
Ge, Ruowen; Tan, Evan; Asada, Haruhiko; Sharghi Namini, Soheila
Cancer is a complex organ whose behavior is not only influenced by genetic and epigenetic changes in cancer cells but also by stromal cells, local extracellular matrix and specific tissue architecture. Intercellular communications within the cancer microenvironment are critical to coordinate the assembly of multiple cell types for an amalgamated form and function of a cancer. Exosomes are small membrane vesicles with an endosome origin that are released by cells into the extracellular environment. They carry a cargo of proteins, lipids, and nucleic acids and transfer their cargo to recipient cells and altering the recipient cells’ biochemical composition, signaling pathways,...

Ruberman, Daniel; Saveliev, Nikolai; Mrowka, Tomasz S
We extend the Atiyah, Patodi, and Singer index theorem for firstorder differential operators from the context of manifolds with cylindrical ends to manifolds with periodic ends. This theorem provides a natural complement to Taubes’ Fredholm theory for general endperiodic operators. Our index theorem is expressed in terms of a new periodic etainvariant that equals the Atiyah–Patodi–Singer etainvariant in the cylindrical setting. We apply this periodic etainvariant to the study of moduli spaces of Riemannian metrics of positive scalar curvature.

Hemmerling, Börge; Wang, Xiaoting; Cappellaro, Paola; Aiello, Clarice Demarchi; Allegra, Michele
Unfortunately, the coauthor Xiaoting Wang’s name has been misspelled in the original article. The correct name is ‘Xiaoting Wang’.

Sabino, C. P.; Garcez, A. S.; Núñez, S. C.; Ribeiro, M. S.; Hamblin, Michael R
Antimicrobial photodynamic therapy (APDT) combined with endodontic treatment has been recognized as an alternative approach to complement conventional root canal disinfection methods on bacterial biofilms. We developed an in vitro model of bioluminescent Candida albicans biofilm inside curved dental root canals and investigated the microbial reduction produced when different light delivery methods are employed. Each light delivery method was evaluated in respect to the light distribution provided inside curved root canals. After conventional endodontic preparation, teeth were sterilized before canals were contaminated by a bioluminescent strain of C. albicans (CEC789). Methylene blue (90 μM) was introduced into the canals and...

Brielle, Shlomi; Kaganovich, Daniel; Gura Sadovsky, Rotem
Recent innovations in cell biology and imaging approaches are changing the way we study cellular stress, protein misfolding, and aggregation. Studies have begun to show that stress responses are even more variegated and dynamic than previously thought, encompassing nanoscale reorganization of cytosolic machinery that occurs almost instantaneously, much faster than transcriptional responses. Moreover, protein and mRNA quality control is often organized into highly dynamic macromolecular assemblies, or dynamic droplets, which could easily be mistaken for dysfunctional “aggregates,” but which are, in fact, regulated functional compartments. The nanoscale architecture of stressresponse ranges from diffractionlimited structures like stress granules, Pbodies, and stress...

Ovaskainen, Otso; Finkelshtein, Dmitri; Kutoviy, Oleksandr; Cornell, Stephen; Bolker, Benjamin; Kondratiev, Yuri; Kutovyi, Oleksandr
Spatial and stochastic models are often straightforward to simulate but difficult to analyze mathematically. Most of the mathematical methods available for nonlinear stochastic and spatial models are based on heuristic rather than mathematically justified assumptions, so that, e.g., the choice of the moment closure can be considered more of an art than a science. In this paper, we build on recent developments in specific branch of probability theory, Markov evolutions in the space of locally finite configurations, to develop a mathematically rigorous and practical framework that we expect to be widely applicable for theoretical ecology. In particular, we show how...

Zhao, Weiwei; Kim, Duk Y.; Zhang, Haijun; Assaf, Badih A.; Heiman, Don; Zhang, ShouCheng; Liu, Chaoxing; Chan, Moses H. W.; Chang, Cuizu; Moodera, Jagadeesh
The discovery of the quantum Hall (QH) effect led to the realization of a topological electronic state with dissipationless currents circulating in one direction along the edge of a twodimensional electron layer under a strong magnetic field[superscript 1, 2]. The quantum anomalous Hall (QAH) effect shares a similar physical phenomenon to that of the QH effect, whereas its physical origin relies on the intrinsic spin–orbit coupling and ferromagnetism[superscript 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. Here, we report the experimental observation of the QAH state in Vdoped (Bi,Sb)[subscript 2]Te[subscript 3] films with the...

