As long-simmering passions related to federal immigration policies have come to a full boil, less noted but no less important debates are taking place at state and local levels with regards to policies affecting immigrants and their children. As states are increasingly diverging in their responses, this report examines how some of the key policies and programs that support long-term integration success are faring in this volatile era.

Bertrand Clarke, Jennifer Clarke

Source: Statist. Surv., Volume 6, 1--73.

Abstract:
We review predictive techniques from several traditional branches of statistics. Starting with prediction based on the normal model and on the empirical distribution function, we proceed to techniques for various forms of regression and classification. Then, we turn to time series, longitudinal data, and survival analysis. Our focus throughout is on the mechanics of prediction more than on the properties of predictors.

The PFC, through its high degree of interconnectivity with cortical and subcortical brain areas, mediates cognitive and emotional processes in support of adaptive behaviors. This includes the formation of fear memories when the anticipation of threat demands learning about temporal or contextual cues, as in trace fear conditioning. In this variant of fear learning, the association of a cue and shock across an empty trace interval of several seconds requires sustained cue-elicited firing in the prelimbic cortex (PL). However, it is unknown how and when distinct PL afferents contribute to different associative components of memory. Among the prominent inputs to PL, the hippocampus shares with PL a role in both working memory and contextual processing. Here we tested the necessity of direct hippocampal input to the PL for the acquisition of trace-cued fear memory and the simultaneously acquired contextual fear association. Optogenetic silencing of ventral hippocampal (VH) terminals in the PL of adult male Long-Evans rats selectively during paired trials revealed that direct communication between the VH and PL during training is necessary for contextual fear memory, but not for trace-cued fear acquisition. The pattern of the contextual memory deficit and the disruption of local PL firing during optogenetic silencing of VH-PL suggest that the VH continuously updates the PL with the current contextual state of the animal, which, when disrupted during memory acquisition, is detrimental to the subsequent rapid retrieval of aversive contextual associations.

SIGNIFICANCE STATEMENT Learning to anticipate threat from available contextual and discrete cues is crucial for survival. The prelimbic cortex is required for forming fear memories when temporal or contextual complexity is involved, as in trace fear conditioning. However, the respective contribution of distinct prelimbic afferents to the temporal and contextual components of memory is not known. We report that direct input from the ventral hippocampus enables the formation of the contextual, but not trace-cued, fear memory necessary for the subsequent rapid expression of a fear response. This finding dissociates the contextual and working-memory contributions of prelimbic cortex to the formation of a fear memory and demonstrates the crucial role for hippocampal input in contextual fear learning.

Neonatal stroke is as frequent as stroke in the elderly, but many pathophysiological injury aspects are distinct in neonates, including immune signaling. While myeloid cells can traffic into the brain via multiple routes, the choroid plexus (CP) has been identified as a uniquely educated gate for immune cell traffic during health and disease. To understand the mechanisms of myeloid cell trafficking via the CP and their influence on neonatal stroke, we characterized the phenotypes of CP-infiltrating myeloid cells after transient middle cerebral artery occlusion (tMCAO) in neonatal mice of both sexes in relation to blood-brain barrier permeability, injury, microglial activation, and CX3CR1-CCR2 signaling, focusing on the dynamics early after reperfusion. We demonstrate rapid recruitment of multiple myeloid phenotypes in the CP ipsilateral to the injury, including inflammatory CD45⁺CD11b⁺Ly6c^highCD86⁺, beneficial CD45⁺CD11b⁺Ly6c^lowCD206⁺, and CD45⁺CD11b⁺Ly6c^lowLy6g^high cells, but only minor leukocyte infiltration into acutely ischemic-reperfused cortex and negligible vascular albumin leakage. We report that CX3CR1-CCR2-mediated myeloid cell recruitment contributes to stroke injury. Considering the complexity of inflammatory cascades triggered by stroke and a role for TLR2 in injury, we also used direct TLR2 stimulation as an independent injury model. TLR2 agonist rapidly recruited myeloid cells to the CP, increased leukocytosis in the CSF and blood, but infiltration into the cortex remained low over time. While the magnitude and the phenotypes of myeloid cells diverged between tMCAO and TLR2 stimulation, in both models, disruption of CX3CR1-CCR2 signaling attenuated both monocyte and neutrophil trafficking to the CP and cortex.

