Growth at any cost is, well, costing us — and we can’t rely on the marketplace to solve the earth’s problems.

David Murray-Hundley, the Grumpy Entrepreneur, shares his six pieces of advice for founders of fast growing companies to help maintain control

A. Seesanea and I. E. Verbitsky
St. Petersburg Math. J. 31 (2020), 557-572.
Abstract, references and article information

How to optimise your website, increase conversions and monetise your online offering

There aren’t a ton of synonyms for the word “hypocrisy.” I’ve become aware of this problem ever since I began writing about the Tara Reade–Joe Biden situation. I keep gravitating towards phrases such as “despicable hypocrisy,” or “partisan hypocrisy,” or “unconscionable hypocrisy,” but you can only go to the well so often. Really, though, I’m not sure how else to describe the actions of someone like Senator Dianne Feinstein.You might recall that it was Feinstein, the ranking member of the Judiciary Committee, who withheld Christine Blasey Ford's allegation of sexual misconduct against Supreme Court nominee Brett Kavanaugh from the Senate so that it could not be properly vetted, in a last-ditch effort to sink the nomination.Feinstein knew that Ford's credibility was brittle -- the alleged victim could not tell us where or when the attack occurred, hadn’t mentioned Kavanugh’s name to anyone for over 30 years, and offered nothing approaching a contemporaneous witness.At first, Feinstein did not want to provide Ford’s name, or a place or time of the alleged attack, or allow the accused to see any evidence against him, denying him the ability to answer the charges.Henceforth this brand of justice could be referred to as “The Joe Biden Standard,” since it’s exactly the kind of show trial the presumptive Democratic nominee promises college kids via Title IX rules.When finally asked about Reade yesterday, Feinstein responded: “And I don’t know this person at all who has made the allegations. She came out of nowhere. Where has she been all these years? He was vice president.”To put this in perspective, when Ford came forward “out of nowhere,” Feinstein said: “Victims must be able to come forward only when they are ready.”What’s changed?During the Kavanaugh hearings Feinstein noted that “sharing an experience involving sexual assault — particularly when it involves a politically connected man with influence, authority and power — is extraordinarily difficult.”Is Biden not a politically connected man with influence, authority, and power? Feinstein is now arguing the opposite: She is saying we should dismiss Reade’s allegations because she failed to come forward against a powerful man earlier.But to answer Feinstein’s question about what Reade has been “up to” the past 27 years: Well, she’s been telling people that Biden had engaged in sexual misconduct. She relayed her story to her former neighbor, her brother, her former co-worker, and at least two other friends. It is also likely that her mother called Larry King Live asking for advice for her daughter the year of the alleged attack.Yesterday a document uncovered by local journalists in California -- somehow missed by Barack Obama’s crack vetting team -- shows Reade’s ex-husband bolstering her claim in 1996 divorce proceedings: “On several occasions [Reade] related a problem that she was having at work regarding sexual harassment, in U.S. Senator Joe Biden's office.”The reaction to the divorce papers has been extraordinary. Biden defenders argue that because Reade alleged “sexual harassment” -- a catch-all term used in the 1990s when men were getting away with despicable behavior far more often -- it proves her story has changed. Biden, through his deputy campaign