gebhart/patrepeval huggingface dataset:
Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice (2001)

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (tau), and the first derivatives of LV pressure rise and fall (dP/dt(max) and dP/dt(min), respectively). During echocardiography, HR was lower in XK than AV mice (250 +/- 14 beats/min in XK vs. 453 +/- 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 +/- 0.08 mm in XK vs. 3.8 +/- 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 +/- 1.2% in XK vs. 40 +/- 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 +/- 24 beats/min) and XK (342 +/- 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 +/- 5 vs. 6.2 +/- 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/dt(max): 4,402 +/- 798 vs. 8,250 +/- 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (tau: 23 +/- 2 vs. 14 +/- 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.
Skill Transfer and Learning by Demonstration in a Realistic Scenario of Laparoscopic Surgery (2003)

Commercially available systems for laparoscopic surgery usually come without operator side force feedback nor instrument-side force sensory.This often leads to increased trauma of tissue.Yet another reason why such systems are not widely accepted for every-day usage is a prolonged operation time, due to time consuming micro-manipulation tasks, e.g.knot tying.We present an approach which tackles both issues.On the one hand we provide a realistic surgical environment including haptic feedback, on the other hand we present basic techniques for partial autonomy.Autonomy will be implemented by combining two established methods of human-robot instruction: learning by demonstration and primitive instantiation.Once presented by the human instructor, subtasks are generalized and partitioned in reusable primitives, which can be recombined in order to solve a priori unknown tasks.
The Mouse Model of Collagen-Induced Arthritis (2004)

Collagen-induced arthritis (CIA) is an experimental autoimmune disease that can be elicited in susceptible strains of rodents (rat and mouse) and nonhuman primates by immunization with type II collagen (CII), the major constituent protein of articular cartilage. Following immunization, these animals develop an autoimmune polyarthritis that shares several clinical and histological features with rheumatoid arthritis. Susceptibility to CIA in rodents is linked to the class II molecules of the major histocompatibility complex (MHC), and the immune response to CII is characterized by both the stimulation of collagen-specific T cells and the production of high titers of antibody specific for both the immunogen (heterologous CII) and the autoantigen (mouse CII). Histologically, murine CIA is characterized by an intense synovitis that corresponds precisely with the clinical onset of arthritis. Because of the pathological similarities between CIA and rheumatoid arthritis, the CIA model has been the subject of extensive investigation. Here, we describe the specifics for establishing the murine model of CIA, including specific requirements for the handling and preparation of the CII antigen, procedures for immunization, selection of susceptible mouse strains for study, and procedures for the evaluation and quantitation of the autoimmune arthritis.
Intraoperative measures of electrically evoked auditory nerve compound action potential. (1994)

A method for recording the electrically evoked whole-nerve action potential (EAP) at the time of cochlear implant surgery is described. Measures of EAP growth with stimulus level and functions describing the rate of recovery of the auditory nerve from the refractory state are reported for patients tested intraoperatively and for a group of patients using the ineraid implant, from whom recordings were made following implantation. Subjects tested intraoperatively were separated into three categories: congenitally deaf children (n = 14), prelingual meningitic children (n = 5), and postingual adults (n = 13). A fourth group consisted of postlingual adults (n = 14) tested postoperatively. Results from all groups showed a similar range of EAP growth and recovery rates across patients. Data from congenitally deaf children formed the exception showing steeper EAP growth functions than other subject groups. Electrically evoked whole-nerve action potential growth and recovery functions of the postoperative group of subjects showed modest correlations to speech perception scores measured after at least 18 months of implant use. The possible use of these measures in fitting an implant to an individual is discussed.
Phosphonoformate and phosphonoacetate derivatives of 5-substituted 2'-deoxyuridines: synthesis and antiviral activity (1988)

The synthesis of potential "combined prodrugs" wherein phosphonoformate or phosphonoacetate was attached to the 5'-position of 2'-deoxyuridine, 2'-deoxythymidine, 5-iodo-2'-deoxyuridine (IDU), 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), or 5-(2-bromovinyl)-2'-deoxyuridine (BVDU) or to the 3'-position of CEDU is described. The antiviral activities of these derivatives and of reference compounds were compared in Vero, HEp-2, and primary rabbit kidney cells against herpes simplex virus types 1 and 2 (HSV-1 and -2). The CEDU and BVDU analogues were also evaluated against systemic and intracutaneous HSV-1 infection in mice. The nature of the 5-substituent proved critical for antiviral activity, since only the 5-iodo-, 5-(2-bromovinyl)-, and 5-(2-chloroethyl)-substituted derivatives were inhibitory to the herpesviruses. Furthermore, the type specificity is determined by the nature of the 5-substituent: the IDU analogues were similarly inhibitory to HSV-1 and -2 whereas the CEDU and BVDU analogues inhibited HSV-2 replication only at considerably higher concentrations than HSV-1. In vivo, several derivatives were shown to possess significant antiviral activity; however, none surpassed its respective parent compound, CEDU or BVDU, in potency. It seems improbable, therefore, that a synergistic effect between PFA or PAA and the nucleoside analogue occurred. The extent of in vitro and in vivo activity of the CEDU and BVDU 5'-phosphonoformates and 5'-phosphonoacetates is most plausibly explained by the ease by which the "combined prodrugs" are hydrolyzed and the parent compound, CEDU and BVDU, respectively, is released.
Nitrogen bridgehead compounds, facile synthesis of bioactive cyanopyrimido[1,2-a]pyrimidinones. (2000)

Synthesis of some new cyanopyrimido[1,2-a]pyrimidinones 5-22 have been achieved via interaction of 2-amino-6-anisyl-5-cyano-4(3H)-pyrimidinone (1) with some heterocycles having a vicinal chloroester, chlorocyano or mercaptocyano group, dimethyl acetylenedicarboxylate, active methylene compounds, ethyl 2-acetyl-3-anisylpropenoate, ethyl 3-aryl-3-cyanopropenoates, ethyl 2-cyano-3-ethoxyacrylate and some enones or enals. Some of the isolated products were subjected to biological screening tests.
Trojan Horse Attacks on Software for Electronic Signatures (2002)

Electronic signatures are introduced by more and more countries as legally binding means for signing electronic documents with the primary hope of boosting e-commerce and e-government. Given that the underlying cryptographic methods are sufficiently strong, attacks by Trojan horse programs on electronic signatures are becoming increasingly popular. Most of the current systems either employ costly or inflexible – yet still inadequate – defence mechanisms or simply ignore the threat. A signatory has to trust the manufacturer of the software that it will work in the intended way. In the past, Trojan horse programs have shown to be of growing concern for end-user computers. Software for electronic signatures must provide protection against Trojan horses attacking the legally relevant signing process. In a survey of commercial of the shelf signature software programs we found severe vulnerabilities that can easily be exploited by an attacker. In this work we propose a secure electronic paper as a countermeasure. It is a collection of preventive and restorative methods that provides, in parallel to traditional signatures on paper, a high degree of protection of the system against untrustworthy programs. We focus our attention on Microsoft Windows NT and Windows 98, two operating systems most likely to be found on the customers' computers. The resulting system is an assembly of a small number of inexpensive building blocks that offers reliable protection against Trojan horse programs attempting to forge electronic signatures.
PLASMA ENTEROGLUCAGON, GASTRIN AND PEPTIDE YY IN CONVENTIONAL AND GERM‐FREE RATS REFED WITH A FIBRE‐FREE OR FIBRE‐SUPPLEMENTED DIET (1989)

Germ-free rats and conventional rats were starved and then refed with either an elemental diet (Flexical), or Flexical plus 30% kaolin, or Flexical plus 30% of a fibre mixture. Plasma levels of enteroglucagon, gastrin and peptide YY (PYY) were all significantly affected by diet. Enteroglucagon and especially PYY were significantly increased by the addition of fermentable fibre to the diet, but only in the conventional, not in the germ-free rats. Gastrin was not affected by the addition of fermentable fibre, but was increased by kaolin. Enteroglucagon and PYY were, however, both very much elevated in the germ-free animals, in which there is no proliferative response to fibre. Enteroglucagon and PYY levels were similar to those usually associated with extreme hyperproliferative states, indicating that it is unlikely that these hormones are involved in the proliferative response of the gastrointestinal tract to dietary fibre, and casting doubt on their role in other responses.
Carrier Generation in Multicomponent Wide-Bandgap Oxides: InGaZnO4 (2013)

To exploit the full potential of multicomponent wide-bandgap oxides, an in-depth understanding of the complex defect chemistry and of the role played by the constituent oxides is required. In this work, thorough theoretical and experimental investigations are combined in order to explain the carrier generation and transport in crystalline InGaZnO4. Using first-principles density functional approach, we calculate the formation energies and transition levels of possible acceptor and donor point defects as well as the implied defect complexes in InGaZnO4 and determine the equilibrium defect and electron densities as a function of growth temperature and oxygen partial pressure. An excellent agreement of the theoretical results with our Brouwer analysis of the bulk electrical measurements for InGaZnO4 establishes the Ga antisite defect, GaZn, as the major electron donor in InGaZnO4. Moreover, we show that the oxygen vacancies, long believed to be the carrier source in this oxide, are scarce. The proposed carrier generation mechanism also explains the observed intriguing behavior of the conductivity in In-rich vs Ga-rich InGaZnO4.
Synthetic antibodies neutralize SARS-CoV-2 infection of mammalian cells (2020)

ABSTRACT Coronaviruses (CoV) are a large family of enveloped, RNA viruses that circulate in mammals and birds. Three highly pathogenic strains have caused zoonotic infections in humans that result in severe respiratory syndromes including the Middle East Respiratory Syndrome CoV (MERS), Severe Acute Respiratory Syndrome CoV (SARS), and the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. Here, we describe a panel of synthetic monoclonal antibodies, built on a human IgG framework, that bind to the spike protein of SARS-CoV-2 (the causative agent of COVID-19), compete for ACE2 binding, and potently inhibit SARS-CoV-2. All antibodies that exhibited neutralization potencies at sub-nanomolar concentrations against SARS-CoV-2/USA/WA1 in Vero E6 cells, also bound to the receptor binding domain (RBD), suggesting competition for the host receptor ACE2. These antibodies represent strong immunotherapeutic candidates for treatment of COVID-19.
Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients (2015)

Clinicaltrials.gov NCT01284322.
A Key Role of Adenosine Diphosphate in the Irreversible Platelet Aggregation Induced by the PAR1-Activating Peptide Through the Late Activation of Phosphoinositide 3-Kinase (1999)

Abstract Although adenosine diphosphate (ADP), per se, is a weak platelet agonist, its role as a crucial cofactor in human blood platelet functions has now been clearly demonstrated in vitro and in vivo. The molecular basis of the ADP-induced platelet activation is starting to be understood since the discovery that 2 separate P2 purinergic receptors may be involved simultaneously in the activation process. However, little is known about how ADP plays its role as a cofactor in platelet activation and which signaling pathway initiated by a specific agonist can be modulated by the released ADP. To investigate these points, we took advantage of a model of platelet activation through the thrombin receptor PAR1 in which both ADP scavengers and phosphoinositide 3-kinase (PI 3-kinase) inhibitors have been shown to transform the classical irreversible aggregation into a reversible one. We have observed that, among the different PI 3-kinase products, the accumulation of phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2] was dramatically and specifically attenuated when ADP was removed by apyrase treatment. A comparison between the effects of PI 3-kinase inhibitors and apyrase strongly suggest that the late, ADP-dependent, PtdIns(3,4)P2accumulation is necessary for PAR1-induced irreversible aggregation. Using selective antagonists, we found that the effect of ADP was due to the ADP receptor coupled to inhibition of adenylyl cyclase. Finally, we found that both ADP and PI 3-kinase play an important role in PAR1-dependent reorganization of the cytoskeleton through a control of myosin heavy chain translocation and the stable association of signaling complexes with the actin cytoskeleton.
Anti-Stokes photoluminescence of InP self-assembled quantum dots in the presence of electric current (1999)

