Atom-resolved imaging with a silicon tip integrated into an on-chip scanning tunneling microscope.

Limited throughput is a shortcoming of the Scanning Tunneling Microscope (STM), particularly when used for atomically precise lithography. To address this issue, we have developed an on-chip STM based on Microelectromechanical-Systems (MEMS) technology. The device reported here has one degree of freedom, replacing the Z axis in a conventional STM.

Al-alkyls as acceptor dopant precursors for atomic-scale devices.

Atomically precise ultradoping of silicon is possible with atomic resists, area-selective surface chemistry, and a limited set of hydride and halide precursor molecules, in a process known as atomic precision advanced manufacturing (APAM). It is desirable to expand this set of precursors to include dopants with organic functional groups and here we consider aluminium alkyls, to expand the applicability of APAM. We explore the impurity content and selectivity that results from using trimethyl aluminium and triethyl aluminium precursors on Si(001) to ultradope with aluminium through a hydrogen mask.

An investigation of the antileishmanial properties of semi-synthetic saponins.

Leishmaniasis is a neglected tropical disease caused by insect-vector borne protozoan parasites of the, species. Whilst infection threatens and affects millions of the global poor, vaccines are absent and drug therapy limited. Extensive efforts have recently been made to discover new leads from small molecule synthetic compound libraries held by industry; however, the number of new chemical entities identified and entering development as anti-leishmanials has been very low.

Advancement of PI3 Kinase Inhibitor Combination Therapies for PI3K-Aberrant Chordoma.

 Targeted inhibitors of the PI3 kinase (PI3K) pathway have shown promising but incomplete antitumor activity in preclinical chordoma models. The aim of this study is to advance methodology for a high-throughput drug screen using chordoma models to identify new combination therapies for chordoma.  Present work is an in vitro study.

Rationale for the advancement of PI3K pathway inhibitors for personalized chordoma therapy.

Purpose: Chordomas are rare and serious tumors with few effective treatments outside of aggressive surgery and radiation. Targeted therapies may present a more effective option for a subset of patients with lesions possessing certain genetic biomarkers.

Methods: A small molecule inhibitor library was tested in patient-derived UM-Chor1 cells to identify targeted therapies with potential efficacy.

A small set of conserved genes, including sp5 and Hox, are activated by Wnt signaling in the posterior of planarians and acoels.

Wnt signaling regulates primary body axis formation across the Metazoa, with high Wnt signaling specifying posterior identity. Whether a common Wnt-driven transcriptional program accomplishes this broad role is poorly understood. We identified genes acutely affected after Wnt signaling inhibition in the posterior of two regenerative species, the planarian Schmidtea mediterranea and the acoel Hofstenia miamia, which are separated by >550 million years of evolution.

UM-Chor1: establishment and characterization of the first validated clival chordoma cell line.

OBJECTIVE Chordomas are rare malignant tumors thought to arise from remnants of the notochord. They can be located anywhere along the axial skeleton but are most commonly found in the clival and sacrococcygeal regions, where the notochord regresses during fetal development. Chordomas are resistant to many current therapies, leaving surgery as the primary method of treatment.

Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines.

Background: Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines.

Methods: E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR).

STAT3 Inhibition as a Therapeutic Strategy for Chordoma.

 Signal transducer and activator of transcription (STAT) proteins regulate key cellular fate decisions including proliferation and apoptosis. STAT3 overexpression induces tumor growth in multiple neoplasms. STAT3 is constitutively activated in chordoma, a tumor with a high recurrence rate despite maximal surgical and radiation treatment.

Targeting Head and Neck Cancer Stem Cells: Current Advances and Future Challenges.

Cancer stem cells (CSCs), or tumor-initiating cells, comprise a subset of tumor cells with demonstrated ability for tumor growth, invasion, metastasis, and resistance to chemotherapy and radiation. Targeting of CSCs remains an attractive yet elusive therapeutic option, with the goal of increasing specificity and effectiveness in tumor eradication, as well as decreasing off-target or systemic toxicity. Research into further characterization and targeted therapy toward head and neck CSCs is an active and rapidly evolving field.

Atomically Traceable Nanostructure Fabrication.

Reducing the scale of etched nanostructures below the 10 nm range eventually will require an atomic scale understanding of the entire fabrication process being used in order to maintain exquisite control over both feature size and feature density. Here, we demonstrate a method for tracking atomically resolved and controlled structures from initial template definition through final nanostructure metrology, opening up a pathway for top-down atomic control over nanofabrication. Hydrogen depassivation lithography is the first step of the nanoscale fabrication process followed by selective atomic layer deposition of up to 2.

teashirt is required for head-versus-tail regeneration polarity in planarians.

Regeneration requires that the identities of new cells are properly specified to replace missing tissues. The Wnt signaling pathway serves a central role in specifying posterior cell fates during planarian regeneration. We identified a gene encoding a homolog of the Teashirt family of zinc-finger proteins in the planarian Schmidtea mediterranea to be a target of Wnt signaling in intact animals and at posterior-facing wounds.

Novel method of cell line establishment utilizing fluorescence-activated cell sorting resulting in 6 new head and neck squamous cell carcinoma lines.

Background: The purpose of this study was to present the establishment of new cell lines, which is important to cancer research.

