jimnoneill/paper-to-field-training huggingface dataset:
Neutralization of Competition Effects in CRISPRi-Based Genetic Circuits via a dCas9 Feedback Regulator

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

CRISPR interference (CRISPRi) has emerged as a powerful tool for modulating complex endogenous transcriptional programs and for building larger scale synthetic genetic circuits [1,2]. \nHowever, highly specific sgRNA-promoter binding is, alone, insufficient to achieve independent transcriptional regulation of multiple targets. Indeed, due to competition for dCas9, the repression ability of one sgRNA reduces significantly when another sgRNA becomes expressed [3]. \nTo solve this problem, decoupling sgRNA-mediated regulatory paths, we created a dCas9 concentration regulator that implements a negative feedback on dCas9 level [4]. This allows any sgRNA to maintain an approximately constant dose-response curve, independent of other sgRNAs. \nWe demonstrate the regulator performance on both single-stage and layered CRISPRi-based genetic circuits, zeroing competition effects of up to 15-fold changes in circuit I/O response encountered without the dCas9 regulator. \nThis recovery was confirmed even varying DNA copy numbers, strains and signaling molecules activating the systems; \nOur dCas9 generator is implemented in a dedicated plasmid, to be easily transported across compatible bacterial strains, thus enabling true scalability of CRISPRi-based transcriptional programs. \nWe establish an important new tool of broad interest for CRISPRi users to either control endogenous transcriptional programs or to create new genetic circuits for any application. \n \n[1] Gao Y, Xiong X, Wong S, et al. Complex transcriptional modulation with orthogonal and inducible dCas9 regulators. Nat Methods 13, 12 (2016). \n[2] Kiani S, Beal J, Ebrahimkhani MR, et al. CRISPR transcriptional repression devices and layered circuits in mammalian cells. Nat Methods 11, 7 (2014). \n[3] Zhang S, Voigt CA. Engineered dCas9 with reduced toxicity in bacteria: implications for genetic circuit design. NAR 46, 20 (2018). \n[4] Huang H-H, Bellato M, Qian Y, et al. dCas9 regulator to neutralize competition in CRISPRi circuits. Nat Commun 12, 1692 (2021).
Marked Improvement in Photoinduced Cell Death by a New Tris-heteroleptic Complex with Dual Action: Singlet Oxygen Sensitization and Ligand Dissociation

Field: Chemistry (Physical Sciences)

The new tris-heteroleptic complex [Ru(bpy)(dppn)(CH3CN)2](2+) (3, bpy = 2,2'-bipyridine, dppn = benzo[i]dipyrido[3,2-a;2',3'-c]phenazine) was synthesized and characterized in an effort to generate a molecule capable of both singlet oxygen ((1)O2) production and ligand exchange upon irradiation. Such dual reactivity has the potential to be useful for increasing the efficacy of photochemotherapy drugs by acting via two different mechanisms simultaneously. The photochemical properties and photoinduced cytotoxicity of 3 were compared to those of [Ru(bpy)2(dppn)](2+) (1) and [Ru(bpy)2(CH3CN)2](2+) (2), since 1 sensitizes the production of (1)O2 and 2 undergoes ligand exchange of the monodentate CH3CN ligands with solvent when irradiated. The quantum yield of (1)O2 production was measured to be 0.72(2) for 3 in methanol, which is slightly lower than that of 1, Φ = 0.88(2), in the same solvent (λirr = 460 nm). Complex 3 also undergoes photoinduced ligand exchange when irradiated in H2O (λirr = 400 nm), but with a low quantum efficiency (<1%). These results are explained by the presence of the low-lying ligand-centered (3)ππ* excited state of 3 localized on the dppn ligand, thus decreasing the relative population of the higher energy (3)dd state; the latter is associated with ligand dissociation. Cytotoxicity data with HeLa cells reveal that complex 3 exhibits a greater photocytotoxicity index, 1110, than does either 1 and 2, indicating that the dual-action complex is more photoactive toward cells in spite of its low ligand exchange quantum yield.
Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants

Field: Medicine (Health Sciences)

