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1.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38535484

ABSTRACT

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. The small footprint of the on-chip STM provides a great opportunity to increase STM throughput by incorporating a number of on-chip STMs in an array to realize parallel STM. The tip methodology adopted for the on-chip STM presented here, which is a batch-fabricated Si tip, makes our design conducive to this goal. In this work, we investigate the capability of this on-chip STM with an integrated Si tip for STM imaging. We integrate the on-chip STM into a commercial ultrahigh-vacuum STM system and perform imaging with atomic resolution on par with conventional STMs but at higher scan speeds due to the higher sensitivity of the MEMS actuator relative to a piezotube. The results attest that it is possible to achieve a parallel and high-throughput STM platform, which is a fully batch-fabricated MEMS STM nanopositioner capable of performing atomic-resolution STM imaging.

2.
Nat Hum Behav ; 7(1): 114-133, 2023 01.
Article in English | MEDLINE | ID: mdl-36192492

ABSTRACT

When speaking to infants, adults often produce speech that differs systematically from that directed to other adults. To quantify the acoustic properties of this speech style across a wide variety of languages and cultures, we extracted results from empirical studies on the acoustic features of infant-directed speech. We analysed data from 88 unique studies (734 effect sizes) on the following five acoustic parameters that have been systematically examined in the literature: fundamental frequency (f0), f0 variability, vowel space area, articulation rate and vowel duration. Moderator analyses were conducted in hierarchical Bayesian robust regression models to examine how these features change with infant age and differ across languages, experimental tasks and recording environments. The moderator analyses indicated that f0, articulation rate and vowel duration became more similar to adult-directed speech over time, whereas f0 variability and vowel space area exhibited stability throughout development. These results point the way for future research to disentangle different accounts of the functions and learnability of infant-directed speech by conducting theory-driven comparisons among different languages and using computational models to formulate testable predictions.


Subject(s)
Speech Acoustics , Speech , Humans , Infant , Acoustics , Bayes Theorem , Phonetics
3.
Mol Cancer Res ; 17(12): 2492-2507, 2019 12.
Article in English | MEDLINE | ID: mdl-31537618

ABSTRACT

The major obstacle in successfully treating triple-negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous preclinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphologic phenotype, which consists of polyploid giant cancer cells giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets. This resistant phenotype is associated with metabolic reprogramming with a shift to a greater dependence on fatty acids and oxidative phosphorylation. We validated both the molecular and histologic features of this model in a clinical cohort of primary chemoresistant TNBCs and identified several metabolic vulnerabilities including a dependence on PLIN4, a perilipin coating the observed lipid droplets, expressed both in the TNBC-resistant cells and clinical chemoresistant tumors treated with neoadjuvant doxorubicin-based chemotherapy. These findings thus reveal a novel mechanism of chemotherapy resistance that has therapeutic implications in the treatment of drug-resistant cancer. IMPLICATIONS: These findings underlie the importance of a novel morphologic-metabolic phenotype associated with chemotherapy resistance in TNBC, and bring to light novel therapeutic targets resulting from vulnerabilities in this phenotype, including the expression of PLIN4 essential for stabilizing lipid droplets in resistant cells.


Subject(s)
Cellular Reprogramming/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Perilipin-4/genetics , Triple Negative Breast Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cellular Reprogramming/genetics , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Lipid Droplets/drug effects , Metabolic Networks and Pathways/drug effects , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology
4.
Sci Rep ; 4: 6196, 2014 Sep 04.
Article in English | MEDLINE | ID: mdl-25186586

ABSTRACT

Titanosaurian sauropod dinosaurs were the most diverse and abundant large-bodied herbivores in the southern continents during the final 30 million years of the Mesozoic Era. Several titanosaur species are regarded as the most massive land-living animals yet discovered; nevertheless, nearly all of these giant titanosaurs are known only from very incomplete fossils, hindering a detailed understanding of their anatomy. Here we describe a new and gigantic titanosaur, Dreadnoughtus schrani, from Upper Cretaceous sediments in southern Patagonia, Argentina. Represented by approximately 70% of the postcranial skeleton, plus craniodental remains, Dreadnoughtus is the most complete giant titanosaur yet discovered, and provides new insight into the morphology and evolutionary history of these colossal animals. Furthermore, despite its estimated mass of about 59.3 metric tons, the bone histology of the Dreadnoughtus type specimen reveals that this individual was still growing at the time of death.


Subject(s)
Fossils , Animals , Argentina , Biological Evolution , Bone and Bones/anatomy & histology , Dinosaurs/classification , Phylogeny
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