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

Experiential Learning: The Case of Training MBA Students in an Asian School

Consulting for a startup company is an effective way for Master of Business Administration (MBA) students to learn about management consulting, and the ways and means of a startup company. This paper discusses the experience of an MBA startup project within the context of a core corporate finance course. The project requires the active engagement of several groups of stakeholders—MBA students, the university’s entrepreneurship incubator, a selection of startup companies, and the project’s academic collaborators. In line with the literature, we find that entrepreneurship education through student-startup collaboration contributes to the students’ entrepreneurial learning, and that the offering of an experiential learning course provides students with the opportunities to work with the external business community that yield positive benefits for students, startups, and the university. Our findings add to the experiential learning literature in business education and show that practice-based learning offers an effective learning experience for students whereby all stakeholders are exposed to various communities of practice that facilitate multiple streams of learning. We provide insights on experiential learning from the implementation of a “new” learning pedagogy for MBA students at an Asian institute of higher learning

Reply to "Comment on `First-principles calculation of the superconducting transition in MgB2 within the anisotropic Eliashberg formalism'"

The recent preprint by Mazin et al. [cond-mat/0212417] contains many inappropriate evaluations and/or criticisms on our published work [Phys. Rev. B 66, 020513 (2002) and Nature 418, 758 (2002)]. The preprint [cond-mat/0212417v1] was submitted to Physical Review B as a comment on one of our papers [Phys. Rev. B 66, 020513 (2002)]. In the reviewing process, Mazin et al. have withdrawn many of the statements contained in cond-mat/0212417v1, however two claims remain in their revised manuscript [cond-mat/0212417v3]: (1) the calculated variations of the superconducting energy gap within the sigma- or the pi-bands are not observable in real samples due to scatterings, and (2) the Coulomb repulsion mu(k,k') is negligibly small between sigma- and pi-states and thus should be approximated by a diagonal 2 x 2 matrix in the sigma and pi channels. Here, we point out that the former does not affect the validity of our theoretical work which is for the clean limit, and that the latter is not correct

Phase 1 clinical trial evaluating the safety and anti-tumor activity of ADP-A2M10 SPEAR T-cells in patients with MAGE-A10+ head and neck, melanoma, or urothelial tumors

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered autologous T-cells that express a high-affinity melanoma-associated antigen (MAGE)-A10-specific T-cell receptor (TCR) targeting MAGE-A10-positive tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-004 is a phase 1, dose-escalation trial to evaluate the safety and anti-tumor activity of ADP-A2M10 in three malignancies (https://clinicaltrials.gov: NCT02989064). METHODS: Eligible patients were HLA-A*02 positive with advanced head and neck squamous cell carcinoma (HNSCC), melanoma, or urothelial carcinoma (UC) expressing MAGE-A10. Patients underwent apheresis; T-cells were isolated, transduced with a lentiviral vector containing the MAGE-A10 TCR, and expanded. Patients underwent lymphodepletion with fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 was administered in two dose groups receiving 0.1×10 RESULTS: Ten patients (eight male and two female) with HNSCC (four), melanoma (three), and UC (three) were treated. Three patients were treated in each of the two dose groups, and four patients were treated in the expansion group. The most frequently reported adverse events grade ≥3 were leukopenia (10), lymphopenia (10), neutropenia (10), anemia (nine), and thrombocytopenia (five). Two patients reported cytokine release syndrome (one each with grade 1 and grade 3), with resolution. Best response included stable disease in four patients, progressive disease in five patients, and not evaluable in one patient. ADP-A2M10 cells were detectable in peripheral blood from patients in each dose group and the expansion group and in tumor tissues from patients in the higher dose group and the expansion group. Peak persistence was greater in patients from the higher dose group and the expansion group compared with the lower dose group. CONCLUSIONS: ADP-A2M10 has shown an acceptable safety profile with no evidence of toxicity related to off-target binding or alloreactivity in these malignancies. Persistence of ADP-A2M10 in the peripheral blood and trafficking of ADP-A2M10 into the tumor was demonstrated. Because MAGE-A10 expression frequently overlaps with MAGE-A4 expression in tumors and responses were observed in the MAGE-A4 trial (NCT03132922), this clinical program closed, and trials with SPEAR T-cells targeting the MAGE-A4 antigen are ongoing

Mrgprd Enhances Excitability in Specific Populations of Cutaneous Murine Polymodal Nociceptors

