Shukai Du and Francisco-Javier Sayas
Math. Comp. 89 (2019), 1745-1782.
Abstract, references and article information

Ricardo G. Durán, Enrique Otárola and Abner J. Salgado
Math. Comp. 89 (2020), 1581-1603.
Abstract, references and article information

Guher Camliyurt, Igor Kukavica and Vlad Vicol
Trans. Amer. Math. Soc. 373 (2020), 3375-3422.
Abstract, references and article information

V. M. Radchenko and N. O. Stefans’ka
Theor. Probability and Math. Statist. 99 (2020), 229-238.
Abstract, references and article information

O. D. Borysenko and D. O. Borysenko
Theor. Probability and Math. Statist. 99 (2020), 67-75.
Abstract, references and article information

S. V. Bodnarchuk and O. M. Kulyk
Theor. Probability and Math. Statist. 99 (2020), 53-65.
Abstract, references and article information

D. Pauly and S. Repin
St. Petersburg Math. J. 31 (2020), 533-555.
Abstract, references and article information

N. V. Krylov
St. Petersburg Math. J. 31 (2020), 509-520.
Abstract, references and article information

The Leisure & Cultural Services Department’s Community Oral History Theatre Project will be launched in Kowloon City District on January 15.

An oral history theatre performance and a sharing session will kick off the project.

The performance will feature an excerpt from the production of Sai Kung, Therefore I Live.

It will be held at Hung Hom Community Hall.

Admission is free with tickets.

Click here for details.

John R. White
May 1, 2014; 27:82-86
From Research to Practice

Secretary for Financial Services & the Treasury Christopher Hui today visited the Companies Registry (CR) to inspect its operation.

Mr Hui visited the New Companies Section, the Public Search Section and the Document Management Section at the registry and spoke with staff there to learn about their work conditions and the services that they provide.

He said: “The COVID-19 pandemic has dealt a heavy blow to Hong Kong's overall economy.

“To help enterprises cope with their operating pressure amid the economic downturn, the Financial Secretary announced in the 2020-21 Budget the waiver of registration fees for annual returns, except for late delivery, charged by the CR for two years.

“And with a view to encouraging the wider use of the CR's electronic services, we also propose to reduce the fees payable in relation to the incorporation of companies, including registration of non-Hong Kong companies, through electronic means by 10%."

The Companies (Fees) (Amendment) Regulation 2020 gazetted today will be tabled at the Legislative Council for negative vetting on May 13 for the waiver and reduction to take effect from October 1.

The waiver of registration fees for annual returns will benefit about 1.4 million companies.

Mr Hui added that he was pleased that the CR has been providing electronic services for filing of documents and company searches.

He appealed to the department to adopt wider use of technology, adding that a business-friendly environment is needed more than ever in the process of economic recovery.

Mr Hui also expressed gratitude to CR staff for their dedication in providing public services amid the pandemic.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

(American Chemical Society) The COVID-19 pandemic has scientists considering a few less-conventional options while vaccines against SARS-CoV-2 are being developed. One option might be the oral polio vaccine. We chatted with one of the researchers proposing the idea -- Robert Gallo, M.D. -- to understand why a vaccine that hasn't been used in the U.S. for two decades might provide short-term protection against this new coronavirus: https://youtu.be/Wqw4aX4c33c.

After you submit a stored process from the SAS Stored Process Web Application, the generated URL is placed into a cell in a Microsoft Excel worksheet. When you click this URL, you expect that the stored process is sub

The SAS Stored Process Server does not create a detailed log file by default. However, you can create a detailed SAS Stored Process Server log file (that will contain information about all of the code that was executed) by using this approach. AUTO

(University of Houston) A University of Houston biomedical researcher is developing a new device to treat babies with blood disorders, because current technology is designed for adults. The ability to perform lifesaving leukapheresis safely and effectively in these most vulnerable pediatric patients will significantly increase their access to highly effective cell-based therapies.

Every summer, rainstorms occur in Hong Kong occasionally, leading to loss of property or even casualties.

(American Marketing Association) The positive outcomes of customer reacquisition more than offset the costs. Successful reacquisition management, though, requires a failure-tolerant company culture and guidelines.

(Max Planck Institute for the Science of Human History) What makes our species unique compared to other hominins? High profile genetic, fossil and material culture discoveries present scientists working in the Late Pleistocene with an ever-more complex picture of interactions between early hominin populations. One distinctive characteristic of Homo sapiens, however, appears to be its global distribution. Exploring how Homo sapiens colonized most of the world's continents in a relatively short period could reveal the exceptional capacities of humans relative to other hominins.

