Sterol 12α-hydroxylase (CYP8B1) is the unique P450 enzyme with sterol 12-oxidation activity, playing an exclusive role in 12α-hydroxylating intermediates along the bile acid (BA) synthesis pathway. Despite the long history of BA metabolism studies, it is unclear whether CYP8B1 catalyzes 12α-hydroxylation of C₂₇ BAs, the key intermediates shuttling between mitochondria and peroxisomes. This work provides robust in vitro evidence that both microsomal and recombinant CYP8B1 enzymes catalyze the 12α-hydroxylation of dihydroxycoprostanic acid (DHCA) into trihydroxycoprostanic acid (THCA). On the one hand, DHCA 12α-hydroxylation reactivity is conservatively detected in liver microsomes of both human and preclinical animals. The reactivity of human tissue fractions conforms well with the selectivity of CYP8B1 mRNA expression, while the contribution of P450 enzymes other than CYP8B1 is excluded by reaction phenotyping in commercial recombinant enzymes. On the other hand, we prepared functional recombinant human CYP8B1 proteins according to a recently published protocol. Titration of the purified CYP8B1 proteins with either C4 (7α-hydroxy-4-cholesten-3-one) or DHCA yields expected blue shifts of the heme Soret peak (type I binding). The recombinant CYP8B1 proteins efficiently catalyze 12α-hydroxylation of both DHCA and C4, with substrate concentration occupying half of the binding sites of 3.0 and 1.9 μM and k_cat of 3.2 and 2.6 minutes^–1, respectively. In summary, the confirmed role of CYP8B1 in 12α-hydroxylation of C₂₇ BAs has furnished the forgotten passageway in the BA synthesis pathway. The present finding might have opened a new window to consider the biology of CYP8B1 in glucolipid metabolism and to evaluate CYP8B1 inhibition as a therapeutic approach of crucial interest for metabolic diseases.

ABSTRACTIntroduction:Health risks associated with short interpregnancy intervals, coupled with women’s desires to avoid pregnancy following childbirth, underscore the need for effective postpartum family planning programs. The antenatal period provides an opportunity to intervene; however, evidence is limited on the effectiveness of interventions aimed at reaching women in the antenatal period to increase voluntary postpartum family planning in low- and middle-income countries (LMICs). This systematic review aimed to identify and describe interventions in LMICs that attempted to increase postpartum contraceptive use via contacts with pregnant women in the antenatal period.Methods:Studies published from January 2012 to July 2022 were considered if they were conducted in LMICs, evaluated an intervention delivered during the antenatal period, were designed to affect postpartum contraceptive use, were experimental or quasi-experimental, and were published in French or English. The main outcome of interest was postpartum contraceptive use within 1 year after birth, defined as the use of any method of contraception at the time of data collection. We searched EMBASE, Global Health, and Medline and manually searched the reference lists from studies included in the full-text screening.Results:We double-screened 771 records and included 34 reports on 31 unique interventions in the review. Twenty-three studies were published from 2018 on, with 21 studies conducted in sub-Saharan Africa. Approximately half of the study designs (n=16) were randomized controlled trials, and half (n=15) were quasi-experimental. Interventions were heterogeneous. Among the 24 studies that reported on the main outcome of interest, 18 reported a positive intervention effect, with intervention recipients having greater contraceptive use in the first year postpartum.Conclusion:While the studies in this systematic review were heterogeneous, the findings suggest that interventions that included a multifaceted package of initiatives appeared to be most likely to have a positive effect.