The Mas-related G protein-coupled receptor D (Mrgprd) is selectively expressed in nonpeptidergic nociceptors that innervate the outer layers of mammalian skin. The function of Mrgprd in nociceptive neurons and the physiologically relevant somatosensory stimuli that activate Mrgprd^-expressing (Mrgprd^+) neurons are currently unknown. To address these issues, we studied three Mrgprd knock-in mouse lines using an ex vivo somatosensory preparation to examine the role of the Mrgprd receptor and Mrgprd+ afferents in cutaneous somatosensation. In mouse hairy skin, Mrgprd, as marked by expression of green fluorescent protein reporters, was expressed predominantly in the population of nonpeptidergic, TRPV1-negative, C-polymodal nociceptors. In mice lacking Mrgprd, this population of nociceptors exhibited decreased sensitivity to cold, heat, and mechanical stimuli. Additionally, in vitro patch-clamp studies were performed on cultured dorsal root ganglion neurons from Mrgprd^(–/–) and Mrgprd^(+/–) mice. These studies revealed a higher rheobase in neurons from Mrgprd^(–/–) mice than from Mrgprd^(+/–) mice. Furthermore, the application of the Mrgprd ligand β-alanine significantly reduced the rheobase and increased the firing rate in neurons from Mrgprd^(+/–) mice but was without effect in neurons from Mrgprd^(–/–) mice. Our results demonstrate that Mrgprd influences the excitability of polymodal nonpeptidergic nociceptors to mechanical and thermal stimuli

Community-acquired pneumonia in children: cell-free plasma sequencing for diagnosis and management.

Community-acquired pneumonia (CAP) is a common cause of pediatric hospital admission. Empiric antibiotic therapy for hospitalized children with serious CAP now targets the most likely pathogen(s), including those that may demonstrate significant antibiotic resistance. Cell-free plasma next-generation sequencing (CFPNGS) was first made available for Pediatric Infectious Diseases physicians in June 1, 2017, to supplement standard-of-care diagnostic techniques. A retrospective chart review was performed for children hospitalized with CAP between June 1, 2017, and January 22, 2018, to evaluate the impact of CFPNGS. We identified 15 hospitalized children with CAP without other underlying medical conditions for whom CFPNGS was performed. CFPNGS identified a pathogen in 13 of 15 (86%) children compared with 47% for those using standard culture and PCR-based methods alone. Changes in antibiotic management were made in 7 of 15 (47%) of children as a result of CFPNGS

Ferroelectric-Domain-Patterning-Controlled Schottky Junction State in Monolayer MoS\u3csub\u3e2\u3c/sub\u3e

We exploit scanning-probe-controlled domain patterning in a ferroelectric top layer to induce nonvolatile modulation of the conduction characteristic of monolayer MoS2 between a transistor and a junction state. In the presence of a domain wall, MoS2 exhibits rectified I-V characteristics that are well described by the thermionic emission model. The induced Schottky barrier height ΦeffB varies from 0.38 to 0.57 eV and is tunable by a SiO2 global back gate, while the tuning range of ΦeffB depends sensitively on the conduction-band-tail trapping states. Our work points to a new route to achieving programmable functionalities in van der Waals materials and sheds light on the critical performance limiting factors in these hybrid systems

Reduction of gas bubbles and improved critical current density in Bi-2212 round wire by swaging

Bi-2212 round wire is made by the powder-in-tube technique. An unavoidable property of powder-in-tube conductors is that there is about 30% void space in the as-drawn wire. We have recently shown that the gas present in the as-drawn Bi-2212 wire agglomerates into large bubbles and that they are presently the most deleterious current limiting mechanism. By densifying short 2212 wires before reaction through cold isostatic pressing (CIPping), the void space was almost removed and the gas bubble density was reduced significantly, resulting in a doubled engineering critical current density (JE) of 810 A/mm2 at 5 T, 4.2 K. Here we report on densifying Bi-2212 wire by swaging, which increased JE (4.2 K, 5 T) from 486 A/mm2 for as-drawn wire to 808 A/mm2 for swaged wire. This result further confirms that enhancing the filament packing density is of great importance for making major JE improvement in this round-wire magnet conductor.Comment: To be published in IEEE Transactions on Applied Superconductivity, 23, xxxxxx (2013

Dual EGFR inhibition in combination with anti-VEGF treatment: a phase I clinical trial in non-small cell lung cancer.

BackgroundPreclinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models.MethodsWe conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response.ResultsThirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD) ≥6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD≥6 months or uPR. Correlation between grade of rash and rate of SD≥6 months/PR was observed (p less than 0.01).ConclusionThe combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC