Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion.

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER-negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER-negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50 % of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple-negative breast cancer cells

Panama Bridge Project

The Panama Bridge project has partnered with Rio Missions Panama to design a bridge for the village of La Gigi, Panama. The mountain community of La Gigi experiences heavy rainfall during the rainy seasons. A stream runs along the community, separating locals from their fields and other communities further up the mountain. While passable during dry seasons, the stream floods and becomes impassable after heavy rains. The residents are effectively cut off from their livelihoods, church, health services, and other communities during this time. To accommodate this need, the Panama Bridge Team has spent the 2019-2020 school year designing an aluminum truss bridge, spanning 90 feet. The design includes a unique construction strategy to deal with challenging site constraints.https://mosaic.messiah.edu/engr2020/1020/thumbnail.jp

Panama Bridge Project

The Panama Bridge project has partnered with Rio Missions Panama to design a bridge for the village of La Gigi, Panama. The mountain community of La Gigi experiences heavy rainfall during the rainy seasons. A stream runs along the community, restricting their access to schools, employment options, and other communities. While passable during dry seasons, the stream floods and becomes impassable after heavy rains. The residents are effectively cut off from their livelihoods, church, health services, and other communities during this time. To accommodate this need, the Panama Bridge Team has spent the last two academic years designing a 90 foot aluminum truss bridge. The design includes a unique construction strategy to deal with challenging site constraints.https://mosaic.messiah.edu/engr2021/1011/thumbnail.jp

Level Sets of the Takagi Function: Local Level Sets

The Takagi function \tau : [0, 1] \to [0, 1] is a continuous non-differentiable function constructed by Takagi in 1903. The level sets L(y) = {x : \tau(x) = y} of the Takagi function \tau(x) are studied by introducing a notion of local level set into which level sets are partitioned. Local level sets are simple to analyze, reducing questions to understanding the relation of level sets to local level sets, which is more complicated. It is known that for a "generic" full Lebesgue measure set of ordinates y, the level sets are finite sets. Here it is shown for a "generic" full Lebesgue measure set of abscissas x, the level set L(\tau(x)) is uncountable. An interesting singular monotone function is constructed, associated to local level sets, and is used to show the expected number of local level sets at a random level y is exactly 3/2.Comment: 32 pages, 2 figures, 1 table. Latest version has updated equation numbering. The final publication will soon be available at springerlink.co

Response to treatment in a prospective national infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/1/ana24594.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134499/2/ana24594_am.pd

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/1/epi13557_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/2/epi13557.pd

Migration and Evolution of giant ExoPlanets (MEEP) I: Nine Newly Confirmed Hot Jupiters from the TESS Mission

Hot Jupiters were many of the first exoplanets discovered in the 1990s, but in the decades since their discovery, the mysteries surrounding their origins remain. Here, we present nine new hot Jupiters (TOI-1855 b, TOI-2107 b, TOI-2368 b, TOI-3321 b, TOI-3894 b, TOI-3919 b, TOI-4153 b, TOI-5232 b, and TOI-5301 b) discovered by NASA's TESS mission and confirmed using ground-based imaging and spectroscopy. These discoveries are the first in a series of papers named the Migration and Evolution of giant ExoPlanets (MEEP) survey and are part of an ongoing effort to build a complete sample of hot Jupiters orbiting FGK stars, with a limiting Gaia $G$-band magnitude of 12.5. This effort aims to use homogeneous detection and analysis techniques to generate a set of precisely measured stellar and planetary properties that is ripe for statistical analysis. The nine planets presented in this work occupy a range of masses (0.55 Jupiter masses (M$_{\rm{J}}$) $<$ M$_{\rm{P}}$ $<$ 3.88 M$_{\rm{J}}$) and sizes (0.967 Jupiter radii (R$_{\rm{J}}$) $<$ R$_{\rm{P}}$ $<$ 1.438 R$_{\rm{J}}$) and orbit stars that range in temperature from 5360 K $<$ Teff $<$ 6860 K with Gaia $G$-band magnitudes ranging from 11.1 to 12.7. Two of the planets in our sample have detectable orbital eccentricity: TOI-3919 b ($e = 0.259^{+0.033}_{-0.036}$) and TOI-5301 b ($e = 0.33^{+0.11}_{-0.10}$). These eccentric planets join a growing sample of eccentric hot Jupiters that are consistent with high-eccentricity tidal migration, one of the three most prominent theories explaining hot Jupiter formation and evolution.Comment: 35 pages, 7 tables, and 14 figures. Submitted to AAS Journals on 2023 Dec 2

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study

Abstract Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P trend = 0.005) but not cases (P trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P trend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P trend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels