gebhart/patrepeval huggingface dataset:
Succinct Non-Interactive Zero Knowledge for a von Neumann Architecture (2013)

We build a system that provides succinct non-interactive zero-knowledge proofs (zk-SNARKs) for program executions on a von Neumann RISC architecture. The system has two components: a cryptographic proof system for verifying satisfiability of arithmetic circuits, and a circuit generator to translate program executions to such circuits. Our design of both components improves in functionality and efficiency over prior work, as follows. Our circuit generator is the first to be universal: it does not need to know the program, but only a bound on its running time. Moreover, the size of the output circuit depends additively (rather than multiplicatively) on program size, allowing verification of larger programs. The cryptographic proof system improves proving and verification times, by leveraging new algorithms and a pairing library tailored to the protocol. We evaluated our system for programs with up to 10,000 instructions, running for up to 32,000 machine steps, each of which can arbitrarily access random-access memory; and also demonstrated it executing programs that use just-in-time compilation. Our proofs are 230 bytes long at 80 bits of security, or 288 bytes long at 128 bits of security. Typical verification time is 5 milliseconds, regardless of the original program’s running time.
Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson’s Disease (2012)

Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-κB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21(rac), but not p21(ras), attenuated the production of ROS from activated microglia. Inhibition of both p21(ras) and p21(rac) activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21(ras) and p21(rac)in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Oral administration of NaPB reduced nigral activation of p21(ras) and p21(rac), protected nigral reduced glutathione, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders.
Oscillating Stereocontrol: A Strategy for the Synthesis of Thermoplastic Elastomeric Polypropylene (1995)

A strategy has been developed for the synthesis of thermoplastic elastomeric polypropylene based on the catalytic activity of the unbridged metallocene bis(2-phenylindenyl)zirconium dichloride [(2-PhInd)(2)ZrCl(2)]. This catalyst was designed to isomerize between achiral and chiral coordination geometries during the polymerization reaction to produce atactic-isotactic stereoblock polymers. The metallocene precursor (2-PhInd)(2)ZrCl(2) in the presence of methylaluminoxane polymerizes propylene to yield rubbery polypropylene. The isotacticity of the polymer, described by the isotactic pentad content, increases with increasing propylene pressure and decreasing polymerization temperature to produce polypropylenes with an isotactic pentad content ranging from 6.3 to 28.1 percent.
Rat liver catalase is sorted to peroxisomes by its C-terminal tripeptide Ala-Asn-Leu, not by the internal Ser-Lys-Leu motif. (1996)

The molecular signal for targeting catalases to peroxisomes has not been defined. In this study, a plant in vivo import system (tobacco BY-2 suspension culture cells) was used to test the current postulate that the peroxisome targeting signal (PTS) for mammalian catalases is the internal Ser-Lys-Leu (SKL) motif found approximately eight amino acid residues from the C-terminus. Elucidation of the catalase PTS has been hampered previously by the ubiquitous presence of catalase in peroxisomes. The current study was possible because antibodies to mammalian catalases did not recognize endogenous, tobacco peroxisome catalase. Rat and mouse liver catalases (Rcat and Mcat), with an internal Ser-His-Ile (SHI) and Ser-His-Met (SHM), respectively, and both with a C-terminal Ala-Asn-Leu (ANL), were expressed transiently in BY-2 cells and targeted to the peroxisomes. Sorting was demonstrated by double-label immunofluorescence colocalization of these catalases with tobacco catalase. Peroxisome targeting of Rcat was abolished as expected when the internal SHI residues were removed by deletion of three C-terminal portions (28, 16, or 11 residues). Surprisingly, peroxisome targeting was still abolished when SHI (or SHL produced by site-directed mutagenesis) were at the extreme C-terminus as a consequence of deleting eight residues. However, when SHL was at the C-terminus in full-sized Rcat via a mutation of ANL-COOH, the enzyme sorted to peroxisomes indicating that the position of the PTS is significant in Rcat. The importance of the internal context of the SHI (or SHL) was examined further by changing ANL-COOH to a non-SKL motif, AGS-COOH. This Rcat did not sort to the peroxisomes, nor did Rcat with its ANL-COOH deleted; these data indicated the necessity of the C-terminal tripeptide. Sufficiency of ANL was demonstrated when chloramphenicol acetyltransferase with an appended ANL-COOH was redirected from the cytosol to peroxisomes. Collectively, these results do not support the internal PTS hypothesis, but indicate that a type 1 PTS slightly divergent from the typical SKL motif serves as the necessary and sufficient PTS for rat liver and probably other eukaryotic catalases.
Overview of the clinical effectiveness of positron emission tomography imaging in selected cancers (2007)

