gebhart/patrepeval huggingface dataset:
<strong>A Maturity Model for the Scientific Review of Clinical Trial Designs and Their Informativeness </strong> (2023)

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study&amp;rsquo;s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (&amp;ldquo;industry&amp;rdquo;), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.
Significance of Acute Posttraumatic Bony Encroachment of the Neural Canal (1989)

Neurologic status (NS) of 80 consecutive patients with acute, traumatic thoracic, thoracolumbar, or lumbar fractures was correlated with the amount of neural canal impingement (NCI) demonstrated by computerized axial tomography (CT). Average NCI was significantly higher in the 34 patients with neurologic deficits, but the range of NCI was similar to that observed in the 46 patients with no deficits. Burst fractures and fractures in the lumbar spine had the highest average NCI but the lowest percentage of patients with neurologic deficits. The immediate, posttraumatic NS of the 80 patients studied did not directly correlate with the percent of NCI demonstrated on their CT scans.
Synthesis of Conformationally Locked Versions of Puromycin Analogues (2008)

Conformationally locked North and South versions of puromycin analogues built on a bicyclo[3.1.0]hexane pseudosugar template were synthesized. The final assembly of the products was accomplished by the Staudinger-Vilarrasa coupling of the corresponding North (2 and 3) and South (6 and 7) 3'-azidopurine carbanucleosides with the Fmoc-protected 1-hydroxybenzotriazole ester of 4-methoxy-L-tyrosine. North azides 2 and 3 were reported earlier. The 3'-azido intermediates 6 and 7 that are necessary for the synthesis of the South puromycin analogues are described herein for the first time.
Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1. (1994)

The Drosophila discs large tumor suppressor protein, dlg, has been shown to regulate the growth of imaginal discs during embryogenesis [Woods, D. F. & Bryant, P. J. (1991) Cell 66, 451-464]. We cloned and sequenced the complete cDNA for a human B-lymphocyte 100-kDa protein that shares 60% amino acid identity with dlg. This human homologue of Drosophila discs large (hdlg) contains a C-terminal domain homologous to the known guanylate kinases, a src homology 3 region motif, and three dlg homology repeats. Two nonhomologous domains that can contain in-frame insertions result in at least four alternatively spliced isoforms of hdlg. Several hdlg RNA transcripts are widely distributed in human and murine tissues, and the protein is localized to regions of cell-cell contact. Protein 4.1, the defining member of a family that includes talin and merlin/schwannomin, has the same cellular localization as hdlg, and two sites within hdlg associate in vitro with the 30-kDa N-terminal domain of protein 4.1.
Variational solution of certain nonlinear eigenvalue problems (1971)

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Milestones in the history of thematic cartography, statistica l graphics, and data visualization (2008)

The graphic portrayal of quantitative information has deep roots. These roots reach into histories of thematic cartography, statistical graphics, and data visualization, which are intertwined with each other. They also connect with the rise of statistical thinking up through the 19th century, and developments in technology into the 20th century. From above ground, we can see the current fruit; we must look below to see its pedigree and germination. There certainly have been many new things in the world of visualization; but unless you know its history, everything might seem novel.
Reduction of Cyclic Carboxylic Anhydrides with Sodium Borohydride (1975)

Cyclic carboxylic anhydrides were reduced to the corresponding lactones with NaBH4. In the case of maleic anhydride (I) and 1, 8-naphthalenedicarboxylic anhydride (XIX), the reduction proceeded further and, both 2-buten-4-olide (II) and γ-butyrolactone (III) were obtained as the product. Reduction of XIX gave the lactone (XX), hemiacetal (XXI), ether (XXII), and dialcohol (XXIII). XXII was presumably derived from XXI by subsequent dehydration reaction.
A square root bound on the minimum weight in quasi-cyclic codes (1983)

We establish a square root bound on the minimum weight in the quasi-cyclic binary codes constructed by Bhargava, Tavares, and Shiva. The proof rests on viewing the codes as ideals in a group algebra over GF (4). Theorem 6 answers a question raised by F. J. MacWilliams and N. J. A. Sloane in {\em The Theory of Error-Correcting Codes.} Theorems 3, 4, and 5 provide information about the way the nonzero entries of a codeword of minimum weight are distributed among the coordinate positions.
Toll-like Receptors, NOD1, and NOD2 in Oral Epithelial Cells (2006)

