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IBM y VON DER HEIDE, compañía especializada en servicios de consultoría de Recursos Humanos, informan que han firmado una importante alianza para expandir su oferta de servicios de Employee Engagement y HR Analytics en toda América Latina. Por medio de las tecnologías de IBM, esta alianza le permitirá a VON DER HEIDE brindar a sus clientes una oferta de consultoría única en el mercado, para transformar estrategias de talento en resultados de negocio.

Ještě minulý týden byly úřední hodiny kontaktních pracovišť Úřadu práce ČR velmi omezené. Pobočky sice v pondělí otevřely, ani dnes ale na úřad nemusíte osobně, většinu záležitostí vyřídíte online. Poradíme jak na to a shrneme, kdy a v jaké výši máte nárok na podporu v nezaměstnanosti.

Wrapped up my Banos trip focus was on Spanish classes but plenty of hiking opportunity and wanted to get dialed into vegetatation soils stability before Malinguapamba MP. Banos is warmer than MP and sets on metamorphic rock with volcanics above. Plent

The 28 or so hours traveling here has proven to be more than worth itWhile the flight from Houston to Santiago was overnight and in the dark the three hours from Santiago to Punta Arenas were spent winging over the Andes. Amazing is a word overused i

A tentativa resultou em pelo menos oito mortes e a prisão até agora de 13 pessoas, incluindo dois cidadãos americanos.

Objectives: Lutetium-177 (¹⁷⁷Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies.

Purpose: This prospective study evaluated the imaging performance of a novel immunological pretargeting positron-emission tomorgraphy (immuno-PET) method in patients with HER2-negative, carcinoembryonic antigen (CEA)-positive, metastatic breast cancer (BC), compared to computed tomography (CT), bone magnetic resonance imaging (MRI), and ¹⁸Fluorodeoxyglucose PET (FDG-PET). Patients and Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq ⁶⁸Ga-IMP288, a histamine-succinyl-glycine peptide given following initial targeting of a trivalent anti-CEA, bispecific, anti-peptide antibody. The gold standards were histology and imaging follow-up. Tumor standard uptake values (SUV_max and SUVmean) were measured, and tumor burden analyzed using Total Tumor Volume (TTV) and Total Lesion Activity (TLA). Results: Total lesion sensitivity of immuno-PET and FDG-PET was 94.7% (1116/1178) and 89.6% (1056/1178), respectively. Immuno-PET had a somewhat higher sensitivity than CT and FDG-PET in lymph nodes (92.4% vs 69.7% and 89.4%, respectively) and liver metastases (97.3% vs 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI and FDG-PET for bone lesions (95.8% vs 90.7% and 89.3%, respectively). In contrast to FDG-PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUV_max, SUVmean, and TTV, TLA was significantly higher with immuno-PET compared to FDG PET (P = 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by ⁶⁸Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive, metastatic BC patients, and warrants further research.

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, ⁶⁴Cu (half-life, 12.7 h) and ²²⁵Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of ⁶⁴Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of ⁶⁸Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, ²²⁵Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n = 6). Tumor size was monitored and compared with that of control mice (n = 6). Results: Dynamic imaging of ⁶⁴Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of ⁶⁴Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for ⁶⁴Cu-FAPI-04 than for ⁶⁸Ga-FAPI-04, except in the heart, and excretion in the urine was higher for ⁶⁸Ga-FAPI-04 than for ⁶⁴Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. ²²⁵Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that ⁶⁴Cu-FAPI-04 and ²²⁵Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.

Convocamos un seminario en línea (webinar) en español en la ocasión del lanzamiento del informe, Creatividad dentro de la crisis: opciones legales para inmigrantes venezolanos en América Latina, que describe donde se han radicado los migrantes venezolanos; las medidas que han utilizado los gobiernos latinoamericanos para regularizar el estatus legal de los migrantes venezolanos; y los esfuerzos por integrar a los recién llegados en sus nuevas comunidades de residencia.

La migración centroamericana a los Estados Unidos comenzó en gran números en los años ochenta, impulsada por la inestabilidad política, los desastres naturales y las dificultades económicas. Aproximadamente 3,4 millones de centroamericanos vivieron en los Estados Unidos en 2015, principalmente de El Salvador, Guatemala y Honduras. Dónde viven en los Estados Unidos, su competencia en inglés, su estado legal, las vías de inmigración, y más, están cubiertos en este artículo.

