Christopher Malyschko was serving a life sentence for arranging the murder of his mother's partner in Katherine in 2011. On Tuesday morning he was found dead in his cell in Darwin's prison.

A young teenage girl is forcibly stripped and kept naked in a police cell for almost an hour after being briefly forced into one of the spit-hoods banned in youth prisons ahead of the Northern Territory royal commission.

What's driving Australian families overseas to gamble on "magical" stem cell treatments at sky-high prices?

Cowboys from around the country will be unable to compete at the National Rodeo Finals this year, after the event was cancelled.

(United States Federal Circuit) - In a vineyard-plaintiff's appeal of a decision of the United States Patent and Trademark Office (PTO) Trademark Trial and Appeal Board dismissing its opposition to an application filed by defendant to register a MAYARI mark for use on wine, the Board's decision is affirmed where substantial evidence supports the Board's finding that plaintiff's registered mark MAYA and defendant's applied-for mark MAYARI are sufficiently dissimilar.

(United States Second Circuit) - Reversed summary judgment for an apparel company in its trademark infringement action. A company that sold leather jackets branded ROGUE contended that a commercial brewery that sold ROGUE-branded beer had infringed its trademark by using the name on t‐shirts and hats. The Second Circuit held that the apparel company was not entitled to summary judgment, because the brewery was the senior user and the evidence did not show that it was precluded by laches.

(United States Second Circuit) - Reversed summary judgment for an apparel company in its trademark infringement action. A company that sold leather jackets branded ROGUE contended that a commercial brewery that sold ROGUE-branded beer had infringed its trademark by using the name on t‐shirts and hats. The Second Circuit held that the apparel company was not entitled to summary judgment, because the brewery was the senior user and the evidence did not show that it was precluded by laches.

(United States Third Circuit) - In plaintiff's suit for preliminary injunctive relief against its former vice president of operations, following defendant's acceptance of a senior executive position with plaintiff's competitor, Hostess Brands, seeking to protect its trade secrets involving plaintiff's popular line of Thomas' English Muffins, of which defendant was one of only seven people who possessed all of the knowledge necessary to replicate the muffins, district court's grant of plaintiff's motion for preliminary injunction is affirmed where: 1) the district court had discretion to enjoin defendant from working at Hostess to the extent this proposed employment threatened to lead to the misappropriation of trade secrets; 2) district court did not abuse its discretion by determining that plaintiff demonstrated a likelihood of success on its misappropriation of trade secrets claim; 3) district court did not abuse its discretion when, faced with evidence of defendant's suspicious conduct during his final weeks at plaintiff, it determined that a stronger remedy was needed in the interim to protect plaintiff from imminent irreparable harm; 4) district court was correct in concluding that the harm of plaintiff's trade secrets being disclosed to Hostess outweighed the harm to defendant of not being able to commence employment at Hostess until the court made a final determination of the merits following a trial; and 5) district court was correct in concluding that the public interest in preventing the misappropriation of plaintiff's trade secrets outweighs the temporary restriction of defendant's choice of employment.

Tonight we will feature music from two great musicians born on this day, Blossom Dearie and Steve Khan! We also have new music by Joey Alexander and Kandace Springs, as well a CapRadio Jazz Classic from Duke Pearson.

Sir Duke! Duke Ellington was born on this day in 1899, and we are going to celebrate accordingly. Numerous Ellington performances and compositions will be heard throughout the evening. We also have a CapRadio Jazz Classic from Freddie Hubbard.

Happy International Jazz Day! Tonight's show will feature music from Stan Getz, John Coltrane, Wayne Shorter, as well as a CapRadio Classic from bassist Gary Peacock!

Tonight's program will feature music from Keith Jarrett, Dizzy Gillespie, John Coltrane and Kenny Garrett, as well as a CapRadio Jazz Classic from Charles Lloyd!

Remembering Richie Cole.

Tonight we celebrate Ron Carter, who was born on this day in 1937! We've also got new music from Wayne Escoffrey and Sinne Eeg, as well as a CapRadio Jazz Classic by Woody Shaw.

Tonight's show features music from Chet Baker, Wes Montgomery and Wayne Shorter. We also celebrate the birthday of Stanley Cowell - who was born on this day in 1941 - with a CapRadio Jazz Classic.

Tonight we feature music by Catherine Russell and Many Katche, as well as a CapRadio Jazz Classic from Wayne Shorter!

From all of us here at CapRadio, happy Big Day of Giving! Tonight's program will feature music from Chet Baker, Wes Montgomery, Charlie Parker and Nat King Cole!

Tonight's program will feature music from Lester Young, Nina Simone, Kenny Garrett and Charlie Parker, as well as some great releases from Posi-Tone Records!