Oral epithelium might be the first barrier against oral bacteria in periodontal tissue. We hypothesized that oral epithelium is endowed with innate immune receptors for bacterial components, which play roles in host defense against bacterial infection without being accompanied by excessive inflammatory responses. We found clear expression of Toll-like receptor (TLR)4 as well as TLR2, and strong expression of NOD1 and NOD2 in normal oral epithelial tissues by immunohistochemical analysis. We also showed that primary oral epithelial cells in culture expressed these molecules using PCR, flow cytometry, and immunostaining. In inflamed oral epithelium, cell-surface localizations of TLR2 and TLR4 were more clearly observed than in healthy tissue. Upon stimulation with synthetic ligands for these receptors, the expression of beta-defensin 2 was markedly up-regulated. These findings indicate that these molecules in oral epithelial cells are functional receptors that induce antibacterial responses.
Prompting by COVID-19 to Rethink the Purpose of Engineering Laboratory Education - Develop Practical Competence to Solve Real-World Problems (2020)

Today’s engineering laboratory education often lacks opportunities for students to practice critical thinking through real-world problems. This particular objective is even harder to achieve through online laboratory experiments. In this article, we summarize our innovation in using a real-world challenge, analyze big data, to empower student data analysis skills in remote teaching platform. This approach allows students to collect data, analyze, and evaluate possible solutions continuously through hands-on experimentation with accessible resources around them. Compared to the video-recorded lab, our method achieves a higher level of learning in Bloom’s taxonomy. To further improve our approach, we summarize our lesson learned from transferring six different engineering laboratory courses online, in response to the COVID-19. A thriving 21st-century learning environment has to embrace agility, create flexibility, adapt to technology, and support virtual team collaborations. © 2020
Voltage-sensitive potassium channels in Limulus ventral photoreceptors. (1978)

The steady-state slope conductance of Limulus ventral photoreceptors increases markedly when the membrane is depolarized from rest. The ionic basis of this rectification has been examined with a voltage-clamp technique. Tail currents that occur when membrane potential is repolarized after having been depolarized have been identified. The tail currents reverse direction at a voltage that becomes more positive when Ko is increased. Rectification is reduced by extracellular 4-aminopyridine and by intracellular injection of tetra-ethyl-ammonium (TEA). These results indicate that the membrane rectification around resting potential is due primarily to voltage-sensitive K+ channels. The increase in gK caused by depolarization is not mediated by a voltage-dependent rise in in Cai++, since intracellular injection of Ca++ causes a decrease rather than an increase in slope conductance. TEA can be used to examine the functional role of the K+ channels because it blocks them without substantially affecting the light-activated Na+ conductance. The effect of TEA on response-intensity curves shows that the K+ channels serve to compress the voltage range of receptor potentials.
Recovery in the Calypso file system (1996)

This article presents the deign and implementation of the recovery scheme in Calypso. Calypso is a cluster-optimized, distributed file system for UNIX clusters. As in Sprite and AFS, Calypso servers are stateful and scale well to a large number of clients. The recovery scheme in Calypso is nondisruptive, meaning that open files remain open, client modified data are saved, and in-flight operations are properly handled across server recover. The scheme uses distributed state amount the clients to reconstruct the server state on a backup node if disks are multiported or on the rebooted server node. It guarantees data consistency during recovery and provides congestion control. Measurements show that the state reconstruction can be quite fast: for example, in a 32-node cluster, when an average node contains state for about 420 files, the reconstruction time is about 3.3 seconds. However, the time to update a file system after a failure can be a major factor in the overall recovery time, even when using journaling techniques.
Traffic Measurements for Cyber Security (2017)

The articles in this special section focus on telecommunication traffic measurements for protecting network security. Computers and open communication networks have become increasingly interwoven with our daily lives and have profoundly changed our societies. While this has significantly increased people’s well being, our growing dependence on an increasingly pervasive, complex, and ever evolving network infrastructure also poses a wide range of cyber security risks with potentially large socio-economic impacts. For example, the increasing number of ill-secured networked devices in combination with growing network capacities enables miscreants to launch disruptive distributed denial of service (DDoS) attacks. Within this context, network traffic measurements and monitoring have become a crucial line of research. It enables us to enhance our understanding of cyber security threats and use this knowledge to develop new ways to detect and mitigate them. Example applications of network measurement research include the analysis of how malicious software proliferates and operates, and how it exploits users’ behavior, assessments of the effectiveness of cyber security countermeasures, of the “badness” of Internet service providers, and estimations of the revenues of cyber criminals.
THE RENAL EXCRETION OF INOSITOL BY NORMAL AND DIABETIC RATS 1 (1954)