Costinot, Arnaud; Donaldson, David John; Vogel, Jonathan; Werning, Ivan
The theory of comparative advantage is at the core of neoclassical trade theory. Yet we know little about its implications for how nations should conduct their trade policy. For example, should import sectors with weaker comparative advantage be protected more? Conversely, should export sectors with stronger comparative advantage be subsidized less? In this article we take a first stab at exploring these issues. Our main results imply that in the context of a canonical Ricardian model, optimal import tariffs should be uniform, whereas optimal export subsidies should be weakly decreasing with respect to comparative advantage, reflecting the fact that countries...

Choe, Han Kyoung; Reed, Michael Douglas; Benavidez, Nora; Montgomery, Daniel P; Soares, Natalie; Yim, Yeong Shin; Choi, Bohyun Gloria; Choe, Han Kyoung; Reed, Michael Douglas
Meaningful social interactions modify behavioral responses to sensory stimuli. The neural mechanisms underlying the entrainment of neutral sensory stimuli to salient social cues to produce social learning remain unknown. We used odordriven behavioral paradigms to ask if oxytocin, a neuropeptide implicated in various social behaviors, plays a crucial role in the formation of learned associations between odor and socially significant cues. Through genetic, optogenetic, and pharmacological manipulations, we show that oxytocin receptor signaling is crucial for entrainment of odor to social cues but is dispensable for entrainment to nonsocial cues. Furthermore, we demonstrate that oxytocin directly impacts the piriform, the...

Gutierrez, Gregory D.; Coropceanu, Igor; Bawendi, Moungi G.; Swager, Timothy M.
A highly efficient thinfilm luminescent solar concentrator (LSC) utilizing two πconjugated polymers as antennae for small amounts of the valued perylene bisimide Lumogen F Red 305 is presented. The LSC exhibits high photoluminescence quantum yield, low reabsorption, and relatively low refractive indices for waveguide matching. A Monte Carlo simulation predicts the LSC to possess exceptionally high optical efficiencies on large scales.

Chileveru, Haritha Reddy; Lim, Shion A.; Chairatana, Phoom; Wommack, Andrew; Chiang, ILing; Nolan, Elizabeth Marie
Human αdefensin 5 (HD5) is a 32residue cysteinerich hostdefense peptide that exhibits broadspectrum antimicrobial activity and contributes to innate immunity in the human gut and other organ systems. Despite many years of investigation, its antimicrobial mechanism of action remains unclear. In this work, we report that HD5[subscript ox], the oxidized form of this peptide that exhibits three regiospecific disulfide bonds, causes distinct morphological changes to Escherichia coli and other Gramnegative microbes. These morphologies include bleb formation, cellular elongation, and clumping. The blebs are up to ∼1 μm wide and typically form at the site of cell division or cell poles....

Simmons, Sean Kenneth; Berger Leighton, Bonnie
Motivation: As genomics moves into the clinic, there has been much interest in using this medical data for research. At the same time the use of such data raises many privacy concerns. These circumstances have led to the development of various methods to perform genomewide association studies (GWAS) on patient records while ensuring privacy. In particular, there has been growing interest in applying differentially private techniques to this challenge. Unfortunately, up until now all methods for finding high scoring SNPs in a differentially private manner have had major drawbacks in terms of either accuracy or computational efficiency.
Results: Here we overcome...

Yu, Yun William; Daniels, Noah; Danko, David C.; Berger Leighton, Bonnie
Many datasets exhibit a welldefined structure that can be exploited to design faster search tools, but it is not always clear when such acceleration is possible. Here, we introduce a framework for similarity search based on characterizing a dataset’s entropy and fractal dimension. We prove that searching scales in time with metric entropy (number of covering hyperspheres), if the fractal dimension of the dataset is low, and scales in space with the sum of metric entropy and informationtheoretic entropy (randomness of the data). Using these ideas, we present accelerated versions of standard tools, with no loss in specificity and little...