Si bien se ha prestado mucha atención a los centroamericanos recién llegados a la frontera entre los Estados Unidos y México, casi la mitad de los aproximadamente 3.5 millones que vivían en los Estados Unidos en 2017 llegaron antes de 2000. Aproximadamente un tercio son ciudadanos estadounidenses y tienden a participar en la fuerza laboral con más frecuencia que otros extranjeros y estadounidenses. Descubra más en este artículo lleno de datos.

WASHINGTON – A pesar de que los gobiernos de América Latina y el Caribe han tomado medidas generosas e innovadoras para lidiar con el desplazamiento forzado desde Venezuela y más recientemente desde Nicaragua, la cálida bienvenida se ha enfriado en algunos lugares a medida que el número de entradas, la presión sobre los servicios públicos y la preocupación del público aumenta.

Aunque colombianos encontraron un refugio cálido en Ecuador después de ser desplazados de su país por una guerra civil que duro décadas, la vida se ha vuelto más difícil para ellos en los últimos años, en parte como resultado del flujo de venezolanos que buscan seguridad. Este artículo se basa en encuestas de migrantes en Quito, comparando y contrastando las experiencias de colombianos y venezolanos, y evaluando sus percepciones de discriminación, victimización y esperanzas para el futuro.

Gaoxiang Jia, Xinlei Wang, Qiwei Li, Wei Lu, Ximing Tang, Ignacio Wistuba, Yang Xie.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1617--1647.

Abstract:
Formalin-fixed paraffin-embedded (FFPE) samples have great potential for biomarker discovery, retrospective studies and diagnosis or prognosis of diseases. Their application, however, is hindered by the unsatisfactory performance of traditional gene expression profiling techniques on damaged RNAs. NanoString nCounter platform is well suited for profiling of FFPE samples and measures gene expression with high sensitivity which may greatly facilitate realization of scientific and clinical values of FFPE samples. However, methodological development for normalization, a critical step when analyzing this type of data, is far behind. Existing methods designed for the platform use information from different types of internal controls separately and rely on an overly-simplified assumption that expression of housekeeping genes is constant across samples for global scaling. Thus, these methods are not optimized for the nCounter system, not mentioning that they were not developed for FFPE samples. We construct an integrated system of random-coefficient hierarchical regression models to capture main patterns and characteristics observed from NanoString data of FFPE samples and develop a Bayesian approach to estimate parameters and normalize gene expression across samples. Our method, labeled RCRnorm, incorporates information from all aspects of the experimental design and simultaneously removes biases from various sources. It eliminates the unrealistic assumption on housekeeping genes and offers great interpretability. Furthermore, it is applicable to freshly frozen or like samples that can be generally viewed as a reduced case of FFPE samples. Simulation and applications showed the superior performance of RCRnorm.

Thomas Staudt, Timo Aspelmeier, Oskar Laitenberger, Claudia Geisler, Alexander Egner, Axel Munk.

Source: Statistical Science, Volume 35, Number 1, 92--111.

Abstract:
Super-resolution microscopy is rapidly gaining importance as an analytical tool in the life sciences. A compelling feature is the ability to label biological units of interest with fluorescent markers in (living) cells and to observe them with considerably higher resolution than conventional microscopy permits. The images obtained this way, however, lack an absolute intensity scale in terms of numbers of fluorophores observed. In this article, we discuss state of the art methods to count such fluorophores and statistical challenges that come along with it. In particular, we suggest a modeling scheme for time series generated by single-marker-switching (SMS) microscopy that makes it possible to quantify the number of markers in a statistically meaningful manner from the raw data. To this end, we model the entire process of photon generation in the fluorophore, their passage through the microscope, detection and photoelectron amplification in the camera, and extraction of time series from the microscopic images. At the heart of these modeling steps is a careful description of the fluorophore dynamics by a novel hidden Markov model that operates on two timescales (HTMM). Besides the fluorophore number, information about the kinetic transition rates of the fluorophore’s internal states is also inferred during estimation. We comment on computational issues that arise when applying our model to simulated or measured fluorescence traces and illustrate our methodology on simulated data.

Otorrhea is common in children with tympanostomy tubes: annually, 2 of 3 children develop 1 or more episodes. Antibiotic-glucocorticoid eardrops are the most effective treatment in both the short- and long-term.

Treatment with antibiotic-glucocorticoid eardrops costs less than oral antibiotics and initial observation in children with tympanostomy tubes who develop otorrhea. Non–health care costs constitute a substantial proportion of the total costs of this condition. (Read the full article)

The entry-level Canon CanoScan LiDE 400 is a software-rich flatbed photo scanner that also handles text documents with ease.

For an occasional-use photograph and document scanner, the entry-level flatbed CanoScan LiDE 300 is a good value, but its LiDE 400 sibling is only $20 more and comes with valuable extras.

Steganos Safe creates secure encrypted storage for your sensitive files. It's very easy to use, and it offers some unique options for maintaining privacy and secrecy.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

ABSTRACT

Mitochondrial Ca²⁺ transport mediated by the uniporter complex (MCUC) plays a key role in the regulation of cell bioenergetics in both trypanosomes and mammals. Here we report that Trypanosoma brucei MCU (TbMCU) subunits interact with subunit c of the mitochondrial ATP synthase (ATPc), as determined by coimmunoprecipitation and split-ubiquitin membrane-based yeast two-hybrid (MYTH) assays. Mutagenesis analysis in combination with MYTH assays suggested that transmembrane helices (TMHs) are determinants of this specific interaction. In situ tagging, followed by immunoprecipitation and immunofluorescence microscopy, revealed that T. brucei ATPc (TbATPc) coimmunoprecipitates with TbMCUC subunits and colocalizes with them to the mitochondria. Blue native PAGE and immunodetection analyses indicated that the TbMCUC is present together with the ATP synthase in a large protein complex with a molecular weight of approximately 900 kDa. Ablation of the TbMCUC subunits by RNA interference (RNAi) significantly increased the AMP/ATP ratio, revealing the downregulation of ATP production in the cells. Interestingly, the direct physical MCU-ATPc interaction is conserved in Trypanosoma cruzi and human cells. Specific interaction between human MCU (HsMCU) and human ATPc (HsATPc) was confirmed in vitro by mutagenesis and MYTH assays and in vivo by coimmunoprecipitation. In summary, our study has identified that MCU complex physically interacts with mitochondrial ATP synthase, possibly forming an MCUC-ATP megacomplex that couples ADP and P_i transport with ATP synthesis, a process that is stimulated by Ca²⁺ in trypanosomes and human cells.

IMPORTANCE The mitochondrial calcium uniporter (MCU) is essential for the regulation of oxidative phosphorylation in mammalian cells, and we have shown that in Trypanosoma brucei, the etiologic agent of sleeping sickness, this channel is essential for its survival and infectivity. Here we reveal that that Trypanosoma brucei MCU subunits interact with subunit c of the mitochondrial ATP synthase (ATPc). Interestingly, the direct physical MCU-ATPc interaction is conserved in T. cruzi and human cells.

ABSTRACT

Bacterial flagellar motility plays an important role in many processes that occur at surfaces or in hydrogels, including adhesion, biofilm formation, and bacterium-host interactions. Consequently, expression of flagellar genes, as well as genes involved in biofilm formation and virulence, can be regulated by the surface contact. In a few bacterial species, flagella themselves are known to serve as mechanosensors, where an increased load on flagella experienced during surface contact or swimming in viscous media controls gene expression. In this study, we show that gene regulation by motility-dependent mechanosensing is common among pathogenic Escherichia coli strains. This regulatory mechanism requires flagellar rotation, and it enables pathogenic E. coli to repress flagellar genes at low loads in liquid culture, while activating motility in porous medium (soft agar) or upon surface contact. It also controls several other cellular functions, including metabolism and signaling. The mechanosensing response in pathogenic E. coli depends on the negative regulator of motility, RflP (YdiV), which inhibits basal expression of flagellar genes in liquid. While no conditional inhibition of flagellar gene expression in liquid and therefore no upregulation in porous medium was observed in the wild-type commensal or laboratory strains of E. coli, mechanosensitive regulation could be recovered by overexpression of RflP in the laboratory strain. We hypothesize that this conditional activation of flagellar genes in pathogenic E. coli reflects adaptation to the dual role played by flagella and motility during infection.