ABSTRACTTraining health workers is one of the biggest challenges and cost drivers when introducing a new contraceptive method or service delivery innovation. PATH developed a digital training curriculum for family planning providers who are learning to offer subcutaneous DMPA (DMPA-SC), including through self-injection, as an option among a range of contraceptive methods. The DMPA-SC eLearning course for health workers includes 10 lessons with an emphasis on informed choice counseling and training clients to self-inject. In partnership with Ministries of Health in Senegal and Uganda, the course was rolled out in select areas in 2019–2020, including during the COVID-19 pandemic when physical distancing requirements restricted in-person training. We conducted evaluations in both countries to assess the practical application of this digital training approach for contraceptive introduction. The evaluation consisted of a post-training survey, an observational assessment conducted during post-training supportive supervision, and an estimation of training costs.In both countries, a majority (88.6% in Uganda and 64.3% in Senegal) scored above 80% on a DMPA-SC knowledge test following the training. In Senegal, where there was a comparison group of providers trained in person, those providers scored similar on the post-test to eLearners. Providers in both groups and in both countries felt more prepared to administer DMPA-SC or offer self-injection to clients after receiving a supervision visit (93%–98% of eLearners felt very prepared after supervision as compared to 45%–72% prior). The evaluation results suggest that digital approaches offer a number of benefits, can be cost-effective, and are most optimal when blended with in-person training and/or supportive supervision.

In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for ¹⁸F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and ¹⁸F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for ¹⁸F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of ¹⁸F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive ¹⁸F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at ¹⁸F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0–72.4 y), and the median PSA at ¹⁸F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3–0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 0.10 or more. An FPSAR of 0.10 or more was identified as an independent predictor of a positive ¹⁸F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96–16.51; P < 0.001). Conclusion: An FPSAR of 0.10 or more after RP independently correlated with increased odds of a positive ¹⁸F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to ¹⁸F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete.

α-Synuclein (α-Syn) aggregation in Lewy bodies and Lewy neurites has emerged as a key pathogenetic feature in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Various factors, including posttranslational modifications (PTMs), can influence the propensity of α-Syn to misfold and aggregate. PTMs are biochemical modifications of a protein that occur during or after translation and are typically mediated by enzymes. PTMs modulate several characteristics of proteins including their structure, activity, localization, and stability. α-Syn undergoes various posttranslational modifications, including phosphorylation, ubiquitination, SUMOylation, acetylation, glycation, O-GlcNAcylation, nitration, oxidation, polyamination, arginylation, and truncation. Different PTMs of a protein can physically interact with one another or work together to influence a particular physiological or pathological feature in a process known as PTMs crosstalk. The development of detection techniques for the cooccurrence of PTMs in recent years has uncovered previously unappreciated mechanisms of their crosstalk. This has led to the emergence of evidence supporting an association between α-Syn PTMs crosstalk and synucleinopathies. In this review, we provide a comprehensive evaluation of α-Syn PTMs, their impact on misfolding and pathogenicity, the pharmacological means of targeting them, and their potential as biomarkers of disease. We also highlight the importance of the crosstalk between these PTMs in α-Syn function and aggregation. Insight into these PTMS and the complexities of their crosstalk can improve our understanding of the pathogenesis of synucleinopathies and identify novel targets of therapeutic potential.

Both preclinical and clinical studies implicate functional impairments of several neuroactive metabolites of the kynurenine pathway (KP), the major degradative cascade of the essential amino acid tryptophan in mammals, in the pathophysiology of neurologic and psychiatric diseases. A number of KP enzymes, such as tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenases (IDO1 and IDO2), kynurenine aminotransferases (KATs), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3-HAO), and quinolinic acid phosphoribosyltransferase (QPRT), control brain KP metabolism in health and disease and are therefore increasingly considered to be promising targets for the treatment of disorders of the nervous system. Understanding the distribution, cellular expression, and regulation of KP enzymes and KP metabolites in the brain is therefore critical for the conceptualization and implementation of successful therapeutic strategies.

BACKGROUND AND PURPOSE:

A cleftlike nonenhancing hypointensity was observed repeatedly in the pituitary gland at the adenohypophysis/neurohypophysis border on contrast-enhanced 3D fat-saturated T1-MPRAGE using clinical 7T MRI. Our primary goal was to assess the prevalence of this finding. The secondary goals were to evaluate the frequency of other incidental pituitary lesions, MRI artifacts, and their effect on pituitary imaging on the contrast-enhanced 3D fat-saturated T1 MPRAGE at 7T.

