Field Effect Transistor Nanosensor for Breast Cancer Diagnostics

Silicon nanochannel field effect transistor (FET) biosensors are one of the most promising technologies in the development of highly sensitive and label-free analyte detection for cancer diagnostics. With their exceptional electrical properties and small dimensions, silicon nanochannels are ideally suited for extraordinarily high sensitivity. In fact, the high surface-to-volume ratios of these systems make single molecule detection possible. Further, FET biosensors offer the benefits of high speed, low cost, and high yield manufacturing, without sacrificing the sensitivity typical for traditional optical methods in diagnostics. Top down manufacturing methods leverage advantages in Complementary Metal Oxide Semiconductor (CMOS) technologies, making richly multiplexed sensor arrays a reality. Here, we discuss the fabrication and use of silicon nanochannel FET devices as biosensors for breast cancer diagnosis and monitoring

Fungal Colonists of Maize Grain Conditioned at Constant Temperatures and Humidities

Fungal colonization of shelled maize (Pioneer 3320) harvested from a field near Furman, South Carolina, in 1992 was determined after 348 and 751 days of continuous storage at each of seven temperatures (10, 15, 20, 25, 30, 35, or 40°C) and four constant relative humidities, giving equilibrium grain moisture contents ranging from 9.4% to 17.5% m.c. in 28 grain conditioning environments. Twenty fungal species infected surface sterilized seeds and were recorded from these conditioned grain treatments, including species commonly found in preharvest maize [e.g. Acremonium zeae, Aspergillus flavus, Fusarium moniliforme (syn. F. verticillioides), Penicillium pinophilum (syn. P. funiculosum), etc.]. Eupenicillium cinnamopurpureum and Monascus ruber were recorded only from conditioned grain treatments. Eurotium chevalieri colonized 50-96% of the kernels from grain conditioning treatments with the highest moisture content for each incubation temperature. Grain samples with \u3e33% E. chevalieri infection had a decreased occurrence of F. moniliforme and A. zeae, and no kernels from these samples germinated. No fungi colonized more than 50% of the kernels conditioned at 30-40°C and 9.4-14.2% m.c. The results of this study indicate that individual patterns of fungal colonization during grain conditioning were a function of the survival rates for preharvest fungal colonists and their potential replacement by E. chevalieri

Extranuclear X-ray Emission in the Edge-on Seyfert Galaxy NGC 2992

We found several extranuclear (r >~ 3") X-ray nebulae within 40" (6.3 kpc at 32.5 Mpc) of the nucleus of the Seyfert galaxy NGC 2992. The net X-ray luminosity from the extranuclear sources is ~2-3 E39 erg/s (0.3-8.0 keV). The X-ray core itself (r <~ 1") is positioned at 9:45:41.95 -14:19:34.8 (J2000) and has a remarkably simple power-law spectrum with photon index Gamma=1.86 and Nh=7E21 /cm2. The near-nuclear (3" <~ r <~ 18") Chandra spectrum is best modelled by three components: (1) a direct AGN component with Gamma fixed at 1.86, (2) cold Compton reflection of the AGN component, and (3) a 0.5 keV low-abundance (Z < 0.03 Zsolar) "thermal plasma," with ~10% of the flux of either of the first two components. The X-ray luminosity of the 3rd component (the "soft excess") is ~1.4E40 erg/s, or ~5X that of all of the detected extranuclear X-ray sources. We suggest that most (~75-80%) of the soft excess emission originates from 1" < r < 3", which is not imaged in our observation due to severe CCD pile-up. We also require the cold reflector to be positioned at least 1" (158 pc) from the nucleus, since there is no reflection component in the X-ray core spectrum. Much of the extranuclear X-ray emission is coincident with radio structures (nuclear radio bubbles and large-scale radio features), and its soft X-ray luminosity is generally consistent with luminosities expected from a starburst-driven wind (with the starburst scaled from L_FIR). However, the AGN in NGC 2992 seems equally likely to power the galactic wind in that object. Furthermore, AGN photoionization and photoexcitation processes could dominate the soft excess, especially the \~75-80% which is not imaged by our observations.Comment: 34 pages AASTEX, 9 (low-res) PS figures, ApJ, in press. For full-resolution postscript file, visit http://www.pha.jhu.edu/~colbert/n2992_chandra.ps.g

An injectable bone marrow-like scaffold enhances T cell immunity after hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for multiple disorders, but deficiency and dysregulation of T cells limit its utility. Here we report a biomaterial-based scaffold that mimics features of T cell lymphopoiesis in the bone marrow. The bone marrow cryogel (BMC) releases bone morphogenetic protein-2 to recruit stromal cells and presents the Notch ligand Delta-like ligand-4 to facilitate T cell lineage specification of mouse and human hematopoietic progenitor cells. BMCs subcutaneously injected in mice at the time of HSCT enhanced T cell progenitor seeding of the thymus, T cell neogenesis and diversification of the T cell receptor repertoire. Peripheral T cell reconstitution increased ~6-fold in mouse HSCT and ~2-fold in human xenogeneic HSCT. Furthermore, BMCs promoted donor CD4+ regulatory T cell generation and improved survival after allogeneic HSCT. In comparison to adoptive transfer of T cell progenitors, BMCs increased donor chimerism, T cell generation and antigen-specific T cell responses to vaccination. BMCs may provide an off-the-shelf approach for enhancing T cell regeneration and mitigating graft-versus-host disease in HSCT

