The Genetic Basis of Hepatosplenic T-cell Lymphoma

Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets

Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1 , JAK3 , STAT3 , and SOCS1 . We also identified mutations in KRAS , TP53 , and TERT . Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes

Internet Gaming Disorder in the DSM-5: Engagement vs. Addiction

The current study aimed to examine the distinction between engagement and addiction in the DSM-5 Internet gaming disorder (IGD) criteria with regards to known negative consequences of IGD. Participants were 216 (62.0% males) gamers. Their ages ranged from 18 to 38 years (M = 23.44, SD = 3.86). Participants completed instruments assessing IGD, sleep quality, negative emotional states, and quality of life. The results showed that only the three addiction items, withdrawal, deception, and relieve negative moods, significantly predicted negative consequences. In contrast, the two engagement items, preoccupation and tolerance, did not significantly predict negative consequences. Overall, the results provided support for the engagement-addiction distinction and contributed to the wider debate on the validity of the other criteria. Limitations include the low Cronbach’s alpha for the sleep quality instrument and the examination of only a subset of known negative consequences of IGD. Future research directions include using other measures of sleep quality, assessing other negative consequences of IGD, and empirically examining the validity of the DSM-5 IGD criteria

Kerf profile and piezoresponse study of the laser micro-machined PMN-PT single crystal using 355 nm Nd:YAG

A systematic study on laser micro-machining of PMN-PT single crystals has been performed. The PMN-PT single crystal has been micromachined using a 355 nm Nd:YAG laser. The kerf profile and cutting quality of the laser micro-machined PMN-PT single crystal were studied as functions of the laser process parameters. It was found that the direct proportional relationship between the depth of the kerf and the laser power provides an effective reference to determine the depth required to be ablated. It is significant for fabricating micro-devices using the single crystal by laser micro-machining. Besides the physical behavior, the piezoresponse of the PMN-PT single crystal has also been investigated by PFM. The results reveal that the laser micro-machining would not affect the macroscopic piezoelectric performance of the PMN-PT single crystal. The present work shows the feasibility of micro-patterning the PMN-PT single crystal into any geometry using a Nd:YAG laser

Temperature-dependent piezoelectric and dielectric properties of charge-ordered Lu2Fe2.1Mn0.9O7

Ferroelectric and piezoelectric properties of layered Lu2Fe2.1Mn0.9O7 ceramic have been investigated by temperature-dependent piezoresponse force microcopy (PFM) and dielectric measurements. The PFM results illustrate the existence of piezoelectric properties and ferroelectric phase transition temperature of about 90 °C at which the piezoelectricity vanishes. This transition temperature is manifested by the appearance of a shoulder at about 90 °C in the temperature-dependent dielectric curve of the poled sample. A macro-to-micro domain transition is proposed to explain this ferroelectric phase transition. Besides, the ferroelectric properties of the Lu2Fe2.1Mn0.9O7 ceramic are further demonstrated by the polarization-electric field hysteresis (P–E) loop measurement

Objective speech quality measure for cellular phone

Cellular phone network speech quality monitoring is a regular task performed by the cellular service providers. Objective speech quality measures are needed in such tasks to provide a reasonably accurate estimate of subjective quality of the network. We performed an experiment to collect real distorted data, conducted a survey to obtain subjective quality measure of the collected speech samples and studied the statistical correlation of 32 objective speech quality measures with the subjective measures. Four of the objective measures were found to be good. Synchronization was found to be important