BACKGROUND AND PURPOSE:

Mechanical thrombectomy is a fundamental intervention for acute ischemic stroke treatment. While conventional techniques are effective, cyclic aspiration (CyA) shows potential for better recanalization rates. We aim to investigate factors affecting CyA and compare them with static aspiration (StA).

BACKGROUND AND PURPOSE:

Vertebrobasilar artery stent placement (VBS) is potentially effective in preventing recurrent posterior circulation strokes; however, the incidences of in-stent restenosis and stented-territory ischemic events based on the location of stent placement have rarely been investigated. We aimed to investigate the characteristics and prognosis of VBS between intracranial and extracranial.

Anorectal malformations (ARMs) constitute a group of congenital defects of the gastrointestinal and urogenital systems. They affect males and females, with an estimated worldwide prevalence of 1 in 5000 live births. These malformations are clinically heterogeneous and can be part of a syndromic presentation (syndromic ARM) or as a nonsyndromic entity (nonsyndromic ARM). Despite the well-recognized heritability of nonsyndromic ARM, the genetic etiology in most patients is unknown. In this study, we describe three siblings with diverse congenital anomalies of the genitourinary system, anemia, delayed milestones, and skeletal anomalies. Genome sequencing identified a novel, paternally inherited heterozygous Caudal type Homeobox 2 (CDX2) variant (c.722A > G (p.Glu241Gly)), that was present in all three affected siblings. The variant identified in this family is absent from population databases and predicted to be damaging by most in silico pathogenicity tools. So far, only two other reports implicate variants in CDX2 with ARMs. Remarkably, the individuals described in these studies had similar clinical phenotypes and genetic alterations in CDX2. CDX2 encodes a transcription factor and is considered the master regulator of gastrointestinal development. This variant maps to the homeobox domain of the encoded protein, which is critical for interaction with DNA targets. Our finding provides a potential molecular diagnosis for this family's condition and supports the role of CDX2 in anorectal anomalies. It also highlights the clinical heterogeneity and variable penetrance of ARM predisposition variants, another well-documented phenomenon. Finally, it underscores the diagnostic utility of genomic profiling of ARMs to identify the genetic etiology of these defects.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).

BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises.

We primary care clinicians, scholars, and leaders ascribe value to Barbara Starfield’s core tenets of primary care—the 4 Cs: first contact, comprehensiveness, coordination, and continuity. In today’s era of rapid technological advancements and dwindling resources, what are the implications for face-to-face interactions of patient-clinician relationships? We propose adding a 5th C: "Contiguity." Contiguity—or physical proximity and presence—is a key dimension that not only enables the necessary technical aspects of a physical exam but also authenticates the most human aspects of a relationship and occurs specifically when we are physically vulnerable and responsible for the other before us. This, in turn, may best enable us to bridge difference and nurture trust with our patients. We measure what we value and, thus, naming Contiguity as a core tenet assures that we will not lose sight of this keystone in a patient’s relationship with their personal physician.

PURPOSE

The impact of digital health on medically underserved patients is unclear. This study aimed to determine the early impact of a digital innovation to grow quality care through an interprofessional care team (DIG IT) on the blood pressure (BP) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of medically underserved patients.

Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.

Most childhood cancers possess distinct clinicopathological profiles from those seen in adulthood, reflecting their divergent mechanisms of carcinogenesis. Rather than depending on the decades-long, stepwise accumulation of changes within a mature cell that defines adult carcinomas, many pediatric malignancies emerge rapidly as the consequence of random errors during development. These errors—whether they be genetic, epigenetic, or microenvironmental—characteristically block maturation, resulting in phenotypically primitive neoplasms. Only an event that falls within a narrow set of spatiotemporal parameters will forge a malignant clone; if it occurs too soon then the event might be lethal, or negatively selected against, while if it is too late or in an incorrectly primed precursor cell then the necessary intracellular conditions for transformation will not be met. The precise characterization of these changes, through the study of normal tissues and tumors from patients and model systems, will be essential if we are to develop new strategies to diagnose, treat, and perhaps even prevent childhood cancer.