Office of Regulatory Affairs Strategies for Building an Integrated National Laboratory Network for Food and Feed

An interconnected network of accredited federal, state, local, tribal, and territorial laboratories is critical to ensuring the safety of the U.S. food supply and the development of the Integrated Food Safety System (IFSS). In 2004, as part of a national policy to defend the U.S. food supply against terrorist attacks, major disasters, and other emergencies, the Food Emergency Response Network (FERN) was created to integrate the nation’s multilevel (i.e., federal, state, local, tribal, territorial) food-testing laboratories to detect, identify, respond to, and recover from a bioterrorism act affecting the safety of the food supply, or a public health emergency/outbreak involving the food supply. Since 2004, federal agencies have invested an estimated $200 million in FERN. The majority of this investment has been in the FERN cooperative agreements with FDA and USDA-FSIS investing$95.8 million and $69 million, respectively. FDA has promoted the accreditation of state laboratories through cooperative agreement funding, investing more than$50 million to fund these grants. On November 11, 2014, the Office of Regulatory Affairs (ORA) requested that the FDA Science Board establish a subcommittee to evaluate current investments in: (1) the FERN cooperative agreement funding program (CAP), and (2) funding for state laboratories to achieve International Organization for Standardization (ISO) accreditation. The goal was to ascertain how ORA can advance and establish an effective integrated laboratory network among ORA, FDA Center, and state public health and food- and feed-testing laboratories. In response to this request, the Science Board created the ORA FERN Cooperative Agreement Evaluation Subcommittee on July 1, 2015. This report summarizes the results of the Subcommittee’s review

Progress Towards the ELROI\u3csup\u3eTM\u3c/sup\u3e Satellite License Plate

The ELROITM System, (Extremely Low Resource Optical Identifier), uses a beacon that could be attached to any object that goes into space and provide a persistent identifier to the space object that can be read out by a small telescope on the ground. This could alleviate the approaching crisis in Space Traffic Management caused by mass launches of small satellites and the formation of large constellations. Identification beacons on all future space objects will simplify satellite operations and greatly relieve our overstressed space tracking and traffic management infrastructure

DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.

BackgroundInduction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.MethodsExpression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.ResultsWe found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.ConclusionsWe identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated

Notch Simultaneously Orchestrates Multiple Helper T Cell Programs Independently of Cytokine Signals

SummaryTwo models are proposed to explain Notch function during helper T (Th) cell differentiation. One argues that Notch instructs one Th cell fate over the other, whereas the other posits that Notch function is dictated by cytokines. Here we provide a detailed mechanistic study investigating the role of Notch in orchestrating Th cell differentiation. Notch neither instructed Th cell differentiation nor did cytokines direct Notch activity, but instead, Notch simultaneously regulated the Th1, Th2, and Th17 cell genetic programs independently of cytokine signals. In addition to regulating these programs in both polarized and nonpolarized Th cells, we identified Ifng as a direct Notch target. Notch bound the Ifng CNS-22 enhancer, where it synergized with Tbet at the promoter. Thus, Notch acts as an unbiased amplifier of Th cell differentiation. Our data provide a paradigm for Notch in hematopoiesis, with Notch simultaneously orchestrating multiple lineage programs, rather than restricting alternate outcomes

Bow Hunter\u27s Syndrome in a Patient with a Right Hypoplastic Vertebral Artery and a Dynamically Compressible Left Vertebral Artery

This is a case report of a 48-year-old man with multiple transient ischemic attacks and a known hypoplastic right vertebral artery (VA) who presented after a syncopal event while turning his head to the left. The objective of this study is to demonstrate the necessity of proper diagnosis and management of cerebrovascular pathology including imaging and surgical intervention in patients with known anatomical anomalies. This study was conducted at Massachusetts, United States of America. Our patient\u27s history was significant for a hypoplastic right VA and a stenotic segment of the right VA at the C3-C4 junction. There was also degeneration of the C3-C4 facet on the left, with osteophyte formation compressing the VA, and a fusion of the C2-C3 segment. Imaging demonstrated obliteration of the left VA flow with head rotation to the left and subsequent reconstitution of flow in the neutral position. After consultation, the patient decided to proceed with surgical management with an anterior cervical discectomy and fusion at the level of C3-C4. Symptoms of vertebrobasilar insufficiency including syncopal episodes resolved after treatment. VA anomalies, although uncommon, are important to understand. Our patient presented with an anomalous right VA, as well as severe degenerative changes to the C2/C3 vertebrae that contributed to the development of Bow Hunter\u27s syndrome. It is essential that proper monitoring and follow-up has to be carried out in patients with abnormal cerebral vasculature to minimize the occurrence of Bow Hunter\u27s syndrome