The strongest evidence for the clinical effectiveness of FDG-PET is in staging NSCLC, restaging HL, staging/restaging colorectal cancer and detection of SPN. Some of these may still require clinical audit to augment the evidence base. Other management decisions require further research to show the impact of FDG-PET on patient management or added value in the diagnostic pathway. It is likely that capital investment will be in the newer PET/CT technology, for which there is less evidence. However, as this technology appears to be slightly more accurate than PET/CT, the PET clinical effectiveness results presented here can be extrapolated to cover PET/CT. PET research could be undertaken on FDG-PET or FDG-PET/CT, using a standard cancer work-up process on typical patients who are seen within the NHS in England. For treatment response and RT planning, the need for larger studies using consistent methods across the UK is highlighted as a priority for all cancers. For all studies, consideration should be given to collaboration across sites nationally and internationally, taking cognisance of the work of the National Cancer Research Institute.
Rational Design of Potent Antagonists to the Human Growth Hormone Receptor (1992)

A hybrid receptor was constructed that contained the extracellular binding domain of the human growth hormone (hGH) receptor linked to the transmembrane and intracellular domains of the murine granulocyte colony-stimulating factor receptor. Addition of hGH to a myeloid leukemia cell line (FDC-P1) that expressed the hybrid receptor caused proliferation of these cells. The mechanism for signal transduction of the hybrid receptor required dimerization because monoclonal antibodies to the hGH receptor were agonists whereas their monovalent fragments were not. Receptor dimerization occurs sequentially--a receptor binds to site 1 on hGH, and then a second receptor molecule binds to site 2 on hGH. On the basis of this sequential mechanism, which may occur in many other cytokine receptors, inactive hGH analogs were designed that were potent antagonists to hGH-induced cell proliferation. Such antagonists could be useful for treating clinical conditions of hGH excess, such as acromegaly.
Deaberration of incoherent wavefront distortion: An approach toward inverse filtering (1997)

Techniques for the correction of ultrasonic wavefront distortion are compared using measured pulse transmission through human breast specimens. The measured data were obtained by recording the pulse signals on each element of a linear array that was moved in elevation to synthesize a two-dimensional aperture. The one-way point spread functions were reconstructed using matched filtering technique, phase conjugation, time-delay compensation, and backpropagation followed by phase conjugation, each with and without amplitude compression. Two measures of performance were compared, the mainlobe diffraction shape and the ratio of the energy outside the mainlobe to the energy inside the mainlobe. Matched filtering, which compensates the phase distortion but also increases the variation in the modulus, performs more poorly than other techniques with respect to both measures. Phase conjugation and time-delay compensation, which leave the magnitude of the wavefront unchanged, have similar beamwidths but phase conjugation is consistently superior with respect to energy ratio. The backpropagation method, which models wavefront distortion using a phase screen at a computed position between the source and aperture, is shown to perform better. The use of a novel amplitude compression that approaches inverse filtering improves the performance of the compensation techniques significantly. This is because inverse filtering optimizes image fidelity, in contrast, for example, to matched filtering, which optimizes SNR. With the amplitude compression method, the results of the one-way experiments show that the mainlobe shape can be recovered down to -30 dB.
Interactions between the human gastrocnemius muscle and the Achilles tendon during incline, level and decline locomotion (2006)

Muscles are required to perform or absorb mechanical work under different conditions. However the ability of a muscle to do this depends on the interaction between its contractile components and its elastic components. In the present study we have used ultrasound to examine the length changes of the gastrocnemius medialis muscle fascicle along with those of the elastic Achilles tendon during locomotion under different incline conditions. Six male participants walked (at 5 km h(-1)) on a treadmill at grades of -10%, 0% and 10% and ran (at 10 km h(-1)) at grades of 0% and 10%, whilst simultaneous ultrasound, electromyography and kinematics were recorded. In both walking and running, force was developed isometrically; however, increases in incline increased the muscle fascicle length at which force was developed. Force was developed at shorter muscle lengths for running when compared to walking. Substantial levels of Achilles tendon strain were recorded in both walking and running conditions, which allowed the muscle fascicles to act at speeds more favourable for power production. In all conditions, positive work was performed by the muscle. The measurements suggest that there is very little change in the function of the muscle fascicles at different slopes or speeds, despite changes in the required external work. This may be a consequence of the role of this biarticular muscle or of the load sharing between the other muscles of the triceps surae.
Preliminary experiments in cooperative human/robot force control for robot assisted microsurgical manipulation (2002)

Reports preliminary experiments with a robot system designed to cooperatively extend a human's ability to perform fine manipulation tasks requiring human judgement, sensory integration and hand-eye coordination. A completed steady-hand robot is reported. A stable force control law is reviewed. Preliminary experiments validate theoretical predictions of stable one-dimensional control of tool-tip forces in contact with both linearly and nonlinearly compliant objects. Preliminary feasibility experiments demonstrate stable one-dimensional robotic augmentation and "force scaling" of a human operator's tactile input.
Unstable Hoogsteen base pairs adjacent to echinomycin binding sites within a DNA duplex. (1989)

The bisintercalation complex present between the DNA octamer [d(ACGTACGT)]2 and the cyclic octadepsipeptide antibiotic echinomycin has been studied by one- and two-dimensional proton NMR, and the results obtained have been compared with the crystal structures of related DNA-echinomycin complexes. Two echinomycins are found to bind cooperatively to each DNA duplex at the CpG steps, with the two quinoxaline rings of each echinomycin bisintercalating between the C.G and A.T base pairs. At low temperatures, the A.T base pairs on either side of the intercalation site adopt the Hoogsteen conformation, as observed in the crystal structures. However, as the temperature is raised, the Hoogsteen base pairs in the interior of the duplex are destabilized and are observed to be exchanging between the Hoogsteen base pair and either an open or a Watson-Crick base-paired state. The terminal A.T base pairs, which are not as constrained by the helix as the internal base pairs, remain stably Hoogsteen base-paired up to at least 45 degrees C. The implications of these results for the biological role of Hoogsteen base pairs in echinomycin-DNA complexes in vivo are discussed.
Natural Killer Cell Mediated Antibody-Dependent Cellular Cytotoxicity in Tumor Immunotherapy with Therapeutic Antibodies (2013)

In the last decade several therapeutic antibodies have been Federal Drug Administration (FDA) and European Medicines Agency (EMEA) approved. Although their mechanisms of action in vivo is not fully elucidated, antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells is presumed to be a key effector function. A substantial role of ADCC has been demonstrated in vitro and in mouse tumor models. However, a direct in vivo effect of ADCC in tumor reactivity in humans remains to be shown. Several studies revealed a predictive value of FcγRIIIa-V158F polymorphism in monoclonal antibody treatment, indicating a potential effect of ADCC on outcome for certain indications. Furthermore, the use of therapeutic antibodies after allogeneic hematopoietic stem cell transplantation is an interesting option. Studying the role of the FcγRIIIa-V158F polymorphism and the influence of Killer-cell Immunoglobuline-like Receptor (KIR) receptor ligand incompatibility on ADCC in this approach may contribute to future transplantation strategies. Despite the success of approved second-generation antibodies in the treatment of several malignancies, efforts are made to further augment ADCC in vivo by antibody engineering. Here, we review currently used therapeutic antibodies for which ADCC has been suggested as effector function.
A simplified mass isotopomer approach to estimate gluconeogenesis rate in vivo using deuterium oxide (2010)

We compare a new simplified (2)H enrichment mass isotopomer analysis (MIA) against the laborious hexamethylentetramine (HMT) method to quantify the contribution of gluconeogenesis (GNG) to total glucose production (GP) in calves. Both methods are based on the (2)H labeling of glucose after in vivo administration of deuterium oxide. The (2)H enrichments of plasma glucose at different C-H positions were measured as aldonitrile pentaacetate (AAc) and methyloxime-trimethylsilyl (MoxTMS) derivatives or HMT by gas chromatography/mass spectrometry (GC/MS). Two pre-ruminating fasted Holstein calves (51 kg body mass, BM, age 7 days) received two oral bolus doses of (2)H(2)O (10 g/kg BM, 70 atom% (2)H) at 7:00 h and 11:00 h after overnight food withdrawal. Blood samples for fractional GNG determination were collected at -24 and between 6 and 9 h after the first (2)H(2)O dose. The ratio of (2)H enrichments C5/C2 represents the contribution of GNG to GP. The (2)H enrichment at C2 was calculated based on the ion fragments at m/z 328 (C1-C6) - m/z 187 (C3-C6) of glucose AAc. The (2)H enrichment at C5 was approximated either by averaging the (2)H enrichment at C5-C6 using the ion fragment of glucose MoxTMS at m/z 205 or by conversion of the C5 of glucose into HMT. The fractional GNG calculated by the C5-C6 average (2)H enrichment method (41.4 +/- 6.9%) compared to the HMT method (34.3 +/- 11.4%) was not different (mean +/- SD, n = 6 replicates). In conclusion, GNG can be estimated with less laborious sample preparation by means of our new C5-C6 average (2)H enrichment method using AAc and MoxTMS glucose derivatives.
Novel Dual Bit Tri-Gate Charge Trapping Memory Devices (2004)

