bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-engineered guide RNA enables DNA loops and contacts modulating repression in E. coli
Authors: Yang Yunshi , Rocamonde-Lago Iris , Shen Boxuan , Berzina Ieva , Zipf Johanna , Högberg Björn
Published: July 2024

RNA serves as information media as well as molecular scaffold in nature and synthetic systems. The single guide RNA (sgRNA) widely applied in CRISPR techniques exemplifies both functions, with a guide region bearing DNA base-pairing information, and a structural motif for Cas9 protein scaffolding. The scaffold region has been modified by fusing RNA aptamers to the tetra-stem loop. The guide region is typically not regarded as a pluggable module as it encodes the essential function of DNA sequence recognition. Here, we investigate a chimera of two sgRNAs, with distinct guide sequences joined by an RNA linker (dgRNA), regarding its DNA binding function and loop induction capability. First, we studied the sequence bi-specificity of the dgRNA and discovered that the RNA linker allows distal parts of double-stranded DNA to be brought into proximity. To test the activity of the dgRNA in organisms, we used the LacZ gene as a reporter and recapitulated the loop-mediated gene inhibition by LacI in E. coli. We found that the dgRNA can be applied to target distal genomic regions with comparable levels of inhibition. The capability of dgRNA to induce DNA contacts solely requires dCas9 and RNA, making it a minimal system to remodel chromosomal conformation in various organisms.
A new approach to RNA synthesis: immobilization of stably and functionally co-tethered promoter DNA and T7 RNA polymerase
Authors: MalagodaPathiranage Kithmie , Banerjee Ruptanu , Martin Craig T
Published: July 2024

Current approaches to RNA synthesis/manufacturing require substantial (and incomplete) purification post-synthesis. We have previously demonstrated the synthesis of RNA from a complex in which T7 RNA polymerase is tethered to promoter DNA. In the current work, we extend this approach to demonstrate an extremely stable system of functional co-tethered complex to a solid support. Using the system attached to magnetic beads, we carry out more than 20 rounds of synthesis using the initial polymerase-DNA construct. We further demonstrate the wide utility of this system in the synthesis of short RNA, a CRISPR guide RNA, and a protein-coding mRNA. In all cases, the generation of self-templated double stranded RNA (dsRNA) impurities are greatly reduced, by both the tethering itself and by the salt-tolerance that local co-tethering provides. Transfection of the mRNA into HEK293T cells shows a correlation between added salt in the transcription reaction (which inhibits RNA rebinding that generates RNA-templated extensions) and significantly increased expression and reduced innate immune stimulation by the mRNA reaction product. These results point in the direction of streamlined processes for synthesis/manufacturing of high-quality RNA of any length, and at greatly reduced costs.
SigAlign: an alignment algorithm guided by explicit similarity criteria
Authors: Bahk Kunhyung , Sung Joohon
Published: July 2024

In biological sequence alignment, prevailing heuristic aligners achieve high-throughput by several approximation techniques, but at the cost of sacrificing the clarity of output criteria and creating complex parameter spaces. To surmount these challenges, we introduce ‘SigAlign’, a novel alignment algorithm that employs two explicit cutoffs for the results: minimum length and maximum penalty per length, alongside three affine gap penalties. Comparative analyses of SigAlign against leading database search tools (BLASTn, MMseqs2) and read mappers (BWA-MEM, bowtie2, HISAT2, minimap2) highlight its performance in read mapping and database searches. Our research demonstrates that SigAlign not only provides high sensitivity with a non-heuristic approach, but also surpasses the throughput of existing heuristic aligners, particularly for high-accuracy reads or genomes with few repetitive regions. As an open-source library, SigAlign is poised to become a foundational component to provide a transparent and customizable alignment process to new analytical algorithms, tools and pipelines in bioinformatics.
Single-mode termination of phage transcriptions, disclosing bacterial adaptation for facilitated reinitiations
Authors: Song Eunho , Han Sun , Uhm Heesoo , Kang Changwon , Hohng Sungchul
Published: July 2024

Bacterial and bacteriophage RNA polymerases (RNAPs) have divergently evolved and share the RNA hairpin-dependent intrinsic termination of transcription. Here, we examined phage T7, T3 and SP6 RNAP terminations utilizing the single-molecule fluorescence assays we had developed for bacterial terminations. We discovered the phage termination mode or outcome is virtually single with decomposing termination. Therein, RNAP is displaced forward along DNA and departs both RNA and DNA for one-step decomposition, three-dimensional diffusion and reinitiation at any promoter. This phage displacement-mediated decomposing termination is much slower than readthrough and appears homologous with the bacterial one. However, the phage sole mode of termination contrasts with the bacterial dual mode, where both decomposing and recycling terminations occur compatibly at any single hairpin- or Rho-dependent terminator. In the bacterial recycling termination, RNA is sheared from RNA·DNA hybrid, and RNAP remains bound to DNA for one-dimensional diffusion, which enables facilitated recycling for reinitiation at the nearest promoter located downstream or upstream in the sense or antisense orientation. Aligning with proximity of most terminators to adjacent promoters in bacterial genomes, the shearing-mediated recycling termination could be bacterial adaptation for the facilitated reinitiations repeated at a promoter for accelerated expression and coupled at adjoining promoters for coordinated regulation.
The RNA helicase DDX39 contributes to the nuclear export of spliceosomal U snRNA by loading of PHAX onto RNA
Authors: Taniguchi Ichiro , Hirose Tetsuro , Ohno Mutsuhito
Published: July 2024

RNA helicases are involved in RNA metabolism in an ATP-dependent manner. Although many RNA helicases unwind the RNA structure and/or remove proteins from the RNA, some can load their interacting proteins onto RNAs. Here, we developed an in vitro strategy to identify the ATP-dependent factors involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export. We identified the RNA helicase UAP56/DDX39B, a component of the mRNA export complex named the transcription-export (TREX) complex, and its closely related RNA helicase URH49/DDX39A as the factors that stimulated RNA binding of PHAX, an adapter protein for U snRNA export. ALYREF, another TREX component, acted as a bridge between PHAX and UAP56/DDX39B. We also showed that UAP56/DDX39B and ALYREF participate in U snRNA export through a mechanism distinct from that of mRNA export. This study describes a novel aspect of the TREX components for U snRNP biogenesis and highlights the loading activity of RNA helicases.
mRNA-specific readthrough of nonsense codons by antisense oligonucleotides (R-ASOs)
Authors: Susorov Denis , Echeverria Dimas , Khvorova Anastasia , Korostelev Andrei A
Published: July 2024

Nonsense mutations account for >10% of human genetic disorders, including cystic fibrosis, Alagille syndrome, and Duchenne muscular dystrophy. A nonsense mutation results in the expression of a truncated protein, and therapeutic strategies aim to restore full-length protein expression. Most strategies under development, including small-molecule aminoglycosides, suppressor tRNAs, or the targeted degradation of termination factors, lack mRNA target selectivity and may poorly differentiate between nonsense and normal stop codons, resulting in off-target translation errors. Here, we demonstrate that antisense oligonucleotides can stimulate readthrough of disease-causing nonsense codons, resulting in high yields of full-length protein in mammalian cellular lysate. Readthrough efficiency depends on the sequence context near the stop codon and on the precise targeting position of an oligonucleotide, whose interaction with mRNA inhibits peptide release to promote readthrough. Readthrough-inducing antisense oligonucleotides (R-ASOs) enhance the potency of non-specific readthrough agents, including aminoglycoside G418 and suppressor tRNA, enabling a path toward target-specific readthrough of nonsense mutations in CFTR, JAG1, DMD, BRCA1 and other mutant genes. Finally, through systematic chemical engineering, we identify heavily modified fully functional R-ASO variants, enabling future therapeutic development.
Intraoperative mapping of epileptogenic foci and tumor infiltration in neuro-oncology patients with epilepsy
Authors: Sun Dongqing , Schaft Eline V , van Stempvoort Bibi M , Gebbink Tineke A , van ‘t Klooster Maryse , van Eijsden Pieter , van der Salm Sandra M A , Willem Dankbaar Jan , Zijlmans Maeike , Robe Pierre A
Published: July 2024

Background

Epileptogenesis and glioma growth have a bidirectional relationship. We hypothesized people with gliomas can benefit from the removal of epileptic tissue and that tumor-related epileptic activity may signify tumor infiltration in peritumoral regions. We investigated whether intraoperative electrocorticography (ioECoG) could improve seizure outcomes in oncological glioma surgery, and vice versa, what epileptic activity (EA) tells about tumor infiltration.

Methods

We prospectively included patients who underwent (awake) ioECoG-assisted diffuse-glioma resection through the oncological trajectory. The IoECoG-tailoring strategy relied on ictal and interictal EA (spikes and sharp waves). Brain tissue, where EA was recorded, was assigned for histopathological examination separate from the rest of the tumor. Weibull regression was performed to assess how residual EA and extent of resection (EOR) related to the time-to-seizure recurrence, and we investigated which type of EA predicted tumor infiltration.

Results

Fifty-two patients were included. Residual spikes after resection were associated with seizure recurrence in patients with isocitrate dehydrogenase (IDH) mutant astrocytoma or oligodendroglioma (HR = 7.6[1.4–40.0], P-value = .01), independent from the EOR. This was not observed in IDH-wildtype tumors. All tissue samples resected based on interictal spikes were infiltrated by tumor, even if the MRI did not show abnormalities.

Conclusions

Complete resection of epileptogenic foci in ioECoG may promote seizure control in IDH-mutant gliomas. The cohort size of IDH-wildtype tumors was too limited to draw definitive conclusions. Interictal spikes may indicate tumor infiltration even when this area appears normal on MRI. Integrating electrophysiology guidance into oncological tumor surgery could contribute to improved seizure outcomes and precise guidance for radical tumor resection.
Comparison of subjectively and objectively measured sleep–wake patterns among patients with primary brain tumors
Authors: Kim Youngdeok , Kenyon Jonathan , Kim Jisu , Willis Kelcie D , Lanoye Autumn , Loughan Ashlee R
Published: July 2024

Background

The sleep diary and wrist-worn actigraphy are widely used to assess sleep disturbances in patients with primary brain tumors (PwPBT) in both clinical and research settings. However, their comparability has not been systematically examined. This study aimed to compare the sleep–wake patterns measured using the subjectively measured Consensus Sleep Diary (CSD) and the objectively measured ActiGraph (AG) actigraphy among PwPBT.

Methods

Sleep–wake patterns were assessed through CSD and AG over 14 consecutive nights across 2 occasions among 30 PwPBT. AG data were processed with AG proprietary and open-source GGIR (GGIR-based approach without the aid of sleep log algorithms), both with and without the assistance of CSD. Thirteen sleep parameters covering sleep–wake times, sleep disruptions, sleep durations, and sleep efficiency were compared using equivalency testing, mean absolute percent error (MAPE), and intra-class correlation. The estimated sleep parameters were correlated with perceived sleep quality and compared across the different sleep measures.

Results

Significant between-measure equivalency was claimed for sleep–wake time parameters (P ≤ .05), with acceptable MAPEs (<10%). Sleep disruption parameters such as wake-after-sleep-onset were not statistically equivalent, with a large MAPE (≥10%) between the measures. Sleep efficiency was equivalent, though varied depending on how sleep efficiency was calculated. For most sleep parameters, ICCs were low and unacceptable (<0.50) suggesting incomparability between the measures. Lastly, CSD-derived sleep parameters exhibited a stronger correlation with perceived sleep quality compared to actigraphy measures.

Conclusions

The findings suggest the incomparability of sleep parameters estimated from different measures. Both subjective and objective measures are recommended to better describe sleep health among PwPBT.
Investigating thermal properties of 2D non-layered material using a NEMS-based 2-DOF approach towards ultrahigh-performance bolometer
Authors: Wang Luming , Wu Song , Zhang Zejuan , Zhu Jiankai , Zou Luwei , Xu Bo , Wu Jiaqi , Zhu Junzhi , Xiao Fei , Jiao Chenyin , Pei Shenghai , Qin Jiaze , Zhou Yu , Xia Juan , Wang Zenghui
Published: July 2024

Two-dimensional (2D) non-layered materials in many aspects differ from their layered counterparts, and the exploration of their physical properties has produced many intriguing findings. However, due to challenges in applying existing experimental techniques to such nanoscale samples, their thermal properties have remained largely uncharacterized, hindering further exploration and device application using this promising material system. Here, we demonstrate an experimental study of thermal conduction in β-In2S3, a typical non-layered 2D material, using a resonant nanoelectromechanical systems (NEMS) platform. We devise a new two-degrees-of-freedom technique, more responsive and sensitive than Raman spectroscopy, to simultaneously determine both the thermal conductivity to be 3.7 W m−1 K−1 and its interfacial thermal conductance with SiO2 as 6.4 MW m−2 K−1. Leveraging such unique thermal properties, we further demonstrate a record-high power-to-frequency responsivity of −447 ppm/μW in β-In2S3 NEMS sensors, the best among drumhead NEMS-based bolometers. Our findings offer an effective approach for studying thermal properties and exploring potential thermal applications of 2D non-layered materials.
Perceptions of Smoking Stigma Among African Americans: A Qualitative Study
Authors: Crittendon Denine R , Brecher Alison C , Okere Samantha , Hass Richard , Frasso Rosemary , Brawer Rickie , Zeigler-Johnson Charnita
Published: July 2024

Introduction

African Americans/Blacks (AAB) are at increased risk for morbidity and mortality from smoking-related diseases including lung cancer (LC). Smoking stigma is believed to be a primary barrier to health care-seeking for people who smoke. Previous studies illustrate that perceptions of smoking vary across populations. However, little is known about the prevalence of smoking stigmas among AAB. The purpose of this study was to increase understanding of the perception of cigarette smoking by AAB.

Aims and Methods

We conducted free-listing interviews in which individuals listed all-thoughts and feelings regarding smoking and health-related questions with a convenience sample of eligible AAB adults (n = 58) in the Philadelphia region. Additionally, we collected participant self-reported demographic data. Data were cleaned and the salience of each term was computed using Anthropac. Graphical methods were then used to determine salient responses across groups stratified by gender, age, education, and smoking status.

Results

The sample had a median age of 51 years and was 67.2% female. Most participants had completed college (58.6%) and had never smoked (74.1%). Regarding their perceptions of people who smoke cigarettes, results showed that “smelly,” “health hazard,” and “judgment” were the most salient terms among all-participants. Overall, “smelly” and “unhealthy” were salient for both males and females. However, “dental,” “dirty,” “addictive,” and “habit” were also salient among males. Phrases such as “unhealthy” and “addictive” were primarily salient for older participants (>51 years) versus “smelly” for younger participants. The term “smelly” was salient among all-education levels. However, “unhealthy” was also salient among those with less than a 4-year college degree. Moreover, the terms “smelly” and “annoying” were most common among people who smoke as opposed to “health hazard” among people who don’t smoke.

Conclusions

We observed that the most stigmatizing language was primarily associated with perceptions of negative social interactions, social judgment, and health-related concerns. Future studies are needed to explore how smoking-related stigmas impact patient adherence to smoking cessation programs and LC screening protocols.

Implications

Little is known about the prevalence of smoking stigmas among AAB. This study explores the AAB perspective of cigarette smoking and related stigmas. Among AAB, smoking is represented by stigmatizing language across gender, age groups, and smoking history. It is primarily associated with negative social interactions, social judgement, and health-related concerns indicating that smoking stigma is a concern for AAB individuals who smoke. Further research is warranted.
Impact of Quantity and Type of Dietary Protein on Cardiovascular Disease Risk Factors Using Standard and Network Meta-analyses of Randomized Controlled Trials
Authors: Yao Yueying , Huang Vanessa , Seah Vernice , Kim Jung Eun
Published: July 2024

Context

Higher protein diets (HPDs) have shown favorable outcomes on weight maintenance and body-composition management; however, their protective effects against cardiovascular diseases (CVDs) remain uncertain and contentious. Furthermore, it is important to consider the influence of other macronutrients in the diet and type of dietary protein when studying HPDs, because this aspect has been overlooked in previous studies.

Objective

We assessed the impacts of quantity and type of dietary protein on CVD risk factors.

Data Sources

A database search was conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library and a total of 100 articles met the eligibility criteria.

Data Extraction

Extracted data from 100 articles were analyzed using standard meta-analysis, and 41 articles were also analyzed using network meta-analysis.

Data Analysis

In the standard meta-analysis, an HPD had significant favorable effects on systolic blood pressure (SBP) (mean difference [MD] = −1.51 mmHg; 95% CI: −2.77, −0.25), diastolic blood pressure (DBP) (MD = −1.08 mmHg; 95% CI: −1.81, −0.35), and flow-mediated dilation (MD = 0.78%; 95% CI: 0.09, 1.47) compared with lower protein diets. The further network meta-analysis supported that the high-protein, high-carbohydrate, low-fat diet was the most recommended diet to ensure a maximum decrease in SBP, DBP, total cholesterol (TC), and low-density-lipoprotein cholesterol (LDL-C). In comparison to animal-protein–rich diets, plant-protein–rich diets (PPRs) exhibited a significant favorable effects on improving TC (MD = −0.12 mmol/L; 95% CI: −0.19, −0.05), triglyceride (MD = −0.05 mmol/L; 95% CI: −0.09, −0.01), LDL-C (MD = −0.11 mmol/L; 95% CI: −0.18, −0.04), and high-density-lipoprotein cholesterol (MD = 0.03 mmol/L; 95% CI: 0.02, 0.04) levels.

Conclusion

Consumption of HPDs and PPRs supports improvements in vascular health and lipid-lipoprotein profiles, respectively. Furthermore, macronutrient composition should be carefully designed in the dietary approach to maximize the effectiveness of HPDs in improving CVD risk factors.

Systematic Review Registration

PROSPERO registration no. CRD42022369931.
Lifileucel: FDA-approved T-cell therapy for melanoma
Authors: Kwong Mei Li M , Yang James C
Published: July 2024

This commentary reports on the history of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy and where TIL fits into the treatment options for metastatic melanoma.
A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hoc analysis of the IDEA-France trial
Authors: Samaille Thomas , Falcoz Antoine , Cohen Romain , Laurent-Puig Pierre , André Thierry , Taieb Julien , Auclin Edouard , Vernerey Dewi
Published: July 2024

Background

We assessed the added value of incorporating carcinoembryonic antigen (CEA) to circulating tumor DNA (ctDNA) and pathological TN (pTN) stage for risk classification in stage 3 colon cancer (CC).

Patients and Methods

We retrospectively analyzed postoperative CEA values in patients with CC from the IDEA-France phase 3 trial. The relation between disease-free survival (DFS) and CEA was modeled through restricted cubic splines. Prognostic value of CEA, ctDNA, and pTN was assessed with the Kaplan-Meier method. Multivariate analysis was used to identify prognostic and predictive factors for DFS.

Results

Among 696 patients (35%), CEA values were retrievable, and for 405 (20%) both CEA and ctDNA were available. An optimized CEA threshold of 2 ng/mL was identified, the 3-year DFS was 66.4% for patients above the threshold and 80.9% for those below (HR, 1.74; 95% CI, 1.33-2.28, P < .001). In multivariate analysis, CEA ≥ 2 ng/mL contributed significantly to model variability, becoming an independent prognostic factor for DFS (HR, 1.82; 95% CI,1.27-2.59), alongside ctDNA (HR, 1.88; 95% CI, 1.16-3.03) and pTN (HR, 1.78; 95% CI, 1.24-2.54). A novel integrated risk classification combining CEA, ctDNA, and pTN stage reclassified 19.8% of pT4/N2 patients as low risk and 2.5% of pT3/N1 patients as high risk. This new classification demonstrated the 3-year DFS of 80.8% for low-risk patients and 55.4% for high-risk patients (HR, 2.66, 95% CI, 1.84-3.86, P < .001).

Conclusions

Postoperative CEA value is a prognostic factor for DFS in stage 3 CC, independently of ctDNA and pTN. It advocates for systematic reporting in future adjuvant trials. Integrating both biomarkers with pTN could refine risk classification in stage 3 CC.
The End of General Gordon
Authors: Strachey Lytton
Published: July 2024

THE END OF GENERAL GORDON
XIX
Authors: Wharton Edith
Published: July 2024

The Parisian Diamond Company—Anglo-American branch.’

Charles Bowen, seated, one rainy evening of the Paris season, in a corner of the great Nouveau Luxe restaurant, was lazily trying to resolve his impressions of the scene into the phrases of a letter to his...
XXI
Authors: Wharton Edith
Published: July 2024

The spring in New York proceeded through more than its usual extremes of temperature to the threshold of a sultry June.

Ralph Marvell, wearily bent to his task, felt the fantastic humours of the weather as only one more incoherence in the general chaos of...
XXVIII
Authors: Wharton Edith
Published: July 2024

‘What do you say to Nice to-morrow, dearest?’ the Princess suggested a few evenings later, as she followed Undine upstairs after a languid evening at bridge with the Duchess and Madame de Trézac.

Half-way down the passage she stopped to open a door and,...
XXXV
Authors: Wharton Edith
Published: July 2024

Within forty-eight hours Ralph’s money was in Moffatt’s hands, and the interval of suspense had begun.

The transaction over, he felt the deceptive buoyancy that follows on periods of painful indecision. It seemed to him that now at last life had freed him from all...
I
Authors: Wharton Edith
Published: July 2024

In the great high-ceilinged library of a private hôtel overlooking one of the new quarters of Paris, Paul Marvell stood listlessly gazing out into the twilight.

The trees were budding symmetrically along the avenue below; and Paul, looking down, saw, between windows and tree-tops, a...
Chapter XIII
Authors: London Jack
Published: July 2024

SO I left Benicia, where John Barleycorn had nearly got me, and ranged wider afield* in pursuit of the whisper from the back of life to come and find. And wherever I ranged, the way lay along alcohol-drenched roads. Men still congregated in...
Chapter XIX
Authors: London Jack
Published: July 2024

WHEN I was with folk who did not drink, I never thought of drinking. Louis did not drink. Neither he nor I could afford it; but, more significant than that, we had no desire to drink. We were healthy, normal, non-alcoholic. Had we been alcoholic,...
Chapter XXI
Authors: London Jack
Published: July 2024

BUT behold! As soon as I went out on the adventure-path I met John Barleycorn again. I moved through a world of strangers, and the act of drinking together made one acquainted with men and opened the way to adventures. It might be in a...
Chapter XXVII
Authors: London Jack
Published: July 2024

AS I succeeded with my writing, my standard of living rose and my horizon broadened. I confined myself to writing and typing a thousand words a day, including Sundays and holidays; and I still studied hard, but not so hard as formerly. I allowed myself...
Chapter XXXIV
Authors: London Jack
Published: July 2024

BACK on the ranch,* in the Valley of the Moon, I resumed my steady drinking. My program was no drink in the morning; first drink-time came with the completion of my thousand words. Then, between that and the midday meal, were drinks numerous...
CHAPTER XVI
Authors: Woolf Virginia
Published: July 2024

Into that same black night, almost, indeed, into the very same layer of starlit air, Katharine Hilbery was now gazing, although not with a view to the prospects of a fine day for duck shooting on the morrow. She was walking up and down...
CHAPTER XVII
Authors: Woolf Virginia
Published: July 2024

When the sun shone, as it did with unusual brightness that Christmas week, it revealed much that was faded and not altogether well-kept-up in Stogdon House and its grounds. In truth, Sir Francis had retired from service under the Government of India with a...
CHAPTER XVIII
Authors: Woolf Virginia
Published: July 2024

But other passengers were approaching Lincoln meanwhile by other roads on foot. A county town draws the inhabitants of all vicarages, farms, country houses, and wayside cottages, within a radius of ten miles at least, once or twice a week to its streets; and...
Chapter II
Authors: Conrad Joseph
Published: July 2024

The only sign of commercial activity within the harbour, visible from the beach of the Great Isabel, is the square blunt end of the wooden jetty which the Oceanic Steam Navigation Company (the O.S.N. of familiar speech) had thrown over the shallow part of...
Chapter III
Authors: Conrad Joseph
Published: July 2024

It might have been said that there he was only protecting his own. From the first he had been admitted to live in the intimacy of the family of the hotel-keeper, who was a countryman of his. Old Giorgio Viola, a Genoese*...
Selected Essays
Authors: Woolf Virginia
Published: July 2024

According to Virginia Woolf, the goal of the essay ‘is simply that it should give pleasure…It should lay us under a spell with its first word, and we should only wake, refreshed, with its last.’ One of the best practitioners of the art she analysed so rewardingly, Woolf displayed her essay-writing skills across a wide range of subjects, with all the craftsmanship, substance, and rich allure of her novels. This selection brings together thirty of her best essays, including the famous ‘Mr Bennett and Mrs Brown’, a clarion call for modern fiction. She discusses the arts of writing and of reading, and the particular role and reputation of women writers. She writes movingly about her father and the art of biography, and of the London scene in the early decades of the twentieth century. Overall, these pieces are as indispensable to an understanding of this great writer as they are enchanting in their own right.
How it Strikes a Contemporary
Authors: Woolf Virginia
Published: July 2024

In the first place a contemporary can scarcely fail to be struck by the fact that two critics at the same table at the same moment will pronounce completely different opinions about the same book. Here, on the right, it is declared a masterpiece...
Memories of a Working Women’s Guild
Authors: Woolf Virginia
Published: July 2024

When you asked me to write a preface to a book which you had collected of papers by working women* I replied that I would be drowned rather than write a preface to any book whatsoever. Books should stand on their own...
Thunder at Wembley
Authors: Woolf Virginia
Published: July 2024

