gebhart/patrepeval huggingface dataset:
Complete Disruption of Autism-Susceptibility Genes by Gene Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons (2019)

(Stem Cell Reports 11, 1211–1225; January 13, 2018) The original representative trace of excitatory post-synaptic current (EPSC) for AFF2−/y was used twice by mistake to generate the ASTN2−/y cropped trace on the top panel of Figure 5A. However, we confirm that the original data was not a duplicate; only the image file was cropped incorrectly as a display figure for the trace. We have made a new Figure 5 with the correct ASTN2 trace cropped in Figure 5A. None of the original data or interpretation of the data was impacted.Figure 5Electrophysiological Phenotyping of KO iPSC-Derived Neurons (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Complete Disruption of Autism-Susceptibility Genes by Gene Editing Predominantly Reduces Functional Connectivity of Isogenic Human NeuronsDeneault et al.Stem Cell ReportsNovember 1, 2018In BriefIn this article, Scherer and colleagues present a human induced pluripotent stem cell (iPSC) knockout resource for functional studies of ten genes associated with autism spectrum disorder. They also show that some of these genes, pertaining to diverse functional categories, can underlie common phenotypes in CRISPR-isogenic iPSC-derived glutamatergic neurons. Full-Text PDF Open Access
Replacement Therapy in Hereditary Angioedema (1980)

Although considerable progress has been made during the past two decades in the use of androgens to prevent attacks of hereditary angioedema, replacement of the deficient C1-inhibitor protein would provide a useful menas of treatment once an attack has begun. We studied the clinical use of C1 inhibitor that was partly purified on a large scale from pooled plasma. The in vivo efficacy and safety of this protein concentrate were evaluated during 11 intravenous infusions in eight patients with hereditary angioedema. Three patients received the C1-inhibitor preparation during an asymptomatic period. Increases in serum C4 activity provided evidence of the biologic activity of the infused inhibitor. Intravenous administration of the concentrate during acute abdominal or laryngeal attacks of hereditary angioedema in five patients resulted in abatement of symptoms in addition to increased serum C4 activity. No untoward effects of the intravenous administration of the C1 inhibitor were observed in these eight patients. Thus, this C1-inhibitor preparation seems to offer the potential for safe, effective replacement therapy and may provide a means of controlling an attack of hereditary angioedema that is in progress.
Communications: Blood Chemistry of Laboratory-Reared Golden Trout (1992)

Golden trout Oncorhynchus aguabonita obtained from a wild stock as fertilized eggs were reared in the laboratory for 21 months. The laboratory-reared golden trout in our study reached sexual maturity earlier and grew more rapidly than wild golden trout do (according to the scientific literature). Male fish averaged 35.6 cm in total length and 426 g in weight, and females averaged 36.2 cm and 487 g. All golden trout were sexually mature when used for hematological analysis. The hematological profile (hematocrit, red blood cells, white blood cells, and thrombocytes) of golden trout was similar to that reported elsewhere for other trout species. Male and female golden trout did not have significantly different thrombocyte counts; however, the immobilization treatment used on the fish (anesthesia versus a blow to the head) resulted in significant treatment differences in thrombocyte numbers and interaction effect of sex in treatment for hematocrits. Gravid female golden trout had significantly higher plasma protein and calcium levels than did males. The ionic compositions of plasma (sodium, potassium, calcium, magnesium, copper, zinc, iron, and chloride) and gallbladder bile (calcium and chloride) were similar to those reported for other salmonids.
Liposomal Enzyme Nanoreactors Based on Nanoconfinement for Efficient Antitumor Therapy (2023)

Enzymatic reactions can consume endogenous nutrients of tumors and produce cytotoxic species and are therefore promising tools for treating malignant tumors. Inspired by nature where enzymes are compartmentalized in membranes to achieve high reaction efficiency and separate biological processes with the environment, we develop liposomal nanoreactors that can perform enzymatic cascade reactions in the aqueous nanoconfinement of liposomes. The nanoreactors effectively inhibited tumor growth in vivo by consuming tumor nutrients (glucose and oxygen) and producing highly cytotoxic hydroxyl radicals (⋅OH). Co-compartmentalization of glucose oxidase (GOx) and horseradish peroxidase (HRP) in liposomes could increase local concentration of the intermediate product hydrogen peroxide (H<sub>2</sub> O<sub>2</sub> ) as well as the acidity due to the generation of gluconic acid by GOx. Both H<sub>2</sub> O<sub>2</sub> and acidity accelerate the second-step reaction by HRP, hence improving the overall efficiency of the cascade reaction. The biomimetic compartmentalization of enzymatic tandem reactions in biocompatible liposomes provides a promising direction for developing catalytic nanomedicines in antitumor therapy.
Estimation of Baroreflex Gain Using a Baroreflex Equilibrium Diagram. (2002)

Two types of closed-loop perturbations can be applied to the arterial baroreflex system. The first (P(D1)) is introduced into the baroreceptors without a direct effect on arterial pressure (AP), whereas the second (P(D2)) initially affects AP. Neck suction and hemorrhage are examples of P(D1) and P(D2), respectively. To estimate the baroreflex open-loop gain (G(Baro)) without knowing the absolute magnitudes of P(D1) and P(D2), we explored a new strategy to estimate G(Baro) by combining P(D1) and P(D2) in a baroreflex equilibrium diagram. In this diagram, the neural arc presents the input-output relationship between baroreceptor pressure input and sympathetic nerve activity (SNA). The peripheral arc presents the input-output relationship between SNA and AP. In 8 anesthetized rabbits, we estimated G(Baro) by multiplying the slopes of the peripheral arc determined from P(D1) and the neural arc determined from P(D2). We also estimated G(Baro) by a conventional open-loop analysis. The G(Baro) values estimated by the equilibrium diagram and the open-loop analysis showed a positive correlation (y = 0.80x + 0.22, r(2) = 0.95) and a standard error of estimate of 0.21 across the animals. We conclude that G(Baro) was estimated well by combining P(D1) and P(D2) in the equilibrium diagram.
Kinetics of Surface-Induced Dissociation of N(CH3)4+ and N(CD3)4+ Using Silicon Nanoparticle Assisted Laser Desorption/Ionization and Laser Desorption/Ionization (2009)

The implementation of surface-induced dissociation (SID) to study the fast dissociation kinetics (sub-microsecond dissociation) of peptides in a MALDI TOF instrument has been reported previously. Silicon nanoparticle assisted laser desorption/ionization (SPALDI) now allows the study of small molecule dissociation kinetics for ions formed with low initial source internal energy and without MALDI matrix interference. The dissociation kinetics of N(CH(3))(4)(+) and N(CD(3))(4)(+) were chosen for investigation because the dissociation mechanisms of N(CH(3))(4)(+) have been studied extensively, providing well-characterized systems to investigate by collision with a surface. With changes in laboratory collision energy, changes in fragmentation timescale and dominant fragment ions were observed, verifying that these ions dissociate via unimolecular decay. At lower collision energies, methyl radical (CH(3)) loss with a sub-microsecond dissociation rate is dominant, but consecutive H loss after CH(3) loss becomes dominant at higher collision energies. These observations are consistent with the known dissociation pathways. The dissociation rate of CH(3) loss from N(CH(3))(4)(+) formed by SPALDI and dissociated by an SID lab collision energy of 15 eV corresponds to log k = 8.1, a value achieved by laser desorption ionization (LDI) and SID at 5 eV. The results obtained with SPALDI SID and LDI SID confirm that (1) the dissociation follows unimolecular decay as predicted by RRKM calculations; (2) the SPALDI process deposits less initial energy than LDI, which has advantages for kinetics studies; and (3) fluorinated self-assembled monolayers convert about 18% of laboratory collision energy into internal energy. SID TOF experiments combined with SPALDI and peak shape analysis enable the measurement of dissociation rates for fast dissociation of small molecules.
The tracker catheter: A new vascular access system (1992)

Technologic advances in dilation equipment have been important in improving angioplasty success rates and in expanding the indications of dilation. Despite these improvements, approximately 7% to 10% of attempted dilations may ultimately fail because of inability to cross the culprit lesion. As angioplasty techniques are applied to an increasingly complex cohort of patients, the ultimate success of a given procedure depends more and more on the ability of the operator to select the appropriate equipment for a given procedure. We report the unique application of a commercially available perfusion catheter which may improve patient outcome during complex angioplasty.
The Development of a Vaccine Against Meningococcus B Using Reverse Vaccinology (2019)

The discovery of vaccine antigens through whole genome sequencing (WGS) contrasts with the classical hypothesis-driven laboratory-based analysis of microbes to identify components to elicit protective immunity. This radical change in scientific direction and action in vaccine research is captured in the term <i>reverse vaccinology</i>. The complete genome sequence of an isolate of <i>Neisseria meningitidis</i> serogroup B (MenB) was systematically analyzed to identify proteins predicted to be secreted or exported to the outer membrane. This identified hundreds of genes coding for potential surface-exposed antigens. These were amplified, cloned in expression vectors and used to immunize mice. Antisera against 350 recombinant antigens were obtained and analyzed in a panel of immunological assays from which 28 were selected as potentially protective based on the -antibody dependent, complement mediated- serum bactericidal activity assay. Testing of these candidate vaccine antigens, using a large globally representative strain collection of Neisseria species isolated from cases of disease and carriage, indicated that no single component would be sufficient to induce broad coverage and that a "universal" vaccine should contain multiple antigens. The final choice of antigens to be included was based on cross-protective ability, assayed by serum bactericidal activity and maximum coverage of the extensive antigenic variability of MenB strains. The resulting multivalent vaccine formulation selected consisted of three recombinant antigens (Neisserial Heparin Binding Antigen or NHBA, Factor H binding protein or fHbp and Neisseria Adhesin A or NadA). To improve immunogenicity and potential strain coverage, an outer membrane vesicle component obtained from the epidemic New Zealand strain (OMVNz) was added to the formulation to create a four component vaccine, called 4CMenB. A series of phase 2 and 3 clinical trials were conducted to evaluate safety and tolerability and to estimate the vaccine effectiveness of human immune responses at different ages and how these were affected by various factors including concomitant vaccine use and lot-to-lot consistency. 4CMenB was approved in Europe in 2013 and introduced in the National Immunization Program in the UK starting from September 2015 when the vaccine was offered to all newborns using a 2, 4, and 12 months schedule., The effectiveness against invasive MenB disease measured at 11 months after the study start and 5 months after the second vaccination was 83% and there have been no safety concerns.
Knowledge Distillation Meets Few-Shot Learning: An Approach for Few-Shot Intent Classification Within and Across Domains (2022)

Large Transformer-based natural language understanding models have achieved state-of-theart performance in dialogue systems. However, scarce labeled data for training, the large model size, and low inference speed hinder their deployment in low-resource scenarios. Few-shot learning and knowledge distillation techniques have been introduced to reduce the need for labeled data and computational resources, respectively. However, these techniques are incompatible because few-shot learning trains models using few data, whereas, knowledge distillation requires sufficient data to train smaller, yet competitive models that run on limited computational resources. In this paper, we address the problem of distilling generalizable small models under the few-shot setting for the intent classification task. Considering in-domain and cross-domain few-shot learning scenarios, we introduce an approach for distilling small models that generalize to new intent classes and domains using only a handful of labeled examples. We conduct experiments on public intent classification benchmarks, and observe a slight performance gap between small models and large models. Overall, our results in both few-shot scenarios confirm the generalization ability of the small distilled models while having lower computational costs.
Regulation of human monocyte cell-surface and soluble CD23 (Fc epsilon RII) by granulocyte-macrophage colony-stimulating factor and IL-3 (1992)

We have investigated the regulation of expression of cell-surface and soluble CD23 (sCD23) by purified human peripheral blood monocytes and in cultures of human whole blood. IL-3, IL-4, and GM-CSF were found to markedly enhance the expression of CD23 on the surface of elutriated monocytes and to increase levels of sCD23 in monocyte-culture supernatants. The induction of CD23 expression by monocytes was confirmed at the mRNA level by Northern blot analysis. The ability of GM-CSF, IL-3, or IL-4 to induce cell-surface CD23 on monocytes was inhibited by specific neutralizing antibodies to the corresponding cytokine. IL-3 and GM-CSF induced maximal surface CD23 expression on monocytes by 24 to 48 h, followed by a slight decline at 72 and 96 h. In contrast, IL-4 induced a progressive increase in monocyte CD23 expression that reached a maximum at approximately 72 h. IL-4, GM-CSF, and IFN-gamma increased both surface and soluble CD23 expression by the monocytic cell line U937, whereas IL-3 had no effect. The plasma from fresh human whole blood or nonstimulated whole blood cultured for 24 to 48 h contained detectable sCD23, and addition of IL-3, IL-4, or GM-CSF to these cultures resulted in increased levels of this molecule. Two-color flow cytometry revealed that IL-3, but not GM-CSF, also enhanced CD23 expression by B cells enriched from PBMC, although the effect of IL-3 was weak in comparison with that of IL-4. These findings may have important implications for the in vivo therapeutic use of these cytokines.
A Structure-Guided Approach to an Orthogonal Estrogen-Receptor-Based Gene Switch Activated by Ligands Suitable for in Vivo Studies (2006)

A strategy to obtain a fully orthogonal estrogen-receptor-based gene switch responsive to molecules with acceptable pharmacological properties is presented. From a series of tetrahydrofluorenones active on the wild-type estrogen receptor (ER) an inactive analogue is chosen as a new lead compound. Coevolution of receptor mutants and ligands leads to an ER-based gene switch suitable for studies in animal models.
MAPK-directed activation of the whitefly transcription factor CREB leads to P450-mediated imidacloprid resistance (2020)

The evolution of insect resistance to pesticides poses a continuing threat to agriculture and human health. While much is known about the proximate molecular and biochemical mechanisms that confer resistance, far less is known about the regulation of the specific genes/gene families involved, particularly by <i>trans</i>-acting factors such as signal-regulated transcription factors. Here we resolve in fine detail the <i>trans</i>-regulation of <i>CYP6CM1</i>, a cytochrome P450 that confers resistance to neonicotinoid insecticides in the whitefly <i>Bemisia tabaci,</i> by the mitogen-activated protein kinase (MAPK)-directed activation of the transcription factor <i>cAMP-response element binding protein</i> (<i>CREB</i>). Reporter gene assays were used to identify the putative promoter of <i>CYP6CM1</i>, but no consistent polymorphisms were observed in the promoter of a resistant strain of <i>B. tabaci</i> (imidacloprid-resistant, IMR), which overexpresses this gene, compared to a susceptible strain (imidacloprid-susceptible, IMS). Investigation of potential <i>trans</i>-acting factors using in vitro and in vivo assays demonstrated that the bZIP transcription factor <i>CREB</i> directly regulates <i>CYP6CM1</i> expression by binding to a cAMP-response element (CRE)-like site in the promoter of this gene. <i>CREB</i> is overexpressed in the IMR strain, and inhibitor, luciferase, and RNA interference assays revealed that a signaling pathway of MAPKs mediates the activation of <i>CREB</i>, and thus the increased expression of <i>CYP6CM1</i>, by phosphorylation-mediated signal transduction. Collectively, these results provide mechanistic insights into the regulation of xenobiotic responses in insects and implicate both the MAPK-signaling pathway and a transcription factor in the development of pesticide resistance.
Synthesis of Novel, Chiral Bicyclo[3.1.0]hex‐2‐ene Amino Acid Derivatives as Useful Synthons in Medicinal Chemistry (2015)

Abstract A short and concise synthesis of novel, chiral bicyclo[3.1.0]hex‐2‐ene amino acid derivatives 13 and 14 has been developed. The key step is a stereo‐ and regioselective allylic amination of exo ‐ and endo ‐methyl bicyclo[3.1.0]hex‐2‐ene‐6‐carboxylates 8 and 9 , which were prepared from 7,7‐dichlorobicyclo[3.2.0]hept‐2‐en‐6‐one ( 1 ). These amino acid derivatives are useful building blocks in medicinal chemistry and can be prepared as chiral compounds by using either (+)‐ 1 or (−)‐ 1 as starting material.
Impact of the Final Rule on the Rate of Clinical Cardiac Arrest Research in the United States (2005)

Background: The federal government placed a moratorium on human emergency resuscitation research in 1993 due to concerns related to informed consent. In 1996, the Food and Drug Administration introduced the Final Rule in order to allow clinical resuscitation research to proceed in special cases without prospective informed consent. It is unclear, however, how this change has impacted the performance of this research. Objectives: To measure the potential impact of the Final Rule by determining the number of clinical cardiac arrest studies performed in the United States (US) before and after 1993, and to compare it with the number of studies performed in the European Union (EU) during the same periods. Methods: A MEDLINE search was performed for cardiac arrest studies that were prospective, interventional, randomized, and performed in the US or EU from 1983 through 2003. Results: Of the 3,115 cardiac arrest publications identified, 66 (2%) met inclusion criteria. Of the 40 studies conducted in the US, 24 (60%) were published prior to or during 1993, whereas of the 27 studies conducted in the EU, six (22%) were published prior to or during 1993 (odds ratio = 0.5; 95% confidence interval = 0.3 to 0.8). Conclusions: There has been a significant decrease in the number of published clinical cardiac arrest trials in the US since 1993. In contrast, there has been a significant increase in the number of published EU trials since 1993. The current informed consent requirements may have reduced the number of clinical cardiac arrest studies performed in the US.
A variable torque motor compatible with magnetic resonance imaging (2009)

High magnetic fields used in magnetic resonance imaging (MRI) do not allow the employment of conventional motors due to various incompatibility issues. This paper reports on a new motor that can operate in or near high field magnets used for MRI. The motor was designed to be operational with the MRI equipment and could be used in a rotating imaging gantry inside the magnet designed for dual modality imaging. Furthermore, it could also be used for image guided robotic interventional procedures inside a MRI system if so desired. The prototype motor was developed using magnetic resonance (MR) compatible materials, and its functionality with MR imaging was evaluated experimentally by measuring the performance of the motor and its effect on the MR image quality. Since in our application, namely, single photon emission tomography, the motor has to perform precise stepping of the gantry in small angular steps the most important parameter is the start-up torque. The experimental results showed that the motor has a start-up torque up to 1.37 Nm and rotates at 196 rpm when a constant voltage difference of 12 V is applied at a magnetic field strength of 1 T. The MR image quality was quantified by measuring the signal-to-noise of images acquired under different conditions. The results presented here indicate that the motor is MR compatible and could be used for rotating an imaging gantry or a surgical device inside the magnet.
Mixing decoded cursor velocity and position from an offline Kalman filter improves cursor control in people with tetraplegia (2013)

Kalman filtering is a common method to decode neural signals from the motor cortex. In clinical research investigating the use of intracortical brain computer interfaces (iBCIs), the technique enabled people with tetraplegia to control assistive devices such as a computer or robotic arm directly from their neural activity. For reaching movements, the Kalman filter typically estimates the instantaneous endpoint velocity of the control device. Here, we analyzed attempted arm/hand movements by people with tetraplegia to control a cursor on a computer screen to reach several circular targets. A standard velocity Kalman filter is enhanced to additionally decode for the cursor's position. We then mix decoded velocity and position to generate cursor movement commands. We analyzed data, offline, from two participants across six sessions. Root mean squared error between the actual and estimated cursor trajectory improved by 12.2 ±10.5% (pairwise t-test, p<;0.05) as compared to a standard velocity Kalman filter. The findings suggest that simultaneously decoding for intended velocity and position and using them both to generate movement commands can improve the performance of iBCIs.
The use of ancient DNA in paleontological studies (1999)

ABSTRACT In the past several years the analysis of ancient DNA has become widely used in paleontology and archeology. DNA has been reported to have been isolated from a variety of organisms up to a hundred million years old. The analysis of these DNA molecules has been used to draw conclusions about phylogenetic relationships, migration of populations, and the emergence of pathogens. It has become apparent, however, that many experimental artifacts are associated with the study of ancient DNA and in several cases the DNA purported to have been of ancient origin has been shown to be due to contamination. This review will summarize the sources of ancient DNA, the information contained within it, the methods of analysis, and the limitations of these techniques.