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Book ; Online: Testing Sumsets is Hard

Chen, Xi / Nadimpalli, Shivam / Randolph, Tim / Servedio, Rocco A. / Zamir, Or

2024

Abstract: ... in A\}$ for some $A \subseteq \mathbb{F}_2^n$. Sumsets are central objects of study in additive combinatorics ...

Abstract	A subset $S$ of the Boolean hypercube $\mathbb{F}_2^n$ is a sumset if $S = \{a + b : a, b\in A\}$ for some $A \subseteq \mathbb{F}_2^n$. Sumsets are central objects of study in additive combinatorics, featuring in several influential results. We prove a lower bound of $\Omega(2^{n/2})$ for the number of queries needed to test whether a Boolean function $f:\mathbb{F}_2^n \to \{0,1\}$ is the indicator function of a sumset. Our lower bound for testing sumsets follows from sharp bounds on the related problem of shift testing, which may be of independent interest. We also give a near-optimal {$2^{O(n/2)} \cdot \mathrm{poly}(n)$}-query algorithm for a smoothed analysis formulation of the sumset refutation problem. Comment: 18 pages
Keywords	Computer Science - Data Structures and Algorithms ; Computer Science - Computational Complexity ; Mathematics - Combinatorics
Publishing date	2024-01-14
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Subset Sum in Time $2^{n/2} / poly(n)$

Chen, Xi / Jin, Yaonan / Randolph, Tim / Servedio, Rocco A.

2023

Abstract: A major goal in the area of exact exponential algorithms is to give an algorithm for the (worst-case) $n$-input Subset Sum problem that runs in time $2^{(1/2 - c)n}$ for some constant $c>0$. In this paper we give a Subset Sum algorithm with worst-case ... ...

Abstract	A major goal in the area of exact exponential algorithms is to give an algorithm for the (worst-case) $n$-input Subset Sum problem that runs in time $2^{(1/2 - c)n}$ for some constant $c>0$. In this paper we give a Subset Sum algorithm with worst-case running time $O(2^{n/2} \cdot n^{-\gamma})$ for a constant $\gamma > 0.5023$ in standard word RAM or circuit RAM models. To the best of our knowledge, this is the first improvement on the classical ``meet-in-the-middle'' algorithm for worst-case Subset Sum, due to Horowitz and Sahni, which can be implemented in time $O(2^{n/2})$ in these memory models. Our algorithm combines a number of different techniques, including the ``representation method'' introduced by Howgrave-Graham and Joux and subsequent adaptations of the method in Austrin, Kaski, Koivisto, and Nederlof, and Nederlof and Wegrzycki, and ``bit-packing'' techniques used in the work of Baran, Demaine, and Patrascu on subquadratic algorithms for 3SUM. Comment: 26 pages, 9 figures
Keywords	Computer Science - Data Structures and Algorithms ; 68Q25
Subject code	004
Publishing date	2023-01-17
Publishing country	us
Document type	Book ; Online
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Article ; Online: Light in the Feet: A Case of Severe Regional Osteoporosis.

Randolph, Attiya / Gaviola, Glenn C / Maiberger, Mary Piazza / Chen, Wen / Sen, Sabyasachi / Karsner, Ryan / Kerr, Gail S

Arthritis care & research

2022 Volume 75, Issue 4, Page(s) 705–711

MeSH term(s)	Humans ; Osteoporosis/complications ; Osteoporosis/diagnostic imaging ; Foot
Language	English
Publishing date	2022-11-26
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.24975
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Zs.A 2446: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 24: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Apolipoprotein E secreted by astrocytes forms antiparallel dimers in discoidal lipoproteins.

Strickland, Michael R / Rau, Michael J / Summers, Brock / Basore, Katherine / Wulf, John / Jiang, Hong / Chen, Yun / Ulrich, Jason D / Randolph, Gwendalyn J / Zhang, Rui / Fitzpatrick, James A J / Cashikar, Anil G / Holtzman, David M

Neuron

2024 Volume 112, Issue 7, Page(s) 1100–1109.e5

Abstract: The Apolipoprotein E gene (APOE) is of great interest due to its role as a risk factor for late-onset Alzheimer's disease. ApoE is secreted by astrocytes in the central nervous system in high-density lipoprotein (HDL)-like lipoproteins. Structural models ...

Abstract	The Apolipoprotein E gene (APOE) is of great interest due to its role as a risk factor for late-onset Alzheimer's disease. ApoE is secreted by astrocytes in the central nervous system in high-density lipoprotein (HDL)-like lipoproteins. Structural models of lipidated ApoE of high resolution could aid in a mechanistic understanding of how ApoE functions in health and disease. Using monoclonal Fab and F(ab')
MeSH term(s)	Astrocytes/metabolism ; Apolipoproteins E/genetics ; Lipoproteins, HDL/chemistry ; Lipoproteins, HDL/metabolism ; Central Nervous System/metabolism ; Apolipoprotein E4/metabolism ; Apolipoprotein E3/metabolism ; Lipoproteins
Chemical Substances	discoidal lipoproteins ; Apolipoproteins E ; Lipoproteins, HDL ; Apolipoprotein E4 ; Apolipoprotein E3 ; Lipoproteins
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2023.12.018
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

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Article ; Online: The efficacy of vitamin E in preventing arthrofibrosis after joint replacement.