It is nature that is the ruin of Wembley; yet it is difficult to see what steps Lord Stevenson, Lieutenant-General Sir Travers Clarke, and the Duke of Devonshire* could have taken to keep her out. They might have eradicated the grass and...
Evening Over Sussex: Reflections in a Motor Car
Authors: Woolf Virginia
Published: July 2024

Evening is kind to Sussex, for Sussex is no longer young, and she is grateful for the veil of evening as an elderly woman is glad when a shade is drawn over a lamp, and only the outline of her face remains. The outline...
Chapter 3
Authors: Lewis Wyndham
Published: July 2024

Tarr’s idea of leisure recognized no departure from the tragic theme of existence: pleasure could take no form that did not include death and corruption—at present Bertha and Humour. Only he wished to play a little longer: it was the last chance he might...
Chapter 8
Authors: Lewis Wyndham
Published: July 2024

The portmanteau fell under the bed; his body crushed into the red balloon of down. Kreisler never sat upon his bed except when about to get into it: for another man it would have replaced the absent armchair, but in those moments...
Chapter 9
Authors: Lewis Wyndham
Published: July 2024

Otto’s compatriots at the Café were sober and thoughtful, with some discipline in their idleness: their monthly monies flowed and ebbed, it was to be supposed, small regular tides frothing monotonously in the form of beer and glasses of cheap sekt. This rather desolate...
Chapter 2
Authors: Lewis Wyndham
Published: July 2024

One certain thing (amongst many uncertainties) about the english club, the Bonnington Club, was that it could not be said as yet to have found itself quite. Its central room (and that was almost all there was of it) reminded you of a Public...
Chapter 7
Authors: Lewis Wyndham
Published: July 2024

People appear with a startling suddenness sometimes out of the fog of Time and Space: so Kreisler appeared—such an apparition! Bertha did not visualize her countryman very readily: and the next day she was surprised when she saw him below her windows. He stared...
Chapter 1
Authors: Lewis Wyndham
Published: July 2024

Painting languished in the Montmartre studio, which was no longer anything but an inconvenient address, requiring a long bus or taxi ride at the end of the day. At this time Tarr’s character performed repeatedly the following manœuvre: his best energies would, once a...
Chapter 4
Authors: Lewis Wyndham
Published: July 2024

They went over to a small, gaudy, quiet Débit on the other side of the Boulevard, Kreisler watching them, but still with his eye upon the door near at hand. Tarr was amused now at his position of dummy:* he enjoyed crossing...
Chapter VIII
Authors: Lewis Sinclair
Published: July 2024

I

The great events of Babbitt’s spring were the secret buying of real-estate options in Linton for certain street-traction officials, before the public announcement that the Linton Avenue Car Line would be extended, and a dinner which was, as he rejoiced to his wife,...
Chapter XIII
Authors: Lewis Sinclair
Published: July 2024

I

It was by accident that Babbitt had his opportunity to address the S. A. R. E. B.

The S. A. R. E. B., as its members called it, with the universal passion for mysterious and important-sounding initials, was the State Association of Real Estate...
Chapter XXVI
Authors: Lewis Sinclair
Published: July 2024

I

As he walked through the train, looking for familiar faces, he saw only one person whom he knew, and that was Seneca Doane, the lawyer who, after the blessings of being in Babbitt’s own class at college and of becoming a corporation-counsel, had...
Chapter XXX
Authors: Lewis Sinclair
Published: July 2024

I

The summer before, Mrs. Babbitt’s letters had crackled with desire to return to Zenith. Now they said nothing of returning, but a wistful “I suppose everything is going on all right without me” among her dry chronicles of weather and sicknesses hinted to...
Chapter XXXII
Authors: Lewis Sinclair
Published: July 2024

I

His wife was up when he came in. “Did you have a good time?” she sniffed.

“I did not, I had a rotten time! Anything else I got to explain?”

“George, how can you speak like— Oh, I don’t know what’s come over you!”...
A Hunger Artist
Authors: Kafka Franz
Published: July 2024

First Sorrow

A trapeze artist—this art, practised high in the music-hall domes, is acknowledged to be one of the most difficult of any attainable by mankind—had so arranged his life, first out of his striving for perfection and later out of habit turned...
The Huntsman Gracchus
Authors: Kafka Franz
Published: July 2024

Two boys were sitting on the wall of the quay, playing at dice. A man was reading a newspaper on the steps of a monument in the shade of the sabre-swinging hero.* A girl was filling her wooden tub with water at...
The Burrow
Authors: Kafka Franz
Published: July 2024

I have fitted out the burrow and it seems to have turned out well. From the outside only a great hollow is actually visible, but this leads nowhere in reality, for after only a few steps you come up against solid natural rock....
The Mysterious Carriage
Authors: Leroux Gaston
Published: July 2024

That fatal night turned out badly for all concerned. La Carlotta fell ill and Christine Daaé vanished after the performance. Two weeks later, she had still not been seen either in the theatre or outside it.