manager Kate Bedingfield, alleges that “more and more inconsistencies” come up every day.Even if Reade didn't tell everyone everything that allegedly happened every time she mentioned the incident, that doesn’t definitively prove anything. If it did, none of us would have ever heard the name Christine Blasey Ford.Indeed, at time of Ford’s evolving story, there was a slew of journalists taking deep dives into the unreliability of memory and trauma and complexities of relaying assault allegations. I assume that science hasn’t changed in two years.Let’s also not forget that, despite Ford’s inconsistencies, Biden still argued that Kavanaugh should be presumed guilty. Why shouldn’t he?It is also quite amazing to see Biden’s defenders implicitly contending that Reade is only credibly claiming that she was sexually harassed for nearly 30 years, so her story must be politically motivated.Even if we concede that Reade is a wily Sanders operative or Putin stooge, what political motive could Reade possibly have had back in 1993 -- after working for Biden -- to smear the senator? What motive did she have to repeat that story to her family before Sanders was a candidate or Putin was running Russia?By the way, liberals have never argued that political motivations should be disqualifying. Ford came forward, by her own admission, because she did not believe the man who had allegedly assaulted her in high school should be given a seat on highest court in the land. Reade says she doesn’t want a man who allegedly assaulted her -- when he was in his 50s -- to hold the most powerful office in the world.Feinstein, of course, isn’t the only one to engage in this kind of transparent double standard. When asked about Reade, the idealist Alexandria Ocasio-Cortez, said, “I’m not sure. Frankly, this is a messy moment, and I think we need to acknowledge that -- that it is not clear-cut.”Where was all this hand-wringing and caution over the messiness of sexual-assault claims when nearly every Democrat and all their allies in the press were spreading Julie Swetnick’s alleged “gang rape” piece? Nowhere.AOC, whose position on Biden has evolved, invited Ana Maria Archila, the women who had famously cornered a weak-kneed senator Jeff Flake in an elevator and yelled at him about Kavanaugh, to the 2019 State of the Union address. Archila now says, “I feel very trapped.”I bet.People point out that there are numerous sexual-misconduct allegations leveled at Donald Trump. Indeed. If they haven’t yet, news outlets should scrutinize and investigate the credibility of those allegations, as they did for Biden but not for Kavanaugh. But it’s important to remember that Trump accuser E. Jean Carroll was given immediate and widespread coverage on cable news, while Reade reportedly wasn’t asked to tell her story by any major network -- save Fox News -- until this week.Of course, most Biden defenders are being purposely obtuse about the debate -- Mona Charen’s recent column is an excellent example. The problem isn’t that Biden is being treated unjustly, or that he should be treated unjustly; it’s that he is being treated justly by the same people who treat others unjustly. Democrats have yet to explain why Biden is afforded every benefit of the doubt but not Kavanaugh, and not millions of college students.Public figures such as Biden have every right to demand fair hearings and due process. Voters have every right to judge the credibility of both accuser and accused. Many women are victims. Many women are victims who are powerless to prove it. And some women are frauds. You can’t keep demanding that our political system adjudicate similar incidents under two completely differ set of rules. It’s untenable.

