gebhart/patrepeval huggingface dataset:
Synthesis of Cortistatin Analogues (2009)

Cortistatins A and J display significant antiangiogenic activity. Several potent water soluble analogues were synthesized that may be suitable to treat ocular and macular degeneration and related angiogenesis-dependent afflictions. The analogue shown in the scheme exceeds the antiangiogenic potency of cortistatin A in vitro.
A theory of cerebellar cortex (1969)

1. A detailed theory of cerebellar cortex is proposed whose consequence is that the cerebellum learns to perform motor skills. Two forms of input-output relation are described, both consistent with the cortical theory. One is suitable for learning movements (actions), and the other for learning to maintain posture and balance (maintenance reflexes).2. It is known that the cells of the inferior olive and the cerebellar Purkinje cells have a special one-to-one relationship induced by the climbing fibre input. For learning actions, it is assumed that:(a) each olivary cell responds to a cerebral instruction for an elemental movement. Any action has a defining representation in terms of elemental movements, and this representation has a neural expression as a sequence of firing patterns in the inferior olive; and(b) in the correct state of the nervous system, a Purkinje cell can initiate the elemental movement to which its corresponding olivary cell responds.3. Whenever an olivary cell fires, it sends an impulse (via the climbing fibre input) to its corresponding Purkinje cell. This Purkinje cell is also exposed (via the mossy fibre input) to information about the context in which its olivary cell fired; and it is shown how, during rehearsal of an action, each Purkinje cell can learn to recognize such contexts. Later, when the action has been learnt, occurrence of the context alone is enough to fire the Purkinje cell, which then causes the next elemental movement. The action thus progresses as it did during rehearsal.4. It is shown that an interpretation of cerebellar cortex as a structure which allows each Purkinje cell to learn a number of contexts is consistent both with the distributions of the various types of cell, and with their known excitatory or inhibitory natures. It is demonstrated that the mossy fibre-granule cell arrangement provides the required pattern discrimination capability.5. The following predictions are made.(a) The synapses from parallel fibres to Purkinje cells are facilitated by the conjunction of presynaptic and climbing fibre (or post-synaptic) activity.(b) No other cerebellar synapses are modifiable.(c) Golgi cells are driven by the greater of the inputs from their upper and lower dendritic fields.6. For learning maintenance reflexes, 2(a) and 2(b) are replaced by2'. Each olivary cell is stimulated by one or more receptors, all of whose activities are usually reduced by the results of stimulating the corresponding Purkinje cell.7. It is shown that if (2') is satisfied, the circuit receptor --> olivary cell --> Purkinje cell --> effector may be regarded as a stabilizing reflex circuit which is activated by learned mossy fibre inputs. This type of reflex has been called a learned conditional reflex, and it is shown how such reflexes can solve problems of maintaining posture and balance.8. 5(a), and either (2) or (2') are essential to the theory: 5(b) and 5(c) are not absolutely essential, and parts of the theory could survive the disproof of either.
Uso de oxigênio puro e shunt veno-arterial nos oxigenadores de membrana (1997)

Cinqüenta pacientes (32 masculinos e 18 femininos) com idade variando entre 31 e 82 anos, peso entre 43 e 98 kg foram submetidos a perfusão normotérmica (34°C a 36°C) e hemodiluição, com o oxigenador de membrana (DMG). Empregou-se um shunt entre a linha arterial e venosa de modo que só uma porcentagem do sangue venoso passou pelo oxigenador. O volume do shunt foi controlado por torniquete graduado e o fluxo constantemente medido por um fluxômetro eletrônico (Biopump). Também a saturação arterial e venosa de hemoglobina foram constantemente medidas por um oxímetro (Oxisat Bentley) colocado na linha de perfusão. Além disso, foram realizadas gasometrias arterial e venosa, cada 20 a 30 min com aparelho de gasometria. O shunt foi colocado antes do filtro arterial, onde a mistura arteriovenosa se completa. O fluxo de perfusão foi mantido com drenagem livre das cavas atingindo em média 45 à 60 ml/kg de peso corporal. Obteve-se saturação arterial de hemoglobina em torno de 90% a 93% e saturação venosa entre 55% e 75%. O hematócrito foi mantido entre 25% e 35%, sendo o mínimo aceito de 20%. Para se obter esses números de saturação de hemoglobina bastou passar 50% do sangue venoso pelo oxigenador, à temperatura corporal entre 34°C e 36°C. Pelas dosagens da gasometria cada 20 min a 30 min, o PH se manteve normal em torno de 7,4, PCO2 entre 20 mmHg e 40 mmHg e PO2 arterial entre 70 mmHg a 90 mmHG. No final da perfusão, ao se aquecer o paciente para 37°C o shunt foi reduzido para ± 30%. A pressão arterial média manteve-se entre 60 mmHg a 80 mmHg. O tempo de perfusão variou de 65 min a 195 min. O sangramento pelos drenos nas primeiras 12 horas do pós-operatório foi entre 350 ml a 650 ml. Nenhum paciente apresentou qualquer grau de disfunção cerebral diagnosticado clinicamente. Houve 2 óbitos hospitalares: 1 paciente, na 2ª semana do pós-operatório, de insuficiência respiratória; outro, de infarto do miocárdio, na 4ª semana. Concluímos que o emprego do shunt veno-arterial e oxigênio puro nos oxigenadores de membrana mostrou ser método adequado para abolir o uso de ar comprimindo e blenders nesses oxigenadores, ao mesmo tempo que, teoricamente, reduz em 40% a 50% os efeitos deletérios ou inflamatórios causados pelos oxigenadores artificiais. Na hipotermia, o método pode ser usado com mais liberdade, conforme trabalho por nós publicado, utilizando oxigenadores de bolhas.
Transcriptional Regulation of the Heme Oxygenase-1 Gene Via the Stress Response Element Pathway (2003)

The heme oxygenase-1 (HO-1) enzyme catalyzes the rate-limiting reaction in the catabolism of heme yielding products with pleiotropic, but ultimately, cytoprotective activities. High levels of HO-1 are frequently detected in various pathological states and generally in states of cellular oxidative stress. Induction of HO-1, regulated at the level of gene transcription, is essential for manifestation of the enzyme's cytoprotective function. Extensive analysis of the mouse gene, and to a lesser extent of the human gene, has identified a common mechanism the stress response element (StRE)/Nrf2 transcription factor pathway for gene regulation in response to a diverse array of HO-1 inducers including the substrate heme, various environmental and industrial toxins, and plant-derived polyphenolic compounds. In addition to Nrf2 complexes, numerous dimeric transcription factors bind to the StRE, permitting induction, repression and overall fine-tuning of gene activity. In principle, the multiplicity of StRE binding proteins also provides for a range of pharmaceutical targets for controlled production of the potentially therapeutic HO-1 protein.
Aerobic biodegradation of untreated polyester–polyether urethanes by newly isolated yeast strains Exophilia sp. NS-7 and Rhodotorula sp. NS-12 (2023)

Polyester-urethanes as the most widely used polyurethanes (PUs) are among the most recalcitrant plastics in natural conditions. Among existing approaches for managing and reducing plastic waste, biodegradation as a promising approach to reduce plastic waste pollution has drawn scientific society's attention in recent years. In this study, two polyester-polyether urethane degrading yeasts were isolated and identified as two new strains of Exophilia sp. NS-7 and Rhodotorula sp. NS-12. The results showed that Exophilia sp. NS-7 is esterase, protease, and urease positive, and Rhodotorula sp. NS-12 can produce esterase and urease. Both strains can degrade Impranil<sup>®</sup> as the sole carbon source with the highest growth rate in 4-6 and 8-12 days, respectively. SEM micrograph revealed PU degradation ability in both strains by showing so many pits and holes in treated films. The Sturm test showed that these two isolates can mineralize PU to CO<sub>2</sub>, and significant decreases in N-H stretching, C-H stretching, C=O stretching, and N-H/C=O bending absorption in the molecular structure of PU were revealed by the FT-IR spectrum. The detection of the deshielding effect in chemical shifts of the H-NMR spectrum after the treatment also confirmed the destructive effects of both strains on PU films.
A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions (2019)

Genetically-engineered mouse models (GEMMs) lacking diseased-associated gene(s) globally or in a tissue-specific manner represent an attractive tool with which to assess the efficacy and toxicity of targeted pharmacological inhibitors. <i>Stat3</i> and <i>Stat5a/b</i> transcription factors have been implicated in several pathophysiological conditions, and pharmacological inhibition of both transcription factors has been proposed to treat certain diseases, such as malignancies. To model combined inhibition of <i>Stat3</i> and <i>Stat5a/b</i> we have developed a GEMM harboring a flox <i>Stat3</i>-<i>Stat5a/b</i> allele (<i>Stat5/3<sup>loxP/loxP</sup></i> mice) and generated mice lacking <i>Stat3</i> and <i>Stat5a/b</i> in hepatocytes (<i>Stat5/3<sup>Δhep</sup></i><sup>/<i>Δhep</i></sup>). <i>Stat5/3<sup>Δhep/Δhep</sup></i> mice exhibited a marked reduction of STAT3, STAT5A and STAT5B proteins in the liver and developed steatosis, a phenotype that resembles mice lacking <i>Stat5a/b</i> in hepatocytes. In addition, embryonic deletion of <i>Stat3</i> and <i>Stat5a/b</i> (<i>Stat5/3<sup>Δ</sup></i><sup>/<i>Δ</i></sup> mice) resulted in lethality, similar to <i>Stat3<sup>Δ</sup></i><sup>/<i>Δ</i></sup> mice. This data illustrates that <i>Stat5/3<sup>loxP/loxP</sup></i> mice are functional and can be used as a valuable tool to model the combined inhibition of <i>Stat3</i> and <i>Stat5a/b</i> in tumorigenesis and other diseases.
The enzyme cost of given metabolic flux distributions, as a function of logarithmic metabolite levels, is convex (2015)

Enzyme costs play a major role in the choice of metabolic routes, both in evolution and bioengineering. Given desired fluxes, necessary enzyme levels can be estimated based on known rate laws and on a principle of minimal enzyme cost. With logarithmic metabolite levels as free variables, enzyme cost functions and constraints in optimality and sampling problems can be handled easily. The set of feasible metabolite profiles forms a polytope in log-concentration space, whose points represent all possible steady states of a kinetic model. We show that enzyme cost is a convex function on this polytope. This makes enzyme cost minimization - finding optimal enzyme profiles and corresponding metabolite profiles that realize a desired flux at a minimal cost - a convex optimization problem.
Nitric Oxide Modulates Cardiac Na + Channel via Protein Kinase A and Protein Kinase G (2001)

We directly tested the effects of nitric oxide (NO) on Na(+) channels in guinea pig and mouse ventricular myocytes using patch-clamp recordings. We have previously shown that NO donors have no observed effects on expressed Na(+) channels. In contrast, NO (half-blocking concentration of 523 nmol/L) significantly reduces peak whole-cell Na(+) current (I(Na)) in isolated ventricular myocytes. The inhibitory effect of NO on I(Na) was not associated with changes in activation, inactivation, or reactivation kinetics. At the single-channel level, the reduction in macroscopic current was mediated by a decrease in open probability and/or a decrease in the number of functional channels with no change in single-channel conductance. Application of cell permeable analogs of cGMP or cAMP mimics the inhibitory effects of NO. Furthermore, the effects of NO on I(Na) can only be blocked by inhibition of both cGMP and cAMP pathways. Sulfhydryl-reducing agent does not reverse the effect of NO. In summary, although NO exerts its action via the known guanylyl cyclase (GC)/cGMP pathway, our findings provide evidence that NO can mediate its function via a GC/cGMP-independent mechanism involving the activation of adynylyl cyclase (AC) and cAMP-dependent protein kinase.
Selective reduction of sulfuric chloride: the structure of the chlorosulfite ion (1994)

N. Kuhn, H. Bohnen, D. Bläser, R. Boese and A. H. Maulitz, J. Chem. Soc., Chem. Commun., 1994, 2283 DOI: 10.1039/C39940002283
MAS platforms as an enabler of enterprise mobilisation: the state of the art (2005)