This first disappearance, which went largely unnoticed, must not...
Apollo’s Lyre
Authors: Leroux Gaston
Published: July 2024

Then they were outside, on the roof. Christine moved easily, with practised steps, as light as a swallow. They looked through the empty spaces between the three low domes and the triangular pediment. She breathed deeply as she gazed out over Paris which nestled...
Additionality, baselines, and the proper accounting for land-based climate change mitigation efforts
Authors: Nolan Connor , Van Paasschen Cecilia A , Field Christopher B
Published: July 2024

Carbon storage and uptake on land is a critical part of climate change mitigation. Each year, up to 30% of anthropogenic emissions are neutralized by the ongoing background land sink. At the same time, greenhouse gas emissions from deforestation and forest degradation are major contributors to climate change. Protecting the background sink, avoiding additional emissions, and increasing removals are all key parts of a climate change mitigation portfolio. However, accurately measuring the true mitigation effects of a given intervention is challenging because of an inherent reliance on a counterfactual—an estimate of what would have happened in the absence of a given intervention. These counterfactuals are handled differently in carbon markets and in national greenhouse gas inventories, which can lead to confusion in accounting for progress on climate change mitigation. In this paper, we review how global carbon budgets, national greenhouse gas inventories, and carbon markets account for land-based carbon fluxes. We also examine the implications for additionality and identify some particularly challenging cases. Finally, we present recommendations moving forward and connect this work to broader challenges relevant to other carbon dioxide removal pathways.
Language models, like humans, show content effects on reasoning tasks
Authors: Lampinen Andrew K , Dasgupta Ishita , Chan Stephanie C Y , Sheahan Hannah R , Creswell Antonia , Kumaran Dharshan , McClelland James L , Hill Felix
Published: July 2024

Abstract reasoning is a key ability for an intelligent system. Large language models (LMs) achieve above-chance performance on abstract reasoning tasks but exhibit many imperfections. However, human abstract reasoning is also imperfect. Human reasoning is affected by our real-world knowledge and beliefs, and shows notable “content effects”; humans reason more reliably when the semantic content of a problem supports the correct logical inferences. These content-entangled reasoning patterns are central to debates about the fundamental nature of human intelligence. Here, we investigate whether language models—whose prior expectations capture some aspects of human knowledge—similarly mix content into their answers to logic problems. We explored this question across three logical reasoning tasks: natural language inference, judging the logical validity of syllogisms, and the Wason selection task. We evaluate state of the art LMs, as well as humans, and find that the LMs reflect many of the same qualitative human patterns on these tasks—like humans, models answer more accurately when the semantic content of a task supports the logical inferences. These parallels are reflected in accuracy patterns, and in some lower-level features like the relationship between LM confidence over possible answers and human response times. However, in some cases the humans and models behave differently—particularly on the Wason task, where humans perform much worse than large models, and exhibit a distinct error pattern. Our findings have implications for understanding possible contributors to these human cognitive effects, as well as the factors that influence language model performance.
Dilated cardiomyopathy mutation in beta-cardiac myosin enhances actin activation of the power stroke and phosphate release
Authors: Bodt Skylar M L , Ge Jinghua , Ma Wen , Rasicci David V , Desetty Rohini , McCammon J Andrew , Yengo Christopher M
Published: July 2024

Inherited mutations in human beta-cardiac myosin (M2β) can lead to severe forms of heart failure. The E525K mutation in M2β is associated with dilated cardiomyopathy (DCM) and was found to stabilize the interacting heads motif (IHM) and autoinhibited super-relaxed (SRX) state in dimeric heavy meromyosin. However, in monomeric M2β subfragment 1 (S1) we found that E525K enhances (threefold) the maximum steady-state actin-activated ATPase activity (kcat) and decreases (eightfold) the actin concentration at which ATPase is one-half maximal (KATPase). We also found a twofold to fourfold increase in the actin-activated power stroke and phosphate release rate constants at 30 μM actin, which overall enhanced the duty ratio threefold. Loaded motility assays revealed that the enhanced intrinsic motor activity translates to increased ensemble force in M2β S1. Glutamate 525, located near the actin binding region in the so-called activation loop, is highly conserved and predicted to form a salt bridge with another conserved residue (lysine 484) in the relay helix. Enhanced sampling molecular dynamics simulations predict that the charge reversal mutation disrupts the E525-K484 salt bridge, inducing conformations with a more flexible relay helix and a wide phosphate release tunnel. Our results highlight a highly conserved allosteric pathway associated with actin activation of the power stroke and phosphate release and suggest an important feature of the autoinhibited IHM is to prevent this region of myosin from interacting with actin. The ability of the E525K mutation to stabilize the IHM likely overrides the enhanced intrinsic motor properties, which may be key to triggering DCM pathogenesis.
Estimating the human bottleneck for contact tracing
Authors: Broda Maximilian D , Borovska Petra , Kollenda Diana , Linka Marcel , de Haas Naomi , de Haas Samuel , de Haas Benjamin
Published: July 2024

The SARS-CoV-2 pandemic has highlighted the importance of contact tracing for epidemiological mitigation. Contact tracing interviews (CTIs) typically rely on episodic memory, which is prone to decline over time. Here, we provide a quantitative estimate of reporting decline for age- and gender-representative samples from the United Kingdom and Germany, emulating >15,000 CTIs. We find that the number of reported contacts declines as a power function of recall delay and is significantly higher for younger subjects and for those who used memory aids, such as a scheduler. We further find that these factors interact with delay: Older subjects and those who made no use of memory aids have steeper decline functions. These findings can inform epidemiological modeling and policies in the context of infectious diseases.
Slant, Extremity, and Diversity: How the Shape of News Use Explains Electoral Judgments and Confidence
Authors: Wang Yiming , Kim Sang Jung , Shan Yuanliang , Sun Yibing , Jiang Xiaoya , Lee Heysung , Borah Porismita , Wagner Michael , Shah Dhavan
Published: July 2024