Prostate cancer is a complex and heterogeneous disease, but a small number of cell lines have dominated basic prostate cancer research, representing a major obstacle in the field of drug and biomarker discovery. A growing lack of confidence in cell lines has seen a shift toward more sophisticated pre-clinical cancer models that incorporate patient-derived tumors as xenografts or explants, to more accurately reflect clinical disease. Not only do these models retain critical features of the original tumor, and account for the molecular diversity and cellular heterogeneity of prostate cancer, but they provide a unique opportunity to conduct research in matched tumor samples. The challenge that accompanies these complex tissue models is increased complexity of analysis. With over 10 years of experience working with patient-derived explants (PDEs) of prostate cancer, this study provides guidance on the PDE method, its limitations, and considerations for addressing the heterogeneity of prostate cancer PDEs that are based on statistical modeling. Using inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) as an example of a drug that induces robust proliferative response, we demonstrate how multi-omics analysis in prostate cancer PDEs is both feasible and essential for identification of key biological pathways, with significant potential for novel drug target and biomarker discovery.
ECG denoising and feature extraction techniques – a review

Field: Computer Science (Physical Sciences)

The electrocardiogram (ECG) is a non-invasive approach for the recording of bioelectric signals generated by the heart which is used for the examination of the electro physical state, the function of the heart, and many cardiac diseases. However, various artefacts and measurement noise usually hinder providing accurate feature extraction such as power line interference, baseline wander, electromyographic noise (EMG) and electrode motion artefact. Therefore, for better analysis and interpretation ECG signals must be noise-free. Most recent and efficient techniques for ECG denoising and feature extraction techniques have been reviewed in this paper, as feature extraction and denoising of ECG are remarkably helpful in cardiology. This paper presents the review of contemporary signal processing techniques such as discrete wavelet transform (DWT), Empirical mode decomposition (EMD), Variational mode decomposition (VMD) and Empirical wavelet transform (EWT) for ECG signal denoising and feature extraction.
Contribution of supervision to the development of advanced practitioners: a qualitative study of pharmacy learners’ and supervisors’ views

Field: Health Professions (Health Sciences)

Objective To apply educational theory to explore how supervision can contribute to the development of advanced practitioners using the example of several postregistration primary care training pathways for pharmacy professionals (pharmacists and pharmacy technicians). Design Qualitative semistructured telephone interviews applying Billet’s theory of workplace pedagogy for interpretation. Setting England. Participants Fifty-one learners and ten supervisors. Primary outcome Contribution of clinical and educational supervision to the development of advanced practitioners in primary care. Results Findings were mapped against the components of Billet’s theory to provide insights into the role of supervision in developing advanced practitioners. Key elements for effective supervision included supporting learners to identify their learning needs (educational supervision), guiding learners in everyday work activities (clinical supervision), and combination of regular prearranged face-to-face meetings and ad hoc contact when needed (clinical supervision), along with ongoing support as learners progressed through a learning pathway (educational supervision). Clinical supervisors supported learners in developing proficiency and confidence in translating and applying the knowledge and skills they were gaining into practice. Learners benefited from having clinical supervisors in the workplace with good understanding and experience of working in the setting, as well as receiving clinical supervision from different types of healthcare professionals. Educational supervisors supported learners to identify their learning needs and the requirements of the learning pathway, and then as an ongoing available source of support as they progressed through a pathway. Educational supervisors also filled in some of the gaps where there was a lack of local clinical supervision and in settings like community pharmacy where pharmacist learners did not have access to any clinical supervision. Conclusions This study drew out important elements which contributed to effective supervision of pharmacy advanced practitioners. Findings can inform the education and training of advanced practitioners from different professions to support healthcare workforce development in different healthcare settings.
Non-communicating Rudimentary Uterine Horn Pregnancy

Field: Medicine (Health Sciences)

Pregnancy in a non-communicating rudimentary horn is an extremely rare form of ectopic gestation. The rudimentary horn may or may not communicate with the uterine cavity with the majority of cases being non-communicating. The patient exhibits features of acute abdomen and carries a high risk of maternal death. Even modern scans remain elusive whereas laparatomy remains the confi rmatory procedure for the diagnosis. Because of the varied muscular constitution in the thickness and distensibility of the wall of the rudimentary horn, pregnancy is accommodated for a variable period of gestation. Here, we report three cases of pregnancy in a non-communicating rudimentary horn of the uterus in different periods of gestation, their outcome and a review of the available literature. Keywords: Mullerian anomalies, non-communicating rudimentary horn pregnancy, surgical management.
Adding Context to Content: The CENS Deployment Center

Field: Computer Science (Physical Sciences)

Scientists and engineers working with embedded networked sensing systems in the environmental sciences are acquiring data at unprecedented rates. Scientific data do not emerge from a vacuum. There is considerable contextual information that surrounds the process of data acquisition that is critical to interpret and analyze data. Current techniques for data sharing involve considerable manual effort to prepare, describe, and transfer this contextual information along with the data itself. This paper reports on a study of the UCLA-based Center for Embedded Networked Sensing (CENS), an interdisciplinary NSF research center that supports collaborations to develop and implement innovative wireless sensor networks. We report here on the development of the CENS Deployment Center, a database for CENS deployment information. The goals of the CENSDC are to facilitate better deployment organization, and to provide a central location for key information that describes the context of data capture. We also describe our plans within CENS to use a tri-partite approach to capture and share sensor data resources using technical recommendations currently being developed within the context of the Open Archive Initiative for Object Reuse and Exchange (OAI-ORE).
Therapeutic Effects of Caloric Stimulation and Optokinetic Stimulation on Hemispatial Neglect

Field: Neuroscience (Life Sciences)

Hemispatial neglect refers to a cognitive disorder in which patients with unilateral brain injury cannot recognize or respond to stimuli located in the contralesional hemispace. Hemispatial neglect in stroke patients is an important predictor for poor functional outcome. Therefore, there is a need for effective treatment for this condition. A number of interventions for hemispatial neglect have been proposed, although an approach resulting in persistent improvement is not available. Of these interventions, our review is focused on caloric stimulation and optokinetic stimulation. These lateralized or direction-specific stimulations of peripheral sensory systems can temporarily improve hemispatial neglect. According to recent functional MRI and PET studies, this improvement might result from the partial (re)activation of a distributed, multisensory vestibular network in the lesioned hemisphere, which is a part of a system that codes ego-centered space. However, much remain unknown regarding exact signal timing and directional selectivity of the network.
OS10.3 Randomized Phase 3 Study Evaluating the Efficacy and Safety of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: CheckMate 143

Field: Medicine (Health Sciences)