Writer-director partners Scott Beck and Bryan Woods dive into the biggest spoilers of their new Hugh Grant thriller.

Jade Ho explains what is possible for university students when they are given opportunities to learn about –and get involved with– social justice and labour issues in their own communities.

The post Students can be agents of change: Talking about activism in universities with Jade Ho appeared first on rabble.ca.

What does 2023's Scottish Health Survey tell us about Scotland's population - from smoking rates to obesity, and alcohol consumption?

A new digital-first Gaelic language production will be launched in Scotland after a joint agreement between BBC Alba and BBC Scotland.

Anna Marie practices equal opportunity violence. Kelley fawns over Sidon Shark (do do do do). Robert is the destroyer of Vitas. Josh is stress. Chris does some Neo Vision shaming. And Alex wonders why he allows this podcast on the site.

The post RPG Cast – Episode 571: “Hospital Hat Trick” appeared first on RPGamer.

Chris gets trolled by the bear cave. Jason sets optics to stun. Josh is hiding in a rest stop bathroom. Kelley stretches harder than she did for The Witch and the Hundred Knight. Also, find out how to increase your poop by 10 and express your opinions about Dragon Quest Soundtracks.

The post RPG Cast – Episode 664: “We Need to Talk About Gambit” appeared first on RPGamer.

Sony Interactive Entertainment in a new video posted to YouTube revealed the PlayStation 5 Slim Digital Edition has been discounted by $70 and will be available for $379.99. The deal runs until December 24 "while supplies last."

No word yet if the standard PlayStation 5 or the recently released PlayStation 5 Pro will be discounted. The standard PS5 is priced at $499.99 and the PS5 Pro is priced at $699.99.

As of the time of writing, the discount isn't available yet at retailers or through PlayStation Direct.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463046/ps5-slim-digital-edition-discounted-to-379-in-the-us-until-december-24/

Ogres, Orcs, and Khorne are all on the way in the upcoming expansion for strategy game Total War: Warhammer 3, and Creative Assembly have just released their latest dev vlog with a few more details on what to expect. There’s still no word on the exact title, although given the established naming convention (Shadows Of Change, Thrones Of Decay), I’m tentatively calling it “Sniffers Of Glue” in honour of the No Think, Only Krump faction selection.

You’ll find the vlog in its full glory below. What’s interesting about this one is that vlog mainstay director Rich Alridge has brought along some new faces: battle designer Josh King and audio director Chris Goldsmith. And, yes, so no-one can accuse me of burying the lede: that audio design involved the enthusiastic, deeply disgusting slurping of porridge and yoghurt, and the jangling of real bones. The source of the bones is not revealed.

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I would never have predicted there'd be an isometric tactics game based on run-and-gun series Metal Slug, yet here Metal Slug Tactics is, and I am here for it. We've been following its development for a while but it's out now on Steam, and seemingly as strong as its demo suggested.

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Putting aside my natural annoyance at Metal Gear Solid Delta: Snake Eater for almost beating out the Twarhammer series in the headline real estate wars, I am more than a little excited to play. Some days, you simply must feast on a tree frog, and while we still don’t have a solid release date, that day doesn’t feel too far away. Good news for stealth fans, and perhaps gooder news for a dozen strapline writers sweating profusely, soiling themselves in anticipation of using “kept you waiting, huh?”.

Until then, I at least have a steady drip feed of new information to keep me sated, the latest of which is the substantial hint that there'll be some new dialogue in the game, as per the video below. Alongside that, the previously pseudonymous Suzetta Miñet - who was credited with voicing EVA in MGS3 and Peace Walker - has revealed herself to be Jodi Benson, the voice of Ariel in Disney’s The Little Mermaid. Cheers for the spot, Automaton West.

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A grand jury has formally charged a 22-year-old man with capital murder and rape in the death of Nabra Hassanen, who was killed on her walk back to a Virginia mosque.

