gebhart/patrepeval huggingface dataset:
The gastrointestinal stimulus to insulin release (1970)

The insulin release after an oral glucose load is both earlier and greater than would be expected from the glycemic stimulus. This augmentation of insulin release has been attributed to humoral factors from the gut. It has been previously demonstrated that secretin is released very rapidly after oral glucose and postulated that it acts as an early trigger to insulin release. This effect would not explain the magnitude of the peak insulin response which occurs about 30 min after peak secretin levels. The present studies, however, demonstrate an additional action of secretin which may explain this. To further study the role of secretin in insulin release in normal subjects, two consecutive 20 min intravenous glucose infusions were administered 150 min apart with and without an intervening secretin infusion (10 U) given to approximate serum secretin levels seen after oral glucose ingestion. A highly significant (P<0.01) potentiation of the insulin response to the post-secretin glucose infusion was observed. This occurred both when secretin was given 7 min or 25 min before glucose. In the latter case, serum secretin was undetectable during the glucose infusion. These studies demonstrate that secretin potentiates the glycemic release of insulin. Despite the augmented insulin response, no consistent change in blood glucose variation was observed. This is consistent with the suggestion that the facilitated disposal of an alimentary glucose load is not dependent solely on enhanced insulin secretion. Secretin appears to have a dual role in insulin release, an early direct stimulation followed by a prolonged potentiation of the glycemic stimulus. The potentiating effect is of such magnitude to suggest that secretin is the dominant factor in the enteric component of insulin release after an oral glucose load.
Enseñar a Profesores de Secundaria con situaciones problemáticas (2003)

En este trabajo se establece un paralelismo entre los diferentes tipos de situaciones problematicas que pueden presentarse en la ensenanza de las Ciencias de la Naturaleza y las que pueden hacerlo en la docencia de la Didactica de las Ciencias de la Naturaleza. El establecimiento de este paralelismo nos permite dar fundamento al trasvase de estrategias y actividades de formacion entre ambos campos, aprovechando la experiencia en el primero para desarrollar nuevas formas de ensenanza en el segundo.
Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines (2019)

mRNA vaccines have the potential to tackle many unmet medical needs that are unable to be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral to fully realizing the potential of mRNA vaccines. Pre-clinical and clinical studies have demonstrated that mRNA delivered intramuscularly (IM) with first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over the past several years, there remains significant opportunity for improvement, as the most advanced LNPs were designed for intravenous (IV) delivery of siRNA to the liver. Here, we screened a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model when administered IM. A subset of compounds was selected and further evaluated for tolerability, immunogenicity, and expression in rodents and non-human primates (NHPs). A lead formulation was identified that yielded a robust immune response with improved tolerability. More importantly for vaccines, increased innate immune stimulation driven by LNPs does not equate to increased immunogenicity, illustrating that mRNA vaccine tolerability can be improved without affecting potency.
Metabolic distinctiveness of ureaplasmas (1986)

Enzymes of the Embden-Meyerhof-Parnas pathway and hexose monophosphate shunt were examined in cytoplasmic extracts of three serovars of Ureaplasma urealyticum. We found no glucose-6-phosphate or 6-phosphogluconate dehydrogenase, hexokinase, phosphoglucose isomerase, aldolase, or lactic dehydrogenase activities. We failed to find cytochrome pigments in extracts and found no significant production of 14CO2 from [U-14C]glucose, nor did we find oxygen-dependent reduced nicotinamide adenine dinucleotide oxidase activity. Lactic acid was found only at trace levels in spent culture fluids. Ureaplasmas are apparently nonfermentative and are unlike all other mollicutes in that they have no detectable oxygen-dependent reduced nicotinamide adenine dinucleotide oxidase activity.
Targeting Chemotherapy Using Antibody-Combined Liposome against Human Pancreatic Cancer Cell-Line. (1995)

