Howe's rank and dual pair correspondence in semistable range

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mathematics, 1998.Includes bibliographical references (p. 126-127).by Hongyu L. He.Ph.D

Is IT Really Becoming a Commodity?

Academics and others have claimed that IT is becoming a commodity input, one that can no longer confer a competitive advantage. If IT is becoming a commodity, the role played by IT in most firms should be akin to that played by utilities. We conduct an event-study to determine whether IT is becoming a commodity. We use the volatility of a firm’s stock price to certain macroeconomic news (news about shrinking or expanding demand) to compare the stock price behavior of utility firms with that of IT firms. We find that although the IT industry as a whole is not becoming a commodity, there are some firms within the IT industry that are similar to a utility. In addition, we find that the view that IT can confer a competitive advantage (as perceived by financial markets) was stronger during the dotcom boom period than at other times in the study period (1980-2007)

E(2)-Equivariant Graph Planning for Navigation

Learning for robot navigation presents a critical and challenging task. The scarcity and costliness of real-world datasets necessitate efficient learning approaches. In this letter, we exploit Euclidean symmetry in planning for 2D navigation, which originates from Euclidean transformations between reference frames and enables parameter sharing. To address the challenges of unstructured environments, we formulate the navigation problem as planning on a geometric graph and develop an equivariant message passing network to perform value iteration. Furthermore, to handle multi-camera input, we propose a learnable equivariant layer to lift features to a desired space. We conduct comprehensive evaluations across five diverse tasks encompassing structured and unstructured environments, along with maps of known and unknown, given point goals or semantic goals. Our experiments confirm the substantial benefits on training efficiency, stability, and generalization

MAPKs activation and mitochondrial depletion are associated with chemotherapy-related cachexia

poster abstractBackground. Cachexia, defined by increased fatigue and loss of muscle function, results from muscle and fat depletion and affects the majority of cancer patients with no effective treatments. Previous studies suggest that chemotherapy itself may contribute to cachexia, although the mechanisms responsible for these derangements are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapyrelated effects on body composition and muscle function. Methods. Chemotherapy regimens routinely used for the therapy of solid tumors were tested in normal CD2F1 mice, followed by assessment of body composition and muscle strength. Mitochondrial activity in muscle sections was evaluated, and TEM imaging in EDL muscle was performed. To determine whether chemotherapy modulates signaling pathways associated with the regulation of muscle mass, Western blotting, qRT-PCR and RNASequencing were utilized. Results. Administration of Folfox (5-FU, leucovorin, oxaliplatin), Folfiri (5-FU, leucovorin, irinotecan) or Gemcitabine/Paclitaxel for up to 5 weeks to normal mice caused marked decreases in adipose tissue and skeletal muscle content, coherent with reduced muscle strength. Notably, ERK1/2/MAPK and p38/MAPK signaling pathways, as well as myostatin expression were significantly up-regulated. TEM analysis unveiled a marked depletion in muscle mitochondrial content and alterations of the sarcomeric structure consistent with loss of muscle structural proteins in the mice receiving chemotherapy. Moreover, the RNA-Sequencing analysis identified several markers associated with mitochondrial homeostasis, lipid metabolism and acute phase response that were significantly affected by Folfiri administration. Conclusions. Our findings suggest that chemotherapy promotes the activation of MAPK- and myostatindependent muscle atrophy and causes mitochondrial depletion and alterations of the sarcomeric units, likely playing a causative role in the occurrence of muscle loss and weakness. Future investigations will clarify whether pharmacologically increasing muscle mass or inhibiting MAPK activation reduces chemotherapy-related cachexia, thereby providing potential pharmacological targets to improve efficacy and tolerance of anticancer drugs

Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs

Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up-regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFβ-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK-dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy

The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway

Publisher’s version made available under a Creative Commons license.The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp) RNAPII transcripts such as small noncoding RNAs (snRNAs), cryptic unstable transcripts (CUTs), and some stable unannotated transcripts (SUTs) that are terminated by an Nrd1, Nab3, and Sen1 (NNS) dependent mechanism. NNS-dependent termination is coupled to RNA 3' end processing and/or degradation by the Rrp6/exosome in yeast. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity. It remains unclear whether Rrp6 is directly involved in termination; however, Rrp6 has been implicated in the 3' end processing and degradation of ncRNA transcripts including CUTs. To determine the role of Rrp6 in NNS termination globally, we performed RNA sequencing (RNA-Seq) on total RNA and perform ChIP-exo analysis of RNA Polymerase II (RNAPII) localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote transcription termination in addition to 3' end RNA processing and/or degradation at specific targets

Fine particle pH and the partitioning of nitric acid during winter in the northeastern United States

Particle pH is a critical but poorly constrained quantity that affects many aerosol processes and properties, including aerosol composition, concentrations, and toxicity. We assess PM1 pH as a function of geographical location and altitude, focusing on the northeastern U.S., based on aircraft measurements from the Wintertime Investigation of Transport, Emissions, and Reactivity campaign (1 February to 15 March 2015). Particle pH and water were predicted with the ISORROPIA-II thermodynamic model and validated by comparing predicted to observed partitioning of inorganic nitrate between the gas and particle phases. Good agreement was found for relative humidity (RH) above 40%; at lower RH observed particle nitrate was higher than predicted, possibly due to organic-inorganic phase separations or nitrate measurement uncertainties associated with low concentrations (nitrate \u3c 1 µg m−3). Including refractory ions in the pH calculations did not improve model predictions, suggesting they were externally mixed with PM1 sulfate, nitrate, and ammonium. Sample line volatilization artifacts were found to be minimal. Overall, particle pH for altitudes up to 5000 m ranged between −0.51 and 1.9 (10th and 90th percentiles) with a study mean of 0.77 ± 0.96, similar to those reported for the southeastern U.S. and eastern Mediterranean. This expansive aircraft data set is used to investigate causes in variability in pH and pH-dependent aerosol components, such as PM1 nitrate, over a wide range of temperatures (−21 to 19°C), RH (20 to 95%), inorganic gas, and particle concentrations and also provides further evidence that particles with low pH are ubiquitous

Enhanced gel formation in binary mixtures of nanocolloids with short-range attraction

© 2018 Author(s). Colloidal suspensions transform between fluid and disordered solid states as parameters such as the colloid volume fraction and the strength and nature of the colloidal interactions are varied. Seemingly subtle changes in the characteristics of the colloids can markedly alter the mechanical rigidity and flow behavior of these soft composite materials. This sensitivity creates both a scientific challenge and an opportunity for designing suspensions for specific applications. In this paper, we report a novel mechanism of gel formation in mixtures of weakly attractive nanocolloids with modest size ratio. Employing a combination of x-ray photon correlation spectroscopy, rheometry, and molecular dynamics simulations, we find that gels are stable at remarkably weaker attraction in mixtures with size ratio near two than in the corresponding monodisperse suspensions. In contrast with depletion-driven gelation at larger size ratio, gel formation in the mixtures is triggered by microphase demixing of the species into dense regions of immobile smaller colloids surrounded by clusters of mobile larger colloids that is not predicted by mean-field thermodynamic considerations. These results point to a new route for tailoring nanostructured colloidal solids through judicious combination of interparticle interaction and size distribution