” 

“The ‘Hosannas’ were justified, even if not for the reasons the Jerusalemites had supposed,” he said. 

This remains true today, he explained. Although it may seem as though God is not answering prayers and leaves people “disappointed,” this is in part because “our expectations remain without an apparent response.”

Christianity, he said, “is based on hope and love, not certainty,” and that while God will not answer all problems with certainty, “He won’t leave us alone.” 

“And here, today, despite everything, at the gates of His and our city, we declare that we really want to welcome Him as our King and Messiah, and to follow Him on His way to His throne, the cross,” he said.  

“But we also ask Him to give us the strength necessary to carry it with His own, fruitful love.”

A competition-record crowd of 32,510 watched Krasnodar take Real Madrid to penalties in their UEFA Youth League play-off, the Spanish side eventually winning 3-0 on spot-kicks.

Jane's Skype conversations with Fariha across the world in Bangladesh helped Fariha learn English while providing an opportunity to share the love of Jesus.

A Neto double, including the extra-time winner 19 seconds from time, secured back-to-back FIFA Futsal World Cup triumphs for Brazil at the expense of regular rivals Spain.

Microsoft hopes to improve its software through AI research while OpenAI can take full advantage of the Azure cloud.

Artificial intelligence consumes immense processing resources, so data centers have to be both more powerful and more energy efficient.

Microsoft realizes you can use the sea as a giant heatsink and save a small fortune in cooling costs.

Denmark overwhelmed Ireland to claim Europe's last FIFA World Cup berth after Sweden ousted Italy to follow Switzerland and Croatia through.

Standard Bank says microlenders such as African Bank or Capitec Bank Holdings will not challenge its dominance in the credit market.

When/Where: Monday, December 11, 2017 at 11:30 am. Legislative Hall in Dover, Delaware The Delaware General Assembly welcomes Wreaths Across America to the First State for the 4th annual ceremony in Dover. “Delaware is proud to participate in the Wreaths Across America Program at our capital in Dover. The mission of the program is to remember, […]

Program will explore what life would be like for a two-month crossing of the Atlantic Ocean from Europe to the New World.

Museum to feature a workshop on cross stitch, a form of embroidery in which X-shaped stitches are used to form a picture.

The 2020 BMW 8 Series Gran Coupe has been launched in India, with prices starting at Rs. 1.29 crore (ex-showroom India). The four-door coupe is being offered in two variants - 840i Gran Coupe and 840i...

The BMW M8 Coupe is the flagship offering from the German auto giant in India and promises a blend of luxury with dynamic performance via a 4.4-litre V8 motor.