Anti-tumor effect of Adriamycin (ADM)-encapsulated and CA19-9 antibody-conjugated artificial lipid membrane follicle liposomes against a human pancreatic cancer cell-line PK-1 was studied in vitro and in vivo. The liposome compound (lipo c ADM = Ab) showed a stronger cell damage than ADM-encapsulated liposome (lipo c ADM) and free ADM, especially when the contact time was short and the concentration was low. The intra-tumor concentration of ADM in the group of i.v. injection of lipo c ADM = Ab showed the highest value, over twice those of lipo c ADM and free ADM after 120 hr. Lipo c ADM = Ab showed a significant inhibitory effect on the tumor growth inhibition test in vivo, and the final tumor weight at the 19th day was 27% in the group of lipo c ADM = Ab and 52% in the group of free ADM as compared with the control. The targeting chemotherapy using liposomes was demonstrated to have a stronger anti-tumor effect than the administration of anti-cancer drug alone owing to enhanced tumor accessibility and good targeting.
A Comparative Study of Reservoir Computing for Temporal Signal Processing (2014)

Reservoir computing (RC) is a novel approach to time series prediction using recurrent neural networks. In RC, an input signal perturbs the intrinsic dynamics of a medium called a reservoir. A readout layer is then trained to reconstruct a target output from the reservoir's state. The multitude of RC architectures and evaluation metrics poses a challenge to both practitioners and theorists who study the task-solving performance and computational power of RC. In addition, in contrast to traditional computation models, the reservoir is a dynamical system in which computation and memory are inseparable, and therefore hard to analyze. Here, we compare echo state networks (ESN), a popular RC architecture, with tapped-delay lines (DL) and nonlinear autoregressive exogenous (NARX) networks, which we use to model systems with limited computation and limited memory respectively. We compare the performance of the three systems while computing three common benchmark time series: H{é}non Map, NARMA10, and NARMA20. We find that the role of the reservoir in the reservoir computing paradigm goes beyond providing a memory of the past inputs. The DL and the NARX network have higher memorization capability, but fall short of the generalization power of the ESN.
Fertility and the aging male. (2011)

In the United States since 1980, the birth rate in women aged > 35 years has increased by nearly 60%, whereas the birth rate for women aged 20 to 34 years has increased by only 10%. The trend in parenthood at an older age has also been seen in men. Since 1980, the fertility rate for men in their 30s has increased by 21% and for men aged 40 years and older, the rate has increased nearly 30%. In contrast, the fertility rate in men younger than age 30 years has decreased by 15%. Age-related infertility will continue to be a problem. A basic understanding of the issues is critical for health care professionals so that they can effectively counsel patients who are considering a delay in childbearing for social reasons or for those seeking fertility treatments. This review details the changes in fertility seen in the aging male.
Luminescence decay kinetics ofMn2+-doped ZnS nanoclusters grown in reverse micelles (2000)

We report the synthesis and luminescence decay kinetics of 1.2-nm ${\mathrm{Mn}}^{2+}$-doped ZnS nanoclusters grown in reverse micelles. The preparation method produces small particles with narrow-size distribution and fluorescence bands near 400--450 nm and 585 nm. Time-dependent fluorescence decay measurements using picosecond, nanosecond, and millisecond techniques reveal relaxation processes on all three time scales. In the doped sample, the red emission detected at 600 nm exhibits a 1--2 ms decay in addition to faster decays with time constants on the order of hundreds of ps, a few ns and tens of \ensuremath{\mu}s. While the slow decay is the same as that of bulk ${\mathrm{Mn}}^{2+}$-doped ZnS, the fast decays are present for both doped and undoped samples and are unique to nanocluster ZnS, which are attributed to deep trap-state emission. The blue luminescence near 400--450 nm is attributed to shallow trap-state emission of ZnS. These results help to resolve the controversy in the literature regarding the lifetime of the ${\mathrm{Mn}}^{2+}$ emission in Mn-doped ZnS nanoparticles.
Mesothelin Expression in Human Lung Cancer (2007)

Mesothelin is expressed on the surface of most lung adenocarcinoma cells. Immunotoxin SS1P is cytotoxic against mesothelin-expressing lung cancer cell lines and merits evaluation as a new therapeutic agent in treating non-small cell lung cancer.
Transition Metal Nanocluster Formation Kinetic and Mechanistic Studies. A New Mechanism When Hydrogen Is the Reductant:  Slow, Continuous Nucleation and Fast Autocatalytic Surface Growth (1997)

Following an overview of the primitive state of mechanistic studies of the formation of nanoclusters, with a focus on LaMer's classic work on the formation of sulfur sols, kinetic and mechanistic studies of the formation of our recently reported novel P2W15Nb3O629- polyoxoanion- and Bu4N+- stabilized Ir∼190-450 (hereafter, Ir(0)∼300) nanoclusters are presented. The work reported consists of the full experimental and other details of the following eight major components: (i) development of an indirectbut easy, continuous, highly quantitative and thus powerfulmethod to monitor the formation of the Ir(0) nanoclusters via their catalytic hydrogenation activity and through the concept of pseudoelementary reaction steps; (ii) application of the appropriate kinetic equations for nucleation and autocatalysis, and then demonstration that these equations fit the observed, sigmoidal-shaped kinetic curves quantitatively with resultant rate constants k1 and k2; (iii) confirmation by a more direct, GLC method that the method in (i) indeed works and does so quantitatively, yielding the same k1 and k2 values within experimental error; (iv) collection of a wealth of previously unavailable kinetic and mechanistic data on the effects on nanocluster formation of added olefin, H2 pressure, anionic nanocluster stabilizer ([Bu4N]9P2W15Nb3O62 in the present case), H2O, HOAc, and temperature; (v) careful consideration and ruling out of other hypotheses, notably that particle-size rate effects alone might account for the observed sigmoidal shaped curves; and then (vi) distillation of the results into a minimalistic mechanism consisting of several pseudoelementary steps. Also presented as part of the Discussion are (vii) a concise but comprehensive review of the literature of transition metal nanocluster formation under H2 as the reducing agent, an analysis which provides highly suggestive evidence that the new mechanism uncovered is a much more general mechanismif not a new paradigmfor transition metal nanoclusters formed under H2 (and, the data argue, probably also for related reducing agents); and (viii) a summary of the seven key predictions of this new mechanism which remain to be tested (four predictions are the expected predominance of magic-number size nanoclusters; designed control of nanocluster size via the living-metal polymer concept; the synthesis of onion-skin structure bi-, tri-, and higher-metallic nanoclusters; and the use of face-selective capping agents as a way to block the autocatalytic surface growth and, thereby, to provide designed-shape nanoclusters). Overall, it is hoped that the resultsthe first new mechanism in more than 45 years for transition metal nanocluster formationwill go far toward providing a firmer mechanistic basis, and perhaps even a new paradigm, for the designed synthesis of new transition metal nanoclusters of prechosen sizes, shapes, and mono- to multimetallic compositions.
Investigation of Scratchpad Memory for Preemptive Multitasking (2012)

We present a multitasking scratchpad memory reuse scheme (MSRS) for the dynamic partitioning of scratchpad memory between tasks in a preemptive multitasking system. We specify a means to compute the worst-case response time (WCRT) and schedulability of task sets executed using MSRS. Our scratchpad-related preemption delay (SRPD) is an analog of cache-related preemption delay (CRPD), proposed in previous work as a way to compute the worst-case cost imposed upon a preempted task by preemption in a multitasking system. Unlike CRPD, however, SRPD is independent of the number of tasks and the local memory size. We compare SRPD with CRPD by experiment and determine that neither dominates the other, i.e. either may be better for certain task sets. However, MSRS leads to improved schedulability versus cache when contention for local memory space is high, either because the local memory size is small, or because the task set is large, provided that the cost of loading blocks from external memory to scratchpad is similar to the cost of loading blocks into cache.
A Pilot Study of Complete Edentulous Rehabilitation with Immediate Function Using a New Implant Design: Case Series (2006)

The results of the present pilot study indicate that fully edentulous jaws with various types of bone can be treated with high success and good esthetics using immediately loaded implants with the presented design, and that favorable marginal bone levels can be maintained.
Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes (1997)

The clinical and genetic relationships of febrile seizures and the generalized epilepsies are poorly understood. We ascertained a family with genealogical information in 2000 individuals where there was an unusual concentration of individuals with febrile seizures and generalized epilepsy in one part of the pedigree. We first clarified complex consanguineous relationships in earlier generations and then systematically studied the epilepsy phenotypes in affected individuals. In one branch (core family) 25 individuals over four generations were affected. The commonest phenotype, denoted as 'febrile seizures plus' (FS+), comprised childhood onset (median 1 year) of multiple febrile seizures, but unlike the typical febrile convulsion syndrome, attacks with fever continued beyond 6 years, or afebrile seizures occurred. Seizures usually ceased by mid childhood (median 11 years). Other phenotypes included FS+ and absences, FS+ and myoclonic seizures, FS+ and atonic seizures, and the most severely affected individual had myoclonic-astatic epilepsy (MAE). The pattern of inheritance was autosomal dominant. The large variation in generalized epilepsy phenotypes was not explained by acquired factors. Analysis of this large family and critical review of the literature led to the concept of a genetic epilepsy syndrome termed generalized epilepsy with febrile seizures plus (GEFS+). GEFS+ has a spectrum of phenotypes including febrile seizures, FS+ and the less common MAE. Recognition of GEFS+ explains the epilepsy phenotypes of previously poorly understood benign childhood generalized epilepsies. In individual patients the inherited nature of GEFS+ may be overlooked. Molecular genetic study of such large families should allow identification of genes relevant to febrile seizures and generalized epilepsies.
Conformationally Constrained β-Amino Acid Derivatives by Intramolecular [2 + 2]-Photocycloaddition of a Tetronic Acid Amide and Subsequent Lactone Ring Opening (2005)

[reaction: see text] The N-Boc-protected N-3-alkenyltetronic acid amides 9 and 12 were prepared from tetronic acid bromide (7) and the corresponding amines 6 and 10 by nucleophilic substitution and subsequent acylation in 71% and 39% overall yield. They underwent an intramolecular [2 + 2]-photocycloaddition upon direct irradiation (lambda = 254 nm) to yield diastereoselectively the strained lactones 15 (76%) and 16 (91%) with a 2-azabicyclo[3.2.0]heptane core. In attempts to defunctionalize the 1-hydroxymethyl substituent of the 2-azabicyclo[3.2.0]heptane skeleton, lactone 15 was converted into mesylate 18 (74% overall yield). Intermolecular substitution reactions on this mesylate, however, proceeded sluggishly or failed completely. Lactone 15 could be opened reductively (Dibal-H) or by substitution with benzylamine to the N-Boc-protected 2-azabicyclo[3.2.0]heptanes 21 (71%) and 22 (81%). Conformationally constrained beta-amino acid derivatives were obtained by quantitative N-Boc deprotection of photocycloaddition product 15, followed by N-functionalization and subsequent lactone ring opening. The N-functionalization was conducted by acylation (to 24-26), alkylation (to 27), tosylation (to 28), and isocyanate addition (to 30). The reactions proceeded in yields of 70-84%. Lactone ring opening reactions were conducted with amines to establish the suitability of this process for library synthesis. As an example, the tripeptide 38 was obtained from photocycloaddition product 15 in an overall yield of 51%.
Mechanism of Intrinsic Transcription Termination and Antitermination (1999)

Gene expression is modulated by regulatory elements that influence transcription elongation by RNA polymerase: terminators that disrupt the elongation complex and release RNA, and regulators that overcome termination signals. RNA release from Escherichia coli RNA polymerase can be induced by a complementary oligonucleotide that replaces the upstream half of the RNA hairpin stem of intrinsic terminator transcripts, implying that RNA hairpins act by extracting RNA from the transcription complex. A transcription antiterminator inhibits this activity of oligonucleotides and therefore protects the elongation complex from destabilizing attacks on the emerging transcript. These effects illuminate the structure of the complex and the mechanism of transcription termination.
Full Scale Simulation of an Integrated Monolithic Heat Sink for Thermal Management of a High Power Density GaN-SiC Chip (2015)

Advances in manufacturing techniques are inspiring the design of novel integrated microscale thermal cooling devices seeking to push the limits of current thermal management solutions in high heat flux applications. These advanced cooling technologies can be used to improve the performance of high power density electronics such as GaN-based RF power amplifiers. However, their optimal design requires careful analysis of the combined effects of conduction and convection. Many numerical simulations and optimization studies have been performed for single cell models of microchannel heat sinks, but these simulations do not provide insight into the flow and heat transfer through the entire device. This study therefore presents the results of conjugate heat transfer CFD simulations for a complex copper monolithic heat sink integrated with a 100 micron thick, 5 mm by 1 mm high power density GaN-SiC chip. The computational model (13 million cells) represents both the chip and the heat sink, which consists of multiple inlets and outlets for fluid entry and exit, delivery and collection manifold systems, and an array of fins that form rectangular microchannels. Total chip powers of up to 150 W at the GaN gates were considered, and a quarter of the device was modeled for total inlet mass flow rates of 1.44 g/s and 1.8 g/s (0.36 g/s and 0.45 g/s for the quarter device), corresponding to laminar flow at Reynolds numbers between 19.5 and 119.3. It was observed that the mass flow rates through individual microchannels in the device vary by up to 45%, depending on the inlet/outlet locations and pressure drop in the manifolds. The results demonstrate that full device simulations provide valuable insight into the multiple parameters that affect cooling performance.
Transcriptional regulation of fatty acid production in higher plants: Molecular bases and biotechnological outcomes (2014)

Acyl lipids are essential constituents found in every plant cell, where they fulfill diverse biological functions. Requirements for acyl chains depend on the cell type considered and vary greatly, implying a tight regulation of de novo fatty acid production in the plastids so that supply fits demand. Data generated by extensive transcriptome analyses carried out in various plant species and the characterization of the WRINKLED1 transcription factor in the model plant Arabidopsis thaliana have first established the importance of transcriptional regulation for modulating the rate of fatty acid production. The fatty acid biosynthetic pathway is indeed subjected to a system of global transcriptional control that coordinates the expression of most genes encoding enzymes of the pathway. Although much remains to be elucidated, the framework of the regulatory system controlling fatty acid biosynthesis in plants is coming into focus. Practical applications: Fatty acids constitute the most abundant form of reduced carbon chains available from nature and plant oils represent the main renewable resource of these fatty acids. Plant oils therefore represent a highly valuable agricultural commodity, the demand for which is increasing rapidly. They are primarily used for food and feed, but they are increasingly being utilized as renewable sources of industrial feedstock and fuel. Knowledge regarding the regulation of fatty production is extensively exploited in the frame of genetic engineering for oilseed crop improvement. Fatty acids constitute the most abundant form of reduced carbon chains available from nature and plant oils represent the main renewable resource of these fatty acids. Plant oils therefore represent a highly valuable agricultural commodity, the demand for which is increasing rapidly. They are primarily used for food and feed, but they are increasingly being utilized as renewable sources of industrial feedstock and fuel. Knowledge regarding the regulation of fatty production is extensively exploited in the frame of genetic engineering for oilseed crop improvement. Data generated by extensive transcriptome analyses carried out in various plant species and the characterization of the WRINKLED1 transcription factor in the model plant Arabidopsis thaliana have established the importance of transcriptional regulation for modulating the rate of fatty acid production. The fatty acid biosynthetic pathway is indeed subjected to a system of global transcriptional control that coordinates the expression of most genes encoding enzymes of the pathway. Recent advance suggest that WRINKLED1 activity may be modulated at the post‐translational level through homo‐dimerization, phosphorylation, and/or ubiquitination.