Book review

The recent field of invasion biology faces a new challenge as 19 eminent ecologists issue a call to "end the bias against non-native species" in the journal Nature.

The post Is ecology biased against non-native species? appeared first on Smithsonian Insider.

A number of strategies used by the police to proactively prevent crimes have proved to be successful at crime reduction, at least in the short term, and most strategies do not harm communities’ attitudes toward police, finds a new report by the National Academies of Sciences, Engineering, and Medicine.

We tend to think of the process of seeing as fairly objective — that our eyes are similar to cameras, neutrally taking in light and turning it into pictures. But research has shown that biases buried beneath our awareness can powerfully shape how we see.

Richer countries have more resources for gathering biodiversity information, creating a biased view of the worlds' species and their distribution. However, a new study argues that there are other reasons why some countries are underrepresented in global biodiversity databases, with low numbers of English speakers, large distances from the database host and low security acting as key barriers to data collection.

The U.N. ambassador is considered a top candidate for secretary of State, but her stock in the firm behind the Keystone XL oil pipeline has raised eyebrows.

Joan Williams, professor and the founding director of the Center for WorkLife Law at the University of California’s Hastings College of the Law, says that it's extremely difficult for organizations to rid their workforces of the unconscious biases that can prevent women and minorities from advancing. But it's not so hard for individual managers to interrupt bias within their own teams. She offers specific suggestions for how bosses can shift their approach in four areas: hiring, meetings, assignments, and reviews/promotions. Leaders who employ these practices, she argues, are able to embrace and reap the advantages of diversity, even in the absence of larger organizational directives. Williams is the author of the HBR article "How the Best Bosses Interrupt Bias on Their Teams."

It has recently been shown that word embeddings encode social biases, with a harmful impact on downstream tasks. However, to this point there has been no similar work done in the field of graph embeddings. We present the first study on social bias in knowledge graph embeddings, and propose a new metric suitable for measuring such bias. We conduct experiments on Wikidata and Freebase, and show that, as with word embeddings, harmful social biases related to professions are encoded in the embeddings with respect to gender, religion, ethnicity and nationality. For example, graph embeddings encode the information that men are more likely to be bankers, and women more likely to be homekeepers. As graph embeddings become increasingly utilized, we suggest that it is important the existence of such biases are understood and steps taken to mitigate their impact.

The standard training algorithm in neural machine translation (NMT) suffers from exposure bias, and alternative algorithms have been proposed to mitigate this. However, the practical impact of exposure bias is under debate. In this paper, we link exposure bias to another well-known problem in NMT, namely the tendency to generate hallucinations under domain shift. In experiments on three datasets with multiple test domains, we show that exposure bias is partially to blame for hallucinations, and that training with Minimum Risk Training, which avoids exposure bias, can mitigate this. Our analysis explains why exposure bias is more problematic under domain shift, and also links exposure bias to the beam search problem, i.e. performance deterioration with increasing beam size. Our results provide a new justification for methods that reduce exposure bias: even if they do not increase performance on in-domain test sets, they can increase model robustness to domain shift.

Vision-and-Language Navigation (VLN) requires an agent to follow natural-language instructions, explore the given environments, and reach the desired target locations. These step-by-step navigational instructions are crucial when the agent is navigating new environments about which it has no prior knowledge. Most recent works that study VLN observe a significant performance drop when tested on unseen environments (i.e., environments not used in training), indicating that the neural agent models are highly biased towards training environments. Although this issue is considered as one of the major challenges in VLN research, it is still under-studied and needs a clearer explanation. In this work, we design novel diagnosis experiments via environment re-splitting and feature replacement, looking into possible reasons for this environment bias. We observe that neither the language nor the underlying navigational graph, but the low-level visual appearance conveyed by ResNet features directly affects the agent model and contributes to this environment bias in results. According to this observation, we explore several kinds of semantic representations that contain less low-level visual information, hence the agent learned with these features could be better generalized to unseen testing environments. Without modifying the baseline agent model and its training method, our explored semantic features significantly decrease the performance gaps between seen and unseen on multiple datasets (i.e. R2R, R4R, and CVDN) and achieve competitive unseen results to previous state-of-the-art models. Our code and features are available at: https://github.com/zhangybzbo/EnvBiasVLN

In a cutting tool for chip removing machining a holder for a cutter has a body received therein and movable with surfaces to bear against the cutter for defining the position of the cutter in the direction of an intended axis of rotation of the holder as well as a screw which may be screwed in a threaded bore in the holder. Spring members are arranged to act between the holder and the body for biasing the body against said screw portions.

