As Low Birth Weight Babies Grow, Can 'Good' Parents Buffer this Adverse Factor? A Research Note.

This research note combines two national Taiwanese datasets to investigate the relationship between low birth weight (LBW) babies, their family background and their future academic outcomes. We find that LBW is negatively correlated with the probability of such children attending university at the age of 18; however, when both parents are college or senior high school graduates, such negative effects may be partially offset. We also show that discrimination against daughters does occur, but only in those cases where the daughters were LBW babies. Moreover, high parental education (HPE) can only buffer the LBW shock among moderately-LBW children (as compared to very-LBW children) and full term-LBW children (as compared to preterm-LBW children).

Joint Channel-and-Data Estimation for Large-MIMO Systems with Low-Precision ADCs

The use of low precision (e.g., 1-3 bits) analog-to-digital convenors (ADCs) in very large multiple-input multiple-output (MIMO) systems is a technique to reduce cost and power consumption. In this context, nevertheless, it has been shown that the training duration is required to be {\em very large} just to obtain an acceptable channel state information (CSI) at the receiver. A possible solution to the quantized MIMO systems is joint channel-and-data (JCD) estimation. This paper first develops an analytical framework for studying the quantized MIMO system using JCD estimation. In particular, we use the Bayes-optimal inference for the JCD estimation and realize this estimator utilizing a recent technique based on approximate message passing. Large-system analysis based on the replica method is then adopted to derive the asymptotic performances of the JCD estimator. Results from simulations confirm our theoretical findings and reveal that the JCD estimator can provide a significant gain over conventional pilot-only schemes in the quantized MIMO system.Comment: 7 pages, 4 figure

Bayes-Optimal Joint Channel-and-Data Estimation for Massive MIMO with Low-Precision ADCs

This paper considers a multiple-input multiple-output (MIMO) receiver with very low-precision analog-to-digital convertors (ADCs) with the goal of developing massive MIMO antenna systems that require minimal cost and power. Previous studies demonstrated that the training duration should be {\em relatively long} to obtain acceptable channel state information. To address this requirement, we adopt a joint channel-and-data (JCD) estimation method based on Bayes-optimal inference. This method yields minimal mean square errors with respect to the channels and payload data. We develop a Bayes-optimal JCD estimator using a recent technique based on approximate message passing. We then present an analytical framework to study the theoretical performance of the estimator in the large-system limit. Simulation results confirm our analytical results, which allow the efficient evaluation of the performance of quantized massive MIMO systems and provide insights into effective system design.Comment: accepted in IEEE Transactions on Signal Processin

Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.

IntroductionAlthough breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors.MethodsParaffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation.ResultsImmunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes.ConclusionsOur findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas.

Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM