gebhart/patrepeval huggingface dataset:
Planning for change in a formal verification of the raft consensus protocol (2016)

We present the first formal verification of state machine safety for the Raft consensus protocol, a critical component of many distributed systems. We connected our proof to previous work to establish an end-to-end guarantee that our implementation provides linearizable state machine replication. This proof required iteratively discovering and proving 90 system invariants. Our verified implementation is extracted to OCaml and runs on real networks. The primary challenge we faced during the verification process was proof maintenance, since proving one invariant often required strengthening and updating other parts of our proof. To address this challenge, we propose a methodology of planning for change during verification. Our methodology adapts classical information hiding techniques to the context of proof assistants, factors out common invariant-strengthening patterns into custom induction principles, proves higher-order lemmas that show any property proved about a particular component implies analogous properties about related components, and makes proofs robust to change using structural tactics. We also discuss how our methodology may be applied to systems verification more broadly.
Antihypertensive effect of alcohol in spontaneously hypertensive rats. (1989)

The influence of ethanol (alcohol) consumption on blood pressure during and after the development of hypertension was examined by using spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP). Normotensive Wistar-Kyoto (WKY) rats were also used for comparison. Substituting alcohol (5-20%) for drinking water at 1 month of age retarded the age-dependent rise of blood pressure in all three strains so that, at 7 months, blood pressure measured by a tail-cuff method was 24 mm Hg, 26 mm Hg, and 41 mm Hg lower in the alcohol-treated WKY rats, SHR, and SHRSP, respectively, than in untreated rats. Significant differences in blood pressure were seen in each strain after only 3 months. Withdrawal of alcohol at this stage caused an acute rise of blood pressure then a return to subnormal levels, which persisted for a further 3 months. Administration of 15% alcohol to adult WKY rats and SHR for 2 months had no significant effect on blood pressure. Increasing alcohol content to 20% for a further 2 months prevented rises of blood pressure in both strains. Thus, although continuous drinking of alcohol does not lower blood pressure, it appears to counteract the development of hypertension in rats.
Anti-HIV-1 Integrase Drugs How Far from the Shelf (2000)

Chemotherapy of HIV-1 infection/AIDS currently employs inhibitors of two products of the viral pol gene, the reverse transcriptase and protease enzymes. However, a third product of the pol gene is essential for retroviral multiplication, the integrase. As no cellular homologue of HIV integrase has been described, potential inhibitors could be relatively nontoxic. Development of HIV-1 integrase inhibitors could have favorable implication for combination therapy, including potential synergy with currently available inhibitors, as well as prevention of the chronic carrier state and the emergence of resistant mutants. Although several classes of putative integrase inhibitors that been described, still no clinically useful anti-integration drugs are available. It is the structural and functional complexity of the integration process together with the limitations of the available in vitro assays that has made it problematic to develop inhibitors of the HIV integrase. In this review we summarize current knowledge concerning the biology of this enzyme and of the integration process, and discuss major classes representatives of integrase inhibitors considering the obstacles to the development of true anti-integrase drugs. Keywords: Anti HIV 1 Integrase Drugs, reverse transcriptase, protease enzymes, histidine cysteine, Integration Process, versus PIC Based assay, HIV 1 Gag Pol gene, vesicular stomatitis virus G, DNA Binders, Integrase Inhibitors, diffeoylquinic acid DCQA CAPE, Chicoric, Nucleotide Analogs Oligonucleotides, azidothymidine AZT, dideoxycytidine monophosphate ddCMP, Fluoro, Hydroxylated Aromatics, sulfated compounds, analogues, vitamin B12, Hydroxycobalamin, Methylcobalamin, adenosylcobalamin, dicyanocobinamide, HIV 1 multiplication, Thiazolothiazepines, Human immunodeficiency virus, Transcripatase, integrase, protease, recombinant IN, pre integration complex, moloney murine leukemia virus, barrier to autointegration factor, aurintricarboxylic acid, quinalizarin, 2 Phosphonylmethoxyethyl guanine
Enhanced tumor control following sequential treatments of photodynamic therapy (PDT) and localized microwave hyperthermia in vivo (1984)

Photodynamic therapy (PDT), or photoradiation therapy (PRT), utilizing hematoporphyrin derivative (HPD) as photosensitizer and an argon-dye laser system as the light source, was used alone and in combination with localized microwave hyperthermia (2450 MHz) to treat axillary tumors of the SMT-F mammary carcinoma in mice. Thirty-minute heat treatments were applied either immediately before or immediately after a standard PDT treatment of 630 nm light at 75 mW/cm2 for 30 min (135 J/cm2) given 24 hr post-7.5 mg/kg HPD, intraperitoneally (i.p.). Tumor control as judged by lack of tumor regrowth 35 days or longer after the combined treatments was compared to that following each treatment when given alone. Little or no enhancement of tumor control was seen when sublethal temperatures of 37.5, 38.5, and 39.5 degrees C were applied for 30 min immediately following the PDT treatment. However, increasing levels of enhancement were seen when heat treatments of 40.5 and 41.5 degrees C or 44.5 degrees C, given for 30 min, were applied immediately before or after the photodynamic treatment.
The Notch 3 intracellular domain represses Notch 1-mediated activation through Hairy/Enhancer of split (HES) promoters (1999)

The Notch signaling pathway is important for cellular differentiation. The current view is that the Notch receptor is cleaved intracellularly upon ligand activation. The intracellular Notch domain then translocates to the nucleus, binds to Suppressor of Hairless (RBP-Jk in mammals), and acts as a transactivator of Enhancer of Split (HES in mammals) gene expression. In this report we show that the Notch 3 intracellular domain (IC), in contrast to all other analysed Notch ICs, is a poor activator, and in fact acts as a repressor by blocking the ability of the Notch 1 IC to activate expression through the HES-1 and HES-5 promoters. We present a model in which Notch 3 IC interferes with Notch 1 IC-mediated activation at two levels. First, Notch 3 IC competes with Notch 1 IC for access to RBP-Jk and does not activate transcription when positioned close to a promoter. Second, Notch 3 IC appears to compete with Notch 1 IC for a common coactivator present in limiting amounts. In conclusion, this is the first example of a Notch IC that functions as a repressor in Enhancer of Split/HES upregulation, and shows that mammalian Notch receptors have acquired distinct functions during evolution.
Circulating endothelial cells in oncology: pitfalls and promises (2008)

Adequate blood supply is a prerequisite in the pathogenesis of solid malignancies. As a result, depriving a tumour from its oxygen and nutrients, either by preventing the formation of new vessels, or by disrupting vessels already present in the tumour, appears to be an effective treatment modality in oncology. Given the mechanism by which these agents exert their anti-tumour activity together with the crucial role of tumour vasculature in the pathogenesis of tumours, there is a great need for markers properly reflecting its impact. Circulating endothelial cells (CEC), which are thought to derive from damaged vasculature, may be such a marker. Appropriate enumeration of these cells appears to be a technical challenge. Nevertheless, first studies using validated CEC assays have shown that CEC numbers in patients with advanced malignancies are elevated compared to healthy controls making CEC a potential tool for among other establishing prognosis and therapy-induced effects. In this review, we will address the possible clinical applications of CEC detection in oncology, as well as the pitfalls encountered in this process.
13C NMR spectra of some substituted furo[3,2‐b] pyrroles (1990)

Abstract 13 C chemical shifts for 16 derivatives of furo[3,2‐ b ] pyrrole substituted at positions 2, 4 and 5 are reported. The J (CH) values were determined for some derivatives. Heterocorrelated 2D 1 H‐ 13 C NMR spectra, selective heteronuclear decoupling and selective INEPT experiments were used for signal assignment.
Reduced receptor binding by a human interferon-gamma fragment lacking 11 carboxyl-terminal amino acids. (1987)

Treatment of recombinant human interferon-gamma (IFN-gamma) with either 1) the arginine-specific proteases clostripain or submaxillaris protease or 2) the broadly specific enzyme pronase produced a stable fragment with m.w. of 15,500. Structural analysis showed that the cleavage occurred between residues 129 and 130 and thus produced a fragment lacking only 11 carboxyl-terminal amino acids. The fragmented and untreated molecules showed identical amino-terminal amino acid sequences and were equally reactive with either polyclonal or monoclonal anti-IFN-gamma. IFN-gamma lacking carboxyl-terminal amino acids displayed a 1000- to 2000-fold reduction in its capacity to bind to cellular IFN-gamma receptors at 4 degrees C. Functionally the fragment showed a 50-fold reduction in its ability to induce antiviral activity in fibroblasts and a 10-fold reduction in its ability to induce Fc receptors on the human histiocytic lymphoma cell line U937. These results thus suggest that the carboxyl terminus of human IFN-gamma contributes significantly to the formation of the receptor-binding site of the molecule.
Aldose Reductase-Regulated Tumor Necrosis Factor-α Production Is Essential for High Glucose-Induced Vascular Smooth Muscle Cell Growth (2007)

Diabetes is associated with increased generation of cytokines and tissue inflammation, but it is unclear how increased cytokine synthesis is causally related to the development of diabetic complications. Here, we report that exposure to high (25 mm) glucose, but not iso-osmotic concentrations of mannitol or 3-methyl glucose, increased TNF-alpha secretion by rat and human aortic smooth muscle cells in culture. The increase in TNF-alpha production was prevented by actinomycin D and cycloheximide, indicating transcriptional activation of TNF-alpha gene. High glucose (HG)-induced TNF-alpha release was specifically inhibited by protein kinase C (PKC)-delta inhibitor (Rottlerin; EMD Biosciences, San Diego, CA), but not PKC-beta2 inhibitor (CGP53353; Tocris Cookson Inc., Ellisville, MO), indicating the possible involvement of PKC-delta in HG signaling. TNF-alpha secretion was also prevented by pretreating cells with aldose reductase (AR) inhibitors, sorbinil or tolrestat and in cells treated with antisense AR mRNA. Inhibition of AR also prevented the increase in TNF-alpha mRNA. Addition of anti-TNF-alpha antibodies or soluble TNF-alpha receptors 1 and 2 to the medium or RNA interference ablation of TNF-alpha attenuated nuclear factor-kappaB activation and prevented HG-stimulated cell growth. These data indicate that AR is required for HG-induced TNF-alpha synthesis and release. In vivo, the release of TNF-alpha by HG leading to autocrine stimulation of TNF-alpha synthesis may be a critical step in the development of the cardiovascular complications of diabetes. Interruption of the autocrine effects of TNF-alpha may be a useful strategy for treating diabetic vasculopathies.
Compressed detection for ultra-wideband impulse radio (2007)

The emerging theory of compressed sensing (CS) not only enables the reconstruction of sparse signals from a small set of random measurements [1, 2], but also provides an universal signal detection approach at sub-Nyquist sampling rates [3, 4]. Compressed signal detection is particularly suitable for impulse ultra-wideband (I-UWB) communications where Nyquist sampling of the signal is a formidable challenge [5]. In this paper, we propose a generalized likelihood ratio test (GLRT) detector for I-UWB receivers based on compressive measurements. Pilot symbol assisted modulation is proposed where received signals are randomly projected and subsequently correlated for data demodulation. The proposed receiver is simple to implement, which has the advantage that neither wideband delay lines nor ultra-fast analog to digital converters (ADC) are required. Given a channel realization, the exact bit error probability (BEP) of the proposed receiver is derived. Approximate BEP is also derived under the Gaussian assumption. Simulation results show that the proposed receiver with moderate compressive measurements has comparable performance to traditional analog autocorrelation (AcR) receivers [6, 7].
Characterization of Adeno-Associated Virus Genomes Isolated from Human Tissues (2005)