(United States Second Circuit) - Partially affirmed, partially vacated and remanded. Affirming the dismissal of Americans with Disabilities Act claims arising from events in 2010-2011 that were untimely, but vacating the dismissal of 2013-2014 claims and Title IX claims.

Editor’s Note: Fifth of a five-part series on Colorado baseball icons. The first four profiled were Scott Bullock, Jenny and Steve Cavnar, Chris Hanks and Jim Danley.

The action thriller is streaming on Quibi.

Beuavais is the newest castmate on ‘RHOBH.’

She admits she was a “hothead.”

Many were appalled to learn the speaker was a porn star.

Removed From Troubles (OPEN for application) Fonts: Pixel / Bitmap (Graphics / Layouts / Effects); Domains (.com) (Web Miscellany)

Mobile phones have become a must for this generation. They are the devices that are the most helpful for all. You can talk to your loved ones, play music, play videos, play games and do many more other things. In… Continue Reading →

Hearing loss caused by the death of sensory hair cells of the inner ear is an unfortunate side effect for many patients treated with aminoglycoside antibiotics or platinum-containing chemotherapy agents. In animal models, induction of heat shock confers substantial otoprotection against aminoglycoside- and cisplatin-induced hair cell death. In this issue of the JCI, Breglio et al. demonstrate that inner ear tissue released exosomes carrying heat shock protein 70 (HSP70) in response to heat stress. HSP70 acted by a paracrine mechanism that engaged the Toll-like receptor 4 (TLR4) on hair cells to protect them from death. Exosomes and the HSP70/TLR4 pathway could thus provide treatment targets for the protection of hair cells from chemically induced death or from other insults, such as noise.

Hair cells, the mechanosensory receptors of the inner ear, are responsible for hearing and balance. Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs, including the widely used aminoglycoside antibiotics. Induction of heat shock proteins (HSPs) confers protection against aminoglycoside-induced hair cell death via paracrine signaling that requires extracellular heat shock 70-kDa protein (HSP70). We investigated the mechanisms underlying this non–cell-autonomous protective signaling in the inner ear. In response to heat stress, inner ear tissue releases exosomes that carry HSP70 in addition to canonical exosome markers and other proteins. Isolated exosomes from heat-shocked utricles were sufficient to improve survival of hair cells exposed to the aminoglycoside antibiotic neomycin, whereas inhibition or depletion of exosomes from the extracellular environment abolished the protective effect of heat shock. Hair cell–specific expression of the known HSP70 receptor TLR4 was required for the protective effect of exosomes, and exosomal HSP70 interacted with TLR4 on hair cells. Our results indicate that exosomes are a previously undescribed mechanism of intercellular communication in the inner ear that can mediate nonautonomous hair cell survival. Exosomes may hold potential as nanocarriers for delivery of therapeutics against hearing loss.

Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.

Alterations in calcium signaling in pancreatic acinar cells can result in pancreatitis. Although pressure changes in the pancreas can elevate cytosolic calcium (Ca2+) levels, it is not known how transient pressure-activated elevations in calcium can cause prolonged calcium changes and consequent pancreatitis. In this issue of the JCI, Swain et al. describe roles for the mechanically activated plasma membrane calcium channels Piezo1 and transient receptor potential vanilloid subfamily 4 (TRPV4) in acinar cells. The authors used genetic deletion models and cell culture systems to investigate calcium signaling. Notably, activation of the Piezo1-dependent TRPV4 pathway was independent of the cholecystokinin (CCK) stimulation pathway. These results elegantly resolve an apparent discrepancy in calcium signaling and the pathogenesis of pancreatitis in pancreatic acinar cells.

Curing HIV infection will require the elimination of a reservoir of infected CD4+ T cells that persists despite HIV-specific cytotoxic T cell (CTL) responses. Although viral latency is a critical factor in this persistence, recent evidence also suggests a role for intrinsic resistance of reservoir-harboring cells to CTL killing. This resistance may have contributed to negative outcomes of clinical trials, where pharmacologic latency reversal has thus far failed to drive reductions in HIV reservoirs. Through transcriptional profiling, we herein identified overexpression of the prosurvival factor B cell lymphoma 2 (BCL-2) as a distinguishing feature of CD4+ T cells that survived CTL killing. We show that the inducible HIV reservoir was disproportionately present in BCL-2hi subsets in ex vivo CD4+ T cells. Treatment with the BCL-2 antagonist ABT-199 was not sufficient to drive reductions in ex vivo viral reservoirs when tested either alone or with a latency-reversing agent (LRA). However, the triple combination of strong LRAs, HIV-specific T cells, and a BCL-2 antagonist uniquely enabled the depletion of ex vivo viral reservoirs. Our results provide rationale for novel therapeutic approaches targeting HIV cure and, more generally, suggest consideration of BCL-2 antagonism as a means of enhancing CTL immunotherapy in other settings, such as cancer.

BACKGROUND The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONS Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).