The Fairfax County Circuit Court indicted Darwin Martinez-Torres of Sterling, Virginia, on Monday on four counts of capital murder for killing Nabra, who was with friends while they had a meal before Ramadan services. Dozens of people had gathered outside the courthouse today, chanting “Justice for Nabra.”

Virginia law has specific conditions for pursuing the death penalty, but the Associated Press reported that the grand jury’s indictment described in graphic detail how Nabra’s killing was grounds for a death penalty against Martinez-Torres. The indictment appears to acknowledge for the first time that the 17-year-old Muslim teen was raped. Under state law, the combination of a rape charge with a premeditated murder charge means the death penalty can be pursued.

Police have said that Martinez-Torres, who is an undocumented immigrant, got into a confrontation on June 18 with a group of teens walking back to the All Dulles Area Muslim Society after grabbing a late meal. He is accused of returning later and beating Nabra with a baseball bat. Police said Nabra’s body was later discovered in a pond. A search warrant affidavit revealed that Martinez-Torres admitted to killing Nabra and had led authorities to where he dumped her body, AP reported.

Nabra’s parents and Muslim advocates have said that Nabra’s death was motivated by hate, but police has said that they will not treat the killing as a hate crime. Instead, police have said it was a road rage incident.

“The reason this guy he hit my daughter is because she’s Muslim,” Nabra’s father Mahmoud Hassanen told WAMU. “Why [didn’t he] hit the boy who bothered him?”

Nabra’s father added that he hoped for the death penalty, while her mother said she wanted Martinez-Torres to serve life in prison.

“I just want people to remember her, and don’t forget her,” Mahmoud told WAMU. “I think nobody can forget her too, for what she did in her life.”

A preliminary hearing for Martinez-Torres reportedly turned emotional on Friday, with Nabra’s parents both shouting at the suspect in court. Nabra’s mother Sawsan Gazzar apparently threw a shoe at Martinez-Torres during the proceedings.

READ MORE: D.C. memorial for slain Muslim teen was set on fire, officials say

The post Man accused of killing Muslim teen indicted on capital murder charges appeared first on PBS NewsHour.

A 61-year-old San Antonio man pleaded guilty to two federal charges in the human smuggling incident that led to the deaths of 10 undocumented immigrants this summer.

James Matthew Bradley Jr., who appeared before a U.S. magistrate judge Monday, pleaded guilty to “one count of conspiracy to transport aliens resulting in death and one count of transporting aliens resulting in death,” according to a statement from the U.S. Attorney’s Office for the Western District of Texas.

The office added that Bradley’s “admission of guilt” meant he packed dozens of unauthorized immigrants into a tractor-trailer for financial gain, adding that the suspect confirmed that details from court documents were “factually correct.”

On July 23, San Antonio Police Department officers responded to a call from a Walmart employee shortly past midnight. Once officers arrived, they found 39 immigrants at the scene. Of those carried in the tractor-trailer, eight were found dead in the rear of the trailer, while two died later at nearby hospitals, the statement said.

Survivors of the incident said there was no air conditioning in the overheated trailer and had to take turns to breath through a hole in the back of the truck for air. Bradley also initially told investigators that he was unaware of the immigrants in the trailer until he had stopped at the Walmart in San Antonio for bathroom break.

The attorney’s office also said Bradley faces up to life in prison with the charges and that he is scheduled to be sentenced in January 2018. Immigrants said there were up to 200 people transported on the trailer and that different fees were quoted to them for the ride north from the U.S.-Mexico border, the statement added.

Jason Buch of San Antonio Express-News told the NewsHour earlier this year that Border Patrol agents in Laredo, Texas, reported an uptick of immigrants using tractor-trailers to get pass checkpoints at the border.

“People are usually going on to major metropolitan areas or regions of the country that employ a lot of immigrant laborers, so, areas with large agriculture industries or construction booms,” Buch said.

The NewsHour’s John Yang learned more about the July human smuggling case and immigration politics from Jason Buch of San Antonio Express News.