Fan, Yingfang / Yuh, Jean / Lekkala, Sashank / Asik, Mehmet D / Thomson, Andrew / McCanne, Madeline / Randolph, Mark A / Chen, Antonia F / Oral, Ebru

Animal models and experimental medicine

2024

Abstract: Background: Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues. Vitamin E is an antioxidant with potential anti-fibroblastic effect. The aim of this study was to establish an arthrofibrosis rat model after ... ...

Abstract	Background: Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues. Vitamin E is an antioxidant with potential anti-fibroblastic effect. The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis. Methods: We simulated knee replacement in 16 male Sprague-Dawley rats. We immobilized the surgical leg with a suture in full flexion. The control groups were killed at 2 and 12 weeks (n = 5 per group), and the test group was supplemented daily with vitamin E (0.2 mg/mL) in their drinking water for 12 weeks (n = 6). We performed histological staining to investigate the presence and severity of arthrofibrosis. Immunofluorescent staining and α2-macroglobulin (α2M) enzyme-linked immunosorbent assay (ELISA) were used to assess local and systemic inflammation. Static weight bearing (total internal reflection) and range of motion (ROM) were collected for functional assessment. Results: The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups. Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue. Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels. The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group. Conclusions: This model is viable for simulating arthrofibrosis after joint replacement. Vitamin E may benefit postsurgical arthrofibrosis, and further studies are needed for dosing requirements.
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ISSN	2576-2095
ISSN (online)	2576-2095
DOI	10.1002/ame2.12388
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Article ; Online: Designing and executing prime editing experiments in mammalian cells.

Doman, Jordan L / Sousa, Alexander A / Randolph, Peyton B / Chen, Peter J / Liu, David R

Nature protocols

2022 Volume 17, Issue 11, Page(s) 2431–2468

Abstract: Prime editing (PE) is a precision gene editing technology that enables the programmable installation of substitutions, insertions and deletions in cells and animals without requiring double-strand DNA breaks (DSBs). The mechanism of PE makes it less ... ...

Abstract	Prime editing (PE) is a precision gene editing technology that enables the programmable installation of substitutions, insertions and deletions in cells and animals without requiring double-strand DNA breaks (DSBs). The mechanism of PE makes it less dependent on cellular replication and endogenous DNA repair than homology-directed repair-based approaches, and its ability to precisely install edits without creating DSBs minimizes indels and other undesired outcomes. The capabilities of PE have also expanded since its original publication. Enhanced PE systems, PE4 and PE5, manipulate DNA repair pathways to increase PE efficiency and reduce indels. Other advances that improve PE efficiency include engineered pegRNAs (epegRNAs), which include a structured RNA motif to stabilize and protect pegRNA 3' ends, and the PEmax architecture, which improves editor expression and nuclear localization. New applications such as twin PE (twinPE) can precisely insert or delete hundreds of base pairs of DNA and can be used in tandem with recombinases to achieve gene-sized (>5 kb) insertions and inversions. Achieving optimal PE requires careful experimental design, and the large number of parameters that influence PE outcomes can be daunting. This protocol describes current best practices for conducting PE and twinPE experiments and describes the design and optimization of pegRNAs. We also offer guidelines for how to select the proper PE system (PE1 to PE5 and twinPE) for a given application. Finally, we provide detailed instructions on how to perform PE in mammalian cells. Compared with other procedures for editing human cells, PE offers greater precision and versatility, and can be completed within 2-4 weeks.
MeSH term(s)	Animals ; Humans ; CRISPR-Cas Systems ; Gene Editing/methods ; DNA Breaks, Double-Stranded ; DNA Repair ; DNA/genetics ; Mammals/genetics ; RNA, Guide, CRISPR-Cas Systems
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2022-08-08
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2244966-8
ISSN	1750-2799 ; 1754-2189
ISSN (online)	1750-2799
ISSN	1754-2189
DOI	10.1038/s41596-022-00724-4
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Article: Delays in Administration of the Second Antibiotic Dose in Patients With Severe Sepsis and Septic Shock.

Randolph, Jana L / Chan, Kin / Albright, Amanda / Chen, Aleda

Hospital pharmacy

2019 Volume 56, Issue 4, Page(s) 247–251

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2019-11-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1468893-1
ISSN	0018-5787
ISSN	0018-5787
DOI	10.1177/0018578719889025
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Zs.B 1758: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 21: Show issues

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Article ; Online: Author Correction: Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos.