The invention provides a zwitterionic-bias material for blood cell selection, being a copolymer formed by zwitterionic structural units and charged structural units wherein the zwitterionic structural unit comprises at least one positively charged moiety and one negatively charged moiety, a distance between the positively charged moiety and the negatively charged moiety is a length of 1˜5 carbon-carbon bonds, and the zwitterionic structural units and charged structural units are randomly arranged to have zwitterionic-bias.

In one embodiment, a magnetic head includes a lower shield, a magnetoresistive (MR) film positioned above the lower shield, the MR film including a pinned layer, an intermediate layer positioned above the pinned layer, and a free layer positioned above the intermediate layer, the free layer being configured for sensing data on a magnetic medium, wherein a track width of the MR film is defined by a width of the free layer in a cross-track direction, a bias layer positioned on both sides of the MR film in the cross-track direction, a track insulating film positioned on both sides of the MR film in the cross-track direction and between the MR film and the bias layer, and an upper shield positioned above the bias layer and the MR film, wherein a length of the free layer in an element height direction perpendicular to an air bearing surface of the magnetic head is less than a length of the pinned layer in the element height direction.

A magnetic read sensor having an antiferromagnetic located embedded within a magnetic shield of the sensor so that the antiferromagnetic layer can pin the magnetization of the pinned layer without contributing to read gap thickness. The sensor is configured with a pinned layer having a free layer structure located within an active area of the sensor and a pinned layer that extends beyond the free layer and active area of the sensor. The antiferromagnetic layer can be located outside of the active and exchange coupled with the extended portion of the pinned layer.

A disk drive is disclosed comprising a disk, and a slider comprising a head, where the head comprises a write component electrically insulated from the slider. A bias voltage is applied to the write component, and a current flowing between the write component and the disk is measured, wherein the current is indicative of a fly height of the head.

The present invention provides an apparatus for enhancing Q factor of an inductor. The apparatus includes a negative resistance generator coupled to the inductor for providing a negative resistance, and a bias circuit coupled to the negative resistance generator for biasing the negative resistance generator.

In a signal communication device, a frequency-selective filter has at least one component that is biased by a control signal to establish a center frequency of the frequency-selective filter. A closed-loop bias generator is provided to generate the control signal and to adjust the control signal based, at least in part, on a comparison of the control signal and a reference signal.

A noise resistant switch control circuit is provided. The circuit includes a low pass filter configured to couple to a first terminal of a switch and a first voltage clamp coupled to the low pass filter. The first voltage clamp is configured to couple to a control terminal of the switch and limit a voltage of the control terminal relative to the first terminal to within a first clamping range. The circuit includes a second voltage clamp coupled to an input terminal of the switch control circuit. The second voltage clamp is configured to couple to the control terminal of the switch. The second voltage clamp is further configured to reduce a level of a control voltage coupled to the second voltage clamp. The circuit includes a bias device configured to couple to the control terminal of the switch and to impress a biasing voltage to the control terminal.

A hard bias (HB) structure for longitudinally biasing a free layer in a MR sensor is disclosed that includes a mildly etched seed layer and a hard bias (HB) layer on the etched seed layer. The HB layer may contain one or more HB sub-layers stacked on a lower sub-layer which contacts the etched seed layer. Each HB sub-layer is mildly etched before depositing another HB sub-layer thereon. The etch may be performed in an IBD chamber and creates a higher concentration of nucleation sites on the etched surface thereby promoting a smaller HB average grain size than would be realized with no etch treatments. A smaller HB average grain size is responsible for increasing Hcr in a CoPt HB layer to as high as 2500 to 3000 Oe. Higher Hcr is achieved without changing the seed layer or HB material and without changing the thickness of the aforementioned layers.