Infection with wild-type adeno-associated virus (AAV) is common in humans, but very little is known about the in vivo biology of AAV. On a molecular level, it has been shown in cultured cells that AAV integrates in a site-specific manner on human chromosome 19, but this has never been demonstrated directly in infected human tissues. To that end, we tested 175 tissue samples for the presence of AAV DNA, and when present, examined the specific form of the viral DNA. AAV was detected in 7 of 101 tonsil-adenoid samples and in 2 of 74 other tissue samples (spleen and lung). In these nine samples, we were unable to detect AAV integration in the AAVS1 locus using a sensitive PCR assay designed to amplify specific viral-cellular DNA junctions. Additionally, we used a second complementary assay, linear amplification-mediated-PCR (LAM-PCR) to widen our search for integration events. Analysis of individual LAM-PCR products revealed that the AAV genomes were arranged predominantly in a head-to-tail array, with deletions and extensive rearrangements in the inverted terminal repeat sequences. A single AAV-cellular junction was identified from a tonsil sample and it mapped to a highly repetitive satellite DNA element on chromosome 1. Given these data, we entertained the possibility that instead of integrated forms, AAV genomes were present as extrachromosomal forms. We used a novel amplification assay (linear rolling-circle amplification) to show that the majority of wild-type AAV DNA existed as circular double-stranded episomes in our tissues. Thus, following naturally acquired infection, AAV DNA can persist mainly as circular episomes in human tissues. These findings are consistent with the circular episomal forms of recombinant AAV vectors that have been isolated and characterized from in vivo transduced tissues.
Improving The Brain Delivery of Gold Nanoparticles by Conjugation with An Amphipathic Peptide (2010)

In this article, we have shown that conjugation of 12 nm GNPs with the amphipathic peptide CLPFFD increases the in vivo penetration of these particles to the rat brain. The C(GNP)-LPFFD conjugates showed a smaller negative charge and a greater hydrophobic character than citrate-capped GNPs of the same size. We administered intraperitoneal injections of citrate GNPs and C(GNP)-LPFFD in rats, and determined the gold content in the tissues by neutron activation. Compared with citrate GNPs, the C(GNP)-LPFFD conjugate improved the delivery to the brain, increasing the concentration of gold by fourfold, while simultaneously reducing its retention by the spleen 1 and 2 h after injection. At 24 h, the conjugate was partially cleared from the brain, and mainly accumulated in the liver. The C(GNP)-LPFFD did not alter the integrity of the blood-brain barrier, and had no effect on cell viability.
Electric‐Field‐Responsive Handle for Large‐Area Orientation of Discotic Liquid‐Crystalline Molecules in Millimeter‐Thick Films (2011)

Current events: An electric-field-responsive handle (see picture) was developed that enables large-area and millimeter-thick unidirectional orientation of columnarly assembled π-conjugated liquid-crystalline molecules. The handles in the columns are hydrogen-bonded and align along the direction of an applied electric field.
On Choosing and Bounding Probability Metrics (2002)

Summary When studying convergence of measures, an important issue is the choice of probability metric. We provide a summary and some new results concerning bounds among some important probability metrics/distances that are used by statisticians and probabilists. Knowledge of other metrics can provide a means of deriving bounds for another one in an applied problem. Considering other metrics can also provide alternate insights. We also give examples that show that rates of convergence can strongly depend on the metric chosen. Careful consideration is necessary when choosing a metric.
iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease (2017)

In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer's disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development.
Evaluation ofOchrobactrum anthropiTRS-2 and its talc based formulation for enhancement of growth of tea plants and management of brown root rot disease (2009)

Ochrobactrum anthropi and its talc based formulation can be considered as an addition to available plant growth promoting rhizobacteria (PGPR) currently being used for field application. The present study offers a scope of utilizing this bacterium for growth promotion and disease management which would help in reduction of the use of chemicals in tea plantations.
Effects of Standardization of Whole Milk with Dry Milk Protein Concentrate on the Yield and Ripening of Reduced-Fat Cheddar Cheese (2003)