An intense anti-Stokes photoluminescence was observed in a structure with InP quantum dots (QD's) in the presence of both a direct electric current and optical pumping below the lowest electron-hole transition in quantum dots. The discovered phenomenon provides clear evidence of deep energy levels in the vicinity of the QD's. A simple model was proposed which allowed us to estimate the energies of the deep states and the lower limit of the product of the electron and hole relaxation rates from the QD's to the deep states.
Ninety-six hour ketamine infusion with co-administered clonidine for treatment-resistant depression: A pilot randomised controlled trial (2016)

Objectives We examined the feasibility of a high-dose, 96-h infusion of ketamine in treatment-resistant depression. Methods Ten participants were randomised to receive a 96-h ketamine infusion, titrated as tolerated to a target rate of 0.6 mg/kg/h, while 10 received a 40-min ketamine infusion (0.5 mg/kg). Both groups received clonidine, titrated to a maximum of 0.6 mg orally daily, during the infusion to mitigate side effects of ketamine. Participants were followed for 8 weeks to examine potential antidepressant effects. Results All 20 participants completed the infusion. Most participants tolerated the infusion well, with minimal psychotomimetic symptoms or blood pressure elevation despite achieving high ketamine concentrations (mean 424 ng/ml for 96-h arm, 156 ng/ml for 40-min arm). There was no rebound hypertension upon discontinuing clonidine. Rapid and sustained improvement in depressive symptoms was observed in both study groups. Higher ketamine concentration was associated with sustained antidepressant response, and was not with greater psychotomimetic side effects, in the 96-h arm. Conclusions This study provides evidence for the feasibility of prolonged ketamine infusions in treatment-resistant depression. Co-administration of clonidine appeared to mitigate ketamine's psychotomimetic effects. Further study is required to investigate the extent to which prolonged ketamine infusions could provide both rapid and sustained improvements in treatment-resistant depression. Clinicaltrials.gov identifier NCT01179009.
Monitoring the Response of Orthotopic Bladder Tumors to Granulocyte Macrophage Colony-Stimulating Factor Therapy Using the Prostate-Specific Antigen Gene as a Reporter (2004)

MB49 cells modified to secrete PSA are a reliable method to evaluate therapeutic modalities for bladder cancer.
Temporally Controlled Site-Specific Mutagenesis in the Germ Cell Lineage of the Mouse Testis1 (2003)

We have obtained a PrP-Cre-ER(T) transgenic mouse line (28.8) that selectively expresses in testis the tamoxifen-inducible Cre-ER(T) recombinase under the control of a mouse Prion protein (PrP) promoter-containing genomic fragment. Cre-ER(T) is expressed in spermatogonia and spermatocytes, but not in Sertoli and Leydig cells. We also established reporter PrP-L-EGFP-L transgenic mice harboring a LoxP-flanked enhanced green fluorescent protein (EGFP) Cre reporter cassette under the control of the same PrP promoter-containing genomic fragment that exhibits prominent EGFP expression in brain and testis. Using the PrP-L-EGFP-L as well as other Cre-reporter mice, we demonstrate that tamoxifen administration efficiently and selectively induces Cre-mediated recombination in the germ cell lineage. The established PrP-Cre-ER(T) line should provide a valuable tool for studying functions of germ cell-expressed genes involved in spermatogenesis.
Overview of single-cell analyses: microdevices and applications (2010)

Numerous microdevices developed for single-cell analyses have been presented in the last decades. Practical usefulness in biological and clinical settings has become an important focus during the development and implementation of new structures and assays. Single-cell analysis has been applied in intracellular research, gene- and protein content and expression, PCR, cell culture and division, clone formation, differentiation, morphology, lysis, separation, sorting, cytotoxicity and fluorescence screens, antibody secretion, etc. as discussed here along with brief descriptions of the technical devices used for the studies, e.g. well-, trap-, pattern-, and droplet-based structures. This review aims to serve as an overview of available techniques for single-cell analysis by describing the different biological single-cell assays that have been performed to date and how each individual application requires a particular device design.
Structure-Based Design and Synthesis of High Affinity Tripeptide Ligands of the Grb2-SH2 Domain (1998)