An electronic circuit, including, a power amplifier adapted to amplify an RF signal and provide it as output from the integrated circuit; a power source that is adapted to provide an unregulated voltage to the power amplifier; a regulator adapted to provide a regulated bias voltage; a subtracter that is adapted to accept a voltage proportional to the unregulated voltage and subtract it from the bias voltage to provide a reference voltage to the power amplifier; wherein the power amplifier is adapted to use the reference voltage to adjust the output from the power amplifier so that it will provide a stable power output.

Differential power amplifier circuitry includes a differential transistor pair, an input transformer, and biasing circuitry. The base contact of each transistor in the differential transistor pair may be coupled to the input transformer through a coupling capacitor. The coupling capacitors may be designed to resonate with the input transformer about a desired frequency range, thereby passing desirable signals to the differential transistor pair while blocking undesirable signals. The biasing circuitry may include a pair of emitter follower transistors, each coupled at the emitter to the base contact of each one of the transistors in the differential transistor pair and adapted to bias the differential transistor pair to maximize efficiency and stability.

A seal assembly is for sealing between a housing and a rotary shaft includes an annular sealing member coupled with the housing and having inner and outer circumferential surfaces and a plurality of projections extending radially from the outer surface and spaced circumferentially about a central axis. Each projection has first and second axial ends and the plurality of projections define first and second projections. An annular biasing member is disposed about the sealing member outer surface and exerts an inwardly directed force on the sealing member. The biasing member has first and second ends and is arranged on the sealing member with the biasing member first end contacting the second end of each first projection and the biasing member second end contacting the first end of each second projection. As such, the biasing member extends axially and circumferentially between the first and second projections.

In one embodiment, a biased fabric is supplied. The biased fabric supply has a first specified width and a first bias angle of warp yarns relative to weft yarns. At least one overfeed roller configured to overfeed fabric from the biased fabric supply at an overfeed rate is provided. At least one spreading arm configured to stretch the fabric to a second specified width and a fabric oven configured to heat the biased fabric supply to a specified temperature and output a balanced crimp and/or elongation biased fabric are also provided.

A method is disclosed of directing bias tows of a fabric to be wrapped around a form to create a fabric preform. The fabric includes at least a first set of bias tows that are generally parallel with one another and a second set of bias tows that are generally parallel with one another but that are not parallel with the first set of bias tows. An edge strip is attached to ends of the first set of bias tows at a first lateral edge of the fabric relative to a feed direction of the fabric onto the form. The edge strip is moved to direct the first set of bias tows. The fabric is wrapped around the form by rotating the fabric and form relative to one another about the central axis of the form to create the fabric preform.

One or more processors reduce bias in a score of a content. The one or more processors determine a predicted pattern of behavior of a user that provided a portion of data used to generate an initial rating of content. The one or more processors generate a modified rating of the content based on a degree of matching between the predicted pattern of behavior of the user and an action of the user that provided the portion of data.

A force biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a first plunger member reciprocally mounted in the internal cavity proximate the lower end of the internal cavity. A spring member is positioned in the internal cavity between the plunger member and the second end of the internal cavity. Three or more conductive bearings are positioned in the internal cavity in contact with the first plunger member and the spring member. A force biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a first plunger member reciprocally mounted in the internal cavity proximate the lower end of the internal cavity and a second plunger member reciprocally mounted in the internal cavity proximate the upper end of the internal cavity. A spring member is positioned in the internal cavity between the first plunger member and the second plunger member. Three or more conductive bearings are positioned in the internal cavity in contact with the first plunger member and the spring member.