Shane M. Folden, special agent in charge of homeland security investigations in San Antonio, said in the statement that the proceeding “helps to close the door on one of the conspirators responsible for causing the tragic loss of life and wreaking havoc on those who survived this horrific incident.”

“This case is a glaring reminder that alien smugglers are driven by greed and have little regard for the health and well-being of their human cargo, which can prove to be a deadly combination,” he added.

Bradley’s co-defendant Pedro Silva Segura was also indicted last month with faces two counts of conspiracy and two counts of transporting undocumented immigrants resulting in serious bodily injury and placing lives in jeopardy.

Segura, 47, is an undocumented immigrant who resides in Laredo, Texas.

The post San Antonio truck driver pleads guilty in fatal human smuggling case appeared first on PBS NewsHour.

After a star explodes, the resulting supernova remnant collapses in on itself and could begin the cycle again, creating generations of stars enriched with heavy elements

Samantha Harvey has won the UK's top fiction prize for a novel that takes place over 24 hours on the International Space Station

It’s the second-shortest book to be awarded the prize.

Emma Raducanu struck a deal to return to one of her favourite tournaments.

In the 1960s and 1970s, NASA spent a lot of time thinking about whether toroidal (donut-shaped) fuel tanks were the way to go with its spacecraft. Toroidal tanks have a bunch of potential advantages over conventional spherical fuel tanks. For example, you can fit nearly 40% more volume within a toroidal tank than if you were using multiple spherical tanks within the same space. And perhaps most interestingly, you can shove stuff (like the back of an engine) through the middle of a toroidal tank, which could lead to some substantial efficiency gains if the tanks could also handle structural loads.

Because of their relatively complex shape, toroidal tanks are much more difficult to make than spherical tanks. Even though these tanks can perform better, NASA simply doesn’t have the expertise to manufacture them anymore, since each one has to be hand-built by highly skilled humans. But a company called Machina Labs thinks that they can do this with robots instead. And their vision is to completely change how we make things out of metal.

The fundamental problem that Machina Labs is trying to solve is that if you want to build parts out of metal efficiently at scale, it’s a slow process. Large metal parts need their own custom dies, which are very expensive one-offs that are about as inflexible as it’s possible to get, and then entire factories are built around these parts. It’s a huge investment, which means that it doesn’t matter if you find some new geometry or technique or material or market, because you have to justify that enormous up-front cost by making as much of the original thing as you possibly can, stifling the potential for rapid and flexible innovation.

On the other end of the spectrum you have the also very slow and expensive process of making metal parts one at a time by hand. A few hundred years ago, this was the only way of making metal parts: skilled metalworkers using hand tools for months to make things like armor and weapons. The nice thing about an expert metalworker is that they can use their skills and experience to make anything at all, which is where Machina Labs’ vision comes from, explains CEO Edward Mehr who co-founded Machina Labs after spending time at SpaceX followed by leading the 3D printing team at Relativity Space.

“Craftsmen can pick up different tools and apply them creatively to metal to do all kinds of different things. One day they can pick up a hammer and form a shield out of a sheet of metal,” says Mehr. “Next, they pick up the same hammer, and create a sword out of a metal rod. They’re very flexible.”

The technique that a human metalworker uses to shape metal is called forging, which preserves the grain flow of the metal as it’s worked. Casting, stamping, or milling metal (which are all ways of automating metal part production) are simply not as strong or as durable as parts that are forged, which can be an important differentiator for (say) things that have to go into space. But more on that in a bit.

The problem with human metalworkers is that the throughput is bad—humans are slow, and highly skilled humans in particular don’t scale well. For Mehr and Machina Labs, this is where the robots come in.

“We want to automate and scale using a platform called the ‘robotic craftsman.’ Our core enablers are robots that give us the kinematics of a human craftsman, and artificial intelligence that gives us control over the process,” Mehr says. “The concept is that we can do any process that a human craftsman can do, and actually some that humans can’t do because we can apply more force with better accuracy.”