One of the main application areas for multi-agent systems technology is enterprise mobilization, wherein the main business process actors are nomadic workers. An agent's autonomy, sociality and intelligence are highly prized features when it comes to supporting those mobile workers who are geographically isolated from the main knowledge source (i.e. the corporate Intranet) and are frequently moving from one location to another. Based on experience gained from two field trials of applications (built using for multi-agent systems technology and running on lightweight handheld devices) that support mobile business processes for telecommunications service provisioning and maintenance, this paper proposes desirable metrics for any multi-agent systems platform intended for enterprise mobilisation use. These metrics are then used to compare a number of existing multi-agent systems platforms, and based on the results, this paper identifies some areas for improvement.
Associations of quantitative susceptibility mapping with Alzheimer's disease clinical and imaging markers (2020)

Altered iron metabolism has been hypothesized to be associated with Alzheimer's disease pathology, and prior work has shown associations between iron load and beta amyloid plaques. Quantitative susceptibility mapping (QSM) is a recently popularized MR technique to infer local tissue susceptibility secondary to the presence of iron as well as other minerals. Greater QSM values imply greater iron concentration in tissue. QSM has been used to study relationships between cerebral iron load and established markers of Alzheimer's disease, however relationships remain unclear. In this work we study QSM signal characteristics and associations between susceptibility measured on QSM and established clinical and imaging markers of Alzheimer's disease. The study included 421 participants (234 male, median age 70 years, range 34-97 years) from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center; 296 (70%) had a diagnosis of cognitively unimpaired, 69 (16%) mild cognitive impairment, and 56 (13%) amnestic dementia. All participants had multi-echo gradient recalled echo imaging, PiB amyloid PET, and Tauvid tau PET. Variance components analysis showed that variation in cortical susceptibility across participants was low. Linear regression models were fit to assess associations with regional susceptibility. Expected increases in susceptibility were found with older age and cognitive impairment in the deep and inferior gray nuclei (pallidum, putamen, substantia nigra, subthalamic nucleus) (betas: 0.0017 to 0.0053 ppm for a 10 year increase in age, p = 0.03 to <0.001; betas: 0.0021 to 0.0058 ppm for a 5 point decrease in Short Test of Mental Status, p = 0.003 to p<0.001). Effect sizes in cortical regions were smaller, and the age associations were generally negative. Higher susceptibility was significantly associated with higher amyloid PET SUVR in the pallidum and putamen (betas: 0.0029 and 0.0012 ppm for a 20% increase in amyloid PET, p = 0.05 and 0.02, respectively), higher tau PET in the basal ganglia with the largest effect size in the pallidum (0.0082 ppm for a 20% increase in tau PET, p<0.001), and with lower cortical gray matter volume in the medial temporal lobe (0.0006 ppm for a 20% decrease in volume, p = 0.03). Overall, these findings suggest that susceptibility in the deep and inferior gray nuclei, particularly the pallidum and putamen, may be a marker of cognitive decline, amyloid deposition, and off-target binding of the tau ligand. Although iron has been demonstrated in amyloid plaques and in association with neurodegeneration, it is of insufficient quantity to be reliably detected in the cortex using this implementation of QSM.
Post Transplant DSA: Independent Factor of Accelerated Arteriosclerosis in Kidney Transplant Population. (2014)