Dual bit operation of fabricated tri-gate nonvolatile memory devices with aggressively scaled oxide-nitride-oxide (ONO) dielectrics is presented for the first time. Compared to a planar cell, the proposed tri-gate device architecture offers higher readout currents and improved electrostatic gate control of the channel region yielding very good scalability of the devices. We have investigated devices with gate lengths in the range L/sub G/=100-220 nm and we focus on their write-erase, retention, and cycling characteristics.
Fusion of adenovirus E1A to the glucocorticoid receptor by high-resolution deletion cloning creates a hormonally inducible viral transactivator. (1989)

The 289-amino-acid E1A protein of adenovirus type 2 stimulates transcription from early viral and certain cellular promoters. Its mechanism is not known, and there exist no temperature-sensitive mutants of E1A that could help to elucidate the details of E1A transcriptional activation. To create for E1A such a conditional phenotype, we fused portions of E1A to the human glucocorticoid receptor (GR) to make transactivation by E1A dependent on the presence of dexamethasone. Nested subsets of the E1A coding region, centered around the 46-amino-acid transactivating domain, were substituted for the DNA-binding domain of the GR. One of the resulting chimeric proteins (GR/E1A-99), which included the entire E1A transactivating domain, stimulated expression from a viral early promoter (E3) exclusively in the presence of hormone. GR/E1A-99 did not transactivate a GR-responsive promoter. It therefore exhibited the promoter specificity of E1A while possessing the hormone inducibility of the GR. Two smaller chimeras that contained only portions of the E1A transactivating domain failed to transactivate E3. These three chimeras were constructed by a novel strategy, high-resolution deletion cloning. In this procedure, series of unidirectional deletions were made with exonuclease III on each side of the E1A coding region at a resolution of 1 to 2 nucleotides. The large number of in-frame fragments present in the collection of deleted clones facilitated the construction of the GR/E1A chimeras and can be used to create many additional fusions.
Ornithine Transport Via Cationic Amino Acid Transporter-1 Is Involved in Ornithine Cytotoxicity in Retinal Pigment Epithelial Cells (2006)

The results suggest that ornithine transport via CAT-1 may play a crucial role in ornithine cytotoxicity in hTERT-RPE cells. Reduction of the ornithine transport via CAT-1 may be a new target for treatment of gyrate atrophy.
A Taxonomy of Multiple-Choice Item-Writing Rules (1989)

Abstract A taxonomy of 43 multiple-choice item-writing rules is presented and discussed. The taxonomy derives from an analysis of 46 authoritative textbooks and other sources in the educational measurement literature. The analysis also leads to a "validity by consensus" for each rule. The taxonomy is viewed as a complete and authoritative set of guidelines for writing multiple-choice items.
Low-pass filters realizable as all-pass sums: design via a new flat delay filter (1999)

This paper describes a new class of maximally flat low-pass recursive digital filters. The filters are realizable as a parallel sum of two all-pass filters, a structure for which low-complexity low-noise implementations exist. Note that, with the classical Butterworth filter of degree N which is retrieved as a special case, it is not possible to adjust the delay (or phase linearity). However, with the more general class of filters described in this paper, the adjustment of the delay becomes possible, and the tradeoff between the delay and the phase linearity can be chosen. The construction of these low-pass filters depends upon a new maximally flat delay all-pole filter, for which the degrees of flatness at /spl omega/=0 and /spl omega/=/spl pi/ are not necessarily equal. For the coefficients of this flat delay filter, an explicit solution is introduced, which also specializes to a previously known result.
Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen (2001)

We report that complete protection against malaria and total inhibition of liver stage development and parasitemia was obtained in 100% of BALB/c mice primed with a replication-defective recombinant adenovirus expressing the circumsporozoite (CS) protein of Plasmodium yoelii (AdPyCS), followed by a booster with an attenuated recombinant vaccinia virus, expressing the same malaria antigen, VacPyCS. We found increased levels of activated CS-specific CD8(+) and CD4(+) T cells, higher anti-sporozoite antibody titers, and greater protection in these mice, when the time between priming and boosting with these two viral vectors was extended from 2 to 8 or more weeks. Most importantly, by using this immunization regimen, the protection of the immunized mice was found to be long-lasting, namely complete resistance to infection of all animals 3 1/2 months after priming. These results indicate that immunization with AdPyCS generates highly effective memory T and B cells that can be recalled long after priming by boosting with VacPyCS.
Chiral Discrimination of Monosaccharides through Gel Formation (1994)

Abstract The cholesterylphenylboronic acid (1) and its complexes with mono saccharides (2 : 1; 1/monosaccharide) were prepared. Many of the isolated complexes form gels in a variety of solvents, some of which display D vs L chiral discrimination. This is the first example of chiral discrimination in a saccharide based gel system.