IMPORTANCE Flagella and motility are widespread virulence factors among pathogenic bacteria. Motility enhances the initial host colonization, but the flagellum is a major antigen targeted by the host immune system. Here, we demonstrate that pathogenic E. coli strains employ a mechanosensory function of the flagellar motor to activate flagellar expression under high loads, while repressing it in liquid culture. We hypothesize that this mechanism allows pathogenic E. coli to regulate its motility dependent on the stage of infection, activating flagellar expression upon initial contact with the host epithelium, when motility is beneficial, but reducing it within the host to delay the immune response.

With high sensitivity in detecting acute brain events such as seizures, FDG PET can be used as an important tool for neurocutaneous melanosis disease monitoring.

Midori Ishii and Bungo Akiyoshi

The kinetochore is a macromolecular protein complex that drives chromosome segregation in eukaryotes. Unlike most eukaryotes that have canonical kinetochore proteins, evolutionarily divergent kinetoplastids, such as Trypanosoma brucei, have unconventional kinetochore proteins. T. brucei also lacks a canonical spindle checkpoint system, and it therefore remains unknown how mitotic progression is regulated in this organism. Here, we characterized, in the procyclic form of T. brucei, two paralogous kinetochore proteins with a CLK-like kinase domain, KKT10 and KKT19, which localize at kinetochores in metaphase but disappear at the onset of anaphase. We found that these proteins are functionally redundant. Double knockdown of KKT10 and KKT19 led to a significant delay in the metaphase to anaphase transition. We also found that phosphorylation of two kinetochore proteins, KKT4 and KKT7, depended on KKT10 and KKT19 in vivo. Finally, we showed that the N-terminal part of KKT7 directly interacts with KKT10 and that kinetochore localization of KKT10 depends not only on KKT7 but also on the KKT8 complex. Our results reveal that kinetochore localization of KKT10 and KKT19 is tightly controlled to regulate the metaphase to anaphase transition in T. brucei.

This article has an associated First Person interview with the first author of the paper.

A new method called MicroMapping can identify nanoscale protein–protein interactions on live cells.

In physics, thermalization, or the trend of sub-systems within a whole to gain a common temperature, is typically the norm. There are situations, however, where thermalization is slowed down or virtually suppressed; examples are when considering the dynamics of electron and nuclear spins in solids. Understanding why this happens and how it can be controlled is presently at the center of a broad effort, particularly for applications in the emerging field of quantum information technologies.

Actor was struck by vehicle during family walk

Character's fate was famously left ambiguous at the end of the seminal gangster drama

In physics, thermalization, or the trend of sub-systems within a whole to gain a common temperature, is typically the norm. There are situations, however, where thermalization is slowed down or virtually suppressed; examples are when considering the dynamics of electron and nuclear spins in solids. Understanding why this happens and how it can be controlled is presently at the center of a broad effort, particularly for applications in the emerging field of quantum information technologies.

An international team has discovered an effective method for controlling the frequency of confined light at the nanoscale in the form of phonon polaritons (light coupled to vibrations in the crystal). The results have now been published in Nature Materials.

Researchers at Purdue University have developed a new technique to dramatically enhance the resolution achievable when imaging intracellular structures with super-resolution fluorescence microscopy. The technique uses the distortions created by a specimen to pinpoint the location of individual molecules, and thereby infer the location of intracellular structures. The technique could be particularly useful in studying […]

Ilios Shipping Company S.A., pleaded guilty in federal court in New Orleans for violating the Act to Prevent Pollution from Ships (APPS) and obstruction of justice, announced Assistant Attorney General Ignacia S. Moreno and U.S. Attorney Jim Letten.

Inovio Pharmaceuticals’ stock has climbed higher and higher over the past month since it said it was working on a speedy COVID-19 vaccine.

Vários mercenários foram mortos e outros presos em La Guaira, em 3 de maio, enquanto tentavam desembarcar na Venezuela como parte de uma conspiração contra o governo Maduro. Em 4 de maio, outros oito mercenários foram presos na cidade costeira de Chuao, no estado de Aragua, entre eles dois ex-veteranos das forças especiais dos EUA.

XVIII Habanos Festival: Once Again Havana Hosts the Major Annual Event of the World's Finest Tobacco, the Habano

Felicitacion Chucho Valdes

XVIII Habanos Festival Opens with Cohiba

International Stars at the Closing of the XVIII Habanos Festival

Felicitacion Chucho Valdes

XVIII Habanos Festival Opens with Cohiba

International Stars at the Closing of the XVIII Habanos Festival