SIGNIFICANCE STATEMENT Stroke during the neonatal period leads to long-term disabilities. The mechanisms of ischemic injury and inflammatory response differ greatly between the immature and adult brain. We examined leukocyte trafficking via the choroid plexus (CP) following neonatal stroke in relation to blood-brain barrier integrity, injury, microglial activation, and signaling via CX3CR1 and CCR2 receptors, or following direct TLR2 stimulation. Ischemia-reperfusion triggered marked unilateral CX3CR1-CCR2 dependent accumulation of diverse leukocyte subpopulations in the CP without inducing extravascular albumin leakage or major leukocyte infiltration into the brain. Disrupted CX3CR1-CCR2 signaling was neuroprotective in part by attenuating monocyte and neutrophil trafficking. Understanding the migratory patterns of CP-infiltrating myeloid cells with intact and disrupted CX3CR1-CCR2 signaling could identify novel therapeutic targets to protect the neonatal brain.

Kesavananda Bharati V. state of Kerala that outlined the basic structure doctrine of the constitution. The judgment was delivered by the largest SC bench so far i.e. 13 judges.

Ashtead Plant Hire Company Limited v Granton Central Developments Limited [2019] CSOH 7 This case involves a landlord and tenant dispute over the proper construction of the rent review provisions in a lease of commercial premises.  The parties ...

Introduction In a recent judgment on an application to vary consent orders relating to the establishment of a confidentiality ring (Bombardier Transportation UK Limited v Merseytravel [2017] EWHC 726 (TCC)), the court decided that despite some conce...

The European Data Protection Board (EDPB) has published a set of guidelines (in draft) for public consultation. These will be absolutely key to providers of online services, such as social media, e-commerce, internet search engines, communication an...

What you need to know UK regulatory guidance has been updated to explain what ‘manifestly unfounded’ and ‘excessive’ means in relation to the individual rights of data subjects under GDPR. This includes but is not limited to ...

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There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

ABSTRACT

Microbes affect vertebrates on timescales from daily to evolutionary, and the cumulative effect of these interactions is immense. However, how microbiomes compare across (host) species is poorly understood, as most studies focus on relatively few species. A recent mBio article by S. J. Song, J. G. Sanders, F. Delsuc, J. Metcalf, et al. (mBio 11:e02901-19, 2019, https://doi.org/10.1128/mBio.02901-19) expands our collective understanding of the vertebrate microbiome by analyzing ~900 species. They demonstrate that patterns within mammals contrast with those within birds. Their results suggest many hypotheses about the role of host ecology and evolution on microbiome variation. Bats, the only volant mammals, appear to contradict many of the general mammal microbiome trends, in some ways resembling birds. What role has powered flight, and the evolution thereof, played in microbiome structure and function? Comparative methods, mechanistic hypotheses, and theory will elucidate this exciting question (and others) that we can ask using Song, Sanders et al.’s data and results.

ABSTRACT

Pseudomonas aeruginosa is an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile of P. aeruginosa appears to converge toward a common metabolic program as the organism adapts to the CF airway environment. However, we still have only a limited understanding of how these transcriptional changes impact metabolic flux at the systems level. To address this, we analyzed the transcriptome, proteome, and fluxome of P. aeruginosa grown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of an airway surfactant, phosphatidylcholine, which is known to be a major carbon source for P. aeruginosa in CF airways. We show that the fluxes of carbon throughout central metabolism are radically different among carbon sources. For example, the newly recognized "EDEMP cycle" (which incorporates elements of the Entner-Doudoroff [ED] pathway, the Embden-Meyerhof-Parnas [EMP] pathway, and the pentose phosphate [PP] pathway) plays an important role in supplying NADPH during growth on glycerol. In contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the reaction catalyzed by isocitrate dehydrogenase(s). Perhaps more importantly, our proteomic and transcriptomic analyses revealed a global remodeling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity of P. aeruginosa; that plasticity allows the organism to seamlessly segue between different carbon sources, maximizing the energetic yield from each.

IMPORTANCE Pseudomonas aeruginosa is an opportunistic human pathogen that is well known for causing infections in the airways of people with cystic fibrosis. Although it is clear that P. aeruginosa is metabolically well adapted to life in the CF lung, little is currently known about how the organism metabolizes the nutrients available in the airways. In this work, we used a combination of gene expression and isotope tracer ("fluxomic") analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We found that carbon is routed ("fluxed") through very different pathways during growth on these substrates and that this is accompanied by an unexpected remodeling of the cell’s electron transfer pathways. Having access to this "blueprint" is important because the metabolism of P. aeruginosa is increasingly being recognized as a target for the development of much-needed antimicrobial agents.

Loni SDM clarified that four employees have tested positive for coronavirus and not all of them, as claimed.

A Joint statement on behalf of the United States and the European Union:

There are major regulatory lapses in the manufacturing of similar biologics in India. The use of scientific audits could strengthen the regulatory system and improve the provision of high quality biosimilars in the country, according to a recent opinion piece [1] by Dr GR Soni, which was published in GaBI Journal.

Cuevas-Cerveró, Aurora and Razquín-Zazpe, Pedro and Parra-Valero, Pablo and Barrios-Martínez, Cristina and Gómez-Hernández, José-Antonio . Accesibilidad informacional y diversidad funcional en el contexto universitario: el caso de la Universidad Complutense de Madrid., 2020 In: Competencia en Información y Políticas para Educación Superior: Estudos Hispano-Brasileiros. Universidad Complutense de Madrid, pp. 132-146. [Book chapter]

Bharatiya Janata Party (BJP) Member of Legislative Assembly (MLA) Ram Kadam has issued a clarification on his 'elope' remark and said that his statement was quoted out of context.

The BJP MLA from Ghatkopar constituency faced a backlash after a video of him where he can be reportedly heard saying that he would kidnap a girl even if she refuses a proposal from a boy and help him elope with her, surfaced on media.

Clarifying his stance on the issue, Kadam told ANI, "A 40-second incomplete video is being circulated by opposition leaders. I would only request them to listen to my complete statement. If my statement has hurt anyone, I won¿t mind expressing regret for the same."

"My statement is being quoted out of context. At that event, I said that all youngsters whether it be a boy or girl should take their parents" in confidence before marrying. If they elope without taking their permission, the parents feel disheartened and it is very wrong to disappoint your parents. After saying so I took a long pause and someone from the audience said something which I repeated on the mike. I also kept speaking after that as well but it was not reported. If I had said anything objectionable, it was being live telecasted and there were a number of journalists present at the venue and someone would have pointed it out. But no one raised an objection because they had heard me completely. To find the true meaning of an address one must listen to it completely," he added.

The BJP MLA made the statement during a 'Dahi Handi' festival organised in Mumbai on the auspicious occasion of 'Janmashtami' on Monday.

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A new review published in i Frontiers in Neuroscience /i explores the current literature and advancements in the applications of neuroscience in law.

Public comments are invited on the discussion draft on the use of profit splits in the context of global value chains, released as part of the work in relation to Action 10 of the BEPS Action Plan.

On 16 December 2014, the OECD invited comments from interested parties on a discussion draft on the use of profit splits in the context of global value chains. This work relates to Action 10 of the BEPS Action Plan. The OECD is grateful to the commentators for their input, and now publishes the comments received.

This paper explores the development of the bioplastics sector and its role in national bioeconomy strategies. It finds that bioplastics are at a disadvantage compared to some other biobased products, notably biofuels, that often benefit from preferential treatment. It also notes that greater efforts are needed at the international level as regards standards to avoid creating barriers to international trade in biobased products.

With gross government debt of 219% of GDP in 2016, Japan’s fiscal situation is in uncharted territory and puts the economy at risk.

The British heavyweight star reacted to Hearn's antics, after the Matchroom Boxing boss' most memorable interview lines were uploaded online for followers to apply to random scenarios.

Basingstoke : Palgrave Macmillan, 2019.

Cham, Switzerland : Palgrave Macmillan, [2019]

[S.l.] : PALGRAVE MACMILLAN, 2019.

Dordrecht ; Norwell, MA : Springer, [2005]

Dewey Library - HC120.E5 O45 2019

Long, Paul, 1967- author

In May last year, we brought you news on Ping.it, a Web-based RSS reader that lets you create tailored feeds by keywords and popularity. At its most basic

complete article

Online Resource

Something I’ve been wanting for a long time, define different regions like a footer section, or side bar and not have to deal with all the contextual styling hassle. A.k.a. “Now that this button is used on a dark background, the button needs to change its colors too. Where should the styles live?”. Here an old post about struggling with contextual styling.

So then the other day I was doing some experiments with using custom properties for Atom’s UI. Turns out, using custom properties might make contextual styling a bit easier. For the rest of the post, let’s switch to a more simple example. A page where the main area is light, but then has a dark hero and footer section. Like this:

In the past, I probably would’ve created variations like Button--dark or overwrote it with header .Button {…}. Depends a bit on the project. Here another approach: Create themes with a set of variables, then apply the theme to the different areas.