\nBACKGROUND: Despite available treatment options for patients (pts) with recurrent glioblastoma (GBM), < 5% of pts survive 5 years beyond initial diagnosis, and no single-agent therapy has demonstrated a survival benefit in the second-line setting, including bevacizumab (bev), which is approved for the treatment of recurrent disease. Nivolumab (nivo), a fully human IgG4 monoclonal antibody that inhibits the programmed death 1 receptor, has provided clinical benefit in multiple cancer types. In cohort 2 of the open-label, phase 3 CheckMate 143 study (NCT02017717), the efficacy and safety of nivo was compared with that of bev in pts with GBM experiencing their first recurrence after prior radiotherapy (RT) and temozolomide (TMZ). METHODS: Pts with no prior VEGF therapy were randomized 1:1 to receive nivo 3 mg/kg Q2W or bev 10 mg/kg Q2W until confirmed disease progression; pts were stratified by the presence/absence of measurable disease. The primary endpoint was overall survival (OS); secondary endpoints were 12-mo OS rate and investigator-assessed progression-free survival (PFS) and objective response rate (ORR) per Response Assessment in Neuro-Oncology criteria. RESULTS: At the time of final analyses (Jan 20, 2017), 369 pts were randomized to the nivo (n = 184) or bev (n = 185) treatment arms; of these pts, 182 received nivo and 165 received bev. At baseline, most pts in the nivo (83%) and bev (84%) arms had measurable disease, and 40% (nivo) and 43% (bev) of pts required corticosteroids, with 14% (nivo) and 15% (bev) receiving â¥ 4 mg/day. Deaths were reported in 154 (nivo) and 147 (bev) pts; median OS was 9.8 mo with nivo and 10.0 mo with bev, and the 12-mo OS rate was 42% in both arms. PFS medians were 1.5 mo (nivo) and 3.5 mo (bev). Among evaluable pts treated with nivo (n = 153) or bev (n = 156), ORRs were 8% (nivo) and 23% (bev); duration of response medians were 11.1 mo (nivo) and 5.3 mo (bev). Treatment-related AEs (TRAEs) occurred in 57% (nivo) and 58% (bev) of pts; the most common TRAEs (â¥ 10% of pts in either arm; nivo vs bev) were fatigue (21% vs 14%) and hypertension (1% vs 22%). Grade 3â4 TRAEs were reported in 18% (nivo) and 15% (bev) of pts. Serious AEs (all causality) were reported in 46% (nivo) and 35% (bev) of pts; seizure (8% vs 6%) and malignant neoplasm progression (11% vs 7%) were the only serious AEs reported in â¥ 5% of pts in either arm. AEs leading to discontinuation occurred in 10% (nivo) and 15% (bev) of pts. CONCLUSIONS: Nivo did not demonstrate an improved OS compared with bev in pts with recurrent GBM. The ORR was lower with nivo than bev; however, responses with nivo were more durable. The safety profile of nivo was consistent with that observed in other tumor types. Studies of nivo in combination with RT Â± TMZ in pts with newly diagnosed GBM are ongoing.
pH-Promoted Exponential Layer-by-Layer Assembly of Bicomponent Polyelectrolyte/Nanoparticle Multilayers

Field: Materials Science (Physical Sciences)

Exponential growth of layer-by-layer (LbL) assembled films is desirable because this method considerably increases the growth rate, resulting in much thicker films in a shorter period of time than is the case with normally linearly grown LbL thin films. For the first time, we demonstrate the exponential LbL (e-LbL) growth of poly(ethyleneimine)/SiO<sub>2</sub> nanoparticles (PEI/SiO<sub>2</sub>) bicomponent thin films that consist mostly of SiO<sub>2</sub> nanoparticles (over 90 wt % obtained by thermogravimetric analysis). These results are in contrast to earlier e-LbL studies, where the film thickness was made up mostly of the polyelectrolyte, with a very small percentage coming from the inorganic nanoparticles. Here, we show that the LbL growth of the PEI/SiO<sub>2</sub> system significantly depends on the pH of the PEI and the SiO<sub>2</sub> solutions. The e-LbL growth will only occur when the film is deposited with PEI at a high pH and SiO<sub>2</sub> at a low pH. The exponential growth was characterized using a quartz crystal microbalance, atomic force microscopy and scanning electron microscopy imaging, and neutron reflectometry. It is demonstrated that e-LbL films can grow to thicknesses as large as 2–3 μm within just 10 bilayers. The findings reported in this article emphasize new opportunities for the e-LbL growth of organic/inorganic bicomponent composite thin films that may have applications as electrically conducting films, hydrophobic films, and brick-and-mortar biomimetic films.
Versatile and Efficient Mechanochemical Synthesis\nof Crystalline Guest⊂Zeolitic Imidazolate Framework Complexes\nby in Situ Host–Guest Nanoconfinement

Field: Chemistry (Physical Sciences)