This flexibility that robot metalworkers offer also enables the crafting of bespoke parts that would be impractical to make in any other way. These include toroidal (donut-shaped) fuel tanks that NASA has had its eye on for the last half century or so.

Machina Labs’ CEO Edward Mehr (on right) stands behind a 15 foot toroidal fuel tank.Machina Labs

“The main challenge of these tanks is that the geometry is complex,” Mehr says. “Sixty years ago, NASA was bump-forming them with very skilled craftspeople, but a lot of them aren’t around anymore.” Mehr explains that the only other way to get that geometry is with dies, but for NASA, getting a die made for a fuel tank that’s necessarily been customized for one single spacecraft would be pretty much impossible to justify. “So one of the main reasons we’re not using toroidal tanks is because it’s just hard to make them.”

Machina Labs is now making toroidal tanks for NASA. For the moment, the robots are just doing the shaping, which is the tough part. Humans then weld the pieces together. But there’s no reason why the robots couldn’t do the entire process end-to-end and even more efficiently. Currently, they’re doing it the “human” way based on existing plans from NASA. “In the future,” Mehr tells us, “we can actually form these tanks in one or two pieces. That’s the next area that we’re exploring with NASA—how can we do things differently now that we don’t need to design around human ergonomics?”

Machina Labs’ ‘robotic craftsmen’ work in pairs to shape sheet metal, with one robot on each side of the sheet. The robots align their tools slightly offset from each other with the metal between them such that as the robots move across the sheet, it bends between the tools. Machina Labs

The video above shows Machina’s robots working on a tank that’s 4.572 m (15 feet) in diameter, likely destined for the Moon. “The main application is for lunar landers,” says Mehr. “The toroidal tanks bring the center of gravity of the vehicle lower than what you would have with spherical or pill-shaped tanks.”

Training these robots to work metal like this is done primarily through physics-based simulations that Machina developed in house (existing software being too slow), followed by human-guided iterations based on the resulting real-world data. The way that metal moves under pressure can be simulated pretty well, and although there’s certainly still a sim-to-real gap (simulating how the robot’s tool adheres to the surface of the material is particularly tricky), the robots are collecting so much empirical data that Machina is making substantial progress towards full autonomy, and even finding ways to improve the process.

An example of the kind of complex metal parts that Machina’s robots are able to make.Machina Labs

Ultimately, Machina wants to use robots to produce all kinds of metal parts. On the commercial side, they’re exploring things like car body panels, offering the option to change how your car looks in geometry rather than just color. The requirement for a couple of beefy robots to make this work means that roboforming is unlikely to become as pervasive as 3D printing, but the broader concept is the same: making physical objects a software problem rather than a hardware problem to enable customization at scale.

Eliminating this pernicious policy should be on the Trump administration's first week to-do list.

NASA said Thursday that the study of UFOs will require new scientific techniques, including advanced satellites as well as a shift in how unexplained sightings are perceived.

Ransomeware attacks against health care organizations are happening at an alarmingly high rate in 2024, putting patient health at risk.

… level with France in the Davis Cup quarterfinals Friday. The 20th-ranked Fognini … all five of his previous Davis Cup matches and beat Fognini recently ….

Three people have been taken to hospital after a car mounted the pavement and smashed into a restaurant in Piccadilly Circus, the Metropolitan Police have said.

Drugs like Ozempic and Wegovy have unexpected effects on the brain, opening up potential new ways to treat depression, anxiety, addiction and Alzheimer’s

After an mRNA vaccine for mpox achieved promising results in monkeys, researchers say it could have several advantages over existing vaccines – but cold storage requirements mean it will be hard to roll out in some hard-hit countries

Medical clowns, who play with children in hospitals, may help them be discharged sooner by reducing their heart rates

Male pattern baldness could soon be a thing of the past, with new hair loss treatments beginning to show tantalising results

Systems that can harvest water from moisture in the atmosphere could offer a valuable water source in the wake of disasters