gebhart/patrepeval huggingface dataset:
Practical reinforcement learning in continuous domains (2000)

Many real-world domains have continuous features and actions, whereas the majority of results in the reinforcement learning community are for finite Markov decision processes. Much of the work that addresses continuous domains either uses discretization or simple parametric function approximators. A drawback to some commonly-used parametric function approximation techniques, such as neural networks, is that parametric methods can "forget" and concentrate representational power on new examples. In this paper, we propose a practical architecture for model-based reinforcement learning in continuous state and action spaces that avoids the above difficulties by using an instance-based modeling technique. We present a method for learning and maintaining a value function estimate using instance-based learners, and show that our method compares favorably to other function approximation methods, such as neural networks. Furthermore, our reinforcement learning algorithm learns an explicit model of the environment simultaneously with a value function and policy. The use of a model is beneficial, first, because it allows the agent to make better use of its experiences through simulated planning steps. Second, the use of a model makes it straightforward to provide prior information to the system in the form of the structure of the environmental model. We extend a technique called generalized prioritized sweeping to the continuous case in order to focus the agent's planning steps on those states where the current value is most likely to be incorrect. We illustrate our algorithm's effectiveness with results on several control domains
Revisiting Experimental Models of Diabetic Nephropathy (2020)

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping.
Application of the Stille Coupling Reaction to the Synthesis of C2‐Substituted endo—exo Unsaturated Pyrrolo[2,1‐c][1,4]benzodiazepines (PBDs). (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Applied Statistics and Probability for Engineers sixth edition (2003)

Teks ini memberikan pendekatan praktis yang berorientasi pada teknik serta ilmu kimia dan fisika. Siswa belajar bagaimana materi tersebut akan relevan dalam karir mereka melalui integrasi di seluruh rangkaian masalah unik yang mencerminkan aplikasi dan situasi yang realistis. Statistik Terapan, Edisi ke-6 cocok untuk kursus satu atau dua jangka waktu dalam probabilitas dan statistik.
Spatio‐temporal texture (SpTeT) for distinguishing vulnerable from stable atherosclerotic plaque on dynamic contrast enhancement (DCE) MRI in a rabbit model (2014)

Vulnerable and stable plaque can be distinguished by SpTeT based features. The SpTeT features, following validation on larger datasets, could be established as effective and reliable imaging biomarkers for noninvasively assessing atherosclerotic risk.
Evaluating the coupling efficiency of phosphorylated amino acids for SPOT synthesis (2008)

A high demand of interest concerning binding assays to study the consequences of posttranscriptional phosphorylation may be addressed by peptide array-based methods. A crucial factor for de novo chemical approaches to generate such arrays is the possibility to rationally permutate phosphorylation events along a huge number of sequences. The simple principle behind this advantage is the stepwise synthesis of peptides, which allows the incorporation of either phosphorylated or nonphosphorylated derivates at serine, threonine, and tyrosine positions. In spite of several reported applications of phosphopeptide arrays, there is, to our best knowledge, no reported analysis of the efficiency of the involved techniques. Here, we analyze different coupling conditions to introduce phosphoamino acids in standard SPOT synthesis. Our results clearly indicate that EEDQ is the preferable activator and can also be used in fully automated SPOT synthesis.
Divergence measures based on the Shannon entropy (1991)

A novel class of information-theoretic divergence measures based on the Shannon entropy is introduced. Unlike the well-known Kullback divergences, the new measures do not require the condition of absolute continuity to be satisfied by the probability distributions involved. More importantly, their close relationship with the variational distance and the probability of misclassification error are established in terms of bounds. These bounds are crucial in many applications of divergence measures. The measures are also well characterized by the properties of nonnegativity, finiteness, semiboundedness, and boundedness.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An efficient chemoenzymatic production of small molecule glucosides with in situ UDP‐glucose recycling (2007)

A one-pot system for efficient enzymatic synthesis of curcumin glucosides is described. The method couples the activities of two recombinant enzymes, UDP-glucose: curcumin glucosyltransferase from Catharanthus roseus (CaUGT2) and sucrose synthase from Arabidopsis thaliana (AtSUS1). UDP, a product inhibitor of UDP-glucosyltransferase, was removed from the system and used for regeneration of UDP-glucose by the second enzyme, AtSUS1. The productivity was increased several-fold and UDP-glucose initially added to the reaction mixture could be reduced to one-tenth of the normal level. The concept of enhancing glucosylation efficiency by coupling a UDP-glucose regeneration system with glucosyltransferases should be applicable to enzymatic production of a wide range of glucosides.
Sural sensory action potential identifies diabetic peripheral neuropathy responders to therapy (2005)

Identifying patients with diabetic peripheral neuropathy (DPN) amenable to therapy is a challenge. To determine whether the amplitude of the sural sensory nerve action potential (sural SNAP) reflects the severity of DPN, an analysis was performed on 205 patients with DPN, identified by an abnormal vibration detection threshold (VDT), who were enrolled in a multinational clinical trial investigating ruboxistaurin (RBX) mesylate. Nerve conduction velocity and response amplitude and latency were measured and compared. VDT was significantly lower in those with preserved sural SNAPs (n = 128) than in those in whom they were absent (n = 77; 21.5 vs. 22.7 JND units, P = 0.002). Thus, preserved sural SNAP denoted less severe DPN. Logistic regression analyses evaluating baseline characteristics, HbA(1c), and baseline symptom scores identified only DPN duration as a factor that might contribute to the presence of sural SNAP (P = 0.004; OR = 0.896). For patients with abnormal VDT, preserved sural SNAP identifies a patient population with less severe DPN who may respond to therapeutic intervention in clinical trials.
A Method to Identify Protein Sequences That Fold into a Known Three-Dimensional Structure (1991)

The inverse protein folding problem, the problem of finding which amino acid sequences fold into a known three-dimensional (3D) structure, can be effectively attacked by finding sequences that are most compatible with the environments of the residues in the 3D structure. The environments are described by: (i) the area of the residue buried in the protein and inaccessible to solvent; (ii) the fraction of side-chain area that is covered by polar atoms (O and N); and (iii) the local secondary structure. Examples of this 3D profile method are presented for four families of proteins: the globins, cyclic AMP (adenosine 3',5'-monophosphate) receptor-like proteins, the periplasmic binding proteins, and the actins. This method is able to detect the structural similarity of the actins and 70- kilodalton heat shock proteins, even though these protein families share no detectable sequence similarity.
Synthesis of Cu-Doped InP Nanocrystals (d-dots) with ZnSe Diffusion Barrier as Efficient and Color-Tunable NIR Emitters (2009)

Efficient Cu-doped InP quantum dots (Cu:InP d-dots) emitters were successfully synthesized by epitaxial growth of a ZnSe diffusion barrier for the dopants. The Cu dopant emission of the Cu:InP/ZnSe core/shell d-dots covered the important red and near-infrared (NIR) window for biomedical applicaitons, from 630 to 1100 nm, by varying the size of the InP host nanocrystals. These new d-dots emitters not only compensate for the emission wavelength of the existing noncadmium d-dots emitters, Cu- and Mn-doped ZnSe d-dots (450-610 nm), but also offer a complete series of efficient nanocrystal emitters based on InP nanocrystals. The one-pot synthetic scheme for the formation of Cu:InP/ZnSe core/shell d-dots was successfully established by systematically studying the doping process, the dopant concentration-dependent photophysical properties, and the dopant diffusion during shell epitaxy, etc. Complete elimination of InP bandgap emission and efficient pure dopant emission (with photoluminescence quantum yield as high as between 35-40%) of the core/shell d-dots were achieved by optimizing the final doping level and the diffusion barrier thickness.
GORDIAN: efficient and scalable discovery of composite keys (2006)

Identification of (composite) key attributes is of fundamental importance for many different data management tasks such as data modeling, data integration, anomaly detection, query formulation, query optimization, and indexing. However, information about keys is often missing or incomplete in many real-world database scenarios. Surprisingly, the fundamental problem of automatic key discovery has received little attention in the existing literature. Existing solutions ignore composite keys, due to the complexity associated with their discovery. Even for simple keys, current algorithms take a brute-force approach; the resulting exponential CPU and memory requirements limit the applicability of these methods to small datasets. In this paper, we describe GORDIAN, a scalable algorithm for automatic discovery of keys in large datasets, including composite keys. GORDIAN can provide exact results very efficiently for both real-world and synthetic datasets. GORDIAN can be used to find (composite) key attributes in any collection of entities, e.g., key column-groups in relational data, or key leaf-node sets in a collection of XML documents with a common schema. We show empirically that GORDIAN can be combined with sampling to efficiently obtain high quality sets of approximate keys even in very large datasets.
Herpes Simplex Virus DNA Vaccine Efficacy: Effect of Glycoprotein D Plasmid Constructs (2000)

The impact of vaccination with plasmid DNA encoding full-length glycoprotein D (gD) from herpes simplex virus (HSV) type 2 (gD2), secreted gD2, or cytosolic gD2 was evaluated in mice and guinea pigs. Immunization with plasmids encoding full-length gD2 or secreted gD2 produced high antibody levels, whereas immunization with DNA encoding cytosolic gD2 resulted in significantly lower antibody titers in both species (P<.001). Vaccination with DNA encoding full-length or secreted gD2 significantly reduced acute disease in mice and guinea pigs (both P<.001) and subsequent recurrent disease in guinea pigs (P<.05). In guinea pigs, immunization with DNA encoding cytosolic gD2 did not protect from acute or recurrent disease, whereas in mice it did protect, but not as well as DNA encoding full-length or secreted gD2. None of the vaccines resulted in improved virus clearance from the inoculation site, and none significantly reduced recurrent disease when used as a therapeutic vaccine in HSV-2-infected guinea pigs.
Levulinic acid from lignocellulosic biomass (2007)

The primary objective of this thesis is to define optimum catalysts, reaction conditions and reactor configurations for the conversion of water hyacinth plant to LA. The conversion of the C6-sugars present in the water hyacinth plant to LA involves several reactions that together form a complex reaction network. A number of side reactions giving rise to by-products formation (e.g., insoluble humin compounds) significantly complicate the catalyst selection and the development of kinetic models. Therfore, a stepwise approach was applied by investigating the individual reactions in the overall reaction scheme separately.
Parallel Processing of Nociceptive and Non-nociceptive Somatosensory Information in the Human Primary and Secondary Somatosensory Cortices: Evidence from Dynamic Causal Modeling of Functional Magnetic Resonance Imaging Data (2011)

Several studies have suggested that, in higher primates, nociceptive somatosensory information is processed in parallel in the primary (S1) and secondary (S2) somatosensory cortices, whereas non-nociceptive somatosensory input is processed serially from S1 to S2. However, evidence suggesting that both nociceptive and non-nociceptive somatosensory inputs are processed in parallel in S1 and S2 also exists. Here, we aimed to clarify whether or not the hierarchical organization of nociceptive and non-nociceptive somatosensory processing in S1 and S2 differs in humans. To address this question, we applied dynamic causal modeling and Bayesian model selection to functional magnetic resonance imaging (fMRI) data collected during the selective stimulation of nociceptive and non-nociceptive somatosensory afferents in humans. This novel approach allowed us to explore how nociceptive and non-nociceptive somatosensory information flows within the somatosensory system. We found that the neural activities elicited by both nociceptive and non-nociceptive somatosensory stimuli are best explained by models in which the fMRI responses in both S1 and S2 depend on direct thalamocortical projections. These observations indicate that, in humans, both nociceptive and non-nociceptive information are processed in parallel in S1 and S2.
Control of porcine reproductive and respiratory syndrome (PRRS) through genetic improvements in disease resistance and tolerance (2012)

Infections caused by porcine reproductive and respiratory syndrome virus (PRRSV) have a severe economic impact on pig production in North America, Europe, and Asia. The emergence and eventual predominance of PRRS in the 1990s are the likely result of changes in the pork industry initiated in the late 1970s, which allowed the virus to occupy a unique niche within a modern commercial production system. PRRSV infection is responsible for severe clinical disease, but can maintain a life-long subclinical infection, as well as participate in several polymicrobial syndromes. Current vaccines lessen clinical signs, but are of limited use for disease control and elimination. The relatively poor protective immunity following vaccination is a function of the virus's capacity to generate a large degree of genetic diversity, combined with several strategies to evade innate and adaptive immune responses. In 2007, the PRRS Host Genetics consortium (PHGC) was established to explore the role of host genetics as an avenue for PRRS control. The PHGC model for PRRS incorporates the experimental infection of large numbers of growing pigs and has created the opportunity to study experimental PRRSV infection at the population level. The results show that pigs can be placed into distinct phenotypic groups, including pigs that show resistance (i.e., low virus load) or pigs that exhibit "tolerance" to infection. Tolerance was illustrated by pigs that gain weight normally in the face of a relatively high virus load. Genome-wide association analysis has identified a region on chromosome 4 (SSC4) correlated with resistance; i.e., lower cumulative virus load within the first 42 days of infection. The genomic region is near a family of genes involved in innate immunity. The region is also associated with higher weight gain in challenged pigs, suggesting that pigs with the resistance alleles don't seem to simultaneously experience reduction in growth, i.e., that resistance and tolerance are not antagonistically related. These results create the opportunity to develop breeding programs that will produce pigs with increased resistance to PRRS and simultaneously high growth rate. The identification of genomic markers involved in actual tolerance will likely prove more difficult, primarily because tolerance is difficult to quantify and because tolerance mechanism are still poorly understood. Another avenue of study includes the identification of genomic markers related to improved response following vaccination.
Long-oligomer microarray profiling in Neurospora crassa reveals the transcriptional program underlying biochemical and physiological events of conidial germination (2005)

To test the inferences of spotted microarray technology against a biochemically well-studied process, we performed transcriptional profiling of conidial germination in the filamentous fungus, Neurospora crassa. We first constructed a 70 base oligomer microarray that assays 3366 predicted genes. To estimate the relative gene expression levels and changes in gene expression during conidial germination, we analyzed a circuit design of competitive hybridizations throughout a time course using a Bayesian analysis of gene expression level. Remarkable consistency of mRNA profiles with previously published northern data was observed. Genes were hierarchically clustered into groups with respect to their expression profiles over the time course of conidial germination. A functional classification database was employed to characterize the global picture of gene expression. Consensus motif searches identified a putative regulatory component associated with genes involved in ribosomal biogenesis. Our transcriptional profiling data correlate well with biochemical and physiological processes associated with conidial germination and will facilitate functional predictions of novel genes in N.crassa and other filamentous ascomycete species. Furthermore, our dataset on conidial germination allowed comparisons to transcriptional mechanisms associated with germination processes of diverse propagules, such as teliospores of the phytopathogenic fungus Ustilago maydis and spores of the social amoeba Dictyostelium discoideum.
Characterization of the individual glucose uptake systems of Lactococcus lactis: mannose‐PTS, cellobiose‐PTS and the novel GlcU permease (2008)

According to previous reports, Lactococcus lactis imports glucose via two distinct phosphoenolpyruvate:phosphotransferase systems (mannose-PTS and cellobiose-PTS) and one or more unknown non-PTS permease(s). GlcU was identified as the sole non-PTS permease involved in the transport of glucose. Additionally, the biochemical properties of PTS(Man), PTS(Cel) and GlcU were characterized in double knockout mutants with glucose uptake restricted to a single system. Transport susceptibility to protonophores indicated that glucose uptake via GlcU is proton-motive force dependent. Competition assays revealed a high specificity of GlcU for glucose. Furthermore, the permease has low affinity for glucose and displays strong preference for the beta-anomer as shown by the profiles of consumption of the two glucose anomers studied by (13)C-NMR. Similar kinetic properties were found for PTS(Cel), while PTS(Man) is a high-affinity system recognizing equally well the two anomeric forms of glucose. Transcripts of the genes encoding the three transporters are present simultaneously in the parent strain NZ9000 as shown by reverse transcription-PCR. Investigation of the distribution of GlcU homologues among bacteria showed that these proteins are restricted to the low-GC Gram-positive Firmicutes. This work completes the identification of the glucose transport systems in L. lactis MG1363.
Amphipathic, α‐helical antimicrobial peptides (2000)

Gene-encoded antimicrobial peptides are an important component of host defense in animals ranging from insects to mammals. They do not target specific molecular receptors on the microbial surface, but rather assume amphipathic structures that allow them to interact directly with microbial membranes, which they can rapidly permeabilize. They are thus perceived to be one promising solution to the growing problem of microbial resistance to conventional antibiotics. A particularly abundant and widespread class of antimicrobial peptides are those with amphipathic, α-helical domains. Due to their relatively small size and synthetic accessibility, these peptides have been extensively studied and have generated a substantial amount of structure–activity relationship (SAR) data. In this review, α-helical antimicrobial peptides are considered from the point of view of six interrelated structural and physicochemical parameters that modulate their activity and specificity: sequence, size, structuring, charge, amphipathicity, and hydrophobicity. It begins by providing an overview of how these vary in peptides from different natural sources. It then analyzes how they relate to the currently accepted model for the mode of action of α-helical peptides, and discusses what the numerous SAR studies that have been carried out on these compounds and their analogues can tell us. A comparative analysis of the many α-helical, antimicrobial peptide sequences that are now available then provides further information on how these parameters are distributed and interrelated. Finally, the systematic variation of parameters in short model peptides is used to throw light on their role in antimicrobial potency and specificity. The review concludes with some considerations on the potentials and limitations for the development of α-helical, antimicrobial peptides as antiinfective agents. © 2000 John Wiley & Sons, Inc. Biopoly 55: 4–30, 2000