A force-biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a first plunger member reciprocally mounted in the internal cavity proximate the lower end of the internal cavity. A spring member is positioned in the internal cavity between the plunger member and the second end of the internal cavity. At least one cavity formed in the plunger member with a conductive bearing in the cavity in electrical contact with the plunger and with the wall of the barrel member. A force-biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a first plunger member reciprocally mounted in the internal cavity proximate the lower end of the internal cavity and a second plunger member reciprocally mounted in the internal cavity proximate the upper end of the internal cavity. A spring member is positioned in the internal cavity between the first plunger member and the second plunger member. At least one cavity formed in the first plunger member with a first conductive bearing in the cavity in electrical contact with the first plunger and with the wall of the barrel member and at least one cavity formed in the second plunger member with a second conductive bearing in the cavity in electrical contact with the second plunger and with the wall of the barrel member.

A force-biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a first plunger member reciprocally mounted in the internal cavity proximate the lower end of the internal cavity. A spring member is positioned in the internal cavity between the plunger member and the second end of the internal cavity. At least one rectangular cavity formed in the plunger member with a movable cylindrical bearing in the cavity that applies a slight transverse force to the plunger member ensuring good electrical contact between the plunger and the wall of the barrel member. A force-biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a first plunger member reciprocally mounted in the internal cavity proximate the lower end of the internal cavity and a second plunger member reciprocally mounted in the internal cavity proximate the upper end of the internal cavity. A spring member is positioned in the internal cavity between the first plunger member and the second plunger member. At least one rectangular cavity formed in the first plunger member with a first movable cylindrical bearing in the cavity that applies a slight transverse force to the first plunger member ensuring good electrical contact between the first plunger member and the wall of the barrel member and at least one rectangular cavity formed in the second plunger member with a second movable cylindrical bearing in the cavity that applies a slight transverse force to the second plunger member ensuring good electrical contact between the second plunger member and the wall of the barrel member

A force biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a split plunger member comprised of an upper split plunger part separated from a lower split plunger part separated by a diagonal cut reciprocally mounted in the internal cavity proximate the lower end of the internal cavity. A spring member is positioned in the internal cavity between the upper split plunger part and the second end of the internal cavity. A force biased spring probe pin assembly includes a barrel member having a barrel wall defining an elongate internal cavity with a lower end and an upper end. The assembly also includes a first split plunger member reciprocally mounted in the internal cavity proximate the lower end of the internal cavity and a second split plunger member reciprocally mounted in the internal cavity proximate the upper end of the internal cavity. The first and second split plunger members are each comprised of two parts: a first upper plunger part separated from a first lower plunger part by a diagonal cut. A spring member is positioned in the internal cavity between the first and second upper split plunger parts. In each split plunger the diagonal surface of the upper split plunger part exerts a transverse force to the diagonal surface of the lower split plunger part ensuring good electrical contact between the lower split plunger member part and the barrel wall.

A sensing device includes an array of sensing elements. Each sensing element includes a photodiode, including a p-n junction, and a local biasing circuit, coupled to reverse-bias the p-n junction at a bias voltage greater than a breakdown voltage of the p-n junction by a margin sufficient so that a single photon incident on the p-n junction triggers an avalanche pulse output from the sensing element. A bias control circuit is coupled to set the bias voltage in different ones of the sensing elements to different, respective values that are greater than the breakdown voltage.

Regular contributor and critic at large Peter Robinson explores how My Fair Lady turned Shaw’s Pygmalion into a fine musical. ===================== his week on Open Air, KALW’s live radio magazine for the Bay Area Performing Arts in Times of Corona, we raise the virtual curtain for the first installment of Open Air’s Corona Radio Theater . Featuring this week is theater company Word for Word ; renowned for bringing short stories from the page to the stage, fully theatricalized; and their reading - on Zoom - of Tobias Wolff's story, Firelight .

We’re biased towards what we pay attention to, and we generally pay more attention to outcomes rather than process. Yet, if we really want to learn from our mistakes or our successes, we have to look at the process as well. On this edition of Two Guys on Your Head, Dr. Art Markman and Dr....

