Search for: All records

Biological therapeutics represent an increasing and critical component of newly approved drugs; however, the inability to deliver biologics intracellularly in a controlled manner remains a major limitation. We have developed a semi-synthetic, tunable phage-like particle (PLP) platform derived from bacteriophage λ. The shell surface can be decorated with small-molecule, biological and synthetic moieties, alone or in combination and in defined ratios. Here, we demonstrate that the platform can be used to deliver biological macromolecules intracellularly and in a controlled manner. Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that has been widely recognized as an ideal target for the treatment of a variety of cancers. Recently, UbV.7.2, a novel biologic derived from the ubiquitin scaffold, was developed for inhibition of USP7, but issues remain in achieving efficient and controlled intracellular delivery of the biologic. We have shown that decoration of PLPs with trastuzumab (Trz), a HER2-targeted therapeutic used in the treatment of various cancers, results in specific targeting and uptake of Trz-PLPs into HER2-overexpressing breast cancer cells. By simultaneously decorating PLPs with Trz and UbV.7.2, we now show that these particles are also internalized by HER2-positive cells, thus providing a means for intracellular delivery of the biologic in a controlled fashion. Internalized particles retain USP7 inhibition activity of UbV.7.2 and alter the metabolic and proteomic landscapes of these cells. This study demonstrates that the λ “designer nanoparticles” represent a powerful system for the intracellular delivery of biologics in a defined dose. 

Quantum spin liquids, exotic phases of matter with topological order, have been a major focus in physics for the past several decades. Such phases feature long-range quantum entanglement that can potentially be exploited to realize robust quantum computation. We used a 219-atom programmable quantum simulator to probe quantum spin liquid states. In our approach, arrays of atoms were placed on the links of a kagome lattice, and evolution under Rydberg blockade created frustrated quantum states with no local order. The onset of a quantum spin liquid phase of the paradigmatic toric code type was detected by using topological string operators that provide direct signatures of topological order and quantum correlations. Our observations enable the controlled experimental exploration of topological matter and protected quantum information processing. 

Realizing quantum speedup for practically relevant, computationally hard problems is a central challenge in quantum information science. Using Rydberg atom arrays with up to 289 qubits in two spatial dimensions, we experimentally investigate quantum algorithms for solving the Maximum Independent Set problem. We use a hardware-efficient encoding associated with Rydberg blockade, realize closed-loop optimization to test several variational algorithms, and subsequently apply them to systematically explore a class of graphs with programmable connectivity. We find the problem hardness is controlled by the solution degeneracy and number of local minima, and experimentally benchmark the quantum algorithm’s performance against classical simulated annealing. On the hardest graphs, we observe a superlinear quantum speedup in finding exact solutions in the deep circuit regime and analyze its origins. 

Abstract The Gravitational-Wave Transient Catalog (GWTC) is a collection of short-duration (transient) gravitational-wave signals identified by the LIGO–Virgo–KAGRA Collaboration in gravitational-wave data produced by the eponymous detectors. The catalog provides information about the identified candidates, such as the arrival time and amplitude of the signal and properties of the signal’s source as inferred from the observational data. GWTC is the data release of this dataset, and version 4.0 extends the catalog to include observations made during the first part of the fourth LIGO–Virgo–KAGRA observing run up until 2024 January 31. This Letter marks an introduction to a collection of articles related to this version of the catalog, GWTC-4.0. The collection of articles accompanying the catalog provides documentation of the methods used to analyze the data, summaries of the catalog of events, observational measurements drawn from the population, and detailed discussions of selected candidates. 

Abstract We report the observation of gravitational waves from two binary black hole coalescences during the fourth observing run of the LIGO–Virgo–KAGRA detector network, GW241011 and GW241110. The sources of these two signals are characterized by rapid and precisely measured primary spins, nonnegligible spin–orbit misalignment, and unequal mass ratios between their constituent black holes. These properties are characteristic of binaries in which the more massive object was itself formed from a previous binary black hole merger and suggest that the sources of GW241011 and GW241110 may have formed in dense stellar environments in which repeated mergers can take place. As the third-loudest gravitational-wave event published to date, with a median network signal-to-noise ratio of 36.0, GW241011 furthermore yields stringent constraints on the Kerr nature of black holes, the multipolar structure of gravitational-wave generation, and the existence of ultralight bosons within the mass range 10⁻¹³–10⁻¹²eV. 

Abstract On 2023 November 23, the two LIGO observatories both detected GW231123, a gravitational-wave signal consistent with the merger of two black holes with masses $137_{-18}^{+23}{M}_{\odot }$and $101_{-50}^{+22}{M}_{\odot }$(90% credible intervals), at a luminosity distance of 0.7–4.1 Gpc, a redshift of $0.40_{-0.25}^{+0.27}$, and with a network signal-to-noise ratio of ∼20.7. Both black holes exhibit high spins— $0.90_{-0.19}^{+0.10}$and $0.80_{-0.52}^{+0.20}$, respectively. A massive black hole remnant is supported by an independent ringdown analysis. Some properties of GW231123 are subject to large systematic uncertainties, as indicated by differences in the inferred parameters between signal models. The primary black hole lies within or above the theorized mass gap where black holes between 60–130M_⊙should be rare, due to pair-instability mechanisms, while the secondary spans the gap. The observation of GW231123 therefore suggests the formation of black holes from channels beyond standard stellar collapse and that intermediate-mass black holes of mass ∼200M_⊙form through gravitational-wave-driven mergers. 

The gravitational-wave signal GW250114 was observed by the two LIGO detectors with a network matched-filter signal-to-noise ratio of 80. The signal was emitted by the coalescence of two black holes with near-equal masses $m_1={33.6}_{-0.8}^{+1.2}{M}_{\odot }$and $m_2={32.2}_{-1.3}^{+0.8}{M}_{\odot }$, and small spins ${\chi }_{1,2}\le 0.26$(90% credibility) and negligible eccentricity $e\le 0.03$. Postmerger data excluding the peak region are consistent with the dominant quadrupolar $(\ell =|m|=2)$mode of a Kerr black hole and its first overtone. We constrain the modes’ frequencies to $\pm 30\%$of the Kerr spectrum, providing a test of the remnant’s Kerr nature. We also examine Hawking’s area law, also known as the second law of black hole mechanics, which states that the total area of the black hole event horizons cannot decrease with time. A range of analyses that exclude up to five of the strongest merger cycles confirm that the remnant area is larger than the sum of the initial areas to high credibility.