Methods: Six new head and neck squamous cell carcinoma cell lines were established using a novel fluorescence-activated cell sorting (FACS) method in order to overcome the barrier of fibroblast overgrowth and the susceptibility of primary tumors to fail in vitro.

Results: Antibodies chosen for specific targeting of epithelial cells and fibroblasts successfully separated cells for line establishment in 6 of 12 attempts, providing an alternative method of establishing head and neck squamous cell carcinoma cell lines.

Evaluation of CD44 variant expression in oral, head and neck squamous cell carcinomas using a triple approach and its clinical significance.

Cancer stem cells possess the qualities of self-renewal, tumorigenesis and the ability to recapitulate a heterogeneous tumor. Our group was the first to isolate head and neck squamous cell carcinoma (HNSCC) stem cells using the cell surface marker CD44. CD44 is a trans-membrane glycoprotein with a multitude of key-functions that regulate cancer cell proliferation and metastasis.

UM-SCC-103: a unique tongue cancer cell line that recapitulates the tumorigenic stem cell population of the primary tumor.

Objective: A new head and neck cancer cell line was developed from a highly aggressive HNSCC of the oral cavity diagnosed in a 26-year-old pregnant woman.

Methods: Cells from the primary tumor were passaged in culture and genotyped as a unique cell line. The resultant cell line was assessed for its ability to replicate the primary tumor.

Generation of a novel dendritic-cell vaccine using melanoma and squamous cancer stem cells.

We identified cancer stem cell (CSC)-enriched populations from murine melanoma D5 syngeneic to C57BL/6 mice and the squamous cancer SCC7 syngeneic to C3H mice using ALDEFLUOR/ALDH as a marker, and tested their immunogenicity using the cell lysate as a source of antigens to pulse dendritic cells (DCs). DCs pulsed with ALDH(high) CSC lysates induced significantly higher protective antitumor immunity than DCs pulsed with the lysates of unsorted whole tumor cell lysates in both models and in a lung metastasis setting and a s.c.

Cancer stem cells: mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma.

Background: Cancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.

Methods: Wound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44(high) and aldehyde dehydrogenase [ALDH](+)) and assess mobility, tumorigenesis, and metastasis.

Muscle cells provide instructions for planarian regeneration.

Regeneration requires both potential and instructions for tissue replacement. In planarians, pluripotent stem cells have the potential to produce all new tissue. The identities of the cells that provide regeneration instructions are unknown.

Head and neck cancer stem cells: the effect of HPV--an in vitro and mouse study.

Objectives: To determine if the behavior of cancer stem cells (CSCs) is affected by human papillomavirus (HPV) status.

Study Design: An in vitro and in vivo analysis of HPV and CSCs.

Setting: University laboratory.

In vitro evaluation of sialyl Lewis X relationship with head and neck cancer stem cells.

Objective: To evaluate in vitro the potential links between sialyl Lewis X (sLeX) and cancer stem cells (CSC) in head and neck squamous cell carcinoma (HNSCC). HNSCC is an aggressive malignancy with high mortality mainly due to metastasis. CSC have emerged as important players in HNSCC metastasis.

Scalable patterning of one-dimensional dangling bond rows on hydrogenated Si(001).

Silicon dangling bonds exposed on the monohydride silicon (001) (Si(001):H) surface are highly reactive, thus enabling site-selective absorption of atoms and single molecules into custom patterns designed through the controlled removal of hydrogen atoms. Current implementations of high-resolution hydrogen lithography on the Si(001):H surface rely on sequential removal of hydrogen atoms using the tip of a scanning probe microscope. Here, we present a scalable thermal process that yields very long rows of single dimer wide silicon dangling bonds suitable for self-assembly of atoms and molecules into one-dimensional structures of unprecedented length on Si(001):H.

Degenerate electronic structure of reconstructed MnSi(1.7) nanowires on Si(001).

Higher manganese silicide nanowires have been grown on the Si(001)-2 × 1 surface by the pre-growth of Bi nanolines. Scanning tunnelling microscope (STM) observations show that the nanowire has a linear surface reconstruction with a periodicity of 0.56 nm, and we propose a reconstruction on their surface to reduce the density of dangling bonds, which forms linear structures matching the dimensions from STM.

UM-SCC-104: a new human papillomavirus-16-positive cancer stem cell-containing head and neck squamous cell carcinoma cell line.

Background: Few human papillomavirus (HPV)(+) head and neck squamous cell carcinoma (HNSCC) cell lines exist. We established University of Michigan-squamous cell carcinoma-104 (UM-SCC-104), a new HPV(+) HNSCC cell line from a recurrent oral cavity tumor, and characterized it for the presence of cancer stem cells (CSCs).

Methods: Tumor cells were tested for biomarker expression by immunohistology, and the presence of HPV was assessed by several methods.

Manganese silicide nanowires on Si(001).

A method for promoting the growth of manganese silicide nanowires on Si(001) at 450 °C is described. The anisotropic surface stress generated by bismuth nanolines blocks the formation of embedded structures and stabilizes the nucleation of manganese silicide islands which grow in a preferred direction, forming nanowires with a band gap of approximately 0.6 eV, matching the reported band gap of MnSi(1.