This episode was originally posted on Jan. 13, 2019. Many external factors can impact the quality and effectiveness of a learning experience: the teacher; the other students in a class; the school’s resources; even the student’s surroundings and home. But what about the internal factors? In this episode of KUT’s podcast “Higher Ed,” Southwestern University...

This indefinite break from sports due to the coronavirus pandemic can be an opportunity to reconsider how we view women and sports.

(United States Second Circuit) - Questions on appeal concern cross-jurisdictional tolling of a class action. Because the appeal presents state law questions that New York’s courts have yet to address, the court certifies the case to the New York Court of Appeals.

(United States Second Circuit) - Questions on appeal concern cross-jurisdictional tolling of a class action. Because the appeal presents state law questions that New York’s courts have yet to address, the court certifies the case to the New York Court of Appeals.

Given all we know about facial recognition tech, it is literally jaw-dropping that anyone could make this claim… especially without being vetted independently.

A group of Harrisburg University professors and a PhD student have developed an automated computer facial recognition software capable of predicting whether someone is likely to be a criminal.

The software is able to predict if someone is a criminal with 80% accuracy and with no racial bias. The prediction is calculated solely based on a picture of their face.

There's a whole lot of "what even the fuck" in CBS 21's reprint of a press release, but let's start with the claim about "no racial bias." That's a lot to swallow when the underlying research hasn't been released yet. Let's see what the National Institute of Standards and Technology has to say on the subject. This is the result of the NIST's examination of 189 facial recognition AI programs -- all far more established than whatever it is Harrisburg researchers have cooked up.

Asian and African American people were up to 100 times more likely to be misidentified than white men, depending on the particular algorithm and type of search. Native Americans had the highest false-positive rate of all ethnicities, according to the study, which found that systems varied widely in their accuracy.

The faces of African American women were falsely identified more often in the kinds of searches used by police investigators where an image is compared to thousands or millions of others in hopes of identifying a suspect.

Why is this acceptable? The report inadvertently supplies the answer:

Middle-aged white men generally benefited from the highest accuracy rates.

Yep. And guess who's making laws or running police departments or marketing AI to cops or telling people on Twitter not to break the law or etc. etc. etc.

To craft a terrible pun, the researchers' claim of "no racial bias" is absurd on its face. Per se stupid af to use legal terminology.

Moving on from that, there's the 80% accuracy, which is apparently good enough since it will only threaten the life and liberty of 20% of the people it's inflicted on. I guess if it's the FBI's gold standard, it's good enough for everyone.

Maybe this is just bad reporting. Maybe something got copy-pasted wrong from the spammed press release. Let's go to the source… one that somehow still doesn't include a link to any underlying research documents.

What does any of this mean? Are we ready to embrace a bit of pre-crime eugenics? Or is this just the most hamfisted phrasing Harrisburg researchers could come up with?

A group of Harrisburg University professors and a Ph.D. student have developed automated computer facial recognition software capable of predicting whether someone is likely going to be a criminal.

The most charitable interpretation of this statement is that the wrong-20%-of-the-time AI is going to be applied to the super-sketchy "predictive policing" field. Predictive policing -- a theory that says it's ok to treat people like criminals if they live and work in an area where criminals live -- is its own biased mess, relying on garbage data generated by biased policing to turn racist policing into an AI-blessed "work smarter not harder" LEO equivalent.

The question about "likely" is answered in the next paragraph, somewhat assuring readers the AI won't be applied to ultrasound images.

With 80 percent accuracy and with no racial bias, the software can predict if someone is a criminal based solely on a picture of their face. The software is intended to help law enforcement prevent crime.

There's a big difference between "going to be" and "is," and researchers using actual science should know better than to use both phrases to describe their AI efforts. One means scanning someone's face to determine whether they might eventually engage in criminal acts. The other means matching faces to images of known criminals. They are far from interchangeable terms.

