gebhart/patrepeval huggingface dataset:
Comparison of Drug Transporter Levels in Normal Colon, Colon Cancer, and Caco-2 Cells:  Impact on Drug Disposition and Discovery (2006)

A critical step in early phase drug development is the determination of oral bioavailability. In part, the ability to predict whether a drug will be effectively transported across the gastrointestinal mucosa can be estimated from the physicochemical properties of the compound. Although advancements through rational drug design have more correctly predicted bioavailability, considerable variability remains to be explained. Transporter expression throughout the gastrointestinal tract may explain much of this variation. ATP-binding cassette (ABC) transporters were the first family of transporters identified to modify bioavailability. More recently, the solute carrier family has also been shown to alter the pharmacokinetic profile of drugs. Currently, the Caco-2 human colon carcinoma cell line is often used by the pharmaceutical industry to evaluate intestinal absorption of drugs; however, in vivo/in vitro permeabilities with carrier mediated drugs do not correlate well, suggesting that Caco-2 transporter expression varies from that of the small intestine. With this is mind, we integrated U133A GeneChip expression data from the NCBIs Gene Expression Omnibus (GEO) collection and then compared the expression pattern of Caco-2 cells to normal colon to determine if the Caco-2 cell line is a reliable model for colonic delivery. Furthermore, transporter expression of Caco-2 cells was compared to that of human colon tumors to assess whether this cell line could be useful to predict drug absorption for colon cancer. Our analysis shows that the expression pattern for Caco-2 cells closely resembles the gene expression profile of transporters within the normal colon, suggesting that this cell line may serve as an in vitro model of colonic drug adsorption. However, the molecular "fingerprint" of Caco-2 was distinctly different from tumor samples, indicating that the Caco-2 model would unlikely predict accurate drug absorption for colon cancer sites.
Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing (2003)

Glucose homeostasis is controlled by insulin in part through the translocation of intracellular glucose transporter 4 to the plasma membrane in muscle and fat cells. Akt/protein kinase B downstream of phosphatidylinositol 3-kinase has been implicated in this insulin-signaling pathway, but results with a variety of reagents including Akt1-/- and Akt2-/- mice have been equivocal. Here we report the application of small interfering RNA-directed gene silencing to deplete both Akt1 and Akt2 in cultured 3T3-L1 adipocytes. Loss of Akt1 alone slightly impaired insulin-mediated hexose transport activity but had no detectable effect on glycogen synthase kinase (GSK)-3 phosphorylation. In contrast, depletion of Akt2 alone by 70% inhibited approximately half of the insulin responsiveness. Combined depletions of Akt1 plus Akt2 in these cells even more markedly attenuated insulin action on glucose transporter 4 movements, hexose transport activity, and GSK-3 phosphorylation. These data demonstrate a primary role of Akt2 in insulin signaling, significant functional redundancy of Akt1 and Akt2 isoforms in this pathway, and an absolute requirement of Akt protein kinases for regulation of glucose transport and GSK-3 in cultured adipocytes.
Dimerization and Isomerization Reactions of α-Lithiated Terminal Aziridines (2007)

The scope of dimerization and isomerization reactions of alpha-lithiated terminal aziridines is detailed. Regio- and stereoselective deprotonation of simple terminal aziridines with lithium 2,2,6,6-tetramethylpiperidide (LTMP) or lithium dicyclohexylamide (LiNCy2) generates trans-alpha-lithiated terminal aziridines. These latter species can then undergo dimerization or isomerization reactions depending on the nature of the N-protecting group. alpha-Lithiated terminal aziridines bearing N-alkoxycarbonyl (Boc) protection undergo N- to C-[1,2] migration to give N-H trans-aziridinylesters. In contrast, aziridines bearing N-organosulfonyl [tert-butylsulfonyl (Bus)] protection undergo rapid dimerization to give 2-ene-1,4-diamines or, if a pendant alkene is present, diastereoselective cyclopropanation to give 2-aminobicyclo[3.1.0]hexanes. All of these reactions were used as key steps in the preparation of synthetically and biologically important targets.
Knowledge Transfer in Permutation Invariant Training for Single-Channel Multi-Talker Speech Recognition (2018)

This paper proposes a framework that combines teacher-student training and permutation invariant training (PIT) for single-channel multi-talker speech recognition. In contrast to most of conventional teacher-student training methods that aim at compressing the model, the proposed method distills knowledge from the single-talker model to improve the multi-talker model in the PIT framework. The inputs to the teacher and student networks are the single-talker clean speech and the multi-talker mixed speech, respectively. The knowledge is transferred to the student through the soft labels generated by the teacher. Furthermore, the ensemble of multiple teachers is exploited with a progressive training scheme to further improve the system. In this framework it is easy to take advantage of data augmentation and perform domain adaptation for multi-talker speech recognition using only untranscribed data. The proposed techniques were evaluated on artificially mixed two-talker AMI speech data. The experimental results show that the teacher-student training can cut the word error rate (WER) by relative 20% against the baseline PIT model. We also evaluated our unsupervised domain adaptation method on an artificially mixed WSJO corpus and achieved relative 30% WER reduction against the AMI PIT model.
The cross-linking of collagen and elastin: enzymatic conversion of lysine in peptide linkage to alpha-aminoadipic-delta-semialdehyde (allysine) by an extract from bone. (1968)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Design of Smart Home Control System Based on ZigBee Technology (2008)

Because of ZigBee technology characteristics of low speed,low power consumption and low cost,the smart home control system based on ZigBee technology was designed.The design idea and realization methods of hardware and software were discussed.The system can meet the basic requirements of home network communication.It is very flexible,efficient and low cost.
Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival (2012)

Bortezomib has shown great promise in the treatment of amyloid light-chain (AL) amyloidosis. We present our experience of 43 patients with AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (CVD) upfront or at relapse. Of these, 74% had cardiac involvement and 46% were Mayo Cardiac Stage III. The overall hematologic response rate was 81.4%, including complete response (CR) in 41.9% and very good partial response with >90% decrease in difference between involved/uninvolved light chain (VGPR-dFLC) in 51.4%. Patients treated upfront had higher rates of CR (65.0%) and VGPR-dFLC (66.7%). The estimated 2-year progression-free survival was 66.5% for patients treated upfront and 41.4% for relapsed patients. Those attaining a CR or VGPR-dFLC had a significantly better progression-free survival (P=.002 and P=.026, respectively). The estimated 2-year overall survival was 97.7% (94.4% in Mayo Stage III patients). CVD is a highly effective regimen producing durable responses in AL amyloidosis; the deep clonal responses may overcome poor prognosis in advanced-stage disease.
Investigations of Metal-Coordinated Peptides as Supramolecular Synthons (2006)

This article describes the synthesis and controlled assembly of four model biological-hybrid scaffolds via coordination of a metal complex to four new tripeptides. Each model tripeptide investigated has either a central pyridyl glycyl or a pyridyl alanyl residue between two terminally protected glycines. All tripeptides were coordinated to their complementary recognition unit, a p-methoxy SCS-Pd pincer complex. The assembly events were fully characterized and investigated by 1H NMR, ES-MS, and isothermal titration calorimetry (ITC) to elucidate how the substitution and spatial distance of the pyridyl moiety to the peptide backbone affects the metal coordination. Using these characterization techniques, we have shown that the metal-coordination events in all cases are fast and quantitative and that the peptide backbones do not interfere with the self-assembly. The ITC analyses showed that the 4-pyridyl tripeptides are the tightest binding ligands toward the palladated pincer complexes with the alanyl derivative being the strongest overall, demonstrating the superiority of the 4-pyridyl peptides over their 3-pyridyl analogues. The measured association constants are comparable to other pincer-pyridine systems in DMSO suggesting that the controlled coordination of the metalated pincer/pyridine interaction is an interesting biological synthon and will allow for the future development of important noncovalent peptide-based hybrid materials.
Macroeconomic Forecasting Using Diffusion Indexes (2002)

This article studies forecasting a macroeconomic time series variable using a large number of predictors. The predictors are summarized using a small number of indexes constructed by principal component analysis. An approximate dynamic factor model serves as the statistical framework for the estimation of the indexes and construction of the forecasts. The method is used to construct 6-, 12-, and 24-monthahead forecasts for eight monthly U.S. macroeconomic time series using 215 predictors in simulated real time from 1970 through 1998. During this sample period these new forecasts outperformed univariate autoregressions, small vector autoregressions, and leading indicator models.
Wavefront fitting with discrete orthogonal polynomials in a unit radius circle (1990)

Zernike polynomials have been used for some time to fit wavefront deformation measurements to a two-dimensional polynomial. Their orthogonality properties make them ideal for this kind of application. The typical procedure consists of first obtaining the fitting using x-y polynomials and then transforming them to Zernike polynomials by means of a matrix multiplication. Here, we present a new method for making this fitting faster by using a set of orthogonal polynomials on a discrete base of data points on a unitary circle.
Sequence motifs for calmodulin recognition (1997)

Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. Three recognition motifs for CaM interaction are discussed in the context of experimental investigations of a variety of CaM target proteins. A modified version of the IQ motif as a consensus for Ca2+-independent binding and two related motifs for Ca2+-dependent binding, termed 18-14 and 1-5-10 based on the position of conserved hydrophobic residues, are proposed. Although considerable sequence diversity is observed among the different binding regions, these three classes of recognition motifs exist for many of the known CaM binding proteins.
Synthesis of 4,4-Disubstituted L-Glutamic Acids by Enzymatic Transamination (2001)

The syntheses of optically pure 4,4-dimethyl-L-glutamic acid as well as (2S,4R)- and (2S,4S)-4-hydroxy-4-methylglutamic acids have been achieved by transamination of the corresponding 2-oxo-4,4-dimethyl- and rac-2-oxo-4-hydroxy-4-methylglutaric acids using glutamic oxalacetic transaminase (GOT).
Effect of various agents on liver regeneration and Walker tumor growth in partially hepatectomized rats. (1966)

Subtotally hepatectomized rats with Walker tumor transplanted into the caudal lobe of the remaining liver at surgery were administered agents which depress or increase the extent of regeneration over periods up to 10.5 days. Of the compounds stimulating liver weight restoration as such, diets supplemented with coramine, butazolidin, 2,4-dithiopyrimidine, thalidomide, and acenaphthene, or the latter hydrocarbon and 9,10-dimethyl-1,2-benzanthracene injected s.c., caused definite increases, whereas thiouracil, disulfiram, and usnic acid gave rise to liver increments which were in the range of the respective controls. Dietary supplements of the inhibitors, nicotinamide, cycloleucine, dl-ethionine, and 6-mercaptopurine or s.c. injection of cortisone acetate elicited decreases but these were not statistically significant. Accordingly, the presence of tumor tended to “normalize” the degree of regeneration. The mean wet tumor weights were not affected by any of the treatments except for a decrease with the diet containing nicotinamide (0.35%) and, possibly, with the 1 supplemented with cycloleucine (0.050%).
Studies on the syntheses of heterocyclic compounds. Part 865. A novel synthesis of indole derivatives by intramolecular nucleophilic aromatic substitution (1981)

Cyclisation of N-(2-bromo-4,5-dimethoxyphenethyl)acetamide (6) afforded 1-acetyl-2,3-dihydro-5,6-dimethoxy-1H-indole (13) by intramolecular nucleophilic aromatic substitution using sodium hydride and cuprous halide in dimethylformamide. The dihydroindoles (14), (15), and (16) were also synthesised from the corresponding amides (8) and (10) and the carbamate (12) in a similar manner. The dihydroindoles (13), (14), and (16) were converted into the indoles (20) and (21) in excellent yield by oxidation and subsequent alkaline hydrolysis. The 2-oxindoles (26) and (27) were also prepared under similar reaction conditions from the phenylacetamide (24) and (25).
Expression of the cytokeratin marker CAM 5.2 in cervical neoplasia (1988)

It has been suggested that cytokeratin CAM 5.2 is a useful marker to indicate malignant transformation and invasive potential in cervical neoplasia. In this study we examined normal ectocervical epithelium, endocervical squamous metaplasia, cervical intra-epithelial neoplasia (CIN) and invasive carcinoma by the indirect immunoperoxidase method using commercially available CAM 5.2. Positive staining was seen in 12 of 42 (28%) invasive carcinomas and in 2 of 26 specimens of CIN III. No positive staining was observed in any case of CIN II (22 specimens), CIN I (19), squamous metaplasia (21) or normal ectocervical epithelium (16). These results suggest that although CAM 5.2 expression is found in only 28% of cervical squamous carcinoma, it is highly specific for malignant transformation of cervical squamous epithelium. In view of its potential diagnostic value in doubtful cases of CIN III and squamous cell carcinoma, the specificity and sensitivity of CAM 5.2 expression in cervical neoplasia need to be examined in other laboratories under various processing schedules.
Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results. (2001)

L-Arginine may be a conditionally essential amino acid in children and adolescents with sickle cell disease, particularly as required substrate in the arginine-nitric oxide pathway for endogenous nitrovasodilation and vasoprotection. Vasoprotection by arginine is mediated partly by nitric oxide-induced inhibition of endothelial damage and inhibition of adhesion and activation of leukocytes. Activated leukocytes may trigger many of the complications, including vasoocclusive events and intimal hyperplasias. High blood leukocyte counts during steady states in the absence of infection are significant laboratory risk factors for adverse complications. L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0.1 g/kg in a pilot Phase II clinical trial during steady states in four homozygous sickle cell disease subjects and one sickle cell-hemoglobin C disease patient (ages 10-18). There soon resulted dramatic improvements in symptoms of well-being, raised plasma arginine levels, and reductions in high total leukocyte and high segmented neutrophil counts toward or to within normal limits. Continued L-citrulline supplementation in compliant subjects continued to lessen symptomatology, to maintain plasma arginine concentrations greater than control levels, and to maintain nearly normal total leukocyte and neutrophil counts. Side effects or toxicity from citrulline were not experienced. Oral L-citrulline may portend very useful for palliative therapy in sickle cell disease. Placebo-controlled, long-term trials are now indicated.
Targeting Strategy for Gene Delivery to Carcinoembryonic Antigen-Producing Cancer Cells by Retrovirus Displaying a Single-Chain Variable Fragment Antibody (1998)

Cancer-specific antigens are promising targets for the specific delivery of certain drugs or genes to cancer cells in cancer therapy. Carcinoembryonic antigen (CEA) is one of the cancer-associated antigens predominantly detected in the gastrointestinal cancer of the colon and stomach. Targeting strategies for CEA-producing cancer cells have been thoroughly developed mainly by the production of monoclonal antibodies to CEA and further single-chain variable fragment (scFv) antibodies. Here, we have generated Moloney murine leukemia virus-derived retroviral vectors co-displaying an anti-CEA scFv-envelope chimeric protein and an unmodified envelope protein to deliver a gene for herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase. The harvested viruses successfully incorporated the chimeric envelope protein as well as the unmodified envelope into the viral particles, and specifically bound to and infected human CEA-producing cancer cells via recognition of CEA, depending on the CEA-producing phenotype of the target cells. These results may have significant implications for the use of scFv directed against tumor-specific antigens for targeting specific antigen-producing cancer cells, a potential step toward in vivo cancer therapy.
1997 Volvo Award Winner in Clinical Studies (1997)