1. Default theme

First let’s define our default theme with a bunch of variables.

[data-theme="default"] {
  --fg:         hsl(0,0%,25%);
  --border:     hsl(0,0%,75%);
  
  --bg:         hsl(0,0%,95%);
  --button-bg:  hsl(0,0%,99%);
  --input-bg:   hsl(0,0%,90%);
}

Then we create some components where we use the variables defined above.

[data-theme] {
  color: var(--fg);
  background-color: var(--bg);
}

.Button {
  color: var(--fg);
  border: 1px solid var(--border);
  background-color: var(--button-bg);
}

.Input {
  color: var(--fg);
  border: 1px solid var(--border);
  background-color: var(--input-bg);
}

And lastly we add the [data-theme="default"] attribute on the body so that our components will pick up the variables.

<body data-theme="default">

If you wonder why use data-theme attributes over classes? Well, no specific reason. Maybe with attributes, it’s a hint that only one theme should be used per element and is more separated from your other classes.

At this point we get this:

See the Pen Contextual styling with custom properties (1/3) by simurai (@simurai) on CodePen.

2. Dark theme

But our designer wants the hero and footer to be dark. Alright, let’s define another theme region.

[data-theme="dark"] {
  --fg:         hsl(0,10%,70%);
  --border:     hsl(0,10%,10%);
  
  --bg:         hsl(0,0%,20%);
  --button-bg:  hsl(0,0%,25%);
  --input-bg:   hsl(0,0%,15%);
}

And add the theme attribute to the header and footer.

<header data-theme="dark">
<footer data-theme="dark">

Which gives us this:

See the Pen Contextual styling with custom properties (2/3) by simurai (@simurai) on CodePen.

The reason why this works is that custom properties cascade and can be overridden on nested elements, just like normal properties.

3. Hero theme

A few months pass and our designer comes back with a redesigned hero section. “To make it look fresh” with a splash of color.

No problem! Just like with the dark theme, we define a new “hero” theme.

[data-theme="hero"] {
  --fg:         hsl(240,50%,90%);
  --border:     hsl(240,50%,10%);
  
  --bg:         hsl(240,33%,30%);
  --button-bg:  hsl(240,33%,40%);
  --input-bg:   hsl(240,33%,20%);
}

<header data-theme="hero">

And here is that fresh hero:

See the Pen Contextual styling with custom properties (3/3) by simurai (@simurai) on CodePen.

It’s also not limited to colors only, could be used for sizes, fonts or anything that makes sense to define as variables.

Benefits

Using these theme “regions” lets your components stay context un-aware and you can use them in multiple themes. Even on the same page.

• Developers can add components, move components around, without having to know about in what context (theme) they live. The markup for the components stays the same.
• Design systems authors can create new components without worrying about where they get used, the variables used in components stay the same.
• Designers can define new theme regions, or change existing ones, without having to make changes to a component’s HTML or CSS, it stays the same.

Less time to talk about who, how and where, more time to talk about the weather. ☔️????

Concerns

Yeah, right. The big question: But does it scale? Can this be used for all use cases.

Ok, I’m pretty sure it doesn’t fit all situations. There are just too many to find a single solution for them all. And I’m actually not sure how well it scales. I guess it works great in these simple demos, but I have yet to find a larger project to test it on. So if you have used (or plan to use) this approach, I’m curious to know how it went.

A concern I can imagine is that the list of variables might grow quickly if themes have totally different characteristics. Like not just a bit darker or lighter backgrounds. Then you might need to have foreground and border colors for each component (or group of components) and can’t just use the general --fg and --border variables. Naming these variables is probably the hardest part.

Update I

@giuseppegurgone made an interesting comment:

in suitcss projects I used to define component level custom props, theme variables and then create themes by mapping the former to the latter suitcss-toolkit

So if I understood it correctly, by mapping theme variables to component variables, you could avoid your theme variables from growing too much and you can decide for each component how to use these theme variables.

Update II

If it’s too early to use custom properties in your project, @szalonna posted an example how to do something similar in SCSS.

Hayden Library - NX161.W54 2018

Hayden Library - PQ7296.J6 A6 2016

Berlin ; New York : Springer, [2005]

Online Resource

Dewey Library - JZ5597.R45 2018

Hayden Library - PN1997.2.M897 P67 2017

Online Resource

Hall, Matthew (Criminologist), author

Brown, Stephen Eugene, 1951- author

Bix, Brian, author