In this work, the\none-pot mechanochemical synthesis was demonstrated\nto be a versatile and efficient method to prepare hybrid guest⊂ZIF\n(ZIF = zeolitic imidazolate framework) materials with high crystallinity,\nand up to 18 functional guest molecules with different sizes, shapes,\nand properties were encapsulated into interior cavities of ZIFs with\nhigh guest loading. These guest molecules can be accommodated within\nthe different cavities of <i>sod</i>- or <i>rho</i>-ZIFs, depending on the sizes of guest. Because of the relatively\nsmall opening of ZIFs, the guest molecules can be immobilized by physical\nimprisonment and cannot be released without destroying the host matrix.\nMore importantly, the obtained guest⊂ZIF materials were endowed\nwith various interesting properties originated from the encaged guest\nmolecules, which significantly extends the functionality of metal–organic\nframeworks. For instance, poly­(ethylene glycol)-decorated nanoparticles\nof a <i>sod</i>-ZIF (i.e., ZIF-8) encapsulating gadolinium\ncomplex exhibit interesting property of magnetic resonance imaging,\nand a <i>rho</i>-ZIF (i.e., MAF-6) with metalloporphyrin\nembedded can be used as an effective heterogeneous catalyst for epoxidation\nof styrene.
Generalized Bed-Load Function Based on Empirical Data

Field: Earth and Planetary Sciences (Physical Sciences)

There exist many bed-load functions in the literature to calculate bed-load transport rates, but none of them fit data from low to high shear stress conditions. This research presents a generalized bed-load function based on empirical data. Specifically, the classic power law in high shear stress conditions is extended to low shear stress conditions by applying a complimentary error function (or logistic function) and using Coles' mathematical idea for the wake law in turbulent boundary layer velocity distribution. The resulting generalized bed-load function agrees well with the classic data sets; it reduces to Huang's 5/3 power law in the very low and the high shear stress conditions, and it is numerically close to Paintal's 16th power law in the transitional regime. It is found that the maximum turbulence-induced lift force and the minimum critical shear stress in the Shields diagram correspond to the inflection point (in terms of logarithmic scale) in the Einstein bed-load diagram, resulting in the most efficient bed-load transport rate. After that, this paper discusses the effects of turbulence-induced lift force, critical shear stress, viscosity, nonlinearity, and uncertainty on bed-load transport. Finally, an example with uncertainty analysis is illustrated for applications.
Emerging Viral Infections and Their Impact on the Global Burden of Neurological Disease

Field: Medicine (Health Sciences)

Abstract Emerging viral infections of the nervous system represent a major global public health concern in the 21st century. They are caused primarily by RNA viruses and are mostly associated with acute or subacute encephalitis. The spectrum of associated central or peripheral nervous system disorders is broad, and results either from a direct viral effect or due to the host immune responses against the infection. Emerging viral infections impose substantial neurological morbidity and mortality, particularly in low- and middle-income regions. In the past five decades, vector-borne viruses primarily transmitted by arthropods, or arboviruses, have been responsible for epidemics with a high burden of neurological disease, like the 2015–2016 Zika virus epidemic in the Americas. Viruses that have become neurovirulent for humans after geographical expansion include West Nile, Dengue, and Zika viruses. Factors such as animal migration, disruption of ecological niches, and cross-species contact have caused old viruses to reappear and cause neurological disease, as is the case of Ebola virus. In addition to these biological challenges, current preventive strategies, vaccination, and diagnostic and therapeutic approaches remain limited. We review the clinical-virological features and global impact of the most relevant emerging viral infections of the nervous system as they are projected over the 21st century.
Approach to recognizing SSVEP by combining CCA with artificial neural network

Field: Computer Science (Physical Sciences)

Steady-state visual evoked potential (SSVEP) is one of popular EEG patterns employed by brain-computer interface (BCI) systems. SSVEP-based BCI systems have some advantages such as high information transfer rate and less training requirement for the users. To develop a SSVEP-based BCI system, the recognition of the primary frequency of SSVEP is critical and may be effectively achieved by using canonical correlation analysis (CCA). Several improved methods based on the traditional CCA method have been proposed. However, very few researches have considered the effectiveness, both by the individual subject itself and by the diversity of feeling imposed on different subjects by the same stimulus frequency, on the result of CCA. To address this issue, a novel method, NNWCCA, is proposed in this paper. NNWCCA first uses standard CCA to calculate the maximum canonical correlation coefficients between the analyzed EEG data with the reference signal of each stimulus frequency, and then employs an artificial neural network, which takes the calculated canonical correlation coefficients as inputs, to finally determine the primary frequency of the SSVEP hidden in the analyzed EEG data. The effectiveness of NNWCCA was verified by using a public SSVEP data.