The 2020 election and its aftermath present an opportunity to understand how audiences’ changing news consumption patterns within an expanded, digitized, and polarized media environment shape electoral judgments. This paper introduces measures that capture individuals’ partisan slant, partisan extremity, and overall diversity of news media use to understand how people interact with the contemporary news ecology. The measures combine self-reported media use with the partisan slant of news outlets along the ideological spectrum. Using these measures, we analyze a two-wave panel survey conducted before and after the 2020 US election to investigate how slant, diversity, and extremity are related to post-election beliefs, including public confidence in the election and the acceptance of fraud claims. Our findings show that Republicans have more insulated news use behaviors in terms of slant and diversity. The analysis also reveals that the slant of people’s news use is associated with post-election fraud beliefs, with right-wing news consumers more likely to believe such claims. However, a diverse news consumption style can moderate misinformation beliefs. Panel analysis points to the role of extreme-right news use in decreasing confidence in the legitimacy of the election.
Composition and Assembly of the Endophytic Fungal Community of Alpine Rhododendron Hosts Along Elevation Gradients
Authors: Zhang Rui , Zhou Xiong-Li , Yang Liu , Long Bo , Shen Shi-Kang
Published: July 2024

Alpine mountain ecosystems are highly sensitive to global warming and threatened by climate change. Elevation gradients are frequently used as space-for-time surrogates for climate change in mountain ecosystems due to their correspondence with climate variables over short geographic distances. However, the distribution patterns of fungal communities in perennial woody plants along elevations in this ecosystem and how elevation and host identity affect them remain unclear. In this work, we used Illumina MiSeq DNA sequencing technology to study the rhizosphere soil fungal community and root and leaf endophytic fungal community assembly of alpine Rhododendron communities across a 3,100- to 4,100-m elevation gradient on Jiaozi Mountain, Southwest China. The abundance and diversity of fungi in different compartments varied among elevation gradients and hosts. The fungal community assembly in each compartment was mainly influenced by stochastic processes. However, the contribution of homogeneous selection, dispersal limitation, and drift varied among host identities and elevations in different compartments. The diversity and composition of rhizosphere soil, root, and leaf guilds and the overall abundance of fungal functional groups tracked the Rhododendron host identity more closely than elevation did. Most indicator taxa of fungi were putative saprotrophs. These findings will improve our understanding of the maintenance of alpine Rhododendron communities along elevation gradients.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Spaceflight-associated pain
Authors: Nelson Ariana M. , Lacinski Ryan A. , Steller Jonathan G.
Published: July 2024

Purpose of review

Consequences of the expanding commercial spaceflight industry include an increase in total number of spaceflight participants and an accompanying surge in the average number of medical comorbidities compared with government-based astronaut corps. A sequela of these developments is an anticipated rise in acute and chronic pain concerns associated with spaceflight. This review will summarize diagnostic and therapeutic areas of interest that can support the comfort of humans in spaceflight.

Recent findings

Painful conditions that occur in space may be due to exposure to numerous stressors such as acceleration and vibration during launch, trauma associated with extravehicular activities, and morbidity resulting directly from weightlessness. Without normal gravitational forces and biomechanical stress, the hostile environment of space causes muscle atrophy, bone demineralization, joint stiffness, and spinal disc dysfunction, resulting in a myriad of pain generators. Repeated insults from abnormal environmental exposures are thought to contribute to the development of painful musculoskeletal and neuropathic conditions.

As humanity invests in Lunar and Martian exploration, understanding the painful conditions that will impede crew productivity and mission outcomes is critical. Preexisting pain and new-onset acute or chronic pain resulting from spaceflight will require countermeasures and treatments to mitigate long-term health effects.
Anesthesia for traumatic brain injury
Authors: Siebers Nys Willem , Steiner Luzius A.
Published: July 2024

Purpose of review

Traumatic brain injury (TBI) presents complex clinical challenges, requiring a nuanced understanding of its pathophysiology and current management principles to improve patient outcomes. Anesthetists play a critical role in care and need to stay updated with recent evidence and trends to ensure high-quality treatment. The Brain Trauma Foundation Guidelines, last updated in 2016, have shown moderate adherence, and much of the current management relies on expert opinions. This literature review synthesizes the current evidence and provides insights into the role of anesthetists in TBI management.

Recent findings

Recent literature has emphasized the importance of tailored anesthetic management principles in treating TBI, focusing on minimizing secondary brain injury during neurosurgical interventions or extracranial surgery. Emerging trends include individualized intracranial pressure approaches and multimodal neuromonitoring for comprehensive assessment of cerebral physiology.

Anesthesia for TBI patients requires a comprehensive approach that balances anesthetic goals with the unique pathophysiological factors of brain injury. Despite recent research expanding our understanding, challenges remain in standardizing protocols and addressing individual patient response variability. Adherence to established management principles, personalized approaches, and ongoing research is crucial for improving the outcomes.