Inositol is excreted in the urine of patients with diabetes mellitus in greatly increased amounts. Although this fact has been known since 1859, the cumbersome analytic procedures for inositol have prevented a thorough study of the mechanism of this abnormality (1). In an earlier publication from this laboratory a microbiologic assay was em- ployed in clinical studies of the urinary excretion by normnal and diabetic humi.an beings (2). The increased amounts of inositol found in the urine of diabetic patients was related to glycosuria rather than to polyuria. The renal clearance of inositol was found to be much higher in diabetic than in non-diabetic patients and the administration of large amounts of glucose intravenously to nondiabetic patients raised the renal clearance of inosi- tol to levels found in uncontrolled diabetic patients.
Biochemical Properties of Wild Mouse Oncornaviruses with Lymphomagenic and Neurotropic Activities (2015)

The close immunologic relation between the group-specific and polymerase proteins of the wild mouse derived and the established strains of mouse type C oncornaviruses, and the lack of any unusual structural polypeptide or RNA components in the wild mouse virions, eliminate the possibility of detectable contamination by a class of virus different from the mouse oncornavirus class in the wild mouse virus preparations. Liquid hybridization studies with a wild mouse viral 70S 3H-RNA and cellular DNA under conditions of DNA excess, suggest that a significant fraction but not all of the virus-specific nucleotide sequences is present in all normal and tumored wild mouse tissues tested. These virus related sequences may possibly be attributed to a hypothetical endogenous inherited type C virus genome(s) carried by all wild mice or to an infection by one or more but not all of the different exogenous strains of wild mouse type C viruses which could possibly be present in the virus preparation used. The findings are consistent with wild mouse derived type C viruses being either entirely exogenous or a mixture of endogenous and exogenous viruses. This interpretation is also consistent with the earlier observation that certain wild mouse type C viruses are exogenously transmitted, transplacentally, and via milk. The possible relation of the virus heterogeneity or the distinct characteristics of the virus surface molecules to the diverse pathogenicity of the wild mouse oncornaviruses is discussed.
Bursting a few balloons regarding the famous DARPA red balloon challenge (2022)

A balloon's-eyeperspective on a unique distributed, time-critical, geo-location problem.
Hemorrhagic Shock Primes for Increased Expression of Cytokine-Induced Neutrophil Chemoattractant in the Lung: Role in Pulmonary Inflammation Following Lipopolysaccharide (1998)

Recent studies have suggested that hemorrhagic shock followed by resuscitation renders patients more susceptible to lung injury by priming for an exaggerated response to a second stimulus, the so-called "two-hit" hypothesis. We investigated the role of C-X-C chemokines in mediating the augmented lung inflammation in response to LPS following resuscitated shock. In a rodent model, animals exposed to antecedent shock exhibited enhanced lung neutrophil sequestration and transpulmonary albumin flux in response to intratracheal LPS. This effect correlated with an exaggerated expression of cytokine-induced neutrophil chemoattractant (CINC) protein and mRNA, but not macrophage-inflammatory protein 2. Strategies designed to inhibit CINC, both anti-CINC Ab and supplementation with the antioxidant N-acetyl-cysteine, prevented the enhanced neutrophil sequestration, suggesting that CINC played a central role in the enhanced leukocyte accumulation following shock plus LPS treatment. Shock alone increased lung nuclear factor-kappaB expression and augmented the response to LPS. Prevention of this effect by N-acetylcysteine supplementation of the resuscitation fluid implicates a role for oxidant stress in the priming for lung inflammation following shock. Finally, alveolar macrophages recovered from shock-resuscitated animals released more CINC protein in vitro in response to LPS than macrophages from sham animals. Considered together, these findings show that augmented release of CINC, in part from primed alveolar macrophages, contributes significantly to the enhanced lung leukosequestration and transpulmonary albumin flux in response to LPS following resuscitated shock.
Understanding association of spleen system with earth on Traditional Chinese Medicine theory (2013)

The theory of the five elements in TCM is a kind of metaphor, which depends on observation and exploration of the natural world and experience of human beings.
Computational models for toxicity prediction (2013)

Drugs used to treat various diseases can cause dose-dependent toxicity or may cause toxicity due to drug-drug interactions in combination with other agents. Toxic effects can be classified based on the target organ or tissue that is affected. End point-based measurements of toxicants in various organs and tissues have helped identify and catalogue the toxicophores responsible for the toxic effects. This chapter reviews methods of assessing genotoxicity, cardiotoxicity, dermal toxicity, hepatotoxicity, nephrotoxicity and receptor-mediated toxicity.
Equality statements for entropy change in open systems (2007)