If you think the above quotes are, at best, disjointed, brace yourself for this jargon-fest which clarifies nothing and suggests the AI itself wrote the pullquote:

“We already know machine learning techniques can outperform humans on a variety of tasks related to facial recognition and emotion detection,” Sadeghian said. “This research indicates just how powerful these tools are by showing they can extract minute features in an image that are highly predictive of criminality.”

"Minute features in an image that are highly predictive of criminality." And what, pray tell, are those "minute features?" Skin tone? "I AM A CRIMINAL IN THE MAKING" forehead tattoos? Bullshit on top of bullshit? Come on. This is word salad, but a salad pretending to be a law enforcement tool with actual utility. Nothing about this suggests Harrisburg has come up with anything better than the shitty "tools" already being inflicted on us by law enforcement's early adopters.

I wish we could dig deeper into this but we'll all have to wait until this excitable group of clueless researchers decide to publish their findings. According to this site, the research is being sealed inside a "research book," which means it will take a lot of money to actually prove this isn't any better than anything that's been offered before. This could be the next Clearview, but we won't know if it is until the research is published. If we're lucky, it will be before Harrisburg patents this awful product and starts selling it to all and sundry. Don't hold your breath.

Because everything is currently terrible, I binge-watched Love is Blind. In case you are planning to do the same, this is a spoiler-free post. You probably know the premise: contestants in this romantic reality romp go on speed dates in little pods. They can’t see their conversation partners, and at the end of the dates […]

This paper documents a new fact, then analyzes its causes and consequences: in most countries, import tariffs and non-tariff barriers are substantially lower on dirty than on clean industries, where an industry’s “dirtiness” is defined as its carbon dioxide (CO2) emissions per dollar of output. This difference in trade policy creates a global implicit subsidy to CO2 emissions in internationally traded goods and so contributes to climate change. This global implicit subsidy to CO2 emissions totals several hundred billion dollars annually. The greater protection of downstream industries, which are relatively clean, substantially accounts for this pattern. The downstream pattern can be explained by theories where industries lobby for low tariffs on their inputs but final consumers are poorly organized. A quantitative general equilibrium model suggests that if countries applied similar trade policies to clean and dirty goods, global CO2 emissions would decrease and global real income would change little.

We estimate valuations of time using detailed consumer choice data from a large European ride hail platform, where drivers bid on trips and consumers choose between a set of potential rides with different prices and waiting times. We estimate consumer demand as a function of prices and waiting times. While demand is responsive to both, price elasticities are on average four times higher than waiting-time elasticities. We show how these estimates can be mapped into values of time that vary by place, person, and time of day. Regarding variation within a day, the value of time during non-work hours is 16% lower than during work hours. Regarding the spatial dimension, our value of time measures are highly correlated both with real estate prices and urban GPS travel flows. A variance decomposition reveals that most of the substantial heterogeneity in the value of time is explained by individual differences as opposed to place or time of day. In contrast with other studies that focus on long run choices we do not find evidence of spatial sorting. We apply our measures to quantify the opportunity cost of traffic congestion in Prague, which we estimate at $483,000 per day.

New York Attorney General Letitia James is investigating allegations of racially discriminatory tactics by Long Island real estate agents as described in a sweeping Newsday report.

The algorithm was based on the faulty assumption that health care spending is a good proxy for wellbeing. But there seems to be a quick fix.

Once antibody tests for the coronavirus are broadly available, will we allow society to be divided into two groups — the immune and non-immune?

The coronavirus outbreak is pummeling LGBTQ Americans, leaving a population already vulnerable to health care and employment discrimination suffering.

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.

(Institute for Operations Research and the Management Sciences) New research to be published in the INFORMS journal Management Science has found popular rideshare platforms exhibit racial and other biases that penalize under-represented minorities and others seeking to use their services.

Around half of trials that supported new cancer drug approvals in Europe between 2014 and 2016 were judged to be at high risk of bias, in a new study. Huseyin Naci,assistant professor of health policy a the London School of Economics joins us to talk about why potential bias may mean potential exaggeration of treatment effects, and could be...