(Cell Press) In a study appearing April 30 in the journal Current Biology, scientists tell the story of three 16th century African slaves identified from a mass burial site in Mexico City. Using a combination of genetic, osteological, and isotope analyses, the scientists determined from where in Africa they were likely captured, the physical hardships they experienced as slaves, and what novel pathogens they may have carried with them across the Atlantic.

(Max Planck Institute for the Science of Human History) Three 16th-century skeletons from a mass burial in Mexico City highlight the role of the transatlantic slave trade in introducing and disseminating new pathogens to the Americas. Researchers from the Max Planck Institute for the Science of Human History and Escuela Nacional de Antropología e Historia in Mexico analyzed skeletal features, genetic data and isotopes to explore the life history of three enslaved Africans and explore the wide-ranging impacts of massive forced migration.

(George Mason University) Nathan Sleeter, Research Assistant Professor, Roy Rosenzweig Center for History and New Media (RRCHNM), is directing a project in which RRCHNM will create three classroom simulations based on events from the history of diplomacy for secondary education instructors.

(Stanford School of Engineering) After analyzing 95 million traffic stop records, filed by officers with 21 state patrol agencies and 35 municipal police forces from 2011 to 2018, a Stanford-led research team concluded that 'police stops and search decisions suffer from persistent racial bias.'

A man has been arrested in connection with the “vile and brutal” murders of 8-year-old Toya Brown and 15-year-old Nyron Taylor, who were shot and killed last evening, revealed Minister of National Security, Dr. Horace Chang. Chang says...

It is possible that the next time you walk into a bar you may find that there is only standing room, and you are among a handful of persons allowed inside. Prime Minister Andrew Holness said that in addition to having a specific gathering rule,...

Samvel K Gularyan
Apr 6, 2020; 0:RA120.001986v1-mcp.RA120.001986
Research

The currently available therapeutic radiopharmaceutical for high-risk neuroblastoma, ¹³¹I-MIBG, is ineffective at targeting micrometastases due to the low linear energy transfer (LET) properties of high-energy beta particles. In contrast, Auger radiation has high-LET properties with nanometer ranges in tissue, efficiently causing DNA damage when emitted in close proximity to DNA. The aim of this study was to evaluate the cytotoxicity of targeted Auger therapy in pre-clinical models of high-risk neuroblastoma. Methods: Using a radiolabeled poly(ADP-ribose) polymerase (PARP) inhibitor, ¹²⁵I-KX1, we delivered an Auger emitter iodine-125 to PARP-1: a chromatin-binding enzyme overexpressed in neuroblastoma. In vitro cytotoxicity of ¹²⁵I-KX1 was assessed in nineteen neuroblastoma cell lines, followed by in-depth pharmacological analysis in a sensitive and resistant pair of cell lines. Immunofluorescence microscopy was used to characterize ¹²⁵I-KX1-induced DNA damage. Finally, in vitro/in vivo microdosimetry was modeled from experimentally derived pharmacological variables. Results: ¹²⁵I-KX1 was highly cytotoxic in vitro across a panel of neuroblastoma cell lines, directly causing double strand DNA breaks. Based on subcellular dosimetry, ¹²⁵I-KX1 was approximately twice as effective compared to ¹³¹I-KX1, whereas cytoplasmic ¹²⁵I-MIBG demonstrated low biological effectiveness. Despite the ability to deliver focused radiation dose to the cell nuclei, ¹²⁵I-KX1 remained less effective than its alpha-emitting analog ²¹¹At-MM4, and required significantly higher activity for equivalent in vivo efficacy based on tumor microdosimetry. Conclusion: Chromatin-targeted Auger therapy is lethal to high-risk neuroblastoma cells with potential use in micrometastatic disease. This study provides the first evidence for cellular lethality from a PARP-1 targeted Auger emitter, calling for further investigation into targeted Auger therapy.

Objectives: Esthesioneuroblastoma (ENB) is rare with limited therapeutic options when unresectable or metastatic; however, expression of somatostatin receptors qualifies it for peptide receptor radionuclide therapy (PRRT). We report outcomes of PRRT in ENB from two referral centers. Methods: Using PRRT databases at two European Neuroendocrine Tumour Society Centers of Excellence, case finding was undertaken between 2004-2018 for patients who had PRRT with recurrent/metastatic ENB deemed unsuitable for further conventional therapies. Evaluations of response using a composite reference standard and for survival were performed. Results: Of seven patients, four had partial response, two had disease stabilization and one had early progression. Possible side effects include worsening CSF-leaks. Median progression-free survival was 17 months (range, 0-30), and median overall survival was 32 months (range, 4–53). Conclusion: PRRT shows promising efficacy and moderate survival duration in unresectable locally advanced or metastatic ENB warranting larger cohort studies incorporating measures of quality of life.