The entropy change of a (non-equilibrium) Markovian ensemble is calculated from (1) the ensemble phase density $p(t)$ evolved as iterative map, $p(t) = \mathbb{M}(t) p(t- Δt)$ under detail balanced transition matrix $\mathbb{M}(t)$, and (2) the invariant phase density $π(t) = \mathbb{M}(t)^{\infty} π(t) $. A virtual measurement protocol is employed, where variational entropy is zero, generating exact expressions for irreversible entropy change in terms of the Jeffreys measure, $\mathcal{J}(t) = \sum_Γ [p(t) - π(t)] \ln \bfrac{p(t)}{π(t)}$, and for reversible entropy change in terms of the Kullbach-Leibler measure, $\mathcal{D}_{KL}(t) = \sum_Γ π(0) \ln \bfrac{π(0)}{π(t)}$. Five properties of $\mathcal{J}$ are discussed, and Clausius' theorem is derived.
P129 Persistent intestinal inflammation leads to surgical intervention in Crohn's patients: a nested case-control study (2017)

Background: Disease flares and hospitalisations have been associated to the need for surgery in patients with Crohn's disease (CD). Endoscopically evident intestinal inflammation one year after diagnosis has been associated with poorer outcomes while a “top down” therapy has been shown to be more beneficial than a step-up approach. Assessing for mucosal healing endoscopically may not be feasible though in daily, routine practice while further evidence is required to support the argument that treating to target alters the disease course. In this study, we aimed to test the hypothesis that ongoing intestinal inflammation as measured by the non-invasive biomarker faecal calprotectin (FCAL) is associated with surgical resection in CD. Methods: From a large IBD cohort of patients currently under follow up at King's College Hospital, London, UK, we identified all the CD patients who were diagnosed locally and had serial FCAL in the context of their routine care (at routine appointments and during flare-ups). Utilising prospectively kept electronic patient records we identified 20 patients, meeting these monitoring criteria, who required a bowel resection for CD ≥12 months after diagnosis (cases) and matched them in a 1:2 ratio with controls based on disease duration. Flares were identified based on the physician assessment and endoscopic or radiologic findings. Continuous variables are summarised as medians followed by interquartile range. The Fisher exact test was used to compare categorical variables, the Mann-Whitney test for continuous variables and the ROC curve for diagnostic analysis. Results: Median time to surgery was 9.5 years (8, 11) [control group follow up: 8 (7, 10), p=0.28]. Right hemicolectomy was the commonest procedure (14, 70%) followed by panproctocolectomy (2, 10%), small bowel resection (2, 10%) and stricturoplasty (2, 10%). Cases and controls did not differ in clinical characteristics or anti-TNF use. Flares and hospitalisations were more common in the cases group [20 (100%) vs. 23 (56%), p=0.0005 and 19 (95%) vs. 19 (48%) p=0.0002, respectively]. The baseline median FCAL, between flares, was 348 (240, 656) in cases and 92 (52, 164) in controls (p<0.001). When measured at 1 year after diagnosis the FCAL (FCAL1) was 549 (52, 1115) and 68 (26, 184) respectively (p<0.001). The area under the curve for FCAL1 to predict surgery was 0.83, 95% CI (0.73, 0.95) while a cut off at 600μg/g provided the highest likelihood ratio [18 (15, 69)]. Conclusions: Persistent intestinal inflammation is associated with flares, hospitalisations and surgery. Our results suggest that controlling intestinal inflammation in CD may alter the natural course of the disease. FCAL performed one year after diagnosis may identify high risk patients.
Correlation between miRNA-124, miRNA-544a, and TNF-α levels in acute spinal cord injury (2022)

The present study was supported by a University-level project of Ningxia Medical University (Project Number: XY2017147).
An expandable embryonic stem cell-derived Purkinje neuron progenitor population that exhibits in vivo maturation in the adult mouse cerebellum (2017)

The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not been possible to efficiently generate Purkinje neuron (PN) progenitors from human or mouse pluripotent stem cells, let alone to develop a methodology for in vivo transplantation in the adult cerebellum. Here, we present a protocol to obtain an expandable population of cerebellar neuron progenitors from mouse embryonic stem cells. Our protocol is characterized by applying factors that promote proliferation of cerebellar progenitors. Cerebellar progenitors isolated in culture from cell aggregates contained a stable subpopulation of PN progenitors that could be expanded for up to 6 passages. When transplanted into the adult cerebellum of either wild-type mice or a strain lacking Purkinje cells (L7cre-ERCC1 knockout), GFP-labeled progenitors differentiated in vivo to establish a population of calbindin-positive cells in the molecular layer with dendritic trees typical of mature PNs. We conclude that this protocol may be useful for the generation and maturation of PNs, highlighting the potential for development of a regenerative medicine approach to the treatment of cerebellar neurodegenerative diseases.