18 February 2019

Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)⁺ compared with AAb^– relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb⁺ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb⁺ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction.

Methods that provide rapid access to radiolabeled antibodies are vital in the development of diagnostic and radiotherapeutic agents for positron emission tomography (PET) or radioimmunotherapy. The human hepatocyte growth factor receptor (c-MET) signaling pathway is dysregulated in a number of malignancies including gastric cancer, and is an important biomarker in drug discovery. Here, we used a photoradiochemical approach to produce ⁸⁹Zr-radiolabeled onartuzumab (a monovalent, anti-human c-MET antibody), starting directly from the fully formulated drug (MetMAb). Methods: Simultaneous ⁸⁹Zr-radiolabeling and protein conjugation was performed in one-pot reactions containing ⁸⁹Zr-oxalate, the photoactive chelate DFO-aryl azide (DFO-ArN3) and MetMAb to give ⁸⁹ZrDFO-azepin-onartuzumab. As a control, ⁸⁹ZrDFO-Bn-NCS-onartuzumab was prepared via a conventional two-step process using pre-purified onartuzumab and DFO-Bn-NCS. Radiotracers were purified by using size-exclusion methods and evaluated by radiochromatography. Radiochemical stability was studied in human serum and immunoreactivity was determined by cellular binding assays using MKN-45 gastric carcinoma cells. PET imaging at multiple time points (0–72 h) was performed in female athymic nude mice bearing subcutaneous MKN-45 xenografts. Biodistribution experiments were performed after the final image. Tumor specificity of ⁸⁹ZrDFO-azepin-onartuzumab was assessed by competitive inhibition (blocking) studies. Results: Initial photoradiosynthesis experiments produced ⁸⁹ZrDFO-azepin-onartuzumab in <15 min. with an isolated decay-corrected radiochemical yield (RCY) of 24.8%, a radiochemical purity (RCP) ~90% and a molar activity (Am) of ~1.5 MBq nmol^-1. Reaction optimization improved the radiochemical conversion (RCC) of ⁸⁹ZrDFO-azepin-onartuzumab to 56.9±4.1% (n = 3), with isolated RCYs of 41.2±10.6% (n = 3), and RCPs >90%. Conventional methods produced ⁸⁹ZrDFO-Bn-NCS-onartuzumab with isolated RCY >97%, RCP >97% and Am ~14.0 MBq nmol^-1. Both radiotracers were immunoreactive and stable in human serum. PET imaging and biodistribution studies showed high tumor uptake for both radiotracers. By 72 h, tumor and liver uptake reached 15.37±5.21 %ID g^-1, 6.56±4.03 %ID g^-1, respectively for ⁸⁹ZrDFO-azepin-onartuzumab (n = 4), and 21.38±11.57 %ID g^-1 and 18.84±6.03 %ID g^-1 for ⁸⁹ZrDFO-Bn-NCS-onartuzumab (n = 4). Blocking experiments gave a statistically significant reduction in tumor uptake (6.34±0.47 %ID g^-1) of ⁸⁹ZrDFO-azepin-onartuzumab (n = 4). Conclusion: Experiments demonstrate that photoradiosynthesis is a viable alternative approach for producing ⁸⁹Zr-radiolabeled antibodies direct in protein formulation buffer which reduces protein aggregation and liver uptake.

Invitation Only Research Event

Event participants

Abebe Aemro Selassie, Director, African Department, International Monetary Fund
Chair: Elizabeth Donnelly, Deputy Head and Research Fellow, Africa Programme, Chatham House

3 October 2019

The Chatham House Africa Programme designed the Sudan Stakeholder Dialogues series to help identify the factors that have led to the current economic crisis, the immediate steps that need to be taken to avert collapse and stabilize the economy, and the longer-term structural reforms required to set Sudan on the path to recovery. The project is funded by Humanity United.

10 October 2019

This briefing note is the result of a collaborative research process with the Zimbabwean private sector, government representatives, industry organizations and experts, drawing on best practice and senior-level insights to identify policy options for long-term economic revival and expansion in Zimbabwe, and pathways for inclusive development.

Research Event

Event participants

Hon Bruno Nabagné Kone, Minister of Construction, Housing and Urban Planning, Republic of Côte d'Ivoire

Research Event

Event participants

Paul Mashatile, Treasurer General, African National Congress (ANC)

Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (~82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (cj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed cj0025c was capable of utilizing known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in cj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not cj0025c. Provision of an alternate sulfur source (2 mM thiosulfate) restored cj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species.

17 December 2019

How is it possible for the directors of the Russian economy to pursue an orthodox stabilization policy with a great measure of success and yet to have achieved so little to stem the growth slowdown? This paper examines the reasons for the divergence in economic management.

Nonalcoholic steatohepatitis has emerged as a major cause of liver diseases with no effective therapies. Here, we evaluate the efficacies and pharmacokinetics of B1344, a long-acting PEGylated FGF21 analog, in a nongenetically modified nonhuman primate species that underwent liver biopsy, and demonstrate the potential for efficacies in humans. B1344 is sufficient to selectively activate signaling from the βKlotho/FGFR1c receptor complex. In cynomolgus monkeys with nonalcoholic fatty liver disease, administration of B1344 via subcutaneous injection for eleven weeks caused a profound reduction of hepatic steatosis, inflammation and fibrosis, and amelioration of liver injury and hepatocyte death as evidenced by liver biopsy and biochemical analysis. Moreover, improvement of metabolic parameters was observed in the monkey, including reduction of body weight and improvement of lipid profiles and glycemic control. To determine the role of B1344 in the progression of murine NAFLD independent of obesity, administration of B1344 were performed in mice fed with methionine and choline deficiency diet. Consistently, B1344 administration prevented the mice from lipotoxicity damage and nonalcoholic steatohepatitis at a dose-dependent manner. These results provide preclinical validation for an innovative therapeutics to NAFLD, and support further clinical testing of B1344 for treating nonalcoholic steatohepatitis and other metabolic diseases in humans.

17 December 2019

How is it possible for the directors of the Russian economy to pursue an orthodox stabilization policy with a great measure of success and yet to have achieved so little to stem the growth slowdown? This paper examines the reasons for the divergence in economic management.

Sean Newcomb entered last June as an All-Star candidate and exited the regular season wondering if he had done enough to earn a spot on Atlanta's postseason roster. The inconsistent nature of his first full Major League season enhances the difficulty of projecting how valuable he might be to the Braves from both an immediate and long-term perspective.

Long a country of emigration and a springboard for migrants aiming to reach Europe, Morocco has emerged as a destination for many sub-Saharan Africans. As more migrants remain in Morocco, the kingdom has implemented policies to aid with integration. But challenges remain, with most of the estimated 700,000 sub-Saharan Africans living in precarious conditions and irregular status despite some legalization programs.

OBJECTIVE

This study investigates two-phase growth patterns in early life and their association with development of islet autoimmunity (IA) and type 1 diabetes (T1D).

As the COVID-19 pandemic begins to take root in Africa, experts say that digitizing financial services could help keep the continent safe

From online petitions to organized walkouts, corporate America is facing increasing employee activism over its business involvement with agencies implementing the federal government's immigration policies. This "cubicle activism," seen at companies ranging from Amazon and Google to Bank of America and Wayfair, has garnered mixed success to date, forcing divestiture from private prison contractors but fewer results in other contexts, as this article explores.

More than 1 million Tajiks migrate to Russia every year—a sizeable outflow for a country of about 9 million people. These high levels of emigration have had major effects for Tajikistan, especially in the generation of remittances that help lift everyday Tajiks out of poverty but have also made the country increasingly dependent on Russia. This article explores challenges faced by Tajik migrants in Russia and the effects of emigration on Tajikistan’s economy and society.

Resilience and strength can often be attained through unexpected routes

-- Read more on ScientificAmerican.com

Dual Language Learners (DLLs) are a growing segment of the Minnesota young child population, and a particularly "superdiverse" one with myriad origins, cultures, and languages—a new reality other states and communities will face. Drawing on interviews with policymakers and service providers, as well as analysis of census data, this report examines what this incredible diversity means for the state’s early childhood policies and programs.

WASHINGTON — Latinos and immigrants are at least twice as likely to lack health insurance coverage as the overall population in three central Kansas City metro counties, a new Migration Policy Institute (MPI) study reveals. In fact, they are four times as likely to be uninsured in Johnson County, Kansas. 

Over the last decade, a number of governments have launched start-up visa programs in the hopes of attracting talented immigrant entrepreneurs with innovative business ideas. With the track record for these programs a mixed one, this report explains how embedding start-up visas within a broader innovation strategy could lead to greater success.

What if we could harness the ocean's movement to protect coastal communities from rising sea levels? Designer and TED Fellow Skylar Tibbits shows how his lab is creating a dynamic, adaptable system of underwater structures that uses energy from ocean waves to accumulate sand and restore eroding shorelines -- working with the forces of nature to build rather than destroy.

States are tweaking voter registration laws for teenage voters and schools are busing students to the polls. Will these efforts help young people get in the habit of voting?

In five northern U.S. states, black students comprise more than a fifth of ELL enrollment.

Food security -- Australia.

Sexual minority youth -- Australia.