Chindelevitch, Leonid; Trigg, Jason A.; Regev, Aviv; Berger Leighton, Bonnie
In their Correspondence entitled, “Do genome‐scale models need exact solvers or clearer standards?”, Ebrahim et al (2015) suggest an unnecessary dichotomy. They discuss the findings of our paper, “An exact arithmetic toolbox for a consistent and reproducible structural analysis of metabolic network models” (Chindelevitch et al, 2014), and suggest that our work highlights the need for better model encoding standards. Moreover, the authors dispute our claims that multiple previously published metabolic network models are unable to produce growth when analyzed with an exact arithmetic approach. They attribute discrepancies between their findings and ours solely to a misinterpretation of the formatting...

Yu, Yun William; Yorukoglu, Deniz; Peng, Jian; Berger Leighton, Bonnie
To the Editor:
Most nextgeneration sequencing (NGS) quality scores are space intensive, redundant and often misleading. In this Correspondence, we recover quality information directly from sequence data using a compression tool named Quartz, rendering such scores redundant and yielding substantially better space and time efficiencies for storage and analysis. Quartz is designed to operate on NGS reads in FASTQ format, but it can be trivially modified to discard quality scores in other formats for which scores are paired with sequence information. Discarding 95% of quality scores resulted, counterintuitively, in improved SNP calling, implying that compression need not come at the expense...

Olken, Benjamin A.
Imagine a nefarious researcher in economics who is only interested in finding a statistically significant result of an experiment. The researcher has 100 different variables he could examine, and the truth is that the experiment has no impact. By construction, the researcher should find an average of five of these variables statistically significantly different between the treatment group and the control group at the 5 percent level—after all, the exact definition of 5 percent significance implies that there will be a 5 percent false rejection rate of the null hypothesis that there is no difference between the groups. The nefarious...

Autor, David H.; Figlio, David; Karbownik, Krzysztof; Roth, Jeffrey; Wasserman, Melanie Sharon
Recent evidence indicates that boys and girls are differently affected by the quantity and quality of family inputs received in childhood. We assess whether this is also true for schooling inputs. Using matched Florida birth and school administrative records, we estimate the causal effect of school quality on the gender gap in educational outcomes by contrasting oppositesex siblings who attend the same sets of schoolsthereby purging family heterogeneityand leveraging withinfamily variation in school quality arising from family moves. Investigating middle school test scores, absences and suspensions, we find that boys benefit more than girls from cumulative exposure to higher quality...

Autor, David H.; Palmer, Christopher John; Pathak, Parag A.; Pathak, Parag
We measure the capitalization of housing market externalities into residential housing values by studying the unanticipated elimination of stringent rent controls in Cambridge, Massachusetts, in 1995. Pooling data on the universe of assessed values and transacted prices of Cambridge residential properties between 1988 and 2005, we find that rent decontrol generated substantial, robust price appreciation at decontrolled units and nearby nevercontrolled units, accounting for a quarter of the $7.8 billion in Cambridge residential property appreciation during this period. The majority of this contribution stems from induced appreciation of nevercontrolled properties. Residential investment explains only a small fraction of the total.

Hasdeo, Eddwi H.; Nugraha, Ahmad R. T.; Dresselhaus, Mildred; Saito, Riichiro
Intensities of the first and the secondorder Raman spectra are calculated as a function of the Fermi energy. We show that the Kohn anomaly effect, i.e., phonon frequency renormalization, in the firstorder Raman spectra originates from the phonon renormalization by the interband electronhole excitation, whereas in the secondorder Raman spectra, a competition between the interband and intraband electronhole excitations takes place. By this calculation, we confirm the presence of different dispersive behaviors of the Raman peak frequency as a function of the Fermi energy for the first and the secondorder Raman spectra, as observed in some previous experiments. Moreover, the...

Lange, Julian Hendrik; Noordam, Michiel J.; van Daalen, Saskia K. M.; Skaletsky, Helen; Clark, Brian A.; Macville, Merryn V.; Page, David C.; Repping, Sjoerd
Amplicons – large, nearly identical repeats in direct or inverted orientation – are abundant in the malespecific region of the human Y chromosome (MSY) and provide targets for intrachromosomal nonallelic homologous recombination (NAHR). Thus far, NAHR events resulting in deletions, duplications, inversions, or isodicentric chromosomes have been reported only for amplicon pairs located exclusively on the short arm (Yp) or the long arm (Yq). Here we report our finding of four men with Y chromosomes that evidently formed by intrachromosomal NAHR between inverted repeat pairs comprising one amplicon on Yp and one amplicon on Yq. In two men with spermatogenic...