Nature biotechnology

2024

Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/s41587-024-02253-9
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Zs.A 2167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Book ; Online: Average-Case Subset Balancing Problems

Chen, Xi / Jin, Yaonan / Randolph, Tim / Servedio, Rocco A.

2021

Abstract: Given a set of $n$ input integers, the Equal Subset Sum problem asks us to find two distinct subsets with the same sum. In this paper we present an algorithm that runs in time $O^*(3^{0.387n})$ in the~average case, significantly improving over the $O^*(3^ ...

Abstract	Given a set of $n$ input integers, the Equal Subset Sum problem asks us to find two distinct subsets with the same sum. In this paper we present an algorithm that runs in time $O^(3^{0.387n})$ in the~average case, significantly improving over the $O^(3^{0.488n})$ running time of the best known worst-case algorithm and the Meet-in-the-Middle benchmark of $O^(3^{0.5n})$. Our algorithm generalizes to a number of related problems, such as the ``Generalized Equal Subset Sum'' problem, which asks us to assign a coefficient $c_i$ from a set $C$ to each input number $x_i$ such that $\sum_{i} c_i x_i = 0$. Our algorithm for the average-case version of this problem runs in~time $\|C\|^{(0.5-c_0/\|C\|)n}$ for some positive constant $c_0$, whenever $C=\{0, \pm 1, \dots, \pm d\}$ or $\{\pm 1, \dots, \pm d\}$ for some positive integer $d$ (with $O^(\|C\|^{0.45n})$ when $\|C\|<10$). Our results extend to the~problem of finding ``nearly balanced'' solutions in which the target is a not-too-large nonzero offset $\tau$. Our approach relies on new structural results that characterize the probability that $\sum_{i} c_i x_i$ $=\tau$ has a solution $c \in C^n$ when $x_i$'s are chosen randomly; these results may be of independent interest. Our algorithm is inspired by the ``representation technique'' introduced by Howgrave-Graham and Joux. This requires several new ideas to overcome preprocessing hurdles that arise in the representation framework, as well as a novel application of dynamic programming in the solution recovery phase of the algorithm. Comment: 44 pages, 5 figures
Keywords	Computer Science - Computational Complexity ; Computer Science - Data Structures and Algorithms ; 68Q25 ; F.2.1
Subject code	006
Publishing date	2021-10-27
Publishing country	us
Document type	Book ; Online
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Article ; Online: First-in-human phase I dose escalation trial of the first-in-class tumor microenvironment modulator VT1021 in advanced solid tumors.

Mahalingam, Devalingam / Harb, Wael / Patnaik, Amita / Bullock, Andrea / Watnick, Randolph S / Vincent, Melanie Y / Chen, Jian Jenny / Wang, Suming / Pestana, Harold / Chao, Judy / Mahoney, James / Cieslewicz, Michael / Watnick, Jing

Communications medicine

2024 Volume 4, Issue 1, Page(s) 10

Abstract: Background: VT1021 is a cyclic peptide that induces the expression of thrombospondin-1 (TSP-1) in myeloid-derived suppressor cells (MDSCs) recruited to the tumor microenvironment (TME). TSP-1 reprograms the TME via binding to CD36 and CD47 to induce ... ...

Abstract	Background: VT1021 is a cyclic peptide that induces the expression of thrombospondin-1 (TSP-1) in myeloid-derived suppressor cells (MDSCs) recruited to the tumor microenvironment (TME). TSP-1 reprograms the TME via binding to CD36 and CD47 to induce tumor and endothelial cell apoptosis as well as immune modulation in the TME. Methods: Study VT1021-01 (ClinicalTrials.gov ID NCT03364400) used a modified 3 + 3 design. The primary objective was to determine the recommended Phase 2 dose (RP2D) in patients with advanced solid tumors. Safety, tolerability, and pharmacokinetics (PK) were assessed. Patients were dosed twice weekly intravenously in 9 cohorts (0.5-15.6 mg/kg). Safety was evaluated using CTCAE version 5.0 and the anti-tumor activity was evaluated by RECIST version 1.1. Results: The RP2D of VT1021 is established at 11.8 mg/kg. VT1021 is well tolerated with no dose-limiting toxicities reported (0/38). The most frequent drug-related adverse events are fatigue (15.8%), nausea (10.5%), and infusion-related reactions (10.5%). Exposure increases proportionally from 0.5 to 8.8 mg/kg. The disease control rate (DCR) is 42.9% with 12 of 28 patients deriving clinical benefit including a partial response (PR) in one thymoma patient (504 days). Conclusions: VT1021 is safe and well-tolerated across all doses tested. RP2D has been selected for future clinical studies. PR and SD with tumor shrinkage are observed in multiple patients underscoring the single-agent potential of VT1021. Expansion studies in GBM, pancreatic cancer and other solid tumors at the RP2D have been completed and results will be communicated in a separate report.
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-024-00433-x
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