The X-ray structure of the Grb2-SH2 domain in complex with a specific phosphopeptide ligand has revealed the existence of an extended hydrophobic area adjacent to the primary binding site of the ligand on the SH2 domain. This has been exploited to design hydrophobic C-terminal groups that improve the binding affinity of the minimal sequence pTyr-Ile-Asn recognized by the Grb2-SH2 domain. The most significant increase in affinity (25-fold compared to that of the reference peptide having a nonsubstituted carboxamide C-terminus) was obtained with a 3-naphthalen-1-yl-propyl group which was predicted to have the largest contact area with the SH2 domain hydrophobic region. This modification combined with replacement of the minimal sequence isoleucine residue by 1-aminocyclohexane carboxylic acid to stabilize the beta-turn conformation required for recognition by the Grb2-SH2 domain resulted in the high affinity (47 nM in an ELISA assay) and selective phosphopeptide Ac-pTyr-Ac6c-Asn-NH(3-naphthalen-1-yl-propyl).
Targeting MCL-1 sensitizes FLT3-ITD-positive leukemias to cytotoxic therapies (2012)

Patients suffering from acute myeloid leukemias (AML) bearing FMS-like tyrosine kinase-3-internal tandem duplications (FLT3-ITD) have poor outcomes following cytarabine- and anthracyclin-based induction therapy. To a major part this is attributed to drug resistance of FLT3-ITD-positive leukemic cells. Against this background, we have devised an antibody array approach to identify proteins, which are differentially expressed by hematopoietic cells in relation to activated FLT3 signaling. Selective upregulation of antiapoptotic myeloid cell leukemia-1 (MCL-1) was found in FLT3-ITD-positive cell lines and primary mononuclear cells from AML patients as compared with FLT3-wild-type controls. Upregulation of MCL-1 was dependent on FLT3 signaling as confirmed by its reversion upon pharmacological inhibition of FLT3 activity by the kinase inhibitor PKC412 as well as siRNA-mediated suppression of FLT3. Heterologously expressed MCL-1 substituted for FLT3 signaling by conferring resistance of hematopoietic cells to antileukemia drugs such as cytarabine and daunorubicin, and to the proapoptotic BH3 mimetic ABT-737. Conversely, suppression of endogenous MCL-1 by siRNA or by flavopiridol treatment sensitized FLT3-ITD-expressing hematopoietic cells to cytotoxic and targeted therapeutics. In conclusion, MCL-1 is an essential effector of FLT3-ITD-mediated drug resistance. Therapeutic targeting of MCL-1 is a promising strategy to overcome drug resistance in FLT3-ITD-positive AML.
Predictions and systematizations of the zinc-blende–wurtzite structural energies in binary octet compounds (1992)

To systematize the wurtzite (W) versus zinc blende (ZB) structural preferences among the binary octet compounds, we have calculated the correponding energy difference \ensuremath{\Delta}${\mathit{E}}_{\mathit{W}\mathrm{\ensuremath{-}}\mathrm{ZB}}^{\mathrm{LDF}}$(AB) for thirteen AB compounds using the local-density formalism (LDF). We then uncovered a linear scaling betwteen \ensuremath{\Delta}${\mathit{E}}_{\mathit{W}\mathrm{\ensuremath{-}}\mathrm{ZB}}^{\mathrm{LDF}}$ and an atomistic orbital-radii coordinate R\ifmmode \tilde{}\else \~{}\fi{}(A,B) that can be simply calculated from the properties of the free A and B atoms. This permits predictions of W-ZB energy differences for all binary compounds and exposes simple chemical trends, including the stabilization of the ZB form in the sequence B=O\ensuremath{\rightarrow}S\ensuremath{\rightarrow}Se\ensuremath{\rightarrow}Te for ${\mathit{A}}^{\mathrm{II}}$${\mathit{B}}^{\mathrm{VI}}$ and A=Ga\ensuremath{\rightarrow}Al\ensuremath{\rightarrow}In for ${\mathit{A}}^{\mathrm{III}}$${\mathit{B}}^{\mathrm{V}}$'s. We propose new structural assignments for the low-temperature ground state of CdSe (ZB) and MgTe (NiAs type).