gebhart/patrepeval huggingface dataset:
Progress toward an artificial vaccine for HIV: identification of helper and cytotoxic T-cell epitopes and methods of immunization. (1991)

Design of a synthetic vaccine for HIV requires basic knowledge of the structure of helper and cytotoxic T-cell epitopes and neutralizing antibody epitopes, of ways to couple these to produce an effective immunogen, and of the role of viral sequence variation on MHC presentation of antigen. T-cell recognition, and cross-reactivity. We have been addressing all these issues for the HIV envelope and more recently also for the reverse transcriptase. We have now identified antigenic sites or epitopes from HIV envelope and reverse transcriptase recognized by cytotoxic T cells from both mice and humans in association with murine class I H-2 and human class I HLA antigens, as well as epitopes recognized by helper T cells in association with class II MHC molecules from both mice and humans. We have identified residues affecting interaction of peptides with MHC molecules and T-cell receptors and have examined the role of viral variability on presentation of these peptides by MHC molecules and recognition by T cells. One CTL epitope peptide was found to be presented by class II MHC molecules as well as class I MHC molecules and to be able to elicit CD4+ helper cells to aid in the induction of CD8+ CTL against the same peptide. One of the helper epitope peptides has been shown to be a powerful carrier for inducing neutralizing antibodies, and we have shown in rhesus monkeys that some of these helper peptides are immunogenic in primates and can elicit helper T cells that greatly augment the antibody response to a challenge in vivo with a suboptimal dose of HIV envelope protein compared to monkeys not given peptides, as one would want a vaccine to do. We have also identified multideterminant regions of the HIV-1 envelope and have made peptides corresponding to these that elicit helper T-cell responses in a large fraction of mouse strains and of outbred humans, as an approach to overcoming the problem of genetic restriction of T-cell responses. We have also developed a way of using purified recombinant proteins to elicit cytotoxic T cells in vivo by immunizing with the proteins incorporated into ISCOMs, and this method could be applied to an artificial vaccine as well. Some of these peptides should be candidates for immunotherapy trials in HIV-infected humans, as well as for vaccine development and diagnostic use.
CYCLIC PHOTOBIOLOGICAL ALGAL H2-PRODUCTION (2002)

Previous work from our laboratory demonstrated the feasibility of using sulfur-deprived algal cultures to photoproduce H2 continuously for 3-4 days (Melis et al., 2000; Ghirardi et al., 2000a). The production of H2 depends mostly on the photosynthetic H2O-oxidation activity of the cultures (Ghirardi et al., 2000 a and b; Kosourov et al., 2002), and requires concomitant operation of O2-consumption pathways (Ghirardi et al., 2000a; Kosourov et al., 2002; Antal et al., submitted). Our research has focused on the elucidation of the pathways involved in H2production under sulfur-deprivation and on approaches to improve the H2 production yield of the process. This year’s results show that (a) H2-production can be optimized by controlling the initial pH of the medium and (b) different maximum amounts of sulfate can be re-added to the system at different points of the sulfur-deprivation process without decreasing H2 production. Moreover, we present evidence from in situ fluorescence measurements, that H2-production during sulfurdeprivation provides the means to re-activate residual photosynthetic electron transport capacity, which is rapidly down-regulated at the establishment of anaerobiosis. These measurements can be used to determine the transition of the cultures to anaerobic conditions and thus serve as a means to monitor the physiological state of the culture from outside the photobioreactor vessel. Finally, we show that different pathways for photosyntheticallygenerated O2 consumption are prevalent during different phases of the process. We conclude that the rates of H2-production in the system are limited by the rates of electron transport from the H2O-oxidizing complex to the hydrogenase under anaerobic conditions, and that these rates can be manipulated, to a certain extent, by changes in pH and addition of sulfate to the medium.
Thermodynamic and Kinetic Study of the Li / MnO2 ⋅ Bi2 O 3 Electrochemical Couple (1998)

cathode material showed improved performance overtypical in primary lithium battery prototype cells. Studies indicate that surface-modified material provided alternative catalytic discharge mechanisms, which lower the activation energy of the cell reaction.
Acyclic analogs of 2'-deoxynucleosides related to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine as potential antiviral agents (1985)

A series of acyclic analogues of 2'-deoxynucleosides related in structure to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) have been synthesized and evaluated for antiviral activity against herpes simplex virus type 1 (F strain). Additionally, the ability of these analogues to function as substrates for the virus-specified thymidine kinase was examined. Phosphorylation by this kinase is essential for antiviral activity. Although the acyclic 4-oxopyrimidine nucleosides were substrates for the kinase, they were devoid of antiviral activity. In the purine series, most analogues similar in structure to DHPG did exhibit significantly lower antiviral activity, indicating that even small modifications in the purine substituents substantially reduce the antiviral potency. The most active agent, 2,6-diaminopurine 27, was only poorly phosphorylated by the viral kinase; therefore, its activity was most likely due to a prior enzymatic deamination to give DHPG. Evaluation of 27 in a mouse encephalitis model has shown it to be nearly as potent as DHPG (1).
Extracorporeal Pressure Monitoring and the Detection of Vascular Access Stenosis (2002)

Prospective monitoring of static venous pressure is an established tool to detect outflow stenoses in a vascular access. However, with this method it is not possible to identify vascular stenoses which are localized between the arterial and venous dialysis needle. We describe a new approach based on both static arterial and venous extracorporeal pressures. Pressure data of 9 dialysis patients with normal vascular access function and 9 patients with stenotic access were analyzed. Extracorporeal pressure was found to depend on the position of the heart relative to the extracorporeal blood circuit. All patients with venous outflow stenoses had an elevated ratio of arterial and venous intra-access pressure to mean arterial pressure. In case of access stenosis between arterial and venous needle the ratio of venous pressure to mean arterial pressure was normal, and only the arterial pressure ratio was elevated. We conclude that combined arterial and venous intraaccess pressure measurement normalized by mean blood pressure detects venous stenosis as well as stenosis between the arterial and venous dialysis needle. To minimize the rate of access thrombosis both arterial and venous intra-access pressure should be monitored.
Grid Long Short-Term Memory (2015)

This paper introduces Grid Long Short-Term Memory, a network of LSTM cells arranged in a multidimensional grid that can be applied to vectors, sequences or higher dimensional data such as images. The network differs from existing deep LSTM architectures in that the cells are connected between network layers as well as along the spatiotemporal dimensions of the data. The network provides a unified way of using LSTM for both deep and sequential computation. We apply the model to algorithmic tasks such as 15-digit integer addition and sequence memorization, where it is able to significantly outperform the standard LSTM. We then give results for two empirical tasks. We find that 2D Grid LSTM achieves 1.47 bits per character on the Wikipedia character prediction benchmark, which is state-of-the-art among neural approaches. In addition, we use the Grid LSTM to define a novel two-dimensional translation model, the Reencoder, and show that it outperforms a phrase-based reference system on a Chinese-to-English translation task.
A Bentazon and Sulfonylurea-sensitive Mutant in Rice and its Application in Hybrid Rice (2009)

A rice bentazon-lethal mutant 8077S obtained by radiation, is being utilized in developing new hybrid rice systems. Genetic analysis revealed that the bentazon-lethal mutant was controlled by a single recessive gene, which is named bel. The mutant can be killed at the seedling stage by bentazon with a lethal dosage at 300 mg/l or above, while this dosage is safe for its F 1 hybrids and all other normal rice. This mutant is also sensitive to all the tested sulfonylurea herbicides and this sensitivity is also controlled by bel. Interestingly, another rice bentazon-lethal mutant Norin8m also obtained by radiation in Japan, was controlled by the allelic locus of bel, which is named as bsl. These two mutant genes were cloned by map-based cloning. Both mutant alleles had a single-base deletion respectively. There is a G deletion in the bel. and a C deletion in the bsl. The wild-type gene bel. encodes a novel cytochrome P450 monooxgenase, named CYP81A6. Otherwise, the use of photo-thermogenic male sterility (P/TGMS) system in two-line hybrid rice breeding is affected greatly by the sterility instability of P/TGMS lines caused by temperature fluctuation beyond their critical temperatures for fertility reversion. To prevent the hybrid seed contamination, we have developed three bentazon-lethal P/TGMS lines using 8077S by backcross and three new hybrid rice varieties using these P/TGMS lines had been registered. When these P/TGMS lines selfed by temperature fluctuation, the seedlings from the selfed seeds can be killed by spraying bentazon at seedling stage but the hybrid seedlings are safety. These new hybrid rice varieties have been cultivated in five provinces in China.
Dynamic Properties of Current-Fed Quadratic Full-Bridge Buck Converter for Distributed Photovoltaic MPP-Tracking Systems (2012)

Interfacing a single photovoltaic (PV) module into either a single-phase or a three-phase inverter requires an interfacing converter with wide conversion ratio and sufficient dynamic headroom. In terms of avoiding issues with common-mode currents between the PV module and the inverter, a converter with galvanic isolation is preferred. This is especially important with the emerging thin-film modules that have larger cell-to-frame parasitic capacitances compared to traditional modules. This paper presents the dynamic properties and analysis of the current-fed quadratic full-bridge buck converter. The foundation for the proposed topology is based on the concept of true current-fed converters that differ fundamentally from the conventional voltage-fed converters. The relevant analytical steady-state equations and the dynamic model are presented with the operational details of the proposed converter. The analytical claims are verified with extensive measurements from a corresponding 190-W prototype. According to the measurements, the prototype performed well in PV application and reached an efficiency of 92% at the maximum power point of the PV module.
CsrA and three redundant small RNAs regulate quorum sensing in <i>Vibrio cholerae</i> (2005)

Bacteria communicate using a process called quorum sensing which involves production, secretion and detection of signalling molecules called autoinducers. Quorum sensing allows populations of bacteria to simultaneously regulate gene expression in response to changes in cell density. The human pathogen, Vibrio cholerae, uses a quorum-sensing circuit composed of parallel systems that transduce information through four redundant regulatory small RNAs (sRNAs) called quorum regulatory RNAs (Qrr) to control the expression of numerous genes, most notably those required for virulence. We show that the VarS/VarA two-component sensory system comprises an additional regulatory input controlling quorum-sensing-dependent gene expression in V. cholerae. VarS/VarA controls transcription of three previously unidentified small regulatory RNAs (sRNAs) that are similar to the sRNAs CsrB and CsrC of Escherichia coli. The three V. cholerae sRNAs, which we name CsrB, CsrC and CsrD, act redundantly to control the activity of the global regulatory protein, CsrA. The VarS/VarA-CsrA/BCD system converges with the V. cholerae quorum-sensing systems to regulate the expression of the Qrr sRNAs, and thus, the entire quorum-sensing regulon.
Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction (2011)

To date, the lack of a suitable human cardiac cell source has been the major setback in regenerating the human myocardium, either by cell-based transplantation or by cardiac tissue engineering. Cardiomyocytes become terminally-differentiated soon after birth and lose their ability to proliferate. There is no evidence that stem/progenitor cells derived from other sources, such as the bone marrow or the cord blood, are able to give rise to the contractile heart muscle cells following transplantation into the heart. The need to regenerate or repair the damaged heart muscle has not been met by adult stem cell therapy, either endogenous or via cell delivery. The genetically stable human embryonic stem cells (hESCs) have unlimited expansion ability and unrestricted plasticity, proffering a pluripotent reservoir for in vitro derivation of large supplies of human somatic cells that are restricted to the lineage in need of repair and regeneration. Due to the prevalence of cardiovascular disease worldwide and acute shortage of donor organs, there is intense interest in developing hESC-based therapies as an alternative approach. However, how to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, resulting in inefficient and uncontrollable lineage-commitment that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity (see a schematic in Fig. 1A). In addition, undefined foreign/animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic. To overcome these obstacles, we have resolved the elements of a defined culture system necessary and sufficient for sustaining the epiblast pluripotence of hESCs, serving as a platform for de novo derivation of clinically-suitable hESCs and effectively directing such hESCs uniformly towards clinically-relevant lineages by small molecules (see a schematic in Fig. 1B). After screening a variety of small molecules and growth factors, we found that such defined conditions rendered nicotinamide (NAM) sufficient to induce the specification of cardiomesoderm direct from pluripotent hESCs that further progressed to cardioblasts that generated human beating cardiomyocytes with high efficiency (Fig. 2). We defined conditions for induction of cardioblasts direct from pluripotent hESCs without an intervening multi-lineage embryoid body stage, enabling well-controlled efficient derivation of a large supply of human cardiac cells across the spectrum of developmental stages for cell-based therapeutics.
Towards 3-Axis FM Mems Gyroscopes: Mechanical Design and Experimental Validation (2019)

Frequency Modulation (FM) has been studied as an innovative working principle for Micro-Electro-Mechanical Systems (MEMS) gyroscopes and as a smart solution for the scale factor stability against environmental fluctuations. In this work, three tuning-fork structures are proposed for a yaw, pitch and monolithic 3-axis FM gyroscope, respectively. Preliminary experimental measurements of the scale factors of the FM gyroscopes prove the expected behavior of the devices. In particular, in this work we show the first experimental proof of a monolithic 3-axis FM gyroscope.
A hybrid strategy with Simplified Optimal Trajectory Control for LLC resonant converters (2012)

In this paper, a Simplified Optimal Trajectory Control (SOTC) for the LLC resonant converters is proposed. During the steady state, linear compensator like PI or PID is used, controlling the switching frequency (f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</sub> ) to eliminate the steady error. However, during load transients, the Simplified Optimal Trajectory Control (SOTC) method takes over, controlling the pulse widths of the driving signals. Using the state-plane analysis, the pulse widths are estimated, letting the state variables track the optimum trajectory locus in the minimum period of time. Experimental results show that digital logic requirement is very small, but the performance improvement is significant.
Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma (2017)

Neuroblastoma is a childhood cancer that is fatal in almost half of patients despite intense multimodality treatment. This cancer is derived from neuroendocrine tissue located in the sympathetic nervous system. Glypican-2 (GPC2) is a cell surface heparan sulfate proteoglycan that is important for neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2 protein is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival compared with patients with low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We have isolated human single-domain antibodies specific for GPC2 by phage display technology and found that the single-domain antibodies can inhibit active β-catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore GPC2 as a potential target in neuroblastoma, we have developed two forms of antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells. Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice. CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma mouse model where tumor metastasis had spread to multiple clinically relevant sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a promising therapeutic target in neuroblastoma.
Definition and Treatment of Arrhythmogenic Cardiomyopathy: An Updated Expert Panel Report (2019)

It is 35 years since the first description of arrhythmogenic right ventricular cardiomyopathy (ARVC) and more than 20 years since the first reports establishing desmosomal gene mutations as a major cause of the disease. Early advances in the understanding of the clinical, pathological and genetic architecture of ARVC resulted in consensus diagnostic criteria, which proved to be sensitive but not entirely specific for the disease. In more recent years, clinical and genetic data from families and the recognition of a much broader spectrum of structural disorders affecting both ventricles and associated with a propensity to ventricular arrhythmia have raised many questions about pathogenesis, disease terminology and clinical management. In this paper, we present the conclusions of an expert round table that aimed to summarise the current state of the art in arrhythmogenic cardiomyopathies and to define future research priorities.
Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 (2002)

C-1027 is a potent antitumor agent with a previously undescribed molecular architecture and mode of action. Cloning and characterization of the 85-kilobase C-1027 biosynthesis gene cluster from Streptomyces globisporus revealed (i) an iterative type I polyketide synthase that is distinct from any bacterial polyketide synthases known to date, (ii) a general polyketide pathway for the biosynthesis of both the 9- and 10-membered enediyne antibiotics, and (iii) a convergent biosynthetic strategy for the C-1027 chromophore from four building blocks. Manipulation of genes governing C-1027 biosynthesis allowed us to produce an enediyne compound in a predicted manner.
Molecular Determinants of Selectivity and Efficacy at the Dopamine D3 Receptor (2012)

The dopamine D3 receptor (D3R) has been implicated in substance abuse and other neuropsychiatric disorders. The high sequence homology between the D3R and D2R, especially within the orthosteric binding site (OBS) that binds dopamine, has made the development of D3R-selective compounds challenging. Here, we deconstruct into pharmacophoric elements a series of D3R-selective substituted-4-phenylpiperazine compounds and use computational simulations and binding and activation studies to dissect the structural bases for D3R selectivity and efficacy. We find that selectivity arises from divergent interactions within a second binding pocket (SBP) separate from the OBS, whereas efficacy depends on the binding mode in the OBS. Our findings reveal structural features of the receptor that are critical to selectivity and efficacy that can be used to design highly D3R-selective ligands with targeted efficacies. These findings are generalizable to other GPCRs in which the SBP can be targeted by bitopic or allosteric ligands.
Characterization of the dominant mutant amylose-extender (Ae1-5180) maize starch (1995)

Maize plants homozygous for the dominant amylose extender allele Ae1-5180 were self-pollinated and crossed onto wild type Ae plants, and vice versa, to obtain endosperms with zero to three doses of the Ae1-5180 allele. Starches from dominant Ae mutant kernels were isolated and analyzed with respect to molecular size distribution, amylose contents (iodine affinity), thermal properties (differential scanning calorimetry), and microscopic structure (scanning electron microscopy). Gel-permeation chromatograms of these starches showed greater proportions of amylose and intermediate fractions than those from normal maize starch. The iodine-staining blue value of the amylopectin peak on the profile results revealed longer amylopectin branch-chain lengths than those of normal corn, which was confirmed by enzyme debranching. The structure of the intermediate component and amylopectin was also revealed by gel-permeation chromatography and high-performance anion-exchange chromatography. Greater dosage of the Ae1-5180 gene did not increase amylose content (33%). The differential scanning calorimetry thermograms indicated that all the mutant starches with different dosages had similar thermal properties. The gelatinization onset temperature (T o ) range was 65.7-67.0°C and the gelatinization range (R) was 54.0-109.7°C. The scanning electron microscope showed that the mutant starches had irregular and round-shaped granules with diameters that ranged from 4 to 18 mm.