Background Animal models and previous reports have suggested a role for anti-HLA antibodies in the development of allograft arteriosclerosis. Our aim was to use an epidemiologic approach to model the respective non-immune and immune parameters associated with development of early arteriosclerosis post transplantation. Methods We included kidney recipients (2004-2010) having evaluation of arteriosclerosis on kidney biopsies performed at 1-year post-transplant (n=744). We assessed the determinants of severe arteriosclerosis (cv Banff score ≥2) using exhaustive evaluation of donor and recipient characteristics, traditional cardiovascular factors and immunological profile in the first year post transplant. Results Two distinct populations were identified according to allograft arteriosclerosis lesions identified at 1-year post transplantation: 1) patients with minimal arteriosclerosis (n=494); 2) patients with severe arteriosclerosis (n=250). As compared to patients with minimal arteriosclerosis, patients with severe arteriosclerosis were significantly older (45±12 vs 52±12, p<0.0001), received older donors (47±16 vs 58±13, p<0.0001) with increased rate of death by cerebrovascular disease (p<0.001), increased cold ischemia time (p<0.0001) and were more sensitized at the time of transplantation. Patients with severe arteriosclerosis and DSA had lower 8 years graft survival as compared to severe arteriosclerosis without DSA (p<0.001). The determinants ofsevere arteriosclerosis at 1 year were i) donor cardiovascular factors: age, male gender, hypertension, diabetes mellitus and dyslipidemia ii) Recipient age, Post transplant recipient systolic blood pressure, diabetes mellitus, LDL blood level iii) rejection episodes and presence of circulating DSA. In the multivariate Cox model, the factors independently associated with severe arteriosclerosis at 1 year post transplantation were: donor age (HR 1.048, p<0.0001), male donor gender (HR 1.048, p<0.0001), Recipient age (HR 1.021, p<0.0185), recipient diabetes post-transplant (HR 3.751, p<0.0042) and the presence of DSA (HR 3.262, p<0.0001). The results were replicated in an independent validation sample of 321 kidney recipients. Conclusion We defined in a large cohort a kidney transplant recipients the independent non-immune and immune determinants of accelerated arteriosclerosis post transplantation with independent association with DSA post transplant.
A Novel Behavior-Based User Authentication Scheme (2015)

User authentication is a crucial and vital part of modern computer systems and a fundamental issue of information security. For decades, most user authentication schemes used traditional username/password-based authentication, which demonstrates more disadvantages than advantages. Its drawbacks are obvious: weak passwords make the authentication system vulnerable to brute-force attacks and dictionary attacks, in which adversaries either randomly or systematically guess userâs password; and improperly stored passwords are prone to theft or tampering. Although mobile devices such as smartphones and wearables have become a recent trend, little change has been made to the traditional authentication technique. A more efficient, reliable, and user-friendly authentication scheme is needed to authenticate the identity of users. In this project, we present a new user-behavior-based authentication scheme (UBAS), which completely removes password authentication. Our scheme can determine if it is appropriate to grant a user access as the user navigates to a predefined geographical location on a digital map by using standard zooming, rotating and panning operations. The key technology behind our scheme is that it constructs the userâs behavior profile by modeling userâs fingers movement. Access will be granted to the legitimate user who not only knows the secret location, but also uses application in his or her unique and personal way. To do that, we have proposed a metric that is capable of detecting abnormal behaviors of intruders. The metric utilizes machine learning algorithms to create a profile for each legitimate user based on their behaviors.\nThe metric has the following advantages: 1) the probability of detecting normal user, as well as intruders who attempt to fool the authentication scheme are high; 2) the probability of mistakenly grant access to intruders is extremely low. Our experiments show that both the storage overhead that saves the userâs profile and the computational overhead that validate userâs identity are extremely low. It holds great promise for current mobile applications and wearable devices, where a userâs behavior data is considered as an important metric to discovery knowledge and hidden information.
Supplemental Figures and Tables from CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype (2023)

&lt;p&gt;Figure S1: HuR inhibition was successfully achieved by CRISPR/cas9 system. Figure S2: HuR inhibition sensitizes cells to drugs. Figure S3: PDA xenografts with HuR inhibition failed to form tumors. Table S1: Lists the three guide RNAs used to generate CRISPR knockout of HuR in MIA PaCa-2 and Hs 766T cell lines. Table S2: Lists the primers used to detect the mutation created by all three guide RNAs in CRISPR knockout of HuR MIA PaCa-2 and Hs 766T cell lines. Table S3: Lists the clones along with their genotypes obtained for all three guide RNAs.&lt;/p&gt;
Electrochemical and chemical oxidation of seven-coordinate Group 5 complexes (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrochemical and chemical oxidation of seven-coordinate Group 5 complexesA. M. Bond, J. W. Bixler, E. Mocellin, S. Datta, E. J. James, and S. S. WrefordCite this: Inorg. Chem. 1980, 19, 6, 1760–1765Publication Date (Print):June 1, 1980Publication History Published online1 May 2002Published inissue 1 June 1980https://pubs.acs.org/doi/10.1021/ic50208a067https://doi.org/10.1021/ic50208a067research-articleACS PublicationsRequest reuse permissionsArticle Views66Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts