An alternative synthesis method for di calcium phosphate (monetite) powders from mediterranean mussel (mytilus galloprovincialis) shells

Marine species, such as corals, sea shells and nacres, attract special interest in bioceramics field for bone graft, bone cements and drug delivery applications. Most of the marine structures are made up of pure calcium carbonate (calcite or aragonite) with a very small amount of an organic matrix. In the past the most common way to transform these structures to hydroxyapatite was hydrothermal transformation method. This current work introduces a new approach for producing fine powders of calcium phosphates from Mediterranean mussel (Mytilus galloprovincialis) shells. A comparative study was carried out to investigate the differences of these powders under only hot plate heating and hot plate heating together with ultrasonic agitation while H3PO4 was added. The temperature of the hotplate was kept constant at 80 degrees C and then, H3PO4 was added drop wise into the solution for 2 hrs. The mixture was then placed into an oven at 100 degrees C for 24 hrs. They were further calcined at 800 degrees C for 3 hrs. XRD, FTIR. and ICP-MS were used to identify the structure and composition. It was found that the final powders were predominantly monetite, with some tricalcium phosphate as a secondary phase. This relatively simple and efficient method can be easily applied to produce calcium phosphate precursor powders for a range of biomedical applications

RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation.

Loss of epithelial differentiation and extracellular matrix (ECM) remodeling are known to facilitate cancer progression and are associated with poor prognosis in patients with lung cancer. We have identified Receptor-interacting serine/threonine protein kinase 4 (RIP4) as a regulator of tumor differentiation in lung adenocarcinoma (AC). Bioinformatics analyses of human lung AC samples showed that poorly differentiated tumors express low levels of RIP4, whereas high levels are associated with better overall survival. In vitro, lung tumor cells expressing reduced RIP4 levels showed enhanced activation of STAT3 signaling and had a greater ability to invade through collagen. In contrast, overexpression of RIP4 inhibited STAT3 activation, which abrogated interleukin-6-dependent induction of lysyl oxidase, a collagen cross-linking enzyme. In an autochthonous mouse model of lung AC initiated by Kras(G12D) expression with loss of p53, Rip4 knockdown tumors progressed to a poorly differentiated state marked by an increase in Hmga2, reduced Ttf1, and enrichment of genes regulating extracellular remodeling and Jak-Stat signaling. Tail vein injections of cells overexpressing Rip4 showed a reduced potential to invade and form tumors, which was restored by co-expression of Stat3. Altogether, our work has identified that loss of RIP4 enhances STAT3 signaling in lung cancer cells, promoting the expression of ECM remodeling genes and cancer dedifferentiation

CWI at TREC 2012, KBA track and Session Track

We participated in two tracks: Knowledge Base Acceleration (KBA) Track and Session Track. In the KBA track, we focused on experi- menting with different approaches as it is the first time the track is launched. We experimented with supervised and unsupervised re- trieval models. Our supervised approach models include language models and a string-learning system. Our unsupervised approaches include using: 1)DBpedia labels and 2) Google-Cross-Lingual Dic- tionary (GCLD). While the approach that uses GCLD targets the central and relvant bins, all the rest target the central bin. The GCLD and the string-learning system have outperformed the oth- ers in their respective targeted bins. The goal of the Session track submission is to evaluate whether and how a logic framework for representing user interactions with an IR system can be used for improving the approximation of the relevant term distribution that another system that is supposed to have access to the session infor- mation will then calculate. the documents in the stream corpora. Three out of the seven runs used a Hadoop cluster provide by Sara.nl to process the stream cor- pora. The other 4 runs used a federated access to the same corpora distributed among 7 workstations

Psychophysical Evaluation of a Variable Friction Tactile Interface

This study explores the haptic rendering capabilities of a variable friction tactile interface through psychophysical experiments. In order to obtain a deeper understanding of the sensory resolution associated with the Tactile Pattern Display (TPaD), friction discrimination experiments are conducted. During the experiments, subjects are asked to explore the glass surface of the TPaD using their bare index fingers, to feel the friction on the surface, and to compare the slipperiness of two stimuli, displayed in sequential order. The fingertip position data is collected by an infrared frame and normal and translational forces applied by the finger are measured by force sensors attached to the TPaD. The recorded data is used to calculate the coefficient of friction between the fingertip and the TPaD. The experiments determine the just noticeable difference (JND) of friction coefficient for humans interacting with the TPaD

Modeling of the Direct Current Generator Including the Magnetic Saturation and Temperature Effects

En este artículo se propone la inclusión del efecto de la temperatura sobre la resistencia de campo al modelo del generador de corriente directa DC1A valido para estudios de estabilidad. Se parte del modelo lineal del generador, luego se incluye el efecto de la saturación magnética y por último el cambio en la resistencia de campo debido a la temperatura producida por la corriente de campo. La metodología aplicada para validar el modelo es la comparación de resultados experimentales y simulaciones de los modelos. La comparación visual de los resultados simulados con resultados experimentales muestra el acierto del modelo propuesto, puesto que presenta el menor error de los modelos comparados. El acierto del modelo propuesto se observa a través del índice Suma Normalizada de Errores Cuadráticos Modificada igual a 3.8979%.In this paper the inclusion of temperature effect on the field resistance on the direct current generator model DC1A, which is valid to stability studies is proposed. First, the linear generator model is presented, after the effect of magnetic saturation and the change in the resistance value due to temperature produced by the field current are included. The comparison of experimental results and model simulations to validate the model is used. A direct current generator model which is a better representation of the generator is obtained. Visual comparison between simulations and experimental results shows the success of the proposed model, because it presents the lowest error of the compared models. The accuracy of the proposed model is observed via Modified Normalized Sum of Squared Errors index equal to 3.8979%

Biological and prognostic impact of apobec-induced mutations in the spectrum of plasma cell dyscrasias

In multiple myeloma (MM), whole exome sequencing (WES) studies have revealed four mutational signatures: two associated with aberrant activities of APOBEC cytidine deaminases (Signatures #2 and #13) and two clock-like signatures associated with "cancer age" (Signatures #1 and #5). Mutational signatures have not been investigated systematically in larger series, nor in other primary plasma cell dyscrasias such as monoclonal gammopathy of unknown significance (MGUS) or primary plasma cell leukemia (pPCL). Finally, while APOBEC activity has been correlated to increased mutational burden and poor-prognosis MAF/MAFB translocations in MM at diagnosis, this has never been confirmed in multivariate analysis in an independent series. To answer these questions, we mined 1151 MM samples from public WES datasets, including samples from the IA9 public release of the CoMMpass trial. The CoMMpass data were generated as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiatives. We also analyzed 6 MGUS/Smoldering MM as well as 5 previously published pPCLs. Extraction of mutational signatures was performed using the NNMF algorithm as previously described (Alexandrov et al. Nature 2013). NNMF in the whole cohort extracted the known 4 signatures pertaining to distinct mutational processes: the two clock-like processes (signatures #1 and #5) and aberrant APOBEC deaminase activity (signatures #2 and #13). While the clock-like processes were more prominent in the cohort as a whole (median 70%, range 0-100%), the APOBEC showed a heterogeneous contribution, more visible in samples with the highest mutation burden. In fact, the absolute and relative contribution of APOBEC activity to the mutational repertoire correlated with the overall number of mutations (r=0.71, p= < 0.0001). As previously described, APOBEC contribution was significantly enriched among MM patients with t(14;16) and with t(14;20) (p<0.001), but the association between relative APOBEC contribution and mutational load remained significant across all cytogenetic subgroups with the exception of t(11;14). In the MGUS/SMM series, APOBEC contribution was generally low. Conversely, APOBEC activity was preponderant in three out of five pPCL samples, all of them characterized by the t(14;16)( IGH / MAF); in the remaining two pPCL the absolute number of APOBEC mutations was similar to MM. Overall, the APOBEC contribution was characterized by a progressive increment from MGUS/SMM to MM and pPCL. We next went on to investigate the prognostic impact of APOBEC signatures at diagnosis. Patients with APOBEC contribution in the 4th quartile had shorter PFS (2-y PFS 47% vs 66%, p<0.0001) and OS (2-y OS 70% vs 85%, p=0.0033) than patients in quartiles 1-3 (Figure 1a-b). This was independent from the association of APOBEC activity with MAF translocations and higher mutational burden, as shown by multivariate analysis with Cox regression (Figure 1c-d). ISS stage III was the only other variable that retained its independent prognostic value for both PFS and OS. We therefore combined both variables and found that co-occurrence of ISS III and APOBEC 4th quartile identifies a fraction of high-risk patients with 2-y OS of 53.8% (95% CI 36.6%-79%), while their simultaneous absence identifies long term survivors with 2-y OS of 93.3% (95% CI 89.6-97.2%). In this study, we provided a global overview on the contribution of mutational processes in the largest whole exome series of plasma cell dyscrasias investigated to date by NNMF. We propose that cases with high APOBEC activity may represent a novel prognostic subgroup that is transversal to conventional cytogenetic subgroups, advocating for closer integration of next-generation sequencing studies and clinical annotation to confirm this finding in independent series