In patients undergoing single-level posterolateral fusion for degenerative spondylolisthesis with spinal stenosis, the use of pedicle screws may lead to a higher fusion rate, but clinical outcome shows no improvement in pain in the back and lower limbs.
Towards an Identification of Odorant Receptors (1993)

The molecular nature and diversity of receptive sites for odorous molecules is a central unanswered issue in olfaction. Based on the enormous resolving power of the olfactory system, which enables the stereospecific discrimination of numerous compounds at low concentrations specific receptor proteins have been proposed. Due to the central role of G-proteins in olfactory signalling it has been predicted that odorant receptors might be members of the superfamily of receptor proteins with seven transmembrane domains. Upon application of degenerated oligonucleotides and the PCR-technology a number of putative odorant receptors have been cloned and sequenced. In situ hybridisation studies using receptor-specific probes have been performed and olfactory neurons specifically expressing a particular receptor subtype are topologically identified in the nasal epithelium of rats. Clones of interest are now being expressed in heterologous systems in order to demonstrate functional activity of these putative receptor proteins and to match defined odorants to identified receptors.
Optical focusing deep inside dynamic scattering media with near-infrared time-reversed ultrasonically encoded (TRUE) light (2015)

Focusing light deep inside living tissue has not been achieved despite its promise to play a central role in biomedical imaging, optical manipulation and therapy. To address this challenge, internal-guide-star-based wavefront engineering techniques--for example, time-reversed ultrasonically encoded (TRUE) optical focusing--were developed. The speeds of these techniques, however, were limited to no greater than 1 Hz, preventing them from in vivo applications. Here we improve the speed of optical focusing deep inside scattering media by two orders of magnitude, and focus diffuse light inside a dynamic scattering medium having a speckle correlation time as short as 5.6 ms, typical of living tissue. By imaging a target, we demonstrate the first focusing of diffuse light inside a dynamic scattering medium containing living tissue. Since the achieved focusing speed approaches the tissue decorrelation rate, this work is an important step towards in vivo deep tissue noninvasive optical imaging, optogenetics and photodynamic therapy.
Finding the right frequency: impact of spectrum availability upon the economics of mobile broadcasting (2006)

This paper discusses the spectrum availability for mobile broadcasting. Technical issues in spectrum like propagation, building penetration loss, terminal antenna gain, interoperability with cellular radios, Doppler, and man made noise are presented. Network cost comparison between different available frequency bands are also discussed.
Evaluation of polyketones with N-cyclic structure as electrode material for electrochemical energy storage: case of tetraketopiperazine unit (2010)

Pursuing the electrochemical evaluation vs. Li of carbonyl-based cyclic structures deriving from the oxocarbon family, polyketones with N-cyclic structure are investigated to probe the potential modifications. In this communication, we specifically report on the electrochemical investigation of our first selected family of heterocycles based on the 2,3,5,6-tetraketopiperazine unit. Working in a systematic way, a series of tetraketopiperazine molecules with quite different R groups as substituents (i.e., phenyl, allyl and propyl functions) have been synthesized and characterized. Such small molecules were found to rapidly solubilise in commonly used electrolytes. To bypass this issue, we have prepared an oligomeric form via acyclic diene metathesis (ADMET). Preliminary results on the poly-N,N′-diallyl-2,3,5,6-tetraketopiperazine oligomer show a sustained reversible capacity of 110 mAh g−1 at near 2.45 V. The insight gained from this work is the fact that two intracyclic nitrogen atoms or a lithiated ene–diolate functionality in the C6-based polyketone cyclic structure induces a similar tuning of the redox potential.
Demonstration of the Casimir Force in the 0.6 to6μmRange (1997)

The vacuum stress between closely spaced conducting surfaces, due to the modification of the zero-point fluctuations of the electromagnetic field, has been conclusively demonstrated. The measurement employed an electromechanical system based on a torsion pendulum. Agreement with theory at the level of 5% is obtained.