Commercial milk protein concentrate (MPC) was used to standardize whole milk for reduced-fat Cheddar cheesemaking. Four replicate cheesemaking trials of three treatments (control, MPC1, and MPC2) were conducted. The control cheese (CC) was made from standardized milk (casein-to-fat ratio, C/F approximately 1.7) obtained by mixing skim milk and whole milk (WM); MPC1 and MPC2 cheeses were made from standardized milk (C/F approximately 1.8) obtained from mixing WM and MPC, except that commercial mesophilic starter was added at the rate of 1% to the CC and MPC1 and 2% to MPC2 vats. The addition of MPC doubled cheese yields and had insignificant effects on fat recoveries (approximately 94% in MPC1 and MPC2 vs. approximately 92% in CC) but increased significantly total solids recoveries (approximately 63% in CC vs. 63% in MPC1 and MPC2). Although minor differences were noted in the gross composition of the cheeses, both MPC1 and MPC2 cheeses had lower lactose contents (0.25 or 0.32%, respectively) than in CC (0.60%) 7 d post manufacture. Cheeses from all three treatments had approximately 10(9) cfu/g initial starter bacteria count. The nonstarter lactic acid bacteria (NSLAB) grew slowly in MPC1 and MPC2 cheeses during ripening compared to CC, and at the end of 6 mo of ripening, numbers of NSLAB in the CC were 1 to 2 log cycles higher than in MPC1 and MPC2 cheeses. Primary proteolysis, as noted by water-soluble N contents, was markedly slower in MPC1 and MPC2 cheeses compared to CC. The concentrations of total free amino acids were in decreasing order CC > MPC2 > MPC1 cheeses, suggesting slower secondary proteolysis in the MPC cheeses than in CC. Sensory analysis showed that MPC cheeses had lower brothy and bitter scores than CC. Increasing the amount of starter bacteria improved maturity in MPC cheese.
A stabilized conforming nodal integration for Galerkin mesh-free methods (2000)

Domain integration by Gauss quadrature in the Galerkin mesh-free methods adds considerable complexity to solution procedures. Direct nodal integration, on the other hand, leads to a numerical instability due to under integration and vanishing derivatives of shape functions at the nodes. A strain smoothing stabilization for nodal integration is proposed to eliminate spatial instability in nodal integration. For convergence, an integration constraint (IC) is introduced as a necessary condition for a linear exactness in the mesh-free Galerkin approximation. The gradient matrix of strain smoothing is shown to satisfy IC using a divergence theorem. No numerical control parameter is involved in the proposed strain smoothing stabilization. The numerical results show that the accuracy and convergent rates in the mesh-free method with a direct nodal integration are improved considerably by the proposed stabilized conforming nodal integration method. It is also demonstrated that the Gauss integration method fails to meet IC in mesh-free discretization. For this reason the proposed method provides even better accuracy than Gauss integration for Galerkin mesh-free method as presented in several numerical examples. Copyright © 2001 John Wiley & Sons, Ltd.
Beraprost Sodium, a Prostaglandin I2 Analogue, Protects Against Advanced Glycation End Products-induced Injury in Cultured Retinal Pericytes (2002)

The results demonstrated that cyclic AMP-elevating agents such as beraprost sodium and forskolin protected retinal pericytes from AGE-induced cytotoxicity through its anti-oxidative properties. Our present study suggests that beraprost sodium may have therapeutic potentials in treatment of patients with early diabetic retinopathy.
Transferrin-Liposome-Mediated Systemic p53 Gene Therapy in Combination with Radiation Results in Regression of Human Head and Neck Cancer Xenografts (1999)

The use of cationic liposomes as nonviral vehicles for the delivery of therapeutic molecules is becoming increasingly prevalent in the field of gene therapy. We have previously demonstrated that the use of the transferrin ligand (Tf) to target a cationic liposome delivery system resulted in a significant increase in the transfection efficiency of the complex [Xu, L., Pirollo, K.F., and Chang, E.H. (1997). Hum. Gene Ther. 8, 467-475]. Delivery of wild-type (wt) p53 to a radiation-resistant squamous cell carcinoma of the head and neck (SCCHN) cell line via this ligand-targeted, liposome complex was also able to revert the radiation resistant phenotype of these cells in vitro. Here we optimized the Tf/liposome/DNA ratio of the complex (LipT) for maximum tumor cell targeting, even in the presence of serum. The efficient reestablishment of wtp53 function in these SCCHN tumor cells in vitro, via the LipT complex, restored the apoptotic pathway, resulting in a significant increase in radiation-induced apoptosis that was directly proportional to the level of exogenous wtp53 in the tumor cells. More significantly, intravenous administration of LipT-p53 markedly sensitized established SCCHN nude mouse xenograft tumors to radiotherapy. The combination of systemic LipT-p53 gene therapy and radiation resulted in complete tumor regression and inhibition of their recurrence even 6 months after the end of all treatment. These results indicate that this tumor-specific, ligand-liposome delivery system for p53 gene therapy, when used in concert with conventional radiotherapy, can provide a new and more effective means of cancer treatment.