Informes Temáticos RCRC: Porqué los Niños Deben Ser la Prioridad #1 en Desastres

Los Informes Temáticos RCRC, en este documento, están diseñados para ser utilizados por las comunidades de la iniciativa RCRC y todas las otras comunidades que buscan elevar la resiliencia de los niños ante desastres a la atención de legisladores locales, estatales y federales u otros responsables de la toma de decisiones. Estos informes también pueden ser utilizados por legisladores y responsables de la toma de decisiones en todos los niveles de gobierno como documentos informativos para comprender mejor los problemas que enfrentan las comunidades en desastres en el contexto de COVID-19 y otros desastres. Se anima a los lectores a explorar los temas y mensajes que más resuenan con su propia comunidad. Para acceder a una versión online e interactiva de los Informes Temáticos RCRC, visite https://rcrctoolbox.org/rcrc-issue-briefs-es/

Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set

The primary cause of morbidity and mortality in patients with multiple myeloma(MM) is an infection. Therefore there is great concern about the susceptibility to the outcome of COVID-19 infected patients with MM. This retrospective study describes the baseline characteristics and outcome data of COVID-19 infection in 650 patients with plasma cell disorders, collected by the International Myeloma Society to understand the initial challenges faced by myeloma patients during COVID-19 pandemic. Analysis were performed for hospitalized MM patients. Among hospitalized patinets, the median age was 69 years, and nearly all patients(96%) had MM. Approximately 36% were recently diagnosed(2019-2020), and 54% of patients were receiving first-line therapy. Thirty-three percent of patients have died, with significant geographic variability, ranging from 27% to 57% of hospitalized patients. Univariate analysis identified age, ISS3, high-risk disease, renal disease, suboptimal myeloma control(active or progressive disease), and one or more comorbidities as risk factors for higher rates of death. Neither history of transplant, including within a year of COVID-19 diagnosis, nor other anti-MM treatments were associated with outcomes. Multivariate analysis found that only age, high-risk MM, renal disease, and suboptimal MM control remained independent predictors of adverse outcome with COVID-19 infection. The management of MM in the era of COVID-19 requires careful consideration of patient and disease-related factors to decrease the risk of acquiring COVID-19 infection, while not compromising disease control through appropriate MM treatment. This study provides initial data to develop recommendations for the management of MM patients with COVID-19 infection

RCRC Issue Briefs: Why Children Should Be the #1 Disaster Priority

The Resilient Children/Resilient Communities Initiative (RCRC) Issue Briefs, in this document, are designed to be used by the RCRC communities and all other communities who are seeking to elevate children’s disaster resilience to the attention of local, state, and federal legislators or other decision-makers. These reports can also be used by legislators and decision–makers at all levels of government as informative briefs to better understand the issues faced by communities in disasters within the context of COVID-19 and other disasters. Readers are encouraged to explore topics and voices that most resonate with their own community. To access an online and interactive version of RCRC Issue Briefs, please visit https://rcrctoolbox.org/rcrc-issue-briefs

Genomic patterns of progression in smoldering multiple myeloma

We analyzed whole genomes of unique paired samples from smoldering multiple myeloma (SMM) patients progressing to multiple myeloma (MM). We report that the genomic landscape, including mutational profile and structural rearrangements at the smoldering stage is very similar to MM. Paired sample analysis shows two different patterns of progression: a “static progression model”, where the subclonal architecture is retained as the disease progressed to MM suggesting that progression solely reflects the time needed to accumulate a sufficient disease burden; and a “spontaneous evolution model”, where a change in the subclonal composition is observed. We also observe that activation-induced cytidine deaminase plays a major role in shaping the mutational landscape of early subclinical phases, while progression is driven by APOBEC cytidine deaminases. These results provide a unique insight into myelomagenesis with potential implications for the definition of smoldering disease and timing of treatment initiation