Fine-Grained Complexity Lower Bounds for Families of Dynamic Graphs

A dynamic graph algorithm is a data structure that answers queries about a property of the current graph while supporting graph modifications such as edge insertions and deletions. Prior work has shown strong conditional lower bounds for general dynamic graphs, yet graph families that arise in practice often exhibit structural properties that the existing lower bound constructions do not possess. We study three specific graph families that are ubiquitous, namely constant-degree graphs, power-law graphs, and expander graphs, and give the first conditional lower bounds for them. Our results show that even when restricting our attention to one of these graph classes, any algorithm for fundamental graph problems such as distance computation or approximation or maximum matching, cannot simultaneously achieve a sub-polynomial update time and query time. For example, we show that the same lower bounds as for general graphs hold for maximum matching and (s,t)-distance in constant-degree graphs, power-law graphs or expanders. Namely, in an m-edge graph, there exists no dynamic algorithms with both O(m^{1/2 - ?}) update time and O(m^{1 -?}) query time, for any small ? > 0. Note that for (s,t)-distance the trivial dynamic algorithm achieves an almost matching upper bound of constant update time and O(m) query time. We prove similar bounds for the other graph families and for other fundamental problems such as densest subgraph detection and perfect matching

On Approximate Envy-Freeness for Indivisible Chores and Mixed Resources

We study the fair allocation of undesirable indivisible items, or chores. While the case of desirable indivisible items (or goods) is extensively studied, with many results known for different notions of fairness, less is known about the fair division of chores. We study envy-free allocation of chores and make three contributions. First, we show that determining the existence of an envy-free allocation is NP-complete even in the simple case when agents have binary additive valuations. Second, we provide a polynomial-time algorithm for computing an allocation that satisfies envy-freeness up to one chore (EF1), correcting a claim in the existing literature. A modification of our algorithm can be used to compute an EF1 allocation for doubly monotone instances (where each agent can partition the set of items into objective goods and objective chores). Our third result applies to a mixed resources model consisting of indivisible items and a divisible, undesirable heterogeneous resource (i.e., a bad cake). We show that there always exists an allocation that satisfies envy-freeness for mixed resources (EFM) in this setting, complementing a recent result of Bei et al. [Bei et al., 2021] for indivisible goods and divisible cake

Natural history of asymptomatic pancreatic cystic neoplasms

AbstractBackgroundThe management of asymptomatic pancreatic cysts is controversial and indications for excision are based on pathology and natural history.ObjectivesThis study aimed to examine outcomes of asymptomatic lesions using a protocol based on size and cyst fluid analysis.MethodsAsymptomatic cysts were identified from a prospectively maintained database. Sequential cross‐sectional imaging studies were assessed, and results of endoscopic ultrasound‐guided aspiration were co‐analysed.ResultsA total of 338 asymptomatic patients underwent evaluation. Overall, 84 cysts were <1.5 cm and 254 were ≥1.5 cm in diameter. Median patient follow‐up was 5.1 years [interquartile range (IQR): 4.1–6.9 years]. In the group in which cysts measured <1.5 cm in diameter, median cyst size was 1.0 cm (IQR: 0.6–1.2 cm) at presentation and increased to 1.2 cm (IQR: 0.7–1.6 cm) during follow‐up. Five (6.0%) patients underwent resection, all within 2 months of presentation. In the group in which cysts measured ≥1.5 cm in diameter, median cyst size was 2.5 cm (IQR: 2.0–3.4 cm) at presentation and increased to 2.7 cm (IQR: 3.0–4.2 cm). A total of 63 (24.8%) patients underwent resection. Surgery was performed with 2 months in 53 (84.1%) patients, within 12 months in four (6.3%) patients and at >12 months post‐presentation in six (9.5%) patients. A total of 70.6% of resected specimens were identified as malignancies or mucinous lesions.conclusionsAsymptomatic cysts of <1.5 cm in diameter can safely be followed by imaging and are expected to undergo little change. A quarter of all asymptomatic cysts measuring ≥1.5 cm are appropriately resected based on imaging and cyst fluid analysis

Hsf1 Activation Inhibits Rapamycin Resistance and TOR Signaling in Yeast Revealed by Combined Proteomic and Genetic Analysis

TOR kinases integrate environmental and nutritional signals to regulate cell growth in eukaryotic organisms. Here, we describe results from a study combining quantitative proteomics and comparative expression analysis in the budding yeast, S. cerevisiae, to gain insights into TOR function and regulation. We profiled protein abundance changes under conditions of TOR inhibition by rapamycin treatment, and compared this data to existing expression information for corresponding gene products measured under a variety of conditions in yeast. Among proteins showing abundance changes upon rapamycin treatment, almost 90% of them demonstrated homodirectional (i.e., in similar direction) transcriptomic changes under conditions of heat/oxidative stress. Because the known downstream responses regulated by Tor1/2 did not fully explain the extent of overlap between these two conditions, we tested for novel connections between the major regulators of heat/oxidative stress response and the TOR pathway. Specifically, we hypothesized that activation of regulator(s) of heat/oxidative stress responses phenocopied TOR inhibition and sought to identify these putative TOR inhibitor(s). Among the stress regulators tested, we found that cells (hsf1-R206S, F256S and ssa1-3 ssa2-2) constitutively activated for heat shock transcription factor 1, Hsf1, inhibited rapamycin resistance. Further analysis of the hsf1-R206S, F256S allele revealed that these cells also displayed multiple phenotypes consistent with reduced TOR signaling. Among the multiple Hsf1 targets elevated in hsf1-R206S, F256S cells, deletion of PIR3 and YRO2 suppressed the TOR-regulated phenotypes. In contrast to our observations in cells activated for Hsf1, constitutive activation of other regulators of heat/oxidative stress responses, such as Msn2/4 and Hyr1, did not inhibit TOR signaling. Thus, we propose that activated Hsf1 inhibits rapamycin resistance and TOR signaling via elevated expression of specific target genes in S. cerevisiae. Additionally, these results highlight the value of comparative expression analyses between large-scale proteomic and transcriptomic datasets to reveal new regulatory connections

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Hemodynamic Analysis Shows High Wall Shear Stress Is Associated with Intraoperatively Observed Thin Wall Regions of Intracranial Aneurysms

Background: Studying the relationship between hemodynamics and local intracranial aneurysm (IA) pathobiology can help us understand the natural history of IA. We characterized the relationship between the IA wall appearance, using intraoperative imaging, and the hemodynamics from CFD simulations. Methods: Three-dimensional geometries of 15 IAs were constructed and used for CFD. Two-dimensional intraoperative images were subjected to wall classification using a machine learning approach, after which the wall type was mapped onto the 3D surface. IA wall regions included thick (white), normal (purple-crimson), and thin/translucent (red) regions. IA-wide and local statistical analyses were performed to assess the relationship between hemodynamics and wall type. Results: Thin regions of the IA sac had significantly higher WSS, Normalized WSS, WSS Divergence and Transverse WSS, compared to both normal and thick regions. Thicker regions tended to co-locate with significantly higher RRT than thin regions. These trends were observed on a local scale as well. Regression analysis showed a significant positive correlation between WSS and thin regions and a significant negative correlation between WSSD and thick regions. Conclusion: Hemodynamic simulation results were associated with the intraoperatively observed IA wall type. We consistently found that elevated WSS and WSSNorm were associated with thin regions of the IA wall rather than thick and normal regions